Case Presentation: A 46-year-old female presented with a 2-day history of shortness of breath, pleuritic chest pain and lower extremity swelling while taking low-molecular weight heparin (LMWH). One month prior she was diagnosed with a left lower extremity DVT after a hysterectomy. She was treated with LMWH with a planned transition to rivaroxaban. Medical history included diabetes mellitus, chronic back pain and uterine fibroids. Prior surgeries included cholecystectomy and Caesarean section. She denied tobacco, alcohol or estrogen use and had no recent travel. She had no family history of hypercoagulability. Her heart rate was 120, blood pressure 139/87, respiratory rate 18 and pulse oximetry 95% on 2L nasal cannula. She was in moderate respiratory distress but able to converse and breath without accessory muscle use. She had asymmetric lower extremity edema. Platelet count was 46,000 and INR 1.3. Lower extremity ultrasound showed extensive DVT in the right leg (common femoral vein to the calf). CT angiography of the chest confirmed bilateral pulmonary emboli and echocardiogram eliminated concern for RV strain. She was initially started on heparin infusion, then changed to argatroban due to concern for heparin-induced thrombocytopenia (HIT). ELISA testing to detect antibodies to the platelet factor 4/heparin complex was positive with an optical density of 2.791. Confirmatory testing with a serotonin release assay was positive. On day 3 platelet count recovered to 164 and she was transitioned to rivaroxaban. Ultrasound at 1 month showed partial resolution of the DVT, and complete resolution by 6 months.
Discussion: Traditionally, argatroban has been used for initial treatment of HIT and warfarin has been used for treatment after the recovery of platelets[1]. Our patient declined warfarin, due to frequent monitoring and bleeding risk. Given the benefits of direct oral anticoagulants (DOAC) in other conditions, we investigated their use for HIT. Due to the low incidence of HIT, data is limited to case reports and retrospective case series, which suggest efficacy of DOAC’s[1-4]. The most convincing evidence was found by Warkentin et al in a retrospective cohort plus literature review documenting 46 cases of HIT treated with rivaroxaban, with only one new thrombosis[1]. For initial treatment of HIT argatroban is the only FDA approved treatment option in the U.S. However, the data supporting its efficacy is limited, and it is only available intravenously thus increasing length of stay and cost. Argatroban is also uncommonly used by clinicians thus increasing its risk due to unfamiliarity with monitoring and dosing. Another alternative, fondaparinux, can be used off-label but fondaparinux-induced thrombocytopenia and treatment failure have been reported[5]. A randomized controlled trial is needed to validate the use of DOACs for treatment of HIT but increasing the amount of cases available can help guide hospitalists when deciding how to manage hospitalized patients with HIT.
Conclusions: This case represents an important success of a novel treatment for an uncommon condition. When practicing evidence-based medicine clinicians consider patient preference, available literature, and personal experience. Our personal experience leads us to suspect safety and efficacy of DOAC use for treatment of HIT after platelet recovery. Patient preference also typically favors DOACs due to convenience of use. Unfortunately, the medical literature is limited in this area, which is why we would like to share our experience.