Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial)
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.
Cardiac surgery patients who developed bleeding within 24 hours of surgery (n= 50).
Prothrombin complex concentrate (n= 25).
Fresh frozen plasma (n= 25).
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.
Coagulation ability when separating from cardiopulmonary bypass with and without fresh frozen plasma: a pilot study
Gen Thorac Cardiovasc Surg. 2020
OBJECTIVE Several strategies are employed for administering fresh frozen plasma (FFP) during weaning from cardiopulmonary bypass (CPB). This study evaluated by coagulation function aimed to compare two strategies of administering FFP in cardiovascular surgery: administering 4 units of FFP before separating from CPB or administering it after weaning from CPB. METHODS Thirty patients who underwent CPB and were expected to receive 8 units of FFP and 20 units of platelet concentrate were randomly allocated into group A (8 units of FFP and 20 units of platelet concentrate administered after separating from CPB) and group B (4 units of FFP administered before separation, and 4 units of FFP and 20 units of platelet concentrate administered after separating from CPB). Thromboelastography (TEG6s((R)), HAEMONETICS Japan GK, Tokyo, Japan) was conducted at four time points before and after separation. Blood test results, blood loss, and required amounts of blood transfusion were compared. The primary outcome was the difference in coagulation function evaluated by TEG6s 90 min after protamine administration. RESULTS Twenty-eight patients were enrolled in the study. Coagulation function after separating from CPB was not significantly different between the groups. Additionally, no significant differences were found in intensive care unit outcomes, such as 24-h transfusion requirements. CONCLUSIONS Coagulation function 90 min after separating from CPB was not significantly different between the groups. Prior FFP administration before separation did not provide significant improvement in coagulation function.
Fresh frozen plasma prime and the level of gammaglobulin after pediatric cardiopulmonary bypass
American journal of clinical and experimental immunology. 2020;9(5):91-100
Different organ perturbation and multiple complications might occur after cardiopulmonary bypass (CPB). A variety of solutions might be used for pump priming with different advantages and disadvantages. The advantage of fresh frozen plasma (FFP) inclusion in pump prime has been shown in post-CPB coagulation management. Acquired hypogammaglobulinemia is the disadvantage of albumin (ALB) pump prime. Our aim was to assess the impact of FFP prime on the post-pump serum level of immunoglobulin G (IgG) and its subclasses. Fifty-six patients under the age of 5 years old who were scheduled for cardiac surgery on CPB were randomly primed with FFP or ALB. Any innate or acquired immune deficiency was considered as exclusion criteria. The pre-CPB and 24-hour post-CPB collected blood samples were analyzed by the nephelometric method for the plasma level of IgG and its four subclasses. Twenty-two patients (mean age and weight of 13 months and 6.8 kilograms) in the ALB prime group and 26 patients (mean age and weight of 15 months and 8.1 kilograms) in the FFP prime group completed the study. Using paired t-test and repeated measures ANOVA test, patients in the ALB prime group had a significant drop in the post-CPB serum level of total IgG (597±138 mg/dL to 379±179 mg/dL, P value <0.001) and its two subclasses of IgG1 and IgG3. In contrast, there was a slight elevation in the serum level of total IgG (549±207 mg/dL to 630±180 mg/dL, P value =0.008) and its two subclasses of IgG2 and IgG4 in patients who had FFP prime solution. In conclusion, compared to the ALB prime solution, FFP inclusion in prime could hamper the pediatric post-CPB induced hypogammaglobulinemia.
Early or late fresh frozen plasma administration in newborns and small infants undergoing cardiac surgery: the APPEAR randomized trial
British Journal of Anaesthesia. 2017;118((5)):788-796.
