Experiences with an activated 4-factor prothrombin complex concentrate (FEIBA) for reversal of warfarin-related bleeding

Background

Current reversal options for warfarin-related bleeding are limited but include fresh frozen plasma, recombinant factor VIIa, or a prothrombin complex concentrate (PCC). There are little data discussing the use of activated 4-factor PCC for warfarin reversal.

Objectives

This review will summarize our experiences with FEIBA (Baxter, Deerfield, IL), an activated 4-factor PCC, for the reversal of warfarin-related bleeding in a community hospital.

Methods

A protocol was put in place in March of 2011, which outlined the use of FEIBA for the emergent reversal of warfarin-related coagulopathy. A low fixed dose was given based on international normalized ratio (INR). For an INR less than 5.0, 500 U of FEIBA was administered. For an INR greater than or equal to 5.0, 1000 U of FEIBA was given. Intravenous vitamin K was given concurrently regardless of INR.

Results

Sixteen patients were treated with FEIBA per the protocol. Average patient age was 73 years. Intracranial hemorrhage was the most common indication for reversal. Mean pre-treatment INR was 3.56 (1.3-6.8); mean post-treatment INR was 1.16 (1.01-1.32). Two of the patients required a second 500-U dose, per the protocol, for an INR that had not yet normalized. Bleeding appeared clinically controlled in 93% of cases. Eighty-seven percent of patients survived to discharge. There were no signs or symptoms of thrombosis in any of the cases.

Conclusions

Emergent reversal of warfarin utilizing a fixed, low dose of FEIBA appears to be efficacious, consistent, and safe. Further comparator studies with other reversal agents are needed.     

Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy

Aims

The purpose of this study was to evaluate the effectiveness of a new, fixed, yet individualized dosing regimen of activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for warfarin reversal in the setting of a life-threatening bleeding in a secondary care center.

Methods

In this report we present a retrospective chart review of 72 patients who received FEIBA and 69 patients who received fresh-frozen plasma (FFP) to reverse the effects of warfarin in a setting of a life-threatening bleeding. In the FEIBA cohort, patients received 500 units of FEIBA when the initial INR was <5 or 1,000 units of FEIBA when initial INR was ≥5.

Results

FEIBA administration resulted in lower subsequent INR when compared with FFP and shorter time elapsed from drug administration to an INR ≤1.4 when compared with FFP. No significant differences in survival or in the length of hospital stay were observed. A higher FEIBA dose induced a bigger decrease in INR than the lower dose. We observed five adverse events (7%) that could potentially be related to FEIBA administration.

Conclusions

The presented dosing regimen results in safe reversal of warfarin-induced coagulopathy, which appears to be faster and more profound than following FFP. Moreover, the use of activated PCC (FEIBA) does not appear to carry an increased risk of thrombotic events when compared to the rate reported for several non-activated PCC preparations.     

Modified version of the American College of Cardiology's recommendation for low-dose prothrombin complex concentrate is effective for warfarin reversal

BackgroundDosing of four factor prothrombin complex concentrate (4PCC) for warfarin reversal remains controversial. Recently, the American College of Cardiology (ACC) recommended a low-dose PCC regimen as an option for warfarin reversal in acute major bleeding. We performed a retrospective study evaluating if a modified version of the ACC guideline recommendations was effective for warfarin reversal in acute major bleeds when compared to traditional variable dosing.MethodsThis was a retrospective cohort study of patients who received 4PCC for warfarin reversal in a 12 month period. We included patients that were ≥18 years of age, received 4PCC for warfarin reversal, and had an initial International Normalized Ratio (INR) of >2. Our primary outcome was the number of patients who had a post-4PCC infusion INR of <1.6.ResultsA total of 60 patients were included in the final analysis with 30 patients stratified to the traditional dosing and low-dose groups, respectively. Patient demographics were similar between both groups. We found no difference in the number of patients who had a post-4PCC infusion INR <1.6 between the traditional dosing and low dosing group (90.0% vs. 86.7%; p = 0.68). Additionally, we found no difference between post-infusion median INRs in each group (1.35 vs. 1.30; p = 0.16). Approximately 1000 units per patient were spared when utilizing the low-dose regimen.ConclusionA modified version of the ACC's low-dose 4PCC option for warfarin reversal achieves similar outcomes for lowering INR values compared to traditional variable dosing regimens.     

