Effect of Aspirin and Dipyridamole on the Interaction of Human Platelets with Sub-Endothelium: Studies Using Citrated and Native Blood

Summary

The effect of aspirin and dipyridamole ingestion on the interaction of platelets with the subendothelium was studied using both citrated blood and directly sampled (native) blood. After obtained control studies, normal human subjects ingested 0.6 g of aspirin, 150 mg of dipyridamole, or a placebo and studies were repeated 1½ hrs later. Subjects continued on placebo, aspirin (0.6 g b.i.d.) or dipyridamole (100 mg q.i.d.) for 6 days and studies were obtained 1½ hrs after the last dose. Blood was circulated through an annular chamber on whose inner core were mounted everted segments of de-endothelialized rabbit aorta. The wall shear rate was 2,600 sec^-1. Surface coverage with adherent platelets and platelet thrombi, as well as several parameters of thrombus dimensions, were evaluated morphometrically. Aspirin ingestion markedly reduced platelet thrombi in citrated blood, – but had a much lesser inhibitory effect in native blood. Platelet adhesion was unaffected in native blood; it was slightly decreased in citrated blood, in contrast to previous findings in which a lower shear rate (800 sec^-1) was used. Ingestion of dipyridamole did not inhibit platelet adhesion or thrombi in either citrated or native blood. The studies indicate that, with the flow conditions used, aspirin is a relatively weak inhibitor of platelet thrombus formation in directly sampled human blood.

Keywords

Acetylsalicylic acid - Dipyridamole - Platelet adhesion - Platelet-subendothelium interaction

