A 78-year-old man is found unresponsive and is brought by ambulance to the emergency department. Upon arrival, the family says he has a complicated medical history and takes multiple medications but has no known drug allergies. Noncontrast CT scan of the head reveals intracranial hemorrhage. The patient is given a recombinant biologic agent that has antigen homology with factor Xa but no catalytic effect. The agent is most likely to antagonize the effects of which of the following drugs?
Anticoagulation reversal for life-threatening bleeding | ||
Drug | Mechanism of action | Reversal |
Warfarin |
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|
Dabigatran |
|
|
Factor Xa inhibitors |
|
|
Heparin |
|
|
mAb = monoclonal antibody; PCC = prothrombin complex concentrate (contains vitamin K–dependent clotting factors). | ||
This patient's intracranial hemorrhage was likely treated with andexanet alfa, a biologic agent that shares homology with factor Xa but has no proteolytic effect. It is administered to patients who have life-threatening bleeding while on a factor Xa inhibitor (eg, rivaroxaban, apixaban). The similarity of andexanet to factor Xa allows it to function as a decoy that binds to factor Xa inhibitors. This restores intravascular coagulation by increasing the availability of endogenous factor Xa, which converts prothrombin to thrombin and generates fibrin clots. Andexanet is reserved for life-threatening bleeding because it is associated with a significant risk of thrombosis.
(Choice B) Aspirin inhibits cyclooxygenase, which prevents platelet aggregation by blocking the generation of thromboxane A2. There is no reversal agent for aspirin widely available. Aspirin does not target factor Xa.
(Choice C) Dabigatran is a direct oral anticoagulant (DOAC) that inhibits circulating and clot-bound thrombin. It is reversed by idarucizumab, a monoclonal antibody fragment that binds to and inhibits dabigatran. Although dabigatran is a DOAC, it targets thrombin rather than factor Xa.
(Choice D) Ticagrelor blocks the P2Y12 adenosine diphosphate receptor on the surface of platelets, which prevents platelet aggregation. Its activity is not mediated by factor Xa.
(Choice E) Warfarin is a vitamin-K antagonist that prevents the generation of vitamin–K dependent clotting factors by blocking epoxide reductase in the liver. It is reversed by the administration of vitamin K.
Educational objective:
Andexanet alfa is a factor Xa decoy that has no proteolytic effect. It is administered to patients on factor Xa inhibitors (eg, rivaroxaban, apixaban) who have life-threatening bleeding in order to reverse the anticoagulation effect.