Haemophilia

Overview

Haemophilia is an inherited, X-linked recessive lifelong bleeding disorder caused by deficiency of clotting factors VIII or IX.

It affects males almost exclusively, while females are usually carriers.

Haemophilia results in impaired thrombin generation and defective fibrin clot formation, leading to prolonged bleeding, particularly into joints and muscles.

The two main types are:

• Haemophilia A: Factor VIII deficiency.

• Haemophilia B: Factor IX deficiency.

Haemophilia A (factor VIII deficiency)

Haemophilia A is the most common hereditary clotting factor deficiency and accounts for approximately 80% of haemophilia cases.

It is caused by deficiency or dysfunction of factor VIII.

Haemophilia B (factor IX deficiency)

Haemophilia B is caused by deficiency of clotting factor IX.

It accounts for approximately 20% of haemophilia cases and is also known as Christmas disease.

Clinical presentation is similar to haemophilia A.

Risk factors

• Male sex.

• Positive family history.

• Carrier mother.

• Spontaneous mutation (de novo cases).

Clinical presentation

Bleeding patterns vary depending on age and severity.

Common features include:

• Spontaneous muscle and joint bleeding without injury.

• Prolonged bleeding after injury, surgery, or procedures.

• Epistaxis.

• Easy bruising.

• Muscle haematomas.

• Recurrent haemarthrosis.

• Post-circumcision bleeding.

• Chronic joint disease.

• Arthropathy and disability.

Common sites of haemarthrosis include:

• Knees.

• Ankles.

• Elbows.

Severe cases may develop:

• Intracranial haemorrhage.

• Retroperitoneal haemorrhage.

• Chronic haemophilic arthropathy.

Classification of haemophilia

Haemophilia severity is classified according to circulating factor VIII or IX levels and predicts bleeding frequency.

Investigations

Screening tests

• Prolonged activated partial thromboplastin time (aPTT).

• Normal prothrombin time (PT).

• Normal platelet count.

Confirmatory tests

• Factor VIII assay for haemophilia A.

• Factor IX assay for haemophilia B.

Additional tests

• Inhibitor screening using aPTT mixing study.

• Bethesda assay (BU) for inhibitor confirmation and quantification.

• Genetic testing where available.

Management of hemophilia

All patients suspected of having haemophilia A or B should be referred to a higher health facility with adequate expertise or a haematology unit.

Non-pharmacological management

• Avoid intramuscular injections.

• Use the smallest gauge needle if injection is necessary.

• Avoid NSAIDs; use paracetamol for pain relief.

• Provide patient and parent education regarding the condition.

• Provide means of alerting healthcare and pharmaceutical personnel.

• Genetic counselling.

• Vaccination against hepatitis A and B where appropriate.

Acute bleeding management

For acute bleeding episodes use RICE:

• Rest.

• Ice/cold pack:

  • Apply for 5 minutes.

  • Remove for 10 minutes.

• Compression.

• Elevation of the affected joint.

For haemarthrosis:

• Avoid incision or aspiration of the affected joint.

• Treat by replacing the specific clotting factor (factor VIII or factor IX concentrate if available).

• Use fresh frozen plasma (FFP) if factor concentrate is unavailable.

• Provide joint support.

• Use paracetamol for pain.

Pharmacological treatment of hemophilia

Avoid NSAIDs.

Haemophilia A (factor VIII deficiency) without inhibitor

Dose depends on bleeding severity.

Minor bleeding:

• Factor VIII IV 20–40 IU/kg.

Major bleeding:

• Factor VIII IV 50–100 IU/kg 12 hourly for 3–5 days or until bleeding stops.

Expected response:

• 1 IU/kg produces approximately 2% rise in factor VIII level.

Half-life:

• Factor VIII: 8–24 hours.

Repeat dosing according to clinical response and factor level monitoring.

Haemophilia B (factor IX deficiency) without inhibitor

Dose depends on bleeding severity.

Minor bleeding:

• Factor IX IV 20–50 IU/kg.

Major bleeding:

• Factor IX IV 100 IU/kg.

Expected response:

• 1 IU/kg produces approximately 1–1.5% rise in factor IX level.

Half-life:

• Factor IX: 16–24 hours.

When factor concentrates are unavailable

• Fresh frozen plasma (FFP) 10–15 ml/kg.

Cryoprecipitate may be considered for haemophilia A when factor VIII concentrate is unavailable.

Inhibitor management

If there is no response to appropriate replacement therapy, test for inhibitors.

An inhibitor is an antibody formed against factor concentrates.

Diagnosis:

• aPTT mixing study.

• Bethesda assay (BU).

Management options:

• High-dose factor concentrate infusion.

OR

• Bypass agents such as FEIBA (factor eight inhibitor bypassing agent).

OR

• Recombinant factor VIIa where available.

OR

• Immune tolerance induction therapy (ITI).

OR

• Plasmapheresis in emergency surgery.

AND

• Antifibrinolytic agents such as tranexamic acid may be used as adjunct treatment except in urinary tract bleeding.

Prophylaxis

Children with severe haemophilia are recommended to receive low-dose prophylaxis with factor concentrate.

Benefits include:

• Prevention of recurrent joint bleeding.

• Prevention of haemophilic arthropathy.

• Preservation of joint function.

Circumcision

Male circumcision should be performed in a hospital where factor concentrate is available.

• Factor concentrate should be given before and after the procedure.

Complications

• Chronic haemophilic arthropathy.

• Joint deformity.

• Disability.

• Intracranial haemorrhage.

• Inhibitor development.

• Transfusion-related infections (historically).

Prevention

• Carrier detection.

• Prenatal diagnosis where available.

• Genetic counselling.

• Safe delivery planning.

• Early prophylaxis for severe disease.

• Multidisciplinary care.