The influence of therapeutic blocking of Gp IIb/IIIa on platelet alpha-granular fibrinogen.
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.
Harrison
P
P
Rayne Institute, St Thomas' Hospital, London.
Wilbourn
B
B
Cramer
E
E
Faint
R
R
Mackie
I J
IJ
Bhattacharya
S
S
Lahiri
A
A
Tenza
D
D
Machin
S J
SJ
Savidge
G F
GF
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000032:analysis; D001760:Bleeding Time; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood*; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D014841:von Willebrand Factor / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D010980:Platelet Membrane Glycoproteins; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D005340:Fibrinogen