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Antithrombin "Chicago": a functionally abnormal molecule with increased heparin affinity causing familial
Blood
|December 1, 1983
Summary
A family exhibits a high rate of spontaneous blood clots due to a defective antithrombin protein. This genetic defect impairs the body's natural clotting regulation, leading to recurrent thrombosis.
Area of Science:
- Genetics
- Hematology
- Molecular Biology
Background:
- Investigated a family with a high incidence of spontaneous thromboembolism across four generations.
- Focused on a 21-year-old male with a history of thrombophlebitis and 46 family members.
Observation:
- Twelve family members experienced deep venous thromboses and/or pulmonary emboli.
- Seven subjects with thrombotic history showed normal immunoreactive antithrombin but reduced progressive antithrombin activity and heparin cofactor activity.
Findings:
- Identified an abnormal antithrombin variant, termed "Chicago," eluting differently from heparin-Sepharose.
- Functionally defective antithrombin molecules showed significantly reduced ability to neutralize thrombin, with or without heparin.
Implications:
- The molecular defect in antithrombin "Chicago" is distinct from previously described abnormal antithrombins.
- Highlights a novel genetic cause of hereditary thrombophilia.
- Suggests potential for targeted anticoagulant therapies based on specific antithrombin defects.