Cardiovascular risk factors are important determinants of platelet-dependent thrombin generation in adult survivors of childhood cancer

Marina Panova-Noeva*, Marie A. Neu, Susan Eckerle, Claudia Spix, Astrid Schneider, Irene Schmidtmann, Henri M. Spronk, Norbert Pfeiffer, Manfred Beutel, Karl J. Lackner, Thomas Muenzel, Hugo ten Cate, Hiltrud Merzenich, Joerg Faber, Philipp S. Wild

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Cardiovascular disease is the most frequent non-malignant cause of morbidity and mortality in adult survivors of childhood or adolescent cancer. Thrombin generation (TG) analysis gives insight in hypercoagulability as an important mechanism linked to cardiovascular risk factors (CVRFs). In 200 individuals, from the cardiac and vascular late sequelae in long-term survivors of childhood cancer study, TG in platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1pM tissue factor was investigated. Endogenous thrombin potential (ETP) and peak height were the analysed parameters of a TG curve. Sex-specific multivariable linear regression analysis adjusted for age and CVRFs was used to assess the clinical determinants of TG. Females presented with higher ETP and peak height compared to males, both in PRP and PFP. Hypertension (beta estimate, ss: 184.8 [90.7; 278.8]), obesity (ss: 161.9 [63.9; 259.5]), and HbA1c (ss: 715.6 [97.4; 1333.8]) were associated with higher ETP in PRP only. ETP in PRP was positively associated with obesity and HbA1c in both males and females and with dyslipidemia (ss: 253.07 [72.92; 433.22]) and systolic hypertension (ss: 436.7 [119.02; 754.39]) in females only. CVRFs showed no association with TG variables in PFP. In conclusion, this study presents an important relation between traditional CVRFs and TG in the presence of platelets only. Sex-specific differences in TG with females presenting with higher TG, particularly those with dyslipidemia and systolic hypertension, were demonstrated. These results highlight the potential of the platelet-coagulant function in identifying cancer survivors at higher risk for adverse cardiovascular events.

Original languageEnglish
Pages (from-to)438-447
Number of pages10
JournalClinical research in cardiology
Issue number4
Publication statusPublished - Apr 2019


  • Cancer survivors
  • Hypertension
  • Thrombin generation
  • Platelets
  • Epidemiology
  • Females

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