skip to main content
ukmla 2026

Haemophilia

X-linked recessive bleeding disorders: haemophilia A (factor VIII deficiency) and haemophilia B (factor IX deficiency) — characterised by spontaneous haemarthroses and prolonged APTT with normal PT

Review date
reviewed 2026-04-05
Reading time
6 min read
Author
Dr Kola Tytler MBBS CertHE MBA MSt MRCGP
Haematology & Oncologyrarechronic
On this page
Condition details
Haematology & Oncology
rare
6 min read
reviewed 2026-04-05
practice ukmla questions →

About This Page

This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.

Key points

  • Haemophilia A: factor VIII deficiency (80% of cases). Haemophilia B (Christmas disease): factor IX deficiency (20%). Both are X-linked recessive
  • Severity by factor level: severe (<1% activity) = spontaneous bleeds; moderate (1-5%) = bleeds after minor trauma; mild (5-40%) = bleeds after surgery/major trauma only
  • Characteristic bleeding pattern: haemarthroses (knees, elbows, ankles), deep muscle haematomas, prolonged bleeding after surgery. NOT petechiae/purpura (that is a platelet problem)
  • Lab: prolonged APTT, NORMAL PT, NORMAL platelets, NORMAL bleeding time. Factor VIII or IX assay confirms diagnosis
  • Treatment: factor replacement (recombinant factor VIII or IX for acute bleeds). Emicizumab (bispecific antibody mimicking factor VIII) for prophylaxis in haemophilia A

Overview

Haemophilia is a group of X-linked recessive bleeding disorders caused by deficiency of coagulation factors in the intrinsic pathway. Haemophilia A (factor VIII deficiency) accounts for approximately 80% of cases and haemophilia B (Christmas disease, factor IX deficiency) for ~20%. Both produce identical clinical phenotypes — the diagnosis is distinguished by factor assays. The X-linked inheritance means that males are affected and females are carriers (though carriers may have factor levels reduced to ~50% and can occasionally be symptomatic).

Epidemiology

Haemophilia A affects approximately 1 in 5,000 male births and haemophilia B approximately 1 in 30,000 male births. There are approximately 6,000 people with haemophilia A and 1,200 with haemophilia B registered in the UK. Approximately 30% of cases arise from new mutations with no family history. With modern factor replacement therapy and comprehensive care, life expectancy is near-normal for patients without inhibitors or severe joint disease.

Clinical Features

Symptoms
Haemarthrosis — painful, swollen joint. The hallmark of severe haemophilia. Knees > elbows > ankles
Deep muscle haematomas — especially iliopsoas (can mimic appendicitis), forearm compartment syndrome
Prolonged bleeding after surgery, dental extraction, or circumcision (often the first presentation in mild haemophilia)
Easy bruising from childhood (large, deep bruises)
Intracranial haemorrhage — life-threatening, may occur after minor head trauma
Haematuria
Signs
Acute haemarthrosis: warm, swollen, painful joint with restricted movement
Chronic arthropathy: fixed flexion deformities, muscle wasting, joint destruction from recurrent bleeds
Large deep bruises (NOT petechiae — petechiae suggest platelet disorder)
Muscle haematomas with compartment syndrome signs

Investigations

First-line
APTTPROLONGED (measures intrinsic pathway: factors VIII, IX, XI, XII). Corrects on mixing study with normal plasma
PTNORMAL (extrinsic pathway is intact)
Platelet count and bleeding timeNORMAL (platelet function is normal in haemophilia)
FibrinogenNORMAL
Second-line
Factor VIII assayLow in haemophilia A. Severity: severe <1%, moderate 1-5%, mild 5-40%
Factor IX assayLow in haemophilia B. Same severity classification
VWF antigen and activityNORMAL in haemophilia A (distinguishes from von Willebrand disease type 3, which can also cause low factor VIII)
Specialist
Inhibitor screen (Bethesda assay)Test for factor inhibitors (alloantibodies against replacement factor) — develops in ~30% of severe haemophilia A patients. Major treatment complication
Genetic testingF8 or F9 gene mutation analysis — for carrier detection, prenatal diagnosis, and prognosis (inversion mutations in intron 22/1 of F8 are commonest cause of severe haemophilia A)

