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Prothrombin Complex Concentrate vs Plasma for Post-Cardiopulmonary Bypass Coagulopathy and Bleeding: A Randomized Clinical Trial
Smith MM, Schroeder DR, Nelson JA, Mauermann WJ, Welsby IJ, Pochettino A, Montonye BL, Assawakawintip C, Nuttall GA
JAMA surgery. 2022
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Abstract
IMPORTANCE Post-cardiopulmonary bypass (CPB) coagulopathy and bleeding are among the most common reasons for blood product transfusion in surgical practices. Current retrospective data suggest lower transfusion rates and blood loss in patients receiving prothrombin complex concentrate (PCC) compared with plasma after cardiac surgery. OBJECTIVE To analyze perioperative bleeding and transfusion outcomes in patients undergoing cardiac surgery who develop microvascular bleeding and receive treatment with either PCC or plasma. DESIGN, SETTING, AND PARTICIPANTS A single-institution, prospective, randomized clinical trial performed at a high-volume cardiac surgical center. Patients were aged 18 years or older and undergoing cardiac surgery with CPB. Patients undergoing complex cardiac surgical procedures (eg, aortic replacement surgery, multiple procedures, or repeated sternotomy) were preferentially targeted for enrollment. During the study period, 756 patients were approached for enrollment, and 553 patients were randomized. Of the 553 randomized patients, 100 patients met criteria for study intervention. INTERVENTIONS Patients with excessive microvascular bleeding, a prothombin time (PT) greater than 16.6 seconds, and an international normalized ratio (INR) greater than 1.6 were randomized to receive treatment with either PCC or plasma. The PCC dose was 15 IU/kg or closest standardized dose; the plasma dose was a suggested volume of 10 to 15 mL/kg rounded to the nearest unit. MAIN OUTCOMES AND MEASURES The primary outcome was postoperative bleeding (chest tube output) from the initial postsurgical intensive care unit admission through midnight on postoperative day 1. Secondary outcomes were PT/INR, rates of intraoperative red blood cell (RBC) transfusion after treatment, avoidance of allogeneic transfusion from the intraoperative period to the end of postoperative day 1, postoperative bleeding, and adverse events. RESULTS One hundred patients (mean [SD] age, 66.8 [13.7] years; 61 [61.0%] male; and 1 [1.0%] Black, 1 [1.0%] Hispanic, and 98 [98.0%] White) received the study intervention (49 plasma and 51 PCC). There was no significant difference in chest tube output between the plasma and PCC groups (median [IQR], 1022 [799-1575] mL vs 937 [708-1443] mL). After treatment, patients in the PCC arm had a greater improvement in PT (effect estimate, -1.37 seconds [95% CI, -1.91 to -0.84]; P < .001) and INR (effect estimate, -0.12 [95% CI, -0.16 to -0.07]; P < .001). Fewer patients in the PCC group required intraoperative RBC transfusion after treatment (7 of 51 patients [13.7%] vs 15 of 49 patients [30.6%]; P = .04); total intraoperative transfusion rates were not significantly different between groups. Seven (13.7%) of 51 patients receiving PCCs avoided allogeneic transfusion from the intraoperative period to the end of postoperative day 1 vs none of those receiving plasma. There were no significant differences in postoperative bleeding, transfusions, or adverse events. CONCLUSIONS AND RELEVANCE The results of this study suggest a similar overall safety and efficacy profile for PCCs compared with plasma in this clinical context, with fewer posttreatment intraoperative RBC transfusions, improved PT/INR correction, and higher likelihood of allogeneic transfusion avoidance in patients receiving PCCs. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02557672.
PICO Summary
Population
Patients undergoing cardiac surgery who developed microvascular bleeding (n= 100).
Intervention
Prothrombin complex concentrate (PCC), (n= 51).
Comparison
Plasma (n= 49).
