2024-03-29T14:52:44Zhttps:/www.ncbi.nlm.nih.gov/pmc/oai/oai.cgioai:pubmedcentral.nih.gov:1661182003-07-25thrombjpmc-open
Point-of-Care Testing of Hemostasis in Cardiac Surgery
Prisco, Domenico
Paniccia, Rita
Thromb J
Review
An excessive perioperative blood loss, that requires transfusion of blood products, sometimes occurs in patients undergoing cardiopulmonary bypass for cardiac surgery. Blood loss and transfusion requirements in these patients may be reduced with a better control of heparin treatment and its reversal. Blood component administration in patients with excessive post-cardiopulmonary bypass bleeding has been empiric for a long time due to turnaround times of laboratory coagulation tests. Devices are now available for rapid, point-of-care assessment of hemostasis alterations to allow an appropriate, targeted therapy. In particular, a quick evaluation of platelet and coagulation defects with new point-of-care devices can optimize the administration of pharmacological and transfusion-based therapy in patients with excessive bleeding after cardiopulmonary bypass.
BioMed Central
2003-05-06
/pmc/articles/PMC166118/
/pubmed/12904262
http://dx.doi.org/10.1186/1477-9560-1-1
Text
en
Copyright © 2003 Prisco and Paniccia; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:1798782003-08-20thrombjpmc-open
Acute coronary disease Athero-Inflammation: Therapeutic approach
Altman, Raul
Thromb J
Review
Antithrombotic therapy is the cornerstone of the treatment of acute coronary syndromes, but there is now evidence which indicates that by blocking inflammation, thrombosis and thus, acute coronary events, could be lowered. The concept of athero-inflammation emerges as the meeting point of different morbidities; dyslipemia, diabetes, hypertension, obesity, immunity, infection, hyperhomocyteinemia, smoking, etc. usual named as risk factors. Thus, beside specific drugs, earliest treatment, in the stage of inflammation, using anti-inflammatory drugs, should be considered since in patients with increased risk of acute coronary process are likely to have many point of origen throughout the coronary arteries. There are a body of evidences for supporting the potential of anti-inflammatory therapy to the prevention of inflammation and atherosclerosis. COX-2 inhibition may decrease endothelial inflammation reducing monocytes infiltration improving vascular cells function, plaque stability and probably resulting in a decrease of coronary atherothrombotic events. Trials including large numbers of patients in prospective double-blind randomized studies worthwhile to confirm the efficacy of NSAID, mainly, COX-2 inhibitors, together with aspirin in the prevention of coronary events in patients with acute coronary disease.
BioMed Central
2003-06-20
/pmc/articles/PMC179878/
/pubmed/12904261
http://dx.doi.org/10.1186/1477-9560-1-2
Text
en
Copyright © 2003 Altman; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:1798792003-08-20thrombjpmc-open
Thrombin generation during cardiopulmonary bypass: the possible role of retransfusion of blood aspirated from the surgical field
Weerwind, Patrick W
Lindhout, Theo
Caberg, Nicole EH
de Jong, Dick S
Thromb J
Original Clinical Investigation
BACKGROUND: In spite of using heparin-coated extracorporeal circuits, cardiopulmonary bypass (CPB) is still associated with an extensive thrombin generation, which is only partially suppressed by the use of high dosages of heparin. Recent studies have focused on the origins of this thrombotic stimulus and the possible role of retransfused suctioned blood from the thoracic cavities on the activation of the extrinsic coagulation pathway. The present study was designed to find during CPB an association between retransfusion of suctioned blood from the pericardium and pleural space, containing activated factor VIIa and systemic thrombin generation. METHODS: Blood samples taken from 12 consenting patients who had elective cardiac surgery were assayed for plasma factor VIIa, prothrombin fragment 1+2 (F(1+2)), and thrombin-antithrombin (TAT) concentrations. Blood aspirated from the pericardium and pleural space was collected separately, assayed for F(1+2), TAT, and factor VIIa and retransfused to the patient after the aorta occlusion. RESULTS: After systemic heparinization and during CPB thrombin generation was minimal, as indicated by the lower than base line plasma levels of F(1+2), and TAT after correction for hemodilution. In contrast, blood aspirated from the thoracic cavities had significantly higher levels of factor VIIa, F(1+2), and TAT compared to the simultaneous samples from the blood circulation (P < 0.05). Furthermore, after retransfusion of the suctioned blood (range, 200–1600 mL) circulating levels of F(1+2), and TAT rose significantly from 1.6 to 2.9 nmol/L (P = 0.002) and from 5.1 to 37.5 μg/L (P = 0.01), respectively. The increase in both F(1+2), and TAT levels correlated significantly with the amount of retransfused suctioned blood (r = 0.68, P = 0.021 and r = 0.90, P = 0.001, respectively). However, the circulating factor VIIa levels did not correlate with TAT and F(1+2 )levels. CONCLUSIONS: These data suggest that blood aspirated from the thoracic cavities during CPB is highly thrombogenic. Retransfusion of this blood may, therefore, promote further systemic thrombin generation during CPB.
BioMed Central
2003-07-15
/pmc/articles/PMC179879/
/pubmed/12904260
http://dx.doi.org/10.1186/1477-9560-1-3
Text
en
Copyright © 2003 Weerwind et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:1798802003-08-20thrombjpmc-open
Risk factors in coronary atherosclerosis athero-inflammation: the meeting point
Altman, Raul
Thromb J
Review
BioMed Central
2003-07-17
/pmc/articles/PMC179880/
/pubmed/12904259
http://dx.doi.org/10.1186/1477-9560-1-4
Text
en
Copyright © 2003 Altman; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:1947762003-09-16thrombjpmc-open
Angiotensin Converting Enzyme and Angiotensin II Type 1 Receptor Polymorphisms in Patients with Coronary Aneurysms
Lamblin, Nicolas
Hermant, Xavier
Lablanche, Jean-Marc
Helbecque, Nicole
Amouyel, Philippe
Bauters, Christophe
Thromb J
Original Clinical Investigation
BACKGROUND: Conflicting results have been reported regarding the association of gene polymorphisms in the renin-angiotensin system (RAS) with different aspects of coronary artery disease (CAD), such as myocardial infarction, neointimal hyperplasia or coronary artery vasomotion. Since previous studies have linked angiotensin II to aneurysmal disease, our study hypothesis was that RAS gene polymorphisms may be associated with aneurysm remodeling in response to CAD. METHODS: The study population was selected from a series of 3862 consecutive patients who underwent coronary angiography in our institution. One hundred and thirteen consecutive patients with at least one coronary aneurysm (CA) were compared to 226 randomized control patients without CA. DNA was extracted from white blood cells. The angiotensin-converting enzyme (ACE) I/D and angiotensin type 1 receptor (AT1-R) A/C polymorphisms were detected using previously published techniques. RESULTS: The distributions of the three ACE genotypes were similar in both groups: CA: 13%, 46%, and 41% for II, ID, and DD respectively; controls: 18%, 41%, and 41% for II, ID, and DD respectively, p = 0.45. The distributions of the three AT1-R genotypes were also similar in both groups: CA: 54%, 41%, and 5% for AA, AC, and CC respectively; controls: 55%, 33%, and 12%, for AA, AC, and CC respectively, p = 0.08. CONCLUSION: Our results provide further information on the role of RAS polymorphisms on specific mechanisms implicated in CAD. Although an activated RAS may theoretically promote aneurysm formation, the 2 RAS polymorphisms analyzed in this study are not associated with this process in coronary arteries.
BioMed Central
2003-08-11
/pmc/articles/PMC194776/
/pubmed/12971828
http://dx.doi.org/10.1186/1477-9560-1-5
Text
en
Copyright © 2003 Lamblin et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:2700842003-11-21thrombjpmc-open
Induction of Tissue Factor Expression in Endothelial Cells by Basic Fibroblast Growth Factor and its Modulation by Fenofibric acid
Kaneko, Takeaki
Fujii, Satoshi
Matsumoto, Akio
Goto, Daisuke
Makita, Naomasa
Hamada, Junichi
Moriuchi, Tetsuya
Kitabatake, Akira
Thromb J
Original Basic Research
BACKGROUND: Tissue factor (TF), expressed in endothelial cells (ECs) and enriched in human atherosclerotic lesions, acts as a critical initiator of blood coagulation in acute coronary syndrome. Basic fibroblast growth factor (bFGF) induces the proliferation and migration of ECs and plays a role in angiogenesis and restoration of endothelial integrity. As TF is implicated in angiogenesis, we studied the effect of bFGF on TF gene and protein expression. Methods: Human umbilical vein ECs (HUVECs) were exposed to bFGF. TF mRNA was assessed by Northern blot and TF protein was assessed by Western blot. TF promoter activity was assessed by transient transfection assay and transcription factor was identified by electro mobility shift assay. RESULTS: bFGF increased TF mRNA and protein expression in HUVECs. Increased TF mRNA was attenuated by inhibition of extracellular signal-regulated kinase kinase in human ECV304 cells. Transient transfection assays of the human TF promoter-luciferase construct (-786/+121 bp) demonstrated that bFGF induced transcription was dependent on the elements within the -197 to -176 bp relative to the transcription start site of the human TF gene. This region contains NF-κB like binding site. Electro mobility shift assay showed that bFGF increased nuclear translocation or DNA binding of NF-κB transcription factor to TF promoter. Nucleotide substitution to disrupt NF-κB like site reduced bFGF stimulated promoter activity. Fenofibric acid, an agonist ligand for the peroxisome proliferator activated receptor-α, reduced basal and bFGF stimulated TF expression. CONCLUSIONS: These results indicate that bFGF may increase TF production in ECs through activation of transcription at NF-κB binding site, and control coagulation in vessel walls. Fibrate can inhibit TF expression and therefore reduce the thrombogenecity of human atherosclerotic lesions.
BioMed Central
2003-10-11
/pmc/articles/PMC270084/
/pubmed/14613528
http://dx.doi.org/10.1186/1477-9560-1-6
Text
en
Copyright © 2003 Kaneko et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:3173782004-01-23thrombjpmc-open
Multivariate relationships between international normalized ratio and vitamin K-dependent coagulation-derived parameters in normal healthy donors and oral anticoagulant therapy patients
Watala, Cezary
Golanski, Jacek
Kardas, Przemyslaw
Thromb J
Original Basic Research
BACKGROUND AND OBJECTIVES: International Normalized Ratio (INR) is a world-wide routinely used factor in the monitoring of oral anticoagulation treatment (OAT). However, it was reported that other factors, e. g. factor II, may even better reflect therapeutic efficacy of OAT and, therefore, may be potentialy useful for OAT monitoring. The primary purpose of this study was to characterize the associations of INR with other vitamin K-dependent plasma proteins in a heterogenous group of individuals, including healthy donors, patients on OAT and patients not receiving OAT. The study aimed also at establishing the influence of co-morbid conditions (incl. accompanying diseases) and co-medications (incl. different intensity of OAT) on INR. DESIGN AND METHODS: Two hundred and three subjects were involved in the study. Of these, 35 were normal healthy donors (group I), 73 were patients on medication different than OAT (group II) and 95 were patients on stable oral anticoagulant (acenocoumarol) therapy lasting for at least half a year prior to the study. The values of INR and activated partial thromboplastin time (APTT) ratio, as well as activities of FII, FVII, FX, protein C, and concentration of prothrombin F1+2 fragments and fibrinogen were obtained for all subjects. In statistical evaluation, the uni- and multivariate analyses were employed and the regression equations describing the obtained associations were estimated. RESULTS: Of the studied parameters, three (factors II, VII and X) appeared as very strong modulators of INR, protein C and prothrombin fragments F1+2 had moderate influence, whereas both APTT ratio and fibrinogen had no significant impact on INR variability. Due to collinearity and low tolerance of independent variables included in the multiple regression models, we routinely employed a ridge multiple regression model which compromises the minimal number of independent variables with the maximal overall determination coefficient. The best-fitted two-component model included FII and FVII activities and explained 90% of INR variability (compared to 93% in the 5-component model including all vitamin K-dependent proteins). Neither the presence of accompanying diseases nor the use of OAT nor any other medication (acetylsalicylic acid, statins, steroids, thyroxin) biased significantly these associations. CONCLUSION: Among various vitamin K-dependent plasma proteins, the coagulation factors II, VII and X showed the most significant associations with INR. Of these variables, the two-component model, including factors II and VII, deserves special attention, as it largely explains the overall variability observed in INR estimates. The statistical power of this model is validated on virtue of the estimation that the revealed associations are rather universal and remain essentially unbiased by other compounding variables, including clinical status and medical treatment. Further, much broader population studies are needed to verify clinical usefulness of methods alternate or compounding to INR monitoring of OAT.
