Platelet function analysed by ROTEM platelet in cardiac surgery after cardiopulmonary bypass and platelet transfusion.

OBJECTIVES: The aim of this study was to investigate whether ROTEM platelet can provide additional information to the traditional ROTEM analysis to guide treatment with platelet transfusions in cardiac surgery and to identify factors triggering platelet administration. BACKGROUND: Platelets play a crucial role in coagulation and haemostasis after cardiac surgery. Excessive bleeding after cardiopulmonary bypass usually requires transfusions of blood products, including platelets. The ROTEM platelet is a novel point-of-care analysis for whole blood. MATERIALS AND METHODS: We included 23 patients scheduled for complex cardiac surgery. ROTEM (in-tem, ex-tem), ROTEM platelet (ARA-tem, ADP-tem and TRAP-tem) and platelet count were analysed before induction of anaesthesia (T0), after cardiopulmonary bypass and protamine reversal (T1) and after platelet transfusion (T2, n = 10). RESULTS: ROTEM and ROTEM platelet tests were all significantly reduced between T0 and T1. ROTEM parameters improved significantly after platelet transfusion. Regarding ROTEM platelet, only TRAP-tem increased between T1 and T2 (P = .008). Factors triggering platelet transfusion were long duration of surgery and time on cardiopulmonary bypass. CONCLUSION: ROTEM platelet with thrombin activation, TRAP-tem, improved significantly, indicating that platelet transfusion may reverse cardiopulmonary bypass-induced platelet dysfunction. Further studies are needed to evaluate whether TRAP-tem can be a valuable analysis regarding indications for transfusion of platelets after extensive cardiac surgery.

Calculation Algorithm Reduces Protamine Doses Without Increasing Blood Loss or the Transfusion Rate in Cardiac Surgery: Results of a Randomized Controlled Trial.

OBJECTIVES: The aim of the study was to investigate whether the HeProCalc algorithm affects heparin and protamine dosage, postoperative blood loss, and transfusion rate. DESIGN: Randomized controlled trial. SETTING: University hospital. PARTICIPANTS: The study comprised 210 cardiac surgery patients undergoing cardiac surgery with cardiopulmonary bypass. Twenty patients were excluded because of re-exploration for localized surgical bleeding (n = 9), violation of protocol (n = 2), aprotinin use (n = 3 and nadir body temperature <32°C (n = 6). INTERVENTIONS: Study participants were randomly assigned to either traditional heparin and protamine dosage based on body weight only (control group) or dosage based on the HeProCalc algorithm (intervention group). MEASUREMENTS AND MAIN RESULTS: The initial median heparin dose was 32,500 IU (interquartile range [IQR] 30,000-35,000) in the intervention group compared with 35,000 IU (IQR 30,000-37,500) (p = 0.025) in the control group. The total heparin dose in the intervention group was 40,000 IU (IQR 32,500-47,500) compared with 42,500 IU (IQR 35,000-50,000) in the control group (p = 0.685). The total protamine dose was 210 mg (IQR 190-240) in the intervention group compared with 350 mg (IQR 300-380) (p < 0.001) in the control group. The ratio of total protamine to initial dose of heparin in the intervention group was 0.62 compared with 1.0 (p < 0.001). The amount of chest tube bleeding after 12 postoperative hours was 320 mL (IQR 250-460) in the intervention group compared with 350 mL (IQR 250-450) (p = 0.754) in the control group. Neither the transfusion rate nor postoperative blood loss differed significantly between the 2 groups. CONCLUSION: Use of the HeProCalc algorithm reduced protamine dosage and the protamine/heparin ratio after cardiopulmonary bypass compared with conventional dosage based on weight without significant effect on postoperative blood loss or the transfusion rate.

An Adjusted Calculation Model Allows for Reduced Protamine Doses without Increasing Blood Loss in Cardiac Surgery.

