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DOI: 10.1055/s-0038-1657677
Variable Platelet Response to Low-dose ASA and the Risk of Limb Deterioration in Patients Submitted to Peripheral Arterial Angioplasty
Publication History
Received 10 1997
Accepted after resubmission 13 May 1997
Publication Date:
12 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199701/lookinside/thumbnails/10-1055-s-0038-1657677-1.jpg)
Summary
A group of 100 patients with intermittent claudication (70 male, 30 female), treated with 100 mg ASA per day, were followed over 18 months after elective percutaneous balloon angioplasty. Platelet function was monitored over a period of 12 months by corrected whole blood aggregometry (CWBA). Upon stimulation by arachidonic acid (AA), adenosine diphosphate (ADP) and collagen, CWBA-results were obtained by an electronic acquisition and evaluation system correcting for hematocrit and platelet count of the blood sample.
All patients showed a completely inhibited platelet response to AA stimulation. Comparison of the CWB A-results with clinical parameters revealed that reocclusions at the site of angioplasty occurred exclusively in male patients for which CWBA failed to prove an inhibition of aggregation upon both agonists, ADP and collagen, and for these patients the risk of complication is at least 87% higher (p = 0.0093).
Only 40% of male patients show the expected effect of ASA on in vitro platelet aggregation at any given point in time and CWBA is capable of predicting those male patients which are at an elevated risk of reocclusion following peripheral angioplasty.
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References
- 1 Ridker PM, Manson JE, Buring JE, Muller JE, Hennekens CH. Circadian Variation of Acute Myocardial Infarction and the Effect of Low-Dose Aspirin in a Randomized Trial of Physicians. Circulation 1990; 82: 897-902
- 2 Lorenz RL, Schacky CV, Weber M, Meister W, Kotzur J, Reichardt B, Theisen K, Weber PC. Improved aortocoronary bypass patency by lowdose aspirin (100 mg daily). Effects on platelet aggregation and thromboxane formation. Lancet 1984; 01 (8389) 1261-1264
- 3 Stein B, Fuster V, Israel DH, Cohen M, Badimon L, Badimon JJ, Chesebro JH. Platelet inhibitor agents in cardiovascular disease: an update. J Am Coll Cardiol 1989; 14 (04) 813-836
- 4 Husted SE, Kraemmer-Nielsen H, Krusell LR, Faergeman O. Acetylsalicylic acid 100 mg and 1000 mg daily in acute myocardial infarction suspects: a placebo-controlled trial. J Intern Med 1989; 226 (05) 303-310
- 5 Lewis HD, Davis JW, Archibald DG. Protective effects of Aspirin against acute myocardial infarction and death in men with unstable angina: Results of a Veterans Administration Cooperative Study. N Engl J Med 1983; 309: 396-403
- 6 Steering Committee of the Physicians’ Health Study Research Group: Final report on the aspirin component of the ongoing physicians’ health study. N Engl J Med 1989; 321: 125-129
- 7 Antiplatelet Trialists’ Collaboration: Collaborative overview of randomised trials of antiplatelet therapy-I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994; 308 (6921) 081-106
- 8 Antiplatelet Trialists’ Collaboration: Collaborative overview of randomised trials of antiplatelet therapy-II: Maintenance of vascular graft or arterial patency by antiplatelet therapy. BMJ 1994; 308 (6922) 159-168
- 9 Misselwitz F, Norden C, Heine H. Individually controlled aspirin in the long-term treatment of patients with chronic arterial diseases. Angiology 1989; 40 (05) 464-471
- 10 Cerletti C, Latini R, Del MaschioA, Galletti F, Dejana E, de Gaetano g. Aspirin kinetics and inhibition of platelet thromboxane generationrelevance for a solution of the “aspirin dilemma”. Thromb Haemost 1985; 53 (03) 415-418
- 11 Bertele V, Falanga A, Tomasiak M, Dejana E, Cerletti C, de Gaetano G. Platelet thromboxane synthetase inhibitors with low doses of aspirin: possible resolution of the “aspirin dilemma”. Science 1983; 220 (4596) 517-519
- 12 The Dutch TIA Trial Study Group: A comparison of two doses of aspirin (30 mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. N Engl J Med 1991; 325 (18) 1261-1266
- 13 Hawiger J. Adhesive interactions of platelets and their blockade. Ann-N-YAcad-Sci 1991; 614: 270-278
- 14 Buchanan MR, Brister SJ. Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically. Can J Cardiol 1995; 11 (03) 221-227
