What is the next step for a patient with protein S and protein C deficiency who develops deep vein thrombosis (DVT) while on rivaroxaban (Xarelto), a direct oral anticoagulant (DOAC), 20mg daily?

From the Guidelines

For a patient with protein S and protein C deficiency who develops deep vein thrombosis (DVT) while on rivaroxaban 20mg daily, the next step should be to switch to therapeutic low molecular weight heparin (LMWH) such as enoxaparin 1 mg/kg twice daily, as this represents a treatment failure on the direct oral anticoagulant (DOAC) and requires escalation of anticoagulation therapy. This decision is based on the understanding that hereditary thrombophilias, such as protein S and protein C deficiency, represent a hypercoagulable state that may require more intensive anticoagulation than DOACs can provide 1.

The American Society of Hematology 2020 guidelines for management of venous thromboembolism discuss the use of direct oral anticoagulants (DOACs) for secondary prevention of recurrent VTE, including the option to use reduced doses of rivaroxaban and apixaban for this purpose 1. However, these guidelines also note that patients with a higher risk of recurrence, such as those with hereditary thrombophilias, were excluded from the studies evaluating the efficacy of lower doses of DOACs for secondary prevention.

Given the moderate certainty in the evidence of effects, and considering the patient's specific condition of having protein S and protein C deficiency, which puts them at a higher risk for recurrence, the use of a more intensive anticoagulation regimen is justified. After stabilization on LMWH for at least 5-7 days, transitioning to warfarin with a target INR of 2.5-3.5 may be considered for long-term management, as it allows for monitoring and dose adjustment based on the patient's response.

Key considerations in the management of this patient include:

• Close monitoring of anticoagulation therapy
• Evaluation by a hematologist or thrombosis specialist to assess for additional thrombophilic conditions or mechanical factors contributing to the treatment failure
• The potential need for more intensive anticoagulation due to the patient's underlying hypercoagulable state
• The importance of patient education on the risks and benefits of anticoagulation therapy and the need for regular follow-up.

From the Research

Patient Management

The patient has developed deep vein thrombosis (DVT) while on rivaroxaban, a direct oral anticoagulant (DOAC), 20mg daily, and has protein S and protein C deficiency.

• The next step would be to consider alternative anticoagulation therapy, as the current treatment has failed to prevent DVT.
• According to 2, apixaban could be an effective alternative for preventing recurrent thrombotic events in patients with inherited thrombophilia, such as protein S and protein C deficiency.
• However, it is essential to note that the patient is currently on rivaroxaban, and switching to another DOAC like apixaban may not be sufficient to prevent further thrombotic events.

Anticoagulation Therapy

• Warfarin has been the traditional anticoagulant used to manage patients with thrombotic disorders caused by protein C or S deficiency, as stated in 2.
• The guidelines for warfarin therapy, as outlined in 3, recommend keeping the international normalized ratio (INR) between 2.0 and 3.0, with a target INR of 2.5.
• However, the use of warfarin may not be the best option for this patient, as they have already developed DVT while on a DOAC.

Direct Oral Anticoagulants (DOACs)

• DOACs have transformed the landscape of antithrombotic therapy, offering a convenient and effective alternative to warfarin, as discussed in 4.
• However, there are scenarios where DOACs may be associated with inferior efficacy or worse safety compared to standard treatment, such as warfarin.
• The patient's protein S and protein C deficiency, combined with the failure of rivaroxaban to prevent DVT, may require a more tailored approach to anticoagulation therapy.

Transitioning Anticoagulants

• When transitioning from one anticoagulant to another, it is crucial to monitor the patient's INR and adjust the dosage accordingly, as highlighted in 5.
• The risk of bleeding and thrombosis must be carefully balanced when switching anticoagulants, particularly in patients with a history of thrombotic events.
• A thorough evaluation of the patient's condition and medical history is necessary to determine the best course of action for transitioning anticoagulants.

Anticoagulant Complications

• Hemorrhage is a significant concern with all anticoagulants, as noted in 6.
• Clinicians must have a sound understanding of anticoagulant pharmacology, dosing, and toxicity to minimize the risk of complications.
• Close monitoring of the patient's condition and regular follow-up appointments are essential to ensure the safe and effective use of anticoagulants.