The influence of therapeutic blocking of Gp IIb/IIIa on platelet α‐granular fibrinogen
Harrison P., Wilbourn B., Cramer E., Faint R., Mackie IJ., Bhattacharya S., TJahiri A., Tenza D., Machin SJ., Savidge GF.
Recent evidence suggests that platelet a‐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.