- 15 Buchanan MR, Rischke JA, Butt R, Turpie AG, Hirsh J, Rosenfeld J. The sex-related differences in aspirin pharmacokinetics in rabbits and man and its relationship to antiplatelet effects. Thromb Res 1983; 29 (02) 125-139
- 16 Fiore LD, Brophy MT, Lopez A, Janson P, Deykin D. The bleeding time response to aspirin. Identifying the hyperresponder. Am J Clin Pathol 1990; 94 (03) 292-296
- 17 Helgason CM, Bolin KM, Hoff JA, Winkler SR, Mangat A, Tortorice KL, Brace LD. Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994; 25 (12) 2331-2336
- 18 Beving H, Eksborg S, Malmgren RS, Nordlander R, Ryden L, Olsson P. Inter-individual variations of the effect of low dose aspirin regime on platelet cyclooxygenase activity. Thromb Res 1994; 74 (01) 39-51
- 19 Lee TK, Ng SK, Huang ZS, Chen YC. Dissociation of inhibitory effects of low-dose ASA on thromboxane production and platelet aggregation in ischemic stroke patients. J Formos Med Assoc 1992; 91 (09) 891-897
- 20 Spranger M, Aspey BS, Harrison MJ. Sex difference in antithrombotic effect of aspirin. Stroke 1989; 20 (01) 34-37
- 21 Schreiner W, Mueller MR, Premauer W, Wolner E. Computerized Acquisition and Evaluation of Whole Blood Aggregometry Data. Comput Biol Med 1991; 21: 435-441
- 22 Mueller MR, Salat A, Pulaki S, Stangl P, Ergun E, Schreiner W, Losert U, Wolner E. Influence of hematocrit and platelet count on impedance and reactivity of whole blood for electrical aggregometry. JPM 1995; 34: 17-22
- 23 Mueller MR, Schreiner W, Wohlfahrt A, Salat A, Wolner E. The influence of sample age on collagen-induced platelet aggregation in whole blood. Thromb Res 1990; 60: 477-487
- 24 Mueller MR, Salat A, Pulaki S, Schreiner W, Ergun E, Koppensteiner R, Losert U, Wolner E. Platelet function after total artificial heart replacement: clinical application and experiment. J Heart Lung Transplant 1993; 12 (03) 450-459
- 25 Mantel N, Byar DP. Evaluation of Response-Time Data Involving Transient States: An Illustration Using Heart-Transplant Data. Journal of the American Statistical Association. 1974. 69. 81-86
- 26 StatXact-Turbo. Statistical Software for Exact Nonparametric Inference. Cytel Software Corporation; Cambridge, MA, USA:
- 27 Willard JE, Lange RA, Hillis LD. The use of aspirin in ischemic heart disease. N Engl J Med 1992; 327 (03) 175-181
- 28 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 1986; 32 (03) 415-423
- 29 Toivanen J, Ylikorkala O, Viinikka L. One milligramme of acetylsalicylic acid daily inhibits platelet thromboxane A2 production. Thromb Res 1984; 35 (06) 681-687
- 30 Mohri H, Ohkubo T. Single-dose effect of enteric-coated aspirin on platelet function and thromboxane generation in middle-aged men. Ann Pharmacother 1993; 27 (04) 405-410
- 31 Philp RB, Paul ML. Salicylate antagonism of acetylsalicylic acid inhibition of platelet aggregation in male and female subjects: influence of citrate concentration. Haemostasis 1986; 16 (05) 369-377
- 32 Pappas JM, Westengard JC, Bull BS. Population variability in the effect of aspirin on platelet function. Implications for clinical trials and therapy Arch Pathol Lab Med 1994; 118 (08) 801-804
- 33 Rao GH, White JG. Influence of various doses of aspirin (in vivo) on platelet arachidonic acid metabolism (ex vivo) and function. Prostaglandins Leukot Essent Fatty Acids 1994; 51 (01) 63-67
- 34 Violi F, Alessandri C, Pratico D, Guzzo A, Ghiselli A, Balsano F. Inhibition of cyclooxygenase-independent platelet aggregation by sodium salicylate. Thromb Res 1989; 54 (06) 583-593
- 35 FitzGerald GA, Oates JA, Hawiger J, Maas RL, Roberts 2d LJ, Lawson JA, Brash AR. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest 1983; 71 (03) 676-688
- 36 Trentalange MJ, Walts LF. A comparison of thromboelastogram and template bleeding time in the evaluation of platelet function after aspirin ingestion. J Clin Anesth 1991; 3 (05) 377-381
- 37 Kretschmer V, Schikor B, Sohngen D, Dietrich G. In vitro bleeding test – a simple method for the detection of aspirin effects on platelet function. Thromb Res 1989; 56 (05) 593-602
- 38 Orlikowski CE, Payne AJ, Moodley J, Rocke DA. Thrombelastography after aspirin ingestion in pregnant and non-pregnant subjects. Br J Anaesth 1992; 69 (02) 159-161
