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.     

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.     

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).

Use and effectiveness of prothrombin complex concentrates vs fresh frozen plasma in gastrointestinal hemorrhage due to warfarin usage in the ED

Objectives

High International Normalized Ratio (INR) level resulting from warfarin use increases the risk of gastrointestinal hemorrhages. We aimed to compare the efficacy of prothrombin complex concentrates (PCC) and fresh frozen plasma (FFP) at lowering the INR level, decreasing active hemorrhages visible by endoscopy, and shortening the length of stay at the emergency department (ED).

Method

This study is a prospective cohort study of consecutive patents with gastrointestinal hemorrhages that received either PCC or FFP. With strict exclusion criteria, only patients over 18 years of age with a high INR level (> 2.1) due to warfarin usage were included.

Results

A total of 40 patients (18 female) were included in the study, 20 each in the PCC and FFP groups. For the PCC group, the mean INR levels at the second and sixth hours were lower than those for the FFP group (second hour INR: 1.53 vs 4.50, P < .01, sixth hour INR: 1.52 vs 2.41, P < .01). Seven patients experienced active bleeding (Forrest 1) in the FFP group, whereas no patient experienced active bleeding in the PCC group based on the Forrest classification (35% vs 0%, P < .01), and only 3 patients in the FFP group underwent invasive/surgical treatment (15% vs 0%, P < .01). The ED length of stay was lower for the PCC group (1.62 days vs 3.46 days, P < .01).

Conclusion

For patients experiencing a gastrointestinal hemorrhage, INR levels were reversed more quickly, there was less active bleeding on endoscopy, and the ED length of stay was lower in the PCC group than in the FFP group.     

Factor Eight Inhibitor Bypassing Agent (FEIBA) for Reversal of Target-Specific Oral Anticoagulants in Life-Threatening Intracranial Bleeding

Introduction

As increasing number of patients present to emergency departments with life threatening hemorrhages, particularly intracranial hemorrhage on anticoagulation physicians must be cognizant of the limitations of the available reversal options. Based upon the available literature, our institution formulated a reversal algorithm for patients with life-threatening bleeding on factor Xa inhibitors by administering factor eight inhibitor bypassing agent (FEIBA) 20 units/kg.

Protocolized use of Factor Eight Inhibitor Bypassing Activity (FEIBA) for the reversal of warfarin induced coagulopathy

IntroductionCoagulopathy due to warfarin in patients with major bleeding was traditionally reversed with fresh frozen plasma and intravenous (IV) vitamin K, but prothrombin complex concentrates (PCC) are increasingly used in the treatment of these patients. Factor Eight Inhibitor Bypassing Activity (FEIBA) is an activated four-factor PCC most commonly used in patients with hemophilia. We aimed to evaluate the efficacy and safety of FEIBA and IV vitamin K for the reversal of warfarin-associated coagulopathy in patients with major bleeding, by measuring the percentage of patients who achieved target INR ≤ 1.5 and the incidence of thrombotic adverse events (TAE).MethodsIn this prospective observational study, we enrolled patients presenting to the Emergency Department (ED) with warfarin associated coagulopathy (INR > 1.5) and major bleeding. Patients received FEIBA using an INR based dosing strategy and IV vitamin K.ResultsIn 43 patients, median initial INR was 4.0 (2.7, 7.3 interquartile range (IQR)). Median time to result the second INR was 45 min (38, 55 IQR) and the median INR was 1.4 (1.3, 1.6 IQR). Out of the 43 patients, 93% achieved the target INR of ≤1.5. In-hospital mortality was 40% (17 patients). There were 11 TAEs in 6 patients (14%); 4 events in 2 patients (5%) were attributed to FEIBA.ConclusionA protocolized use of FEIBA and IV vitamin K resulted in the efficacious reversal of warfarin-induced coagulopathy in patients with major bleeding. TAEs occurred in 14% of patients and were attributed to FEIBA in 5% of patients.     

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.     

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.     

