Aprotinin shows both hemostatic and antithrombotic effects during off-pump coronary artery bypass grafting.
BACKGROUND
Hemostatic drugs are widely thought to be unnecessary and potentially detrimental in off-pump coronary artery bypass graft surgery (OPCABG), despite well-established use in on-pump surgery. In a randomized, prospective OPCABG trial, we assessed efficacy and safety of aprotinin through a comprehensive assessment of graft patency and hematologic function.


METHODS
Sixty patients were randomly assigned to full-dose aprotinin or placebo. Heparin was titrated to a kaolin-based activated clotting time of greater than 300 seconds. Exclusionary criteria included creatinine greater than 2 mg/dL, conversion to on-pump CABG, and preoperative GPIIb/IIIa inhibition. Hematologic assessments were obtained preoperatively, at the end of surgery, and on days 1 and 3: mean platelet volume, thrombin generation (prothrombin fragment 1.2 assay), and aspirin resistance using a modified thrombelastography, whole blood aggregometry, 11-dehydro-thromboxane B2 levels, and flow cytometry. Thrombotic events were defined as postoperative myocardial infarction by electrocardiography or elevated troponin I, clinical stroke by examination and head computed tomography, and bypass graft failure by multichannel computed tomography angiography on day 5.


RESULTS
Aprotinin was associated with a significant reduction in intraoperative and postoperative blood loss compared with placebo but had no effect on transfusion rates. Patients treated with aprotinin had significantly fewer thrombotic events (3% versus 23%, p < 0.05, Fisher's exact test) and less postoperative aspirin resistance (20% versus 46%, respectively, p < 0.05, Fisher's exact test). Postoperative prothrombin fragment 1.2 level was reduced by aprotinin use.


CONCLUSIONS
Aprotinin reduced perioperative bleeding after OPCABG. Preserved aspirin sensitivity in the aprotinin group may explain the observed reduction in thrombotic events and might be related to the suppression of perioperative and transmyocardial thrombin formation.
Poston
Robert S
RS
Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA. rposton@smail.umaryland.edu
White
Charles
C
Gu
Junyan
J
Brown
James
J
Gammie
James
J
Pierson
Richard N
RN
Lee
Andrew
A
Connerney
Ingrid
I
Avari
Thrity
T
Christenson
Robert
R
Tandry
Udaya
U
Griffith
Bartley P
BP
D007611:Aprotinin / Q000627:therapeutic use*; D001241:Aspirin / Q000494:pharmacology; D015415:Biomarkers; D001780:Blood Coagulation Tests; D016063:Blood Loss, Surgical; D047549:Coronary Artery Bypass, Off-Pump; D023903:Coronary Restenosis / Q000453:epidemiology; D004311:Double-Blind Method; D004351:Drug Resistance; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006083:Graft Occlusion, Vascular / Q000453:epidemiology; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D011183:Postoperative Complications / Q000453:epidemiology / Q000517:prevention & control; D019106:Postoperative Hemorrhage / Q000453:epidemiology / Q000517:prevention & control*; D011446:Prospective Studies; D011516:Prothrombin / Q000032:analysis; D020521:Stroke / Q000453:epidemiology; D013916:Thrombelastography; D013917:Thrombin / Q000032:analysis; D013927:Thrombosis / Q000453:epidemiology / Q000517:prevention & control*
D015415:Biomarkers; D005343:Fibrinolytic Agents; D006490:Hemostatics; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D007611:Aprotinin; D013917:Thrombin; D001241:Aspirin