Haemophilia

• Haemophilia is a congenital, X-linked recessive bleeding disorder caused by deficient or defective coagulation factor VIII (haemophilia A) or factor IX (haemophilia B). Both factors are part of the intrinsic pathway, so their deficiency produces an isolated prolongation of the activated partial thromboplastin time (aPTT) with a normal prothrombin time (PT) and normal platelet count.
• Severity is graded by the residual factor activity: severe (under 1%), moderate (1 to 5%), or mild (above 5%). The lower the factor level, the more frequent and spontaneous the bleeding. ^[2]
• The hallmark of severe disease is recurrent haemarthrosis and deep muscle haematoma, with additional risk of intracranial haemorrhage, gastrointestinal and urinary tract bleeding, and prolonged bleeding after any injury or procedure.
• Diagnosis is clinical plus laboratory: prolonged aPTT that corrects on a mixing study, with a low factor VIII or IX assay. Genetic testing confirms the mutation and allows carrier detection and prenatal diagnosis. ^{[1] [7]}
• Treatment is replacement of the missing factor, with desmopressin for responsive mild haemophilia A, emicizumab for prophylaxis (especially with inhibitors), and emerging gene therapy. Regular prophylaxis is the standard of care for severe disease and is the only strategy that changes the natural history of bleeding and prevents haemophilic arthropathy. ^{[4] [5] [11][12]}

By the end of this page you should be able to:

1. Explain why factor VIII and IX deficiency causes bleeding, and how the resulting laboratory pattern arises.
2. Classify haemophilia as severe, moderate or mild from a factor level and predict the likely bleeding pattern.
3. Recognise the typical presentations (haemarthrosis, deep muscle bleed, intracranial haemorrhage, post-procedural bleeding) and their warning signs.
4. Interpret the coagulation screen and factor assays, including the meaning of a mixing study that does or does not correct.
5. Describe the main management options, their indications and how each works, and how inhibitors and prophylaxis are handled.
6. Counsel a family about inheritance, carrier status and testing.
7. Outline low-resource and perioperative care.

Haemophilia A is by far the commonest form, accounting for about 80% of people with haemophilia, and its overall prevalence is estimated at 3 to 20 cases per 100,000 population. ^[1] The World Federation of Hemophilia (WFH) estimates that about 850,000 people worldwide have haemophilia, of whom only about 272,000 have been identified so far (Annual Global Survey 2024), so most remain undiagnosed. ^[13] Haemophilia B is clinically indistinguishable but is a distinct disorder with a different gene and treatment profile. ^[12]

This page covers both forms together, with differences highlighted where they matter for treatment.

• Distribution. Haemophilia affects all ethnic groups. ^[1] The World Federation of Hemophilia estimates that hundreds of thousands of people are affected worldwide, with a large undiagnosed fraction, reflects the particular problem in countries without comprehensive clotting-factor programmes. ^{[1] [13]}
• Sex. Because the genes lie on the X chromosome, affected individuals are almost always male. Females are usually carriers; symptomatic females occur with skewed X-chromosome inactivation, Turner syndrome, or an affected father plus a carrier mother. ^{[1] [7]}
• New mutations. About 30 to 33% of newly diagnosed cases have no family history, reflecting spontaneous (de novo) mutations in the factor VIII gene. ^[1] Every boy with unexplained bleeding therefore needs full evaluation even without a family history.
• Mortality. Intracranial haemorrhage used to kill about 75% of those who suffered it; with modern replacement this has fallen to about 30%, and life expectancy with comprehensive care approaches that of the general population. ^{[1] [2]}

Both factors are encoded by genes on the X chromosome: F8 (factor VIII) at Xq26 and F9 (factor IX). Inheritance is X-linked recessive. ^{[1] [7]}

• A carrier mother passes the affected X to roughly half her sons (who then have haemophilia) and half her daughters (who become carriers).
• An affected father passes the gene to all of his daughters, none of his sons.
• Genetic testing is now the definitive way to establish the mutation, predict inhibitor risk, counsel relatives and plan prenatal diagnosis. ^[7]

Mutation spectrum in haemophilia A:

