Prothrombin Complex Concentrate Group Research Articles

Efficacy of human prothrombin complex concentrate in the treatment of warfarin overdose in patients receiving warfarin for mechanical heart valve replacement.

Warfarin, a widely utilized anticoagulant, is paramount for preventing thromboembolic events in patients with mechanical heart valve replacements. However, its narrow therapeutic index can lead to over-anticoagulation and overdose, resulting in serious health risks. This study examines the efficacy of human prothrombin complex concentrate (PCC) in managing warfarin overdose, in comparison with traditional treatments. A retrospective analysis was conducted on 162 adults who presented with warfarin overdose (INR > 5.0) at a tertiary care hospital between 2016 and 2020. Participants were divided into 2 groups-those treated with PCC (n = 57) and those treated with conventional methods (n = 105), including vitamin K and fresh frozen plasma. The primary outcome was the rate of reaching the target (International Normalized Ratio) INR within 24 hours. Secondary outcomes included transfusion requirements, thromboembolic events, adverse reactions, 30-day mortality, and length of hospital stay. PCC demonstrated significant efficacy, with 89.5% of patients achieving the target INR within 24 hours, compared to 64.8% in the control group (P < .05). The PCC group also had reduced transfusion requirements and a shorter average hospital stay. There was no significant difference in thromboembolic events or adverse reactions between the 2 groups, and the reduced 30-day mortality in the PCC group was not statistically significant. Human prothrombin complex concentrate is associated with rapid reaching the target INR, decreased transfusion needs, and shortened hospitalization, making it a promising option for warfarin overdose management. While the results are encouraging, larger, multicenter, randomized controlled trials are necessary to further validate these findings and optimize PCC administration protocols.

Deterioration free discharge comparison of andexanet-alfa and prothrombin complex concentrates (PCC) for reversal of factor Xa inhibitor associated bleeds.

Given the paucity of comparative efficacy data and the difference in cost between andexanet-alfa and prothrombin complex concentrates (PCC), debates continue regarding optimal cost-effective therapy for patients who present with major bleeding associated with oral factor Xa inhibitors. Available literature comparing the cost-effectiveness of the reversal agents is limited, and the large difference in price between therapy options has led many health systems to exclude andexanet-alfa from their formularies.To evaluate the clinical outcomes and cost of PCC compared to andexanet-alfa for patients with factor Xa inhibitor associated bleeds.We performed a quasi-experimental, single health system study of patients treated with PCC or andexanet-alfa from March 2014 to April 2021. Deterioration-free discharge, thrombotic events, length of stay, discharge disposition, and cost were reported.170 patients were included in the PCC group and 170 patients were included in the andexanet-alfa group. Deterioration-free discharge was achieved in 66.5% of PCC-treated patients compared to 69.4% in the andexanet alfa-treated patients. 31.8% of PCC-treated patients were discharged home compared to 30.6% in the andexanet alfa-treated patients. The cost per deterioration-free discharge was $20,773.62 versus $5230.32 in the andexanet alfa and 4F-PCC group, respectively.Among patients that experienced a bleed while taking a factor Xa inhibitor, there was no difference in clinical outcomes for patients treated with andexanet-alfa compared to PCC. Although there was no difference in the clinical outcomes, there was a significant difference in cost with andexanet-alfa costing approximately four times as much as PCC per deterioration-free discharge.

Four-Factor Prothrombin Complex Concentrate in Left Ventricular Assist Device Implantation: Inverse Propensity Score-Weighted Analysis.

