+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor



Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor



Thrombosis and Haemostasis 110(1): 62-75



Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 052935132

Download citation: RISBibTeXText

PMID: 23636277

DOI: 10.1160/th13-01-0069


Related references

The hemostatic system in peripheral arterial disease 2. variations in factor viii components factor viii coagulant activity factor viii related antigen von willebrand factor before and after venous occlusion. Thrombosis Research 22(5-6): 559-564, 1981

Venous thrombosis in a family with defective release of vascular plasminogen activator and elevated plasma factor VIII/von Willebrand's factor. American Journal of Medicine 74(1): 33-39, 1983

Studies on factor viii during coagulation process part 1 levels of factor viii pro coagulant factor viii related antigen and von willebrand factor in plasma and serum of normal children patients with hemophilia a or von willebrands disease. Journal of the Nagoya Medical Association 29(1): 61-68, 1978

Direct radio immune detection in human plasma of the association between factor viii pro coagulant protein and von willebrand factor and the interaction of von willebrand factor bound pro coagulant factor viii with platelets. Blood 61(6): 1164-1173, 1983

Comparison of six commercial plasma references for factor VIII, factor IX and von Willebrand factor. On behalf of the Subcommittee for Factor VIII and IX of the Scientific and Standardization Committee of the ISTH. Thrombosis and Haemostasis 74(3): 987-989, 1995

Rapid quantitative separation of factor viii anti hemophilic factor from factor viii von willebrand factor in human plasma with solid phase poly electrolytes. Circulation Suppl. 54(2): II-120, 1976

Factor VIII-von Willebrand factor binding defects in autosomal recessive von Willebrand disease type Normandy and in mild hemophilia A. New insights into factor VIII-von Willebrand factor interactions. Acta Haematologica 121(2-3): 102-105, 2009

Influence of nutritional factors on plasma concentration of factor ii and factor vii factor viii factor ix factor x and on the rate of synthesis of serum albumin new born rabbits. Biology of the Neonate 20(5-6): 436-447, 1972

Detection of carriers of hemophilia a activities of factor viii pro coagulant factor viii inhibitor neutralizing material anti human factor viii antibody neutralizing material factor viii related antigen and von willebrand factor in plasma of female carriers. Journal of the Nagoya Medical Association 29(1): 47-60, 1978

Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand's disease. Journal of Clinical Investigation 60(2): 390-404, 1977

Factor viii von willebrand factor complex only the 440000 subunit of endothelial cell derived von willebrand factor forms a complex with purified plasma factor viiic. Thrombosis & Haemostasis 58(1): 356, 1987

Thrombocytopenia with large platelets and increased platelet binding of factor viii von willebrand factor without aggregation with exogenous factor viii von willebrand factor a new entity. Thrombosis & Haemostasis: 79, 1983

Cerebral venous thrombosis associated with thyrotoxicosis, the use of desmopressin and elevated factor VIII/von Willebrand factor. Bmj Case Reports 2016:, 2016

High factor VIII antigen levels increase the risk of venous thrombosis but are not associated with polymorphisms in the von Willebrand factor and factor VIII gene. British Journal of Haematology 115(1): 156-158, 2001

Ultracentrifugation studies of purified factor viii von willebrand factor complex revealed von willebrand factor dimer as the factor viii binding protein. Blut 60(2): 153, 1990