Air Ambulance Delivery and Administration of Four‐factor Prothrombin Complex Concentrate Is Feasible and Decreases Time to Anticoagulation Reversal

Objectives

The objective was to evaluate the feasibility, safety, and preliminary efficacy of four‐factor prothrombin complex concentrate (4‐factor PCC) administration by an air ambulance service prior to or during transfer of patients with warfarin‐associated major hemorrhage to a tertiary care center for definitive management (interventional arm) compared to patients receiving 4‐factor PCC following transfer by air ambulance or ground without 4‐factor PCC treatment (conventional arm).

Methods

This was a retrospective chart review of patients presenting to a large academic medical center. All patients presenting to the emergency department (ED) treated with 4‐factor PCC from April 1, 2014, through June 30, 2016, were identified. For this study, only transfer patients with an International Normalized Ratio (INR) > 1.5 actively treated with warfarin were included. The primary outcome was the proportion of patients with an INR ≤ 1.5 upon tertiary care hospital arrival, and the secondary efficacy outcome was difference in time to achievement of INR ≤ 1.5. Additional safety and efficacy objectives included difference in thromboembolic complications, length of stay, intensive care unit length of stay, and inpatient mortality between groups.

Results

Of the 72 included patients, a higher proportion of patients in the interventional group had an INR ≤ 1.5 on ED arrival (proportion difference = 0.82, 95% confidence interval = 0.64–0.92, p < 0.0001) and significantly reduced time to observed INR ≤ 1.5 (181 minutes vs. 541 minutes, p = 0.001). No differences were observed in thromboembolic complications or patient‐centered outcomes with the exception of mortality, which was significantly higher in patients in the interventional group. This group was also observed to have lower Glasgow Coma Scale score and higher intubation rates prior to transfer and treatment.

Conclusions

Dispatch of an air ambulance carrying 4‐factor PCC with administration prior to transfer is feasible and leads to more rapid improvement in INR among patients with warfarin‐associated major hemorrhage.

     

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.     

TEG® and RapidTEG® are unreliable for detecting warfarin-coagulopathy: a prospective cohort study

Background

Thromboelastography^® (TEG) utilizes kaolin, an intrinsic pathway activator, to assess clotting function. Recent published studies suggest that TEG results are commonly normal in patients receiving warfarin, despite an increased International Normalized Ratio (INR). Because RapidTEG? includes tissue factor, an extrinsic pathway activator, as well as kaolin, we hypothesized that RapidTEG would be more sensitive in detecting a warfarin-effect.

Methods

Included in this prospective study were 22 consecutive patients undergoing elective cardioversion and receiving warfarin. Prior to cardioversion, blood was collected to assess INR, Prothrombin Time, TEG, and RapidTEG.

Results

INR Results: 2.8?±?0.5 (1.6 to 4.2). Prothrombin Time Results: 19.1?±?2.2 (13.9. to 24.3). TEG Results (Reference Range): R-Time: 8.3?±?2.7 (2–8); K-Time: 2.1?±?1.4 (1–3); Angle: 62.5?±?10.3 (55–78); MA: 63.2?±?10.3 (51–69); G: 9.4?±?3.5 (4.6-10.9); R-Time within normal range: 10 (45.5%) with INR 2.9?±?0.3; Correlation coefficients for INR and each of the 5 TEG variables were insignificant (P?>?0.05). RapidTEG Results (Reference Range): ACT: 132?±?58 (86–118); K-Time: 1.2?±?0.5 (1–2); Angle: 75.4?±?5.2 (64–80); MA: 63.4?±?5.1 (52–71); G: 8.9?±?2.0 (5.0-11.6); ACT within normal range: 9 (40.9%) with INR 2.7?±?0.5; Correlation coefficients for INR and each of the 5 RapidTEG variables were insignificant (P?>?0.05).

Conclusions

TEG, using kaolin activation, and RapidTEG, with kaolin and tissue factor activation, were normal in a substantial percent of warfarin patients, despite an increased INR. The false-negative rate for detecting warfarin coagulopathy with either test is unacceptable. The lack of correlation between INR and all TEG and RapidTEG components further indicates that these methodologies are insensitive to warfarin effects. Findings suggest that intrinsic pathway activation may mitigate detection of an extrinsic pathway coagulopathy.     

