The clinical and genetic landscape of early-onset thrombophilia in Japan.
Pediatr Blood Cancer
; 71(3): e30824, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38155150
ABSTRACT
OBJECTIVES:
To determine the optimal management for early-onset thrombophilia (EOT), the genetic and clinical features of protein C (PC)-, protein S (PS)-, or antithrombin (AT)-deficient patients of ≤20 years of age were studied in Japan. METHODS/RESULTS:
Clinical and genetic information of all genetically diagnosed cases was collected through the prospective, retrospective study, and literature review. One-hundred-one patients had PC (n = 55), PS (n = 29), or AT deficiency (n = 18). One overlapping case had PC- and PS-monoallelic variant. Fifty-five PC-deficient patients (54%) had 26 monoallelic or 29 biallelic variant(s), and 29 (29%) PS-deficient patients had 20 monoallelic or nine biallelic variant(s). None of the patients had AT-biallelic variants. The frequent low-risk allele p.K193del (PC-Tottori) was found in five patients with monoallelic (19%) but not 29 with biallelic variant(s). The most common low-risk allele p.K196E (PS-Tokushima) was found in five with monoallelic (25%) and six with biallelic variant(s) (67%). One exceptional de novo PC variant was found in 32 families with EOT. Only five parents had a history of thromboembolism. Thrombosis concurrently developed in three mother-newborn pairs (two PC deficiency and one AT deficiency). The prospective cohort revealed the outcomes of 35 patients three deaths with PC deficiency and 20 complication-free survivors. Neurological complications were more frequently found in patients with PC-biallelic variants than those with PC-, PS-, or AT-monoallelic variants (73% vs. 24%, p = .019).CONCLUSIONS:
We demonstrate the need for elective screening for EOT targeting PC deficiency in Japan. Early prenatal diagnosis of PC deficiency in mother-infant pairs may prevent perinatal thrombosis in them.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombose
/
Deficiência de Proteína S
/
Trombofilia
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Deficiência de Antitrombina III
/
Deficiência de Proteína C
Limite:
Female
/
Humans
/
Newborn
/
Pregnancy
País/Região como assunto:
Asia
Idioma:
En
Revista:
Pediatr Blood Cancer
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Japão