Membrane Glycoprotein Loss from Circulating Platelets: Inhibition by Dipyridamole and Aspirin

Platelet senescence during circulation has been suggested by evidence for the decreased size and hemostatic effectiveness of older platelets. We previously reported that when platelets are labeled simultaneously with [125I]-diazodiiodosulfanilic acid (I), which reacts with surface exposed plasma membrane glycoproteins, and 51cr, which reacts with soluble cytoplasmic material, the disappearance of I is more rapid than Cr (J Lab Clin Med, 88:247, 1976). We postulated that platelet surface material may be lost during reversible contact interactions in the process of hemostasis. To test this hypothesis we studied the survival of doubly labeled platelets in 5 rabbits treated with dipyridamole (D) (5 mg/kg IV at 0.5, 3 and 23 hours after infusion of labeled platelets) and aspirin (ASA) (25 mg/kg IV at 0.5 hours after infusion) in comparison with 13 control rabbits (untreated or given the drug diluent fluids in the same regimen). The diluent fluids had no effect. D and ASA had no effect on Cr disappearance but prolonged the disappearance rate of I so that it was equal to Cr. In control rabbits, the T½ of Cr (33.3 + 7.9 (SD) hours) was greater than I (19.5±3.6, ± < 0.001). In treated rabbits, the T½ of Cr (36.0 ± 5.3) was not different from that of I (30.8 ± 8.1, p > 0.2). The T½ of both Cr and I in the treated rabbits were greater than that of I in the control rabbits (p < 0.001) but not different from the T½ of Cr in the control rabbits (p > 0.5). We conclude that platelet surface glycoprotein loss is a continuous process in the normal circulation, possibly related to the changes of platelet senescence. The effect of D and ASA suggests that the membrane glycoprotein loss may occur during hemostatic encounters.