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Describe haemophilia with its genetics, clinical features and laboratory diagnosis.

Pathology · 2nd Professional — Para-Clinical

Definition and Genetics

Haemophilia is an inherited deficiency of a coagulation factor, causing delayed, deep bleeding.

Type	Deficient factor	Share	Inheritance
Haemophilia A	Factor VIII	About 85%	X-linked recessive
Haemophilia B (Christmas disease)	Factor IX	About 15%	X-linked recessive
Haemophilia C	Factor XI	Rare	Autosomal — affects both sexes

Males are affected; females are carriers. A daughter of an affected father is an obligate carrier; a son of a carrier has a 50% chance of disease
About 30% arise from a new mutation with no family history at all
A and B are clinically indistinguishable and are separated only by factor assay

Severity and Clinical Features

Severity	Factor level	Bleeding pattern
Severe	Under 1%	Spontaneous bleeding into joints and muscles from infancy
Moderate	1–5%	Bleeding after minor trauma
Mild	5–40%	Bleeding only after significant trauma or surgery; may present in adulthood after a dental extraction

Haemarthrosis is the hallmark — the knee, elbow and ankle; painful and warm, and repeated episodes produce synovial hypertrophy, cartilage destruction and crippling haemophilic arthropathy with a "target joint"
Muscle haematoma — the iliopsoas haematoma can be occult and cause femoral nerve palsy and shock
Delayed bleeding after surgery or dental extraction, often after the patient has been sent home
Intracranial haemorrhage is the commonest cause of death
NO petechiae — platelet function is normal

CLINICAL PEARL

Haemophilia bleeds late and deep; ITP bleeds early and superficially. The platelet plug forms normally in haemophilia, so the initial bleeding stops — and then restarts hours later when the unstabilised plug breaks down. That single observation explains the whole clinical picture and distinguishes it at the bedside.

Laboratory Findings

Test	Result
APTT	Prolonged
PT / INR	Normal
Platelet count	Normal
Bleeding time	Normal
Mixing study with normal plasma	APTT corrects — confirming a deficiency rather than an inhibitor
Factor VIII or IX assay	Reduced — diagnostic and defines severity
Von Willebrand factor	Normal — distinguishing it from von Willebrand disease

Applied Aspects

Treatment is factor replacement — recombinant factor VIII or IX; prophylaxis two or three times weekly in severe disease prevents arthropathy and has transformed outcomes
Desmopressin (DDAVP) releases stored factor VIII from endothelium and is useful in mild haemophilia A only — it does nothing in haemophilia B
Tranexamic acid is a useful adjunct for mucosal and dental bleeding
Inhibitors (alloantibodies against the infused factor) develop in up to 30% of severe haemophilia A and are the major complication of treatment; suspected when bleeding stops responding
Avoid intramuscular injections, aspirin and NSAIDs; give vaccines subcutaneously
Historically, transfusion-transmitted HIV and hepatitis C devastated the haemophilia population before viral inactivation and recombinant products; it remains the reason plasma-derived products are treated with such caution
Gene therapy is now licensed for both types and offers the prospect of a durable cure

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