Hemophilia

Dr. Anamika Priyadarshinee

Learning objectives
• Describe the etiopathogenesis and complications of Hemophilia A and
Hemophilia B
Hemophilia A (Factor VIII Deficiency)
• Hemophilia A, the most common hereditary disease associated with
life-threatening bleeding, is caused by mutations in factor VIII, an
essential cofactor for factor IX in the coagulation cascade.

• Inherited as an X-linked recessive trait and thus

affects mainly males and homozygous females.
Rarely, excessive bleeding occurs in heterozygous
females
• The frequency of haemophilia varies in different races, the highest
incidence being in populations of Britain, Northern Europe and
Australia
PATHOGENESIS.
• Haemophilia A is caused by quantitative reduction of factor VIII in 90% of
cases, while 10% cases have normal or increased level of factor VIII with
reduced activity.
• Factor VIII is synthesised in hepatic parenchymal cells and regulates the
activation of factor X in intrinsic coagulation pathway.
• Factor VIII circulates in blood complexed to another larger protein, von
Willebrand’s factor (vWF), which comprises 99% of the factor VIII-vWF
complex.
• Normal haemostasis requires 25% factor VIII activity.
• Though occasional patients with 25% factor VIII level may develop bleeding,
most symptomatic haemophilic patients have factor VIII levels below 5%.
CLINICAL FEATURES.
• Patients of haemophilia suffer from bleeding for hours or days after
the injury.
• The clinical severity of the disease correlates well with plasma level of
factor VIII activity.
• Haemophilic bleeding can involve any organ but occurs most
commonly as recurrent painful haemarthroses and muscle
haematomas, and sometimes as haematuria.
• Spontaneous intracranial haemorrhage and oropharyngeal bleeding
are rare, but when they occur they are the most feared complications.
LABORATORY FINDINGS.
• The following tests are abnormal:
1. Whole blood coagulation time is prolonged in severe cases only.
2. Prothrombin time is usually normal.
3. Activated partial thromboplastin time (APTT or PTTK) is typically
prolonged.
4. Specific assay for factor VIII shows lowered activity. The diagnosis of
female carriers is made by the findings of about half the activity of
factor VIII, while the manifest disease is associated with factor VIII
activity below 25%.
Treatment
• Factor VIII replacement therapy, consisting of factor VIII concentrates
or plasma cryoprecipitates.
Christmas Disease (Haemophilia B)
• Inherited deficiency of factor IX (Christmas factor or plasma
thromboplastin component) produces Christmas disease or haemophilia
B.
• Haemophilia B is rarer than haemophilia A; its estimated incidence is 1 in
100,000 male births.
• The inheritance pattern and clinical features of factor IX deficiency are
indistinguishable from those of classic haemophilia but accurate
laboratory diagnosis is critical since haemophilia B requires treatment
with different plasma fraction.
• The usual screening tests for coagulation are similar to those in classic
haemophilia but bioassay of factor IX reveals lowered activity.
TREATMENT.
• Therapy in symptomatic haemophilia B consists of infusion of either
fresh frozen plasma or a plasma enriched with factor IX.
Complication of hemophilia
• Besides the expected possibilities of complications of hepatitis,
chronic liver disease and AIDS, the replacement therapy in factor IX
deficiency may activate the coagulation system and cause thrombosis
and embolism