Hemophilia A (Classic Hemophilia;
Factor VIII Deficiency)
Ø The most common inherited coagulation disorder (after Von Willebrand Disease).
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The factor VIII gene is on the X chromosome so inheritance
is sex-linked with the severe disease occurring in males.
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Hemophilia A accounts for 80–85% of all cases of hemophilia
with a prevalence of approximately 1
in 5,000–10,000 male births.
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Genetic changes of the factor VIII gene.
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Each son has a 50% chance of inheriting the affected gene.
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Approximately 30% of the affected individuals have no
positive family history of the disease.
Clinical
Features
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These range from severe spontaneous bleeding, especially
into joints (hemarthroses) and muscles, to mild symptoms, depending on the
factor VIII level.
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Generally individuals with > 30% activity do not have
hemophilia symptoms.
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Onset in early childhood (e.g. post-circumcision).
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Pseudotumours as a result of extensive bleeds.
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Hemarthrosis (usually in severe cases) is the most common
feature of severe hemophilia.
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Joint bleeds, particularly into the knee and ankle.
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Chronic debilitating joint disease caused by repeated
bleeds.
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Increased risk of post-operative or post-traumatic
hemorrhage.
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Subcutaneous hematomas can begin with slight trauma and
spread to involve a large mass of tissue, causing purple discoloration of the
skin.
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Epistaxis is rare in hemophilia.
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Hematuria.
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Deep muscle bleeding.
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Excess bleeding from dental extractions.
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Bleeding with intramuscular injections.
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Delayed bleeding after minor cuts.
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The most common cause of death (after exclusion of viral
infections transmitted by the replacement product) is intracranial hemorrhage,
which can occur spontaneously or after trauma.
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Mild deficiencies can be asymptomatic and unsuspected until
a surgical procedure or major traumatic injury results in severe bleeding.
Laboratory
Data
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APTT >> ↑
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PT >> N
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PFA-100 test >> N
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Plasma Factor VIII >> ↓
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Von Willebrand factor (vWF) >> N
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Carriers have factor VIII levels in plasma approximately 50%
of normal. If the levels are <40% they may have clinical features of mild
hemophilia. DNA analysis is helpful in carrier detection and antenatal
diagnosis.
Treatment
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Infusions of factor VIII (either recombinant or concentrate
from normal donated plasma “Cryoprecipitate”).
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Avoid aspirin, other antiplatelet drugs and intramuscular
injections.
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Gene Therapy.
Complications
of Treatment
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Infections.
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Neutralizing antibodies (inhibitors) to factor VIII in 15%
of severe patients may require:
§
Immunosuppressive therapy,
§
Treatment with porcine factor VIII, or
§
Plasma exchange.
Hemophilia B (Factor IX
Deficiency; Christmas Disease)
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15–20% of hemophilia.
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~1 in 30.000 males.
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Factor IX is coded by a gene close to the gene for factor
VIII.
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Specific Factor IX Assay.
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Bleeding episodes are treated with high - purity factor IX
concentrates. Because of its longer biological half-life, infusions do not have
to be given as frequently as do factor VIII concentrates in haemophilia A.
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Recombinant factor IX.
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Gene Therapy.
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Clinical features & other laboratory data are
same as in hemophilia A.
