Protein S deficiency is a type of inherited thrombophilia associated with increased risk of venous thromboembolism.
A 27-year-old white woman with a past medical history of intravenous drug abuse and hepatitis C presented to the emergency department with a 4-day history of severe chest pain, shortness of breath, and vomiting. She had been admitted earlier in the month with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis and signed herself out against medical advice without completing antibiotic therapy. Blood cultures confirmed MRSA and she was again diagnosed with MRSA endocarditis. Pharmacy staff performed medication reconciliation and all home medications were resumed, including Xarelto (rivaroxaban). Pharmacy staff did not see an indication for Xarelto and investigated further.
Upon investigation, pharmacy staff discovered 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).1 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.1
Is Xarelto the best therapeutic option for this patient? Given the patient’s history of noncompliance with her antibiotic and anticoagulation/ antithrombotic therapy, warfarin would not be a good option due the importance of compliance with the medication, the need for bridging anticoagulation, and the required periodic international normalized ratio monitoring.2 Xarelto is a factor Xa inhibitor, and newer agents such as oral direct thrombin and factor Xa inhibitors are gaining in popularity for the treatment of VTE and for VTE prophylaxis in patients without inherited thrombophilia. There are no data that prove the newer agents are any less safe or effective than warfarin treatment in these patients.
Since the patient is of childbearing age and warfarin is pregnancy category X, warfarin would not be a good option. Pradaxa (dabigatran), a direct thrombin inhibitor, would be a safe and effective option; however, it requires twicedaily dosing for VTE prophylaxis, which would present a compliance issue for this patient. Eliquis (apixaban), a factor Xa inhibitor, is a pregnancy category B drug, but it also requires twice-daily dosing and would pose a compliance issue for this patient.1-3 The pharmacist concluded that Xarelto, which is pregnancy category C, was the best therapeutic option for this patient due to its once-daily dosing for VTE prophylaxis, lack of monitoring requirements, and more desirable pregnancy category.
Jerry Barbee, PharmD, BCPS, is a clinical pharmacist at HCA West Florida Hospital. Jaclyn Chessher, PharmD, is a clinical pharmacist at HCA West Florida Hospital. Ambree Gober is a 2015 PharmD candidate at Auburn University’s Harrison School of Pharmacy. Matt Savoie is a 2015 PharmD candidate at Auburn University’s Harrison School of Pharmacy.