• The most common severe mutation is an inversion in intron 22, accounting for around half of severe haemophilia A, produced by recombination between homologous sequences about 500 kb telomeric to the F8 gene. ^{[1] [7]}
• An inversion in intron 1 accounts for about 1 to 4% of severe cases. ^[7]
• The remainder are point mutations, small insertions or deletions, duplications and deep intronic changes. ^[7]
• In mild and moderate disease the mutation is often a missense change, and genotype can partly predict responsiveness to desmopressin. ^[7]

Carrier status and counselling:

• A carrier has one normal and one affected X. Because of random X-inactivation, clotting factor (FVIII or FIX) levels vary: about one third of carriers have levels low enough to cause abnormal bleeding and need treatment, and an earlier study found reduced factor levels in 23% of carriers. ^{[2] [7]}
• Pedigree analysis and a factor level alone are not enough to diagnose carrier status; genetic testing is required. ^[7]
• Presumptive carriers should be identified through genetic counselling from about the age of 16, with information about reproductive options (acceptance of risk, prenatal diagnosis, preimplantation genetic diagnosis). ^[2]
• Prenatal diagnosis has moved from fetal blood sampling at 20 to 22 weeks to chorionic villus sampling at 11 to 14 weeks. ^{[2] [7]}

Haemophilia B is worth considering alongside A: it is caused by F9 mutations, is managed on the same principles, but does not respond to desmopressin (factor IX is not released) and is treated with factor IX concentrates or gene therapy. ^[12]

The intrinsic tenase complex (factors VIIIa and IXa) activates factor X; thrombin is then generated, fibrinogen is converted to fibrin and the platelet plug is stabilised. Without factor VIII or IX this step collapses, so the initial platelet plug is normal but it is never reinforced by fibrin. Bleeding is therefore delayed, and clots that do form are fragile and more easily lysed.

The clinical behaviour follows directly:

• Spontaneous bleeding occurs once the factor level is low enough that everyday micro-trauma overcomes the residual haemostatic reserve. The threshold for this is roughly the severe (under 1%) and, to a lesser extent, moderate (1 to 5%) range.
• Joints are a preferred site: the synovium is highly vascular and bleeding recurs in the same joint.
• Repeated haemarthrosis leads to synovitis driven by iron deposition in the synovium, progressive cartilage and bone damage, and ultimately haemophilic arthropathy. Joints that bleed three or more times non-traumatically within six months are called target joints (Canadian (Price et al. 2007) criteria instead use three or more bleeds in a consecutive three-month period). ^{[2] [10]}
• Muscle bleeding, especially into closed compartments (iliopsoas, forearm), can compress nerves and vessels and become life-threatening.
• The earliest haemarthrosis may be preceded by an "aura" of warmth, tingling and reduced movement: this is the moment to give factor, because treating at this stage is most effective at stopping bleeding and preventing damage. ^[1]

Grossly and microscopically the changes are those of chronic synovitis and cartilage destruction: synovial hyperplasia, haemosiderin-laden macrophages, cartilage fibrillation and, in advanced disease, joint-space narrowing and bony deformity. Iron deposition in synovium is considered a principal driver. ^{[2] [1]} MRI and musculoskeletal ultrasound (including the HEAD-US score) detect these changes before they become irreversible; importantly, soft-tissue changes can still reverse, but cartilage and bone changes do not. ^[2]

• Severe (under 1%): spontaneous bleeding 1 to 6 times per month, including haemarthroses and intramuscular haemorrhage; bleeding after minimal trauma. ^[1]
• Moderate (1 to 5%): bleeding usually after mild to moderate injury; spontaneous bleeding is uncommon but can occur. ^{[1] [2]}
• Mild (6% or more): bleeding only after surgery or major trauma; patients may remain undiagnosed for years or decades. ^{[1] [2]}

Haemarthrosis is the hallmark of severe haemophilia and is the main cause of long-term disability. ^[1]

• An acute haemarthrosis presents with pain, warmth, swelling, tenderness and restricted movement; the patient may describe the aura (warmth and tingling) before anything is visible.
• The most commonly affected joints are the knee, elbow and ankle; the hip is less commonly involved (bulky muscles protect it), and small joints of the hand and spine are rarely involved. ^[1]
• Recurrent bleeding produces chronic synovitis (persistence beyond three months), progressive cartilage and bone damage, and haemophilic arthropathy. ^[2]