BioMed Central
2003-11-30
/pmc/articles/PMC317378/
/pubmed/14969588
http://dx.doi.org/10.1186/1477-9560-1-7
Text
en
Copyright © 2003 Watala et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:3314202004-02-07thrombjpmc-open
The antithrombotic profile of aspirin. Aspirin resistance, or simply failure?
Altman, Raul
Luciardi, Héctor L
Muntaner, Juan
Herrera, Ramón N
Thromb J
Review
BioMed Central
2004-01-14
/pmc/articles/PMC331420/
/pubmed/14723795
http://dx.doi.org/10.1186/1477-9560-2-1
Text
en
Copyright © 2004 Altman et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:4064202004-05-12thrombjpmc-open
Decreased soluble cell adhesion molecules after tirofiban infusion in patients with unstable angina pectoris
Ercan, Ertugrul
Bozdemir, Huseyin
Tengiz, Istemihan
Sekuri, Cevad
Aliyev, Emil
Akilli, Azem
Akin, Mustafa
Thromb J
Original Clinical Investigation
AIM: The inflammatory response, initiated by neutrophil and monocyte adhesion to endothelial cells, is important in the pathogenesis of acute coronary syndromes. Platelets play an important role in inflammatory process by interacting with monocytes and neutrophils. In this study, we investigated the effect of tirofiban on the levels of cell adhesion molecules (soluble intercellular adhesion molecule-1, sICAM-1, and vascular cell adhesion molecule-1, sVCAM-1) in patients with unstable angina pectoris (AP). METHODS: Thirty-five patients with unstable AP (Group I), ten patients with stable AP (Group II) and ten subjects who had angiographycally normal coronary arteries (Group III) were included the study. Group I was divided into two subgroups for the specific treatment regimens: Group IA (n = 15) received tirofiban and Group IB (n = 20) did not. Blood samples for investigating the cell adhesion molecules were drawn at zero time (baseline; 0 h) in all patients and at 72 h in Group I. RESULTS: The baseline levels of sICAM-1 and sVCAM-1 were higher in Group I than in Groups II and III. They were higher in Group IA than in Group IB. However, the sICAM-1 and sVCAM-1 levels decreased significantly in Group IA after tirofiban infusion. In contrast, these levels remained unchanged or were increased above the baseline value in Group IB at 72 h. CONCLUSION: The levels of cell adhesion molecules in patients with unstable AP decreased significantly after tirofiban infusion. Inhibition of platelet function by specific glycoprotein IIb/IIIa antagonists may decrease platelet-mediated inflammation and the ischemic end-point.
BioMed Central
2004-04-01
/pmc/articles/PMC406420/
/pubmed/15059285
http://dx.doi.org/10.1186/1477-9560-2-4
Text
en
Copyright © 2004 Ercan et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:4155592004-05-21thrombjpmc-open
Cardiac thrombi in a patient with protein-C and S deficiencies: a case report
Ercan, Ertugrul
Tengiz, Istemihan
Sekuri, Cevad
Sahin, Fahri
Aliyev, Emil
Akin, Mustafa
Acıkel, Unal
Thromb J
Case Report
BioMed Central
2004-03-28
/pmc/articles/PMC415559/
/pubmed/15046637
http://dx.doi.org/10.1186/1477-9560-2-2
Text
en
Copyright © 2004 Ercan et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:4164912004-05-23thrombjpmc-open
Use of venous thromboprophylaxis and adherence to guideline recommendations: a cross-sectional study
Vallano, Antonio
Arnau, Josep Maria
Miralda, Gaietà Permanyer
Pérez-Bartolí, Jaume
Thromb J
Original Clinical Investigation
BACKGROUND: Consensus Conferences and Guidelines for deep vein thrombosis prophylaxis have been published, which recommend the use of prophylactic heparins in patients with risk of venous thromboembolism (VTE). The aim of this study was the assessment of the prophylaxis of VTE and the adherence to accepted guideline recommendations throughout the hospital. METHODS: A cross-sectional study was carried out in a teaching hospital after guidelines were implemented. Patients' risk factors of deep vein thrombosis, risk categories of patients, and prophylaxis used in different wards were recorded. Appropriate adherence to the guidelines was analysed. RESULTS: Of 397 patients, prophylaxis was used in 231 patients (58%), and low-molecular-weight heparins (LMWH) were used in 224 of them (97%). Patients with prophylaxis had a higher mean number of risk factors (SD) than those without prophylaxis [3.1 (1.4) vs 1.9 (1.4); p < 0.05)]. Prophylaxis was used in 72% and 90% of moderate and high-risk patients respectively. Appropriate adherence to all guideline recommendations was observed in 42% of patients. Adherence to guidelines was high as regards the use of prophylaxis according to patients' risk factors (78%) and the use of appropriate types of prophylaxis (99%), but was low regarding appropriate heparin dosage (47%) and preoperative dosage (37%). Appropriate prophylaxis use was higher in critical care and surgical wards than in medical wards. CONCLUSION: Prophylaxis of VTE is generally used in risk patients, but appropriate adherence to guidelines is less frequent and variable among different wards. Continuing medical education, discussion and dissemination of guidelines, and regular clinical audit are necessary to improve prophylaxis of VTE in clinical practice.
BioMed Central
2004-04-01
/pmc/articles/PMC416491/
/pubmed/15059286
http://dx.doi.org/10.1186/1477-9560-2-3
Text
en
Copyright © 2004 Vallano et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:4256002004-06-18thrombjpmc-open
Nadroparine calcium or enoxaparine in acute coronary syndrome patients suffering renal insufficiency: The nadroparin versus enoxaparin (NaVe) study design
Gurfinkel, Enrique P
Perel, Cecilia
Pombo, Gonzalo
Thromb J
Original Clinical Investigation
In the general population, mild renal impairment is associated with increases risk for coronary artery disease and stroke, suggesting that cardiovascular disease begins to develop early in the natural history of renal dysfunction. Patients with renal failure are known to be at increased risk of death following acute myocardial infarction or congestive heart failure. In such sense, anticoagulation in addition to antiplatelet inhibitor drugs became the standard of care, particularly, among high risk unstable angina patients associated with a scarce side effects. The Nadroparin calcium Versus Enoxaparin (NaVe) Study will evaluate in a head to head basis the anti Xa activity reached by nadroparine or enoxaparine, both low molecular weight heparins, in patients at high risk for ischemic episodes, and renal insufficiency to eventually be undergone to angiographic diagnosis studies, and in consequence proposing the best anticoagulant strategies for these patients before being invasively treated. Patients will be randomly assigned to one of the two groups: Group 1: thirty patients will be given with subcutaneous enoxaparine injections into the abdominal wall in a dose of 0,85 mg/kg every 12 hours for a maximum of 48 hours. A saline infusion dose will be given in between. Total number of injections: 6. Group 2:Thirty patients will be receiving subcutaneous injections into the abdominal wall in a doses of 30% less in relationship with his / her body weight every 8 hours for a maximum of 48 hours. In order to achieve the goal of the study, the antiXa activity will be measure using venous blood samples taken as follows: Group 1:*Within 3(rd )and 4 hour of the second doses of HBPM for enoxaparine.*Within 11 th and 12 th hour next to fourth doses of enoxaparine. Group 2: *Within 3(rd )and 4 th hour next to 3(rd )doses of HBPM for the nadroparine.*Within 7(th )and 8(th )hour next to 4(th )doses HBPM for the nadroparine. The primary end point is to analyze during the in-hospital stay phase the stability of the anti Xa activity within the therapeutic ranges which will be estimated between 0.5 to 1.0 IU during the first 48 hours.
BioMed Central
2004-06-08
/pmc/articles/PMC425600/
/pubmed/15186495
http://dx.doi.org/10.1186/1477-9560-2-6
Text
en
Copyright © 2004 Gurfinkel et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:4414132004-07-02thrombjpmc-open
MRI of coronary artery atherosclerosis in rabbits: Histopathology-MRI correlation and atheroma characterization
Sharma, Rakesh
Singh, Ram B
Thromb J
Original Basic Research
BACKGROUND AND OBJECTIVES: We report in vivo magnetic resonance imaging (MRI) characteristics and histopathology correlation of the thrombus formation in atherosclerosis the rabbit animal model. DESIGN AND METHODS: Atherosclerosis was induced in white male rabbits with vegetable ghee followed oxidized diet. Baseline MRI of atherosclerosis-recruited rabbits was done and later animals were used for atheroma histopathology characterization. Contiguous cross-sectional T2-weighted fast spin echo MRI images were compared by coronary histopathology. In all animals, coronary aortic wall thickening and atheroma size was measured using MRI. RESULTS: MRI images and digitized histological sections confirmed intraluminal thrombus in 6 (67%) of the 9 animals. MRI data showed correlation with the histopathology for aortic wall thickness (R(2 )= 0.82, P < 0.0001), lumen area (R(2 )= 0.88, P < 0.0001) and plaque size (R(2 )= 0.77, P < 0.0001). Optimized TE and TR parameters and multicontrast enhancement generated better MRI visibility of vulnerable plaque components. The MRI data evaluated % stenosis, plaque burden. Frequency of plaques, plaque height in aorta and coronary artery atheroma was also assessed by histology. In vivo, MRI determined the presence and size of the thrombus in this animal model of atherosclerosis and histopathology defined the plaque disruption. CONCLUSION: The combination of in vivo MRI and comparison with histopathology images of rabbit coronary thrombus may be a research tool for understanding of the pathogenesis of acute coronary plaques.
BioMed Central
2004-05-15
/pmc/articles/PMC441413/
/pubmed/15144559
http://dx.doi.org/10.1186/1477-9560-2-5
Text
en
Copyright © 2004 Sharma and Singh; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:5243632004-10-29thrombjpmc-open
Relationship between CRP and hypofibrinolysis: Is this a possible mechanism to explain the association between CRP and outcome in critically ill patients?
