A pilot randomized clinical trial of cryopreserved versus liquid-stored platelet transfusion for bleeding in cardiac surgery: The cryopreserved versus liquid platelet-New Zealand pilot trial
Vox sanguinis. 2021
BACKGROUND AND OBJECTIVES Platelets for transfusion have a shelf-life of 7 days, limiting availability and leading to wastage. Cryopreservation at -80°C extends shelf-life to at least 1 year, but safety and effectiveness are uncertain. MATERIALS AND METHODS This single centre blinded pilot trial enrolled adult cardiac surgery patients who were at high risk of platelet transfusion. If treating clinicians determined platelet transfusion was required, up to three units of either cryopreserved or liquid-stored platelets intraoperatively or during intensive care unit admission were administered. The primary outcome was protocol safety and feasibility. RESULTS Over 13 months, 89 patients were randomized, 23 (25.8%) of whom received a platelet transfusion. There were no differences in median blood loss up to 48 h between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 10(3) /μl vs. 157 × 10(3) /μl, median difference 39.5 ×10(3) /μl, p = 0.03). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24-h blood loss, red cell transfusion or a composite bleeding outcome. CONCLUSION This pilot randomized controlled trial demonstrated the feasibility of the protocol and adds to accumulating data supporting the safety of this intervention. Given the clear advantage of prolonged shelf-life, particularly for regional hospitals in New Zealand, a definitive non-inferiority phase III trial is warranted.
Adult cardiac surgery patients who were at high risk of platelet transfusion, enrolled in the CLIP-NZ Pilot study (n= 89).
Cryopreserved platelet transfusion (n= 49).
Liquid-stored platelet transfusion (n= 40).
The primary outcome was protocol safety and feasibility. Over 13 months, 89 patients were randomized, 23 (25.8%) of whom received a platelet transfusion. There were no differences in median blood loss up to 48 hours between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 10(3) /μl vs. 157 × 10(3) /μl, median difference 39.5 ×10(3) /μl). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24 hours blood loss, red cell transfusion or a composite bleeding outcome.
Transfusing Platelets During Bypass Rewarming in Neonates Improves Postoperative Outcomes: A Randomized Controlled Trial
World Journal for Pediatric & Congenital Heart Surgery. 2020;11(1):71-76
BACKGROUND In neonates, transfusion of platelets after hemodilution from cardiopulmonary bypass (CPB) has been standard. We hypothesize that platelet administration during the rewarming phase before termination of CPB would reduce coagulopathy, enhance hemostasis, reduce transfusion, and improve postoperative outcomes after neonatal cardiac surgery. METHODS A prospective, randomized trial was performed in 46 neonates. Controls received platelets only at the end of bypass with other blood products to assist in hemostasis. The treatment group received 10 mL/kg of platelets during the rewarming phase of bypass after cross-clamp release. After protamine, transfusion and perioperative management protocols were identical and constant among groups. RESULTS Two neonates in each group were excluded secondary to postoperative need for extracorporeal support. Controls (n = 21) and treatment patients (n = 21) were similar in age, weight, case complexity, associated syndromes, single ventricle status, and CPB times. Compared to controls, the treatment group required 40% less postbypass blood products (58 ± 29 vs 103 ± 80 mL/kg, P = .04), and case completion time after protamine administration was 28 minutes faster (P = .016). The treatment group required fewer postoperative mediastinal explorations for bleeding (P = .045) and had a lower fluid balance (P = .04). The treatment group had shorter mechanical ventilation (P = .016) and length of intensive care unit times (P = .033). There were no 30-day mortalities in either group. CONCLUSION Platelet transfusion during the rewarming phase of neonatal cardiac surgery was associated with reduced bleeding and improved postoperative outcomes, compared to platelets given after coming off bypass. Further studies are necessary to understand mechanisms and benefits of this strategy.
