Iron Deficiency and the Risk of Sinusitis-Related Cerebral Sinus Thrombosis

Introduction: A rare but feared complication of sinusitis is cerebral sinus thrombosis (CST). While iron deficiency has previously been suggested as a risk factor for CST by inducing a reactive thrombocytosis, it has never been shown to increase the risk of CST of an infectious origin.

Methods: We conducted a retrospective matched-cohort study using the TriNetX database. ICD-10 codes and lab values were used to identify patients ages 0-18 with sinusitis. Relative risk, odds ratio, and linear regression analyses were used to determine how the rate of infectious-CST varied based on lab findings within one year prior to CST. Abnormalities on CBC suggestive of iron deficiency were identified as an elevated red blood cell distribution width (RDW) or a decreased mean corpuscular volume (MCV). Dedicated iron studies included iron saturation, iron-binding capacity, serum iron, and ferritin.

Results: In a cohort of 1.2 million children with sinusitis, unmatched analysis showed 49,663 had CBC abnormalities suggestive of iron deficiency, 0.3% (n = 128) of whom eventually developed CST. Of 1,034,440 patients without CBC abnormalities, 0.02% (n=203) developed CST—translating to a relative risk of 13.1 (p < 0.0001). Abnormal dedicated iron labs had a relative risk of 14.9 (p < 0.0001). Linear regression revealed a strong positive correlation between RDW and CST (p < 0.0001, R² = 0.87) and a strong negative correlation with MCV and CST (p = 0.0162, R² = 0.71).

On matched analysis, sinusitis patients with CBC abnormalities had significantly higher rates of CST compared to those without CBC abnormalities (aRR=5.45, 95% CI 3.384,8.778, p< 0.0001). Similarly, patients with abnormalities on dedicated iron laboratory tests had a significantly higher risk of developing CST (aRR=4.00, 95% CI 2.272, 7.042, p< 0.0001).

Conclusions: Both overt and potentially subtle signs of iron deficiency on CBC, like an increase in the RDW or a decrease in MCV, are associated with a significantly increased risk of sinusitis-related CST within one year. These findings emphasize the importance of identifying and addressing iron deficiency in children with sinusitis.