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Thrombin-generating capacity in patients with von Willebrand’s disease

From the Unite d’Hemostase Clinique, Hopital Edouard Herriot, Lyon, France (LR, RF, CN, YD); Laboratoire d’Hemostase, Hopital Edouard Herriot, Lyon, France (LR, JCB, BC, CN, YD); Synapse bv, CARIM, University of Maastricht, The Netherlands (SB, CH); EA 3735, University of Lyon I, Lyon, France (JCB, CN, YD)

Correspondence: Yesim Dargaud, MD, PhD, Unité d’Hemostase Clinique Hôpital Edouard Herriot Pavillon E 5, place d’Arsonval, 69003 Lyon, France. E-mail: ydargaud{at}univ-lyon1.fr

Background and Objectives: on Willebrand’s disease (VWD) is the most common hereditary bleeding disorder. Its severity can be classified on the basis of von Willebrand factor (VWF) and factor VIII (FVIII) plasma levels and according to the clinical relevance of bleeding episodes. However, patients with very low VWF activity may exhibit a mild bleeding tendency. The basis for this heterogeneous clinical expression of the deficit is still poorly understood. We investigated the relationship between thrombin generation and levels of factor VIII, VWF and clinical bleeding tendency.

Design and Methods: Thrombin generation was measured in platelet-rich (PRP) and platelet-poor plasma (PPP) from 53 patients with VWD.

Results: We observed a statistically significant higher risk of bleeding in patients with a low thrombin peak in PRP (OR=14.5; 95% CI=5–41.3). Similar results were found in PPP (OR=8.71; 95% CI=3.4–22.3). Two parameters of the thrombin generation curve, peak height and thrombin generation speed (slope), correlated significantly with VWF:RCo and FVIII levels both in PPP and in PRP. Regression analysis showed that thrombin generation was mainly dependent on plasma FVIII activity.

Interpretation and Conclusions: Our results suggest that the thrombin generation test, in combination with routine FVIII and VWF measurements, could be of interest in the assessment of the individual bleeding risk in patients with VWD.

Key words: von Willebrand’s disease, factor VIII, thrombin generation assay, bleeding phenotype, von Willebrand factor.