Iron Deficiency: a Novel Risk Factor of Recurrence in Patients After Unprovoked Venous Thromboembolism

Introduction: Patients with unprovoked venous thromboembolism (VTE) are at high risk of recurrence; however, its predictors remain largely unknown. There is evidence that iron is implicated in the pathophysiology of thrombosis.

Objectives: We aimed to investigate whether iron deficiency (ID) affects the risk of recurrence in patients after unprovoked VTE.

Patients And Methods: In this prospective cohort study, we examined 229 consecutive patients aged 65 years or younger with the first-ever episode of unprovoked VTE within 6 to 12 months prior to enrollment. The exclusion criteria were as follows: hemoglobin levels of less than 11 g/dl, heart failure, diabetes, cancer, serum creatinine levels exceeding 120 μM, and previous or current use of iron or erythropoiesisstimulating agents, or both. ID was defined as serum ferritin levels below 30 μg/l. Recurrent VTE was recorded during a 24-month follow-up.

Results: ID was observed in 47 patients (21%). In a multivariate regression model, the presence of ID was associated with female sex, elevated C-reactive protein (CRP), anemia and reduced hemoglobin levels (all P <0.05). In a multivariate model, the presence of ID (or low serum ferritin levels) and elevated CRP levels, but not anemia, predicted VTE recurrence during 24 months. The hazard ratio adjusted for CRP and the presence of anemia was 3.17 for ID (95% confidence interval [CI], 1.20-8.38; P = 0.02) and 0.64 for serum ferritin levels (95% CI, 0.43-0.94; P = 0.02).

Conclusions: ID may represent a novel risk factor for VTE recurrence in young and middle-aged patients following an unprovoked episode.