Language：English   Publisher：Journal of Perinatology  

Objective: This prospective study compared PIVKA-II and PT-INR levels in infants who received two vitamin K (VK) prophylactic regimens. Methods: A single institution administered 119 healthy newborns 2 mg of VK syrup. Infants were assigned to a 3-time regimen (n = 56) with VK at birth, five days (5D), and 1-month-old (1 M), or a 13-time regimen (n = 63) with VK at birth, 5D, and then weekly for 11 weeks. Results: The 13-time regimen significantly lowered PIVKA-II and reduced PT-INR at 1 M in both breastfed (PIVKA-II: 18–16 mAU/mL, p = 0.02; PT-INR: 1.37–1.13, p < 0.01) and formula-fed infants (PIVKA-II: 18–15 mAU/mL, p = 0.01; PT-INR: 1.54–1.24, p < 0.01), compared to baseline measurements taken at 5D. The 3-time regimen did not significantly alter PIVKA-II levels and only improved PT-INR (2.00–1.50, p < 0.01) in formula-fed infants. Conclusion: The 13-time VK regimen significantly enhanced coagulation profiles more effectively than the 3-time regimen.

DOI： 10.1038/s41372-024-01981-9

Web of Science

Scopus

PubMed

Language：English   Publisher：Pediatric Blood and Cancer  

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.

DOI： 10.1002/pbc.30824

Web of Science

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PubMed

Publisher：金原出版  

DOI： 10.18888/sh.0000002834

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1543209120

CiNii Research

Language：English   Publisher：AJP Reports  

Ductus arteriosus aneurysm (DAA) asymptomatically occurs in newborn infants and resolves spontaneously. High-risk DAA with compression, rupture, and thrombosis requires early surgical intervention. Newborn infants have the highest risk of thrombosis among pediatric patients, but the genetic predisposition is difficult to determine in infancy. We herein report a neonatal case of massive thromboses in DAA and pulmonary artery. Desaturation occurred in an active full-term infant 2 days after birth. Echocardiography and contrast-enhanced computed tomography indicated thrombotic occlusion of the DAA and pulmonary artery thrombus. Urgent thrombectomy and ductus resection were successfully performed. After 6 months of anticoagulant therapy, the dissociated low plasma activity levels of protein S from protein C suggested protein S deficiency. A genetic study of PROS1 identified a heterozygous variant of protein S K196E, a low-risk variant of thrombophilia in Japanese populations. There have been seven reported cases with neonatal-onset symptomatic thromboses of DAA involving the pulmonary artery. All survived without recurrence after surgical intervention in five and anticoagulant therapy alone in two. Two newborns had a heterozygous methylenetetrahydrofolate reductase (MTHFR) variant, but information on thrombophilia was not available for any other cases. A genetic predisposition may raise the risk of DAA thrombosis, leading to rapid progression.

DOI： 10.1055/a-2101-7738

Web of Science

Scopus

PubMed

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese   Publisher：(株)日本臨床社  

Language：Japanese   Publisher：金原出版(株)  

＜文献概要＞KEY POINTS　・小児の血液凝固・線溶系検査は,まれな重症疾患の治療開始時期を逸せぬよう,最小の検査項目数と検体量で迅速に施行し,結果を正しく判断する.・適切な検査項目を選択するために,凝固系,凝固制御系,線溶系の年齢に応じた成熟過程を理解し,検査項目ごとに特徴を把握する.・凝固と線溶は生体防御のため相反する機能の複雑な制御系である.成人患者よりも検体採取手技の影響も受けやすいため,1つの検査結果だけでなく複数の結果から複合的に凝固・線溶系の状態を把握することが重要である.

Language：Japanese   Publisher：(株)医学書院  

Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

小児血栓症患者における遺伝素因の報告が増えている。小児期は年齢ごとに発症リスクが異なり,遺伝素因の寄与度も様々である。20歳までに発症する血栓症のうち遺伝素因が関与するものを"早発型遺伝性血栓症(early-onset thrombophilia,EOT)"として登録し,網羅的文献検索と併せて本邦患者の遺伝的背景と臨床経過を明らかにした。患者の60%以上をプロテインC(PC)欠乏症が占め,その半分以上が片アレル変異の保有者だった。年齢とともにプロテインS(PS)およびアンチトロンビン欠乏症が増加して主体となった。6～8歳の発症はなかった。日本人高頻度・低リスクバリアントのPC-TottoriとPS-Tokushimaも確認されたが,前者は重症PC欠乏症の発症に寄与していなかった。解析した32家系中de novo発症は1家系のみで,周産期の同時発症母子例が3家系あった。PC欠乏症を標的に適切なEOTスクリーニングを行って周産期血栓症から母子を守ることが期待される。(著者抄録)

Language：Japanese   Publisher：日本産婦人科・新生児血液学会  

新生児期の血栓症は希少な事例と考えられてきたが、医療の高度化と疾患認識の広がりにより報告数が増加している。さらに、日本人小児の血栓性素因における遺伝性プロテインC欠乏症の重要性が示されてきた。今回私たちは新生児血栓症の全国調査を行い、遺伝性プロテインC欠乏症の遺伝学的効果と、遺伝学的検査の悉皆性を示すことができた。今後は調査対象を小児から成人に達するまでに拡大し、小児患者とその家族を血栓症から守る個別化医療の確立を目指す。(著者抄録)