Clopidogrel-Related Refractory Bleeding after Coronary Artery Bypass Graft Surgery: A Rationale for the Use of Coagulation Factor Concentrates?
DOI:
https://doi.org/10.1532/HSF98.20041122Abstract
Clopidogrel, an irreversible ADP-receptor antagonist, inhibits platelet aggregation mediated by reduced activation of glycoprotein receptor IIb/IIIa. Clopidogrel in combination with aspirin has been shown to be superior to aspirin alone for treating unstable angina, but clopidogrel recipients have shown increases in blood loss, transfusion requirements, and rate of reoperation after cardiac surgery. We describe a patient who had taken clopidogrel 75 mg daily until the day prior to coronary artery bypass graft surgery. Severe postoperative bleeding developed and was refractory to conventional hemostatic therapy consisting of 19 units of packed red blood cell concentrates, 16 of fresh frozen plasma, 8 of platelet apheresis concentrates plus high-dose treatment with aprotinin (500.000 kallikrein-inhibiting units/h) and administration of 0.3 3g/kg 1-deamino-8-D-arginine vasopressin (DDAVP). Two reoperations were performed, but surgical hemostasis was not achieved, so 100 3g/kg recombinant activated factor VII was applied to generate sufficient thrombin to stop the bleeding. This treatment approach reduced the bleeding. Then, to promote clot formation and firmness, 2 g of fibrinogen and 1250 IU of factor XIII were administered, and the bleeding finally stopped. No further transfusions were required, and the patient was discharged from the hospital on day 10 after the operation. This case suggests that in clopidogrel-related bleeding refractory to conventional hemostatic therapy, hemostasis may be achieved by a stepwise administration of coagulation factor concentrates.References
Goedje O, Haushofer M, Lamm P, Reichart B. 1998. The effect of factor XIII on bleeding in coronary surgery. Thorac Cardiovasc Surg 46:263-7.nKam PCA, Nethery CM. 2003. The thienopyridine derivatives (platelet adenosine diphosphate receptor antagonists), pharmacology and clinical developments. Anaesthesia 58:28-35.nLey SJ. 2001. Quality care outcomes in cardiac surgery: the role of evidence-based practice. AACN Clin Issues 12:606-17.nMonroe DM, Hoffmann MJ, Oliver JA, Roberts HR. 1997. Platelet activity of high-dose factor VIIa is independent of tissue factor. Br J Haematol 99:542-7.nMoulton MJ, Creswell LL, Mackey ME, et al. 1996. Reexploration for bleeding is a risk factor adverse outcomes after cardiac operations. J Thorac Cardiovasc Surg 111:1037-46.nMueller T, Haltmayer M, Poelz W, Haidinger D. 2003. Monitoring aspirin 100 mg and clopidogrel 75 mg therapy with the PFA-100 device in patients with peripheral artery disease. Vasc Endovasc Surg 37(2):117-23.nSare GM, Lloyd FR, Stower MJ. 2002. Life-threatening haemorrhage after extracorporeal shockwave lithotripsy in a patient taking clopidogrel. BJU International 90;4:469.nSchroeder V, Chatterjee T, Kohler HP. 2001. Influence of blood coagulation factor XIII and FXIII Val34Leu on plasma clot formation measured by thrombelastography. Thromb Res 104(6):467-74.nSharis PJ, Cannon CP, Loscalzo J. 1998. The antiplatelet effects of ticlopidine and clopidogrel. Ann Intern Med 129:394-405.nYende S, Wunderink RG. 2001. Effect of clopidogrel on bleeding after coronary artery bypass surgery. Crit Care Med 29(12):2271-5.nYusuf S, Zhao F, Mehta SR, et al. 2001. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345(7):494-502.n
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