A Pilot Trial of Platelets Stored Cold versus at Room Temperature for Complex Cardiothoracic Surgery
BACKGROUND This pilot trial focused on feasibility and safety to provide preliminary data to evaluate the hemostatic potential of cold-stored platelets (2° to 6°C) compared with standard room temperature-stored platelets (20° to 24°C) in adult patients undergoing complex cardiothoracic surgery. This study aimed to assess feasibility and to provide information for future pivotal trials. METHODS A single center two-stage exploratory pilot study was performed on adult patients undergoing elective or semiurgent complex cardiothoracic surgery. In stage I, a two-armed randomized trial, platelets stored up to 7 days in the cold were compared with those stored at room temperature. In the subsequent single-arm stage II, cold storage time was extended to 8 to 14 days. The primary outcome was clinical effect measured by chest drain output. Secondary outcomes were platelet function measured by multiple electrode impedance aggregometry, total blood usage, immediate and long-term (28 days) adverse events, length of stay in intensive care, and mortality. RESULTS In stage I, the median chest drain output was 720 ml (quartiles 485 to 1,170, n = 25) in patients transfused with room temperature-stored platelets and 645 ml (quartiles 460 to 800, n = 25) in patients transfused with cold-stored platelets. No significant difference was observed. The difference in medians between the room temperature- and cold-stored up to 7 days arm was 75 ml (95% CI, -220, 425). In stage II, the median chest drain output was 690 ml (500 to 1,880, n = 15). The difference in medians between the room temperature arm and the nonconcurrent cold-stored 8 to 14 days arm was 30 ml (95% CI, -1,040, 355). Platelet aggregation in vitro increased after transfusion in both the room temperature- and cold-stored platelet study arms. Total blood usage, number of adverse events, length of stay in intensive care, and mortality were comparable among patients receiving cold-stored and room temperature-stored platelets. CONCLUSIONS This pilot trial supports the feasibility of platelets stored cold for up to 14 days and provides critical guidance for future pivotal trials in high-risk cardiothoracic bleeding patients.
A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP-I trial
BACKGROUND Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval. STUDY DESIGN AND METHODS The Cryopreserved vs. Liquid Platelet (CLIP) study was a double-blind, pilot, multicenter RCT involving high-risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid-stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought. RESULTS A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid-stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, -343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid-stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid-stored PLTs (difference between groups, 1 unit [95% CI, -3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh-frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, -0.03 to 2.0 units]; p = 0.012). There were no between-group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group. CONCLUSION In this pilot RCT, compared to liquid-stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted.
Administration of platelets to ruptured abdominal aortic aneurysm patients before open surgery: a prospective, single-blinded, randomised study
Transfusion Medicine (Oxford, England). 2018;28((5):):386-391
BACKGROUND In patients undergoing open surgery for a ruptured abdominal aortic aneurysm (rAAA), survivors demonstrate a high platelet count, and proactive administration of platelets (and fresh frozen plasma) appears to influence mortality. OBJECTIVES This trial investigated the effect of platelets administered before transport to surgery. METHODS In a prospective study design, patients were randomised to receive platelets (intervention; n = 61) or no platelets (control; n = 61) before transport to vascular surgery from 11 local hospitals. The study was terminated when one of the vascular surgical centres implemented endovascular repair for rAAA patients. RESULTS Thirty days after surgery, mortality was 36% for patients with intervention vs 31% for controls (P = 0.32). Post-operative thrombotic events (14 vs 15; P = 0.69), renal failure (11 vs 10; P = 0.15) and pulmonary insufficiency (34 vs 39; P = 0.15) were similar in the two groups of patients. No adverse reactions to platelet administration were observed. In addition, length of stay in the intensive care unit was unaffected by intervention. CONCLUSIONS For patients planned for open repair of a rAAA, we observed no significant effect of early administration of platelets with regard to post-operative complications and stay in the ICU or in hospital and also no significant effect on mortality.
