HEMOPHILIAS

General Overview:

• Hemophilia A: Deficiency of factor VIII (commonest type).
• Hemophilia B: Deficiency of factor IX (Christmas factor).
• Hemophilia C: Deficiency of factor XI (plasma thromboplastin antecedent).
• All produce similar manifestations but differ in severity.

Hemophilia A (Classical Hemophilia)

• Most serious bleeding disorder (though VWD is most common).
• Severe hereditary coagulation disorder.
• Deficiency of factor VIII.
• Transmission: X-linked recessive trait (carrier female, affected male; typically from mother’s side).
• Family History: Positive in most cases, but can be de novo mutation.

Severity Classification

Classification	Factor level (%)	Bleeding phenotype
Severe	<1	Spontaneous bleeding (especially large joints)
Moderate	1 - 5	Bleeding on minor trauma
Mild	6 - 40	Bleeding on major trauma/surgery

Clinical Picture

Can appear from very early life (median age of discovery around 10 months when crawling/walking):

• Easy bruising and large subcutaneous hematomas.
• Prolonged bleeding after circumcision or cuts.
• Newborns: Risk of intracranial hemorrhage (rare).
• Deep Hematomas: Intramuscular (e.g., calf, spinal muscles) after slight trauma.
• Mucous Membrane Bleeding: Epistaxis, dental, GIT bleeding.
• Hematuria.
• Hemarthroses (Hallmark): Bleeding into large joints (Knee, Ankle, Elbow) causing pain, swelling, and potential crippling/loss of motor function.
• Dangerous Sites: CNS (intracranial/spinal), intraocular, neck (retropharyngeal), retroperitoneal.

deep echymosis hemarthrosis in ankle - bracelet should be worn all the time

Investigations

• Coagulation Profile:
  • Prolonged aPTT: Usually >120 seconds.
  • Normal PT (intrinsic pathway affected).
  • Normal Bleeding Time.
  • Normal Platelet Count (CBC).
• Factor VIII Assay: Reduced level (assess degree for severity).
• Prenatal Diagnosis: Available for families with history.
• Clinical context: Large hematoma after IM vaccination.

Treatment

General Considerations:

• Prevention: Avoid trauma, wear medical bracelet at all times.
• Injections: Avoid IM; use subcutaneous, nasal, or oral routes for vaccinations.
• Blood sampling: Avoid large veins.
• Monitoring: Mother should observe for changes in joint size (early hemarthrosis).

Replacement Therapy (Factor VIII):

• Prophylactic: Regular doses to normalize hemostasis.
  • Severe (<1%): 3x weekly for Hemophilia A; 2x weekly for Hemophilia B.
  • Start if joint hemorrhage occurs or in mild/moderate cases with hemarthrosis.
• Active Bleeding/Surgery: Every 12 hours.
  • Mild-Moderate: Raise factor to 35–50%.
  • Severe/Life-threatening: Raise level to 100%.
• Products: Plasma-derived, monoclonal-antibody purified, recombinant FVIII.

Pharmacotherapy:

• Desmopressin (DDAVP): IV, SC, or intranasal. Stimulates endogenous release of FVIII:C and vWF. Sufficient for mild forms.

Multidisciplinary Care:

• Physiotherapy: Preserve muscle strength, avoid immobilization damage.
• Orthopedic: Treatment for arthritis.
• Psychological support.

Rox Factor VIII (Technical Specifications)

For qualitative changes in distribution of Factor VIII activity in plasma and Factor VIII containing hemophilia:

• 2 x Reagent 1: 0.015
• 2 x Reagent 2: 0.025
• 1 x Tris: (Kcal buffer, 1000)
• 2 x FITC: (Cytosine, 1000)
• 1 x 10^6 U/ml (pH 4.4)
• 1 x 10^6 U/ml (pH 4.4)

---

Hemophilia B (Christmas Disease)

• Transmission: X-linked recessive trait.
• Deficiency: Factor IX. (9)
• Manifestations: Similar to Hemophilia A but often milder.
• Treatment: Factor IX concentrate (prophylaxis 2x weekly).

---