A myeloma paraprotein with specificity for platelet glycoprotein IIIa in a patient with a fatal bleeding disorder.
Impaired platelet aggregation, normal shape change, and agglutination and normal ATP secretion and thromboxane synthesis in response to high concentrations of thrombin or arachidonic acid were found in a patient with multiple myeloma and hemorrhagic tendency. The purified IgG1 kappa or its F(ab1)2 fragments induced similar changes when added in vitro to platelet-rich plasma from normal subjects. In addition, the paraprotein inhibited adhesion to glass microbeads, fibrin clot retraction, and binding of radiolabeled fibrinogen or von Willebrand factor to platelets exposed to thrombin or arachidonic acid without affecting intraplatelet levels of cAMP. The radiolabeled para-protein bound to an average of 35,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets from a patient with Glanzmann's thrombasthenia. Immunoprecipitation studies showed that the platelet antigen identified by the paraprotein was the glycoprotein IIIa. Furthermore, binding of radiolabeled prostaglandin E1 (PGE1) to resting platelets as well as binding of von Willebrand factor to platelets stimulated with ristocetin were entirely normal in the presence of patient's inhibitor. These studies indicate that bleeding occurring in dysproteinemia may be the result of a specific interaction of monoclonal paraproteins with platelets. In addition, our data support the concept that the interaction of fibrinogen and/or von Willebrand factor with the platelet glycoprotein IIb-IIIa complex is essential for effective hemostasis.
D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000502:physiology; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D005340:Fibrinogen / Q000378:metabolism; D006471:Gastrointestinal Hemorrhage / Q000097:blood / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D008970:Molecular Weight; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology; D009194:Myeloma Proteins / Q000302:isolation & purification / Q000502:physiology*; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D008565:Membrane Proteins; D009194:Myeloma Proteins; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D005340:Fibrinogen