759: Fixed-Dose Prothrombin Complex Concentrate in Vitamin K Antagonist-Related Intracerebral Hemorrhage

IntroductionThere is currently little evidence for the optimal dosing strategy of four-factor prothrombin complex concentrates (PCC) in vitamin K antagonist (VKA)-related bleeds. The generally accepted dosing strategy is the use of a variable dose calculated using patient-specific characteristics as per manufacturer’s instruction. However, evidence exists that the use of a fixed low dose of 1000 international units of factor IX (IU fIX) might also suffice. Recent studies indicate that in terms of haemostatic effectiveness, the fixed dosing strategy might be even superior to the variable dosing strategy. The PROPER3 (PROthrombin complex concentrate: Prospective Evaluation and Rationalisation, number 3) study aims to confirm the non-inferiority, and explore superiority, in haemostatic effectiveness of the fixed PCC dosing strategy compared with the variable dosing strategy in VKA-related extracranial bleeding emergencies.Methods and analysisThe study is designed as a randomised controlled multicentre non-inferiority trial. Eligibility criteria are an indication for PCC due to VKA-related extracranial bleeding in subjects 18 years of age or older. The control group will receive a variable dose, determined by patient-specific bodyweight and international normalised ratio. The intervention group is dosed a fixed 1000 IU fIX PCC. Primary outcome is the haemostatic effectiveness of both treatments, as defined by the 2016 International Society on Thrombosis and Haemostasis (ISTH) criteria. The sample size is set at 155 patients per treatment arm, requiring 310 patients in total. Non-inferiority on the proportion (risk) difference of the primary outcome will be evaluated using the asymptotic Wald test for non-inferiority. The non-inferiority margin is set at 6%. The primary analysis will be based on the per-protocol population.Ethics and disseminationStudy results will be published in an international journal, communicated to discipline-specific associations and presented at (inter)national meetings and congresses.Trial registration numberEUCTR2014-000392-33; Pre-results.

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Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage

Annals of Neurology ◽

10.1002/ana.25134 ◽

2018 ◽

Vol 83 (1) ◽

pp. 186-196 ◽

Cited By ~ 66

Author(s):

Stefan T. Gerner ◽

Joji B. Kuramatsu ◽

Jochen A. Sembill ◽

Maximilian I. Sprügel ◽

Matthias Endres ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Vitamin K ◽

Oral Anticoagulant ◽

Prothrombin Complex Concentrate ◽

Vitamin K Antagonist ◽

Hematoma Enlargement

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Abstract WP304: Prothrombin Complex Concentrate Rapidly Reverses Coagulopathy but does not Alter Mortality in Warfarin Intracerebral Hemorrhage

Stroke ◽

10.1161/str.44.suppl_1.awp304 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Xuemei Cai ◽

Susannah Orzell ◽

Sarah Suh ◽

Linda Bresette ◽

Farzaneh Sorond ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Vitamin K ◽

Conventional Therapy ◽

Prothrombin Complex Concentrate ◽

International Normalized Ratio ◽

Fresh Frozen Plasma ◽

Thromboembolic Complication ◽

Complication Rates ◽

Significant Difference ◽

Fresh Frozen

INTRODUCTION: Warfarin-associated intracerebral hemorrhage (wICH) remains the most lethal form of iatrogenic stroke. Conventional therapy with fresh frozen plasma (FFP) and intravenous vitamin K takes up to 30 hrs to normalize the international normalized ratio (INR). Prothrombin complex concentrate (PCC) does not require cross-match and is fast acting. We hypothesized that PCC can rapidly reverse coagulopathy and reduce mortality in wICH. Methods: We identified 130 consecutive adult wICH patients over five years from a prospectively collected database. 33 patients were excluded for death or withdrawal of care within 48 hours of admission and 8 patients were excluded for antecedent head trauma, leaving 89 patients for analysis. Forty patients received FFP and vitamin K (conventional therapy) and 49 received PCC in addition to conventional therapy. We compared 6-month mortality, time to INR normalization, quantity of FFP transfused, and thromboembolic complication rates between the two groups. We used logistic regression to adjust for important confounders. Results: PCC-treated and conventional therapy patients had similar distributions of age, sex, co-morbidities, ICH location, initial blood pressure and INR. PCC-treated patients had a higher incidence of intraventicular hemorrhage (IVH) (67% vs 33%). PCC-treated patients required less FFP (mean 6.8 units vs 3.3 units, p<0.0001) and had faster time to INR normalization (mean 3.8 hrs vs 9.8 hrs, p<0.0001). Incidence of ICH expansion was low in both groups. There was no difference in the incidence of deep venous thrombosis and pulmonary embolism (p=0.236) or troponin elevation (p=0.573). There was no significant difference in 6-month mortality (p=0.437) after adjusting for age, ICH location, ICH volume, and presence of IVH. Conclusions: PCC use in wICH was associated with shorter time to INR normalization and reduced FFP transfusion but was not associated with 6-month mortality in this cohort. There was no difference in thromboembolic complication rates between PCC-treated and FFP and vitamin K treated patients. Prospective trials of PCC are necessary to determine if its use can improve morbidity and mortality in wICH and to identify potential subgroups of wICH patients who may benefit from PCC.

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How does prothrombin complex concentrate compare with fresh frozen plasma for the reversal of vitamin K antagonist treatment?

Cochrane Clinical Answers ◽

10.1002/cca.1155 ◽

2016 ◽

Author(s):

Anna Wrzosek

Keyword(s):

Vitamin K ◽

Prothrombin Complex Concentrate ◽

Fresh Frozen Plasma ◽

Vitamin K Antagonist ◽

Fresh Frozen ◽

Frozen Plasma

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ORAL ANTICOAGULANTS IN THE TREATMENT OF VENOUS THROMBOEMBOLIC COMPLICATIONS: FOCUS ON APIXABAN

Medical Council ◽

10.21518/2079-701x-2017-7-56-62 ◽

2017 ◽

pp. 56-62 ◽

Cited By ~ 1

Author(s):

M. Yu. Gilyarov ◽

E. V. Konstantinova

Keyword(s):

Vitamin K ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Vitamin K Antagonist ◽

Fixed Dose ◽

Vein Thrombosis ◽

Venous Thromboembolic ◽

Deep Vein

Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a common condition associated with a significant clinical and economic burden. Anticoagulant therapy is the mainstay of treatment for VTE. Current guidelines recommend the use of either low molecular weight heparins or fondaparinux overlapping with and followed by a vitamin K antagonist for the initial treatment of VTE, with the vitamin K antagonist continued when long-term anticoagulation is required. These traditional anticoagulants have practical limitations that have led to the development of direct oral anticoagulants that directly target either Factor Xa or thrombin and are administered at a fixed dose without the need for routine coagulation monitoring. The paper reviews results of the trials of apixaban application for treatment and/or long-term secondary prevention of VTE. The paper analyses effectiveness and safety of apixaban in different groups of patients, as well as features of apixaban application in every day practice.

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