title: Identification of a unique type of thrombopathy of human platelets: defect in the exposure of active fibrinogen receptors in a patient with Friedreich's ataxia.
abstract: Platelets of a patient with Friedreich's ataxia have been investigated because of a codiagnosis of thrombasthenia. No aggregation occurred in response to adenosine diphosphate, platelet activating factor-acether, a stimulatory antiplatelet monoclonal antibody, or phorbol myristate acetate, although platelet aggregation could be induced with thrombin, the calcium ionophore A23187, or high concentrations of collagen. Shape change, adenosine triphosphate secretion, and the responses of the platelets' protein phosphorylation systems to all agonists were normal. Immunologic analysis of the patient's radiolabeled platelet surface proteins revealed normal levels of glycoproteins IIB and IIIa. However, no iodine 125-fibrinogen binding occurred after stimulation of the patient's platelets with adenosine diphosphate. In contrast, pretreatment of the patient's platelets with the proteolytic enzyme alpha-chymotrypsin resulted in the exposure of active 125I-fibrinogen binding sites. The patient's platelets exhibited normal aggregation to fibrinogen after their pretreatment with chymotrypsin and with elastases derived either from porcine pancreas or from human granulocytes. A murine monoclonal antibody directed against the human platelet membrane glycoproteins IIb and IIIa calcium-dependent epitope and rabbit polyclonal anti-human platelet membrane and human anti-P1A1 antibodies immunoprecipitated glycoproteins IIb and IIIa and a 66 kd cleavage product of glycoprotein IIIa from sodium dodecyl sulfate-Triton X-100 extracts of the patient's proteolytically treated platelets. The patient appears to exhibit a unique type of thrombopathy involving a defect in the exposure of fibrinogen receptors. The association between the neurologic disorder and the platelet defect is still unclear.
authors.affiliation: University of Vermont, Department of Psychiatry, Burlington 05405.
authors.forename: E
authors.initials: E
authors.lastname: Kornecki
authors.forename: B A
authors.initials: BA
authors.lastname: Cooper
authors.forename: Y H
authors.initials: YH
authors.lastname: Ehrlich
mesh_terms: D000328:Adult; D001791:Blood Platelet Disorders / Q000150:complications*; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005621:Friedreich Ataxia / Q000150:complications* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D005340:Fibrinogen