Muscle haematoma accounts for 10 to 25% of haemorrhagic episodes in severe haemophilia, and about 75% of people with severe haemophilia experience one during their life. ^[1]

• Iliopsoas haematoma is life-threatening: vague lower abdominal/upper thigh pain, the hip held flexed and internally rotated, an inability to extend the hip and a distinctive gait, with femoral nerve compression from the accumulating blood. ^[1]
• Intramuscular injections can themselves cause haematoma; hence they are avoided or performed only with adequate factor cover. ^{[1] [2]}
• Muscle bleeding is confirmed and mapped with imaging (ultrasound, CT or MRI). ^[1]

Intracranial haemorrhage is a serious cause of morbidity and mortality and is more dangerous in those under 18 years. ^[1] Warning signs include:

• sudden severe headache or neck pain, repeated vomiting, seizures, double vision, lethargy, behavioural change, sudden difficulty walking or using an arm;
• less specific signs such as shock, hypotension and anaemia may be the only clues. ^[1]

Prompt diagnosis (CT or MRI) and early replacement reduce mortality and neurological sequelae; note that multiple unpredicted bleeding sites may be present. ^[1]

• Renal/urinary: haematuria is a troublesome and potentially obstructive burden; flank pain and sudden abdominal pain must be investigated for hydronephrosis or ureteral obstruction from clot. ^[1]
• Gastrointestinal: bleeding can be spontaneous or from ordinary causes; upper GI bleeding has historically been a notable cause of death. Helicobacter pylori increases the risk. ^[1]
• Mucosal and post-procedural: post-circumcision and post-dental-extraction bleeding are common first presentations, especially in mild disease and in sporadic cases. The oral cavity has high fibrinolytic activity, so dental work needs both factor and an antifibrinolytic. ^[1]
• Gum, sublingual, vertebral bleeding is uncommon. ^[1]
• Easy bruising, ecchymoses (buttocks during crawling), and bleeding after vaccination or minor trauma may be the first signs in a child without family history. ^[1]
• Bleeding into joints in haemophilia is painful and inflames; the patient is usually alert to the "aura" that heralds it. ^[1]

Female carriers can bleed: pregnancy/childbirth complications, menorrhagia, surgical bleeding and postpartum haemorrhage are all increased. ^[2] Reduced bone density (osteopenia/osteoporosis) has also been described in haemophilia, probably related to reduced physical activity from joint disease. ^[1]

Haemophilia is one of several disorders producing a prolonged aPTT with a normal PT. The table summarises the common possibilities.

Clinical picture plus haemostatic screen is the starting point. ^[1]

• Full blood count and platelets: normal platelet count and morphology. ^[1]
• PT: normal (extrinsic/common pathway intact). ^[1]
• aPTT / PTT: prolonged. Most reagents are more sensitive to factor VIII, XI and XII deficiency than to factor IX, and may miss a mild deficiency (30 to 50% of normal). ^[1]
• Thrombin time (TT): normal (no fibrinogen or direct thrombin inhibitor problem).
• vWF antigen/activity: check in new mild cases, to exclude von Willebrand disease type 2N or 3, in which factor VIII is low because vWF is abnormal. ^[1]

The combination of a prolonged aPTT with normal PT, TT and platelet count is the classic pattern. ^[1]

Performs the crucial first discrimination: is the prolonged aPTT due to a factor deficiency or an inhibitor?

• Mix patient plasma 1:1 with normal pooled plasma. A factor deficiency corrects (aPTT shortens to the reference range, typically to less than 50% of the original). An inhibitor does not correct. ^[1]
• Because factor VIII autoantibodies are time- and temperature-dependent, incubation for 1 to 2 hours at 37 C is essential: an immediate mix may misleadingly correct. ^{[1] [6]}
• Correction on a mixing study does not fully exclude a weak factor VIII inhibitor or heparin contamination; if the clinical picture suggests acquired haemophilia, assay further. ^[6]

