Improving Outcomes and Reducing Costs for Cancer Associated Thrombosis Using a Centralized Service: The Cleveland Clinic Experience
Authors: Rabinovich Emma , Shrotriya Shiva , McCrae Keith R. , Bartholomew John R. , Silver Bernard J. , Adams Kristine , Khorana Alok A. 
Published: October 2019

Abstract
Background: Venous thromboembolism (VTE) is a leading cause of mortality, morbidity, and hospitalization in cancer patients. Despite convincing evidence that treatment with low molecular weight heparin (LMWH) offers the best outcomes for patients with acute VTE, there exists a great variation in care, with up to 60% of patients in the United States not receiving LMWH. We instituted a centralized service for care of cancer patients with suspected deep venous thrombosis (DVT) and/or pulmonary embolism (PE) at Taussig Cancer Institute of the Cleveland Clinic in August 2014. We hypothesized that a cancer-associated thrombosis (CAT) clinical service that provides standardized management would reduce variation in care, and lower rates of recurrence, bleeding, and hospitalization in this patient population.
Methods: We conducted a prospective cohort study of patients seen by the CAT clinical service. We collected data regarding demographics, cancer types, VTE characteristics, treatment recommendations, and outcomes in these patients. Outcome data included VTE recurrence, major or clinically relevant nonmajor bleeding according to International Society on Thrombosis and Haemostasis definitions, hospitalization, and mortality.
Results: The study population comprised 221 patients with suspected VTE seen by the CAT clinical service between August 2014 and July 2015. Patients were 51% female, with a median age of 62±13 years. Hematologic malignancies (23%, N=50 of 221), breast cancer (10%, N=22 of 221), brain cancer (10%, N=22 of 221), pancreatic cancer (10%, N=21 of 221), and lung cancer (10%, N=21 of 221) were among the most commonly observed cancer types. VTE was diagnosed in 51 patients (23%, N=51 of 221). Of these, 39 patients (76%) had DVT, 5 (10%) had PE, and 7 (14%) had both. Hospitalization for VTE was necessary in only 24% (N=13 of 51) of cases. The mean and median costs of hospitalization for VTE (all costs) were US$7,656 and US$2,842, respectively, whereas the mean and median costs of outpatient treatment of VTE were US$1,160 and US$824 respectively.
Initial treatment for 94% (N=48 of 51) of patients was with enoxaparin. Other treatments included warfarin (2%, N=1 of 51), heparin (2%, N=1 of 51), and apixaban (2%, N=1 of 51). Of patients started on enoxaparin, 71% (N=34 of 48) remained on enoxaparin for the duration of their care, while 16% (N=8 of 48) were bridged to warfarin after a median of 9 days and 10% (N=5 of 48) were taken off anticoagulants due to bleeding or other considerations. Common causes for transitioning to warfarin were financial considerations (50%, N=4 of 8), patient preference (38%, N=3 of 8), and poor renal function (13%, N=1 of 8). VTE recurred in 14% (N=7 of 51) of patients with a median follow-up of 3.5 months. Recurrences occurred in 9% (N=3 of 34) of patients on enoxaparin monotherapy, in 22 % (N=2 of 9) of patients started on or bridged to warfarin and 33% (N=2 of 6) of patients taken off anticoagulation. A total of 10 recurrent VTE events occurred in 7 patients. Of these, 4 required hospitalization. The mean and median costs of hospitalization for recurrence (all costs) were US$19,528 and US$18,627, respectively. The mean and median costs of initial outpatient care (excluding drug costs) for recurrent VTE were US$998 and US$728, respectively.
Major or clinically relevant bleeding was seen in 14% (N=7 of 51) of patients on anticoagulants, with 86% (N=6 of 7) requiring hospitalization. The risk of bleeding in patients on enoxaparin (15%, N=5 of 34) was similar to that seen in patients who bridged to warfarin (14%, N=1 of 8). The mean and median costs of hospitalization for bleeding (all costs) were US$11,754 and US$8,806 respectively.
Conclusions: Centralizing care of CAT reduces treatment variation and appears to improve patient related outcomes including the need for VTE-related hospitalizations and recurrent VTE. Substantial cost savings can be achieved by avoiding unnecessary hospitalization for appropriate patients and by reducing recurrence and bleeding rates with appropriate therapy.

Disclosures
McCrae: Halozyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Syntimmune: Consultancy; Momenta: Consultancy. Bartholomew:Boehringer Ingelheim: Consultancy; Daiichi Sankyo: Consultancy. Khorana:Pfizer: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; sanofi: Consultancy, Honoraria.