Fibrinogen-independent aggregation and deaggregation of human platelets: studies in two afibrinogenemic patients.
Platelets from two afibrinogenemic patients were used to determine whether fibrinogen is essential for platelet aggregation and to examine whether released fibrinogen contributes to the stabilization of platelet aggregates when platelets have been induced to aggregate and release their granule contents by stimulation with thrombin. The addition of adenosine diphosphate (ADP) to platelet-rich plasma (PRP) or to suspensions of washed platelets from the afibrinogenemic patients caused the formation of small aggregates, which was either not inhibited or only slightly inhibited by the F(ab')2 fragments of an antibody to fibrinogen but was inhibited by an antibody (10E5) to glycoprotein IIb/IIIa. Thus there is a component of ADP-induced platelet aggregation that is not dependent on fibrinogen or other plasma proteins but is dependent on glycoprotein IIb/IIIa. There was little difference in the extent of aggregation and the release of granule contents of normal and afibrinogenemic platelets in response to the release-inducing agents collagen, platelet-activating factor (PAF), sodium arachidonate, or thrombin. With normal or afibrinogenemic platelets, aggregation by thrombin (0.2 U/mL or higher) was not inhibited by the F(ab')2 fragments of an antibody to human fibrinogen. Deaggregation by combinations of inhibitors of platelets aggregated by 1 U/mL thrombin showed no difference between platelets from afibrinogenemic and control subjects, indicating that released fibrinogen does not make a major contribution to the stabilization of platelet aggregates formed by thrombin stimulation.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000347:Afibrinogenemia / Q000097:blood* / Q000503:physiopathology; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D002918:Chymotrypsin / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000502:physiology*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology
D000906:Antibodies; D006629:Hirudins; D007140:Immunoglobulin Fab Fragments; D010980:Platelet Membrane Glycoproteins; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D004492:Edetic Acid; D002918:Chymotrypsin; D013917:Thrombin