• Factor VIII or factor IX assay (one-stage, two-stage or chromogenic; chromogenic is the ISTH reference) confirms and quantifies the defect. ^[1]
• Haemophilia A and B are separated by which factor is low.
• Severity is assigned from the activity (see the table below).
• Inhibitor screening: Bethesda (or Nijmegen-modified Bethesda) assay, expressed in Bethesda units (BU), where 1 BU is the amount of inhibitor that neutralises 50% of factor VIII activity after 2 hours at 37 C. ^{[1] [6]}
• Repeat testing: factor VIII rises with inflammation, stress and excitement, so a borderline result in a mildly affected person may need repeat assay with the patient rested and well. ^[1]
• Also test liver function and blood-borne virus status (HBV, HCV, HIV), historically relevant in people treated with older plasma products. ^[1]

• Cranial CT/MRI for suspected intracranial haemorrhage.
• Ultrasound/CT/MRI to map muscle haematoma.
• Joint imaging: musculoskeletal ultrasound (HEAD-US for early synovitis) and MRI for cartilage and bone change in haemophilic arthropathy. ^[2]

There is no formal disease definition beyond a documented low factor level with an appropriate inheritance pattern or mutation. In practice the severity grade is what guides management.

Treat any suspected significant bleed early: the first 2 hours matter. ^[1]

• Factor replacement is the cornerstone. For a joint, muscle or mucosal bleed give the missing factor intravenously and continue until haemostasis and pain allow mobilisation. Early treatment, ideally at the aura stage, limits synovial damage.
• Rest, ice, compression and elevation (RICE) plus immobilisation of the affected joint; avoid weight-bearing until the bleed stops.
• Analgesia: avoid aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 selective agents where possible, because of gastric bleeding risk and anti-platelet effects. Paracetamol (acetaminophen) is the routine analgesic; opioids for severe pain. ^[1]
• Never give intramuscular injections unless clotting factor cover has been provided; venepuncture and procedures are also done with factor cover. ^[1]
• Tense haemarthrosis may warrant arthrocentesis under adequate factor replacement to relieve pain and limit cartilage damage. ^[1]
• Intracranial or life-threatening bleeding demands immediate factor replacement, reversal of any anticoagulant effect and urgent imaging, coordinated with the haemophilia centre.
• Tranexamic acid is a useful adjunct for mucosal bleeding (see below). ^[9]
• Antifibrinolytics are avoided if there is haematuria (risk of renal tract clot obstruction).

Prophylaxis (regular factor replacement to prevent bleeding, rather than treat it) is the standard of care for patients with a severe bleeding phenotype, and is the only intervention that changes the natural history of the disease and prevents haemophilic arthropathy. ^{[4] [5]}

• The WFH recommends prophylaxis for paediatric and adult patients with severe haemophilia (including moderate disease with a severe bleeding phenotype) at all times, ^[4] and Kreuth V proposes prophylaxis be available to all patients regardless of availability of factor. ^[5]
• Start early: ideally before the age of 3 (some consensus documents say by 2 years), and before joint disease develops; children started before 6 have better long-term joint outcomes. ^{[4] [5]}
• Regimens vary from high-dose (25 to 40 IU/kg every other day for standard half-life factor VIII, or twice weekly for factor IX) to low-dose regimens (once or twice weekly, lower doses), which are widely used in resource-constrained settings and still outperform on-demand treatment. ^[4]
• Individualise dose and interval using the phenotype, joint status, activity level and pharmacokinetics rather than one fixed schedule. ^[4]
• Target trough levels: historically 1% (converting severe to a moderate phenotype); with standard half-life products a trough of 1 to 2% is typical. With extended half-life (EHL) products the consensus target is a minimum trough of 3 to 5% to preserve joint status. ^{[4] [5]}
• Extended half-life factor VIII and IX allow longer intervals between doses, higher troughs and better adherence, and are suitable for patients with and without inhibitors (the latter depending on product). Standard factor VIII circulates with a half-life of about 12 hours (12 to 18 hours for plasma-derived product) bound to von Willebrand factor. ^{[1] [2] [8] [12]}
• Episodic (on-demand) treatment after a bleed is inferior to prophylaxis for joint outcomes but is all that is possible where factor is scarce. ^[4]