We compare the effect of intraoperative administration of four-factor prothrombin complex concentrates (PCCs) versus fresh frozen plasma (FFP) on major bleeding, transfusions, and complications. Out of 138 patients undergoing left ventricle assist device (LVAD) implantation, 32 received PCCs as first-line hemostatic agents and 102 FFP (standard group). The crude treatment estimates indicated that, compared with the standard group, the PCC group required more FFP units (odds ratio [OR]: 4.17, 95% confidence interval [CI]: 1.58-11; p = 0.004) intraoperatively, whereas a greater number of patients received FFP at 24 hours (OR: 3.01, 95% CI: 1.19-7.59; p = 0.021) and less packed red blood cells (RBC) at 48 hours (OR: 0.61, 95% CI: 0.01-1.21; p = 0.046). After the inverse probability of treatment weighting (IPTW) adjusted analyses, in the PCC group there was still a higher number of patients who required FFP (OR: 2.9, 95% CI: 1.02-8.25; p = 0.048) or RBC (OR: 6.23, 95% CI: 1.67-23.14; p = 0.007] at 24 hours and RBC at 48 hours (OR: 3.09, 95% CI: 0.89-10.76; p = 0.007). Adverse events and survival were similar before and after the ITPW adjustment. In conclusion, the PCCs, although relatively safe with respect to thrombotic events, were not associated with a reduction of major bleeding and blood product transfusions.

Comparison of Prothrombin Complex Concentrate with Activated Factor VII Use for Bleeding Following Cardiopulmonary Bypass in Children.

This study aims to compare the efficacy and safety of activated recombinant factor VII (rFVIIa) and prothrombin complex concentrate (PCC) in the treatment of bleeding complications following surgery requiring cardiopulmonary bypass (CPB) in children. This is a retrospective chart review of a single institution comprising patients aged 0 to 18 years old with congenital heart disease. Patients must have received either PCC or rFVIIa after coming off CPB. Our primary efficacy endpoint is time in the operating room from off-CPB to pediatric intensive care unit admission. Our primary safety endpoint is thrombosis through 30 days. Our primary efficacy outcome was significantly shorter in the PCC group compared with the rFVIIa group (P < .0001). Similarly, secondary efficacy outcomes of packed red blood cell administration, chest tube output, and transfusion exposures all significantly favored PCC administration. However, CPB time was significantly longer, and body temperatures were significantly lower, in the rFVIIa group. Safety outcomes, including our primary safety outcome of thrombosis through 30 days, were similar between the two groups. This study questions whether PCC could be favored over rFVIIa for hemostasis in children with congenital heart disease following CPB surgery. In addition, this study has found no difference when comparing PCC and rFVIIa in terms of safety outcomes, particularly thrombosis events. There are several limitations to this study due to the retrospective nature of the design and the differences between the two study groups. Despite the limitations, this study suggests that relatively early administration of PCC could be favored over delayed administration of rFVIIa to control recalcitrant post-CPB bleeding in the operating room.

Prothrombin Complex Concentrate vs Plasma for Post–Cardiopulmonary Bypass Coagulopathy and Bleeding

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. To analyze perioperative bleeding and transfusion outcomes in patients undergoing cardiac surgery who develop microvascular bleeding and receive treatment with either PCC or plasma. 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. 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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT02557672.

Prophylactic fresh frozen plasma versus prothrombin complex concentrate for preprocedural management of the coagulopathy of liver disease: A systematic review

BackgroundThe optimal prophylactic preprocedural management of patients with coagulopathy due to liver disease is not known. ObjectivesOur objective was to compare the efficacy and safety of fresh frozen plasma (FFP) with prothrombin complex concentrate (PCC) in the preprocedural management of patients with coagulopathy of liver disease. MethodsWe conducted a systematic review to examine published evidence regarding treatment with FFP or PCC in adults with coagulopathy of liver disease undergoing an invasive procedure. Direct comparisons and single‐arm studies were eligible. Efficacy outcomes included major bleeding, mortality, and correction of prothrombin time (PT) and/or international normalized ratio (INR). Safety outcomes included thrombosis and transfusion‐related complications. ResultsA total of 95 articles were identified for full‐text review. Nine studies were eligible and included in the review. No randomized trials comparing FFP versus PCC were identified. Only two studies directly compared FFP versus PCC. In these studies, PCC appeared to result in higher rates of correction of PT/INR, but bleeding outcomes were not different. In the single‐arm studies, bleeding events appeared low overall. Volume overload was the most common recorded adverse event in patients receiving FFP. Thromboembolic events occurred rarely, but exclusively in the PCC group. Due to heterogeneity in study definitions and bias, meta‐analysis was not possible. Our study found no evidence to favor a specific product over another. ConclusionsInsufficient data exist on the effects of FFP versus PCC administration before invasive procedures in patients with coagulopathy of liver disease to make conclusions with respect to relative efficacy or safety.

Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery

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. 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. 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. 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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT04114643.

A Comparison of Prothrombin Complex Concentrate and Recombinant Activated Factor VII for the Management of Bleeding With Cardiac Surgery.

Bleeding following cardiac surgery that warrants transfusion of blood products is associated with significant complications, including increased mortality at 1 year following surgery. Factor concentrates, such as prothrombin complex concentrate (PCC), or recombinant activated factor VII (rFVIIa) have been used off-label for bleeding in cardiac surgery that is refractory to conventional therapy. The objective of this retrospective study is to assess the hemostatic effectiveness of 4-factor PCC or rFVIIa for bleeding after a broad range of cardiac surgeries. Patients were included if they were at least 18 years of age and had undergone cardiac surgery with bleeding requiring intervention with 4-factor PCC or rFVIIa. There were no differences observed in the number of packed red blood cells (4-factor PCC: 2 units vs. rFVIIa: 2 units), fresh frozen plasma (0 units vs. 1 unit) or platelet (2 units vs. 2 units) transfusions following the administration of 4-factor PCC or rFVIIa. The patients in the rFVIIa group, required more cryoprecipitate than those in the 4-factor PCC group (4-factor PCC: 2 units (range 0-6) vs. rFVIIa: 2 units (range 0-8), p = 0.03). There were no differences in secondary outcomes of chest tube output at 2, 6, 12 and 24 hours, nor was there a difference in reexploration rates or the median length of stay in the intensive care unit. Thromboembolic complications at 30 days were similar between the two groups (4-factor PCC: 13% vs. rFVIIa 26%, p = 0.08). The total median dose requirement for 4-factor PCC was 1000 units (15 units/kg) and 2 mg (20 mcg/kg) for rFVIIa. The results demonstrate feasibility of utilizing the minimum amount of drug in order to achieve a desired effect. Both 4-factor PCC and rFVIIa appear to be safe and effective options for the management of bleeding associated with cardiac surgery.

Reversal of warfarin anticoagulation in geriatric traumatic brain injury due to ground-level falls

BackgroundThe efficacy of prothrombin complex concentrate (PCC) compared with fresh frozen plasma (FFP) for reversal of oral anticoagulants has not been investigated in geriatric patients suffering intracranial hemorrhage (ICH) due...

Prothrombin Complex Concentrate-induced Disseminated Intravascular Coagulation Can Be Prevented by Coadministering Antithrombin in a Porcine Trauma Model.

The risk of thromboembolic complications with prothrombin complex concentrates (PCCs) appears low when used for reversal of vitamin K antagonists but might be different in other indications (e.g., trauma). A difference in risk could arise from the plasma ratio of pro- versus anticoagulant proteins. This study used a porcine trauma model to investigate combined treatment with PCC and antithrombin. The hypothesis was that antithrombin can modulate prothrombotic effects and prevent adverse events of PCC. Nine treatment groups (n = 7 per group) were included: control (placebo), PCC (50 IU/kg), PCC plus antithrombin (three groups, with antithrombin doses of 12.5, 25, or 50 IU/kg), fibrinogen concentrate (100 mg/kg) plus PCC, fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg, tranexamic acid (15 mg/kg) plus fibrinogen concentrate plus PCC, and tranexamic acid plus fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg. In each group, bilateral femur fractures and thorax contusion were followed 60 min later by blunt liver injury. Study treatment was then administered, and animals were subsequently observed for 210 min. Total blood loss (mean ± SD) was statistically significantly lower in all three PCC plus antithrombin groups (PCC plus antithrombin dose of 50 IU/kg, 672 ± 63 ml; PCC plus antithrombin dose of 25 IU/kg, 535 ± 72 ml; and PCC plus antithrombin dose of 12.5 IU/kg, 538 ± 50 ml) than in the PCC group (907 ± 132 ml), which in turn had statistically significantly reduced bleeding versus the control group (1,671 ± 409 ml). Signs of disseminated intravascular coagulation were apparent with PCC monotherapy, and early deaths occurred with fibrinogen concentrate plus PCC, attributable to pulmonary emboli. Antithrombin was protective against both of these effects: signs of disseminated intravascular coagulation were absent from the PCC plus antithrombin groups, and there were no early deaths in the group with fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg. According to this trauma model, 50 IU/kg PCC increases the risk of disseminated intravascular coagulation and other thromboembolic complications, most notably when coadministered with fibrinogen concentrate. The addition of antithrombin appears to reduce this risk.

