title: Clopidogrel-related refractory bleeding after coronary artery bypass graft surgery: a rationale for the use of coagulation factor concentrates?
abstract: 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 microg/kg 1-deamino-8-D-arginine vasopressin (DDAVP). Two reoperations were performed, but surgical hemostasis was not achieved, so 100 microg/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.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Charité--University Medicine Berlin, Campus Charité Mitte, Berlin, Germany. christian.von_heymann@charite.de
authors.forename: C
authors.initials: C
authors.lastname: von Heymann
authors.forename: H
authors.initials: H
authors.lastname: Schoenfeld
authors.forename: M
authors.initials: M
authors.lastname: Sander
authors.forename: S
authors.initials: S
authors.lastname: Ziemer
authors.forename: H
authors.initials: H
authors.lastname: Grubitzsch
authors.forename: C
authors.initials: C
authors.lastname: Spies
mesh_terms: D000077144:Clopidogrel; D001026:Coronary Artery Bypass; D023903:Coronary Restenosis / Q000188:drug therapy* / Q000601:surgery*; D004334:Drug Administration Schedule; D015942:Factor VIIa / Q000627:therapeutic use*; D005176:Factor XIII / Q000627:therapeutic use; D005340:Fibrinogen / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced* / Q000628:therapy*; D006488:Hemostasis, Surgical; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012086:Reoperation; D019233:Retreatment; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D005340:Fibrinogen; D005176:Factor XIII; D000077144:Clopidogrel; D015942:Factor VIIa; D013988:Ticlopidine