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
- 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.