Outcome
The primary outcome was postoperative bleeding (chest tube output) from the initial postsurgical intensive care unit admission through midnight on postoperative day 1. There was no significant difference in chest tube output between the plasma and PCC groups (median [IQR], 1022 [799, 1575] mL vs. 937 [708, 1443] mL). After treatment, patients in the PCC group had a greater improvement in prothombin time, (effect estimate, -1.37 seconds, 95% CI [-1.91, -0.84]) and international normalized ratio (effect estimate, -0.12, 95% CI [-0.16, -0.07]). Fewer patients in the PCC group required intraoperative red blood cell transfusion after treatment (7 of 51 patients [13.7%] vs. 15 of 49 patients [30.6%]); total intraoperative transfusion rates were not significantly different between groups. Seven (13.7%) of 51 patients receiving PCCs avoided allogeneic transfusion from the intraoperative period to the end of postoperative day 1 vs. none of those receiving plasma. There were no significant differences in postoperative bleeding, transfusions, or adverse events.
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The use of FEIBA for refractory bleeding in cardiac surgery - a systematic review
Khoury W, Servito M, Wang L, Baranchuk A, Callum J, Payne D, El-Diasty M
Expert Review of Cardiovascular Therapy. 2022
Abstract
INTRODUCTION Significant blood loss during cardiac surgery is associated with a significant increase in morbidity and mortality. Factor Eight Inhibitor Bypassing Activity (FEIBA), a hemostatic bypassing agent mainly used in hemophiliac patients, has also been used for intractable surgical bleeding during cardiac surgical procedures in non-hemophiliac patients. However, concerns exist that its use may be linked to increased incidence of perioperative adverse effects including thrombotic complications. AREAS COVERED A systematic literature search was performed on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases for all studies that reported the administration of FEIBA for treatment of bleeding during adult cardiac surgery in non-hemophiliac patients. After selecting of title and abstracts, two authors assessed the methodological quality of the full-text articles prior to final inclusion in the manuscript. EXPERT OPINION The safety profile of FEIBA was determined through an aggregate count of adverse events. Major complications included renal failure, re-operation for unresolved bleeding, postoperative mortality, and thromboembolic events. Overall, there is insufficient robust evidence to make a definitive conclusion about the safety or efficacy of using of FEIBA as a hemostatic agent in the setting of cardiac surgery.
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Prothrombin complex concentrate in cardiac surgery for the treatment of coagulopathic bleeding
Hayes, K., Fernando, M. C., Jordan, V.
The Cochrane Database of Systematic Reviews. 2022;11(11):Cd013551
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Abstract
BACKGROUND Coagulopathy following cardiac surgery is associated with considerable blood product transfusion and high morbidity and mortality. The treatment of coagulopathy following cardiac surgery is challenging, with the replacement of clotting factors being based on transfusion of fresh frozen plasma (FFP). Prothrombin complex concentrate (PCCs) is an alternative method to replace clotting factors and warrants evaluation. PCCs are also an alternative method to treat refractory ongoing bleeding post-cardiac surgery compared to recombinant factor VIIa (rFVIIa) and also warrants evaluation. OBJECTIVES Assess the benefits and harms of PCCs in people undergoing cardiac surgery who have coagulopathic non-surgical bleeding. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase and Conference Proceedings Citation Index-Science (CPCI-S) on the Web of Science on 20 April 2021. We searched Clinicaltrials.gov (www. CLINICALTRIALS gov), and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch/), for ongoing or unpublished trials. We checked the reference lists for additional references. We did not limit the searches by language or publication status. SELECTION CRITERIA We included randomised controlled trials (RCTs) and non-randomised trials (NRSs). DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS Eighteen studies were included (4993 participants). Two were RCTs (151 participants) and 16 were NRSs. Both RCTs had low risk of bias (RoB) in almost all domains. Of the 16 NRSs, 14 were retrospective cohort analyses with one prospective study and one case report. The nine studies used in quantitative analysis were judged to have critical RoB, three serious and three moderate. 