PB2426 CLINICAL MANIFESTATION OF HEREDITARY THROMBOPHILIA IN CHILDREN
Authors: S. Hoduleva, A. Silin, I. Romashevskaya, A. Demidenko, Y. Yarets, A. Klimenkov, E. Mitsura
Journal: HemaSphere (2019)

Background: Venous thromboembolism (VTE) in children is becoming a more frequent problem. The pathogenesis of thrombosis is complex: thrombophilia, background disease, trigger factor. Special attention should be deserved to hereditary thrombophilia (HT), which from childhood can be accompanied by persistent disorders in the hemostasis system and significantly increase the risk of thrombosis. Aims: To assess the influence of HT on the development of venous thromboembolic complications in children. Methods: We have examined 24 patients aged from 1 day to 18 years, who had various types of thrombotic manifestations (n = 20) or the threat thereof taking into account the family history (n = 4). The average age of children was 5.6 years, the ratio of girls to boys was 1.4 / 1.0. All patients underwent a full laboratory examination aimed at the diagnosis of HT and antiphospholipid syndrome (APS): levels of antithrombin III (ATIII), protein C and S, antibodies to β2‐glycoprotein and cardiolipin, lupus anticoagulant, homocysteine level. Molecular genetic testing included thrombogenic mutations and polymorphisms. Results: In half of the cases of VTE, the lower extremity deep vein thrombosis of was diagnosed. Venous sinus thrombosis ‐ in 20% of the examined (n = 4); pulmonary artery thromboembolism in one case; thrombosis in the pool of the portal and superior vena cava ‐ in 35%. VTE recurrences were observed in 20% of cases. The diagnosis of HT is verified in 62.5% of all examined children and in 55% of children with thrombosis. The HT variants were distributed in the following way: 33.3% ‐ mutation in the FV Leiden (het) gene; 20% ‐ in the prothrombin G20210A (het) gene; AT III deficiency was diagnosed in three patients (20%); combined mutations in MTHFRC‐677T (T/T) and PAI‐1 (4G/4G) genes‐ 26.7%. MTHFRC‐677T (T/T) mutations in two cases were accompanied by moderate hyperhomocysteinemia. Trigger factors for VTE not associated with HT were background diseases and its associated complications: acute lymphoblastic leukemia (n = 4); parenteral nutrition (n = 1); operative interventions (n = 2); autoimmune diseases (n = 2) and APS (n = 1). Clinical manifestation of HT in 63.3% of cases was observed in patients over 10 years old. In 72.7% of cases, VTE occurred spontaneously. The earliest spontaneous VTE was detected in a child at the age of 1 day (portal vein thrombosis). In 75% of cases of recurrent VTE, HT has occurred. Summary/Conclusion: Hereditary thrombophilia is a sign of the potential risk of thrombosis in children. Clinical manifestation of VTE occurs at any location, at any age, but significantly more often in children older than 10 years. The presence of HT is a high risk factor for recurrent and spontaneous VTE. Diagnosis of HT is reasonable to carry out in all cases of VTE in children, which is important not only for assessment of the risk of repeated thrombotic episodes, but also for selecting the antithrombotic therapy regimen and optimizing preventive measures.