Abstract Body: Introduction
Previous studies identified a possible association between indoor radon concentrations and increased risk of stroke; however, the underlying biological mechanisms are unclear. We therefore investigated the associations between indoor radon concentrations and leukocyte and platelet counts to explore inflammation and thrombosis as potential mechanisms of radon-related stroke.

Methods
We conducted a repeated measures study in a prospective cohort of post-menopausal women enrolled in the Women’s Health Initiative (WHI) in 1993-1998 and examined at 5 visits over 19 years in 40 US centers. At each visit, we excluded women with hematologic malignancy, medication use affecting leukocyte/platelet counts, or extreme values of them. We estimated time-varying indoor radon concentrations (pCi/L) at geocoded, address-specific participant locations based on the 1993 US Geological Survey radon index and categorized them according to US EPA action levels: <2, 2-4, and >4 pCi/L. We also measured cell counts (cells/μL) in blood drawn at each visit on automated counters at local laboratories following standard quality assurance procedures. We imputed missing covariates (demographic; social; behavioral; clinical; environmental) by chained equations. Then we estimated covariate-adjusted, radon and log-transformed cell count associations using linear, mixed-effects models including a participant-level random intercept and a visit-year fixed effect.

Results
Among 157,044 women at baseline (mean age: 63; 85% white; 9% African American, 5% Hispanic; 4% other; mean leukocyte and platelet counts: 5,866/μL and 247,619/μL), we found positive radon-platelet count and negative radon-leukocyte count associations (both p<0.001). At radon concentrations of 2-4 and >4 pCi/L, fully-adjusted platelet counts (95% confidence intervals) were 1,002 (215-1,788) and 2,934 (1,885-3,983) cells/μL higher and leukocyte counts were 38 (25-50) and 65 (48-81) cells/μL lower than at <2 pCi/L. Indeed, platelet counts increased by 625 cells/μL (457-792) and the leukocyte counts decreased by 9 cells/μL (6-12) per unit increase in the radon index.

Conclusion
Our findings suggest radon-related stroke risk may be partly thromboembolic in origin and could involve activation or suppression of hematopoietic stem cells in the myeloid or lymphoid lineages. Further research is needed to clarify the hematologic effects of indoor radon and their potential roles in increased cerebrovascular risk.