Higher Concentrations of Heparin and Hirudin are Required to Inhibit Thrombin Generation in Tissue Factor-Activated Cord Compared to Adult Plasma

Abstract

In standard clotting assays plasma samples are markedly diluted and high amounts of initiator are added to trigger clot formation. Under these conditions, adult plasma clots faster than neonatal plasma and only 30–50% of peak adult thrombin activity can be produced in neonatal plasma. It was reported that decreased concentrations of heparinoids are required to inhibit thrombin generation in plasma from newborns to the same extend as in adults due to reduced neonatal thrombin potential (TP). Plasma activation by addition of low amounts of lipidated tissue factor (TF) in combination with only slight dilution of plasma samples probably better reflects the conditions in vivo and allows sensitive detection of the effects of anticoagulants on thrombin generation. We have shown recently that under these conditions cord plasma clots faster and higher amounts of thrombin are generated compared to adult plasma. In accordance, we show in the present study that higher amounts of the anticoagulants heparin and hirudin are required in cord plasma for effective inhibition of thrombin generation compared to adult plasma: Prolongation of clotting time and suppression of TP were significantly more pronounced in adult plasma under low coagulant challenge compared with that in cord plasma. In contrast, prolongation of clotting time and suppression of TP were significantly more pronounced in cord plasma under high coagulant challenge. Our results suggest that in neonates effects of anticoagulants very much depend on the type of activation used to initiate clotting and doses of anticoagulants can not be derived from studies done in adults, and that higher doses of thrombin inhibitors may be required.