The Effect of Anticoagulant Choice on Venous Thromboembolism Recurrence and Bleeding in Sickle Cell Disease

Patients with sickle cell disease (SCD) experience accelerated morbidity and mortality. Venous thromboembolism (VTE), a risk factor for early mortality in SCD, occurs in 11-12% of patients with SCD by the age of 40. While indefinite anticoagulation is indicated in the SCD population, there is limited understanding of comparative efficacy and hemorrhagic risk of individual anticoagulation agents in this population. We reviewed the use of anticoagulation for treatment of VTE in patients with SCD at our institution to begin to address these questions.

A retrospective chart review of all patients with SCD 18 years of age and older (currently alive or deceased) who received care at Boston Medical Center/Boston University between 2003 and 2018 was performed. VTE was defined as deep venous thrombosis (DVT) diagnosed by duplex ultrasound or pulmonary embolism (PE) diagnosed by either ventilation-perfusion scanning or computed tomography angiography. The primary efficacy outcome was the number of VTE events which occurred while the patient was receiving anticoagulation. The primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Hemostasis 2005 guidelines.

The medical records of 233 patients with SCD were reviewed; VTE was identified in 55 (23.6%) patients. Sixty-five percent were female. In these 55 patients, a total of 94 VTE events occurred. Fifteen (16.0%) were catheter-associated upper extremity DVTs. For the first event, initial outpatient treatment consisted of warfarin in 56%, low-molecular-weight heparin (LMWH) in 18.2%, rivaroxaban in 9.1%, apixaban in 5.5%, and fondaparinux in 3.6%. The median length of treatment was 7.3 (median: 6, IQR: 3-12) months. Recurrent VTEs occurred in 27 (49%) patients with a total of 39 recurrent events. Among the recurrent events, thirteen (33.0%) were treatment failures occurring during anticoagulation therapy (see Table 1): 7 of 37 (18.9%) on warfarin, 2 of 20 (10.0%) on LMWH, and 4 of 15 (26.7%) on rivaroxaban. Death from recurrent VTE occurred in two patients; one occurred while a patient was therapeutic on warfarin. Major bleeding occurred in two patients (3.6%); in both cases, this was intracranial hemorrhage while on warfarin.

In this retrospective study, there was a high rate of VTE recurrence despite anticoagulation in patients with SCD. Treatment failure was highest with warfarin and rivaroxaban, although adherence was difficult to assess. Risk of hemorrhage and death appears higher in those prescribed warfarin. These data affirm the need for long-term anticoagulation in most patients with SCD with a VTE and support the use of direct oral anticoagulants as a first-line agent.

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