PB1231 - Micropartical-associated thrombin generation in patients with hemophilia A.

Background: The main goal of hemophilia treatment is to restore effective hemostasis in patients to prevent and control bleeding. It is known that clot formation is the result of multiple interactions between endothelium, clotting factors and other players of coagulation process, including microparticles (MP). MP express tissue factor (TF) and phospholipids on their surface that can enhance the procoagulation potential of plasma.

Aims: To estimate the MP significance for thrombin generation in patients with hemophilia receiving prophylactic therapy.

Methods: The blood was obtained from 63 patients with hemophilia A before and 1 hour after FVIII concentrate injection. Reference blood samples were obtained from 30 healthy people. Thrombin generation was measured in platelet-free plasma with Calibrated Automated Thrombinography using PRP-reagent (containing 1pM rTF) and MP-reagent (containing 4µM phospholipids). Endogenous thrombin potential (ETP, nM*min) and peak thrombin (Peak, nM) were evaluated. Statistical analysis of the results was performed by non-parametric methods (median (Me), Q1-Q3 interval and Mann-Whitney U test), Statistica 10.0. P< 0,05 was considered significant.

Results: PRP-reagent and MP-Reagent allow to estimate thrombin generation which depends on procoagulant phospholipids and TF, respectively. The thrombin generation parameters with both of reagents in patents before FVIII injection were significantly lower, than in controls. After FVIII admission both Peak and ETP became significantly higher than it was at the baseline, and significantly exceeded the normal range (Table 1).

Conclusion(s): The FVIII concentrates may enhance the coagulation potential of hemophilia patients partly by increasing of MP’s ability to drive thrombin generation. MP carrying TF play may be more visible role in this process, but it needs further investigation.