bleeding after cardiopulmonary bypass ( cpb ) is still a concern for coronary artery bypass graft surgery ( cabg ) and an important factor in terms of morbidity and mortality rates in patients undergoing cardiac operations . between 30% and 70% of open heart surgery patients will require blood product transfusion.1 although small , the risk of transmitting hepatitis , human immunodeficiency virus , cytomegalovirus , or other infectious agents remains a concern . coagulopathy is multi - factorial , and platelet dysfunction and plasmin - induced fibrinolytic activity are known as the major contributors to the process.2 aprotinin , a serine protease inhibitor from the bovine lung , and the synthetic anti - fibrinolytic drugs , tranexamic acid ( ta ) and e - amino - n - caproic acid ( eaca ) , given before cpb have been shown to reduce mediastinal bleeding postoperatively.37 anti - fibrinolytic drugs have been demonstrated to be as effective as aprotinin in reducing bleeding and the use of allogeneic blood products , both in high - risk patients and routine patients undergoing cardiac operations.8 anti - fibrinolytic drugs are much cheaper than aprotinin and equally effective in reducing bleeding during cardiac operations . furthermore , given recent reports on the adverse effects of aprotinin on graft patency and survival,9 , 10 we sought to recruit a homogeneous patient population undergoing elective cabg in order to estimate the influence of low - dose aprotinin and ta on perioperative bleeding , need for allogeneic transfusion , and hemostasis . after institutional approval was obtained for this double - blind , clinical , randomized trial , all patients scheduled for cabg in our center between 21 march 2008 and 21 march 2009 were included in this study . the inclusion criteria were comprised of on - pump cabg and patients consent , and the exclusion criteria comprised history of hemorrhagic tendency and blood dyscrasia , history of plavix use , known hepatic , renal , and metabolic diseases , use of other anti - coagulation drugs like coumadin for valvular disease and arrhythmias and streptokinase , emergency surgery , rheumatic heart disease , known allergy to aprotinin or transamine and prohibition for their use on the grounds of acquired visual defects and retinal disease , subarachnoid hemorrhage , disseminated intravascular coagulation , gall bladder disease , leukemia , embolization , and vein thrombosis . the patients demographic and clinical data such as age , sex , history of cigarette smoking , and other concomitant diseases were collected ( table 1 ) . after the patients provided informed written consent , they were blindly randomized into three groups of 50 persons . in group a ( aprotinin ) , after the test dose , 1 million units of aprotinin was added to the pump prime solution ; in group b ( transamine ) , 1 gr of transamine was added to the pump prime solution and another 1 gr was used intravenously after the discontinuation of the pump ; and in group c ( control ) , 250 cc of normal saline was utilized as placebo after the induction of anesthesia . the amounts of mediastinal and plural blood shed were measured after six , twelve , and twenty - four hours , and the data were stored in a computer . packed red cell was transfused for a hematocrit concentration < 30% , and fresh frozen plasma was transfused based on abnormal prothrombin times and bleeding rates . postoperative complications like postoperative myocardial infarction ( based on rise in cardiac enzyme , change in ecg , and change in the ejection fraction estimated by echocardiography ) , neurological complications ( estimated by clinical examination and ct - scanning ) , redo - operations for surgical bleeding and pericardial effusion , kidney complications ( rise in serum creatinine and low urinary output < 0.5 cc per minute ) , and other complications were studied . the parametric data of the patients were compared using an unpaired student t - test for the quantitative data and k2 for the qualitative data . the distribution of sex ( p value = 0.308 ) , age ( p value = 0.973 ) , cigarette smoking ( p value = 0.720 ) , hyperlipidemia ( p value = 0.707 ) , diabetes ( p value = 0.960 ) , and hypertension ( p value = 0.786 ) was the same in all the groups ( table 1 ) , and there was no important statistical difference between these variables . the amounts of blood drainage from chest and mediastinal drains were significantly less in the aprotinin and transamine groups than the amount in the placebo group , and this was statistically important ( p value < 0.001 ) . only 2 patients needed reoperation for bleeding : 1 in group b and 1 in group c ; both of the cases were surgical bleeding and there was no statistically important difference with regard to need for reoperation between the three groups ( p value = 0.998 ) ( table 3 ) . other complications after surgery in the three groups were statistically the same , with there being no statistically significant difference between the three groups ( table 3 ) . there were 8 cases of postoperative myocardial infarction ( based on rise in cardiac enzyme , change in ecg , and change in the ejection fraction estimated by echocardiography ) : 4 in group c , 2 in group a , and 2 in group b ( p value = 0.730 ) ( table 3 ) . two patients in group c were re - operated on for pericardial effusion , and 2 patients ( 1 in the placebo group and 1 in the aprotinin group ) had neurological complications . renal complications were observed in 2 ( 4% ) patients in the transamine group and 1 in each of the other groups . all the neurological and renal complications were reversed before the patients were discharged from hospital . all the complications had a good course , and all the patients were discharged uneventfully from