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Andexanet alfa
0%
0/35
Cryoprecipitate
Fresh frozen plasma
37%
13/35
Protamine sulfate
11%
4/35
Prothrombin complex concentrate
49%
17/35
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This patient’s presentation with an acute headache described as the “worst” headache of her life with signs of meningeal irritation (limited neck flexion) and the Cushing triad (hypertension, bradycardia, and respiratory depression) is indicative of a subarachnoid hemorrhage with resulting increased intracranial pressure. This patient is on anticoagulation (prolonged PT and elevated INR) and thus reversal of anticoagulation is indicated, which can be achieved with an infusion of prothrombin complex concentrate (PCC). In patients with an intracranial hemorrhage demonstrated on brain imaging (e.g., non-contrast head computed tomography), discontinuation of all anticoagulants and reversal of anticoagulation is indicated. Patients on warfarin, which inhibits activation of vitamin K and synthesis of vitamin K-dependent clotting factors (i.e., factors II, VII, IX, and X), should receive the 4-factor PCC which contains all of the vitamin K-dependent factors. Since the effects of PCC are transient, intravenous vitamin K should also be administered, although the benefits of vitamin K are not realized until 12-24 hours after administration. Additionally, patients with concomitant acetaminophen and warfarin use are at risk of a drug interaction that causes a supratherapeutic INR (above the therapeutic threshold of 2-3) and an increased risk of bleeding. The mechanism of this drug interaction is not fully understood, but likely includes inhibition of the vitamin K cycle by acetaminophen metabolites. Tomaselli et al. review the management of bleeding in patients on oral anticoagulants. The authors find that reversal of anticoagulation is generally indicated in patients with critical site bleeds, such as in the central nervous system, pericardial tamponade, hemothorax, and compartment syndrome. The authors recommend the use of 4-factor PCC for the reversal of warfarin. Incorrect Answers: Answer 1: Andexanet alfa is an inactive, decoy factor Xa molecule that binds factor Xa inhibitors (e.g., apixaban, edoxaban, or rivaroxaban) to reverse anticoagulation. Factor Xa inhibitors are commonly used in the treatment of atrial fibrillation, but this patient is not on a factor Xa inhibitor. Answer 2: Cryoprecipitate is created by thawing and centrifuging fresh frozen plasma and collecting the precipitate, which is rich in factor VIII. Consequently, cryoprecipitate can be used in factor VIII deficiency (i.e., hemophilia A) bleeding when factor concentrates are unavailable, though its role has largely been supplanted by factor concentrates. It would not be appropriate for the reversal of warfarin because it does not contain vitamin K-dependent clotting factors. Answer 3: Fresh frozen plasma contains all of the clotting factors, so it can be used as a second-line agent for the reversal of warfarin. However, PCC is the first-line agent. Answer 4: Protamine sulfate is a peptide that binds and inactivates unfractionated and low molecular weight heparin (LMWH), although it is less effective at reversing the effects of LMWH. It is not indicated for the reversal of warfarin. Bullet Summary: The first-line agent for the reversal of warfarin (e.g., in patients with intracranial hemorrhage who are on warfarin) is prothrombin complex concentrate.
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