Combined defect in membrane expression and activation of platelet GPIIb–IIIa complex without primary sequence abnormalities in myeloproliferative disease

Abstract

Summary. Defects in glycoprotein (GP)IIb±IIIa or in its activation may cause abnormal platelet aggregation and a bleeding diathesis. We report studies in a 67-year-old man with a myeloproliferative disease and markedly abnormal platelet responses. By flow cytometry, platelet binding of two complex-specific anti-GPIIb±IIIa monoclonal antibodies (mAbs), A2A9 and 10E5, was ,50% of normal. An enzyme-linked immunosorbent assay (ELISA) using immobilized kistrin showed 18% of normal membrane GPIIb±IIIa complex. By immunoblot analysis, GPIIb and GPIIIa levels in platelet lysates and membranes were near normal. Activation of GPIIb±IIIa, monitored with mAb PAC-1, was markedly decreased (, 20% of normal) in response to ADP, thrombin and platelet-activating factor (PAF); expression of ligand-induced binding sites (LIBS) was # 30% of normal. Signal transduction-independent LIBS expression, induced by echistatin, was ,60% of normal, suggesting that the integrin present had intact ligand-binding capability. Sequence analysis of GPIIb and GPIIIa cDNA, and platelet mRNA levels for both subunits, were normal. These findings document an acquired combined defect in membrane expression (secondary to a defect in post-translational processing of the complex) and inside-out signallingdependent activation of the GPIIb±IIIa complex.

Increased circulating platelet–neutrophil, platelet–monocyte complexes, and platelet activation in patients with ulcerative colitis: A comparative study

“…These platelets are active, but they still circulate in blood and they neither form aggregates with other platelets nor adhere to vascular lesions [19]. Various studies demonstrated that The values given are as median (range).…”