Zouaoui Boudjeltia, Karim
Piagnerelli, Michael
Brohée, Dany
Guillaume, Michel
Cauchie, Philippe
Vincent, Jean-Louis
Remacle, Claude
Bouckaert, Yves
Vanhaeverbeek, Michel
Thromb J
Original Clinical Investigation
BACKGROUND-: Endothelial cell dysfunction may be implicated in the development of multiple organ failure (MOF) by a number of mechanisms. Among these, altered fibrinolysis promotes fibrin deposition, which may create microvascular alterations during inflammation. Elevated concentrations of C-reactive protein (CRP), especially when these persist over time, are correlated with an increased risk of MOF and death. CRP may inhibit fibrinolysis by inducing plasminogen activator inhibitor-1 (PAI-1) release from human aortic endothelial cells. Moreover, the administration of recombinant CRP in volunteers may increase circulating PAI-1 levels. In this study, we tested the hypothesis that CRP is associated with hypofibrinolysis in intensive care patients with and without sepsis. METHODS-: We studied the association of inflammation and abnormal fibrinolysis in intensive care unit (ICU) patients with (n = 11) and without (n = 21) sepsis. The inflammatory response was assessed by serum concentration of C-reactive protein (CRP), a marker of the acute phase reaction, which increase rapidly in the inflammatory response, and the plasma fibrinolytic capacity was evaluated by the Euglobulin Clot Lysis Time (ECLT), determined by a new semi-automatic method. RESULTS-: ECLT was significantly higher in septic than non-septic patients (1104 ± 439 vs 665 ± 275 min; p = 0.002) and was significantly correlated with CRP concentration (R(2 )= 0.45; p < 0.001). In a multivariate analysis, CRP was the strongest predictor of ECLT (R(2 )= 0.51, F = 25.6, p < 0.001). In addition, the overall ICU length of stay was significantly correlated with CRP (R(2 )= 0.264, p = 0.003) and ECLT (R(2 )= 0.259, p = 0.003). CONCLUSION-: In critically ill patients a significant correlation thus exists between plasma fibrinolytic capacity and serum CRP levels. Our data were obtained in the first 24 hours of ICU admission or of sepsis, thus, the relation between CRP and hypofibrinolysis appeared very quickly. This finding is compatible with a link between inflammation and abnormal fibrinolysis, and may explain the negative prognostic value of CRP in critically ill patients.
BioMed Central
2004-09-30
/pmc/articles/PMC524363/
/pubmed/15456513
http://dx.doi.org/10.1186/1477-9560-2-7
Text
en
Copyright © 2004 Boudjeltia et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an open-access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5267632004-11-12thrombjpmc-open
Traumatic deep vein thrombosis in a soccer player: A case study
Echlin, Paul S
Upshur, Ross EG
McKeag, Douglas B
Jayatilake, Harsha P
Thromb J
Case Report
A 42 year-old male former semi-professional soccer player sustained a right lower extremity popliteal contusion during a soccer game. He was clinically diagnosed with a possible traumatic deep vein thrombosis (DVT), and sent for confirmatory tests. A duplex doppler ultrasound was positive for DVT, and the patient was admitted to hospital for anticoagulation (unfractionated heparin, warfarin). Upon discharge from hospital the patient continued oral warfarin anticoagulation (six months), and the use of compression stockings (nine months). He followed up with his family doctor at regular intervals for serial coagulation measurements, and ultrasound examinations. The patient's only identified major thrombotic risk factor was the traumatic injury. One year after the initial deep vein thrombosis (DVT) the patient returned to contact sport, however he continued to have intermittent symptoms of right lower leg pain and right knee effusion. Athletes can develop vascular injuries in a variety of contact and non-contact sports. Trauma is one of the most common causes of lower extremity deep vein thrombosis (DVT), however athletic injuries involving lower extremity traumatic DVT are seldom reported. This diagnosis and the associated risk factors must be considered during the initial physical examination. The primary method of radiological diagnosis of lower extremity DVT is a complete bilateral duplex sonography, which can be augmented by other methods such as evidence-based risk factor analysis. Antithrombotic medication is the current standard of treatment for DVT. Acute thrombolytic treatment has demonstrated an improved therapeutic efficacy, and a decrease in post-DVT symptoms. There is a lack of scientific literature concerning the return to sport protocol following a DVT event. Athletic individuals who desire to return to sport after a DVT need to be fully informed about their treatment and risk of reoccurrence, so that appropriate decisions can be made.
BioMed Central
2004-10-14
/pmc/articles/PMC526763/
/pubmed/15485571
http://dx.doi.org/10.1186/1477-9560-2-8
Text
en
Copyright © 2004 Echlin et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an open-access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5353422004-12-10thrombjpmc-open
Platelet-derived NO slows thrombus growth on a collagen type III surface
Williams, Robert H
Nollert, Matthias U
Thromb J
Original Basic Research
Nitric oxide (NO) is a free radical that plays an important role in modulating platelet adhesion and aggregation. Platelets are a source of vascular NO, but since erythrocytes avidly scavenge NO, the functional significance of platelet-derived NO is not clear. Our purpose was to determine if NO from platelets affects platelet thrombus formation in the presence of anticoagulated whole blood in an in vitro parallel plate flow system. We studied platelet adhesion and aggregation on a collagen type III surface in the presence of physiologically relevant fluid mechanical shear stress. We found that certain receptor mediated agonists (insulin and isoproterenol) caused a concentration dependent reduction in thrombus formation at a shear rate of 1000 s(-1). This effect was mediated by NO since it was abolished in the presence of the NO inhibitor L-nitro-arginine-methyl-ester (L-NAME). As expected, at venous levels of shear rate (100 s(-1)) neither of the agonists had any effect on thrombus formation since platelet adhesion does not depend on activation at these low levels of shear. Interestingly, at a shear rate of 2000 s(-1 )the addition of L-NAME caused an increase in platelet coverage suggesting that shear, by itself, induces NO production by platelets. This is the first demonstration of shear stress causing platelets to produce an inhibitor of platelet activation. These results demonstrate that the development of a platelet thrombus is regulated in a complex way and that platelets produce functionally significant amounts of NO even in the presence of whole blood.
BioMed Central
2004-11-15
/pmc/articles/PMC535342/
/pubmed/15544706
http://dx.doi.org/10.1186/1477-9560-2-11
Text
en
Copyright © 2004 Williams and Nollert; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5355342004-12-12thrombjpmc-open
Recombinant activated factor VII (rFVIIa) as salvage treatment for intractable hemorrhage
Aggarwal, Anita
Malkovska, Vera
Catlett, Joseph P
Alcorn, Kirsten
Thromb J
Case Report
BACKGROUND: Recently, there has been an increased use of recombinant activated factor VII (rFVIIa) to promote hemostasis in various hemorrhagic conditions. The objective of this study was to determine the outcome of patients treated with rFVIIa who had intractable bleeding associated with cardiac surgery (CSP) or as a result of other causes (OBP). METHODS: The medical records of 40 consecutive patients treated with rFVIIa were retrospectively reviewed for blood product use before and after treatment. In all patients, rFVIIa was given only after all other measures to stop bleeding had failed. The number of transfused units of red cells (R), platelets (P), fresh frozen plasma (F), and cryoprecipitate (C) were determined both before and after administration of rFVIIa, and the results compared. Mortality at 4 hours and 30 days was assessed. Patients dying within 4 hours of rFVIIa administration were not evaluable for response. Patient characteristics were also assessed as risk factors for mortality. RESULTS: Twelve of 24 CSP survived for more than 4 hours. These 12 patients required an average of 17 units (U) of R, 18 U of P, 18 U of F and 15 U of C pre-treatment compared to an average of 6 U, 10 U, 9 U and 4 U of R, P, F and C respectively, post-treatment. These differences were statistically significant. For the OBP, 11 of 16 survived more than four hours. These 11 patients required an average of 10 U of R, 11 U of P, 14 U of F and 10 U of C pretreatment compared to an average of 1 U, 2 U, 2 U and 0 U of R, P, F, and C respectively, post-treatment. With the exception of C, there was a statistically significant decrease in blood product use following treatment with rFVIIa. Of the survivors in each group, 6 of 12 CSP and 2 of 11 OBP died between 3 and 30 days post-treatment from causes other than bleeding. Mortality at 30 days for CSP and OBP survivors was 50% and 18% respectively, whereas overall 30 day mortality was 75% for CSP and 44% for OBP. CONCLUSIONS: rFVIIa is effective in decreasing blood product use and promoting hemostasis in patients with intractable bleeding associated with cardiac surgery and a variety of other causes.
BioMed Central
2004-11-05
/pmc/articles/PMC535534/
/pubmed/15530167
http://dx.doi.org/10.1186/1477-9560-2-9
Text
en
Copyright © 2004 Aggarwal et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5358102004-12-17thrombjpmc-open
Thromboembolic events and haematological diseases: a case of stroke as clinical onset of a paroxysmal nocturnal haemoglobinuria
Granata, Gianluca
Izzo, Tiziana
Di Micco, Pierpaolo
Bonamassa, Barbara
Castaldo, Giampiero
Viggiano, Vito Giuseppe
Picillo, Ugo
Castaldo, Giuseppe
Niglio, Alferio
Thromb J
Case Report
Some haematological diseases are associated to an increased risk of thromboembolic events. We report a case of paroxysmal nocturnal haemoglobinuria (PNH) in which a cerebrovascular event represented the first clinical manifestation of disease. PNH is associated to thromboembolic events, generally of venous districts often involving unusual locations such as mesenteric vessels, sagittal veins, inferior vena cava and renal veins. To our knowledge arterial thrombotic episodes are rare and the involvement of arterial cerebral vessels is exceptional. Then, our case points out the importance of investigating about haematological disorders in all patients presenting with a stroke, in which the common predisposing conditions are excluded.
BioMed Central
2004-11-11
/pmc/articles/PMC535810/
/pubmed/15538949
http://dx.doi.org/10.1186/1477-9560-2-10
Text
en
Copyright © 2004 Gianluca et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5382742004-12-19thrombjpmc-open
Blood coagulation and the risk of atherothrombosis: a complex relationship
Spronk, Henri MH
van der Voort, Danielle
ten Cate, Hugo
Thromb J
Review
The principles of Virchov's triad appear to be operational in atherothrombosis or arterial thrombosis: local flow changes and particularly vacular wall damage are the main pathophysiological elements. Furthermore, alterations in arterial blood composition are also involved although the specific role and importance of blood coagulation is an ongoing matter of debate. In this review we provide support for the hypothesis that activated blood coagulation is an essential determinant of the risk of atherothrombotic complications. We distinguish two phases in atherosclerosis: In the first phase, atherosclerosis develops under influence of "classical" risk factors, i.e. both genetic and acquired forces. While fibrinogen/fibrin molecules participate in early plaque lesions, increased activity of systemic coagulation is of no major influence on the risk of arterial thrombosis, except in rare cases where a number of specific procoagulant forces collide. Despite the presence of tissue factor – factor VII complex it is unlikely that all fibrin in the atherosclerotic plaque is the direct result from local clotting activity. The dominant effect of coagulation in this phase is anticoagulant, i.e. thrombin enhances protein C activation through its binding to endothelial thrombomodulin. The second phase is characterized by advancing atherosclerosis, with greater impact of inflammation as indicated by an elevated level of plasma C-reactive protein, the result of increased production influenced by interleukin-6. Inflammation overwhelms protective anticoagulant forces, which in itself may have become less efficient due to down regulation of thrombomodulin and endothelial cell protein C receptor (EPCR) expression. In this phase, the inflammatory drive leads to recurrent induction of tissue factor and assembly of catalytic complexes on aggregated cells and on microparticles, maintaining a certain level of thrombin production and fibrin formation. In advanced atherosclerosis systemic and vascular wall driven coagulation becomes more important and elevated levels of D-dimer fragments should be interpreted as markers of this hypercoagulability.
