Homozygous antithrombin deficiency type II causing neonatal thrombosis

Area of Science:

• Genetics
• Hematology
• Pediatrics

Background:

• Antithrombin (AT) deficiency is a rare inherited condition increasing thrombosis risk.
• Type II AT deficiency specifically impacts the heparin-binding site, affecting anticoagulant function.
• Homozygous deficiency is exceptionally rare and presents unique clinical challenges.

Observation:

• Four unrelated children presented with severe, spontaneous venous and/or arterial thromboembolic events shortly after birth.
• All affected children had homozygous antithrombin deficiency type II (p.Leu131Phe mutation).
• Clinical presentation included life-threatening thrombotic events in the neonatal period.

Findings:

• Homozygous AT deficiency type II can manifest with severe neonatal thrombosis.
• AT activity levels in affected individuals may be reduced or appear normal, complicating diagnosis.
• Standard heparin anticoagulation can be ineffective in severe AT deficiency.

Implications:

• This condition highlights the importance of considering severe congenital thrombophilia in neonates with unexplained thrombosis.
• Prompt diagnosis is critical for initiating effective treatment, including AT concentrate substitution.
• Management requires careful consideration of anticoagulation strategies, potentially involving vitamin K antagonists.