Inherited Pro-Thrombotic Risk Factors in Children of South Moravia Region, Czech Republic
Authors: Zapletal Ondrej , Blatny Jan , Janousova Eva 
Published: October 2019

Abstract
Abstract 5136

Introduction:
Pro-thrombotic risk factors are associated with increased risk of thrombosis. Some of them are inherited, but clinical manifestation of thrombosis in childhood is rare. It is most likely to appear in the adulthood. When leading to thrombosis during childhood, risk factors must be either very strong (e. g. homozygous deficiency of natural coagulation inhibitors), or must act together with other, usually acquired factors.

Aims:
- To analyse data of children referred for thrombophilia screening to Thrombosis Haemostasis centre, Dpt. of Paediatric Haematology University Hospital Brno, Czech Republic in years 2005–09.
- To specify the characteristics of that cohort and identify the reasons for referral.
-To determine prevalence of respective risk factors (RF) in children within study cohort.
-To analyse possible correlation between related RF findings (ProC Global and FV Leiden, Protein C, Protein S; homocystein and MTHFR C677T polymorphism).

Methods:
We have collected data of all consecutive children aged from 0 to 18 years referred to our out-patient clinic for assessment of inherited thrombophilia in years 2005–2009 for any reason. Data recorded for each patient were as follows: age, gender, reason for assessment, thrombotic event and its type (if applicable) and vascular anomalies. Laboratory examinations done: FV Leiden mutation, Prothrombin gene mutation G20210A, MTHFR C677T polymorphism, protein C, protein S and Antithrombin levels, coagulation activity of F VIII, ProC Global test, homocystein and lipoprotein (a) level. Data were statistically analyzed to reach the aims of the study.

Results:
Data of 849 Caucasian children aged 0–18 years were available for analysis, 475 girls (55. 9 %) and 374 boys (44. 1 %). Median age was 11 years at the time of referral, boys 10 years, girls 13 years. Reasons for thrombophilia screening were as follows: family history of thrombosis/thrombophilia (70. 6 %), vascular anomaly (10. 8 %), thrombotic event (8 %) and others (10. 6 %). Thrombophilia screening was in more than 70 % of children performed before 15 years of age. Thrombotic event has been recorded in 79 patients (9. 3 %), both arterial (37. 6 %) and venous (63. 3 %). Adolescent patients had significantly more thrombotic events than younger children. Most of them were venous thromboses. Ischemic strokes and other arterial events were relatively more frequent in younger children. Frequency of “positive” laboratory findings in the studied cohort were as follows: MTHFR 60. 3 %, positive ProC Global test findings 58. 1 %, FV Leiden (heterozygous)37 %, hyperlipoproteinemia (a) 28. 5 %, protein S deficiency 11. 3 %, high FVIII activity 9. 4 %, Prothrombin gene mutation (heterozygous) 7. 7 %, Antithrombin deficiency 2. 7 %, elevation of homocystein 1. 6 % and protein C deficiency 1 %. Findings have confirmed high sensitivity of ProC Global test to the pathology in protein C pathway, particularly to FV Leiden mutation (sensitivity 98. 4 %). There was no statistically significant relation between homocystein level and MTHFR polymorphism status. Prevalence of RF in study cohort was found to be similar to the literature data. Deficiencies of natural coagulation inhibitors (AT, PC and PS) were rare, pro-thrombotic mutations were more frequent. Data suggest, that role of inherited pro-thrombotic risk factors in the development of thrombotic event in children is not the major one. It is very likely, that more potent risk factors, often acquired ones, are often important for development of thrombotic event during childhood.

Conclusions:
In our centre, we assessed proximately 170 children referred for thrombophilia screening per year. The incidence is thus 8 children per 10000. During 2005–09the main reason for referral was positive family history, but children were often referred in younger age, than recommended. The evidence available to date suggests that it is neither necessary nor useful to examine asymptomatic children before they reach puberty. Finding of inherited thrombophilia, and thus possibility to use measures preventing eventual thrombotic event, are more important in adolescence and adulthood rather than in younger age. In children with thrombotic event, however, it is recommended to screen for inherited risks. Diagnosis and treatment of thrombotic event in children requires a specialised care and relevant expertise of the Paediatric Thrombosis Haemostasis centre.

Disclosures:
No relevant conflicts of interest to declare.