287 Frequency of factor ii, factor v leiden and mthfr mutations in children with cancer

Thrombosis is an increasingly recognized complication of malignancy, occurring in up to 20% of patients with cancer. Cancer-associated thrombosis is linked with poor prognosis, being the second leading cause of death in cancer patients. The pathogenesis is complex, and includes multiple genetic and acquired factors. There is significantly less knowledge about thrombosis in pediatric cancer population compared to adults. Besides, the role of inherited thrombophilia in all cancer patients with thrombosis is still unclear. The aim of this study was to examine the role of genetic thrombophilic defects in cancer-associated thrombosis in children. The study included 47 children (13 girls and 34 boys) with newly diagnosed cancer, treated at the Division of Hematology and Oncology, Department of Pediatrics, Clinical Hospital Centre Rijeka, between January 2010 and December 2015. Thirty-six patients had hematological malignancies and 11 patients had solid tumors. The median age was 8.8 years (range 0.4 – 19.3 years). Molecular tests on samples of isolated DNA comprised genetic polymorphisms of Factor V (FV Leiden G1691A), prothrombin (FII G20210A) and the enzyme methylenetetrahydrofolate reductase (MTHFR C677T). In the study group, 8.5% were heterozygous for Factor V Leiden, 6.4% were heterozygous for prothrombin G20210A mutation, 6.4% were homozygous for MTHFR C677T mutation, and 10.6% had combined thrombophilic defects. The prevalence of thrombophilic defects was in accordance with the prevalence in general population. There was no difference between boys and girls, and between patients with hematological malignancies and solid tumors. The rate of thrombosis was 8.5%. Three patients had upper extremity deep venous thrombosis and 1 had right atrial thrombosis. In half (2/4) of patients combined Factor V Leiden and MTHFR C677T heterozygosity were identified. Our data suggest that inherited thrombophilia is not related to cancer pathogenesis in children. Inherited thrombophilia may play a role in the pathogenesis of cancer-associated thrombosis. A better understanding of the interactions between genetic and non-genetic causes will help to improve the prophylactic and treatment strategies for thrombosis pediatric oncology patients.