Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample

TY - JOUR

T1 - Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample

AU - Panova-Noeva, Marina

AU - Wagner, Bianca

AU - Nagler, Markus

AU - Arnold, Natalie

AU - Prochaska, Jürgen H

AU - Eckerle, Susan

AU - Spronk, Henri M

AU - Merzenich, Hiltrud

AU - Wingerter, Arthur

AU - Schneider, Astrid

AU - Danckwardt, Sven

AU - Ten Cate, Hugo

AU - Faber, Jörg

AU - Wild, Philipp S

PY - 2019/12/27

Y1 - 2019/12/27

N2 - Female sex is a risk factor for long-term adverse outcome in cancer survivors, however very little is known for the underlying pathophysiological mechanisms rendering the increased risk. This study investigated sex-specifically the relation between thrombin generation (TG) with and without presence of platelets and vascular function in 200 adult survivors of a childhood cancer compared to 335 population-based control individuals. TG lag time, peak height and endogenous thrombin potential (ETP) measured in presence and absence of platelets were correlated to reflection index (RI) and stiffness index (SI). A sex-specific correlation analysis showed a negative relation in female survivors for platelet-dependent peak height and/or ETP and RI only. An age adjusted linear regression model confirmed the negative association between RI and platelet-dependent ETP (beta estimate: -6.85, 95% confidence interval: -12.19,-1.51) in females. Adjustment for cardiovascular risk factors resulted in loss of the association, whereby arterial hypertension and obesity showed the largest effects on the observed association. No other relevant associations were found in male and female cancer survivors and all population-based controls. This study demonstrates a link between platelet coagulant and vascular function of resistance vessels, found in female cancer survivors, potentially mediated by the presence of arterial hypertension and obesity.

AB - Female sex is a risk factor for long-term adverse outcome in cancer survivors, however very little is known for the underlying pathophysiological mechanisms rendering the increased risk. This study investigated sex-specifically the relation between thrombin generation (TG) with and without presence of platelets and vascular function in 200 adult survivors of a childhood cancer compared to 335 population-based control individuals. TG lag time, peak height and endogenous thrombin potential (ETP) measured in presence and absence of platelets were correlated to reflection index (RI) and stiffness index (SI). A sex-specific correlation analysis showed a negative relation in female survivors for platelet-dependent peak height and/or ETP and RI only. An age adjusted linear regression model confirmed the negative association between RI and platelet-dependent ETP (beta estimate: -6.85, 95% confidence interval: -12.19,-1.51) in females. Adjustment for cardiovascular risk factors resulted in loss of the association, whereby arterial hypertension and obesity showed the largest effects on the observed association. No other relevant associations were found in male and female cancer survivors and all population-based controls. This study demonstrates a link between platelet coagulant and vascular function of resistance vessels, found in female cancer survivors, potentially mediated by the presence of arterial hypertension and obesity.

KW - Adult

KW - Blood Coagulation Tests

KW - Blood Platelets/physiology

KW - Blood Vessels/physiopathology

KW - Cancer Survivors

KW - Child

KW - Female

KW - Humans

KW - Male

KW - Neoplasms/blood supply

U2 - 10.1038/s41598-019-56626-1

DO - 10.1038/s41598-019-56626-1

M3 - SCORING: Journal article

C2 - 31882836

VL - 9

SP - 20090

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -