Phospholipid content, expression and support of thrombin generation of neonatal platelets.

AIM: Newborns have, despite low clotting factors and poor in vitro platelet function, a well functioning haemostasis. We investigated whether phospholipids (PL) in neonatal platelets differ from those in adult platelets in their exposure on the platelet surface, and their effect on thrombin generation. METHODS: The effect of newborn and adult platelets on thrombin generation (TG) was measured by means of calibrated automated thrombography (CAT), and in a purified system. In addition, clotting times were measured. Phosphatidylserine (PS)-exposure was measured by flow cytometry. The amount of PL was determined by means of mass-spectrometry (Materials and Methods section in Supporting Information online). RESULTS: In comparison with adults the clotting times in platelet-rich plasma of newborns were less shortened by adding calciumionophore. No differences in the support of TG between neonatal and adult platelets were found by means of CAT. In the purified system, TG was increased by ionophor-stimulated platelets but no difference was evident between newborn and adult platelets. Flow cytometric analysis showed no difference between adult and newborn platelets. Results of mass-spectrometry showed a very similar pattern of phospholipid-content of adult and newborn platelets. CONCLUSION: Our results do not provide any evidence that a different phospholipid-expression of neonatal platelets may alter TG in neonates.

Combined effects of eptifibatide and anticoagulants: differences between LMWH and UH or rH in thrombin generation inhibition but not in platelet aggregation inhibition.

Aim of our study was to investigate effects of eptifibatide and anticoagulants on platelet aggregation and thrombin generation under low and high coagulant challenge in tissue factor-activated platelet rich plasma using a model allowing simultaneous determination of the time course of platelet aggregation and thrombin generation. Eptifibatide exerted a dose-dependent anti-aggregating effect under both high and significantly stronger under low coagulant challenge. Combination of eptifibatide and anticoagulants resulted in significant additive prolongation of the lag phase until the onset of platelet aggregation, more pronounced under low coagulant challenge. Under high, but not under low coagulant challenge combination of eptifibatide and anticoagulants had a significant synergistic inhibitory effect on platelet aggregation. Under low coagulant challenge combination of eptifibatide with LMWH, but not with UH, or rH, resulted in significantly reduced thrombin potential, F 1+2 generation, and FXa formation compared to measurements in the absence of eptifibatide. We demonstrate a synergistic effect of eptifibatide and anticoagulants on platelet aggregation inhibition and an additional inhibitory effect of LMWH and eptifibatide on thrombin generation. Our results support the notion that combination of eptifibatide and anticoagulants might be beneficial in atherosclerotic disease to palliate the thrombogenic potency of ruptured atherosclerotic plaques.