Secondary Polycythemia and the Risk of Venous Thromboembolism (VTE) Among Hospitalized Patients in the United States

Introduction:The prevalence of secondary polycythemia is on the rise due to increasing prevalence of obesity, sleep apnea and other chronic cardiopulmonary diseases. While polycythemia vera is well known to increase the risk of VTE, the impact of secondary polycythemia on the development of VTE is less clear.

Methods: We utilized the Nationwide Inpatient Sample (NIS) database to identify all adults ≥18 years with secondary polycythemia (ICD-9-CM code 289.0) diagnosed during 2011. NIS is the largest all-payer inpatient database in the US that captures about 20% of all US hospitalizations. The outcome of interest was acute VTE identified using corresponding ICD codes for DVT or PE. We also identified the presence of the following confounding factors: malignancy, venous catheterization, long bone fracture, infection, trauma, mechanical intubation, congestive heart failure (CHF), pregnancy, length of hospital stay >5 days, stroke and prior history of VTE. Multivariate logistic regression was used to assess the impact of secondary polycythemia on the occurrence of VTE controlling the above confounding factors. Multicollinearity was assessed using variance inflation factor (VIF). All p-values were 2 sided, and the level of significance was chosen at 0.05. Statistical analysis was done using STATA 13.0 (StataCorp, College Station, TX) taking into account the complex sampling design of the database.

Results: A total of 3,972 hospitalizations with a primary or secondary diagnosis of secondary polycythemia were identified out of a total of 6,840,854 hospitalizations. Concurrent diagnosis of VTE was seen in 4.8% of patients with secondary polycythemia (n=190) as opposed to 2.3% of patients without secondary polycythemia (n=161,122) (odds ratio, OR 2.07; 95% confidence interval, CI 1.75-2.45; p value <0.01). In a multivariate analysis, secondary polycythemia continued to have a significantly greater risk of concurrent VTE (adjusted OR 1.87; 95% CI 1.58-2.22; p value <0.01) after adjusting for confounders including age, stroke, malignancy, infection, history of VTE, long bone fracture, trauma, CHF, pregnancy, mechanical intubation, nephrotic syndrome and hospital stay >5 days. No evidence of multicollinearity was noted in the final regression model (maximum VIF of 1.13).

Conclusion:

Within the limitations of the study design, our retrospective study indicates an independent association between secondary polycythemia and VTE in patients admitted in the hospital, however, this does not imply causality. Further, our study does not answer whether the use of therapeutic phlebotomy reduces the risk of VTE in patients with secondary polycythemia.