Background Heparin dosage for anticoagulation during cardiopulmonary bypass (CPB) is commonly calculated based on the patient's body weight. The protamine-heparin ratio used for heparin reversal varies widely among institutions (0.7-1.3 mg protamine/100 IU heparin). Excess protamine may impair coagulation. With an empirically developed algorithm, the HeProCalc program, heparin, and protamine doses are calculated during the procedure. The primary aim was to investigate whether HeProCalc-based dosage of heparin could reduce protamine use compared with traditional dosages. The secondary aim was to investigate whether HeProCalc-based dosage of protamine affected postoperative bleeding. Patients and Methods We consecutively randomized 40 patients into two groups. In the control group, traditional heparin and protamine doses, based on body weight alone, were given. In the treatment group, the HeProCalc program was used, which calculated the initial heparin bolus dose from weight, height, and baseline activated clotting time and the protamine dose at termination of CPB. Results We analyzed the results from 37 patients, after exclusion of three patients. Equal doses of heparin were given in both groups, whereas significantly lower mean doses of protamine were given in the treatment group versus control group (211 ± 56 vs. 330 ± 61 mg, p < 0.001). Postoperative bleeding was less in the HeProCalc group (280 ± 229 mL) as compared with the control group (649 ± 279 mL). However, this difference was not found statistically significant (p = 0.074). Conclusion HeProCalc-based dosage of heparin and protamine allowed for reduced protamine use after CPB compared with when conventional calculations were used. Furthermore, HeProCalc-based regimen for heparin reversal suggested less postoperative bleeding, although the difference between the groups was not statistically significant.

Adenosine diphosphate-induced single-platelet count aggregation and bleeding in clopidogrel-treated patients undergoing coronary artery bypass grafting.

OBJECTIVES: To investigate the association between adenosine diphosphate (ADP)-induced platelet aggregation measured by single-platelet count testing and postoperative blood loss in clopidogrel-treated patients with acute coronary syndromes undergoing coronary artery bypass grafting (CABG). DESIGN: Prospective observational study. SETTING: Clinical study in one cardiac surgery center. PARTICIPANTS: Eighty-eight patients treated with clopidogrel (300-600 mg loading dose followed by 75 mg daily) within 7 days before CABG. INTERVENTIONS: Platelet function was assessed preoperatively by single-platelet count ADP-induced platelet aggregation. Postoperative blood loss and transfusion requirements were recorded. MEASUREMENTS AND MAIN RESULTS: There was no significant association between ADP-induced platelet aggregation and blood loss 12 hours postoperatively (estimate -7.51; 95% confidence interval [CI]: -16.9-1.9; p = 0.12). ADP-induced platelet aggregation was associated significantly with the number of platelet concentrates administered within 24 hours after surgery (incidence rate ratio [IRR] 0.95; 95% CI: 0.92-0.98; p<0.01), but not to the number of packed red blood cells (IRR 0.98; 95% CI: 0.95-1.01; p = 0.14). CONCLUSIONS: Preoperative ADP-induced platelet aggregation measured by single-platelet count testing in clopidogrel-treated patients with acute coronary syndromes undergoing CABG was not associated with postoperative blood loss or packed red blood cells transfused, but was associated significantly with number of platelet concentrates administered during the initial 24 postoperative hours.

Correlation between point-of-care platelet function testing and bleeding after coronary artery surgery.

OBJECTIVES: To investigate whether point-of-care platelet function testing immediately before coronary artery bypass grafting correlates to postoperative blood loss and transfusion requirements. DESIGN: Blood samples from 50 patients on antiplatelet therapy were analysed by Plateletworks(®). Thirty-three of the patients had received clopidogrel, 300-600 mg loading dose followed by 75 mg once daily, within 7 days. Postoperative chest drainage volume was recorded every hour. RESULTS: Plateletworks(®) ADP-induced platelet aggregation correlated significantly to postoperative chest drainage volume at 5 hours (r = -0.83; p < 0.01) and 12 hours (r = -0.55; p < 0.01), and the tertile of patients with the lowest aggregation had higher postoperative transfusion requirements (p < 0.01) and about three times larger chest drainage volume than remaining patients during the first 5 hours after surgery (p < 0.01). Cessation of clopidogrel correlated to chest drainage volume at 5 hours (r = -0.48; p < 0.01) and 12 hours (r = -0.47; p < 0.01) after surgery. CONCLUSIONS: The significant correlation between Plateletworks(®) ADP-induced platelet aggregation and blood loss suggests that this test may be useful to predict risk of excessive bleeding and to guide timing of surgery and bleeding treatment in patients undergoing coronary artery bypass grafting.

