Aplastic Anemia Nearly Triples Risk of VTE

The systemic inflammation that characterizes aplastic anemia (AA) may also contribute to a greater risk of venous thromboembolism (VTE), giving patients with AA a 2.6-fold higher risk of developing deep vein thrombosis (DVT) or pulmonary embolism (PE) compared with patients without AA, according to a study conducted in Taiwan and published in Thrombosis Research.

The study authors, led by Chun-Liang Lin, MD, from Taichung Hospital in Taiwan, evaluated the incidence and risk of VTE in a nationwide, retrospective cohort study of 4,001 patients who were newly diagnosed with AA between 2000 and 2010. Patients were selected from the National Health Insurance Research Database, which contains health information for most of Taiwan’s population.

Dr. Lin and co-authors compared incidence of VTE between the AA cohort and a control cohort of patients without AA who were matched by sex, age, comorbidities, and year of index date (n=15,998). Patients were excluded if they had a previous diagnosis of DVT or PE at baseline or were <20 years of age with incomplete demographic information. Patients were followed until DVT or PE diagnosis, withdrawal from the program, or the end of 2011.

Most patients were male (51.9% in both cohorts) and ≥65 years of age (56.4% in both cohorts). The mean patient age was 63.7±18.5 years in the AA cohort and 63.6±18.5 years in the control cohort.

Patients with AA were more likely to have comorbidities (including diabetes, hypertension, cerebrovascular accident, heart failure, lower leg fracture, surgery, and cancer) than the control group (standardized differences >0.1). The overall incidence of VTE was >4 times higher in patients with AA than in control patients: 42.3 per 10,000 person-years versus 10.2 per 10,000 person-years, for a crude sub-hazard ratio (SHR) of 3.12 (95% CI 2.26-4.32). After the researchers adjusted for potential confounding factors, the risk of VTE remained significantly higher in patients with AA (adjusted SHR [aSHR] = 2.56, 95% CI 1.81-3.63).

After 11,585 and 90,016 person-years of follow-up for patients with AA and the control patients, respectively, the overall incidence density rate of DVT also was significantly higher in AA patients than controls, but AA was not associated with a higher incidence density rate of PE:

  • DVT: 38.0 vs. 9.66 per 10,000 person-years (aSHR=2.42; 95% CI 1.68-3.49)
  • PE: 14.6 vs. 3.99 per 10,000 person-years (aSHR=1.78; 95% CI 0.98-3.22)

PE risk appeared to be highest in patients 50-54 years old in the AA cohort, compared with control patients in the same age range (aSHR=24.8; 95% CI 4.72-130.8).

“The incidence density rate of developing DVT increased with age in both cohorts,” the authors noted, with an aSHR of 10.1 (95% CI 3.88-26.1) for patients 50-64 years old and an aSHR of 2.57 (95% CI 0.69-9.51) in those ≤49 years. This is likely explained, they wrote, by the observation that “with increasing age, people become less active and susceptible to developing DVT through blood stasis and clots.”

Notably, when patients were stratified with or without comorbidities, AA seemed to confer an additional risk even when no additional comorbidities were present (aSHR=2.52; 95% CI 1.10-5.77).

Because VTE is a common health problem in patients with acute leukemia, the researchers also compared the risk of VTE between the study’s AA cohort and a previously published cohort of adults with newly diagnosed acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL). The incidence of VTE was higher in the AA cohort than in the leukemia cohort (42.3 vs. 40.3 per 10,000 person-years), but was not significant on multivariable analysis. variates. This finding suggests “that a multidisciplinary team should be involved for providing holistic care to patients with AA,” the authors wrote.

Though this study indicates that patients with AA have an increased risk of VTE, it is limited by its retrospective design, and factors that may not be accounted for in analyses in the control group. In addition, data on the severity of AA and treatment information were lacking, which may have influenced the outcomes of the study.

Lin CL, Lin CL, Tzeng SL, et al. Aplastic anemia and risk of deep vein thrombosis and pulmonary embolism: a nationwide cohort study. Thromb Res. 2017;149:70-5.