Desmopressin is the treatment of choice for responsive mild haemophilia A. It releases endothelial vWF and factor VIII, raising FVIII by roughly 2 to 4 times baseline. ^{[9] [10]}

• Dose: 0.3 microg/kg intravenously or subcutaneously, given in the lab/on the ward; the intranasal dose is weight-based at 150 microg for patients under 50 kg and 300 microg for those 50 kg or more. ^[10]
• Give intravenously in 20 to 50 mL saline over 30 minutes. ^[9]
• Best given 30 minutes (IV) to 90 to 120 minutes (intranasal/subcutaneous) before the procedure or bleed expected to be treated. ^{[9] [10]}
• Fluid restriction is needed for 24 hours afterwards (hyponatraemia risk). Tachyphylaxis limits the response, typically after one to two doses, so desmopressin should not be relied on for haemostatic support lasting 2 to 3 days; doses are given no more often than about every 48 hours. ^{[3] [9]}
• Ineffective in haemophilia B (factor IX is not released) and in severe haemophilia A where baseline FVIII is under about 5%. ^[10]
• A therapeutic trial with laboratory measurement is needed in every patient before relying on it. ^[9]

Tranexamic acid is an antifibrinolytic that is effective for mucosal bleeding and as adjunct to factor in dental or surgical procedures. ^[9]

• Dose: 25 mg/kg by mouth every 6 to 8 hours, or 10 mg/kg intravenously every 6 to 8 hours, for mild/moderate mucosal haemorrhage. ^[9]
• Also useful as a mouthwash after dental work and for menorrhagia.
• Avoid in haematuria (risk of obstructive urinary clots) and in a history of acute thrombosis, DIC or thrombotic microangiopathy. ^[3]

Emicizumab (Hemlibra) is a bispecific antibody that bridges activated factor IX and factor X, mimicking activated factor VIII. It is a first-line prophylactic agent in haemophilia A with inhibitors, and is also licensed for HA without inhibitors. ^{[8] [9]}

• Subcutaneous, with a half-life of 4 to 5 weeks. ^[8]
• Dosing: loading 3 mg/kg once weekly for 4 weeks, then maintenance of 1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks. ^[8]
• It normalises the aPTT, so aPTT cannot be used to monitor coagulation in patients on emicizumab; chromogenic assays distinguish emicizumab-driven from residual FVIII activity. ^[8]
• aPCC must not be used concomitantly with emicizumab (thrombotic microangiopathy risk); if a bypassing agent is needed, recombinant factor VIIa (rFVIIa) is the agent of choice. ^{[3] [8]}
• Contraindicated/less appropriate in haemophilia B (no FIX target).

The first licensed haemophilia A gene therapy is valoctocogene roxaparvovec (Roctavian), approved for adults with severe haemophilia A without inhibitors and without detectable antibodies to adeno-associated virus serotype 5. ^[11]

• Mechanism: a single intravenous infusion of an AAV5 vector delivering a B-domain-deleted FVIII transgene to hepatocytes, producing endogenous FVIII. ^[11]
• Dose: 6 x 10^13 vector genomes per kg body weight. ^[11]
• FVIII activity typically rises into the mild haemophilia range (FVIII 5 to under 40% of normal) with major reductions in bleeds and factor use; activity declines year on year and the long-term balance is still studied. ^[11]
• Liver safety: the commonest adverse event is a transient rise in ALT, treated with corticosteroids; candidate selection and monitoring of hepatitis, steatosis, liver stiffness and ALT are essential before and after infusion. ^[11]
• Gene therapy for haemophilia B (FIX vectors) is approved in some jurisdictions with more durable FIX expression.

• Inhibitors develop in a substantial minority of people with severe haemophilia A treated with factor VIII (less often in B).
• Classification by titre (low vs high) determines treatment options and eligibility for immune tolerance therapy (ITI). ITI involves regular, prolonged factor exposure to eradicate the inhibitor and remains standard even in the emicizumab era. ^[8]
• Acute bleeding with a high-titre inhibitor: use a bypassing agent. rFVIIa dosing: 90 to 120 microg/kg pre-operatively plus 10 mg/kg intravenous tranexamic acid, then every 2 hours peri-operatively, tapering post-operatively; activated prothrombin complex concentrate (aPCC) is an alternative with doses continued until haemostasis. ^[3]
• Concomitant emicizumab plus aPCC is avoided because of thrombosis/TMA risk; rFVIIa is the preferred bypass. ^{[3] [8]}
• ITI dosing is set by specialist protocols; local regimens apply.