1. PCC versus standard treatment Evidence from RCTs showed PCCs are likely to reduce the number of units transfused compared to standard care (MD -0.89, 95% CI -1.78 to 0.00; participants = 151; studies = 2; moderate-quality evidence). Evidence from NRSs agreed with this, showing that PCCs may reduce the mean number of units transfused compared to standard care but the evidence is uncertain (MD -1.87 units, 95% CI -2.53 to -1.20; participants = 551; studies = 2; very low-quality evidence). There was no evidence from RCTs showing a difference in the incidence of red blood cell (RBC) transfusion compared to standard care (OR 0.53, 95% CI 0.20 to 1.40; participants = 101; studies = 1; low-quality evidence). Evidence from NRSs disagreed with this, showing that PCCs may reduce the mean number of units transfused compared to standard care but the evidence is uncertain (OR 0.54, 95% CI 0.30 to 0.98; participants = 1046; studies = 4; low-quality evidence). There was no evidence from RCTs showing a difference in the number of thrombotic events with PCC compared to standard care (OR 0.68 95% CI 0.20 to 2.31; participants = 152; studies = 2; moderate-quality evidence). This is supported by NRSs, showing that PCCs may have no effect on the number of thrombotic events compared to standard care but the evidence is very uncertain (OR 1.32, 95% CI 0.87 to 1.99; participants = 1359; studies = 7; very low-quality evidence). There was no evidence from RCTs showing a difference in mortality with PCC compared to standard care (OR 0.53, 95% CI 0.12 to 2.35; participants = 149; studies = 2; moderate-quality evidence). This is supported by evidence from NRSs, showing that PCCs may have little to no effect on mortality compared to standard care but the evidence is very uncertain (OR 1.02, 95% CI 0.69 to 1.51; participants = 1334; studies = 6; very low-quality evidence). Evidence from RCTs indicated that there was little to no difference in postoperative bleeding (MD -107.05 mLs, 95% CI -278.92 to 64.83; participants = 151, studies = 2; low-quality evidence). PCCs may have little to no effect on intensive care length of stay (RCT evidence: MD -0.35 hours, 95% CI -19.26 to 18.57; participants = 151; studies = 2; moderate-quality evidence) (NRS evidence: MD -18.00, 95% CI -43.14 to 7.14; participants = 225; studies = 1; very low-quality evidence) or incidence of renal replacement therapy (RCT evidence: OR 0.72, 95% CI 0.14 to 3.59; participants = 50; studies = 1; low-quality evidence) (NRS evidence: OR 1.46, 95% CI 0.71 to 2.98; participants = 684; studies = 2; very low-quality evidence). No studies reported on additional adverse outcomes. 2. PCC versus rFVIIa For this comparison, all evidence was provided from NRSs. PCC likely results in a large reduction of RBCs transfused intra-operatively in comparison to rFVIIa (MD-4.98 units, 95% CI -6.37 to -3.59; participants = 256; studies = 2; moderate-quality evidence). PCC may have little to no effect on the incidence of RBC units transfused comparative to rFVIIa; evidence is very uncertain (OR 0.16, 95% CI 0.02 to 1.56; participants = 150; studies = 1; very low-quality evidence). PCC may have little to no effect on the number of thrombotic events comparative to rFVIIa; evidence is very uncertain (OR 0.51, 95% CI 0.23 to 1.16; participants = 407; studies = 4; very low-quality evidence). PCC may have little to no effect on the incidence of mortality (OR 1.07, 95% CI 0.38 to 3.03; participants = 278; studies = 3; very low-quality evidence) or intensive care length of stay comparative to rFVIIa (MD -40 hours, 95% CI -110.41 to 30.41; participants = 106; studies = 1; very low-quality evidence); evidence is very uncertain . PCC may reduce bleeding (MD -674.34 mLs, 95% CI -906.04 to -442.64; participants = 150; studies = 1; very low-quality evidence) and incidence of renal replacement therapy (OR 0.29, 95% CI 0.12 to 0.71; participants = 106; studies = 1; very low-quality evidence) comparative to rFVIIa; evidence is very uncertain. No studies reported on other adverse events. AUTHORS' CONCLUSIONS PCCs could potentially be used as an alternative to standard therapy for coagulopathic bleeding post-cardiac surgery compared to FFP as shown by moderate-quality evidence and it may be an alternative to rFVIIa in refractory non-surgical bleeding but this is based on moderate to very low quality of evidence.