Four-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A retrospective evaluation

PurposePrevious trials investigating usage of four-factor prothrombin complex concentrate (4F-PCC) excluded patients with various thrombotic risk factors. The objective of this study was to evaluate the safety and effectiveness of 4F-PCC in a real-world setting based on an institutional protocol that does not have strict exclusion criteria.MethodsThis was a retrospective study of adult patients who received 4F-PCC. The primary outcome was a confirmed thromboembolism within 14 days after 4F-PCC administration. Secondary outcomes included international normalized ratio (INR) correction to <1.5 at first draw and incidence of INR rebound for patients undergoing reversal of warfarin and hemostatic effectiveness for patients experiencing a bleed.ResultsNinety-three patients received 4F-PCC. Sixty-three (67.7%) were reversed for bleeding and 30 (32.3%) for surgery. Eleven patients (11.8%) developed a thromboembolism within 14 days. The median (interquartile range) time to event was 5 (2-7) days. Significant risk factors were heparin-induced thrombocytopenia (P= .01) and major surgery within 14 days (P= .02), as well as the presence of >6 thrombotic risk factors (P= .01). For patients post-warfarin reversal, 45/63 (71.4%) achieved INR correction at first draw, 55/63 (87.3%) achieved INR correction within 24 hours, and 14/55 (25.5%) experienced INR rebound. Of these 14 patients, 8 (57.1%) did not receive concomitant vitamin K.Conclusions4F-PCC was associated with a notable thromboembolic risk. All patient-specific risk factors should be considered prior to administration. 4F-PCC remains a useful agent for warfarin reversal. Lack of concomitant vitamin K may contribute to INR rebound.     

Multi-centered evaluation of a novel fixed-dose four-factor prothrombin complex concentrate protocol for warfarin reversal

IntroductionPrevious studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal.MethodsThis was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications.ResultsA total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC.ConclusionA fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.     

Fixed-dose prothrombin complex concentrate for emergent warfarin reversal among patients with intracranial hemorrhage

IntroductionFour-factor prothrombin complex concentrate (4PCC) is the preferred reversal agent for warfarin reversal, although the ideal dose is unknown. Fixed-dose 4PCC offers simplified dosing compared to standard-dosing algorithms with potentially lower risks of thromboembolic complications given lower doses are typically utilized.MethodsRetrospective, observational, multicentered, pre- post- study of patients who received 4PCC for warfarin reversal among four hospitals within the same regional health system. Standard-dose patients received variable doses ranging from 25 to 50 units/kg based on total body weight and initial INR and fixed-dose patients received 2000 units. The primary outcome was achievement of a target INR ≤ 1.4 on the first post-4PCC INR result.ResultsAfter exclusions, 48 and 42 patients were analyzed in the standard-dose and fixed-dose groups, respectively. There was no difference in the ability to achieve a target INR of ≤1.4 (82.6% vs 81.5%, p = 0.14). Both groups received the same median dose of 2000 units, although fixed-dose patients actually received a higher weight-based dose than standard-dose patients (27 units/kg vs 24.5 units/kg).ConclusionA fixed-dose 4PCC regimen of 2000 units among patients with ICH was as effective as standard-dose 4PCC for INR reversal among patients with ICH. However, fixed-doses of 2000 units at times exceeded standard 4PCC doses which may be contradictory to the goals of fixed-dose 4PCC for warfarin reversal.     

Prothrombin complex concentrate for the urgent reversal of warfarin. Assessment of a standard dosing protocol

BackgroundOctaplex®, a six factor prothrombin complex concentrate (PCC), has recently been approved for use in Canada. The optimal dose of Octaplex has yet to be established and our study was designed to monitor the efficacy of a low standard dose.Study design and methodsPatients on warfarin treatment in need of urgent reversal for bleeding, invasive procedures or surgery were given a standard dose of 40 ml (1000 IU FIX, 14 IU/kg). We conducted a retrospective chart review of 231 patients.ResultsPatients given concurrent frozen plasma (FP) for reversal were eliminated from the study. Overall, 150 patients were reviewed and divided into three groups: (1) non-CNS bleeders, (2) CNS bleeders, and (3) non-bleeders. Correction of INR to 1.5 or less was achieved to the same extent in each group. Patients with active bleeding had the least successful bleeding cessation and patients with intracranial bleeding had the most dismal outcome compared to non-intracranial bleeders.ConclusionsOur data suggests that Octaplex, when given as a low standard dose is effective at INR reversal with 76% of our patients correcting to an INR of 1.5 or less. It appears that this dose is sufficient for non-bleeding patients. Bleeding patients may benefit most from a dose increase to achieve more complete reversal and patients with intracranial bleeding should achieve more complete reversal within 2 h of presentation.     

