Wednesday, August 20, 2008

Antifibrinolytics by Bharesh Dedhia

Bharesh Dedhiae
Aminocaproic acid (EACA, Amicar) and its analogue, tranexamic acid (TA) are derivatives of the amino acid lysine. Both of these drugs inhibit the proteolytic activity of plasmin and the conversion of plasminogen to plasmin by plasminogen activators. Plasmin cleaves fibrinogen and a series of other proteins involved in coagulation. Tranexamic acid is 6 to 10 times more potent than e-aminocaproic acid. Most of the early studies using antifibrinolytic agents showed decreased mediastinal drainage in patients treated with EACA. However, many of these studies lacked controls, were retrospective, and not blinded .In 350 patients undergoing coronary artery bypass grafting (CABG), Del Rossi reported using a low dose of EACA a significant decrease in mediastinal drainage and red blood cell (RBC) transfusion with no difference in myocardial infarction (MI) or stroke . Vander Salm recently reported a reduction in chest tube drainage in 51 patients who received EACA. In addition, there were no differences in platelet function between EACA and the placebo group, and no differences in blood transfusion. Horrow later studied TA given in a prophylactic manner prior to skin incision for primary CABG surgery. The 12 hour postop blood loss was 496 ml in the TA group compared to 750 ml in the placebo group. However, transfusions were not different. In another study they again found decreased chest tube drainage in patients receiving TA compared to those receiving placebo, but found no increased benefit by administering DDAVP concurrently .In the literature there have been a small number of thrombotic complications between patients receiving lysine analogs. Although the design of these studies have not been routinely prospective, the incidence of these complications in routine CABG is low, and a small number of patients have been studied. Prospective studies evaluating safety issues including the risk of perioperative MI, graft patency, and renal dysfunction still need to be studied. TA is approved for use in the US to prevent bleeding in patients with hereditary angioedema undergoing teeth extraction, but has no FDA indication for use in CPB. Most studies report lysine analogues in first-time CABG where the risk of bleeding is low, and not in complex cases. A large RCT is needed before widespread use can be advocated.Bharesh Dedhia