Defining the Risk: Benefit Ratio of Venous Thromboembolism (VTE) Prophylaxis in Hospitalized Cancer Patients

Introduction: VTE affects 1.6-1.8/1000 hospitalized patients per year; active cancer increases the rate of VTE 6-fold. Despite the high risk of VTE, studies show cancer patients receive inpatient VTE prophylaxis at a lower rate than general medical patients. In addition, VTE prophylaxis is often held for a platelet value of <50x10⁹/L, despite a lack of evidence. Current recommendations for all inpatients with cancer (and no contraindication to blood thinners) are to receive prophylactic anticoagulation, regardless of an increased bleeding tendency in this population. A formal risk:benefit ratio of inpatient VTE prophylaxis for cancer patients has not been evaluated to date.

Methods: The Michigan Hospital Medicine Safety Consortium, a 49 hospital quality collaborative, has prospectively collected data on VTE risk factors and outcomes in medical patients > 18 years of age. Exclusion criteria include surgical patients, pregnancy, admission to the ICU or for palliative care, therapeutic anticoagulation, diagnosis of acute thrombus, history of VTE within 6 months, and length of stay < 2 days. We compared rates of VTE prophylaxis, bleeding and new VTE between cancer and general medicine patients who were eligible for prophylaxis (i.e. no contraindications including active bleed within 3 months, coagulopathy, or high risk brain metastasis). Student's t-test was used for continuous variables and chi-square for categorical data. Logistic regression was used to calculate odds ratio (OR). The number needed to treat and number needed to harm were used to derive a risk:benefit ratio.

Results: Between 7/2012-7/2015, 86,634 admissions were captured in the cohort; 70,086 were eligible for VTE prophylaxis and included in this analysis. 22% of cases had a diagnosis of cancer.

Of cancer admissions, 89.5% had solid tumors, 13.5% hematologic malignancies, 3.4% both and 20% metastatic disease. Active treatment for cancer was delivered <6 months from index admission in 32.1%, within 6-12 mo in 3.2%, >12 mo in 44.4% and no treatment or unknown in 20.3%.

When compared to general medical admissions, cancer admissions were more likely to receive VTE prophylaxis (72.16% vs 69.21%, p<0.001), and have a new VTE out to 90 days post discharge despite prophylaxis (0.91% vs 0.45%, p<0.001, unadjusted OR 2.07 (95% CI 1.6-2.7)). There was no difference in VTE rate with regard to platelet count in cancer cases (0.43% for plt < 50 vs 1.08% for plt ≥ 50, p=0.10). Among all patients receiving VTE prophylaxis, bleeding was more common in cancer cases (major bleeding 0.84% vs 0.58%, p=0.005; minor bleeding 1.80% vs 1.36%, p=0.002). Among cancer cases, bleeding rates were higher in patients with platelet <50 vs ≥ 50 (major bleed 4.86% vs 1.88%, p<0.001; minor bleed 2.88% vs 1.7%, p=0.04).

Conclusions: In this prospective inpatient cohort, we compared general medicine to cancer cases and found cancer admissions received VTE prophylaxis at a higher rate. This is different than previously reported data, likely due to the exclusion of patients with contraindications to prophylaxis. However, despite prophylaxis, cancer patients had a higher rate of VTE during admission and 90 days post discharge as well as more bleeding complications. The risk:benefit ratio of VTE prophylaxis is 6 times worse in cancer patients due to bleeding. While bleeding occurs more frequently in cancer patients with platelet count <50x10⁹/L, VTE occurs at a similar rate regardless of platelet count, meaning that cancer patients are at high risk of both clotting and bleeding. Recommendations for inpatient VTE prophylaxis for cancer patients require a targeted approach to identify a subset who would most benefit from VTE prophylaxis.