Suboptimal effect of a three-factor prothrombin complex concentrate (Profilnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose

BACKGROUND: Plasma transfusion is standard therapy for urgent warfarin reversal in the United States. "Four-factor" prothrombin complex concentrate (PCC), available in Europe, has advantages over plasma therapy for warfarin reversal; however, only "three-factor" PCCs (containing relatively low Factor [F]VII) are available in the United States.
STUDY DESIGN AND METHODS: The efficacy of a three-factor PCC for urgent warfarin reversal was evaluated in 40 patients presenting with supratherapeutic international normalized ratio (ST-INR > 5.0) with bleeding (n = 29) or at high risk for bleeding (n = 11). In 13 patients, pre- and posttherapy vitamin K-dependent factors were assayed. Historical controls (n = 42) treated with plasma alone were used for rate of ST-INR correction comparison.
RESULTS: Treatment with plasma alone (mean, 3.6 units) lowered the INR to less than 3.0 in 63 percent of historical controls. Low-dose (25 U/kg) and high-dose (50 U/kg) PCC alone lowered INR to less than 3.0 in 50 and 43 percent of patients, respectively. Additional transfusion of a small amount of plasma (mean, 2.1 units) increased the rate of achieving an INR of less than 3.0 to 89 and 88 percent for low- and high-dose PCC therapy, respectively. FII, F IX, and FX increments were similar for PCC-treated patients with or without supplemental plasma; FVII was significantly higher in the PCC plus plasma group compared to the PCC-only group (p = 0.001).
CONCLUSION: Three-factor PCC does not satisfactorily lower ST-INR due to low FVII content. Infusion of a small amount of plasma increases the likelihood of satisfactory INR lowering.     

Is there a difference in efficacy,safety, and cost-effectiveness between 3-factor and 4-factor prothrombin complex concentrates among trauma patients on oral anticoagulants?

PurposeThe aim of this study was to compare the efficacy, safety, and cost-effectiveness of 3-factor prothrombin complex concentrate (3F-PCC) vs 4-factor prothrombin complex concentrate PCC (4F-PCC) in trauma patients requiring reversal of oral anticoagulants.Materials and methodsAll consecutive trauma patients with coagulopathy (international normalized ratio [INR] ≥ 1.5) secondary to oral anticoagulants who received either 3F-PCC or 4F-PCC from 2010 to 2014 at 2 trauma centers were reviewed. Efficacy was determined by assessing the first INR post–PCC administration, and successful reversal was defined as INR less than 1.5. Safety was assessed by reviewing thromboembolic events, and cost-effectiveness was calculated using total treatment costs (drug acquisition plus transfusion costs) per successful reversal.ResultsForty-six patients received 3F-PCC, and 18 received 4F-PCC. Baseline INR was similar for 3F-PCC and 4F-PCC patients (3.1 ± 2.3 vs 3.4 ± 3.7, P = .520). The initial PCC dose was 29 ± 9 U/kg for 3F-PCC and 26 ± 6 U/kg for 4F-PCC (P = .102). The follow-up INR was 1.6 ± 0.6 for 3F-PCC and 1.3 ± 0.2 for 4F-PCC (P = .001). Successful reversal rates in patients were 83% for 4F-PCC and 50% for 3F-PCC (P = .022). Thromboembolic events were observed in 15% of patients with 3F-PCC vs 0% with 4F-PCC (P = .177). Cost-effectiveness favored 4F-PCC ($5382 vs $3797).ConclusionsThree-factor PCC and 4F-PCC were both safe in correcting INR, but 4F-PCC was more effective, leading to better cost-effectiveness. Replacing 3F-PCC with 4F-PCC for urgent coagulopathy reversal may benefit patients and institutions.     

