Interaction of normal, thrombasthenic, and Bernard-Soulier platelets with immobilized fibrinogen: defective platelet-fibrinogen interaction in thrombasthenia

Abstract

Fibrinogen is required for normal platelet adhesion to glass and aggregation by adenosine diphosphate (ADP), epinephrine, thrombin, and connective tissue, The abnormalities of platelet function in fibrinogen-free medium are similar to those found in thrombasthenia, raising the possibility that the platelets in this disorder do not interact with fibrinogen normally. To investigate the fibrinogen-platelet interaction, highly purified fibrinogen was covalently coupled to solid beads, which were then used to develop an assay in which platelets agglutinate the beads when they interact with the fibrinogen. Unstimulated normal platelets agglutinated the beads; the agglutination could be inhibited by EDTA, lidocaine, sodium azide, antifibrinogen Fab′2, and exogenous fibrinogen in solution. Aspirin caused no inhibition, while high doses of PGE1 and apyrase produced only partial inhibition. ADP and epinephrine dramatically enhanced the agglutination. Platelet-rich plasma from two patients with Bernard-Soulier syndrome also agglutinated the beads. In contrast, the platelet-rich plasma from two patients with thrombasthenia completely failed to agglutinate the beads, even with the addition of ADP and epinephrine. The inability of thrombasthenic platelets to agglutinate fibrinogen beads confirms the presence of an abnormality in interaction with fibrinogen, and since with normal platelets this interaction is independent of platelet aggregation, it suggests that the abnormal fibrinogen interaction may be the cause of the platelet aggregation defect in thrombasthenia.