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Haematologica 2019 Volume 104(12):2512-2518
Coagulation & its Disorders
Incidence and features of thrombosis in children with inherited antithrombin deficiency
Belén de la Morena-Barrio,1 Christelle Orlando,2 María Eugenia
de la Morena-Barrio,1 Vicente Vicente,1 Kristin Jochmans2 and Javier Corral1
1Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, CIBERER, Murcia, Spain and 2Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel) Department of Haematology, Brussels, Belgium
*BM-B and CO contributed equally to this work.
ABSTRACT
Pediatric thromboembolism (≤18 years) is very rare (0.07- 0.14/10,000/year) but may be more prevalent in children with severe thrombophilia (protein C, protein S or antithrombin deficiency). The aim of this study was to define the prevalence and clinical characteristics of pediatric thrombosis in subjects with inherited antithrombin deficiency. Our observational retrospective multicentric study from two countries recruited 968 patients of any age from 441 unrelated families with geneti- cally, biochemically and functionally characterized antithrombin deficiency. Seventy-three subjects (7.5%) developed thrombosis before 19 years of age. Two high-risk periods for thrombosis were identified: adolescence (12-18 years, n=49) with thrombus localization (lower limb deep venous thrombo- sis or pulmonary embolism) and triggering factors common to adults (oral contraceptives, surgery or pregnancy); and the neonatal period (<30 days, n=15) with idiopathic thrombosis at unusual sites. The clinical evaluation of pediatric thrombosis in subjects with antithrombin deficiency revealed: i) a high prevalence of cerebral sinovenous thrombosis (n=13, 17.8%), mainly at young age (8 neonates and 4 children <6 years); ii) severe out- come with fatality in six cases (3 neonates, two of them homozygous for p.Leu131Phe). The majority of subjects (76.7%) carried quantitative type I deficiency. This retrospective analysis includes the largest cohort of subjects with inherited antithrombin deficiency so far and provides strong evidence for an increased risk of pediatric thrombosis associated with this throm- bophilia (300-fold compared with the general population: 0.41%/year vs. 0.0014%/year, respectively). Our results support testing for antithrombin deficiency in children of affected families, particularly in case of type I defi- ciency.
Introduction
Thromboembolism is a life-threatening event that significantly contributes to the global disease burden.1 Age is the main risk factor for developing venous throm- boembolism (VTE).2 Thrombosis in the pediatric population is rare, with incidences ranging from 0.07 to 0.14 per 10,000 children aged ≤18 years per year. Nowadays, these numbers are growing as a result of better diagnosis, improved survival of chil- dren with severe underlying diseases, and increased use of invasive procedures and instruments.3 Pediatric thrombosis is recognized as an important complication of severe medical conditions such as sepsis, cancer, congenital heart disease, and the use of pharmaceutical drugs such as asparaginase and estrogen-containing contra- ceptives. Surgery and invasive procedures, particularly placement of central venous catheters, are thrombogenic conditions involving around 50% of pediatric VTE, a number that rises to more than 90% in neonates.4 According to data obtained from case series, case-control studies, registries and cohort studies, thrombophilia is a
Correspondence:
JAVIER CORRAL/
javier.corral@carm.es
KRISTIN JOCHMANS
kristin.jochmans@uzbrussel.be
Received: October 31, 2018. Accepted: April 9, 2019. Pre-published: April 11, 2019.
doi:10.3324/haematol.2018.210666
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/12/2512
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