Aprotinin decreases postoperative bleeding and number of transfusions in patients on clopidogrel undergoing coronary artery bypass graft surgery: a double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Clopidogrel, an irreversible platelet inhibitor, is used to treat patients with unstable angina. These patients often present for coronary artery bypass graft surgery (CABG) and are at increased risk for perioperative bleeding. The current investigation evaluates the impact of aprotinin on bleeding and transfusion requirements in clopidogrel-treated patients undergoing CABG. METHODS AND RESULTS: Seventy-five consecutive patients with unstable angina, administered clopidogrel <5 days before CABG, were randomized. Using a double-blind design, patients received full-dose aprotinin (n =37) or saline (n =38). Elapsed times between the last dose of clopidogrel and start of the operation were similar between the 2 groups [aprotinin, 58+/-28 hour (mean+/- SD); control, 54+/-27 hour; P=0.86], as were age (aprotinin, 66.4+/-10 years; control, 68.3+/-10 years; P=0.51), number of distal anastomoses (aprotinin, 3.6+/-1.0; control, 3.7+/-1.0; P=0.79), operative times (aprotinin, 192+/-48 minutes; control, 200+/-53 minutes; P=0.55), and lowest intraoperative hemoglobin level (aprotinin, 87+/-14 g/L; control, 88+/-14 g/L; P=0.60). Postoperative bleeding was 760+/-350 mL in aprotinin-treated patients versus 1200+/-570 mL (P<0.001) in control. During the hospital stay, patients in the aprotinin group received 1.2+/-1.5 and 0.1+/-0.4 U of erythrocytes and platelets, respectively, versus 2.8+/-3.2 (P=0.02) and 0.9+/-1.4 (P=0.002) units in the control. In the aprotinin group, 53% of patients received transfusions, whereas 79% of controls were exposed to blood products (P=0.02). CONCLUSIONS: Intraoperative aprotinin decreases postoperative bleeding and the number of transfusions in patients undergoing CABG and treated with clopidogrel <5 days before surgery.

Aprotinin reduces the antiplatelet effect of clopidogrel.

Aprotinin reduces bleeding and transfusion rates in patients undergoing coronary surgery while on clopidogrel. However, safety studies have indicated that aprotinin may have a possible adverse effect related to an increased incidence of thromboembolic events. We therefore studied the adenosinediphosphate (ADP) mediated platelet aggregation before and after administration of aprotinin in patients on clopidogrel. Fifteen clopidogrel-treated patients with acute coronary syndrome undergoing coronary surgery were studied. ADP-mediated platelet aggregation and platelet count ratio (%) were measured before and after a bolus dose [2 x 10(6) kallikrein inhibiting units (KIU)] of aprotinin. Aprotinin induced an increased aggregation in 11 of 15 patients (73%), and a decrease was registered in two patients (13%). The median (25th/75th percentile) ADP-mediated platelet aggregation before and after aprotinin was 84% (76/91) and 94% (86/97, P<0.01). Clopidogrel non-responders with >90% aggregation (n=4) had a median aggregation of 94.5% (91.5/97.5) vs. 82% (73/87, P<0.01) in the responders (n=11). The median increase in platelet aggregation after aprotinin was 8% (5/20) in the responders vs. 0% (-5.25/3, P<0.01) in the non-responders. Aprotinin increased ADP induced platelet aggregation from 84 to 94% in patients on clopidogrel, which corresponds to a median decrease in relative platelet inhibition of >50%.

