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TRP X40 Hormonal status and link to hypercoagulability in adult survivors of childhood cancer

Funding period: 01.08.2019 – 31.07.2020

Project Summary

Improvement in early detection and modern cancer treatment has resulted in steady increase in childhood cancer survivors. Unfortunately, adult childhood cancer survivors manifest excess cardiovascular risk throughout survivorship with circulatory diseases overtaking from subsequent neoplasms the leading cause of excess mortality.

The pathological mechanisms for an increased risk of cardiovascular diseases (CVD) are not well elucidated yet. Signs of premature atherosclerosis have been reported in childhood cancer survivors, particularly in those exposed to total body radiation. Increased intima media thickness, arterial stiffness and plaque formation were displayed more frequently in cancer survivors compared to siblings who had never been diagnosed with cancer. Current knowledge suggests that atherosclerosis commonly develops in individuals burdened with the classical risk factors as obesity, dyslipidemia, arterial hypertension and smoking. However, in childhood cancer survivors, atherosclerosis may precede the development of the traditional cardiovascular risk factors. Chronic inflammation and endothelial dysfunction are well known features of atherosclerosis. In addition, enhanced coagulation is increasingly recognized as important driver of atherosclerosis development and progression. Both inflammation and endothelial dysfunction can upregulate blood coagulation towards a hypercoagulable state and contribute to an increased the risk for CVD. Furthermore, in case of cancer survivors, female sex is a risk factor for numerous long-term adverse outcomes, however very little is known for the underlying pathophysiological mechanisms rendering the increased risk. Whether ovarian insufficiency following cancer therapy and cancer itself in the adolescence and adulthood could be held responsible for female predominance of inferior long-term outcome is not yet fully elucidated. Our recent findings in a subsample of the CVSS study identified platelet-related hypercoagulability for cancer survivors with obesity and hypertension. In addition, females presented with higher thrombin generation potential compared to male cancer survivors, both in presence and absence of platelets. Hormonal derangement including infertility has been reported in adult survivors of childhood cancer. Female cancer survivors, particularly those exposed to alkylating agents, have impaired ovarian reserve and often experience symptoms associated with hormone deprivation. Estrogen was shown to have an important role in delaying the onset of atherothrombotic events in females. Whether, estrogen deprivation due to the cancer-related therapy is the underlying cause of hypercoagulability in female cancer survivors, deserves further investigation. Therefore, this proposal aims to investigate the relation between hormonal status and thrombin generation parameters measured in platelet poor plasma of the subjects enrolled in the CVSS cohort.

Principal Investigator

MD, MSc, PhD Marina Panova-Noeva
MD, MSc, PhD Marina Panova-Noeva

Junior group leader

06131 17-6050