Desmopressin Effect on Acetylsalicylic Acid Impaired Platelet Punction

Abstract

The mechanism of DDAVP's shortening of acetylsalicylic acid (ASA) prolonged bleeding times was investigated. Sixteen healthy subjects received two dosages of ASA (100 mg) in 12 hours. Twenty four hours after the first ASA application and again after 32 hours DDAVP was administered intravenously (0.4 μLg/kg). The trial was terminated after 48 hrs. In between, blood samples were drawn and analyzed for the in vivo bleeding time (Simplate^® time), in vitro bleeding test (IVBT, Thrombostat 4000), von Willebrand factor antigen (vWf:Ag), Ristocetin cofactor activity (vWf R:Co), plasma β-thromboglobulin (β-TG), platelet ATP/ADP, platelet aggregation (collagen, ADP, arachidonic acid), and plasma and platelet thromboxane levels. Simplate ^® time (BT) and IVBT showed an excellent inverse correlation with vWf R:Co (r² _BT = 0.97 and r² _1VBT = 0.99, respectively) during the time when DDAVP was administered, suggesting the involvement of plasma vWF in DDAVP's shortening of the bleeding time. The involvement of plasma thromboxane in this mechanism could be excluded. In addition, DDAVP hampered platelet aggregation tests, possibly due to the inhibition of the release reaction (reduced β-TG in plasma) by a direct interaction with platelets.