PICO Summary
Population
Patients of all age groups undergoing cardiac surgery who had coagulopathic bleeding (18 studies, n= 4,993).
Intervention
Prothrombin complex concentrates (PCCs).
Comparison
Standard therapy (current institutional protocol for bleeding diathesis), fresh frozen plasma (FFP) and recombinant factor VIIa (rFVIIa).
Outcome
Of the 18 studies included, two were randomised controlled trials (RCTs), and 16 were non‐randomised trials (NRSs). PCCs compared to standard therapy: PCCs had an overall reduction in red blood cell (RBC) transfusion (both units of RBC transfusion and incidence of RBC transfusion) when compared to FFP. There was potentially no reduction in chest drain output (bleeding) in the RCTs. There was no difference in the reported outcomes of blood clots, death, intensive care stay and the requirement of dialysis in both RCTs and NRSs. The RCTs had moderate to low quality of evidence and the NRS had very low to low quality of evidence. PCCs compared to rFVIIa: PCCs had a large reduction in red blood cell transfusion when compared to rFVIIa. The quality of this evidence was moderate. For the remaining outcomes, two studies found that there was no difference in blood clots, death, bleeding into drains, intensive care stay and the requirement for dialysis. The quality of the evidence for these outcomes was very low.
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The association of prothrombin complex concentrates with postoperative outcomes in cardiac surgery: an observational substudy of the FIBRES randomized controlled trial
Bartoszko J, Callum J, Karkouti K
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2021
Abstract
PURPOSE The mainstay of therapy for coagulation factor deficiency in cardiac surgical patients is frozen plasma (FP); however, prothrombin complex concentrates (PCCs) may offer logistical and safety advantages. As there is limited comparative evidence, we conducted this study to explore the association of comparable PCC or FP doses with transfusion and outcomes. METHODS This was a post hoc analysis of a multicentre randomized trial comparing fibrinogen concentrate with cryoprecipitate (FIBRES trial) in bleeding cardiac surgical patients. This analysis included 415 patients who received only PCC (n = 72; 17%) or only FP (n = 343; 83%) for factor replacement. The main outcomes of interest were red blood cell (RBC) and platelet transfusion within 24 hr of cardiopulmonary bypass. Secondary outcomes included postoperative adverse events. Associations were examined by hierarchical generalized estimating equation models adjusted for demographic and surgical characteristics. RESULTS The median [interquartile range (IQR)] PCC dose was 1,000 [1,000-2,000] units, while the median [IQR] FP dose was 4 [2-6] units. Each unit of FP was independently associated with increased adjusted odds of RBC (1.60; 95% confidence interval [CI], 1.36 to 1.87; P < 0.01) and platelet transfusion (1.40; 95% CI, 1.15 to 1.69; P < 0.01) while each 500 units of PCC was independently associated with reduced adjusted odds of RBC (0.67; 95% CI, 0.50 to 0.90; P < 0.01) and platelet transfusion (0.80; 95% CI, 0.70 to 0.92; P < 0.01). Adverse event rates were comparable. CONCLUSIONS In cardiac surgical patients with post-cardiopulmonary bypass bleeding, PCC use was associated with lower RBC and platelet transfusion than FP use was. Prospective, randomized clinical trials comparing FP with PCC in this setting are warranted.
