Rivaroxaban for inherited thrombophilia: A case study

A 27-year-old white female with a past medical history of IV drug abuse and hepatitis C presented to the emergency department with a four-day history of severe chest pain, shortness of breath, and vomiting. She had been admitted earlier in the month with endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) and signed herself out against medical advice without completing antibiotic therapy.

Blood cultures confirmed MRSA and she was again diagnosed with MRSA endocarditis. Pharmacy performed medication reconciliation and all home medications were resumed, including rivaroxaban (Xarelto; Janssen). Pharmacy did not see an indication for rivaroxaban and further investigation was performed.

Upon investigation, pharmacy discovered that the patient had a diagnosis of Protein S deficiency. Protein S deficiency is a type of inherited thrombophilia associated with increased risk of venous thromboembolism (VTE). Protein S is an endogenous vitamin K-dependent anticoagulant that acts as a nonenzymatic cofactor for activated protein C (aPC).

The primary effect of aPC is to inactivate coagulation factors Va and VIIIa, which help activate factors II and X, respectively. Inactivating factors II and X halts the clotting cascade; however, a deficiency in Protein S would diminish this effect and cause a procoagulant state.

Is rivaroxaban the best therapeutic option for this patient?

See also: Cardiologists are prescribing rivaroxaban more than warfarin

Possible options

In light of this patient’s history of noncompliance with her antibiotic and anticoagulation/antithrombotic therapy, warfarin would not be a good option, since its dosing is reliant on medication compliance, the need for bridging anticoagulation, and laboratory INR monitoring.

Newer agents such as oral direct thrombin and factor Xa inhibitors are gaining in popularity for the treatment of VTE and VTE prophylaxis in patients without inherited thrombophilia. However, no data state that they are safer or more effective than warfarin treatment in these patients.

Because the patient is of child-bearing age, warfarin would not be a good option for her. Dabigatran etexilate (Pradaxa; Boehringer Ingelheim), a direct thrombin inhibitor, would be a safe and effective option; however, it requires twice-a-day dosing for VTE prophylaxis and therefore would present a compliance issue for this patient.

Apixaban (Eliquis; Bristol-Myers Squibb), an oral factor Xa inhibitor, has a pregnancy category B status, but it also requires twice-daily dosing and would pose a compliance issue for the patient.

See also: Rivaroxaban has more indications

Best option for patient

The pharmacist concluded that rivaroxaban would be the best therapeutic option for the patient because of its once-daily dosing regimen for VTE prophylaxis, lack of monitoring requirements, and more desirable pregnancy category.

The patient had no medical insurance and was able to obtain her medication at no cost through a program offered by the manufacturer.

Owing to a lack of controlled trials for the use of newer agent anticoagulants in inherited thrombophilia, studies are needed to assess safety and efficacy.

Sources

1. Witt DM, Nutescu EA, Haines ST. “Venous thromboembolism.” In: DiPiro JT, Talbert RL, Yee GC, et al, editors. Pharmacotherapy: A pathophysiologic approach. 8th ed. New York, NY: McGraw-Hill Medical; 2011: 311–352.

2. Falck-Ytter Y, Francis CW, Johnson NA, et al. “Prevention of VTE in orthopedic surgery patients,” American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. 9th ed., 2012;141(2):e278S–e325S.   

Jaclyn Chessher and Jerry Barbee and are clinical pharmacists and preceptors for students and residents at a community hospital in Pensacola, Fla. Ambree Gober and Matt Savoie are completing their advanced pharmacy practice training.