Kcentra Prothrombin Complex Concentrate
Warfarin inhibits the vitamin K dependent pathway that is necessary to synthesize functional coagulation factors II, VII, IX and X and the antithrombotic Proteins C and S. Vitamin K is the only specific antidote to warfarin. Even though IV administration of vitamin K begins to noticeably correct the INR within two hours after administration, plasma is often ordered for emergency reversal of warfarin induced anticoagulation. As documented in the May 2012 issue of the Clinical Laboratory Letter, the higher the INR the greater the correction per unit of plasma. Plasma transfusion is largely ineffective in correcting an INR of 2.2 or below.
In April 2013, FDA approved the use of Kcentra for the urgent reversal of acquired coagulation deficiency due to warfarin treatment among adult patients with acute major bleeding. In December, FDA extended its approval to include reversal of warfarin therapy for patients who require urgent, invasive medical procedures.
Kcentra is the brand name for a four factor Prothrombin Complex Concentrate which contains vitamin K dependent coagulation factors II, VII, IX and X and the antithrombotic Proteins C and S. Kcentra is indicated for emergent reversal of acquired coagulation factor deficiency induced by warfarin in adult patients with acute major bleeding or who need urgent surgery or another invasive procedure. Repeat dosing with Kcentra is not supported by clinical data and is not recommended.
Kcentra reduces INR and increases vitamin K dependent coagulation factor levels more rapidly than plasma and with much smaller volume. For example, a typical dose of 2000 units of Kcentra is reconstituted to a volume of 80 mL and is given IV push. Four bags of plasma is approximately 1000 mL and must be administered much more slowly to prevent circulatory overload. Additional time is required to thaw frozen plasma and determine a patient’s blood type. KCentra is supplied as a lyophilized powder that is reconstituted with 20 to 40 mL of sterile water at the bedside. The actual potency of Factors II, VII, IX and X, Proteins C and S in each vial is printed on each carton, but for convenience it is supplied as 500 and 1000 unit vials based on Factor IX concentration. Saint Luke’s Health Systems’ order sets for intracerebral hemorrhagic stroke and subarachnoid hemorrhagic stroke include a simplified dosing regimen based on body weight in kilograms and INR level. Generally, doses range between 2000 units for a person with an INR less than 4.0 and body weight <80 kg to 3500 units for a person with an INR of 4.0 or greater and body weight of 80 kg or higher. These doses correspond to 20-40 units of Factor IX per kg of body weight. Forty two patients who were anticoagulated with warfarin and developed intracerebral hemorrhage, subarachnoid hemorrhage or subdural hemorrhage have been treated with Kcentra since November 2013. Pretreatment INR ranged from 1.8 to 19.0. In each case Kcentra corrected the INR to 1.3 or less almost immediately upon infusion.
Vitamin K should be administered concurrently to patients receiving Kcentra to maintain vitamin K-dependent clotting factor levels because coagulation Factor VII has a short in vivo half life of 7 hours and Factor IX has a large volume of distribution.
Kcentra is contraindicated in patients with:
- Known anaphylactic or severe systemic reactions to any components in Kcentra including heparin, coagulation factors and human albumin
- Disseminated intravascular coagulation
- Heparin-induced thrombocytopenia
The most common adverse reactions observed in subjects receiving Kcentra are headache, nausea/vomiting, arthralgia, and hypotension. Arterial and venous thromboembolic complications have been reported in patients receiving Kcentra. Its use may not be suitable in patients with a history of thromboembolic events in the prior 3 months.
Kcentra is much more expensive than plasma. The medical record must clearly document the medical need to urgently correct warfarin induced anticoagulation to increase the likelihood of reimbursement.