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Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery: A Randomized Pilot Trial
Karkouti K, Bartoszko J, Grewal D, Bingley C, Armali C, Carroll J, Hucke HP, Kron A, McCluskey SA, Rao V, et al
JAMA network open. 2021;4(4):e213936
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Abstract
IMPORTANCE Approximately 15% of patients undergoing cardiac surgery receive frozen plasma (FP) for bleeding. Four-factor prothrombin complex concentrates (PCCs) have logistical and safety advantages over FP and may be a suitable alternative. OBJECTIVES To determine the proportion of patients who received PCC and then required FP, explore hemostatic effects and safety, and assess the feasibility of study procedures. DESIGN, SETTING, AND PARTICIPANTS Parallel-group randomized pilot study conducted at 2 Canadian hospitals. Adult patients requiring coagulation factor replacement for bleeding during cardiac surgery (from September 23, 2019, to June 19, 2020; final 28-day follow-up visit, July 17, 2020). Data analysis was initiated on September 15, 2020. INTERVENTIONS Prothrombin complex concentrate (1500 IU for patients weighing ≤60 kg and 2000 IU for patients weighing >60 kg) or FP (3 U for patients weighing ≤60 kg and 4 U for patients weighing >60 kg), repeated once as needed within 24 hours (FP used for any subsequent doses in both groups). Patients and outcome assessors were blinded to treatment allocation. MAIN OUTCOMES AND MEASURES Hemostatic effectiveness (whether patients received any hemostatic therapies from 60 minutes to 4 and 24 hours after initiation of the intervention, amount of allogeneic blood components administered within 24 hours after start of surgery, and avoidance of red cell transfusions within 24 hours after start of surgery), protocol adherence, and adverse events. The analysis set comprised all randomized patients who had undergone cardiac surgery, received at least 1 dose of either treatment, and provided informed consent after surgery. RESULTS Of 169 screened patients, 131 were randomized, and 101 were treated (54 with PCC and 47 with FP), provided consent, and were included in the analysis (median age, 64 years; interquartile range [IQR], 54-73 years; 28 [28%] were female; 82 [81%] underwent complex operations). The PCC group received a median 24.9 IU/kg (IQR, 21.8-27.0 IU/kg) of PCC (2 patients [3.7%; 95% CI, 0.4%-12.7%] required FP). The FP group received a median 12.5 mL/kg (IQR, 10.0-15.0 mL/kg) of FP (4 patients [8.5%; 95% CI, 2.4%-20.4%] required >2 doses of FP). Hemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group (P = .25) nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group (P = .28). The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 14.0 U (IQR, 8.0-20.0 U) in the FP group (ratio, 0.58; 95% CI, 0.45-0.77; P < .001). After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 10.0 U (IQR, 6.0-16.0 U) in the FP group (ratio, 0.80; 95% CI, 0.59-1.08; P = .15). For red blood cells alone, the median numbers were 1.5 U (IQR, 0.0-4.0 U) in the PCC group and 3.0 U (IQR, 1.0-5.0 U) in the FP group (ratio, 0.69; 95% CI, 0.47-0.99; P = .05). During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells (P = .24). Adverse event profiles were similar. CONCLUSIONS AND RELEVANCE This randomized clinical trial found that the study protocols were feasible. Adequately powered randomized clinical trials are warranted to determine whether PCC is a suitable substitute for FP for mitigation of bleeding in cardiac surgery. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04114643.
PICO Summary
Population
Cardiac surgery patients (n= 101).
Intervention
Prothrombin complex concentrate (PCC group, n= 54).
Comparison
Frozen plasma (FP group, n= 47).
Outcome
Haemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group, nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group. The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U in the PCC group and 14.0 U in the FP group. After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U in the PCC group and 10.0 U in the FP group. For red blood cells alone, the median numbers were 1.5 U in the PCC group and 3.0 U in the FP group. During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells. Adverse event profiles were similar.
