LAUSR

Mechanical circulatory support (MCS) improves survival and quality of life in patients with advanced heart failure and is therefore increasingly prevalent. Although ongoing advances in MCS have improved outcomes, the thromboembolic risk remains high, warranting anticoagulation with warfarin.1 Patients requiring MCS may also have clotting factor deficiencies complicating anticoagulation. With factor VII (FVII) deficiency, baseline prothrombin time (PT) and international normalized ratio (INR) are elevated, precluding monitoring with traditional INR goals. An alternative strategy involves monitoring two vitamin K dependent factors with the longest half-lives: factor II (FII) and factor X (FX). Minimum activities to achieve hemostasis for FII, FX, and FVII are 20–40%, 15–25%, and ⩾5%, respectively, theoretically translating into a therapeutic window while mitigating bleeding.2,3 Factor activities correlate linearly with INR; thus, associated INR ranges can be used for downstream monitoring.4 Herein we describe four patients with FVII deficiency requiring warfarin for MCS (Table 1). The institutional review boards from both hospitals approved this case series. Each patient had baseline elevated PT which completely corrected with a 1:1 mix with pooled plasma. Incubated mixing studies were not performed given the low suspicion for an underlying inhibitor. Partial thromboplastin times were normal. Individual factor activities were consistent with FVII deficiency. None had vitamin K deficiency or liver disease (including congestive hepatopathy) based on liver function studies. None had personal or family histories of bleeding with trauma or surgery. Congenital etiology was not ascertained as FVII gene sequencing was not readily available. Warfarin was administered with a goal FII of 20–40% or FX of 15–25%, and FVII of ⩾5%. Patient 1 underwent HeartMate IITM (HMII; Thoratec Corp., Pleasanton, CA, USA) implantation as destination therapy, achieved goal factor levels, and did not experience any hematologic events. Patient 2 underwent biventricular paracorporeal MCS as a bridge-to-transplant. Two and five months later, he experienced a pulmonary embolus (PE) and ischemic stroke, respectively, while FII activity was therapeutic. Warfarin was increased to achieve an INR as close to 3.5 as possible and he stayed on this regimen until transplant. Patient 3 underwent HMII implantation as a bridge-totransplant and achieved goal factor levels. She had two gastrointestinal bleeds (GIB) from arterial-venous malformations, which were likely secondary to physiologic effects of continuous flow MCS, and treated with argon photocoagulation. Patient 4 underwent HMII implantation as destination therapy. Goal FII activity was not achieved due to borderline FVII activity. One month later he developed pump thrombosis. After device exchange, warfarin was re-initiated with goal factor activities achieved. He later developed a GIB from a polyp treated with polypectomy. We extrapolated from scant available literature to devise a warfarin strategy for MCS in the setting of FVII deficiency. MCS is associated with coagulation activation, shear stress on high molecular weight von Willebrand multimers, and physiologic sequelae of reduced arterial pulse pressure. Because the addition of FVII deficiency complicates the balance between bleeding and thrombosis, the therapeutic window for warfarin is narrow. Owing to the complexity of such cases, a multidisciplinary team comprised of cardiology, surgery, hematology, pharmacy, and anticoagulation services should be encouraged. Warfarin management in the setting of FVII deficiency and mechanical circulatory support