Preventing joint damage is the central goal of modern care. ^{[2] [4]}

• Prophylaxis started early before any joint bleed, the strongest protective measure.
• Treat joint bleeds at the aura stage to stop synovitis developing.
• Physiotherapy: exercise programmes, strengthening, orthoses, gait retraining; skilled physical therapists are essential to comprehensive care. ^[2]
• Joint monitoring: clinically with the Hemophilia Joint Health Score (HJHS) and imaging (musculoskeletal ultrasound/HEAD-US; MRI where needed) to detect subclinical bleeds ("micro-haemorrhages") before damage is irreversible. ^[2]
• Management of chronic synovitis (lasting beyond three months): factor optimisation, physiotherapy, radiosynovectomy/synovectomy; orthopaedic surgery (osteotomy, arthroplasty, arthrodesis) for advanced arthropathy. ^[2]
• Activity counselling: safe physical activity is encouraged; contact and high-injury sports are discouraged unless factor cover is in place.
• Dental and oral health: brushing training and 6-monthly dental checks reduce mucosal bleeding risk. ^[2]

Surgery is now safe with planning. ^[3]

• Coordinate with the haemophilia centre in advance; pre-operative factor levels and inhibitor status; consider chromogenic assays in patients on emicizumab.
• Give factor pre-operatively and maintain post-operative levels as required; for major surgery with inhibitors, rFVIIa or aPCC regimens as above, with most rFVIIa regimens using 90 to 120 microg/kg pre-operatively plus 10 mg/kg IV tranexamic acid. ^[3]
• Catheters and angiography can dislodge thrombus/tumour fragments in vascular contexts; in haemophilia, minimise unnecessary intravascular manipulation. ^[3]
• Tranexamic acid is an effective adjunct in trauma and orthopaedic surgery in haemophilia and, in available studies, does not increase thromboembolism risk. ^[3]
• For patients on emicizumab undergoing surgery, the haemostatic potential of emicizumab alone is insufficient for major procedures; bypass with rFVIIa, avoiding aPCC. ^[3]

Where factor concentrate, emicizumab or gene therapy is unavailable or scarce: ^{[2] [4]}

• Low-dose prophylaxis (once or twice weekly, lower doses) remains clearly superior to on-demand treatment in preventing arthropathy and is cost-feasible. ^[4]
• Maximise the cheap adjuncts: desmopressin for mild haemophilia A, tranexamic acid for mucosal bleeding, early mobilisation, physiotherapy, RICE and joint protection.
• Diagnose early from the isolated prolonged aPTT with a normal PT and platelet count, and contact regional experts; the wfH/HTC model (shared-care/twinning) can build local capacity. ^[2]
• Use plasma judiciously where concentrates are unavailable; virus-inactivated recombinant or plasma-derived concentrates are preferred to cryoprecipitate/fresh frozen plasma. ^[2]
• Avoid unsafe injections; intramuscular injections without factor cover cause disabling haematomas.
• Treat Helicobacter pylori to reduce GI bleeding risk. ^[1]
• Refer early to a bleeding-disorders centre; major surgery should be done where factor, imaging and surgical haemostasis are available.

Acquired haemophilia A (AHA) is a rare but life-threatening autoimmune disease: autoantibodies neutralise factor VIII in people (men and women) with no previous bleeding history, typically older adults and postpartum women. ^[6]

• Presentation: sudden bruising, deep haematoma or postoperative bleeding with an unexplained prolonged aPTT; the mixing study does not correct.
• Approximately 10% of patients do not present with bleeding, so an unexplained prolonged aPTT must never be ignored before invasive procedures. ^[6]
• Diagnosis: isolated prolonged aPTT, FVIII low, mixing study not correcting; quantify the inhibitor with the Nijmegen-modified Bethesda assay. Exclude lupus anticoagulant and heparin. ^[6]
• Treatment priorities: (1) control bleeding with a bypassing agent (rFVIIa or aPCC) or recombinant porcine FVIII; (2) eradicate the autoantibody with immunosuppression (corticosteroids, cyclophosphamide and/or rituximab); median time to remission about 5 weeks. ^[6]
• Mucosal bleeds may benefit from tranexamic acid. ^[8]
• AHA remission is usually achieved, but relapse can occur; monitor FVIII after immunosuppression is withdrawn.

