Fibrinogen interaction with human platelets: effect of other coagulation factors, prostaglandins and platelet inhibitors.
Fibrinogen (fg) binding to platelets is a critical step in the formation of the hemostatic plug. The interaction requires platelet stimulation and the induction of receptor sites on the platelet membrane. In this paper we report on the effect of other clotting factors on 125I-labeled fg binding to gel filtered human platelets. The action of exogenously added or endogenously synthesized prostaglandins and the effect of antiplatelet drugs were also investigated. Prothrombin and active factor X enhance ADP-induced platelet-fg binding whereas active factor VIII and active factor IX, separately or combined, are without effect. Human prothrombin complex (PC) factor concentrates (II-VII-IX-X) cause significant enhancement of platelets-fg binding; this effect is most likely due to activated factors and/or traces of thrombin present in the preparation. In the concentration used, these clotting factors and the PC factor concentrates failed to aggregate platelets in platelet rich plasma. Acetylsalicylic acid, carbenicillin and the calcium channel blocking agents verapamil and nifedipine showed variable degrees of inhibition of ADP-induced platelet-fg binding. Chlorpromazine and propranolol were without effect. Estrogen and progesterone had some enhancing effect on binding. These results suggest that, when the hemostatic mechanism is initiated, thromboxane A2 synthesis and activated prothrombin complex factors significantly enhance fg binding to platelets, a key step in hemostasis. Inhibitors of aggregation do not necessarily impede platelet fibrinogen interaction.
Al-Mondhiry
H
H
The Division of Hematology, Department of Medicine, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Ballard
J O
JO
McGarvey
V
V
D000244:Adenosine Diphosphate / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism*; D039341:Receptors, Fibrinogen / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism
D001779:Blood Coagulation Factors; D010975:Platelet Aggregation Inhibitors; D011453:Prostaglandins; D039341:Receptors, Fibrinogen; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D005340:Fibrinogen