Use of thrombin generation test for monitoring hemostasis in coronary bypass surgery
Clinical Hemorheology and Microcirculation. 2017;66((1):):57-66
To evaluate the parameters of the thrombin generation test (TGT) in coronary artery disease (CAD) patients on prolonged aspirin therapy during on-pump coronary artery bypass grafting (CABG) after donor platelet concentrate transfusion. A total of 148 patients with CAD on prolonged aspirin therapy (75-100 mg/day) who have undergone elective on-pump CABG were consecutively included in the study. Patients were divided randomly into two groups. Group 1 (n = 76) received donor platelet transfusions after cardiopulmonary bypass, whereas Group 2 (n = 72) did not. TGT parameters were measured using an analyzer at pre-, intra-, and early postoperative periods. Activation of the endogenous thrombin potential was observed in patients on prolonged aspirin therapy in the pre- and intraoperative periods, as confirmed by high peak thrombin and increased velocity index. The activation time of the prothrombinase complex and thrombin generation time were greater than the control group. The blood hemostatic potential in patients who did not receive transfusions in the early postoperative period decreased up to the level of the control group in the extended time parameters. Hemostatic potential in plasma in patients on aspirin was preserved. Given the laboratory test results and clinical data, platelet concentrate transfusion is unnecessary for prevention.
Poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit can reduce transfusion of platelet products compared to heparin-coated circuit during aortic arch surgery
Journal of Artificial Organs : the Official Journal of the Japanese Society for Artificial Organs. 2016;19((3):):233-40
Several coating techniques for extracorporeal circulation have been developed to reduce the systemic inflammatory response during cardiopulmonary bypass (CPB). We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethylacrylate (PMEA)- and heparin-coated CPB circuits in total aortic arch replacement (TAR) with the prolonged use of the bypass technique. Twenty patients who underwent elective TAR were divided randomly into two equal groups: group P (n = 10) to use PMEA-coated circuits and group H (n = 10) to use heparin-coated circuits. Clinical outcomes, hematological variables, and acute phase inflammatory response were analyzed perioperatively. Demographic, CPB, and clinical outcome data were similar for both groups. Hemoglobin and platelet count showed similar time-course curves. However, the amount of platelet products transfused intraoperatively was significantly larger in group H (group P 26.0 +/- 7.0 units; group H 33.0 +/- 6.7 units, p = 0.04). Total protein, and albumin levels were significantly higher in group P during and after the operation (total protein, p = 0.04; albumin, p = 0.02). The use of PMEA-coated circuit is associated with retainment of perioperative plasma proteins levels and may help to reduce transfusion of platelet products in TAR in comparison with the heparin-coated circuit.
Liberal versus restrictive transfusion strategy of platelet concentrate and cryoprecipitate in thoracic aortic surgery: A multicenter randomized trial
Abstracts of the HAA 2014 Annual Scientific Meeting. 2014;:407.. Abstract No. P192
Frozen platelets for rural Australia: the CLIP trial
Anaesthesia & Intensive Care. 2013;41((6):):804-5.
Postoperative complications associated with transfusion of platelets and plasma in cardiac surgery
BACKGROUND Studies in cardiac surgery have reported increased postoperative morbidity and mortality after allogeneic red blood cell (RBC) transfusions. Whether platelet (PLT) and/or plasma transfusions are a marker for more concomitant RBC transfusions or are independently associated with complications after cardiac surgery is unknown. STUDY DESIGN AND METHODS Data from two randomized controlled studies were combined to analyze the effects of PLT and/or plasma transfusions on postoperative infections, length of stay in the intensive care unit (ICU), all-cause mortality, and mortality in the presence or absence of infections in the postoperative period. RESULTS After adjusting for confounding factors, plasma units and not RBC transfusions were associated with all-cause mortality. White blood cell (WBC)-containing RBC transfusions and PLT transfusions were associated with mortality occurring in the presence of or after infections. The number of (WBC-containing) RBC transfusions was also significantly associated with postoperative infections and with ICU stay for 4 or more days. CONCLUSION Although it is difficult to separate the effects of blood components, we found that in cardiac surgery, perioperative plasma transfusions are independently associated with all-cause mortality. WBC-containing RBC transfusions and PLT transfusions are independently associated with mortality in the presence of infections in the postoperative period. Future transfusion studies in cardiac surgery should concomitantly consider the possible adverse effects of all the various transfused blood components.