Background: In newborns and small infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) and blood priming, it is unclear whether there is reduced blood loss if fresh frozen plasma (FFP) is added to the CPB priming volume. This single-centre, randomized trial tested the hypothesis that the administration of FFP after CPB (late FFP group) is superior to FFP priming (early FFP group) in terms of postoperative bleeding and overall red blood cell (RBC) transfusion. Methods: Seventy-three infants weighing <10 kg were randomly allocated to receive FFP to supplement RBCs in the CPB priming solution ( n =36) or immediately after CPB ( n =37). The primary endpoint was a difference in postoperative blood loss; secondary endpoints included the amount of RBCs and FFP transfused through the first 48 postoperative hours. Results: All patients were included in the analysis. Patients in the late FFP arm had greater postoperative mean blood loss than patients in the early FFP arm [33.1 ( sd 20.6) vs 24.1 (12.9) ml kg -1 ; P =0.028], but no differences in transfusions were found. The subgroup of cyanotic heart disease patients had comparable results, but with greater use of RBCs in the late FFP group. Conclusions: In infants undergoing cardiac surgery, FFP in the priming solution appears slightly superior to late administration in terms of postoperative bleeding. Clinical trial registration: www.ClinicalTrials.gov , NCT02738190.
Fresh frozen plasma for cardiovascular surgery
Cochrane Database of Systematic Reviews.. 2015;((7)):CD007614.
BACKGROUND Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of bleeding. The purpose of this review is to assess the risk of mortality for patients undergoing cardiovascular surgery who receive FFP. OBJECTIVES To evaluate the risk to benefit ratio of FFP transfusion in cardiovascular surgery for the treatment of bleeding patients or for prophylaxis against bleeding. SEARCH METHODS We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE (OvidSP, 1946 to 21 April 2015), EMBASE (OvidSP, 1974 to 21 April 2015), PubMed (e-publications only: searched 21 April 2015), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 21 April 2015). We also searched the references of all identified trials and relevant review articles. We did not limit the searches by language or publication status. SELECTION CRITERIA We included randomised controlled trials in patients undergoing major cardiac or vascular surgery who were allocated to a FFP group or a comparator (no plasma or an active comparator, either clinical plasma (any type) or a plasma-derived blood product). We included participants of any age (neonates, children and adults). We excluded studies of plasmapheresis and plasma exchange. DATA COLLECTION AND ANALYSIS Two authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two authors assessed risk of bias in the included studies and extracted data independently. We took care to note whether FFP was used therapeutically or prophylactically within each trial. MAIN RESULTS We included 15 trials, with a total of 755 participants for analysis in the review. Fourteen trials compared prophylactic use of FFP against no FFP. One study compared therapeutic use of two types of plasma. The timing of intervention varied, including FFP transfusion at the time of heparin neutralisation and stopping cardiopulmonary bypass (CPB) (seven trials), with CPB priming (four trials), after anaesthesia induction (one trial) and postoperatively (two trials). Twelve trials excluded patients having emergency surgery and nine excluded patients with coagulopathies.Overall the trials were small, with only four reporting an a priori sample size calculation. No trial was powered to determine changes in mortality as a primary outcome. There was either high risk of bias, or unclear risk, in the majority of trials included in this review.There was no difference in the number of deaths between the intervention arms in the six trials (with 287 patients) reporting mortality (very low quality evidence). There was also no difference in blood loss in the first 24 hours for neonatal/paediatric patients (four trials with 138 patients; low quality evidence): mean difference (MD) -1.46 ml/kg (95% confidence interval (CI) -4.7 to 1.78 ml/kg); or adult patients (one trial with 120 patients): MD -12.00 ml (95% CI -101.16 to 77.16 ml).Transfusion with FFP was inferior to control for preventing patients receiving any red cell transfusion: Peto odds ratio (OR) 2.57 (95% CI 1.30 to 5.08; moderate quality evidence). There was a difference in prothrombin time within two hours of FFP transfusion in eight trials (with 210 patients; moderate quality evidence) favouring the FFP arm: MD -0.71 seconds (95% CI -1.28 to -0.13 seconds). There was no difference in the risk of returning to theatre for reoperation (eight trials with 398 patients; moderate quality evidence): Peto OR 0.81 (95% CI 0.26 to 2.57). Only one included study reported adverse events as an outcome and reported no significant adverse events following FFP transfusion. AUTHORS' CONCLUSIONS This review has found no evidence to support the prophylactic administration of FFP to patients without coagulopathy undergoing elective cardiac surgery. There was insufficient evidence about treatment of p
