How to manage excessive bleeding in a patient taking Rivaroxaban (Xarelto) (Direct Oral Anticoagulant)?

From the Guidelines

Managing excess bleeding in patients on rivaroxaban requires immediate medical attention, and the most effective approach is to administer the specific reversal agent andexanet alfa, as recommended by the 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants 1. For patients taking rivaroxaban, the dosage of andexanet alfa depends on the timing of the last dose, with a low dose (400 mg IV bolus followed by 4 mg/min infusion for up to 120 minutes) administered if the last dose was taken ≥8 hours prior, and a high dose (800 mg IV bolus followed by 8 mg/min infusion for up to 120 minutes) administered if the last dose was taken <8 hours prior or the timing is unknown 1. Some key points to consider in managing bleeding in patients on rivaroxaban include:

• Discontinuing rivaroxaban and assessing the severity of bleeding
• Administering activated charcoal if rivaroxaban was taken within 8 hours
• Using supportive measures such as fluid resuscitation, blood product transfusion, and identifying and treating the bleeding source
• Monitoring laboratory parameters, including complete blood count, coagulation parameters, and renal function tests
• Reassessing the need for anticoagulation and considering alternative anticoagulants or dosing adjustments once bleeding is controlled It is also important to note that andexanet alfa has been shown to be effective in reversing the anticoagulant effects of rivaroxaban, with a significant reduction in anti-FXa activity and excellent or good hemostasis achieved in the majority of patients 1. If andexanet alfa is unavailable, prothrombin complex concentrate (PCC) at 25-50 units/kg can be used as an alternative, although the evidence for its effectiveness is limited 1. Overall, the management of bleeding in patients on rivaroxaban requires a comprehensive approach that takes into account the severity of bleeding, the timing of the last dose, and the availability of reversal agents.

From the FDA Drug Label

Overdose of XARELTO may lead to hemorrhage. Discontinue XARELTO and initiate appropriate therapy if bleeding complications associated with overdosage occur. The use of activated charcoal to reduce absorption in case of XARELTO overdose may be considered. Due to the high plasma protein binding, rivaroxaban is not dialyzable. Partial reversal of laboratory anticoagulation parameters may be achieved with use of plasma products. An agent to reverse the anti-factor Xa activity of rivaroxaban is available.

To manage excessive bleeding in a patient taking Rivaroxaban (Xarelto), the following steps should be taken:

• Discontinue Rivaroxaban
• Consider using activated charcoal to reduce absorption
• Plasma products may be used to partially reverse laboratory anticoagulation parameters
• An agent to reverse the anti-factor Xa activity of rivaroxaban is available and should be considered for use 2 Key considerations include:
• Rivaroxaban is not dialyzable due to high plasma protein binding

From the Research

Management of Excessive Bleeding in Patients Taking Rivaroxaban

• Discontinuation of rivaroxaban 20 to 30 hours before an elective surgery is sufficient to normalize the associated bleeding risk, as long as the renal and liver function is normal 3
• In the event of an emergency operation, effective rivaroxaban concentrations might be present, and prophylactic dose of factor concentrates is not recommended 3
• For minor bleeding, a temporary discontinuation of rivaroxaban is recommended, whereas for clinically relevant major or severe bleeding events, a mechanical compression or a limited surgical i.e. interventional treatment is required 3
• Supportive measures such as the administration of blood products or tranexamic acid might be beneficial 3
• In the event of life-threatening bleeding, haemodynamic supportive measures and a comprehensive haemostasis management, as well as the application of PCC, are required 3

Reversal Agents for Rivaroxaban

• Andexanet alfa, a recombinant protein analogue of factor Xa, has been approved by the US Food and Drug Administration for patients treated with rivaroxaban or apixaban who require reversal of anticoagulation owing to life-threatening or uncontrolled bleeding 4, 5
• Prothrombin complex concentrates (PCCs) may be used as a reversal agent for rivaroxaban, although their use is not approved by the US Food and Drug Administration 6, 7, 5
• Tranexamic acid (TXA) has been investigated as a potential reversal agent for rivaroxaban, but its efficacy is unknown 7

Treatment Strategies for Bleeding Associated with Rivaroxaban

• Support and observation are likely to be effective for the majority of patients with minor bleeding due to the short half-life of rivaroxaban 6
• In severe life-threatening hemorrhage, clotting-factor substitutes, such as PCCs, may be appropriate in certain situations 6
• The administration of a specific agent to reverse factor Xa inhibition, such as andexanet alfa, may be clinically indicated in certain settings, such as when rivaroxaban was given less than 12 hours earlier or in the event of a catastrophic bleed 4