Fixed Versus Variable Dosing of Prothrombin Complex Concentrate in Vitamin K Antagonist-Related Intracranial Hemorrhage: A Retrospective Analysis

Rahat Amadkhan Abdoellakhan,Korné Jellema,Karina Meijer,Ishita Parveen Miah,Nakisa Khorsand

doi:10.1007/s12028-016-0248-8

Abstract

BackgroundMillions of patients receive vitamin K antagonist (VKA) therapy worldwide. Annually 0.2–1 % of all VKA users develops an intracranial hemorrhage (ICH). Prothrombin complex concentrate (PCC) is administered to restore the INR ≤ 1.5 in an attempt to limit hematoma growth. In order to facilitate PCC dosing, our hospital recently changed from a variable dose based on bodyweight, baseline- and target-INR, to a fixed 1000 IU fIX PCC dosing protocol for ICH.MethodsIn a before and after design, we compared successful achievement of an INR ≤ 1.5 with a fixed dosing strategy versus the variable dosing strategy of PCC in patients presenting with intracranial bleeding complications of VKA. Data of the two cohorts of patients were retrospectively collected from medical records.ResultsA median dosage of 1750 IU was given per patient in the variable dose group (n = 25) versus 1000 IU in the fixed dose group (n = 28). In the intention-to-treat analysis, 96 % achieved an INR ≤ 1.5 after an initial dose in the variable dose cohort compared to 68 % in the fixed dose cohort (p = 0.01). An additional dose was given in 2 (8 %) versus 9 (32 %) patients, respectively (p = 0.04). The median door-to-PCC-order time was 42 versus 32 min (p = 0.37) and the door-to-needle time was 81, respectively 60 min (p = 0.42).ConclusionThe fixed dose protocol necessitates additional PCC infusions more frequently to achieve a target INR ≤ 1.5. Door-to-order and door-to-needle time were shorter but, in this small cohort, not significantly so. The effect on clinical outcome remains unknown.

Highlights

Vitamin K antagonists (VKA) are used worldwide in primary and secondary prophylaxis of thromboembolic events
In order to facilitate Prothrombin complex concentrate (PCC) dosing, our hospital recently changed from a variable dose based on bodyweight, baseline- and target-international normalized ratio (INR), to a fixed 1000 IU fIX PCC dosing protocol for intracranial hemorrhage (ICH)
In a before and after design, we compared successful achievement of an INR B 1.5 with a fixed dosing strategy versus the variable dosing strategy of PCC in patients presenting with intracranial bleeding complications of vitamin K antagonist (VKA)

Summary

Introduction

Vitamin K antagonists (VKA) are used worldwide in primary and secondary prophylaxis of thromboembolic events. A major risk of VKA is the occurrence of intracranial hemorrhage (ICH). ICH is seen in 0.2–1.0 % of the anticoagulated population annually [1, 2]. 20 % of all ICH is associated with use of anticoagulants [1,2,3], with high mortality ranging from 40 to 60 % [4]. Rapid reversal of anticoagulant therapy in the management of ICH is crucial to reduce the risk of hematoma enlargement [5,6,7], which is in turn associated with poor outcome [8, 9]. 0.2–1 % of all VKA users develops an intracranial hemorrhage (ICH). In order to facilitate PCC dosing, our hospital recently changed from a variable dose based on bodyweight, baseline- and target-INR, to a fixed 1000 IU fIX PCC dosing protocol for ICH

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Results

Discussion

Conclusion