Overview
Definition
Inherited bleeding disorders caused by deficiencies of specific clotting factors (Factor VIII in Hemophilia A, Factor IX in Hemophilia B).
Epidemiology
Hemophilia A is much more common than B. Because it is X-linked recessive, it almost exclusively affects males.
Etiology & Risk Factors
- X-linked recessive genetic mutation.
- Hemophilia A = Factor VIII deficiency.
- Hemophilia B (Christmas Disease) = Factor IX deficiency.
Clinical Symptoms
- Hemarthrosis (spontaneous bleeding into joints, leading to severe pain and swelling, most commonly the knee)
- Intramuscular hematomas
- Prolonged bleeding after dental extractions or minor surgeries
- Intracranial hemorrhage (a major cause of death)
Clinical Approach
Diagnosis
- Coagulation Studies: Prolonged aPTT (intrinsic pathway defect), Normal PT (extrinsic pathway intact), Normal Platelet count, Normal Bleeding Time
- Mixing study: aPTT corrects when mixed with normal plasma (proves a factor deficiency rather than an inhibitor)
- Factor Assays (Gold Standard): Specific deficiency of Factor VIII or IX determines the type
Management
- Factor replacement therapy (IV recombinant Factor VIII or IX) during acute bleeding or prophylactically
- Desmopressin (DDAVP) for mild Hemophilia A (stimulates release of vWF and Factor VIII from endothelial cells)
- Emicizumab (bispecific antibody) for Hemophilia A prophylaxis
Complications
- Hemophilic arthropathy (joint destruction from recurrent bleeding)
- Development of factor inhibitors (antibodies neutralizing the replacement factors)