- 39 Stampfer MJ, Jakubowski JA, Deykin D, Schafer AI, Willett WC, Hennekens CH. Effect of altemate-day and enteric-coated aspirin on platelet aggregation, bleeding time, and thromboxane A2 levels in bleeding-time blood. Am J Med 1986; 81: 400-404
- 40 De Caterina R, Lanza M, Manca G, Strata GB, Maffei S, Salvatore L. Bleeding time and bleeding: an analysis of the relationship of the bleeding time test with parameters of surgical bleeding. Blood 1994; 84 (10) 3363-3370
- 41 Bom GVR. Quantitative investigation into the aggregation of blood platelets. J Physiol 1962; 16: 67-68
- 42 Taylor RR, Strophair J, Sturm M, Vandongen R, Beilin LJ. Time dependence of whole blood aggregation in response to platelet activating factor (PAF). Thromb Haemostasis 1988; 59 (02) 162-163
- 43 Hardeman MR, Vreeken J, Goedhart PT, Oosting PR. Transient aggregation resistance of human blood platelets in fresh plasma. I. Methodology. Thromb Res 1989; 54 (06) 719-731
- 44 Ingerman-Wojenski C, Smith B, Silver MJ. Evaluation of electrical aggregometry: comparison with optical aggregometry, secretion of ATP, and accumulation of radiolabeled platelets. J Lab Clin Med 1983; 101: 44-52
- 45 Clemmons RM, Bliss EL, Dorsey-Lee MR, Seachord CL, Meyers KM. Platelet function, size and yield in whole blood and in platelet-rich plasma prepared using differing centrifugation force and time in domestic and food-producing animals. Thromb Haemost 1983; 50 (04) 838-843
- 46 Cardinal DC, Flower RJ. The electronic aggregometer: A novel device for assessing platelet behavior in blood. JPM 1980; 03: 135-158
- 47 Boyd DG, Davis RB. Observations on human platelet aggregation in native whole blood: synergism and sensitivity to aggregating agents in vitro. Thromb Res 1988; 50 (03) 429-436
- 48 Russell-Smith N, Flower RJ, Cardinal DC. Measuring platelet and leucocyte aggregation/adhesion responses in very small volumes of whole blood. JPM 1981; 06: 315-333
- 49 Mackie IJ, Jones R, Machin SJ. Platelet impedance aggregation in whole blood and its inhibition by antiplatelet drugs. J Clin Pathol 1984; 37: 874-878
- 50 Valles J, Santos MT, Marcus AJ, Safier LB, Broekman MJ, Islam N, Ullman HL, Aznar J. Downregulation of human platelet reactivity by neutrophils. Participation of lipoxygenase derivatives and adhesive proteins. J Clin Invest 1993; 92 (03) 1357-1365
- 51 Valles J, Santos MT, Aznar J, Marcus AJ, Martinez-Sales V, Portoles M, Broekman MJ, Safier LB. Erythrocytes metabolically enhance collageninduced platelet responsiveness via increased thromboxane production, adenosine diphosphate release, and recruitment. Blood 1991; 78 (01) 154-162
- 52 De La CruzJP, Pavia J, Bellido I, De La Cuesta SanchezF. Effect of trifiusal and acetylsalicylic acid on platelet aggregation in human whole blood: influence of red blood cells and leukocytes. Methods Find Exp Clin Pharmacol 1988; 10 (06) 363-367
- 53 Sathiropas P, Marbet GA, Sahaphong S, Duckert F. Detection of small inhibitory effects of acetylsalicylic acid (ASA) by platelet impedance aggregometry in whole blood. Thromb Res 1988; 51 (01) 55-62
- 54 Zwierzina WD, Kunz F, Kogelnig R, Herold M. Sex-related differences in platelet aggregation in native whole blood. Thromb Res 1987; 48 (02) 161-171
- 55 Brezinski DA, Nesto RW, Serhan CN. Angioplasty triggers intracoronary leukotrienes and lipoxin A4. Impact of aspirin therapy. Circulation 1992; 86 (01) 56-63
- 56 Watala C, Gwozdzinski K. Effect of aspirin on conformation and dynamics of membrane proteins in platelets and erythrocytes. Biochem Pharmacol 1993; 45 (06) 1343-1349
- 57 Winocour PD, Watala C, Perry DW, Kinlough-Rathbone RL. Decreased platelet membrane fluidity due to glycation or acetylation of membrane proteins. Thromb Haemost 1992; 68 (05) 577-582
- 58 Burris SM, Smith SM, Rao GHR, White JG. Aspirin treatment reduces platelet resistance to deformation. Arteriosclerosis 1987; 07: 385-388
- 59 Smith SM, Burris SM, Rao GHR, White JG. Epinephrine-induced reversal of aspirin effects on platelet deformability. Thromb Res 1988; 51: 35-44
- 60 Schwartz L, Bourassa MG, Lesperance J, Aldridge HE, Kazim F, Salvatori VA, Henderson M, Bonan R, David PR. Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med 1988; 318 (26) 1714-1719
- 61 Terres W, Hamm CW, Ruchelka A, Weilepp A, Kupper W. Residual platelet function under acetylsalicylic acid and the risk of restenosis after coronary angioplasty. J Cardiovasc Pharmacol 1992; 19 (02) 190-193