BioMed Central
2004-12-01
/pmc/articles/PMC538274/
/pubmed/15574198
http://dx.doi.org/10.1186/1477-9560-2-12
Text
en
Copyright © 2004 Spronk et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5450512005-01-23thrombjpmc-open
The risk of hemorrhagic complications in hospital in-patients who fall while receiving antithrombotic therapy
Bond, Andrew J
Molnar, Frank J
Li, Marilyn
Mackey, Marlene
Man-Son-Hing, Malcolm
Thromb J
Original Clinical Investigation
BACKGROUND: The use of antithrombotic agents and falls are independently associated with an increased risk of hemorrhagic injury. However, few studies have delineated the risk of fall-related hemorrhagic complications in persons who are taking antithrombotic therapy. The objective of this study was to compare the rates of fall-related hemorrhagic injury in hospital in-patients who are taking and not taking antithrombotic therapy. METHODS: A 4-year retrospective chart review of consecutive patients who fell during admission to a 500-bed tertiary-care teaching hospital was conducted. Major hemorrhagic injuries including subdural hematomas and major bleeding/cuts, patients' use of antithrombotic medication (warfarin, aspirin, clopidogrel and heparin) and their anticoagulation status at the time of their fall were recorded. RESULTS: A total of 2635 falls in 1861 patients were reviewed. Approximately 10% of falls caused major hemorrhagic injury. One fall resulted in a subdural hematoma. Persons taking warfarin were less likely to suffer a fall-related major hemorrhagic injury compared with persons not taking antithrombotic therapy (warfarin, 6%; no therapy, 11%; p = 0.01). Logistic regression showed that fall-related major hemorrhagic injury was associated with female gender (odds ratio 1.6; 95% CI 1.3, 2.1), use of aspirin (odds ratio 1.4; 95% CI 1.1, 1.8) and use of clopidogrel (odds ratio 2.2; 95% CI 1.1, 4.8), but not with the use of warfarin or heparin, or the intensity of anticoagulation. CONCLUSIONS: In this study, compared with persons taking no antithrombotic therapy, those taking warfarin had lower rates of fall-related hemorrhagic injuries. The absolute rate of the development of fall-related intracranial hemorrhagic injury such as subdural hematomas was low, even in persons taking warfarin. These counter-intuitive results may be due to selection bias, and suggest that physicians are very conservative in selecting patients for warfarin therapy, choosing only those who are sufficiently healthy to be at much lower than average risk of suffering fall-related hemorrhagic injuries. This phenomenon may lead to physicians overestimating the potential for fall-related major hemorrhagic injury in persons taking antithrombotic therapy, with the possible denial of warfarin therapy to many of those who would benefit. This perception may contribute to the care gap between the number of patients who would theoretically derive overall benefit from warfarin therapy and those who are actually receiving it.
BioMed Central
2005-01-07
/pmc/articles/PMC545051/
/pubmed/15638939
http://dx.doi.org/10.1186/1477-9560-3-1
Text
en
Copyright © 2005 Bond et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5558492005-04-02thrombjpmc-open
Clotting state after cardioversion of atrial fibrillation: a haemostasis index could detect the relationship with the arrhythmia duration
Hatzinikolaou-Kotsakou, Eleni
Kartasis, Zafirios
Tziakas, Dimitrios
Stakos, Dimitrios
Hotidis, Athanasios
Chalikias, Georgios
Bourikas, Georgios
Hatseras, Dimitrios I
Thromb J
Original Clinical Investigation
BACKGROUND: Fibrin D-dimer levels have been advocated as an useful clinical marker of thrombogenesis. HYPOTHESIS: We hypothesized that i) there is a hyperclotting state after the return of atrial fibrillation to sinus rhythm, ii) the measurement of plasma D-Dimer levels might be a good screening tool of this clotting status, and iii) the duration of arrhythmia influences the haemostasis measured by plasma D-Dimer levels. METHODS: Forty-two patients with atrial fibrillation undergoing cardioversion were divided into two groups: in Group A (n = 24,14 male, 56 ± 11 years) the duration of atrial fibrillation was 72 hours or more (142.7 ± 103.8 hours), in Group B (n = 18, 10 male, 61 ± 13 years) the duration of atrial fibrillation was less than 72 hours (25 ± 16 hours). Plasma fibrin D-dimer levels were measured by enzyme immunoassay before, and 36 hours after, cardioversion. The change of plasma D-dimer levels 36 hours after cardioversion was calculated as delta-D-dimer. RESULTS: There were no significant differences in demographic, clinical, and echocardiographic data, and the success of cardioversion between the two groups. Compared to the control, the baseline D-dimer levels were significantly higher in both groups. The delta D-dimer levels were significantly higher in Group A than in Group B (p < 0.005). Furthermore, plasma D-dimer levels 36 hours after cardioversion (r = 0.52, p = 0.0016) and delta-D-dimer levels (r = 0.73, p < 0.0001) showed significant correlations with the duration of atrial fibrillation. CONCLUSION: The longer duration of the atrial fibrillation episode could lead to a more prominent cardiovascular hyperclotting state after cardioversion, and the mean changes of plasma D-Dimer levels could be used as an useful clinical marker of the clotting state after atrial systole return.
BioMed Central
2005-03-06
/pmc/articles/PMC555849/
/pubmed/15748296
http://dx.doi.org/10.1186/1477-9560-3-2
Text
en
Copyright © 2005 Hatzinikolaou-Kotsakou et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:10799552005-04-15thrombjpmc-open
A hypothesis-generating study to evaluate platelet activity in diabetics with chronic kidney disease
Brophy, Donald F
Martin, rika J
Gehr, Todd WB
Carr, Marcus E
Thromb J
Original Clinical Investigation
BACKGROUND: It is well described that diabetes mellitus is a hypercoagulable state. It is also known that patients with renal dysfunction have impaired platelet aggregation and function. It is not well described how renal dysfunction affects the hypercoagulability associated with diabetes. This post-hoc sub-group analysis compares platelet function, clot structure and thrombin generation time at baseline, and following enoxaparin exposure in three groups of subjects. METHODS: 30 total subjects were evaluated in the three groups: Group I: normal controls (n = 10), Group II: subjects with renal dysfunction but without diabetes (n = 13), and Group III: subjects with concomitant diabetes and renal dysfunction (n = 7). For each subject, platelet contractile force (PCF), clot elastic modulus (CEM) and thrombin generation time (TGT) were simultaneously measured in whole blood at baseline, and following increasing enoxaparin antifactor Xa activity exposure. The group means for each parameter were determined and compared using one-way analysis of variance, with post-hoc Tukey-Kramer test. RESULTS: At baseline, subjects in Group III (diabetics with concomitant renal dysfunction) display significantly enhanced platelet activity, as measured by PCF (p = 0.003) and CEM (p = 0.03), relative to the non-diabetic Groups I and II. Subjects in Group II (renal dysfunction without diabetes) had significantly prolonged TGT values relative to controls when the antifactor Xa activity concentration reached 0.5 (p = 0.007), 1.0 (p = 0.005) and 3.0 IU/mL (p < 0.0001), respectively. There were no differences between Group II and Group III with respect to TGT at these antifactor Xa activity concentrations. When the antifactor Xa activity concentration reached 3.0 IU/mL, Groups II and III formed significantly less rigid blood clots (CEM p = 0.003) and also trended toward reduced PCF (p = 0.06) relative to Group I. CONCLUSION: This hypothesis-generating sub-group analysis suggests that at baseline, patients with concomitant diabetes and renal dysfunction have significantly enhanced platelet activity (PCF), and form more rigid blood clots (CEM) compared to controls and subjects with renal dysfunction but no diabetes. This may suggest that the presence of renal dysfunction does not ameliorate the hypercoagulable state associated with diabetes. Secondly, it appears that subjects with renal dysfunction but without diabetes have an enhanced response to enoxaparin relative to controls.
BioMed Central
2005-03-29
/pmc/articles/PMC1079955/
/pubmed/15796773
http://dx.doi.org/10.1186/1477-9560-3-3
Text
en
Copyright © 2005 Brophy et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:10878862005-04-30thrombjpmc-open
Rates of clinically apparent heparin-induced thrombocytopenia for unfractionated heparin vs. low molecular weight heparin in non-surgical patients are low and similar
Locke, Charles FS
Dooley, John
Gerber, Jonathan
Thromb J
Review
With the growing use of low-molecular-weight heparins (LMWH) for the treatment and prevention of venous thromboembolism (VTE), it is important to provide an evidence-based comparison with unfractionated heparin (UFH) concerning rates of heparin-induced thrombocytopenia (HIT). Such comparisons are essential in clinical decision-making and cost-modeling. In this paper we review data regarding non-surgical (medical) patients. We conclude that the lack of uniform evaluation and standardized testing for HIT in the current literature precludes making a reliable estimate of the relative risk of HIT in UFH vs. LMWH in either the treatment or prevention of VTE in non-surgical patients. However, current data suggest that the risk of thrombocytopenia and HIT is low and similar for non-surgical patients who receive either LMWH or UFH.
BioMed Central
2005-04-04
/pmc/articles/PMC1087886/
/pubmed/15807892
http://dx.doi.org/10.1186/1477-9560-3-4
Text
en
Copyright © 2005 Locke et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:10878872005-04-30thrombjpmc-open
VTE Risk assessment – a prognostic Model: BATER Cohort Study of young women
Heinemann, Lothar AJ
DoMinh, Thai
Assmann, Anita
Schramm, Wolfgang
Schürmann, Rolf
Hilpert, Jan
Spannagl, Michael
Thromb J
Original Clinical Investigation
BACKGROUND: Community-based cohort studies are not available that evaluated the predictive power of both clinical and genetic risk factors for venous thromboembolism (VTE). There is, however, clinical need to forecast the likelihood of future occurrence of VTE, at least qualitatively, to support decisions about intensity of diagnostic or preventive measures. MATERIALS AND METHODS: A 10-year observation period of the Bavarian Thromboembolic Risk (BATER) study, a cohort study of 4337 women (18–55 years), was used to develop a predictive model of VTE based on clinical and genetic variables at baseline (1993). The objective was to prepare a probabilistic scheme that discriminates women with virtually no VTE risk from those at higher levels of absolute VTE risk in the foreseeable future. A multivariate analysis determined which variables at baseline were the best predictors of a future VTE event, provided a ranking according to the predictive power, and permitted to design a simple graphic scheme to assess the individual VTE risk using five predictor variables. RESULTS: Thirty-four new confirmed VTEs occurred during the observation period of over 32,000 women-years (WYs). A model was developed mainly based on clinical information (personal history of previous VTE and family history of VTE, age, BMI) and one composite genetic risk markers (combining Factor V Leiden and Prothrombin G20210A Mutation). Four levels of increasing VTE risk were arbitrarily defined to map the prevalence in the study population: No/low risk of VTE (61.3%), moderate risk (21.1%), high risk (6.0%), very high risk of future VTE (0.9%). In 10.6% of the population the risk assessment was not possible due to lacking VTE cases. The average incidence rates for VTE in these four levels were: 4.1, 12.3, 47.2, and 170.5 per 10(4 )WYs for no, moderate, high, and very high risk, respectively. CONCLUSION: Our prognostic tool – containing clinical information (and if available also genetic data) – seems to be worthwhile testing in medical practice in order to confirm or refute the positive findings of this study. Our cohort study will be continued to include more VTE cases and to increase predictive value of the model.
