JACC: Platelet response under 70% safe for off-pump CABG
High percentages of platelet inhibitory response to clopidogrel can predict increased blood loss and transfusion requirements post-off-pump CABG with a cutoff value of 70 percent for increased risk of transfusion, despite the proximity of clopidogrel exposure, according to a study published Dec. 7 in the Journal of the American College of Cardiology.

Multiple patients undergoing CABG surgery may be at risk for platelet inhibition. “In view of post-operative blood loss, cardiopulmonary bypass has deleterious effects on the coagulation system and off-pump coronary artery bypass graft (OPCABG) has been proposed as an alternative surgical technique to reduce the risk of transfusion requirement in patients with recent exposure to antiplatelet therapy, but with conflicting results,” the authors wrote.

Young-Lan Kwak, MD, PhD, of the Yonsei University Health System in Seoul, South Korea, and colleagues set out to evaluate the association of the percentage of platelet inhibitory response to clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) as assessed by modified thromboelastography (TEG) with bleeding and transfusion requirement after OPCABG surgery.

Kwak and colleagues enrolled 100 patients between December 2007 and March 2009 who were administered 100 mg of clopidogrel and 75 mg of aspirin within five days of OPCABG surgery. The study’s primary endpoint was post-operative bleeding and transfusion in relation to the tertile distribution of the percentage of platelet inhibitory response to clopidogrel.

The patients were split into two groups: dual-antiplatelet therapy continued until one day before surgery (50 patients) and those who continued dual-antiplatelet therapy until three days prior to surgery (50 patients).

The researchers reported that compared with patients in the first and second tertiles, patients in the third tertile had higher amounts of post-op blood loss. In addition, a higher number of patients in the third tertile required packed red blood cells and fresh frozen plasma transfusions when compared to those in the first and second tertiles.

The researchers noted that incidences of major adverse cardiac event rates and morbidity, as well as changes in troponin T, were similar for all tertiles. However, patients in the third tertile saw longer post-op hospital length of stay. The researchers noted that patients in the third tertile had an 11-fold increased risk of requiring transfusion of allogeneic blood products.

“By avoiding cardiopulmonary bypass, OPCABG has been demonstrated to be a significant factor associated with reduced transfusion requirement regardless of recent clopidogrel exposure and has been proposed as an alternative surgical technique to reduce hemorrhagic complications,” the authors wrote. “Therefore, OPCABG provides an excellent model with which to assess the clinical utility of platelet function assay when assessing post-operative blood loss and transfusion requirement because it is devoid of a major confounding variable on the coagulation system, cardiopulmonary bypass.”

The authors said that TEG platelet mapping assay can provide quantitative analysis of hemostatic status and platelet function. In addition, it can provide a cutoff value of the percentage of platelet inhibitory response to clopidogrel for transfusion requirement after surgery.

“Regardless of the proximity of clopidogrel exposure, patients exhibiting a percentage of platelet inhibitory response to clopidogrel of under 70 percent may safely undergo OPCABG without an increased risk of transfusion requirement,” the authors concluded. “Clinicians are confronted with complex decisions regarding the use of dual-antiplatelet therapy and cessation before surgical revascularization. The findings of the current study might implicate a potential role of modified TEG in deciding the timing of OPCABG in patients who need continued antiplatelet therapy without forfeiting the ischemic benefit.”

“What this study does not say is even more important than what it does say, and it should stimulate further studies. Is this test the best tool to identify the potential bleeders during or after surgery?” wrote Gilles Montalescot, MD, PhD, of the Institut de Cardiologie, Hôpital Pitié-Salpêtrière in Paris, and colleagues in an accompanying editorial.

In addition, they asked, “Is the cutoff value of 70 percent obtained with the TEG platelet mapping assay the ideal threshold for the risk of bleeding? Is this value the same for on-pump surgery? How does it correlate with established point of care assays that have been used in clinical outcome studies performed in stented patients? Is there another threshold for the risk of ischemic events, and shall we now define an optimal surgery window for platelet reactivity to operate on patients?

“We need to realize that the risk of bleeding associated with CABG surgery does not obviate the need for clinical trials evaluating other hard endpoints,” the authors wrote. Montalescot et al wrote that genetic testing and other diagnostic tools and drug therapy can help improve the predictability of platelet function assays and “generate concerted scientific action with anesthetists and cardiac surgeons.”