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A new kid on the block: Outcomes with Kcentra 1 year after approval
Allison E Berndtson1, Wan-Ting Huang, Kevin Box
1From the Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery (A.E.B., L.K., L.N.G., A.M.S., R.C.), Department of Pharmacy (W.-T.H., K.B.), and Division of Neurosurgery (D.W.), University of California, San Diego, La Jolla, California.
Insights
Four-factor prothrombin complex concentrate (4F-PCC) effectively reverses warfarin-induced coagulopathy in trauma patients. This treatment provides sustained INR reduction for over 48 hours, with no reported thromboembolic complications.
Area of Science:
- Trauma care
- Hematology
- Pharmacology
Background:
- Aging populations increase trauma admissions with coagulopathy.
- Warfarin-induced coagulopathy requires effective reversal agents.
- Four-factor prothrombin complex concentrate (4F-PCC) offers an alternative to fresh frozen plasma for emergent INR reversal.
Purpose of the Study:
- To review the initial clinical experience with Kcentra (4F-PCC) in trauma patients.
- To evaluate the efficacy and safety of 4F-PCC for warfarin reversal in a US academic trauma center.
Main Methods:
- Retrospective review of trauma patients receiving 4F-PCC for warfarin reversal (July 2013-July 2014).
- Univariate analysis of demographics, injury data, coagulation parameters, 4F-PCC dosage, and outcomes.
- Included assessment of INR changes, vitamin K use, thromboelastography, and complications.
Main Results:
- Twenty-six patients received 4F-PCC; 34.6% for intracranial hemorrhage.
- Mean INR decreased from 5.7 to 1.5 post-administration and remained low (<1.5) for 48 hours.
- No in-hospital mortality or thromboembolic complications observed; 66.7% of ICH patients had radiographic progression but only 11.1% clinical progression.
Conclusions:
- 4F-PCC is effective in reversing elevated INRs in trauma patients with warfarin-induced coagulopathy.
- The reversal effect of 4F-PCC is sustained for over 48 hours.
- 4F-PCC demonstrates a favorable safety profile with no thromboembolic events in this cohort.
Background:
As the population ages, more trauma patients are admitted with coagulopathy. Fresh frozen plasma is effective in reversing coagulopathy caused by warfarin; however, it is not appropriate for all patients. Prothrombin complex concentrates (PCCs) are an alternative for patients who require emergent reversal, minimal-volume administration and who have a supratherapeutic international normalized ratio (INR). A four-factor PCC initially approved in Europe is now available in the United States. We sought to review our experience with Kcentra (4F-PCC) in the first year following Food and Drug Administration approval.
Methods:
All trauma patients admitted to an academic Level 1 trauma center between July 15, 2013, and July 15, 2014, who received 4F-PCC for reversal of warfarin-induced coagulopathy were reviewed. 4F-PCC was given as per protocol. Univariate analysis was performed to examine patient demographics, injury characteristics, coagulation studies, 4F-PCC dose, vitamin K use, transfusions, response to reversal, duration of reversal, complications, and mortality.
Results:
Twenty-six patients met study criteria. Of these patients, 34.6% were reversed because of intracranial hemorrhage. The mean INR decreased from 5.7 ± 6.1 (range, 1.6-30) to 1.5 ± 0.4 (range, 1.2-2.6) after 4F-PCC administration. One patient (3.8%) received concurrent fresh frozen plasma. For patients with an initial INR greater than 5.0, the mean INR decreased from 12.0 ± 8.2 to 1.6 ± 0.5. Forty-eight hours following 4F-PCC administration, mean INR for all patients remained 1.4 ± 0.4 (range, 1.0-2.6). Of the patients, 80.8% received vitamin K over this period. Fourteen patients had a pre-4F-PCC thromboelastogram; four were hypocoagulable. Two patients had repeat thromboelastograms after 4F-PCC was given, which demonstrated normal coagulation. Of the patients with intracranial hemorrhage, 66.7% showed radiographic progression of the initial insult on post-4F-PCC head computed tomography, while only 11.1% progressed clinically. In-hospital mortality was 0%. There were no thromboembolic complications.
Conclusion:
4F-PCC effectively reverses elevated INRs in trauma patients with warfarin-induced coagulopathy, with results lasting more than 48 hours after administration.
Level Of Evidence:
Therapeutic study, level V.
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