Evidence-based use of FFP: the influence of a priming strategy without FFP during CPB on postoperative coagulation and recovery in pediatric patients
OBJECTIVE Although fresh frozen plasma (FFP) is one of the most commonly used hemostatic agents in clinical specialties today, there is little evidence available supporting its administration. Our present study observed the effects of a priming strategy without FFP during cardiopulmonary bypass (CPB) on postoperative coagulation and clinical recovery in pediatric patients, aiming to supply new evidence for evidence-based use of FFP. METHOD Eighty pediatric patients with congenital heart disease undergoing cardiac surgery with CPB were randomized to receive either 10-20 ml/kg 4% succinylated gelatin (Gelofusine, GEL group, n = 40) or 1-2 units FFP (FFP group, n = 40) in the pump prime. Rapid-thromboelastography (r-TEG) and functional fibrinogen level were measured before skin incision and 15 minutes after heparin reversal. We recorded the volume of chest tube drainage, transfusion requirements and the dosage of pharmacological agents. The ventilation time, ICU length of stay and hospitalization time after surgery were also collected. RESULTS After heparin neutralization, there were significantly elevated levels of fibrinogen in the FFP group, which were manifested by r-TEG parameters MAf and FLEV. No significant differences were observed between the two groups in postoperative bleeding, transfusion requirements and the usage of pharmacological agents. Recovery time was also comparable between the two groups. CONCLUSION In conclusion, prophylactic use of FFP in the priming solution does not provide clinical benefits as presumed. Artificial colloids, such as Gelofusine, can be used safely and effectively as a substitute for FFP in the pump prime. TEG is an effective assessment tool to evaluate postoperative coagulation function in pediatric patients.Copyright © The Author(s) 2014.
The influence of cardiopulmonary bypass priming without FFP on postoperative coagulation and recovery in pediatric patients with cyanotic congenital heart disease
European Journal of Pediatrics. 2014;173((11):):1437-43.
UNLABELLED Transfusion guidelines have been produced for the evidence-based use of fresh frozen plasma (FFP). However, the inappropriate use of FFP is still a worldwide problem, especially in the prophylactic settings. In the present study, 100 cyanotic pediatric patients (age 6 months to 3 years) undergoing cardiac surgery with cardiopulmonary bypass (CPB) were randomized to receive either 10-20 ml/kg FFP (FFP group, n=50) or 10-20 ml/kg 4 % succinylated gelatin (Gelofusine, GEL group, n=50) in the priming solution. Rapid thromboelastography (r-TEG) was measured before skin incision and 15 min after heparin neutralization. Postoperative renal and hepatic function, mediastinal chest tube drainage, transfusion requirements, and recovery time were observed. The relationships between hematologic and demographic data and postoperative bleeding volume were also analyzed. The results showed that there were significantly elevated levels of fibrinogen (r-TEG parameters: fibrinogen contribution to maximal amplitude (MAf) and fibrinogen level (FLEV)) in the FFP group compared to the GEL group. The postoperative blood loss, total transfusion requirements, and recovery time were not significantly different between the two groups, indicating that there were no obvious clinical benefits of using FFP in the priming. The maximal amplitude (MA) of r-TEG measured after heparin neutralization was correlated with the 6-h postoperative bleeding volume. In addition, preoperative fibrinogen level rather than FFP priming was an independent predictor of postoperative blood loss. CONCLUSION Prophylactic use of FFP in the priming solution does not have obvious clinical benefits in cyanotic congenital heart disease (CCHD) patients. Gelofusine, an artificial colloid, is a safe and effective substitute of FFP in the priming solution. Furthermore, r-TEG can be used as a "real-time" assessment tool to evaluate postoperative bleeding and guide transfusion after cardiac surgery in pediatric patients.
Fresh frozen plasma in pump priming for congenital heart surgery: evaluation of effects on postoperative coagulation profiles using a fibrinogen assay and rotational thromboelastometry
Yonsei Medical Journal. 2013;54((3):):752-62.
