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A cell-based model of coagulation and the role of factor VIIa

Created: 18/1/2006
 
Although this classical model of coagulation supports laboratory tests of coagulation disorders, it does not adequately explain the mechanisms leading to haemostasis in vivo. In particular, it does not explain why certain patients demonstrate a haemorrhagic tendency; nor does it allow accurate prediction of which patients will actually bleed. A cell-based model of haemostasis has been developed which will replace the classical model of the coagulation cascade. Research has shown that haemostasis occurs on different cell surfaces in three overlapping steps: initiation, amplification and propagation. The first phase, or initiation, occurs on a tissue factor (TF)-bearing cell. In the amplification phase, platelets and co-factors are activated in order to prepare for large-scale thrombin generation. Finally, propagation occurs on the surface of platelets, and results in the propagation of large amounts of thrombin.

When compared with the traditional cascade hypothesis, the cell-based conceptual model of haemostasis allows a more fundamental understanding of the clinical problems observed in some coagulation disorders by focusing on the central role of specific cell surfaces in controlling and directing the haemostatic process. Using this model, haemophilia may be charcterised by a failure of platelet-surface thrombin generation in the final propagation stage of the haemostatic process. High-dose recombinant FVIIa (NovoSeven) has shown considerable success as a therapy for haemophiliacs and inhibitor patients. This success may be attributable to enhanced thrombin production, and may partially compensate for the deficiency of FIX or FVIII. The research, which has led to the development of the cell-based model, is the work of Dr Maureane Hoffman’s team, Department of Pathology, Duke University Medical Center, USA.







References


A cell-based model of hemostasis.
Hoffman M and Monroe DM 3rd.
Thromb Haemost 2001; 85(6): 958-65.

A cell-based model of coagulation and the role of factor VIIa.
Hoffman M.
Blood Rev 2003; 17 Suppl 1: S1-5.

ArticleDate:20060118
SiteSection: Article
 
   
    
                                            
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