Platelet unresponsiveness to collagen: Involvement of glycoprotein Ia-IIa (α2β1 integrin) deficiency associated with a myeloproliferative disorder

We studied a 66-year-old man with a myeloproliferative disorder who presented with a prolonged bleeding time and marked thrombocytosis (platelet count, 3,980×10 9 /l). There was no part history of a bleeding disorder. The patient had normal coagulation data. His platelets completely lacked collagen-induced platelet aggregation and adhesion, but showed normal responses to other agonists. All family members tested showed normal platelet aggregation with collagen, Analysis of 125 I surface-labeled platelets by two-dimensional SDS gel electrophoresis disclosed absence of the spot corresponding to platelet membrane GPIa (α 2 ) but no other significant deficiencies of major platelet glycoproteins i.e., GPIb, IIb-III-a, and IV. Immunoisolation studies of the patient's platelets indicated that neither anti-GPIa nor antiGPIIa (β 1 ) monoclonal antibody (mAb) isolated any surface membrane proteins correrponding to GPIa. GPVI, a putative collagen receptor, was immunoisolated from the platelets. Indirect immunofluorescence study using flow cytometry confirmed that the patient's platelets were totally deficient in surface expression of the GPIa-IIa complex (α 2 b 1 integrin). In contrast, phytohemoagglutinin-activated T-lymphocytes from the patient expressed normal concentrations of this complex. the data suggest that our patient had an acquired deficiency of the platelet GPIa-IIa complex, due to a myeloproliterative disorder, which might account for the absence of responsiveness of his platelet to collagen