Prospective Evaluation of a Fixed-Dose 4-Factor Prothrombin Complex Concentrate Protocol for Urgent Vitamin K Antagonist Reversal

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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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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