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Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial)
Green L, Roberts N, Cooper J, Agarwal S, Brunskill SJ, Chang I, Gill R, Johnston A, Klein AA, Platton S, et al
Anaesthesia. 2020
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Editor's Choice
Abstract
There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg(-1) based on factor IX) or fresh frozen plasma (15 ml.kg(-1) ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α(2) -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.
PICO Summary
Population
Cardiac surgery patients who developed bleeding within 24 hours of surgery (n= 50).
Intervention
Prothrombin complex concentrate (n= 25).
Comparison
Fresh frozen plasma (n= 25).
Outcome
There were 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α(2) -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels.
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Prothrombin complex concentrate in cardiac surgery: A systematic review and meta-analysis
Roman M, Biancari F, Ahmed AB, Agarwal S, Hadjinikolaou L, Al-Sarraf A, Tsang G, Oo AY, Field M, Santini F, et al
The Annals of Thoracic Surgery. 2018
Abstract
BACKGROUND Prothrombin complex concentrate (PCC) has recently emerged as effective alternative to fresh frozen plasma (FFP) in treating excessive perioperative bleeding. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of PCC administration as first-line treatment for coagulopathy following adult cardiac surgery. METHODS We searched PubMed/MEDLINE, EMBASE, and the Cochrane Library from inception to the end of March 2018 to identify eligible articles. Adult patients undergoing cardiac surgery and receiving perioperative PCC were compared to those receiving FFP. RESULTS A total of 861 adult patients from 4 studies were retrieved. No randomized studies were identified. Pooled odds ratio (OR) showed that PCC cohort was associated with a significant reduction in the risk of RBC transfusion (OR: 2.22; 95% confidence interval [CI] 1.45-3.40) and units of RBC received (OR: 1.34; 95%CI: 0.78-1.90). No differences were observed between the groups for re-exploration for bleeding (OR: 1.09; 95%CI: 0.66-1.82), chest drain output at 24 hours (OR: 66.36; 95%CI: -82.40-216.11), hospital mortality (OR: 0.94; 95%CI: 0.59-1.49), stroke (OR: 0.80; 95%CI: 0.41-1.56), and occurrence of acute kidney injury (OR: 0.80; 95%CI: 0.58-1.12). A trend toward increased risk of renal replacement therapy was observed in the PCC group (OR: 0.41; 95%CI: 0.16-1.02). CONCLUSIONS In patients with significant bleeding following cardiac surgery, PCC administration seems to be more effective than FFP in reducing perioperative blood transfusions. No additional risks of thromboembolic events or other adverse reactions were observed. Randomized controlled trials are needed to definitively establish the safety of PCC in cardiac surgery.
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Prothrombin complex concentrates in pediatric cardiac surgery: the current state and the future
Ashikhmina E, Said S, Smith MM, Rodriguez V, Oliver WC Jr, Nuttall GA, Dearani JA, Schaff HV
The Annals of Thoracic Surgery. 2017;104((4):):1423-1431
Abstract
BACKGROUND After decades of practice of pediatric cardiac surgery, postoperative bleeding due to the immaturity of hemostasis, hemodilution, and hypothermia remains a concern. Recently, a new approach for adult coagulopathy after bypass has emerged. Prothrombin complex concentrates (PCCs), designed to treat bleeding in hemophilia patients, are safely and efficiently used off label for hemorrhage after bypass. However, optimal dosing, indications and contraindications, and laboratory tests to assess the efficacy of PCC use in children have not yet been established. This literature review outlines the challenges of bypass-related coagulopathy, the pharmacology, and the experience in use of PCCs, with a focus on their potential in pediatric cardiac surgery. METHODS After a thorough literature search of MEDLINE, Scopus, and Ovid databases using the term "prothrombin complex concentrate AND pediatric," 23 relevant articles were selected. RESULTS The data supporting successful use of PCCs in acquired coagulopathy after cardiac surgery in adults have been increasing. Although small volume, low immunogenicity, efficiency, and speed in correcting coagulopathy are attractive qualities of PCCs for pediatric practice, current evidence is only anecdotal. The main concerns are unknown dosing regimens, the inability to closely monitor the effects of PCCs in real time, and a possibility of thrombotic complications, which can be particularly devastating in young congenital cardiac patients whose lives frequently depend upon the patency of artificial shunts. CONCLUSIONS Extensive, high-quality research is warranted to fill in the gaps of knowledge regarding using PCCs in pediatric cardiac practice.
