Abstract:

Objective: To assess the value of thrombin generation test (TGT) for predicting hemorrhagic tendencyin patients with von Willebr and disease (vWD). Methods: A total of 38 vWD patients from Shanghai Ruijin Hospital during January 2018 to July 2019 were enrolled, and were divided into three groups: mild bleeding group (8 mild bleeders, type 1 patients), moderate bleeding group (14 moderate bleeders, including 8 type 2A patients and 6 type 2M patients) and severe bleeding group (16 severe bleeders, including 2 type 2N patients, 6 severe type 1 patients and 8 type 3 patients). Five healthy subjects in the same age were served as the control group. Platelet-poor plasma samples were prepared by centrifugation. The difference in thrombin-generating capacity between patients and controls were tested by TGT, which was activated with 1 pmol/L tissue factor(TF) and 5 pmol/L TF, respectively. The correlations of vWF∶Ag, vWF∶Act, FⅧ∶C with TGT parameters [Peak value, endogenous thrombin potential (ETP), time to peak (ttPeak)] were also studied. Results: Under 1 pmol/L TF activation, the Peak value of TGT in controls was significantly higher than those in mild, moderate and severe bleeders (P<0.000 1), and the Peak value in severe bleeders was significantly lower than those in mild and moderate cases. (P=0.000 1). Furthermore, ETP and ttPeakvalues showed significant difference between severe bleeding group and the other groups. While TGT was activated with 5 pmol/L TF, the difference in TGT parameters decreased between groups. There was no significant difference in Peak values between controls and mild bleeders, and ETP and ttPeakvaluesdid not differ significantly between the groups (P>0.05). In addition, FVIII∶C levels had a good correlation with Peak values measured at 1 pmol/L TF activation (R²=0.65), whilev WF∶Ag and vWF∶Act were weakly correlated with any of TGT parameters at 1 pmol/L or 5 pmol/LTF activation (R²<0.50). Conclusions: Activated with 1 pmol/L TF, Peak value of TGT may serve as a useful laboratory tool to evaluate thehemorrhagic tendency in different types of vWD.

Key words: von Willebrand disease, Thrombin generation test, Hemorrhagic tendency