Management

UKHCDO Guidelines on Haemophilia + WFH Guidelines
1
Acute bleeding episodes
  • Factor replacement: recombinant factor VIII (haemophilia A) or factor IX (haemophilia B) — given IV to raise factor level to target appropriate for bleed severity
  • Joint bleeds: raise factor to 40-60%. Major surgery: raise to 80-100%
  • Desmopressin (DDAVP): for MILD haemophilia A only — releases stored VWF and factor VIII. Not effective in severe disease or haemophilia B
  • Tranexamic acid: adjunctive for mucosal bleeding (oral, dental). AVOID in haematuria (risk of clot in renal tract)
2
Prophylaxis
  • Regular factor replacement 2-3 times/week (haemophilia A) or 1-2 times/week (haemophilia B) to maintain trough level >1%
  • Emicizumab (bispecific antibody mimicking factor VIIIa): SC injection weekly/fortnightly/monthly — revolutionised haemophilia A prophylaxis, effective even with inhibitors
  • Fitusiran (anti-thrombin siRNA): newer agent for both haemophilia A and B with or without inhibitors
3
Inhibitor management
  • Inhibitors develop in ~30% of severe haemophilia A — make factor replacement ineffective
  • Bypassing agents for acute bleeding: recombinant factor VIIa (NovoSeven) or FEIBA (activated prothrombin complex concentrate)
  • Immune tolerance induction (ITI): high-dose daily factor VIII to eliminate inhibitor — success rate ~70%
4
Comprehensive care
  • Managed through Haemophilia Comprehensive Care Centres (HCCCs)
  • Multidisciplinary: haematologist, physiotherapist, specialist nurse, psychologist, orthopaedic surgeon
  • AVOID intramuscular injections, aspirin, and NSAIDs (use COX-2 inhibitors if needed)
  • Hepatitis A/B vaccination (historical risk from plasma-derived products)

Complications

  • Chronic haemophilic arthropathy: Recurrent haemarthroses → synovial hypertrophy → cartilage destruction → fixed deformity. The main cause of long-term disability
  • Inhibitors: Alloantibodies against replacement factor — the most challenging treatment complication. Develop in ~30% of severe haemophilia A
  • Intracranial haemorrhage: The most common cause of haemophilia-related death
  • Compartment syndrome: From muscle haematomas — surgical emergency
  • Blood-borne infections: Historical — HIV and hepatitis C from contaminated plasma products in 1970s-80s. Now eliminated with recombinant products
UKMLA Exam Tips
  • 1Prolonged APTT + normal PT + normal platelets = think haemophilia (or VWD). The APTT measures the intrinsic pathway
  • 2Haemophilia = deep bleeds (joints, muscles). Platelet disorders = superficial bleeds (petechiae, mucosal). This distinction is high-yield
  • 3Haemophilia A (factor VIII, 80%) vs B (factor IX, 20%) — clinically identical, only factor assays distinguish them
  • 4X-linked recessive: males affected, females carriers. ~30% are new mutations with no family history
  • 5DDAVP works in MILD haemophilia A only (releases stored factor VIII). No use in severe or in haemophilia B
  • 6Emicizumab has transformed haemophilia A prophylaxis — SC injection, works even with inhibitors

Put your reading into practice

Topic-specific question practice is not linked for this article yet.

Choose UKMLA questions from the existing bank. General exam practice covers your selected topics; it is not filtered to this article. Your usual question-bank access applies.

Choose UKMLA practice

After your session, return to this section to revisit the reading and choose your next review.

Verified Sources & References

UKHCDO Guidelines — Haemophilia
WFH Guidelines — Management of Haemophilia (2020)
Your learning path

Save your place and choose what comes next

sign in to save your learning

Haematology & Oncology · Article 23 of 28