High versus low fixed-dose four factor-prothrombin complex concentrate for warfarin reversal in patients with intracranial hemorrhage

BackgroundFour-factor prothrombin complex concentrate 4F-PCC is the standard of care for warfarin reversal in patients with major bleed or requiring urgent surgery. Although the 4F-PCC dose is weight and international normalized ratio (INR) based, for practical purposes, a fixed-dose approach has been explored, especially for rapid reversal. We report our experience using two different fixed-dose 4F-PCC for warfarin reversal in patients presenting with intracranial hemorrhage (ICH).Study design and methodsWe completed a retrospective chart review comparing high (4000 units) versus low (2000 units) dose 4F-PCC by evaluating patient characteristics, laboratory data, and pre-and post-4F-PCC brain imaging.ResultsThere was no significant difference between patient characteristics or INR correction (≤1.5) between the two groups. Eighty percent (12/15) of patients who received the low dose 4F-PCC had either improved or stable brain imaging as compared to 88% (14/16) of patients who received the high dose PCC. When the eight patients (4 from each arm of the study) who required neurosurgery were excluded, only two patients in each arm had worse imaging after 4F-PCC.ConclusionThere was no significant difference between the INR correction and the brain imaging changes in patients with an ICH who received either the high or the low fixed-dose 4F-PCC for warfarin reversal.     

Reversal of Vitamin K Antagonist (VKA) effect in patients with severe bleeding: a French multicenter observational study (Optiplex) assessing the use of Prothrombin Complex Concentrate (PCC) in current clinical practice

Introduction

Prothrombin Complex Concentrate (PCC) is a key treatment in the management of bleeding related to Vitamin K antagonists (VKA). This study aimed to evaluate prospectively PCC use in patients with VKA-related bleeding in view of the French guidelines published in 2008.

Methods

All consecutive patients with VKA-related bleeding treated with a 4-factor PCC (Octaplex^®) were selected in 33 French hospitals. Collected data included demographics, site and severity of bleeding, modalities of PCC administration, International Normalized Ratio (INR) values before and after PCC administration, outcomes and survival rate 15 days after infusion.

Results

Of 825 patients who received PCC between August 2008 and December 2010, 646 had severe bleeding. The main haemorrhage sites were intracranial (43.7%) and abdominal (24.3%). Mean INR before PCC was 4.4 ± 1.9; INR was unavailable in 12.5% of patients. The proportions of patients who received a PCC dose according to guidelines were 15.8% in patients with initial INR 2-2.5, 41.5% in patients with INR 2.5-3, 40.8% in patients with INR 3-3.5, 26.9% in patients with INR > 3.5, and 63.5% of patients with unknown INR. Vitamin K was administered in 84.7% of patients. The infused dose of PCC did not vary with initial INR; the mean dose was 25.3 ± 9.8 IU/Kg. Rates of controlled bleeding and target INR achievement were similar, regardless of whether or not patients were receiving PCC doses as per the guidelines. No differences in INR after PCC treatment were observed, regardless of whether or not vitamin K was administered. INR was first monitored after a mean time frame of 4.5 ± 5.6 hours post PCC. The overall survival rate at 15 days after PCC infusion was 75.4% (65.1% in patients with intracranial haemorrhage). A better prognosis was observed in patients reaching the target INR.

Conclusions

Severe bleeding related to VKA needs to be better managed, particularly regarding the PCC infused dose, INR monitoring and administration of vitamin K. A dose of 25 IU/kg PCC appears to be efficacious in achieving a target INR of 1.5. Further studies are required to assess whether adjusting PCC dose and/or better management of INR would improve outcomes.     

Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms

BACKGROUND: An excessive anticoagulant effect because of coumarins is frequently encountered. Objective: To review available literature on the management of warfarin-associated coagulopathy and to propose evidence-based treatment algorithms. METHODS: Data sources were Medline and Embase. Papers published between 1966 and December 2005 describing randomized trials or prospective cohort studies evaluating treatments for coumarin-associated coagulopathy were abstracted. RESULTS: Low dose oral vitamin K rapidly and reliably returns the international normalized ratio (INR) to the usual therapeutic range in non-bleeding patients. Simple withholding of acenocumarol results in rapid correction of its anticoagulant effect. The impact of oral vitamin K on phenprocumon-associated coagulopathy cannot be determined from available literature. Intravenous vitamin K and coagulation factors should be given to patients with major or life-threatening hemorrhage. The optimal dose and type of coagulation factor is not known. CONCLUSIONS: Vitamin K therapy is an effective treatment for INR prolongation in patients with coumarin-associated coagulopathy; coagulation factor replacement is required, in addition, in patients with major bleeding or with indication for immediate correction of their INR. Clinical trials powered to detect differences in rates of bleeding and thrombosis are now required to determine if vitamin K reduces the risk of bleeding without causing thrombosis in non-bleeding patients with prolonged INR.     