Keywords

bleeding time - Thrombostat - acetylsalicylic acid - Desmopressin - thromboxane

• References

• 1 Hamberg MJ, Svensson J, Samuelsson B. Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci USA 72: 2994-2995 1975;
• 2 Mielke CH. Influence of aspirin on platelets and the bleeding time. Am J Med 74: 72-78 1983;
• 3 Smith JB, Willis AL. Aspirin selectively inhibits prostaglandin production in human platelets. Nature (New Biol) 231: 235-237 1971;
• 4 Roth GL, Majerus PW. The mechanism of the effect of aspirin on human platelets. Acetylation of a particulate fraction protein. J Clin Invest 56: 624-630 1975;
• 5 Moncada S, Vane JR. Arachidonic acid metabolites and the interactions between platelets and blood vessel walls. N Engl J Med 300: 1142-1147 1979;
• 6 Fields WS, Lemak NA, Frankowsky RF, Hardy RJ. Controlled trial of aspirin in cerebral ischemia. Stroke 8: 301-316 1977;
• 7 Barnett JJM, McDonald JWD, Sackett DL. Aspiri—effective in males threatened with stroke. Stroke 9: 295-298 1978;
• 8 Bousser MG, Eschwege E, Haguenau M, Lefaucounier JM, ThibuIt N, Touboul D, Touboul PJ. “ACICLA” controlled trial of aspirin and dipyridamole in the secondary prevention of a thrombotic cerebral ischemia. Stroke 14: 5-14 1983;
• 9 Breddin K, Loew D, Lechner K, Überla K, Walter E. Secondary prevention of myocardial infarction: A comparison of acetylsalicylic acid, placebo and phenprocoumon. Haemostasis 9: 325-344 1980;
• 10 Cairns JA, Gent M, Singer J, Finnie KJ, Frogatt GM, Holder DA, Jablonsky G, Kostuk WJ, Melendez LJ, Myers MG, Sackett DL, Sealey BJ, Tanser PH. Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial. N Engl J Med 313: 1369-1375 1985;
• 11 Lorenz RL, Weber M, Kotzur J, Theissen K, von Schacky C, Meister W, Reichardt B, Weber PC. Improved aortocoronary bypass patency by low dose aspirin (100 mg daily). Lancet 1: 1261-1264 1984;
• 12 Rubin RN. Aspirin and post surgery bleeding. Ann Intern Med 89: 1006 1978;
• 13 Cash JD, Gader AMA, Da Costa J. The release of plasminogen activator and factor VIII by LVP, AVP, DDAVP, AT III and OT in man. Br J Haematol 27: 363-364 1974;
• 14 Mannucci PM, Aberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 30: 81-93 1975;
• 15 Di Michele DM, Hathaway WE. Use of DDAVP in inherited and acquired platelet dysfunction. Am J Hematol 33: 39-45 1990;
• 16 Mannucci PM, Vincente V, Vianello L, Cattaneo M, Alberca I, Coccato MP, Faioni E, Mari D. Controlled trial of Desmopressin in liver cirrhosis and other conditions associated with a prolonged bleeding time. Blood 67: 1148-1153 1986;
• 17 Warrier AJ, Lusher JM. DDAVP: A useful alternative to blood components in moderate hemophilia A and von Willebrand disease. J Pediatr 102: 228-233 1983;
• 18 Wijermans PW, van-Dorp DB. Hermansky-Pudlak syndrome: correction of bleeding time by l-desamino-8D-arginine vasopressin. Am J Hematol 30: 154-157 1989;
• 19 Lekas MD, Crowley JP. Easy bruisability, aspirin intolerance, and response to DDAVP. Laryngoscope 103: 156-159 1993;
• 20 Pfueller SL, Howard MA, White JG, Menon C, Berry EW. Shortening of bleeding time by l-deamino-8-arginine vasopressin (DDAVP) in the absence of platelet von Willebrand factor in gray platelet syndrome. Thromb Haemost 58: 1060-1063 1987;
• 21 Boysen G, Boss AH, Odum N, Olsen JS. Prolongation of bleeding time and inhibition of platelet aggregation by low-dose acetylsalicylic acid in patients with cerebrovascular disease. Stroke 15: 241-243 1984;
• 22 Patrono C, Ciabattoni G, Pinca E, Pugliese F, Castrucci GG, De Salvo A, Satta MA, Peskar BA. Low-dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res 17: 317-327 1980;
• 23 Kuster LJ, Frolich JC. Platelet aggregation and thromboxane release induced by arachidonic acid, collagen, ADP and platelet activating factor following low dose acetylsalicylic acid in man. Prostaglandins 32: 415-423 1986;
• 24 Kretschmer V, Schikor D, Söhngen D, Dietrich G. In-vitro bleeding test—a simple method for the detection of aspirin effects on platelet function. Thromb Res 56: 593-602 1989;
• 25 Marx R, Schulte F. Über einen klinischen Schnelltest zur Erfassung von hereditären und erworbenen Thrombocytopathien. Blut 24: 137-141 1972;
• 26 Mielke CH, Kaneshiro MM, Maher IA, Weiner IM, Rapaport SI. The standardized nonnal Ivy bleeding time and prolongation by aspirin. Blood 34: 204-215 1969;
• 27 Channing Rodgers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemostl 6: 1-20 1990;
• 28 Dietrich G, Weber D, Kretschmer V. In-vitro bleeding test; standardization of the methodical procedure. Lab Med 17: 317-323 1993;
• 29 Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Chern 15: 45-52 1966;
• 30 Brinkhous KM, Read MS. Preservation of platelet receptors for platelet aggregation factor by air drying, freezing, or lyophilization: new stable preparations for von Willebrand factor assays. Thromb Res 13: 591-597 1978;
• 31 Holmsen H, Holmsen I, Bernhard A. Microdetermination of adenosine diphosphate and adenosine triphosphate in plasma with firefly luciferase system. Anal Biochem 17: 456-466 1966;
• 32 Schweer H, Kammer J, Kühl PG, Seyberth HW. Determination of peripheral plasma prostanoid concentration: An unreliable index of 'in vivo' prostanoid activity. Eur J Clin Pharmacol 164: 156-163 1987;
• 33 Schweer H, Meese CO, Fürst O, Kühl PG, Seyberth H. Tandem mass spectrometric detennination of 11-dehydrothromboxane B₂ in plasma and urine. Anal Biochem 164: 156-163 1987;
• 34 Mielke CH. Aspirin prolongation of the template bleeding time: Influence of venostasis and direction of incision. Blood 60: 1139-1142 1982;
• 35 Nuotto E, Gardin A, Paasonen MK, Metsä-Ketelä T, Caminisiou U. Effect of acetylsalicylic acid on plasma thromboxane B₂ and platelet aggregation in man. Eur J Clin Pharmacol 25: 313-317 1983;
• 36 Dale J, Thaulow E, Myhre E, Parry J. The effect of a thromboxane synthetase inhibitor, dazoxiben, and acetylsalicylic acid on platelet function and prostaglandins metabolism. Thromb Haemost 50: 703-706 1983;
• 37 Yang X, Disa J, Koneti Rao A. Effect of l-desamino-8-D-arginine vasopressin (DDAVP) on human platelets. Thromb Res 59: 809-818 1990;