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 u nder pressure in the filterometer the platelets aggregated and blocked the filter. von Willebrand factor (vWF) and glycoprotein (Gp) IIb/III a and calcium were involved. Results with anti-GpIb were equivocal. We now report that all the anti-GpIb antibodies studied, glycocalicin, a s well as some concentrations of aurin tricarboxylic acid caused plate let aggregation in the pre-filter blood and therefore could not be use d 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 respon sible for platelet retention at 0-5 s. Progressive platelet retention studied between 20 and 40 s required high shear and GpIIb/IIIa after t he calcium influx mediated by GpIb/vWF binding. When GpIb was inhibite d, GpIIb/IIIa could not function normally, so GpIb inhibition resulted in decreased aggregation both at 0-5 a and at 20-40 s. Anti-GpIIb/III a caused a minimal decrease in retention at 0-5 s and marked inhibitio n at 20-40 s. These findings fit and amplify concepts derived from oth er high shear methodologies. A diagram is presented of the events lead ing up to the final 'passivation' of the 'thrombus' in the filter when the surface of the aggregated platelets becomes unattractive. Blood C oag Fibrinol 9:453-461 (C) 1998 Lippincott Williams &Wilkins.