BioMed Central
2005-04-18
/pmc/articles/PMC1087887/
/pubmed/15836797
http://dx.doi.org/10.1186/1477-9560-3-5
Text
en
Copyright © 2005 Heinemann et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:10878882005-04-30thrombjpmc-open
Adrenal failure followed by status epilepticus and hemolytic anemia in primary antiphospholipid syndrome
Gerner, Patrick
Heldmann, Michael
Borusiak, Peter
Bures, Vladimir
Wirth, Stefan
Thromb J
Case Report
We report on a 14 year old boy who presented with the symptoms abdominal pain, fever and proteinuria. A hematoma in the region of the right pararenal space was diagnosed. Prothrombin time and activated partial thromboplastin time were prolonged, lupus anticoagulant and anticardiolipin antibodies were positive and serum cortisol was normal. Ten days after admission the boy suddenly suffered generalized seizures due to low serum sodium. As well, the patient developed hemolytic anemia, acute elevated liver enzymes, hematuria and increased proteinuria. At this time a second hemorrhage of the left adrenal gland was documented. Adrenal function tests revealed adrenal insufficiency. We suspected microthromboses in the adrenals and secondary bleeding and treated the boy with hydrocortisone, fludrocortisone and phenprocoumon. CONCLUSION: Adrenal failure is a rare complication of APS in children with only five cases reported to date. As shown in our patient, this syndrome can manifest in a diverse set of simultaneously occurring symptoms.
BioMed Central
2005-04-18
/pmc/articles/PMC1087888/
/pubmed/15836793
http://dx.doi.org/10.1186/1477-9560-3-6
Text
en
Copyright © 2005 Gerner et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:11818272005-07-30thrombjpmc-open
Comparison of incidence/risk of venous thromboembolism (VTE) among selected clinical and hereditary risk markers: A community-based cohort study
Spannagl, Michael
Heinemann, Lothar AJ
DoMinh, Thai
Assmann, Anita
Schramm, Wolfgang
Schürmann, Rolf
Thromb J
Review
BACKGROUND: Little information is available from community-based long-term VTE cohort studies to compare the absolute thrombosis risk of established clinical and genetic risk factors. MATERIALS AND METHODS: The occurrence of venous thromboembolism (VTE) was observed during a 10-year observation period in the BAvarian ThromboEmbolic Risk (BATER) study, a cohort study of 4337 women (age 18–55 years). We collected data on demographics, reproductive life, lifestyle, conditions/diseases, and particularly potential risk factors for VTE with a self-administered questionnaire. The objective was to present incidence rates of VTE and to show relative risk estimated associated with different clinical and genetic risk factors. RESULTS: 34 new, by diagnostic means confirmed VTE events occurred during the observation time of 32,656 women-years (WY). The overall incidence of VTE was 10.4 per 10(4 )WY. The incidence rates varied markedly among different risk cohorts. The highest incidence was observed in women with previous history of VTE, followed by family history of VTE. None of the measured "genetically-related risk markers" (antithrombin, protein C, FVL, prothrombin mutation, or MTHFR) showed a significant VTE risk. CONCLUSION: Most of the discussed VTE risk factors showed no significant association with the occurrence of new VTEs due to smallness of numbers. Only first-degree family history of VTE and own history of a previous VTE event depicted a significant association with future VTE. Clinical information seems to be more important to determine future VTE risk than genetically related laboratory tests.
BioMed Central
2005-07-20
/pmc/articles/PMC1181827/
/pubmed/16029515
http://dx.doi.org/10.1186/1477-9560-3-8
Text
en
Copyright © 2005 Spannagl et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:11832502005-08-06thrombjpmc-open
Review of "Thrombosis in Clinical Practice"
Altman, Raul
Thromb J
Book Review
BioMed Central
2005-07-15
/pmc/articles/PMC1183250/
/pubmed/16022732
http://dx.doi.org/10.1186/1477-9560-3-7
Text
en
Copyright © 2005 Blann et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:11928202005-08-27thrombjpmc-open
Resistance to aspirin is increased by ST-elevation myocardial infarction and correlates with adenosine diphosphate levels
Borna, Catharina
Lazarowski, Eduardo
van Heusden, Catharina
Öhlin, Hans
Erlinge, David
Thromb J
Original Clinical Investigation
BACKGROUND: To be fully activated platelets are dependent on two positive feedback loops; the formation of thromboxane A(2 )by cyclooxygenase in the platelets and the release of ADP. We wanted to evaluate the effect of aspirin on platelet function in patients with acute coronary syndromes and we hypothesized that increased levels of ADP in patients with acute coronary syndromes could contribute to aspirin resistance. METHODS: Platelet activity in 135 patients admitted for chest pain was assessed with PFA-100. An epinephrine-collagen cartridge (EPI-COLL) was used for the detection of aspirin resistance together with an ADP-collagen cartridge (ADP-COLL). ADP was measured with hplc from antecubital vein samples. Three subgroups were compared: chest pain with no sign of cardiac disease (NCD), NonST-elevation myocardial infarction (NSTEMI) and STEMI. RESULTS: Platelet activation was increased for the STEMI group compared NCD. Aspirin resistance defined as <193 sec in EPI-COLL was 9.7 % in NCD, and increased to 26.0 % (n.s.) in NSTEMI and 83.3 % (p < 0.001) in STEMI. Chronic aspirin treatment significantly reduced platelet aggregation in NCD and NSTEMI, but it had no effect in STEMI. Plasma levels of ADP were markedly increased in STEMI (905 ± 721 nmol/l, p < 0.01), but not in NSTEMI (317 ± 245), compared to NCD (334 ± 271, mean ± SD). ADP levels correlated with increased platelet activity measured with ADP-COLL (r = -0.30, p < 0.05). Aspirin resistant patients (EPI-COLL < 193 sec) had higher ADP levels compared to aspirin responders (734 ± 807 vs. 282 ± 187 nmol/l, mean ± SD, p < 0.05). CONCLUSION: Platelets are activated and aspirin resistance is more frequent in STEMI, probably due to a general activation of platelets. ADP levels are increased in STEMI and correlates with platelet activation. Increased levels of ADP could be one reason for increased platelet activity and aspirin resistance.
BioMed Central
2005-07-26
/pmc/articles/PMC1192820/
/pubmed/16045804
http://dx.doi.org/10.1186/1477-9560-3-10
Text
en
Copyright © 2005 Borna et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:11928212005-08-27thrombjpmc-open
Intracardiac thrombus in Behçet's disease: Two case reports
Hammami, Sonia
Mahjoub, Silvia
Ben-Hamda, Khaldoun
Brahem, Radhia
Gamra, Habib
Ben Farhat, Mohamed
Thromb J
Case Report
Intracardiac thrombus in Behçet's disease is an extremely rare manifestation. We report two such cases. A 20-year-old man presented with dyspnoea, cough and haemoptysis. Right heart thrombus associated with pulmonary artery aneurysm and thromboembolism was identified by helical CT and transoesophageal echocardiography. The second case was a 29-year-old male admitted for fever and chest pain. A diagnosis of right atrial thrombosis associated with pulmonary embolism and hyperhomocysteinemia was made. Due to the absence of haemodynamic compromise, medical management consisting of immunosupressive and anticoagulation therapy was adopted which resulted in complete dissolution of the thrombus with dramatic clinical improvement in both cases of clinical status. Conclusion: intracardiac thrombus is a rare complication of Behçet's disease. As shown in our patients, medical treatment should be considered as the first line.
BioMed Central
2005-07-25
/pmc/articles/PMC1192821/
/pubmed/16042810
http://dx.doi.org/10.1186/1477-9560-3-9
Text
en
Copyright © 2005 Hammami et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:12155252005-09-17thrombjpmc-open
Analysis of blood coagulation in mice: pre-analytical conditions and evaluation of a home-made assay for thrombin-antithrombin complexes
Sommeijer, Dirkje W
van Oerle, René
Reitsma, Pieter H
Timmerman, Janneke J
Meijers, Joost CM
Spronk, Henri MH
ten Cate, Hugo
Thromb J
Original Basic Research
BACKGROUND: The use of mouse models for the study of thrombotic disorders has gained increasing importance. Methods for measurement of coagulation activation in mice are, however, scarce. The primary aim of this study was to develop a specific mouse thrombin-antithrombin (TAT) ELISA for measurement of coagulation activation and to compare it with two commercially available assays for human TAT complexes. In addition, we aimed to improve methods for mouse plasma anticoagulation and preparation. METHODS AND RESULTS: First, for the measurement of TAT-complexes in plasma a mouse specific TAT-ELISA was developed using rabbit polyclonal antibodies raised against mouse thrombin and rat antithrombin, respectively. This ELISA detected an increase in TAT levels in a mouse model of endotoxemia. Two commercial human TAT ELISAs appeared to be less specific for mouse thrombin-rat antithrombin complexes. Second, to prevent clotting of mouse blood sodium citrate was either mixed with blood during collection in a syringe or was injected intravenously immediately prior to blood collection. Intravenous sodium citrate completely inhibited blood coagulation resulting in plasma with consistently low TAT levels. Sodium citrate mixed with blood during collection resulted in increased TAT levels in 4 out of 16 plasma samples. Third, heparinase was added to plasma samples after in vivo injection of different heparin doses to test its neutralizing effect. Heparinase neutralized up to a 20 U of heparin/mouse and resulted in accurate APTT and factor VIII determinations. CONCLUSION: These procedures and reagents for plasma preparation and coagulation testing will improve studies on thrombotic disorders in mice.
BioMed Central
2005-08-22
/pmc/articles/PMC1215525/
/pubmed/16115315
http://dx.doi.org/10.1186/1477-9560-3-12
Text
en
Copyright © 2005 Sommeijer et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:12248802005-09-22thrombjpmc-open
Homocysteine, MTHFR C677T gene polymorphism, folic acid and vitamin B 12 in patients with retinal vein occlusion
Ferrazzi, Paola
Di Micco, Pierpaolo
Quaglia, Ilaria
Rossi, Lisa Simona
Bellatorre, Alessandro Giacco
Gaspari, Giorgio
Rota, Lidia Luciana
Lodigiani, Corrado
Thromb J
Original Clinical Investigation
BACKGROUND: Many available data have suggested that hyperhomocysteinaemia, an established independent risk factor for thrombosis (arterial and venous), may be associated with an increased risk of retinal vein occlusion (RVO). AIM OF THE STUDY: To evaluate homocysteine metabolism in consecutive caucasian patients affected by RVO from Northern Italy. PATIENTS AND METHODS: 69 consecutive patients from Northern Italy (mean age 64.1 ± 14.6 yy) with recent RVO, were tested for plasma levels of homocysteine (tHcy: fasting and after loading with methionine), cyanocobalamine and folic acid levels (CMIA-Abbot) and looking for MTHFR C677T mutation (Light Cycler-Roche) and compared to 50 volunteers, enrolled as a control group. RESULTS: Fasting levels of tHcy were significantly higher in patients than in controls: mean value 14.7 ± 7.7 vs 10.2 ± 8 nmol/ml. Post load levels were also significantly higher: mean value 42.7 ± 23.7 vs 30.4 ± 13.3 nmol/ml; Total homocysteine increase was also evaluated (i.e. Δ-tHcy) after methionine load and was also significantly higher in patients compared to control subjects: mean Δ-tHcy 27.8 ± 21.5 vs 21.0 ± 16 nmol/ml (normal value < 25 nmol/ml). Furthermore, patients affected by RVO show low folic acid and/or vitamin B12 levels, although differences with control group did not reach statistical significance. Heterozygous and homozygous MTHFR mutation were respectively in study group 46% and 29% vs control group 56% and 4%. CONCLUSION: our data confirm that hyperhomocysteinaemia is a risk factor for RVO, and also that TT genotype of MTHFR C677T is more frequently associated with RVO: if the mutation per se is a risk factor for RVO remains an open question to be confirmed because another study from US did not reveal this aspect. Hyperomocysteinemia is modifiable risk factor for thrombotic diseases. Therefore, a screening for tHcy plasma levels in patients with recent retinal vein occlusion could allow to identify patients who might benefit from supplementation with vitamins and normalization of homocysteine levels, in fasting and after methionine load.
