Deaths Due to Thrombotic Versus Bleeding Events within 90 Days of Cancer Associated Thrombosis
Authors: Wilks Mailey L , Poudel Shyam K. , Park Deborah Y. , Jia Xuefei , Pinkava Vicki , O'Brien Meghan , Tripp Barb , Song Jung-Min , McCrae Keith R. , Khorana Alok A. , Angelini Dana E. 
Published: October 2019

Abstract
Background:
Current guidelines recommend anticoagulation for the treatment of cancer associated thrombosis (CAT). In addition to risk of recurrent VTE, cancer patients are also at risk of bleeding complications. However, little is described in regards to bleeding risk, especially in the direct oral anticoagulant (DOAC) era. Although clinical trials have captured bleeding rates with low molecular weight heparin (LMWH) and DOACs, they have not described fatality rates due to bleeding events vs. progression of acute VTE. To better understand whether or not patients are more likely to die from a VTE occurrence or from a fatal major bleed with anticoagulation treatment, we sought to analyze the cause of death in cancer patients from a thrombotic event vs. a bleeding event within 90 days of diagnosis of CAT.
Methods:
We evaluated a prospective cohort of patients referred to our centralized CAT clinic at the Cleveland Clinic Taussig Cancer Institute from 8/2014-5/2018. We evaluated clinical characteristics, anticoagulation prescription, and death from cancer progression, VTE or major bleed within 90 days of initial VTE diagnosis. Date of death was determined by documented date of death or date of last contact. Major bleed was defined using the ISTH definition for major bleeding. Statistical methods included wilcoxon rank sum tests and fisher's exact tests where appropriate. Multivariable analysis was performed to identify risk factors associated with the cause of death within 90 days.
Results:
Data from 1100 patients were included in the analysis, of which 103 (9.4%) patients died during the follow up period. Of these patients, 46 died within 90 days of an acute VTE event which represents our study cohort. Average age was 68.7 years [SD 9.7] and 95.7% of patients had stage 4 disease. Isolated distal DVT events comprised 46.0% of our cohort and 54.0% were proximal events. Enoxaparin was used in 60.9% of cases, rivaroxaban in 23.9%, warfarin in 4.3%, and no anticoagulation (due to contraindication) in 10.9%. Cause of death was determined to be secondary to cancer progression in 80.4%, VTE in 6.5% and major bleed in 13.0%. After multivariable analysis, older age was associated with a higher risk of death from a major bleed (p=0.01). Proximal VTE events were associated with a higher risk of VTE related death compared to distal thrombosis (p<0.001). There was no difference in cause of death based on gender or type of anticoagulation, p=1.00 and p=0.80, respectively. There was no difference in cause of death when timeline of 7 days, 30 days, and 90 days post VTE event were compared, p=0.14.
Conclusions:
This study demonstrates that cancer patients with VTE occurrence are at high risk of death within 90 days. Notable characteristics of our patient cohort were advanced age and stage 4 disease. There was no notable difference in cause of death regardless of type of anticoagulant used or gender. Bleeding related death was notably higher than VTE related death in our patient population, specifically in older individuals. We intend to further evaluate these findings in a larger cohort. This study adds to the limited literature of bleeding events during the treatment of CAT in the DOAC era.

Disclosures
Khorana: Bayer: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Janssen: Consultancy.