• References

• 1 Weiss HJ. Antiplatelet therapy. N Eng J Med 1978; 298 1344-1349 and 1403-1406
• 2 Samuelsson B. The role of prostaglandin endoperoxides and tromboxanes in human platelets. Prostaglandins in Hematology. Silver MJ, Smith JB, Kocsis JJ. (eds) New York: Spectrum; pp 01-10
• 3 Roth GJ, Stanford N, Majerus PW. Acetylation of prostaglandin synthetase by aspirin. Proc Nat Acad Sci (USA) 1975; 72: 3073-3076
• 4 Weiss HJ, Aledort LM, Kochwa S. The effect of salicylates on the hemostatic properties of platelets in man. J Clin Invest 1968; 47: 2169-2180
• 5 Didisheim P. Inhibition by dipyridamole of arterial thrombosis in rats. Thromb Diath Haemorrh 1968; 20: 257-266
• 6 Emmons PR, Harrison MJ G, Honour AJ, Mitchell JR A. Effect of a pyrimido-pyrimidine derivative on thrombus formation in the rabbit. Nature 1965; 208: 255-257
• 7 Arfors KE, Hint HC, Dhall DP. Counteraction of platelet activity at sites of laser-induced endothelial trauma. Brit Med J 1968; 4: 430-431
• 8 Harker LA, Slichter SJ. Studies of platelet and fibrinogen kinetics in patients with prosthetic heart valves. N Eng J Med 1970; 283: 1302-1305
• 9 Mills DC B, Smith JB. The influence on platelet aggregation of drugs that affect the accumulation of adenosine 3’: 5’-cyclic monophosphate in platelets. Biochem 1971; 121: 185-196
• 10 Eliasson R, Bygdeman S. Effect of dipyridamole and two pyrimidopyrimidine derivatives on the kinetics of human platelet aggregation and on platelet adhesiveness. Scand J Clin Lab Invest 1969; 24: 145-151
• 11 Cucianu MP, Nishizawa EE, Mustard JF. Effect of pyrimidopyrimidine compounds on platelet function. J Lab Clin Med 1971; 77: 958-974
• 12 Rajah SM, Crow MJ, Penny AF, Ahmad R, Watson DA. The effect of dipyridamole on platelet function: correlation with blood levels in man. Brit J Clin Pharm 1977; 4: 129-133
• 13 Moncada S, Korbut R. Dipyridamole and other phosphodiesterase inhibitors act as antithrombotic agents by potentiating endogenous prostacyclin. Lancet 1978; 1: 1286-1289
• 14 Gorman RR, Bunting S, Miller VV. Modulation of human platelet adenyl cyclase by prostacyclin (PGI). Prostaglandins 1977; 13: 377-388
• 15 Salzman EW. Cyclic AMP and platelet function. N Eng J Med 1972; 286: 358-363
• 16 Baumgartner HR. The role of blood flow in platelet adhesion, fibrin deposition, and formation of mural thrombi. Microvasc Res 1973; 5: 167-169
• 17 Tschopp T, Weiss HJ, Baumgartner H. Decreased adhesion of platelets to subendothelium in von Willebrand’s disease. J Lab Clin Med 1974; 83: 296-300
• 18 Weiss HJ, Turitto VT, Baumgartner HR. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. I. Shear-dependent decrease of adhesion in von Willebrand’s disease and the Bernard-Soulier syndrome. J Lab Clin Med 1978; 92: 750-764
• 19 Tschopp TB, Weiss HJ, Baumgartner HR. Interaction of platelets with subendothelium in thrombasthenia: normal adhesion, impaired aggregation. Experientia 1975; 31: 113-116
• 20 Weiss HJ, Tschopp TB, Baumgartner HR, Sussman II, Johnson MM, Egan JJ. Decreased adhesion of giant (Bernard-Soulier) platelets to subendothelium – further implications on the role of the von Willebrand factor in hemostasis. Am J Med 1974; 57: 920-925
• 21 Weiss HJ, Tschopp TB, Baumgartner HR. Impaired interaction (adhesion-aggregation) of platelets with the subendothelium in storage-pool disease and after aspirin ingestion – a comparison with von Willebrand’s disease. N Eng J Med 1975; 293: 619-623
• 22 Baumgartner HR. Effects of anticoagulation on the interaction of human platelets with subendothelium in flowing blood. Schweiz Med Wochenschr 1976; 106: 1367-1368
• 23 Baumgartner HR. Effects of acetylsalicylic acid, sulfinpyrazone, and dipyridamole on platelet adhesion and aggregation in flowing native and anticoaguled blood. Haemostasis 1979; 8: 340-352
• 24 Baumgartner HR, Turitto VT, Weiss HJ. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. Relationships among platelet adhesion, thrombus dimensions and fibrin formation. J Lab Clin Med 1980; 95: 208-221
• 25 Weiss HJ, Rogers J. Thrombocytopathia due to abnormalities in platelet release reaction – studies on six unrelated patients. Blood 1972; 39: 187-209
• 26 Zak SB, Tallan HH, Quinn GP, Fratta I, Greengard P. The determination and physiological distribution of dipyridamole and its glucuronides in biological materials. J Pharm Exper Therap 1963; 141: 392-398
• 27 Steel R GD, Torrie JH. Principles and Procedures of Statistics. New York: McGraw-Hill; 1960. pp 099-131
• 28 Weiss HJ, Turitto VT. Prostaglandin I₂ (prostacyclin) inhibits platelet adhesion and thrombus formation on subendothelium. Blood 1979; 53: 244-250
• 29 Baumgartner HR, Tschopp TB, Meyer D. Shear rate dependent inhibition of platelet adhesion and aggregation on collagenous surfaces by antibodies to human Factor VIII/von Willebrand factor. Brit J Haemat 1980; 44: 127-139
• 30 Jaffe EA, Weksler BB. Recovery of endothelial cell prostacyclin production after inhibition by low doses of aspirin. J Clin Invest 1979; 63: 532-535
• 31 Baenziger NL, Becherer PR, Majerus PW. Characterization of prostacyclin synthesis in cultured human arterial smooth muscle cells, venous endothelial cells, and skin fibroblasts. Cell 1979; 16: 967-974
• 32 Turitto VT, Baumgartner HR, Weiss HJ. The effect of shear rate on platelet interaction with subendothelium exposed to citrated human blood. Microvasc Res 1980; 19: 352
• 33 Kinlough-Rathbone RL, Groves HM, Casenave JP, Richardson MustardJ F. Effect of dipyridamole and aspirin on platelet adherence to damaged rabbit aortas in vitro and in vivo. Fed Proc 1978; 37: 269 (abst).
• 34 Haslam R. Role of cyclic nucleotides in the inhibition of platelet function by physiological and pharmacological agents. Thromb Haemostas 1979; 42: 86 (abst).
• 35 DiMinno G, Silver MH, DeGaetano G. Ingestion of dipyridamole reduced inhibitory effect of prostacyclin on human platelets. Lancet 1979; 2: 701-702