BioMed Central
2005-09-07
/pmc/articles/PMC1224880/
/pubmed/16144556
http://dx.doi.org/10.1186/1477-9560-3-13
Text
en
Copyright © 2005 Terrazzi et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:12369652005-09-29thrombjpmc-open
Catheter-related septic thrombophlebitis of the great central veins successfully treated with low-dose streptokinase thrombolysis and antimicrobials
Volkow, Patricia
Cornejo-Juárez, Patricia
Arizpe-Bravo, Ana Berta
García-Méndez, Jorge
Baltazares-Lipp, Enrique
Pérez-Padilla, Rogelio
Thromb J
Case Report
BACKGROUND: Septic thrombophlebitis is an iatrogenic life-threatening disease associated with use of central venous devices and intravenous (IV) therapy. In cancer patients receiving chemotherapy, vein resection or surgical thrombectomy in large central venous lines is time-consuming, can delay administration of chemotherapy, and therefore can compromise tumor control. Experience with thrombolysis has been published for catheter-related thrombosis but for septic thrombosis, this experience is scarce. RESULTS: We describe three patients with cancer and septic thrombophlebitis of central veins caused by Staphylococcus aureus treated with catheter removal, thrombolysis, and intravenous (IV) antibiotics. In our reported cases, an initial bolus of 250,000 international units (IU) of streptokinase administered during the first h followed by an infusion of 20,000–40,000 IU/h for 24–36 h through a proximal peripheral vein was sufficient to dissolve the thrombus. After thrombolyisis and parenteral antibiotic for 4–6 weeks the septic thrombosis due to Staphylococcus aureus solved in all cases. No surgical procedure was needed, and potential placement of a catheter in the same vein was permitted. CONCLUSION: Thrombolysis with streptokinase solved symptoms, cured infection, prevented embolus, and in all cases achieved complete thrombus lysis, avoiding permanent central-vein occlusion.
BioMed Central
2005-08-22
/pmc/articles/PMC1236965/
/pubmed/16111500
http://dx.doi.org/10.1186/1477-9560-3-11
Text
en
Copyright © 2005 Volkow et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:12627842005-10-23thrombjpmc-open
Heparin-induced thrombocytopenia: an update
Franchini, Massimo
Thromb J
Review
Heparin-induced thrombocytopenia (HIT) is the most important and most frequent drug-induced, immune-mediated type of thrombocytopenia. It is associated with significant morbidity and mortality if unrecognized. In this review, we briefly discuss the main features of heparin-induced thrombocytopenia, particularly analyzing the most recent advances in the pathophysiology, diagnosis and treatment of this syndrome.
BioMed Central
2005-10-04
/pmc/articles/PMC1262784/
/pubmed/16202170
http://dx.doi.org/10.1186/1477-9560-3-14
Text
en
Copyright © 2005 Franchini; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:12664012005-10-27thrombjpmc-open
Elevated levels of procoagulant microparticles in a patient with myocardial infarction, antiphospholipid antibodies and multifocal cardiac thrombosis
Morel, O
Jesel, L
Freyssinet, JM
Toti, F
Thromb J
Case Report
Circulating procoagulant microparticles (MP) are pathogenic markers of enhanced coagulability associated to a variety of disorders and released from stimulated vascular cells. When derived from endothelial cells, MP were found characteristic of thrombotic propensity in primary antiphospholipid syndrome (APS). The prothrombotic status of a patient with antiphospholipid antibodies (APL), a past history of mesenteric vein thrombosis and presenting myocardial infarction and extensive intracardiac thrombosis was examined by measurement of circulating procoagulant MP. MP of platelet and endothelial origins were highly elevated with respect to values detectable in patients with myocardial infarction and no history of APS (6- and 3-fold elevation, respectively) or in healthy volunteers (13- and 25-fold elevation, respectively). In this particular patient, with moderate APL titer, a drastic release of procoagulant MP could have contributed to thrombus growth and the development of extensive intracardiac thrombosis.
BioMed Central
2005-10-11
/pmc/articles/PMC1266401/
/pubmed/16219103
http://dx.doi.org/10.1186/1477-9560-3-15
Text
en
Copyright © 2005 Morel et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:12914092005-11-26thrombjpmc-open
Towards a standardization of thrombin generation assessment: The influence of tissue factor, platelets and phospholipids concentration on the normal values of Thrombogram-Thrombinoscope assay
Gerotziafas, Grigoris T
Depasse, François
Busson, Joël
Leflem, Lena
Elalamy, Ismail
Samama, Meyer M
Thromb J
Original Basic Research
BACKGROUND: Thrombin generation assay was developed several years ago to mimic physiological coagulation mechanisms but it had important limitations. Thrombogram-Thrombinoscope assay using a fluorogenic substrate, allows obtaining thrombin generation curves in non-defibrinated platelet rich plasma (PRP) in a fully automated manner. METHODS: We standardised the methodology of Thrombogram-Thrombinoscope and we evaluated the precision of thrombin generation parameters (lag-time, maximum concentration of thrombin [Cmax], time required to reach Cmax [Tmax] and endogenous thrombin potential ETP) using different concentrations of recombinant human tissue factor, platelets or phospholipids. Normal values of thrombin generation assay were established in optimal experimental conditions. RESULTS: In the presence of low TF concentrations (final dilution of thromboplastin in plasma: 1/1000–1/2000) the Thrombogram assay showed intra-assay and inter-assay coefficients of variation lower than 9%. Thrombin generation parameters showed an important inter-individual variability and the coefficients of variation ranged from 18% to 50%. In PRP the lag-time, Cmax and Tmax but not the ETP, were influenced by TF concentration. Thrombin generation parameters were not influenced by variations of platelet concentration from 50 × 10(9)/l to 400 × 10(9)/l. The addition of synthetic procoagulant phospholipids in PPP strongly influenced all the parameters of thrombogram. For all the parameters of thrombogram a threshold effect was observed in the presence of phspholipid concentrations equal or higher to 4 μM. In frozen-thawed PRP the lag-time and the Tmax were significantly reduced and the Cmax was increased compared to the fresh PRP, but the ETP, the intra assay and the inter-assay coefficients of variation were similar in both test-systems. CONCLUSION: Thrombogram-Thrombinoscope assay performed in fresh or in frozen-thawed PRP has an acceptable precision, with low inter-assay and intra-assay coefficient of variations. The concentration of TF is determinant for the normal values of the studied parameters of thrombin generation. When the assay is performed in PPP, thrombin generation parameters are influenced by the concentration of procoagulant synthetic phospholipids. The optimal experimental conditions were obtained in the presence of 1/1000 final dilution of thromboplastin, a platelet count higher than 50 × 10(9)/l and a synthetic phospholipid concentration higher than 4 μM.
BioMed Central
2005-10-26
/pmc/articles/PMC1291409/
/pubmed/16250908
http://dx.doi.org/10.1186/1477-9560-3-16
Text
en
Copyright © 2005 Gerotziafas et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:13088692005-12-08thrombjpmc-open
Increased PAI-1 plasma levels and risk of death from dengue: no association with the 4G/5G promoter polymorphism
Mairuhu, ATA
Setiati, TE
Koraka, P
Hack, CE
Leyte, A
Faradz, SMH
ten Cate, H
Brandjes, DPM
Osterhaus, ADME
Reitsma, PH
van Gorp, ECM
Thromb J
Original Clinical Investigation
BACKGROUND: Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue. METHODS: A total of 194 patients admitted to the Dr. Kariadi Hospital in Semarang, Indonesia, with clinical suspected severe dengue virus infection were enrolled. Blood samples were obtained on day of admission, days 1, 2 and 7 after admission and at a 1-month follow-up visit. Plasma concentrations of PAI-1 were measured using a sandwich ELISA kit. The PAI-1 4G/5G polymorphism was typed by allele-specific PCR analysis. RESULTS: Concentrations of PAI-1 on admission and peak values of PAI-1 during admission were higher than the values measured in healthy controls. Survival was significantly worse in patients with PAI-1 concentrations in the highest tertile (at admission: OR 4.7 [95% CI 0.9–23.8], peak value during admission: OR 6.3 [95%CI 1.3–30.8]). No association was found between the PAI-1 4G/5G polymorphism, and PAI-1 plasma concentrations, dengue disease severity and mortality from dengue. CONCLUSION: These data suggest that the 4G/5G polymorphism has no significant influence on PAI-1 concentrations in dengue virus infected patients and is not associated with the risk of death from dengue. Other factors contributing to the variability of PAI-1 plasma concentrations in patients with dengue need to be explored.
BioMed Central
2005-11-07
/pmc/articles/PMC1308869/
/pubmed/16274483
http://dx.doi.org/10.1186/1477-9560-3-17
Text
en
Copyright © 2005 Mairuhu et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:13105152005-12-10thrombjpmc-open
Intermittent pneumatic compression for prevention of pulmonary thromboembolism after gynecologic surgery
Suzuki, Nao
Kataoka, Fumio
Higashiguchi, Atsushi
Hirao, Takeshi
Ezawa, Sachiko
Nomura, Hiroyuki
Tomita, Akiyo
Susumu, Nobuyuki
Aoki, Daisuke
Thromb J
Original Clinical Investigation
BACKGROUND: To investigate the incidence of pulmonary embolism and risk factors for this condition after obstetric and gynecologic surgery, as well as the efficacy of intermittent pneumatic compression. METHODS: A total of 6,218 patients operated at Keio University Hospital excluding obstetric or infertility-related surgery and uterine cervical conization were evaluated retrospectively to determine the preventive effect of intermittent pneumatic compression on postoperative pulmonary embolism. RESULTS: Pulmonary embolism occurred in 42 patients (0.68%). Multivariate analysis showed that malignancy, blood transfusion, and a body mass index ≥25 kg/m(2 )or ≥28 kg/m(2 )were independent risk factors for postoperative pulmonary embolism. A significantly lower incidence of pulmonary embolism occurred in patients receiving pneumatic compression postoperatively versus those without it. Among gynecologic malignancies, endometrial cancer was a significant risk factor for pulmonary embolism. CONCLUSION: Preventive measures, including intermittent pneumatic compression, should be taken to avoid postoperative pulmonary thromboembolism in the gynecology field.
BioMed Central
2005-11-19
/pmc/articles/PMC1310515/
/pubmed/16297244
http://dx.doi.org/10.1186/1477-9560-3-18
Text
en
Copyright © 2005 Suzuki et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:13153472005-12-16thrombjpmc-open
Large mobile thrombus in non-atherosclerotic thoracic aorta as the source of peripheral arterial embolism
Malyar, Nasser M
Janosi, Rolf A
Brkovic, Zoran
Erbel, Raimund
Thromb J
Case Report
The presence of thrombi in the atherosclerotic and/or aneurysmatic aorta with peripheral arterial embolism is a common scenario. Thrombus formation in a morphologically normal aorta, however, is a rare event. A 50 years old woman was admitted to the mergency department for pain, coldness, and anesthesia in the the left foot. She had a 25 years history of cigarette smoking, a history of postmenopausal hormone replacement therapy (HRT), hypercholesterolemia and hyperfibrinogenemia. An extensive serologic survey for hypercoagulability, including antiphospholipid antibodies, and vasculitis disorders was negative. Transesophageal echocardiography revealed a large, pedunculated and hypermobile thrombus attached to the aortic wall 5 cm distal of the left subclavian artery. The patient was admitted to the surgery department, where a 15 cm long fresh, parietal thrombus could be removed from the aorta showing no macroscopic wall lesions or any other morphologic abnormalities. This case report demonstrates the possibility of evolving a large, pedunculated thrombus in a morphologically intact aorta in a postmenopausal woman with thrombogenic conditions such as hyperfibrinogenemia, hypercholesterolemia, smoking and HRT. For these patients, profiling the individual risk and weighing the benefits against the potential risks is warranted before prescribing HRT.
BioMed Central
2005-11-29
/pmc/articles/PMC1315347/
/pubmed/16316468
http://dx.doi.org/10.1186/1477-9560-3-19
Text
en
Copyright © 2005 Malyar et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:13250442006-01-05thrombjpmc-open
Anticoagulant treatment at a specialized outpatient anticoagulant therapy unit, a descriptive study
Ekblom, Kim
Hultdin, Johan
Carlberg, Bo
Strand, Tage
Thromb J
Original Clinical Investigation
BACKGROUND: The indications for continuous oral anticoagulant treatment, the target interval and the procedures for withdrawing treatment have changed in the last 10 years. METHODS: Patients on continuous oral anticoagulant treatment at the Outpatient Anticoagulant Clinic at Umeå University Hospital in 2002 were included in a descriptive study (n = 900). 263 of those had a mechanical heart valve prosthesis. Only patient records for patients with other indications than mechanical heart valve prosthesis were examined. 582 of those records were found. In the 55 remaining patients some clinical information was retrieved from the computerised warfarin dosage database. These latter, more unsure clinical data, are presented separately. Anticoagulant treatment was discontinued if lack of proper indication or presence of too high risk for hemorrhagic complications were found. RESULTS: The prevalence of continuous oral anticoagulant treatment in the uptake area was 0.65%. The most common target interval was INR 2.1–3.0, but patients with a mechanical heart valve prosthesis were often treated more aggressively, i.e. with a higher INR target interval. Of the patients on continuous treatment, 26.6% of the INR values were outside 2.0–3.0. The most common reasons for oral anticoagulant treatment were atrial fibrillation or mechanical heart valve prosthesis, in contrast to earlier findings in studies of our population in 1987 and 1990. We found 90 patients (10.0%) without proper indication for oral anticoagulant treatment or too high risk, and their treatment was discontinued. CONCLUSION: In patients on oral anticoagulant therapy, re-evaluation of indications and risks resulted in a substantial number of treatment withdrawals. There have been major changes in treatment indications during the last decade, possibly due to rapid development of knowledge in the field of thrombosis risk factors. Treatment should be re-considered once a year.
BioMed Central
2005-12-08
/pmc/articles/PMC1325044/
/pubmed/16336670
http://dx.doi.org/10.1186/1477-9560-3-20
Text
en
Copyright © 2005 Ekblom et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:13252682006-01-07thrombjpmc-open
Socio economic crisis and mortality. Epidemiological testimony of the financial collapse of Argentina
Gurfinkel, Enrique P
Bozovich, Gerardo E
Dabbous, Omar
Mautner, Branco
Anderson, Frederick
Thromb J
Original Clinical Investigation
BACKGROUND: Natural disasters, war, and terrorist attacks, have been linked to cardiac mortality. We sought to investigate whether a major financial crisis may impact on the medical management and outcomes of acute coronary syndromes. METHODS: We analyzed the Argentine cohort of the international multicenter Global Registry of Acute Coronary Events (GRACE). The primary objective was to estimate if there was an association between the financial crisis period (April 1999 to December 2002) and in- hospital cardiovascular mortality, with the post-crisis period (January 2003 to September 2004) as the referent. Each period was defined according to the evolution of the Gross Domestic Product. We investigated the demographic characteristics, diagnostic and therapeutic procedures, morbidity and mortality. RESULTS: We analyzed data from 3220 patients, 2246 (69.8%) patients in the crisis period and 974 (30.2%) in the post-crisis frame. The distribution of demographic and clinical baseline characteristics were not significantly different between both periods. During the crisis period the incidence of in-hospital myocardial infarction was higher (6.9% Vs 2.9%; p value < 0.0001), as well as congestive heart failure (16% Vs 11%; p value < 0.0001). Time to intervention with angioplasty was longer during the crisis, especially among public sites (median 190 min Vs 27 min). The incidence proportion of mortality during hospitalization was 6.2% Vs 5.1% after crisis. The crude OR for mortality was 1.2 (95% C.I. 0.87, 1.7). The odds for mortality were higher among private institutions {1.9 (95% C.I. 0.9, 3.8)} than for public centers {1.2 (95% C.I. 0.83, 1.79)}. We did not observe a significant interaction between type of hospital and crisis. CONCLUSION: Our findings suggest that the financial crisis may have had a negative impact on cardiovascular mortality during hospitalization, and higher incidence of medical complications.
BioMed Central
2005-12-13
/pmc/articles/PMC1325268/
/pubmed/16351728
http://dx.doi.org/10.1186/1477-9560-3-22
Text
en
Copyright © 2005 Gurfinkel et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:13435902006-01-22thrombjpmc-open
Systemic coagulation parameters in mice after treatment with vascular targeting agents
Unruh, Maike
Grunow, Andrea
Gottstein, Claudia
Thromb J
Original Basic Research
BACKGROUND: Vascular targeting of malignant tumors has become a clinically validated new treatment approach with clear patient benefit. However clinical studies have also revealed that some types of vascular targeting agents (VTAs) are prone to coagulation system side effects. It is therefore essential to predetermine coagulation parameters in preclinical studies. As of to date, this has rarely been done, predominantly due to technical issues. The goal of this study was to establish and apply a standardized process, whereby systemic coagulation activation can be routinely measured in mice. RESULTS: We have evaluated a number of sampling techniques and coagulation tests regarding their suitability for this purpose. We were able to adapt two assays measuring soluble fibrin, a marker for a prethrombotic status. Thus, soluble fibrin could be measured for the first time in mice. All assays were validated in a positive control model for systemic coagulation activation, i.e. lipopolysaccharide-induced endotoxemia. Based on our results, we selected a panel of coagulation tests, which are both feasable and informative for preclinical testing of VTAs: soluble fibrin, thrombin-antithrombin complexes, free antithrombin III, white blood cell counts and platelet counts. The effect of tumor transplants on coagulation parameters was evaluated using this panel. We then applied this set of assays in treatment studies with a VTA developed in our laboratory to investigate a potential systemic coagulation activation. CONCLUSION: We have established a standardized panel of assays that can be used to test murine blood samples for coagulation activation in preclinical studies. All tests are feasible to perform in any research laboratory without specialized equipment. In addition, this is the first report to measure soluble fibrin, an early marker of systemic coagulation activation, in mice. The panel was applied on tumor bearing mice and mice treated with a VTA. We suggest its general application for coagulation activation analyses in mice.
BioMed Central
2005-12-10
/pmc/articles/PMC1343590/
/pubmed/16336690
http://dx.doi.org/10.1186/1477-9560-3-21
Text
en
Copyright © 2005 Unruh et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:13523462006-01-28thrombjpmc-open
Plasma D-dimer concentration in patients with systemic sclerosis
Lippi, Giuseppe
Volpe, Alessandro
Caramaschi, Paola
Salvagno, Gian Luca
Montagnana, Martina
Guidi, Gian Cesare
Thromb J
Original Clinical Investigation
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disorder of the connective tissue characterized by widespread vascular lesions and fibrosis. Little is known so far on the activation of the hemostatic and fibrinolytic systems in SSc, and most preliminary evidences are discordant. METHODS: To verify whether SSc patients might display a prothrombotic condition, plasma D-dimer was assessed in 28 consecutive SSc patients and in 33 control subjects, matched for age, sex and environmental habit. RESULTS AND DISCUSSION: When compared to healthy controls, geometric mean and 95% confidence interval (IC95%) of plasma D-dimer were significantly increased in SSc patients (362 ng/mL, IC 95%: 361–363 ng/mL vs 229 ng/mL, IC95%: 228–231 ng/mL, p = 0.005). After stratifying SSc patients according to disease subset, no significant differences were observed between those with limited cutaneous pattern and controls, whereas patients with diffuse cutaneous pattern displayed substantially increased values. No correlation was found between plasma D-dimer concentration and age, sex, autoantibody pattern, serum creatinine, erythrosedimentation rate, nailfold videocapillaroscopic pattern and pulmonary involvement. CONCLUSION: We demonstrated that SSc patients with diffuse subset are characterized by increased plasma D-dimer values, reflecting a potential activation of both the hemostatic and fibrinolytic cascades, which might finally predispose these patients to thrombotic complications.
BioMed Central
2006-01-18
/pmc/articles/PMC1352346/
/pubmed/16420700
http://dx.doi.org/10.1186/1477-9560-4-2
Text
en
Copyright © 2006 Lippi et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:13689672006-02-16thrombjpmc-open
Detection and quantification of lupus anticoagulants in plasma from heparin treated patients, using addition of polybrene
Jacobsen, Eva M
Trettenes, Elin J
Wisløff, Finn
Abildgaard, Ulrich
Thromb J
Original Basic Research
BACKGROUND: Lupus anticoagulants prolong clotting times in phospholipid-dependent coagulation tests. Lupus Ratio assays are integrated tests for lupus anticoagulants that may be based on APTT, RVVT or dPT clotting times. If a patient is being treated with unfractionated heparin, however, the heparin prolong clotting times and the diagnosis of lupus anticoagulant is invalidated. Commercial assays may have heparin neutralising agents added to their reagents. However, the type and efficacy of the heparin neutralisation is often not documented. We wanted to test the influence and efficacy of heparin neutralisers in the Lupus Ratio assay. METHODS: Several heparin neutralisers were tested, and polybrene was chosen for further testing. Unfractionated heparin and/or polybrene were added to normal plasma and to plasma from patients with or without lupus anticoagulant and clotting times compared before and after the additions. Lupus anticoagulant-positive patients were given 5000 IU i.v. of unfractionated heparin and plasma was collected just before and five minutes after the injection. Lupus Ratios were calculated after polybrene was added to the postinjection samples. RESULTS: The Lupus Ratio became slightly lower when polybrene was added to plasma without heparin. Plasma heparinised in vitro and plasma from patients that had received heparin, both had Lupus Ratios nearly identical to the Lupus Ratios calculated before any additions. CONCLUSION: By addition of polybrene to a final concentration of 7.9 μg/ml in test plasma, Lupus Ratio may be determined in lupus anticoagulant-negative as well as positive plasmas irrespective of the presence of heparin 0.0 – 1.3 U/ml.
