Hemophilia is the most common inherited severe bleeding disorder, characterized by deficiency of clotting factor VIII (Hemophilia A) or factor IX (Hemophilia B). It is an X-linked recessive disorder and predominantly affects males, while females are typically carriers.

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

Although von Willebrand disease (VWD) is the most common inherited bleeding disorder overall, this section focuses exclusively on hemophilia A and B.

Types of Hemophilia

A. Hemophilia A (Factor VIII Deficiency)

• Accounts for ~80% of cases

• Caused by deficiency or dysfunction of factor VIII

• Approximately 30–33% arise from spontaneous mutation

• X-linked inheritance

B. Hemophilia B (Factor IX Deficiency)

• Accounts for ~20% of cases

• Also known as Christmas disease

• Clinical presentation similar to Hemophilia A

• X-linked inheritance

Classification by Severity

Severity is determined by circulating factor level:

Severity predicts bleeding frequency and guides prophylaxis decisions.

Risk Factors

• Male sex

• Positive family history

• Carrier mother

• Spontaneous mutation (de novo cases)

Clinical Presentation

Bleeding pattern varies with age.

Infants

• Soft tissue bleeding

• Oral mucosal bleeding

• Post-circumcision bleeding

Children & Adolescents

• Recurrent hemarthrosis (knees, ankles, elbows)

• Muscle hematomas

• Prolonged bleeding after minor injury

Adults

• Chronic joint disease

• Disability due to arthropathy

Common Clinical Features

Hemophilia A

• Spontaneous joint bleeding

• Muscle hematomas

• Retroperitoneal hemorrhage

• Epistaxis

• Easy bruising

• Postoperative bleeding

• Hemophilic arthropathy (chronic complication)

Hemophilia B

• Clinical features similar to Hemophilia A

• Generally less common

Diagnostic Criteria

Diagnosis is based on:

1. Clinical bleeding history

2. Family history

3. Laboratory confirmation

Investigations

Screening Tests

• Prolonged aPTT

• Normal PT

• Normal platelet count

• Normal bleeding time

Confirmatory Tests

• Factor VIII assay (Hemophilia A)

• Factor IX assay (Hemophilia B)

Additional Tests

• Inhibitor screening (mixing study)

• Bethesda assay for inhibitor quantification

• Genetic testing for mutation identification

Management

All suspected cases should be referred to a specialized hemophilia treatment center.

A. Non-Pharmacological Management

• Avoid intramuscular injections

• Avoid NSAIDs (use paracetamol for pain)

• Use smallest gauge needle if injection necessary

• Joint immobilization during acute hemarthrosis

• Physiotherapy for joint preservation

• Genetic counseling

• Vaccinate against hepatitis A & B

B. Pharmacological Management

1. Hemophilia A (No Inhibitor)

Dose depends on severity of bleed.

Minor Bleeding

• Factor VIII: 20–40 IU/kg

Major Bleeding

• Factor VIII: 50–100 IU/kg

Expected response:

• 1 IU/kg → 2% rise in factor VIII

Half-life:

• 8–12 hours (up to 24 hrs in some cases)

Repeat dosing based on clinical response and factor level monitoring.

2. Hemophilia B (No Inhibitor)

Minor Bleeding

• Factor IX: 20–50 IU/kg

Major Bleeding

• Factor IX: 100 IU/kg

Expected response:

• 1 IU/kg → 1–1.5% rise in factor IX

Half-life:

• 16–24 hours

3. When Factor Concentrates Are Unavailable

• Fresh Frozen Plasma (FFP): 10–15 ml/kg

• Cryoprecipitate (for Hemophilia A if FVIII concentrate unavailable)

Inhibitor Management

Inhibitors are antibodies against factor VIII or IX.

Suspect if:

• Poor clinical response

• Failure of expected factor rise

Confirm with:

• Mixing study

• Bethesda assay (BU)

Management Options

• High-dose factor concentrate

• Bypass agents:

  • Activated prothrombin complex concentrate (FEIBA)

  • Recombinant factor VIIa (NovoSeven)

• Immune tolerance induction (ITI)

• Plasmapheresis (emergency surgery)

• Adjunct antifibrinolytics (except in urinary tract bleeding)

Prophylaxis

Primary Prophylaxis

• Regular low-dose factor concentrate in severe hemophilia

• Initiated before joint damage

Secondary Prophylaxis

• After first joint bleed to prevent recurrence

Complications

• Chronic hemophilic arthropathy

• Joint deformity

• Disability

• Intracranial hemorrhage

• Inhibitor development

• Transfusion-related infections (historically)

Prevention

• Carrier detection

• Prenatal diagnosis

• Genetic counseling

• Safe delivery planning

• Early prophylaxis in severe cases

• Multidisciplinary care