Anti-glycoprotein Ib causes platelet aggregation: different effects of blocking glycoprotein Ib and glycoprotein IIb/IIIa in the high shear filterometer.
In 1987 we reported that when blood was forced through a fine filter under pressure in the filterometer the platelets aggregated and blocked the filter. von Willebrand factor (vWF) and glycoprotein (Gp) IIb/IIIa and calcium were involved. Results with anti-GpIb were equivocal. We now report that all the anti-GpIb antibodies studied, glycocalicin, as well as some concentrations of aurin tricarboxylic acid caused platelet aggregation in the pre-filter blood and therefore could not be used in the filterometer. Using two different molecules that prevent vWF binding to GpIb and two anti-GpIIb/IIIa antibodies at two pressures it has now been shown that GpIb, vWf and high shear are primarily responsible for platelet retention at 0-5 s. Progressive platelet retention studied between 20 and 40 s required high shear and GpIIb/IIIa after the calcium influx mediated by GpIb/vWF binding. When GpIb was inhibited, GpIIb/Ila could not function normally, so GpIb inhibition resulted in decreased aggregation both at 0-5 s and at 20-40 s. Anti-GpIIlb/IIIa caused a minimal decrease in retention at 0-5 s and marked inhibition at 20-40 s. These findings fit and amplify concepts derived from other high shear methodologies. A diagram is presented of the events leading up to the final 'passivation' of the 'thrombus' in the filter when the surface of the aggregated platelets becomes unattractive.
O'Brien
J R
JR
St. Mary's Hospital, Portsmouth, UK.
Etherington
M D
MD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005260:Female; D005374:Filtration; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000276:immunology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology; D012212:Rheology; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors
D000906:Antibodies; D000911:Antibodies, Monoclonal; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; C023592:glycocalicin; D014841:von Willebrand Factor; D001312:Aurintricarboxylic Acid; D002118:Calcium