Platelet unresponsiveness to collagen: involvement of glycoprotein Ia-IIa (alpha 2 beta 1 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, 3,890 x 10(9)/l). There was no past 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 125I surface-labeled platelets by two-dimensional SDS gel electrophoresis disclosed absence of the spot corresponding to platelet membrane GPIa (alpha 2) but no other significant deficiencies of major platelet glycoproteins i.e., GPIb, IIb-IIIa, and IV. Immunoisolation studies of the patient's platelets indicated that neither anti-GPIa nor anti-GPIIa (beta 1) monoclonal antibody (mAb) isolated any surface membrane proteins corresponding 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 (alpha 2 beta 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 myeloproliferative disorder, which might account for the absence of responsiveness of his platelet to collagen.
Handa
M
M
Department of Blood Center, Keio University, Tokyo, Japan.
Watanabe
K
K
Kawai
Y
Y
Kamata
T
T
Koyama
T
T
Nagai
H
H
Ikeda
Y
Y
D000208:Acute Disease; D000368:Aged; D001760:Bleeding Time; D003094:Collagen / Q000494:pharmacology*; D018450:Disease Progression; D017809:Fatal Outcome; D006801:Humans; D016023:Integrins / Q000172:deficiency*; D007951:Leukemia, Myeloid / Q000097:blood; D008297:Male; D009196:Myeloproliferative Disorders / Q000097:blood* / Q000150:complications; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests; D038981:Receptors, Collagen; D013922:Thrombocytosis / Q000097:blood / Q000209:etiology
D016023:Integrins; D038981:Receptors, Collagen; D003094:Collagen