Thrombotic and Bleeding Complications in Patients with Cancer Undergoing Lower Extremity Arthroplasty; An Administrative Database Study

Background:

Cancer is an independent risk factor for thrombosis and bleeding. With advancing cancer directed treatments and improved survival, elective orthopedic surgery including total hip arthroplasty (THA) and total knee arthroplasty (TKA) are increasingly offered to cancer survivors or patients with cancer on long term therapy. However, there is limited data on the post-surgical incidence of thrombotic and bleeding complications for this high-risk subpopulation. Estimating the risk of venous thromboembolism (VTE) and bleeding in patients with cancer and identifying risk factors can help clinicians risk stratify accurately and individualize thromboprophylaxis.

Objective:

To compare the rates of 30-day post-operative venous thromboembolism and bleeding in patients with cancer who undergo lower extremity arthroplasty (THA/TKA) to patients without cancer.

Methods:

This was an IRB exempt retrospective cohort study that used deidentified patient data from MarketScan commercial claims database from March 1^st 2017 to September 30^th 2019. We included patients that underwent THA or TKA and had continuous insurance enrollment 3 months prior to the surgical procedure. Variables extracted included demographics, comorbidities (obesity, history of VTE/bleeding, chronic kidney disease, and hereditary/acquired hypercoagulable states), surgical details (type of procedure and length of stay (LOS)), and pharmacologic thromboprophylaxis (aspirin vs other anticoagulants). Patients with a billing code for malignancy (excluding non-invasive skin cancer) up to 36 months prior to the surgery were included in the cancer cohort. The primary outcomes included post-surgical VTE and bleeding complications at 30 days after index surgery, based on prior validated billing codes. A 1:1 propensity score matching analysis was performed to match cancer to non-cancer patients based on demographics, comorbidities, surgical characteristics and compare cumulative incidence rates of VTE and Bleeding. We used a logistic regression model to identify risk factors associated with 30-day post-surgical VTE.

Results:

Of a total cohort of 132,237 patients, 8.7% (n=11,441) had concomitant cancer diagnosis, with a median age of 63 years (IQR 58-71), including 57.5% female. The majority (59.7%) underwent TKA. The most common primary malignancy sites were breast (21.9%), hematologic malignancies (20.6%), male genitourinary (17.8%), renal (6.8%), and endocrine (6.1%). In the propensity matched analysis the standardized mean differences for features including demographics, surgical features, acquired and hereditary hypercoagulable states, and use of thromboprophylaxis between the cancer and non-cancer cohort (n=11,439 each) were <0.05, indicating the cohorts were well matched.

The cumulative incidence of VTE at 30 days in patients with cancer was 2.9% (95% CI 2.6% - 3.2%) vs 2.4% (95% CI 2.2 - 2.7) in non-cancer patients (p=0.03). Similarly, the cumulative incidence of bleeding events after surgery was 2.2% (95% CI 1.9 - 2.5) for patients with cancer vs 1.8 (95% CI 1.6 - 2.1) in the non-cancer group (p=0.01).

In the multivariable analysis a diagnosis of cancer was associated with a significantly increased risk of 30-day VTE (OR 1.2, 95% CI 1.0 - 1.4; p=0.03). Other factors that were associated with increased risk of VTE were age > 65 (OR 1.4, 95% CI 1.1 - 1.6; p=0.0005), prior history of VTE (OR 5.8, 95% CI 4.3 - 7.7; p=<0.0001), hereditary hypercoagulable state (OR 3.8, 95% CI 2.4 - 5.8; p=<0.0001), the presence of antiphospholipid antibody or lupus anticoagulant (OR 1.8, 95% CI 1.1 - 2.9; p=0.02), and length of stay of more than 3 days (OR 2.1, 95% CI 1.6 - 2.6; p=<0.0001). Between TKA and THA, TKA had increased risk of VTE at 30 days after the procedure (OR 1.2, 95% CI 1.0 - 1.4; p=0.03). The 30-day VTE risk was not significantly associated with the use of aspirin vs other anticoagulants (OR 0.7, 95% CI 0.4 - 1.2; p=0.18).

Conclusion:

In this large administrative claims-based database, the rates of bleeding and thrombotic complications were significantly higher in patients undergoing total knee and hip arthroplasty with a concomitant cancer diagnosis. These data highlight the need for risk stratified tailored thromboprophylaxis and patient education in patients with cancer undergoing elective orthopedic surgery.

Patell:Merck Research: Consultancy, Other: Personal fees.