Aprotinin is not associated with postoperative renal impairment after primary coronary surgery.

BACKGROUND: Studies on the safety of aprotinin in coronary artery surgery have given conflicting results. Therefore, we studied the possible link between perioperative aprotinin treatment and renal dysfunction in patients undergoing first-time coronary surgery with a high risk of bleeding. METHODS: We performed a matched cohort study, comparing 200 patients receiving high-dose aprotinin with 200 patients receiving tranexamic acid during primary isolated coronary surgery. Patients were matched according to age, sex, and presence of acute coronary syndrome. Primary outcome was fractional change in creatinine clearance. Secondary outcomes were other evaluations of postoperative renal function, mortality, stroke, reoperation for bleeding, and transfusion requirements. RESULTS: The groups were similar in baseline characteristics except that triple-vessel disease and history of myocardial infarction were more prevalent in the aprotinin group. No significant differences were found in fractional change in creatinine clearance (-11% versus -12%, medians, p = 0.75) or any other assessments of postoperative renal function between the tranexamic acid and the aprotinin group. Adverse event rates were similar: early mortality (3.5% versus 4.5%, p = 0.80), stroke (1.5% versus 2%, p = 1.0), reoperation for bleeding (3.5% versus 2.5%, p = 0.77), and 5-year survival (87% versus 84%, p = 0.17). Patients in the aprotinin group received fewer transfusions (48% versus 60.5%, p = 0.02), fewer units of packed red blood cells (2.0 versus 1.4, p = 0.02) and plasma (1.3 versus 0.5, p < 0.001), but more units of platelets (0.1 versus 0.2, p = 0.02). CONCLUSIONS: Aprotinin treatment during primary coronary surgery was not associated with impaired postoperative renal function in comparison with patients treated with tranexamic acid.

Aprotinin reduces bleeding and blood product use in patients treated with clopidogrel before coronary artery bypass grafting.

BACKGROUND: An increased proportion of patients undergoing urgent coronary artery bypass graft surgery (CABG) is being treated with clopidogrel, an irreversible platelet inhibitor. Clopidogrel in combination with aspirin is known to augment bleeding, transfusion requirements, and reoperation rates after CABG. Aprotinin, a protease inhibitor, is approved for use in cardiac surgery to reduce bleeding. The aim of this study was to investigate whether or not intraoperative use of aprotinin decreases bleeding and number of transfusions after CABG in patients treated with clopidogrel less than 5 days before surgery. METHODS: We retrospectively reviewed the medical records of all consecutive patients, with preoperative clopidogrel exposure less than 5 days before surgery, who underwent urgent CABG at our institution during 1 year (n = 33). Eighteen patients received a full-dose aprotinin regime intraoperatively whereas 15 patients not receiving aprotinin served as a control group. RESULTS: The two groups were comparable with respect to baseline characteristics and operative data. Mean postoperative bleeding was 710 mL (95% confidence interval [CI]: 560 to 860) in the aprotinin group versus 1,210 mL (95% CI: 860 to 1550) in the control group (p = 0.004). The aprotinin group received fewer transfusions of packed red blood cells (0.9 U, 95% CI: 0.1 to 1.7, versus 2.7 U, 95% CI: 1.4 to 4.1; p = 0.01), platelets (0.1 U, 95% CI: 0 to 0.3, versus 0.6 U, 0.2 to 0.9; p = 0.02), and fewer blood product units (1.1 U, 95% CI: 0.1 to 2.0, versus 3.7 U, 95% CI: 2.1 to 5.4; p = 0.002). There were 3 reoperations for bleeding, all in the control group (p = 0.05). CONCLUSIONS: Aprotinin reduces bleeding, transfusion requirements of packed red blood cells, platelets, and total blood units in patients on clopidogrel undergoing urgent CABG.