Contemporary Reversal of Oral Anticoagulation in Intracerebral Hemorrhage.

Author(s): Bower, Matthew M; Sweidan, Alexander J; Shafie, Mohammad; Atallah, Steven; Groysman, Leonid I; Yu, Wengui

Utility of 4-Factor Prothrombin Complex Concentrate in Trauma and Acute-Care Surgical Patients.

Since 2013, prothrombin complex concentrate (PCCs) have been approved in the United States for the reversal of anticoagulation induced by vitamin K antagonists. However, there has been limited investigation into their use in trauma and acute-care surgery (ACS). To investigate the role that 4-factor PCC may have in reversing anticoagulation in the setting of trauma and ACS. All trauma and ACS patients who presented between March 14, 2014, and August 1, 2015, were included in this retrospective descriptive analysis. Patients receiving 4-factor PCC were compared with patients receiving fresh frozen plasma (FFP) alone. The following data were collected from medical records: age, sex, race, international normalized ratio (INR) at admission (baseline) and after reversal, blood products given, dosing of medication, injury severity score, length of stay, thromboembolic event, death during admission, and death within 90 days after admission. There were 188 trauma and ACS patients who required reversal of anticoagulation. Of these, 98 patients received FFP and 90 received PCC. Patients who received PCC were at increased risk for death during admission (20% vs 9.2% for FFP group) or within 90 days (39% vs 15%, respectively). Patients in the PCC group had a higher median baseline INR (2.9 vs 2.5 in the FFP group) and a lower postintervention INR (1.4 vs 1.8); consequently, the decrease in INR was greater in the PCC group than in the FFP group (1.5 vs 0.7, respectively). The number of total units of packed red blood cells transfused was significantly higher in patients receiving PCC. Patients receiving PCC had worse outcomes than those who received FFP. Given that these differences may have resulted from baseline differences between groups, these results mandate further prospective analysis of the use of PCC in trauma and ACS patients.

A Retrospective Propensity Score-Matched Early Thromboembolic Event Analysis of Prothrombin Complex Concentrate vs Fresh Frozen Plasma for Warfarin Reversal Prior to Emergency Neurosurgical Procedures

Reversal of therapeutic anticoagulation prior to emergency neurosurgical procedures is required in the setting of intracranial hemorrhage. Multifactor prothrombin complex concentrate (PCC) promises rapid efficacy but may increase the probability of thrombotic complications compared to fresh frozen plasma (FFP). To compare the rate of thrombotic complications in patients treated with PCC or FFP to reverse therapeutic anticoagulation prior to emergency neurosurgical procedures in the setting of intracranial hemorrhage at a level I trauma center. Sixty-three consecutive patients on warfarin therapy presenting with intracranial hemorrhage who received anticoagulation reversal prior to emergency neurosurgical procedures were retrospectively identified between 2007 and 2016. They were divided into 2 cohorts based on reversal agent, either PCC (n = 28) or FFP (n = 35). The thrombotic complications rates within 72 h of reversal were compared using the χ2 test. A multivariate propensity score matching analysis was used to limit the threat to interval validity from selection bias arising from differences in demographics, laboratory values, history, and clinical status. Thrombotic complications were uncommon in this neurosurgical population, occurring in 1.59% (1/63) of treated patients. There was no significant difference in the thrombotic complication rate between groups, 3.57% (1/28; PCC group) vs 0% (0/35; FFP group). Propensity score matching analysis validated this finding after controlling for any selection bias. In this limited sample, thrombotic complication rates were similar between use of PCC and FFP for anticoagulation reversal in the management of intracranial hemorrhage prior to emergency neurosurgical procedures.

