The Relation between Coagulant and Vascular Function in Adult Survivors of Childhood Cancer

Scientific Research Question: The pathological mechanisms for an increased risk of cardiovascular diseases (CVD) in adult childhood cancer survivors are not well elucidated yet. Endothelial dysfunction has been implicated in these individuals. Thrombin generation in presence of platelets is emerging as potential assay to assess individual risk for CVD. We recently reported on increased platelet-dependent thrombin generation in adult survivors of childhood cancer compared with a general population control group. Whether platelet-related hypercoagulability is linked with endothelial dysfunction remains unknown. The aim of this study is to investigate the relation between coagulation potential and vascular function in 200 adult survivors of a childhood cancer, sex specifically.

Methodology: Endogenous thrombin potential (ETP), measured by the calibrated automated thrombogram, in platelet rich plasma (PRP) and platelet free plasma (PFP) was correlated to vascular function measurements, reflexion index (RI) and reactive hyperemia index (RHI) assessed by photo and pneumatic plethysmography, respectively. The relation between ETP and vascular function measurements was assessed sex-specifically by Spearman rank correlation coefficient (Rs) and multivariable linear regression analysis adjusted for age and presence of conventional cardiovascular risk factors (CVRFs).

Findings: Female cancer survivors presented with higher ETP, measured both in PRP (p < 0.001) and PFP (p < 0.001), lower RI (p < 0.001) and no difference for RHI (p = 0.13) compared with male survivors. The correlation coefficient for the whole sample between ETP in PRP and RI was stronger compared with RI and ETP in PFP (Rs = −0.24 vs Rs = −0.16, respectively). The sex-stratified analysis showed the highest correlation between ETP in PRP and RI in females (Rs = −0.42). For males, both ETP in PRP and in PFP were not correlated to RI (Rs = 0.01 and Rs = 0.02, respectively). The linear regression model for ETP adjusted for age confirmed the negative association with RI in PRP (β estimate: −7.61 [95% confidence interval:−12.63, −2.59]) in females only. Further adjusting for conventional CVRFs resulted in loss of the observed association (β: −4.12 [−9.26, 1.02]). No relevant associations were found for RI in males and for RHI in both males and females.

Conclusions: This study demonstrates a link between platelet-related hypercoagulability and vascular function of resistance vessels measured by digital volume plethysmography in female cancer survivors, which is potentially mediated by the presence of traditional CVRFs.

No conflict of interest has been declared by the author(s).