Thursday, April 7, 2016

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.



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