Use of prothrombin complex concentrate for management of coagulopathy after cardiac surgery: a propensity score matched comparison to plasma

BackgroundAn important cause of coagulopathy in cardiac surgery is impaired thrombin generation. While plasma is often used to correct this element of the coagulopathy, studies in vitro suggest that prothrombin complex concentrates (PCCs) might be more effective. Comparative data, however, are scant. MethodsWe compared the outcomes of those who received only plasma with those who received PCCs (with or without plasma) for management of coagulopathy in patients who underwent cardiac surgery with cardiopulmonary bypass at a single institution from 2012 to 2016. Propensity score matching was used to obtain between-group balance. Primary outcome was avoidance of perioperative red cell transfusions. Other outcomes were incidence of massive transfusion (more than nine red cell units), refractory bleeding (requiring factor VIIa), and adverse events. ResultsOf 6362 patients, 1151 (18.2%) received plasma without any PCCs, and 204 (3.2%) received PCCs, either with (n=125) or without plasma (n=79). Overall, patient risk-profile was higher in the PCCs group. In a well-balanced propensity score match that included 117 patients per group, the odds ratio (OR) for red cell avoidance was 2.4-fold [95% confidence interval (CI) 1.2–4.8] higher in the PCCs group. Massive transfusion (OR 0.58; 95% CI 0.33–1.0) and refractory bleeding (OR 0.49; 95% CI 0.24–1.03) incidences were almost significantly lower in the PCCs group. The adverse event profiles were similar. ConclusionsOur exploratory study suggests that the use of PCCs as part of a multifaceted coagulation management strategy may have blood-sparing effects. Their incorporation into clinical practice, however, must await determination of their risk-benefit profile via multicentre randomised trials.

Impact of Prothrombin Complex Concentrate on Blood Use, Cost, and Outcomes in Heart Transplantation

Left ventricular assist device (LVAD) recipients undergoing heart transplantation have increased bleeding risk. We compared conventional warfarin reversal with fresh frozen plasma vs 4-factor prothrombin complex concentrate (PCC) and the effect on transfusion requirements, blood bank costs, and clinical outcomes. A retrospective review identified 60 consecutive LVAD recipients undergoing heart transplantation divided into two groups: 30 (no PCC) received fresh frozen plasma and 30 (PCC) received PCC. Patient characteristics, intraoperative and postoperative transfusion requirements, short-term clinical outcomes, and blood bank costs were compared. PCC association with transfusion requirements was assessed by multivariate linear regression. Patients who received PCC were younger (50 ± 11 vs 57 ± 13 years, p= 0.02), fewer had ischemic cardiomyopathy (23% vs 60%, p= 0.01), had more than one prior sternotomy (7% vs 30%, p= 0.04), and had higher preoperative hemoglobin (11.8 ± 1.8 vs 10.4 ± 1.8 g/dL, p= 0.01). The PCC group had a significantly shorter bypass time (185 vs 217 minutes, p= 0.01), received less fresh frozen plasma (2 vs 5 units, p= 0.03), cryoprecipitate (0 vs 2 units, p= 0.05), and total blood products (9 vs 13.5 units, p= 0.03) intraoperatively, and was less likely to require delayed sternal closure (3% vs 23%, p= 0.05). On multivariate linear regression, PCC was significantly associated with decreased intraoperative transfusion (β= -6.09, p= 0.02). There was no difference in thromboembolic events or in-hospital death. Total blood bank costs were $4,949 for PCC and $3,677 for no PCC (p= 0.01). Although more costly, PCC reduced transfusion requirements and delayed sternal closure in heart transplant recipients bridged with LVAD, justifying its use over traditional warfarin reversal.

Prothrombin Complex Concentrate Reduces Blood Product Utilization in Heart Transplantation.

