In Vitro Studies of the Interaction of Heparin, Low Molecular Weight Heparin and Heparinoids with Platelets

Abstract

Heparin, low molecular weight heparins, and heparinoids were studied for their ability to inhibit the aggregation of platelets by various agonists and for their ability to adhere to collagen. Heparin was a very effective inhibitor of aggregation with collagen and with ristocetin as it was with adhesion to collagen. The heparinoids showed little effect on aggregation or adhesion. Heparan sulfate and pentosan polysulfate did show slight inhibitory activity against collagen aggregation and adhesion and both interacted with the antibody induced by heparin therapy. It is of interest that dermatan sulfate and the pentasaccharide were almost inert in these experiments, and are unlikely to induce bleeding by inhibition of platelet function. It is highly probable that interference with the interaction of von Willebrand factor with platelets and collagen is a major mechanism for bleeding in the heparinized patient.

Comparison of Hemorrhagic Effect of Heparin and Human Activated Protein C with Use of Thrombostat 4000

“…Since there was no change in the platelet count, hematocrit or fibrinogen content, it appears that heparin inhibited platelet adhesion to the collagen membrane and platelet thrombus formation. Some re ports have indicated that heparin inhibits both von Willebrand factor-platelet binding and von Willebrand factor-dependent platelet function [10,24]. Using a hemostatometer, which can detect platelet reactivity to shear stress by measuring the blood perfusion pres sure through a polyethylene tube with holes, John et al [11,12] demonstrated that heparin inhibited the platelet reactivity.…”

“…One of the reasons for this is thought to be that APC binds to membrane phospholipids and exerts its anticoagulant activity only in the solid phase where a clot is formed [9], whereas heparin binds with antithrombin III and exerts its anticoagulant effect in the fluid phase. Furthermore, Mcssmorc et al [10] and John et al [11,12] indicated that heparin inhibited platelet function, and this may be another mechanism by which hemorrhage de velops. In this regard, the interaction of APC with platelets is still unknown.…”

SR 90107A/Org 31540, a Novel Anti‐Factor Xa Antithrombotic Agent

“…In contrast, in the same range of concentrations, heparin and low molecular weight heparins inhibited platelet aggregation (21). Preliminary results obtained either by means of aggregation tests or ELISA detection of antibodies bound to multimolecular PF4-heparin complex indicated that SR 90107A/Org 3 1540 did not crossreact in v i m with antibodies present in the plasma of patients with heparin associated thrombocytopenia (13,21, Amiral et al, submitted).…”

Fondaparinux Sodium

“…[16] In vitro and in vivo, fondaparinux approved for the prevention of VTE recurrence, [52] a study evaluathad no direct effect on Factor IIa. [39] It also does not bind significantly to platelet factor 4 in manufacturer's prescribing information, [11,54] and drug interaction plasma from patients with heparin-induced thrombocytopenia studies in healthy volunteers. [39] It also does not bind significantly to platelet factor 4 in manufacturer's prescribing information, [11,54] and drug interaction plasma from patients with heparin-induced thrombocytopenia studies in healthy volunteers.…”