PURPOSE In this prospective study, the effects of fresh frozen plasma (FFP) included in pump priming for congenital heart surgery in infants and children on post-bypass coagulation profiles were evaluated. MATERIALS AND METHODS Either 20% albumin (50-100 mL) or FFP (1-2 units) was added to pump priming for patients randomly allocated into control or treatment groups, respectively. Hematologic assays, including functional fibrinogen level, and rotational thromboelastometry (ROTEM) were measured before skin incision (baseline), after weaning from cardiopulmonary bypass (CPB) and heparin reversal, and at 24 hours (h) in the intensive care unit (ICU). RESULTS All the baseline measurements were comparable between the control and treatment groups of infants and children. After heparin reversal, however, significantly higher fibrinogen levels and less reduced ROTEM parameters, which reflect clot formation and firmness, were demonstrated in the treatment groups of infants and children. At 24 h in the ICU, hematologic assays and ROTEM measurements were comparable between the control and treatment groups of infants and children. Transfusion requirements, excluding FFP in pump prime, and postoperative bleeding were comparable between the control and treatment groups of infants and children. CONCLUSION Although clinical benefits were not clearly found, the inclusion of FFP in pump priming for congenital heart surgery in infants and children was shown to improve the hemodilution-related hemostatic dysfunction immediately after weaning from CPB and heparin reversal.
Peroperative effects of fresh frozen plasma and antithrombin III on heparin sensitivity and coagulation during nitroglycerine infusion in coronary artery bypass surgery
Blood Coagulation & Fibrinolysis. 2011;22((7):):593-9.
Nitroglycerin (NTG) reduces the anticoagulant effects of heparin and may lead to heparin resistance. Fresh frozen plasma (FFP) and antithrombin III (ATIII) may be used for the treatment of heparin resistance. We aimed to compare the effects of FFP and ATIII on heparin requirement, coagulation parameters, and bleeding in patients undergoing coronary artery bypass graft surgery (CABGS) with moderate dose of intraoperative NTG infusion. Forty-eight patients undergoing CABGS with NTG infusion were randomly allocated to three groups. Group C served as control, whereas the patients in group P received FFP and those in group A received ATIII after anesthesia induction. ATIII activity and coagulation parameters were measured at five different times intraoperatively. Total heparin requirement, heparin consumption, and heparin sensitivity were calculated. ATIII activity and ACT were significantly higher and activated partial thromboplastin time and fibrinogen level were significantly lower during cardiopulmonary bypass in group A than in groups P and C. Heparin sensitivity was significantly higher and total heparin requirement and consumption were significantly lower in ATIII group than in other groups. ATIII administration increases heparin sensitivity and decreases heparin requirements compared with FFP in patients undergoing CABGS with peroperative NTG infusion. ATIII may be preferred to FFP in patients with heparin resistance due to NTG infusion undergoing CABGS.
Comparison of fresh frozen plasma and prothrombin complex concentrate for the reversal of oral anticoagulants in patients undergoing cardiopulmonary bypass surgery: a randomized study
Vox Sanguinis. 2010;99((3):):251-60.
BACKGROUND Fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC) reverse oral anticoagulants. We compared PCC and FFP intraoperative administration in patients undergoing heart surgery with cardiopulmonary bypass (CPB). METHODS Forty patients [with international normalized ratio (INR)≥ 2·1] assigned semi-urgent cardiac surgery were randomized to receive either FFP (n = 20) or PCC (n = 20). Prior to CPB, they received either 2 units of FFP or half of the PCC dose calculated according to body weight, initial INR and target INR ( ≤ 1·5). After CPB and protamine administration, patients received either another 2 units of FFP or the other half PCC dose. Additional doses were administered if INR was still too high ( ≥ 1·5). RESULTS Fifteen minutes after CPB, more patients reached INR target with PCC (P = 0·007): 7/16 patients vs. 0/15 patients with FFP; there was no difference 1 h after CPB (6/15 patients with PCC vs. 4/15 patients with FFP reached target). Fifteen minutes after CPB, median INR (range) decreased to 1·6 (1·2-2·2) with PCC vs. 2·3 (1·5-3·5) with FFP; 1 h after CPB both groups reached similar values [1·6 (1·3-2·2) with PCC and 1·7 (1·3-2·7) with FFP]. With PCC, less patients needed additional dose (6/20) than with FFP (20/20) (P < 0·001). Both groups differed significantly on the course of factor II (P = 0·0023) and factor X (P = 0·008) over time. Dilution of coagulation factors was maximal at CPB onset. Safety was good for both groups, with only two related oozing cases with FFP. CONCLUSION PCC reverses anticoagulation safely, faster and with less bleeding than FFP.