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Life threatening bleeding under adequate oral anticoagulation. Cases 4a, b
Ch Aegerter1, St Fontana, Ch Fux
1Central Haematology Laboratory, Inselspital, University Hospital Bern, 3010 Bern, Switzerland.
Hamostaseologie
|August 19, 2003
Summary
Two men experienced severe bleeding despite phenprocoumon treatment due to increased factor IX sensitivity. A genetic mutation in factor IX explained their adverse reaction to the anticoagulant therapy.
Area of Science:
- Hematology
- Pharmacogenetics
- Internal Medicine
Background:
- Phenprocoumon is a vitamin K antagonist anticoagulant used to prevent thrombosis.
- Monitoring anticoagulant therapy with the International Normalized Ratio (INR) is crucial for patient safety.
- Activated partial thromboplastin time (aPTT) is another laboratory test used in coagulation monitoring.
Observation:
- Two male patients presented with severe, recurrent bleeding episodes while on phenprocoumon therapy.
- Despite therapeutic INR levels, patients exhibited prolonged aPTT.
- Coagulation factor levels were normal, except for significantly reduced factor IX levels, mimicking hemophilia B.
Findings:
- Patients demonstrated an exaggerated response to phenprocoumon, specifically related to factor IX.
- Genetic analysis revealed a missense mutation (ALA-10) in the factor IX propeptide in both patients.
- Vitamin K administration led to normalization of factor IX and aPTT in one patient, supporting the diagnosis.
Implications:
- This case highlights a rare genetic predisposition to phenprocoumon-induced bleeding due to factor IX abnormalities.
- Genetic screening for factor IX mutations may be warranted in patients with unexplained prolonged responses to vitamin K antagonists.
- Understanding such pharmacogenetic variations is essential for optimizing anticoagulant therapy and preventing adverse events.