Warfarin Reversal

Need for Urgent VKA Reversal

Up to 6.5% of patients on anticoagulant therapy will experience a major bleeding event affecting their soft tissue, gastrointestinal tract, or urinary tract. Approximately 1% of patients will develop a fatal bleed, often an intracranial hemorrhage (ICH).14

When a patient does have a major or life-threatening hemorrhage, urgent reversal of the VKA anticoagulant is necessary so that the patient can be assessed and receive other treatments as needed.10

Current Practices for VKA Reversal

Several options exist for reversal of VKA anticoagulation, including anticoagulant dose omission or withdrawal, administration of Vitamin K (oral or IV), fresh frozen plasma (FFP), and prothrombin complex concentrates (PCCs).14

In the US, plasma is more commonly used for this purpose than PCCs, but plasma has several disadvantages11:

  • The effects of plasma on VKA reversal are often incomplete
  • Plasma requires thawing and ABO typing prior to administration
  • Plasma carries a number of risks, including volume overload and virus transmission
  • Plasma is also associated with transfusion-related acute lung injury (TRALI), the most common cause of transfusion-related death.

These disadvantages can be minimized or avoided with the use of PCCs. PCCs do not require a cross-match, provide faster and more complete factor replacement, have enhanced safety because of virus inactivation, do not pose a risk of volume overload, and can be infused in 15 to 30 minutes.11, 12

In the few prospective studies comparing the efficacy of plasma to PCCs for anticoagulation reversal, PCCs were found to be effective in shortening the time to INR correction; none of these trials were powered to detect a resulting difference in hemostasis.15, 16, 17

Importance of 4F-PCC

Only 4F-PCCs contain all the necessary Vitamin K‐dependent coagulation factors as well as the two Vitamin K‐dependent anticoagulant proteins, Protein C and Protein S. 3F-PCCs do not contain Proteins C and S, and have only low levels of Factor VII.6, 7

However, until the approval of Kcentra in 2013, no 4F-PCC product was available in the United States. Emergency departments often used plasma, or other therapies, such as recombinant Factor VIIa (rFVIIa), Factor Eight Inhibitory Bypassing Activity (FEIBA), or 3F-PCC concomitantly 17 administered with Vitamin K. These treatments have limitations; for example, the short half-life of rFVIIa, the therapeutic delay of FFP, and the suboptimal reversal of 3F-PCC.14

While there is an inherent risk of thrombosis with reversal of anticoagulant therapy, activated factors indicated for hemophilia, such as rFVIIa, have been associated with increased risk when used off-label.18, 19

How Kcentra Can Help

Kcentra, a 4F-PCC containing coagulation Factors II, VII, IX, and X, as well as antithrombotic Proteins C and S, is designed to selectively restore the procoagulant and antithrombotic protein deficiencies induced by VKAs.

  • Kcentra rapidly replenishes deficient levels of circulating clotting factors and can be prepared and administered quickly and conveniently without the need for thawing or ABO-typing.
  • Because the coagulation factors in Kcentra are approximately 25 times more concentrated than those in plasma, a much lower infusion volume is required.1
  • A multi-step pathogen inactivation and removal process, including heat treatment and virus filtration, is used to reduce the risk of transmission of infectious agents.
  • Kcentra is indicated for the urgent reversal of Vitamin K antagonist (VKA, eg, warfarin) therapy in adult patients with acute major bleeding and is an effective alternative to plasma in this patient population.
Home Why Use Kcentra Warfarin Reversal
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Important Safety Information

Kcentra®, Prothrombin Complex Concentrate (Human), is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA—eg, warfarin) therapy in adult patients with acute major bleeding or the need for urgent surgery or other invasive procedure. Kcentra is for intravenous use only.

WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS

Patients being treated with Vitamin K antagonist therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the risk of thromboembolic events, especially in patients with history of such events. Resumption of anticoagulation therapy should be carefully considered once the risk of thromboembolic events outweighs the risk of acute bleeding. Both fatal and nonfatal arterial and venous thromboembolic complications have been reported in clinical trials and postmarketing surveillance. Monitor patients receiving Kcentra, and inform them of signs and symptoms of thromboembolic events. Kcentra was not studied in subjects who had a thromboembolic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within the prior 3 months. Kcentra might not be suitable for patients with thromboembolic events in the prior 3 months.

Kcentra is contraindicated in patients with known anaphylactic or severe systemic reactions to Kcentra or any of its components (including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin). Kcentra is also contraindicated in patients with disseminated intravascular coagulation. Because Kcentra contains heparin, it is contraindicated in patients with heparin-induced thrombocytopenia (HIT).

Hypersensitivity reactions to Kcentra may occur. If patient experiences severe allergic or anaphylactic type reactions, discontinue administration and institute appropriate treatment.

In clinical trials, the most frequent (≥2.8%) adverse reactions observed in subjects receiving Kcentra were headache, nausea/vomiting, hypotension, and anemia. The most serious adverse reactions were thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.

Kcentra is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.

The safety and efficacy of Kcentra in pediatric use have not been studied, and Kcentra should be used in women who are pregnant or nursing only if clearly needed.

Please see full prescribing information for Kcentra.

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CSL Behring
Kcentra is manufactured by CSL Behring GmbH and distributed by CSL Behring LLC.
Kcentra® and Beriplex® are registered trademarks of CSL Behring GmbH.
Biotherapies for Life® is a registered trademark of CSL Behring LLC
All other products mentioned are trademarks or registered trademarks of their respective companies.
© 2017 CSL Behring. The product information presented on this site is intended for US residents only.
KCT15-11-0051 12/2015