Background: Factor V(Leiden) (fV(Leiden)) predisposes to thrombosis by enhancing thrombin formation. This study tested the hypothesis that fV(Leiden) inhibits fibrinolysis in vivo.
Methods And Results: Radiolabeled clots were injected into the jugular veins of wild-type mice and mice heterozygous (fV(+/Q)) or homozygous (fV(Q/Q)) for fV(Leiden). Mean percent clot lysis 5 hours later was significantly reduced in fV(Q/Q) mice (14.3+/-3.6%, n=13) compared with wild-type mice (40.2+/-7.0%, n=17; P<0.01) and intermediate in fV(+/Q) mice (29.4+/-8.7%, n=9; P<0.03 versus fV(Q/Q), P=0.36 versus wild type). The rate of in vitro lysis of plasma clots prepared from fV(+/Q) or fV(Q/Q) mice was significantly slower than that of wild-type plasma clots, whereas in vitro clot lysis did not differ significantly between groups after inhibiting thrombin-activatable fibrinolysis inhibitor.
Conclusions: fV(Leiden) inhibits fibrinolysis in vivo, suggesting an additional pathway by which this mutation promotes thrombosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1161/01.CIR.0000148781.87906.C0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Temporal Association between Hampton's Hump Pulmonary Embolism and First-Dose ChAdOx1 nCov-19 Vaccine in a Patient with Activated Protein C Resistance.
Vaccines (Basel)
October 2022
Radiologicum Wieden, 1040 Vienna, Austria.
A 58-year-old man presented to his practitioner with right-sided pleuritic chest pain, dyspnea, and fatigue 18 days following the first dose of the ChAdOx1 nCov-19 vaccine. Chest radiography showed a basal wedge-shaped consolidation indicative of a Hampton’s hump in the right lower lobe, which was confirmed by subsequent computed tomography pulmonary angiography. The major laboratory abnormalities were a markedly elevated D-dimer level of 7.
View Article and Find Full Text PDFCharacterization of thrombophilia-related plasmas evaluated by anticoagulants-mediated thrombin and plasmin generation assays.
Blood Coagul Fibrinolysis
September 2022
Department of Pediatrics, Nara Medical University, Kashihara.
Disturbances in the balance between coagulation, anticoagulation and fibrinolysis may lead to thrombosis or haemorrhage. Simultaneous assessments of thrombin and plasmin facilitate overall understandings of pathological haemostasis, especially for thrombophilia. Here, we characterized coagulation-fibrinolysis potentials in plasmas with thrombophilia using anticoagulants-mediated thrombin-plasmin generation assay (T/P-GA).
View Article and Find Full Text PDFThe effect of SARS-Co-V2 infection on prothrombotic and anticoagulant factors in dialysis patients.
Artif Organs
July 2022
UCL Department of Nephrology, Royal Free Hospital, Faculty of Medical Sciences, University College London, London, UK.
Background: Patients with COVID-19 infection are at increased risk of thrombosis. We wished to determine whether this was is due to an increase in prothrombotic or reduction in anticoagulant factors and whether heparin would be an appropriate anticoagulant.
Methods: We measured routine coagulation and prothrombotic factors in dialysis patients after a positive COVID-19 test between March 2020 -April 2021.
Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation.
Sci Rep
July 2020
Departments of Biochemistry and Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
In haemostasis and thrombosis, platelet, coagulation and anticoagulation pathways act together to produce fibrin-containing thrombi. We developed a microspot-based technique, in which we assessed platelet adhesion, platelet activation, thrombus structure and fibrin clot formation in real time using flowing whole blood. Microspots were made from distinct platelet-adhesive surfaces in the absence or presence of tissue factor, thrombomodulin or activated protein C.
View Article and Find Full Text PDFRevisiting the activated protein C-protein S-thrombomodulin ternary pathway: Impact of new understanding on its laboratory investigation.
Transfus Apher Sci
August 2019
International Consultancy in Blood Components Quality/Safety Improvement, Audit/ Inspection and DDR Strategies, London, UK. Electronic address:
Although suspected conceptually in the 60 s, Protein C and Protein S activities in hemostasis were investigated and reported from the mid-80 s, followed by the discovery of Thrombomodulin, an endothelial cell membrane associated protein, playing the most important heamostatic role. These 3 proteins act in regulating thrombogenesis and protecting against thrombo-embolic events. When blood is activated, any trace of circulating thrombin is captured by Thrombomodulin in the microcirculation, making thrombin become an anticoagulant through its capacity to activate Protein C to Activated Protein C, which operates as a sentinel in blood coagulation, in the form of a complex with free Protein S, to block any new blood activation site, and more especially circulating activated Factors V and VIII.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!