Thrombin generation in factor VIII-depleted neonatal plasma: Nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor

Abstract

Background: Bleeding in hemophilic neonates has a low incidence. A possible explanation for this could be the peculiarities of the neonatal hemostatic system, especially low levels of the inhibitors tissue factor pathway inhibitor (TFPI) and antithrombin (AT). Objective: We investigated the influence of an elevation of these inhibitors to adult levels on the thrombin generation (TG) in normal neonatal plasma and factor (F) VIII-depleted neonatal plasma by means of incubation with anti-FVIII-antibodies. Patients/methods: TG was measured after activation with low amounts of tissue factor (TF) by using Calibrated Automated Thrombography. Results: TG in FVIII-depleted neonatal plasma was nearly as high as in normal neonatal plasma.TG decreased after elevation ofAT in both neonatal plasmas. After elevation of TFPI TG decreased much more in FVIII-depleted neonatal plasma than in normal neonatal plasma. After elevation of both inhibitors their synergistic effect led to a stronger decrease of TG in FVIIIdepleted neonatal plasma. TG measured in plasma of one hemophilic newborn showed the same pattern as in FVIII depleted neonatal plasma. Conclusion: Our observation provides a biochemical basis for the rare bleeding in hemophilic neonates and shows the important role of the natural inhibitors in the hemostatic system of hemophilic patients. © 2006 International Society on Thrombosis and Haemostasis.