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Comparison between prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP) for the urgent reversal of warfarin in patients with mechanical heart valves in a tertiary care cardiac center
Fariborz FB, Golpira R, Najafi H, Totonchi Z, Salajegheh S, Bakhshandeh H, Hashemian F
Iranian Journal of Pharmaceutical Research. 2015;14((3)):877-85.
Abstract
Fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) reverse oral anticoagulants such as Warfarin. We compared the standard dosage of FFP and PCC in terms of efficacy and safety for patients with mechanical heart valves undergoing interventional procedures while receiving Warfarin. Fifty patients were randomized (25 for each group) with mechanical heart valves [international normalized ratio (INR) >2.5]. FFP dosage was administered based on body weight (10-15 mL/Kg), while PCC dosage was administered based on both body weight and target INR. INR measurements were obtained at different time after PCC and FFP infusion. The mean +/- SD of INR pre treatment was not significantly different between the PCC and FFP groups. However, over a 48-hour period following the administration of PCC and FFP, 76% of the patients in the PCC group and only 20% of the patients in the FFP group reached the INR target. Five (20%) patients in the PCC group received an additional dose of PCC, whereas 17 (68%) patients in the FFP group received a further dose of FFP (P=0.001). There was no significant difference between the two groups in Hb and Hct before and during a 48-hour period after PCC and FFP infusion. As regards safety monitoring and adverse drug reaction screening in the FFP group, the INR was high (INR > 2.5) in 86% of the patients. There was no report of hemorrhage in both groups. PCC reverses anticoagulation both effectively and safely while having the advantage of obviating the need to extra doses.
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Randomized, double-blinded, placebo-controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery
Ranucci M, Baryshnikova E, Crapelli GB, Rahe-Meyer N, Menicanti L, Frigiola A, Surgical Clinical Outcome REsearch Group
Journal of the American Heart Association.. 2015;4((6))
Abstract
BACKGROUND Postoperative bleeding after heart operations is still a common finding, leading to allogeneic blood products transfusion. Fibrinogen and coagulation factors deficiency are possible determinants of bleeding. The experimental hypothesis of this study is that a first-line fibrinogen supplementation avoids the need for fresh frozen plasma (FFP) and reduces the need for any kind of transfusions. METHODS AND RESULTS This was a single-center, prospective, randomized, placebo-controlled, double-blinded study. One-hundred sixteen patients undergoing heart surgery with an expected cardiopulmonary bypass duration >90 minutes were admitted to the study. Patients in the treatment arm received fibrinogen concentrate after protamine administration; patients in the control arm received saline solution. In case of ongoing bleeding, patients in the treatment arm could receive prothrombin complex concentrates (PCCs) and those in the control arm saline solution. The primary endpoint was avoidance of any allogeneic blood product. Patients in the treatment arm had a significantly lower rate of any allogeneic blood products transfusion (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.84, P=0.015). The total amount of packed red cells and FFP units transfused was significantly lower in the treatment arm. Postoperative bleeding was significantly (P=0.042) less in the treatment arm (median, 300 mL; interquartile range, 200 to 400 mL) than in the control arm (median, 355 mL; interquartile range, 250 to 600 mL). CONCLUSIONS Fibrinogen concentrate limits postoperative bleeding after complex heart surgery, leading to a significant reduction in allogeneic blood products transfusions. No safety issues were raised. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471730.Copyright © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.