Hemophilia: An Overview

Hemophilia A (Classic Hemophilia; Factor VIII Deficiency)

Ø   The most common inherited coagulation disorder (after Von Willebrand Disease).

Ø     The factor VIII gene is on the X chromosome so inheritance is sex-linked with the severe disease occurring in males.

Ø     Hemophilia A accounts for 80–85% of all cases of hemophilia with a prevalence of approximately 1 in 5,000–10,000 male births.

Ø     Genetic changes of the factor VIII gene.

Ø     Each son has a 50% chance of inheriting the affected gene.

Ø     Approximately 30% of the affected individuals have no positive family history of the disease.

Clinical Features

Ø     These range from severe spontaneous bleeding, especially into joints (hemarthroses) and muscles, to mild symptoms, depending on the factor VIII level.

Ø     Generally individuals with > 30% activity do not have hemophilia symptoms.

Ø     Onset in early childhood (e.g. post-circumcision).

Ø     Pseudotumours as a result of extensive bleeds.

Ø     Hemarthrosis (usually in severe cases) is the most common feature of severe hemophilia.

Ø     Joint bleeds, particularly into the knee and ankle.

Ø     Chronic debilitating joint disease caused by repeated bleeds.

Ø     Increased risk of post-operative or post-traumatic hemorrhage.

Ø     Subcutaneous hematomas can begin with slight trauma and spread to involve a large mass of tissue, causing purple discoloration of the skin.

Ø     Epistaxis is rare in hemophilia.

Ø     Hematuria.

Ø     Deep muscle bleeding.

Ø     Excess bleeding from dental extractions.

Ø     Bleeding with intramuscular injections.

Ø     Delayed bleeding after minor cuts.

Ø     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.

Ø     Mild deficiencies can be asymptomatic and unsuspected until a surgical procedure or major traumatic injury results in severe bleeding.

Laboratory Data

Ø     APTT >> ↑

Ø     PT >> N

Ø     PFA-100 test >> N

Ø     Plasma Factor VIII >> ↓

Ø     Von Willebrand factor (vWF) >> N

Ø     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

Ø     Infusions of factor VIII (either recombinant or concentrate from normal donated plasma “Cryoprecipitate”).

Ø     Avoid aspirin, other antiplatelet drugs and intramuscular injections.

Ø     Gene Therapy.

Complications of Treatment

Ø     Infections.

Ø     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)

Ø     15–20% of hemophilia.

Ø     ~1 in 30.000 males.

Ø     Factor IX is coded by a gene close to the gene for factor VIII.

Ø     Specific Factor IX Assay.

Ø     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.

Ø     Recombinant factor IX.

Ø     Gene Therapy.

Ø     Clinical features & other laboratory data are same as in hemophilia A.