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.     

Retrospective evaluation of a method to predict fresh-frozen plasma dosage in anticoagulated patients

In the United States, fresh-frozen plasma (FFP) is commonly used for urgent reversal of warfarin; however, dosage recommendations are difficult to find. If validated, a proposed method that uses a nonlinear relationship between international normalized ratio (INR) and clotting factor activity (CFa) would be useful. This study retrospectively evaluated a proposed equation with adult medical inpatients who received FFP for warfarin reversal. For each patient the equation was used to predict the dose of FFP required to achieve the observed change in INR, which was then compared to the actual dose. The equation was considered successful if the predicted dose was within +/-20% of the actual dose. Subgroup analyses included subjects who received concomitant vitamin K; subjects with supratherapeutic INRs (>3); and subjects with significantly elevated INRs (>5). Of the 209 patients screened, 91 met criteria for inclusion in the study. Use of the equation to calculate the predicted dose of FFP was successful in 11 patients (12.1%) with use of actual body weight for prediction and in 23 patients (25.3%) with use of ideal body weight (P = 0.02). The equation performed similarly in all subgroups analyzed. The mean predicted FFP dose was significantly greater than the actual dose in all patients when actual body weight was used (925.2 mL vs. 620.6 mL; P < 0.001). Least-squares regression modeling of repeat INR (converted to CFa) produced a model that accounted for 57% of the variance in repeat INR. The value predicted from the model was closer to the actual CFa than was the value predicted from the published equation in every comparison, but it was statistically different only when actual body weight was used. This study revealed that a published equation for calculation of FFP dose to reverse oral anticoagulation resulted in doses that were significantly higher than the actual dose. Use of ideal body weight improved accuracy but was still not successful for the majority of patients. Until trials are able to prospectively demonstrate the accuracy of a dose-prediction model for FFP, dosing will remain largely empiric.     

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.     

Optimizing warfarin reversal – an ex vivo study

Summary.  Background: Warfarin reversal is a common clinical situation. This is commonly performed using vitamin K and, depending on the urgency, fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), or activated factor VII. Even though PCCs are widely used, the ideal dosing regimen is far from established. Objectives: To verify differences in warfarin reversal patterns using FFP, recombinant FVIIa (rFVIIa), and PCC; and to test the hypothesis that supratherapeutic International Normalized Ratios (INRs) might not correlate with thrombin generation (TG) and identify the ideal concentrations of PCC required to reverse various INR thresholds. Methods: We studied the effects of FFP, rFVIIa and Beriplex  P/N on the INR and TG, using the calibrated automated thrombography assay in ex vivo warfarinized plasma. Plasmas with different INRs were spiked with different concentrations of Beriplex  P/N. Results: Beriplex  P/N was the only agent that completely normalized TG and the INR. The endogenous thrombin potential (ETP) and the peak thrombin showed a significant negative correlation with all INRs. The ETP and velocity of TG reached a plateau at an INR of ∼ 4.0. A concentration equivalent to a dose of 30 IU kg⁻¹ Beriplex  P/N normalized the ETP, the INR, FII, FVII, FIX and FX of samples with INRs  ≥ 4.0. Higher doses resulted in hypercoagulable TG patterns. A concentration equivalent to a dose of 20 IU kg⁻¹ was sufficient to reverse warfarin at an INR range of 2.0–3.9, as judged by the same tests. Conclusions: Warfarin reversal algorithms could be simplified with the adoption of this strategy utilizing two doses of PCC, depending on the INR of the patient. This would also lead to cost reductions and, possibly, a reduction in thrombotic risk.     

Comparison of drug administration logistics between prothrombin complex concentrates and plasma in the emergency department

Background

Prothrombin complex concentrate (PCC) is used as an alternative to fresh frozen plasma (FFP) for emergency bleeding. The primary objective of this study was to compare the time from order to start of administration between 3-factor PCC (PCC3), 4-factor (PCC4), and FFP in the emergency department (ED). The secondary objective was to evaluate the effect of an ED pharmacist on time to administration of PCCs.