hospital ( table 3 ) . in the transamine group , 35 ( 70% ) patients did not require blood transfusion , 4 patients needed one unit of packed cell , and 1 patient received six units of packed cell . in the aprotinin group , 19 ( 38% ) patients received one unit of packed cell . in the placebo group , 23 ( 46% ) patients received one unit of packed cell , 5 ( 10% ) patients received two units , and 1 received four units of packed cell . a meta - analysis of multiple studies in the existing literature shows that aprotinin and anti - fibrinolytic drugs can reduce mediastinal chest tube drainage by 30% in comparison with placebos.11 whereas delivery protocols are uniform for aprotinin , they still vary widely for ta and eaca . the effect of ta and aprotinin on reducing blood loss after cardiac surgery is clear;12 be that as it may , a meta - analysis of randomized studies of eaca versus placebo could not show a significant effect in reducing transfusion requirements.13 ta has been shown to be both as effective as aprotinin in reducing coagulopathy - caused bleeding after cpb and cheaper than aprotinin.12 ta is emerging as the drug of choice for reducing coagulopathy - caused bleeding . in addition , concerns have been raised recently regarding the adverse effects of aprotinin on the renal system and final outcome.10 we , therefore , designed the present study to investigate not only the benefits of low - dose ta and low - dose aprotinin in terms of reducing blood loss and allogeneic transfusion but also their effects on various coagulation factors . in a low - risk patient population , ta was shown to decrease mediastinal bleeding after cardiac operations as early as 1990.14 a similar result was reported in the studies by karski and associates from toronto.15 the first significant study of a uniform patient population undergoing coronary surgery was conducted by roussou and colleagues,16 who retrospectively studied 415 patients undergoing cabg excluding emergency and redo operations . the first 209 patients were operated on without ta , and the subsequent 206 patients with a 2 gr bolus of ta followed by 8 gr during the procedure . chest tube drainage in the control group was 1,114 ml versus 803 ml in the study group . a double - blind , randomized , placebo - controlled study was carried out by the brook - army medical center17 on patients undergoing primary coronary artery operations . in that study , ta was commenced at 15 mg / kg before cpb and was continued at 1 mg / kg for five hours : the bleeding was reduced from 1,202 ml in the placebo group versus 1,020 ml in the ta group . since then , multiple prospective studies have shown the efficacy of ta , by comparison with aprotinin or eaca.9 , 18 these studies mostly included patient populations that were at high risk for bleeding in conjunction with those of primary myocardial revascularization . since 1998 , there have also been a few studies containing placebo groups with primary myocardial revascularization ; these investigations used high - dose ta or administered ta well into the postoperative period . with improved cpb and surgical techniques , blood loss is small after routine primary cabg even without resorting to antifibrinolytics.18 consequently , it is a valid question to ask whether the addition of low - dose ta or aprotinin , as was administered in the present study , is beneficial . in light of our findings , our control patients bled only 540ml in twenty - four hours , but the use of ta and aprotinin significantly reduced this even further to 355 and 380 ml . both aprotinin and ta , even when administered in low doses , can significantly reduce blood loss and transfusion requirement in cabg without importantly increasing mortality and morbidity .
background : cardiovascular operations are associated with an inherent bleeding tendency that sometimes leads to severe bleeding and transfusion requirement . pharmacological intervention to minimize post - bypass bleeding and blood product transfusions 
 has received increasing attention from both medical and economic viewpoints.methods:this double - blind , randomized , placebo - controlled clinical trial recruited three groups of patients ( each group consisting of 50 patients ) undergoing on - pump coronary artery bypass graft surgery ( cabg ) and blindly randomized them to receive either low aprotinin , tranexamic acid , or placebo . 
 the results were , subsequently , evaluated and compared between the groups . 
 all the patients were operated on by one surgeon and the same surgery team.results:the following variables were similar between the groups , and there was no statistically significant difference between the groups in terms of these variables : age ( p value = 0.308 ) , sex ( p value = 0.973 ) , hyperlipidemia ( p value = 0.720 ) , hypertension ( p value = 0.786 ) , smoking ( p value = 0.72 ) , and diabetes ( p value = 0.960 ) . 
 the amounts of drainage from chest tubes were less in the aprotinin and tranexamic acid groups than the amount in the placebo group ; the difference was statistically important ( p value < 0.001 ) . 
 there was no statistically significant difference with respect to need for reoperation for bleeding between the three groups ( p value = 0.998 ) . 
 complications following surgery in the three groups were statistically the same and not significantly different . 
 all the complications ( myocardial infarction , pericardial effusion , neurological complication and renal complication ) had a good course , and all the patients were discharged from the hospital uneventfully . 
 there was no mortality in any group.conclusion:low-dose aprotinin and tranexamic acid can significantly reduce blood loss and transfusion requirement in cabg without importantly increasing mortality and morbidity .