IJCS | Volume 33, Nº3, May / June 2020

240 Lima et al. Unfractionated bovine heparin safety Int J Cardiovasc Sci. 2020; 33(3):235-242 Original Article the first two hours or 300 ml/h in the first 3 hours. Over longer periods, the maximum volume of blood loss is 1,000 ml in the first 4 hours or 1,200 ml in the first 5 hours. However, these values are always individualized considering the patient’s hemodynamic status, blood volume, other coagulation factors to be corrected and bleeding tendency. Our study showed data quite comparable to the published values for bovine and porcine UFH groups, with volume bleeding within the normal limits described above. Two patients presented bleeding above normal levels. Abnormal bleeding can lead to further surgical intervention. Some risk factors have been identified in need for surgical re-exploration due to bleeding in cardiac surgery with ECC and include advanced age, presence of renal failure, non-coronary surgery, prolonged ECC, and thrombolytic therapy 48 hours before the surgical procedure, 5 among others. The percentage of re-operation observed in the bovine UFH group was 0.98%, well below the published values, ranging from 3 to 5%. In the porcine UFH group, the rate of re-operation was similar to that published (3.08%). 20,21 The systemic response to heparin may present differences among individuals, with either favorable or adverse effects from its anti-coagulant properties. 22,23 Therefore, monitoring its use and the safety of its effectiveness are fundamental to avoid clot formation during ECC. This study presented two cases of thrombotic complications, one from each treatment group. Published data show that ACT values ​above 400 seconds are considered safe during ECC. 24,25 Our study showed that the bovine UFH used was effective in the patient’s anticoagulation, maintaining ACT levels above 400 seconds for most patients during the whole procedure. Three patients (1.47%) presented ACTs less than 400 seconds after the initial dose of bovine UFH but no clinical report of pro-coagulation changes; correction with a dose of heparin (usually 50 mg) was made to reach the target level. Some patients presented ACT values of over 2,000 seconds, which are considered uncoagulable, but patients did not show any complication. The reasons for the discrepancy between the high ACT value and the lack of bleeding in these cases are not clear from the clinical records. In their 25-year review of coronary artery bypass grafting surgeries, Sellman et al., 26 reported a 3.7% rate of bleeding re-operations not related to a specific site, suggesting the presence of blood dyscrasia. 26 However, in our study, both groups seem to respond similarly in clinical terms; the procedure was safe and reached baseline ACT levels after protamine administration without any adverse medical event. A few patients (23.5%of bovine UFH and 35.4%of porcine UFH) needed an additional dose of protamine. The reversibility of heparin by protamine is usually observed with a protamine dose of about 75 to 120%of the bovine heparin dose administered, while porcine UFH requires a higher dose of protamine for its neutralization. 27 Gomes et al., 28 found no statistically significant difference between bovine and porcine heparin regarding the dosage used, ACT, total bleeding after surgery and protamine dosage needed for neutralization. 28 Performing surgical studies as clinical randomized trials is challenging. 29,30 Observational studies serve to fill the gap by evaluating real-life situations, thus being closer to external validity. Our research has the limitation of being descriptive only, because of its exploratory and retrospective nature, where patients were submitted to surgery in different years, by different teams and following non-standard procedures. However, we were not looking for comparative results at this point. Rather, we aimed to report the use of bovine UFH in routine medical practice. This preliminary analysis of safety supports larger, comparable studies. Conclusion In conclusion, this study contributes to more clinical data available concerning the use of bovine UFH. The adverse events reported were expected according to the nature of the drug, and bovine UFHwas safe for on-pump cardiac surgery. Acknowledgment The authors acknowledge comprehensive editorial and writing assistance from Mariana Matos M.D., medical writer.  The research teampresented part of the study results as a poster in the 45 th Brazilian Congress of Cardiovascular Surgery in 2018.  Author contributions Conception and design of the research: Torres FAL, Torres ACB, Cordeiro TMG. Acquisition of data: Torres FAL, Torres ACB, Ribeiro A, Maia CO, Almeida FP, Roceto J, Matkovski JA, Kovalski MG, Pizato VA. Analysis and interpretation of the data: Torres FAL,