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Recent evidence suggests that platelet alpha-granule fibrinogen (fg) is derived from the plasma pool. Since platelets from patients with Type I Glanzmann's thrombasthenia (GT) are deficient in intracellular fibrinogen (fg) it was hypothesized that Gp IIb/IIIa could mediate the uptake of fg. To study the potential role of Gp IIb/IIIa in intracellular fg trafficking, the influence of therapeutic blocking of Gp IIb/IIIa on platelet fg was studied in 12 patients with stable ischaemic heart disease. Patients were either given a single intravenous dose of the monoclonal antibody 7E3 Fab (n = 4) or a combination of bolus and continuous infusion up to 24 (n = 3), 36 (n = 3) or 96 h (n = 2). All patients showed grossly prolonged bleeding times with a significant reduction of ex-vivo ADP induced aggregation. Although, surface Gp IIb/IIIa binding sites were consistently reduced in all patients, there was a variable but delayed decrease in platelet fg relative to vWf:Ag in only six out of the 12 patients studied. The reduction in fg appeared dependent upon both dosage and duration of Gp IIb/IIIa blockade. The study provides further evidence for the novel role of Gp IIb/IIIa in the intracellular trafficking of fg to platelet and megakaryocytic alpha-granules.

Type

Journal article

Publication Date

1992

Volume

82

Pages

721 - 728

Keywords

von Willebrand Factor/im [Immunology] Adult Aged Antibodies, Monoclonal/im [Immunology] Antigens/an [Analysis] Bleeding Time Blood Platelets/im [Immunology] *Blood Platelets/me [Metabolism] *Cytoplasmic Granules/me [Metabolism] *Fibrinogen/me [Metabolism] Human Middle Age *Myocardial Ischemia/bl [Blood] Platelet Count Platelet Membrane Glycoproteins/im [Immunology] *Platelet Membrane Glycoproteins/ph [Physiology] Support, Non-U.S. Gov't