Urgent reversal of warfarin with prothrombin complex concentrate

BACKGROUND: When life-threatening bleeding occurs in patients on warfarin, timely reversal becomes imperative. In the USA, warfarin effect is commonly reversed with fresh frozen plasma (FFP). The use of FFP is complicated by delays in correction, volume overload and often, inadequate correction. OBJECTIVE: Evaluate the feasibility and efficacy of a protocol for rapid administration of prothrombin complex concentrate (PCC) in the setting of the urgent need for reversal of warfarin. METHODS/PATIENTS: We instituted a policy for rapid delivery and administration of PCC. Appropriate patients received 25-50 U kg(-1) of PCC. The prothrombin time (PT)/International Normalized Ratios (INR) was recorded before and immediately after dosing, and 24 h postdosing. Patients requiring surgical interventions were cleared for the operating room (OR) immediately. Fifty-eight patients were treated, with a median age of 75.5 years (range 26-92). RESULTS: The median INR on presentation was 3.8 (1.4-52.8). Immediately following PCC administration the median INR was 1.3 (0.9-5.7), only two patients with INRs exceeding 2.0. The benefit was maintained at 24 h with a median INR of 1.5 (1.1-3.4). Four patients experienced thrombotic events during their hospitalization, (two deep vein thrombosis, two non-q-wave myocardial infarction) although none was attributed to PPC therapy. CONCLUSIONS: PCC administration is an effective treatment modality for the correction of warfarin anticoagulation in the urgent setting. Advantages over FFP include more timely correction, absence of volume overload and potentially more complete correction. Broader use of PCC in this setting appears to be appropriate.     

Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin,but not in that induced by dabigatran etexilate

Summary. Background: Both established oral anticoagulants such as warfarin and newer agents such as dabigatran etexilate (DE) effectively prevent thromboembolic disease, but may provoke bleeding. Limited clinical data exist linking oral anticoagulant reversal and bleeding tendency, as opposed to surrogate laboratory markers. Objective: To quantify bleeding in warfarin‐anticoagulated and DE‐anticoagulated mice by tail transection with or without pretreatment with potential reversal agents: prothrombin complex concentrate (PCC); activated PCC (APCC); recombinant factor VIIa (rFVIIa); or murine fresh‐frozen plasma (FFP). Methods: CD1 mice were given warfarin or DE by gavage, and the effects on in vitro coagulation assays, volume of blood loss and the bleeding time following tail transection injury were evaluated with different reversal agents. Results: PCC (14.3 IU kg^?1), but not rFVIIa (3 mg kg^?1) or FFP (12 mL kg^?1), normalized blood loss and bleeding time in mice with warfarin‐induced elevations of mean prothrombin time at two intensities (prothrombin time ratios of either 4.3 or 24). Neither separate nor combined PCC and/or rFVIIa treatment nor APCC (100 U kg^?1) treatment significantly reduced blood loss in mice anticoagulated with 60 mg kg^?1 DE 75 min prior to tail transection. Both combined PCC plus rFVIIa treatment and APCC treatment significantly reduced bleeding time in the DE‐treated mice. Conclusions: Our data suggest that PCC treatment prevents excess bleeding much more effectively in warfarin‐induced coagulopathy than in DE‐induced coagulopathy.     

Evaluation of Fixed-Dose Four-Factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal in Patients with Intracranial Hemorrhage

Background

Different strategies exist for dosing four-factor prothrombin complex concentrate (PCC4) for international normalized ratio (INR) reversal in the setting of life-threatening bleeding. Fixed doses ranging from 1000 IU to 1750 IU have demonstrated efficacy similar to weight-based dosing, however, few studies look exclusively at intracranial hemorrhage (ICH).

