Low inhibitor levels allow fast and sufficient thrombin generation in tissue factor-activated cord plasma

Abstract number: P0075

Cvirn^*‡ G., Gallistl^* S., Juergens†‡ G., Muntean^* W.

†‡ ^*‡ ^*Ludwig Boltzmann Research Institute, Austria;

Clinically observed excellent hemostasis in neonates despite low levels of clotting factors is not completely understood so far. Therefore, we investigated whether physiological low levels of the inhibitor protein C (PC) facilitate thrombin formation in tissue factor (TF) activated plasma samples. PC was activated by endogenously generated thrombin after addition of soluble thrombomodulin (TM). Thrombin and PC generation curves were monitored by using subsampling methods and the chromogenic substrates S2238 and S2366, respectively. In both cord and adult plasma, approximately same amounts of activated PC (APC) were generated. However, the capability of APC to suppress thrombin formation was significantly more pronounced in adult than in cord plasma. Addition of 4 nM of TM decreased the thrombin potential (TP) in cord plasma by 10%, and in adult plasma by 52% in the presence of 5 pM TF. We demonstrate that this low anticoagulant action of PC is attributable to the low levels of tissue factor pathway inhibitor (TFPI) and antithrombin (AT) physiologically present in cord plasma. Addition of 4 nM TM decreased the TP by 58% in cord plasma adjusted to contain TFPI and AT at adult levels in the presence of 5 pM TF. Thus, the low anticoagulant capacity of the three inhibitors APC, TFPI, and AT in cord plasma allowed enhanced thrombin formation associated with shorter clotting times compared to adult plasma when low amounts of TF were applied. Although our laboratory experiments do not allow definite conclusions for various clinical situations, our data might contribute to explain excellent hemostasis in neonates despite low levels of procoagulants. This study was supported by a grant from the ‘Gesellschaft zur Förderung der Gesundheit des Kindes (INVITA)’ and from the Frans Lanyar-Stiftung