• Haemophilic arthropathy and target joints from recurrent haemarthrosis. ^{[1] [2]}
• Chronic synovitis and limited range of movement. ^[2]
• Muscle contracture, compartment syndromes and pseudotumours (rare) from organised haematomas. ^[1]
• Inhibitors changing treatment options.
• Intracranial haemorrhage, still the leading cause of bleeding-related death. ^[1]
• Reduced bone density. ^[1]
• Blood-borne infections (HCV, HIV) in older patients treated before viral inactivation; no longer expected with current products. ^[1]
• Haematuria, renal obstruction and GI bleeding. ^[1]

• With early prophylaxis and comprehensive care, life expectancy approaches normal and joint health is preserved. ^{[2] [4]}
• Prognosis is worst for untreated severe disease (recurrent haemarthroses, arthropathy, intracranial bleeds). ^[1]
• Mild disease is compatible with a normal life but carries a higher intracranial haemorrhage mortality than the general population. ^[2]

• Carrier detection and counselling from adolescence. ^[2]
• Prenatal diagnosis (chorionic villus sampling at 11 to 14 weeks) where available. ^{[2] [7]}
• Neonates at risk: delay circumcision until the defect is excluded by factor assay; factor VIII is physiologically raised in neonates, so results must be interpreted carefully. ^[1]
• Vaccination: haemophilic children receiving plasma products should receive hepatitis A and B vaccination according to national programmes; those on recombinant product only may not need routine vaccination against these. ^[1]
• Avoid inhibitors/minimise risk with appropriate product choice and the lowest effective exposure in the first 50 days; follow haemophilia centre policy.
• Screen for inhibitors periodically, especially in the first 50 exposure days and before surgery. ^[3]

• Pregnancy and childbirth: factor levels rise in pregnancy; carriers still risk postpartum haemorrhage. Plan delivery with a haemophilia centre; factor cover and avoidance of forceps/vacuum protect against neonatal intracranial bleeding. ^[2]
• Children: prophylaxis started as early as possible; physiotherapy; accident prevention and appropriate activity; careful interpretation of neonatal testing. ^{[1] [4]}
• Older adults: comorbidities (cardiovascular disease, cancer) interact with treatment choice; inhibitors and gene therapy eligibility differ.
• Females with low factor levels are treated like mild haemophilia, with full cover for procedures. ^[2]

• Haemophilia is an X-linked recessive deficiency of factor VIII (A) or factor IX (B), causing an isolated prolonged aPTT with normal PT and platelets.
• Severity: severe under 1%, moderate 1 to 5%, mild 6% or more, with bleeding becoming more spontaneous as the level falls.
• Hallmark presentations are recurrent haemarthrosis, deep muscle haematoma (especially iliopsoas), intracranial haemorrhage and prolonged post-procedural bleeding.
• Diagnose by the clinical picture, a mixing study that corrects, and a low factor assay; exclude von Willebrand disease in new mild cases.
• Factor replacement is the cornerstone; desmopressin helps responsive mild haemophilia A only; emicizumab and gene therapy are modern options.
• Prophylaxis is the standard of care in severe disease and is the only way to prevent haemophilic arthropathy.
• Avoid NSAIDs/aspirin and intramuscular injections; use tranexamic acid (25 mg/kg by mouth or 10 mg/kg IV, every 6 to 8 hours) for mucosal bleeding.
• Acquired haemophilia presents suddenly in adults with a non-correcting aPTT; treat bleeding with bypassing agents and eradicate the antibody with immunosuppression. ^[6]
• Carrier counselling and prenatal diagnosis are integral to care.

Carrier testing and counselling; Von Willebrand disease; Coagulation cascade; Arthropathy of haemophilia; Blood transfusion and plasma products; Joint imaging in bleeding disorders.