Current practices for the reversal of warfarin before cardiac surgery include the use of vitamin K and fresh frozen plasma (FFP) to reduce the risk of bleeding. Although the 2010 International Society of Heart and Lung Transplantation guidelines acknowledge the use of prothrombin complex concentrate (PCC), there is no clear consensus on its efficacy. The objective of this study was to assess the efficacy of four-factor (4-F) PCC administration in patients requiring warfarin reversal before heart transplantation by determining blood product utilization perioperatively. Twenty-one patients who received 4-F PCC for warfarin reversal before heart transplantation were compared to a similar cohort of 39 patients who did not receive 4-F PCC, from January 2011 to July 2015. Blood product utilization was collected retrospectively for the 24-hour preoperative, intraoperative, and 48-hour postoperative periods. Patients receiving 4-F PCC required fewer blood products in all three time periods. In the 24-hour preoperative period, 22 (56%) patients in the control group and 2 (10%) patients in the 4-F PCC groups received blood products (p<0.001). Intraoperatively, all patients received blood products. The 4-F PCC group required fewer units of packed red blood cells (median 3 vs 7 units, p<0.001) and FFP (median 4 vs 9 units, p<0.001). In the 48-hour postoperative period, 20 (51%) patients in the control group and 5 (24%) patients in the 4-F PCC group received blood products (p=0.04). 4-F PCC is associated with reduced blood product utilization 24hours preoperatively and intraoperatively. Historically, the majority of patients require FFP for warfarin reversal preoperatively. In this single-center study, a significant reduction in the need for FFP was demonstrated with the use of 4-F PCC.

Prothrombin Complex Concentrate Versus Fresh Frozen Plasma for Vitamin K Antagonist Reversal in Acutely Bleeding Patients: A Retrospective Study

▪IntroductionVitamin K antagonist (VKA) drugs require immediate reversal in VKA-treated patients with major bleeding or requiring urgent surgery. 4-factor prothrombin complex concentrates (PCCs)are approved for urgent VKA reversalbecause they reverse the international normalized ratio (INR) more rapidly than fresh frozen plasma (FFP). Studies comparing the clinical benefits of PCC and FFP have focused on VKA reversal prior to urgent surgery. Few data comparing laboratory and clinical outcomes of patients receiving PCC or FFP for major hemorrhage have been published, and these pertain to intracranial hemorrhage (ICH) only. Given the complexity of performing randomized studies in this setting, observational studies are relevant to inform on this issue.AIMSTo compare the effects of PCC versus FFP on patient outcomes in VKA-associated major hemorrhage. The primary outcomes were the rate of INR reversal and blood product utilization. The secondary outcome was duration of intensive care and total hospital admission.MethodsWe performed a retrospective, single-center study of consecutive unselected patients receiving a 4-factor PCC for VKA reversal because of hemorrhage between January 2012 and April 2015 compared to consecutive unselected patients treated with FFP for the same indication from January 2010-December 2011, a period prior to introduction of PCC at the Meir Medical Center. Patients were identified by review of clinical and blood bank electronic medical records. We analyzed patient demographics, indication for VKA, underlying illnesses, aspirin use, site and severity of hemorrhage, INR pre- and post reversal, rate of INR reversal, transfusion requirements and duration of hospitalization, treatment.Results56 patients received PCC and were compared to 56 patients treated with FFP. In the PCC group 17 patients had ICH and 25 had gastrointestinal hemorrhage compared to 17 and 31 patients respectively in the FFP group. Patients were adjusted for age, sex, presence of renal failure, active cancer, aspirin use, site of hemorrhage, pre-treatment INR and hemoglobin concentration and hemorrhagic shock at presentation. Outcomes: Median time to INR of ≤1.3 was 0.5 (range 0.5-1.5) vs 15.5 (range 5-96) hours for PCC vs FFP respectively, P<0.001). Packed red cell transfusion did not differ between the groups: median =1(range 0-13) in the PCC group and median= 2(range=2-10) in the FFP group (P=0.3), but more FFP was transfused in the FFP vs PCC group median =0(range 0-8) in the PCC group and median= 4(range=2-8) in the FFP group (P<0.001). Duration of hospital admission was longer in the FFP (median=7 days, range 1-93) vs PCC patients (median =6 days, range=1-35) (P=0.04).ConclusionThis is the first observational study comparing PCC and FFP for VKA-related hemorrhage to our knowledge and the first study of PCC versus FFP for extracranial VKA-related hemorrhage. PCC was more effective than FFP in for reversal of the INR and was associated with less overall FFP use but not packed red cell transfusion. Similarly hospital admission duration was shorter among the PCC patients. Larger studies are required to determine whether PCC confers other clinical benefits over FFP for VKA reversal in acutely bleeding patients. DisclosuresEllis:Boehringer Ingelheim: Speakers Bureau; Bayer: Speakers Bureau; Pfizer: Speakers Bureau.

Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial

Haematoma expansion is a major cause of mortality in intracranial haemorrhage related to vitamin K antagonists (VKA-ICH). Normalisation of the international normalised ratio (INR) is recommended, but optimum haemostatic management is controversial. We assessed the safety and efficacy of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with VKA-ICH. We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2·0 were randomly assigned (1:1) by numbered sealed envelopes to 20 mL/kg of intravenous FFP or 30 IU/kg of intravenous four-factor PCC within 1 h after initial cerebral CT scan. The primary endpoint was the proportion of patients with INR 1·2 or lower within 3 h of treatment initiation. Masking of treatment was not possible, but the primary analysis was observer masked. Analyses were done using a treated-as-randomised approach. This trial is registered with EudraCT, number 2008-005653-37, and ClinicalTrials.gov, number NCT00928915. Between Aug 7, 2009, and Jan 9, 2015, 54 patients were randomly assigned (26 to FFP and 28 to PCC) and 50 received study drug (23 FFP and 27 PCC). The trial was terminated on Feb 6, 2015, after inclusion of 50 patients after a safety analysis because of safety concerns. Two (9%) of 23 patients in the FFP group versus 18 (67%) of 27 in the PCC group reached the primary endpoint (adjusted odds ratio 30·6, 95% CI 4·7-197·9; p=0·0003). 13 patients died: eight (35%) of 23 in the FFP group (five from haematoma expansion, all occurring within 48 h after symptom onset) and five (19%) of 27 in the PCC group (none from haematoma expansion), the first of which occurred on day 5 after start of treatment. Three thromboembolic events occurred within 3 days (one in the FFP group and two in the PCC group), and six after day 12 (one and five). 43 serious adverse events (20 in the FFP group and 23 in the PCC group) occurred in 26 patients. Six serious adverse events were judged to be FFP related (four cases of haematoma expansion, one anaphylactic reaction, and one ischaemic stroke) and two PCC related (ischaemic stroke and pulmonary embolism). In patients with VKA-related intracranial hemorrhage, four-factor PCC might be superior to FFP with respect to normalising the INR, and faster INR normalisation seemed to be associated with smaller haematoma expansion. Although an effect of PCC on clinical outcomes remains to be shown, our data favour the use of PCC over FFP in intracranial haemorrhage related to VKA. Octapharma.

Safety of Prothombin Complex Concentrate to Control Excess Bleeding During Continuous Flow LVAD Insertion.

In cardiovascular surgery, hemostatic complexities require the provision of blood products to control bleeding as well as the use of a number of hemostatic agents, some of which cause significant morbidity. Among these agents is prothrombin complex concentrates (PCC), however there is no clear consensus on PCC use in cardiovascular surgery. To investigate the safety of PCC in patients undergoing left ventricular assist device (LVAD) placement, we reviewed our single institution experience to examine the incidence of thromboembolic events and a variety of hospital markers including morbidity and mortality. A retrospective review was conducted of patients who underwent LVAD placement between January 2010 and October 2012. Patients who received intraoperative PCC constituted the PCC group (n = 41) and those who did not constituted the non-PCC group (n = 27). The overall incidence of thromboembolic events at 3 months postoperative was 12 (29.3%) in the PCC group compared with six (22.2%) in the non-PCC group, respectively (p > 0.05). Morbidity did not differ between groups and one patient in the PCC group died. The intraoperative use of PCC in LVAD insertion does not appear to be associated with a significant increase in thromboembolic events; however, larger randomized trials are needed to confirm these findings.

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.

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.