The Clinical Use of Prothrombin Complex Concentrate

Background

Prothrombin complex concentrate (PCC) is an inactivated concentrate of factors II, IX, and X, with variable amounts of factor VII. Guidelines recommend the use of PCC in the setting of life-threatening bleeds, but little is known on the most effective dosing strategies and how the presenting international normalized ratio affects response to therapy.

Objectives

This review aims to highlight available data on monitoring techniques, address shortcomings of currently available data, the reversal of life-threatening and critical bleeds with PCC, and how this product compares to other therapeutic options used in critically ill patients.

Discussion

PCC has been identified as a potential therapy for critically bleeding patients, but patient-specific factors, product availability, and current data should weigh the decision to use it. Most data exist regarding patients experiencing vitamin K antagonist-induced bleeding, more specifically, those with intracranial hemorrhage. PCC has also been studied in trauma-induced hemorrhage; however, it remains controversial, as its potential benefits have the abilities to become flaws in this setting.

Conclusion

Health care professionals must remain aware of the differences in products and interpret how three- versus four-factor products may affect patients, and interpret literature accordingly. The clinician must be cognizant of how to progress when treating a bleeding patient, propose a supported dosing scheme, and address the need for appropriate factor VII supplementation. At this point, PCC cannot be recommended for first-line therapy in patients with traumatic hemorrhage, and should be reserved for refractory bleeding until more data are available.     

Extended International Normalized Ratio testing intervals for warfarin‐treated patients

Essentials

• Warfarin typically requires International Normalized Ratio (INR) testing at least every 4 weeks.
• We implemented extended INR testing for stable warfarin patients in six anticoagulation clinics.
• Use of extended INR testing increased from 41.8% to 69.3% over the 3 year study.
• Use of extended INR testing appeared safe and effective.

Summary

Background

A previous single‐center randomized trial suggested that patients with stable International Normalized Ratio (INR) values could safely receive INR testing as infrequently as every 12 weeks.

Objective

To test the success of implementation of an extended INR testing interval for stable warfarin patients in a practice‐based, multicenter collaborative of anticoagulation clinics.

Methods

At six anticoagulation clinics, patients were identified as being eligible for extended INR testing on the basis of prior INR value stability and minimal warfarin dose changes between 2014 and 2016. We assessed the frequency with which anticoagulation clinic providers recommended an extended INR testing interval (> 5 weeks) to eligible patients. We also explored safety outcomes for eligible patients, including next INR values, bleeding events, and emergency department visits.

Results

At least one eligible period for extended INR testing was identified in 890 of 3362 (26.5%) warfarin‐treated patients. Overall, the use of extended INR testing in eligible patients increased from 41.8% in the first quarter of 2014 to 69.3% in the fourth quarter of 2016. The number of subsequent out‐of‐range next INR values were similar between eligible patients who did and did not have an extended INR testing interval (27.3% versus 28.4%, respectively). The numbers of major bleeding events were not different between the two groups, but rates of clinically relevant non‐major bleeding (0.02 per 100 patient‐years versus 0.09 per 100 patient‐years) and emergency department visits (0.07 per 100 patient‐years versus 0.19 per 100 patient‐years) were lower for eligible patients with extended INR testing intervals than for those with non‐extended INR testing intervals.

Conclusions

Extended INR testing for stable warfarin patients can be successfully and safely implemented in diverse, practice‐based anticoagulation clinic settings.

     

Bilateral Phlegmasia Cerulea Dolens After Warfarin Reversal for Acute Rectal Bleeding: A Case Report

Background

Deep vein thrombosis (DVT) is a common disease that is diagnosed in approximately 1 in 1000 adults annually. Extensive DVT can lead to life- or limb-threatening diagnoses such as phlegmasia cerulea dolens (PCD), phlegmasia alba dolens, and venous gangrene. PCD, also known as massive iliofemoral venous thrombosis, is rare, and a severe complication of DVT.