Cerebral infarction in a heterozygote with variant antithrombin III

Area of Science:

• Cardiovascular Medicine
• Hematology
• Genetics

Background:

• Familial qualitative antithrombin III deficiency is a rare inherited bleeding disorder.
• Cerebral infarction in young adults can be linked to thrombophilia.
• Antithrombin III plays a crucial role in regulating coagulation.

Observation:

• A 33-year-old male presented with recurrent transient ischemic attacks and confirmed cerebral infarction.
• Diagnostic evaluations revealed normal antithrombin III antigen and progressive activity but low heparin cofactor activity in the patient and his father.
• Genetic analysis did not identify mutations in key exons of the antithrombin III gene.

Findings:

• The patient exhibited a heterozygous qualitative deficiency of antithrombin III.
• The identified antithrombin III variant, named "Antithrombin III Nagasaki," demonstrated defective heparin binding.
• This qualitative defect, despite being heterozygous, was associated with ischemic stroke.

Implications:

• Abnormal antithrombin III variants with impaired heparin binding can cause ischemic stroke in young adults.
• Early diagnosis and genetic counseling are crucial for families with qualitative antithrombin III deficiency.
• Further research into antithrombin III variants can improve understanding of thrombotic disorders.