Long-term discontinuation of warfarin in a patient with HeartMate 3 left ventricular assist device without thromboembolic events

Abstract

The gold standard therapy for end-stage heart failure is cardiac transplantation. However, in the face of a donor shortage, a mechanical assist device such as the left ventricular assist device HeartMate 3 (Abbott Laboratories, Abbott Park, IL, USA) serves as bridging therapy to transplantation and/or destination therapy. Current guidelines recommend anticoagulation with a vitamin K antagonist in combination with low-dose aspirin. We herein report a challenging anticoagulation regimen in a patient with a HeartMate 3 in whom systemic anticoagulation with warfarin was not feasible for 4 years because of low compatibility and a rare X-factor deficiency. This is a rare hematological disorder, estimated to affect approximately 1 in every 500,000 to 1,000,000 people in the general population. The patient finally received a modified anticoagulation regimen involving the combination of rivaroxaban and clopidogrel without warfarin. Under this regimen, the patient remained free of thromboembolic complications for 4 years with in situ placement of the left ventricular assist device. This case illustrates that under specific circumstances, long-term absence of warfarin therapy is feasible in patients with a HeartMate 3.

Introduction

Heart transplantation is the gold standard treatment for end-stage heart failure; however, donor hearts are still rare. To overcome the organ shortage, a mechanical assist device such as the left ventricular assist device (LVAD) HeartMate 3 (Abbott Laboratories, Abbott Park, IL, USA) is a recommended option. The HeartMate 3 is a well-investigated assist device with low risks of pump thrombosis, stroke, and bleeding events. ¹ There is an international recommendation regarding anticoagulation management in patients with a HeartMate 3. It suggests using aspirin in addition to warfarin, with a target international normalized ratio (INR) of 2.0 to 3.0. ² We herein report a challenging anticoagulation regimen in a patient with a HeartMate 3 in whom systemic anticoagulation with warfarin was not feasible for 4  years because of low compatibility and a rare X-factor deficiency.

Case report

A man in his early 50s with end-stage chronic heart failure underwent HeartMate 3 implantation in February 2017 after providing consent for treatment. His coagulation function was checked through a standard preoperative coagulation screening and showed no abnormalities. Through the use of postoperative unfractionated heparin, a target activated partial thromboplastin time of 50 to 55 s was achieved. However, the postoperative care was then prolonged because of difficulties in INR management. Despite administered up to 10 tablets of warfarin per day, we could only achieve an INR of 1.5. Hematological tests and a genetic investigation where then initiated, which revealed that all vitamin K-dependent parameters, including the prothrombin time (Quick test) and factors II, VII, und X, were decreased under warfarin therapy. Blood platelets were within normal values. The level of factor X was lower than the levels of factors II and VII. After an interdisciplinary discussion, we changed the anticoagulation therapy to warfarin combined with clopidogrel 75 mg once a day. In addition, the therapy was optimized according to the coagulation findings, and vitamin K supplements were used to stabilize the patient’s condition. Because of the poorly controlled coagulation, the patient required multiple long-term hospital stays with intravenous heparin bridging. The patient also experienced depressive episodes necessitating psychiatric treatment. Consequently, we switched the therapy to rivaroxaban with clopidogrel. The patient remained off warfarin for 4 years until he died of septic multiorgan failure caused by a driveline infection. Serial transthoracic echocardiography, blood tests, and computed tomography of the chest in the outpatient clinic had excluded thrombosis of the LVAD at that time. A postmortem examination was not performed. The reporting of this case conforms to the CARE guidelines. ³

Discussion

Stroke occurs at an incidence of approximately 10% after HeartMate 3 implantation and is caused by embolic or hemorrhagic factors. ⁴ Several long-term studies have focused on the optimal anticoagulation regimen for patients with a HeartMate 3. Sowder et al. ⁵ reported that a lower target INR of 1.8 to 2.2 may be safe after implantation of the HeartMate 3. Factor X plays a central role in coagulation. It is dependent on vitamin K and is produced in the liver. In patients with factor X deficiency, the complete blood count, red cell count, and bleeding time are within the normal range. However, the prothrombin time, activated partial thromboplastin time, and thrombin time are prolonged. The current literature lacks reports of the discontinuation of recommended antithrombotic therapy for ≥1 year with normal device function and without thromboembolic complications. A patient who underwent interruption of anticoagulation for 19 months because of gastrointestinal bleeding was reported by Fiedler et al. ⁶ In our case, we stopped warfarin because of a heterozygous factor X deficiency and treated the patient with a combination of rivaroxaban and clopidogrel for 4 years. In their review, Loyaga-Rendon et al. ⁷ found that non-vitamin K antagonist oral anticoagulant therapy with apixaban or dabigatran is an alternative therapy without a risk of bleeding or thromboembolic complications.

Because of the rarity of factor X deficiency, evidence-based management guidelines for these patients are lacking, which can make postoperative care challenging.

Conclusion

The globally accepted recommendation for anticoagulation in patients with LVADs is a combination of warfarin and aspirin. However, an alternative recommendation should be considered in patients who cannot tolerate warfarin or phenoprocoumon or, as in this case, in patients with a heterozygous factor X deficiency. There are now several reports on effective antithrombotic therapy with non-vitamin K antagonist oral anticoagulants such as apixaban or dabigatran. Our case involving a patient with a HeartMate 3 who survived for 4 years without thromboembolic events indicates that rivaroxaban may also represent a possible alternative. Further larger cohort studies are necessary to confirm this.