BioMed Central
2006-01-25
/pmc/articles/PMC1368967/
/pubmed/16436199
http://dx.doi.org/10.1186/1477-9560-4-3
Text
en
Copyright © 2006 Jacobsen et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:13736082006-02-18thrombjpmc-open
Ineffective off-label use of recombinant activated factor VII in a case of bone-marrow transplantation-related gastrointestinal bleeding
Eller, P
Pechlaner, C
Wiedermann, CJ
Thromb J
Case Report
BACKGROUND: For patients with a normal coagulation system, who experience serious bleeding, sound evidence for recombinant activated factor VII (rFVIIa) as an effective haemostatic agent is only scarcely available so far from controlled clinical trials. In systematic reviews on the clinical use of rFVIIa, treatment failures were only rarely reported. CASE PRESENTATION: We present a 45-year old, Caucasian male with persistent intestinal bleeding due to enterocolitis associated with cytomegalovirus infection and acute graft-versus-host-disease. He had received allogeneic peripheral blood stem cell transplantation from an unrelated HLA-identical donor because of chronic myelogenous leukaemia diagnosed two years earlier. Bleeding started at day 18 after transplantation with bloody diarrhea, which was treated with multiple transfusions of fresh frozen plasma, platelet, and red blood cell concentrates, and continued relentlessly, despite all efforts, including continued transfusions, high-dose prednisolone, broad antibiotic and antiviral coverage, and tranexamic acid. Recombinant FVIIa was started at boluses of 90–120 μg/kg every 4–8 hours. Despite more than 10 doses, recurrent severe bleeding progressed to refractory shock, multiorgan failure and death. CONCLUSIONS: Little can be concluded from single case reports of clinical improvement, because publication bias in favour of positive effects is likely. Our case suggests that rFVIIa is not a panacea, in particular for severe bleeding after bone-marrow transplantation. As long as rigorous, controlled studies or comprehensive registries are lacking, conventional interventions remain the standard of care in non-haemophilic patients with severe bleeding.
BioMed Central
2006-01-18
/pmc/articles/PMC1373608/
/pubmed/16420687
http://dx.doi.org/10.1186/1477-9560-4-1
Text
en
Copyright © 2006 Eller et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:14022632006-03-16thrombjpmc-open
Recent acquisitions in the pathophysiology, diagnosis and treatment of disseminated intravascular coagulation
Franchini, Massimo
Lippi, Giuseppe
Manzato, Franco
Thromb J
Review
Disseminated intravascular coagulation (DIC) is a disorder characterized by both acute generalized, widespread activation of coagulation, which results in thrombotic complications due to the intravascular formation of fibrin, and diffuse hemorrhages, due to the consumption of platelets and coagulation factors. Systemic activation of coagulation may occur in a variety of disorders, including sepsis, severe infections, malignancies, obstetric or vascular disorders, and severe toxic or immunological reactions. In this review, we briefly report the present knowledge about the pathophysiology and diagnosis of DIC. Particular attention is also given to the current standard and experimental therapies of overt DIC.
BioMed Central
2006-02-21
/pmc/articles/PMC1402263/
/pubmed/16504043
http://dx.doi.org/10.1186/1477-9560-4-4
Text
en
Copyright © 2006 Franchini et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:14591082006-05-11thrombjpmc-open
Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis
Altman, Raul
Scazziota, Alejandra Silvia
Herrera, Maria de Lourdes
Gonzalez, Claudio
Thromb J
Original Basic Research
BACKGROUND: Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG) in vitro. METHODS AND RESULTS: TG was quantified by time parameters: lag time (LT) and time to peak (TTP), and by amount of TG: peak of TG (PTG) and area under thrombin formation curve after 35 minutes (AUC→(35min)) in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT) technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA), ADP, and collagen (Col). In addition, the effects of recombinant activated FVII (rFVIIa) alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p < 0.05) and PTG and AUC→(35min )were significantly increased (p < 0.05) in platelet rich plasma activated with AA, ADP, Col, and rFVIIa compared to non-activated platelet rich plasma from normal subjects (p = 0.01). Furthermore platelet rich plasma activated by the combined effects of rFVIIa plus AA, ADP or Col had significantly reduced LT and TTP and increased AUC→(35min )(but not PTG) when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. CONCLUSION: Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis.
BioMed Central
2006-04-21
/pmc/articles/PMC1459108/
/pubmed/16630353
http://dx.doi.org/10.1186/1477-9560-4-5
Text
en
Copyright © 2006 Altman et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:15264162006-08-03thrombjpmc-open
Oral heparin: status review
Arbit, Ehud
Goldberg, Michael
Gomez-Orellana, Isabel
Majuru, Shingai
Thromb J
Review
Unfractionated heparin and low molecular weight heparin are the most commonly used antithrombotic and thromboprophylactic agents in hospital practice. Extended out-of-hospital treatment is inconvenient in that these agents must be administered parenterally. Current research is directed at development of a safe and effective oral antithrombotic agent as an alternative for the effective, yet difficult to use vitamin K antagonists. A novel drug delivery technology that facilitates transport of drugs across the gastrointestinal epithelium has been harnessed to develop an oral dosage form of unfractionated heparin. Combining unfractionated heparin with the carrier molecule, sodium N-(8 [2-hydroxybenzoyl]amino) caprylate, or SNAC has markedly increased the gastrointestinal absorption of this drug. Preclinical and clinical studies to-date suggests that oral heparin-SNAC can confer a clinical efficacious effect; further confirmation is sought in planned clinical trials.
BioMed Central
2006-05-10
/pmc/articles/PMC1526416/
/pubmed/16686945
http://dx.doi.org/10.1186/1477-9560-4-6
Text
en
Copyright © 2006 Arbit et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:15338042006-08-08thrombjpmc-open
Antithrombin III (AT) and recombinant tissue plasminogen activator (R-TPA) used singly and in combination versus supportive care for treatment of endotoxin-induced disseminated intravascular coagulation (DIC) in the neonatal pig
Davis-Jackson, Rachel
Correa, Hernan
Horswell, Ronald
Sadowska-Krowicka, Halina
McDonough, Kathleen
Debata, Chittaranjan
Gardner, Renee'
Penn, Duna
Thromb J
Original Basic Research
BACKGROUND: Disseminated intravascular coagulation (DIC) is a pathological disturbance of the complex balance between coagulation and anticoagulation that is precipitated by vascular injury, acidosis, endotoxin release and/or sepsis and characterized by severe bleeding and excessive clotting. The innately low levels of coagulation factors found in newborn infants place them at extremely high risk for DIC. Anecdotal reports suggest that either anticoagulant or fibrinolytic therapy may alleviate some of the manifestations of DIC. To test the hypothesis that replacement of both anticoagulants and fibrinolytics may improve survival and outcome better than either single agent or supportive care alone, we utilized a neonatal piglet model of endotoxin-induced DIC. METHODS: DIC was induced in twenty-seven neonatal pigs (7 to 14 days of age) by intravenous administration of E. coli endotoxin (800 μg/kg over 30 min). The piglets were divided into 4 groups on the basis of treatment protocol [A: supportive care alone; B: Antithrombin III (AT, 50 μg/kg bolus, 25 μg/kg per hr continuous infusion) and supportive care; C: Recombinant Tissue Plasminogen Activator (R-TPA, 25 μg/kg per hr continuous infusion) and supportive care; D: AT, R-TPA and supportive care] and monitored for 3 primary outcome parameters (survival time, macroscopic and microscopic organ involvement) and 4 secondary outcome parameters (hematocrit; platelet count; fibrinogen level; and antithrombin III level). RESULTS: Compared with supportive care alone, combination therapy with AT and R-TPA resulted in a significant improvement of survival time, hematocrit, AT level, macroscopic and microscopic organ involvement, p < 0.05. Compared with supportive care alone, R-TPA alone significantly reduced macroscopic organ involvement and AT alone increased AT levels. CONCLUSION: The findings suggest that combining AT, R-TPA and supportive care may prove more advantageous in treating the clinical manifestations of DIC in this neonatal pig model than either single modality or supportive care alone.
BioMed Central
2006-05-18
/pmc/articles/PMC1533804/
/pubmed/16707024
http://dx.doi.org/10.1186/1477-9560-4-7
Text
en
Copyright © 2006 Davis-Jackson et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:15404202006-08-12thrombjpmc-open
Haemostasis, inflammation and renal function following exercise in patients with intermittent claudication on statin and aspirin therapy
Collins, Patrick
Ford, Isobel
Croal, Bernard
Ball, Derek
Greaves, Michael
Macaulay, Ewan
Brittenden, Julie
Thromb J
Original Clinical Investigation
BACKGROUND: Previous studies have suggested that exercise in patients with intermittent claudication (IC) may induce a systemic thrombo-inflammatory response. The effect of secondary prevention therapy on this response is unknown. This study aimed to investigate the effects of treadmill exercise on markers of coagulation activation, inflammation and renal function in patients with IC, receiving aspirin and statin therapy compared to healthy controls. METHODS: Samples were taken before, immediately and 1 hour after exercising on a treadmill in 20 patients with IC and 20 healthy volunteers. Interleukin-6 (IL-6), thrombin-anti-thrombin complex (TAT) and fibrin D-dimer were measured by ELISA. High sensitivity CRP (HsCRP) and urinary albumin were measured via a nephelometric technique, urinary protein via a turbidometric assay and N-acetyl-β-D-glucosaminidase (NAG) via a colorimetric assay. RESULTS: Elevated baseline levels of Hs-CRP, IL-6, white cell counts, D-dimer and urinary NAG occurred in patients with IC compared to volunteers (p > 0.05). Following exercise there was no increase in Hs CRP or IL-6. D-dimer levels significantly increased following exercise in the patients and volunteers. TAT levels increased immediately after exercise in the patient group only and were significantly increased at 1 hour in both patients and volunteers. A transient rise in the protein creatinine ratio occurred in both groups (p < 0.007), and in albumin creatinine ratio in the patient group. There was no change in urinary NAG. CONCLUSION: Elevated markers of inflammation occurred in patients with IC on statin and aspirin therapy but these did not increase following exercise. However, acute exercise resulted in a prothrombotic state evident in both groups, although this was more prolonged in patient with IC. The clinical significance of these findings in patients who are known to be at an increased risk of cardiac and other thrombotic event are unclear.
BioMed Central
2006-07-18
/pmc/articles/PMC1540420/
/pubmed/16848885
http://dx.doi.org/10.1186/1477-9560-4-9
Text
en
Copyright © 2006 Collins et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:15503842006-08-18thrombjpmc-open
An update on prevention of venous thromboembolism in hospitalized acutely ill medical patients
Samama, Meyer Michel
Kleber, Franz-Xaver
Thromb J
Review
Both the recently updated consensus guidelines published by the American College of Chest Physicians, and the International Union of Angiology recommend thromboprophylaxis with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) in medical patients at risk of VTE. However, no guidance is given regarding the appropriate dosing regimens that should be used for thromboprophylaxis in this patient group. LMWH (enoxaparin and dalteparin) and UFH have been shown to be effective for thromboprophylaxis in at-risk hospitalized medical patients. Although LMWH once daily (o.d.) has been shown to be as effective as UFH three times daily (t.i.d.) for thromboprophylaxis in at-risk medical patients, there are no data to show that UFH twice daily (b.i.d) is as effective as either LMWH o.d. or UFH t.i.d. On the basis of currently available evidence, the LMWHs enoxaparin and dalteparin are more attractive alternatives to UFH for the prevention of VTE in hospitalized medical patients because of their convenient once-daily administration and better safety profile, demonstrated in terms of reduced bleeding, HIT, and other adverse events.
BioMed Central
2006-07-03
/pmc/articles/PMC1550384/
/pubmed/16817957
http://dx.doi.org/10.1186/1477-9560-4-8
Text
en
Copyright © 2006 Samama and Kleber; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai%3Apubmedcentral.nih.gov%3A1562367!!!oai_dc!thrombj