Fresh Frozen Plasma Dosing for Warfarin Reversal: A Practical Formula

ObjectiveTo provide a practical formula for fresh frozen plasma (FFP) dosing for warfarin reversal.Patients and MethodsWe reviewed data on all adult patients who received a total of 7778 units of FFP for warfarin reversal at Sentara Norfolk General Hospital (Norfolk, VA) between April 1, 2009, and March 31, 2010. Patients with advanced liver disease, consumptive or dilutional coagulopathy, and administration of activated factor VII or prothrombin complex concentrate were excluded. First, we used regression analysis on the FFP1 subset (patients whose international normalized ratio [INR] was checked before and after 1 FFP administration) and derived a simple formula: DeltaINR (PreINR – PostINR) after 1 FFP = a × PreINR + b, where PreINR and PostINR are the INR values before and after FFP administration, respectively, and a and b are constants. In the validation step, the formula obtained for the FFP1 subset was repeatedly applied to the FFP2 (patients who received 2 units of FFP back-to-back without an intervening INR check), FFP3, and FFP4 subsets.ResultsA total of 956 patients were included. The formula DeltaINR after 1 FFP = 0.57 × PreINR – 0.72 explained 82.6% of the total variance in INR change in the FFP1 subset (n=308; P<.01). Including age, sex, weight, FFP-to-PostINR interval, or administration of vitamin K marginally improved the model. Repeated application of the FFP1 formula to the FFP2 to 4 subsets combined confirmed the accuracy of the FFP1 formula across the entire data set (n=643; R²=95% between predicted and actual DeltaINR; P<.01).ConclusionThis formula provides a practical and accurate method for FFP dosing for warfarin reversal.     

Audit of warfarin reversal using a new Octaplex reduced dose protocol

IntroductionProthrombin Complex Concentrate (PCC) is increasingly used for the emergency reversal of the effects of Vitamin K antagonists due to the increased use of the latter. There is no consensus on dosage protocols for its use. There is evidence that small fixed doses are effective. We report the result of the use of a simple three dose level protocol i.e. 2000 IU for CNS bleeds, 1500 IU for other bleeds and 1000 IU for non bleeders.MethodsData was prospectively collected over a 6 month period on all patients receiving PCC (Octaplex). These included clinical indication, dose given, INR test results, delay in treatment, and patients' demographics.ResultsThe protocol was followed in only 40%; 24% were given a larger dose and 35% a smaller dose than we recommended. Despite this the INR was corrected (≤1.5) in 56 (83.6%) out of the 67 patients studied. The average delay in getting INR results was 1 hour 14 minutes and delay between releasing the PCC from blood bank to infusion was 3 hours.ConclusionA simple three level low fixed dose protocol is cost effective in reversing the majority of patients' anticoagulation. Delay in initiating treatment for the reversal of VKA and adherence to protocols remained problematic.     

Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital

Introduction

Major blood loss can often be life-threatening and is most commonly encountered in the settings of surgery and trauma. Patients receiving anticoagulant therapy are also at increased risk of bleeding. We investigated the use of a prothrombin complex concentrate (PCC; Beriplex P/N, CSL Behring, Marburg, Germany) to treat severe bleeding in a variety of settings: cardiac surgery, warfarin therapy and other surgery.

Methods

Thirty consecutive patients who had received PCC were identified from blood transfusion records. For cardiac surgery and warfarin reversal, PCC was administered in accordance with hospital protocols. PCC was administered to cardiac and other surgical patients responding poorly to recognized blood products, whereas it was administered first-line to patients with life-threatening bleeds and requiring warfarin reversal, in accordance with British Committee for Standards in Haematology guidelines. We conducted a retrospective analysis of patient records in order to ascertain PCC dose, use of other blood products and response to PCC (clotting screen results before and after PCC administration, haemostasis achievement, and survival).

Results

Six patients (20%) were excluded because of inadequate documentation (n = 5) or acquired haemophilia (n = 1). Therefore, 24 patients were included in the analysis: coronary artery bypass graft (n = 5), mitral/aortic valve replacement (n = 2), other surgery (n = 9) and warfarin reversal (n = 8). Most patients (83.3%) received no more than 1500 IU of Beriplex P/N 500. Considerable reduction in administration of other blood products was seen during the 24 hours after PCC administration. Partial or complete haemostasis was achieved in 14 out of 18 cases (77.8%). In total, 12 out of 24 patients (50%) died during the study; two-thirds of the deaths were considered unrelated to bleeding. No thrombotic complications or adverse drug reactions were observed.

Conclusion

This study emphasizes the value of PCC in reversing the effects of oral anticoagulant therapy in bleeding patients. It also demonstrates the potential value of PCC in controlling bleeding in patients undergoing cardiac and other surgical procedures. The use of PCC in bleeding patients without hereditary or anticoagulation-related coagulopathy is novel, and further investigation is warranted. In the future, it may be possible to use PCC as a substitute for fresh frozen plasma in this setting; adequate documentation is crucial for all blood products.