Coagulation Disorders (Haemophilia & von Willebrand)

Meet the patient

A 4-year-old boy is brought in with a swollen, hot, painfully flexed right knee that appeared "for no reason" at nursery. He bruised easily as a toddler and bled for hours after a circumcision. His mother's brother died of a bleed as a child. The APTT is prolonged, the PT and platelet count are normal, and the mixing study corrects.^[1]

The second patient is a 19-year-old woman with heavy periods since menarche, frequent nosebleeds, and a mother and sister with the same. Her APTT is borderline and her platelet count is normal.^[2]

Two patients, two arms of haemostasis. The boy has failed secondary haemostasis (a missing clotting factor — haemophilia); the woman has failed primary haemostasis (a platelet-plug problem — von Willebrand disease). The site and the timing of the bleeding tell you which arm broke before any test is run.^[1][2]

One cascade, two arms, two bleeding patterns

Which protein of the cascade is missing decides where the bleeding happens. Haemophilia is a defect of the fibrin-forming arm, so the clot is weak and delayed and the patient bleeds deep and late — into joints, muscles and the brain, often hours after injury, with rebleeding. VWD is a defect of the platelet-plug arm, so the patient bleeds immediately and superficially — from mucous membranes.^[1][2]

Haemophilia is deficiency of factor VIII (haemophilia A, about 80 percent) or factor IX (haemophilia B / Christmas disease, about 20 percent) — both X-linked recessive, so males are affected and females are carriers. A small family of rare factor deficiencies (XI, VII, V, X, XIII, fibrinogen) is mostly autosomal recessive, each with its own signature.^[1]

Modern treatment has transformed these conditions. Recombinant factor VIII and IX, the subcutaneous bispecific antibody emicizumab, non-factor rebalancing therapies and AAV-vector gene therapy have turned haemophilia from a crippling, life-shortening disease into a manageable chronic one with near-normal life expectancy where the therapies are funded.^[1][4]

The face-off — haemophilia, VWD, acquired

^{[1] [10] [14] [16] [17]}

Severity — the factor level, not the bleeding history

Severity is graded by the endogenous factor activity, and it sets the tempo. This is the single most important prognostic variable in haemophilia.^[1]

• Severe — factor level under 1 percent: spontaneous bleeds (joints, muscles, intracranial) from infancy, 2 to 5 a month without prophylaxis.
• Moderate — factor level 1 to 5 percent: bleeding after minor trauma or surgery; occasional spontaneous bleeds.
• Mild — factor level 5 to 40 percent: bleeding only after significant trauma, surgery or dental work; may escape diagnosis until adulthood.^[1]

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Who gets it

Haemophilia affects about 1 in 5000 male live births (A) and 1 in 30,000 (B). Because it is X-linked, all ethnicities are equally affected and males bleed while females carry. About 30 percent of cases are de novo mutations with no family history — so a negative family history does not exclude haemophilia in a boy with a suggestive bleeding pattern. Symptomatic female carriers occur with skewed X-inactivation, Turner syndrome or homozygosity.^[1]

VWD is the commonest inherited bleeding disorder — a symptomatic prevalence of up to 1 in 100 (the much higher screening estimates are mostly asymptomatic low-vWF individuals). Type 1 is about 75 percent, type 2 about 20 to 25 percent, type 3 rare. Blood group O lowers vWF by about 25 percent — the commonest reason for a borderline-low vWF in someone with trivial bleeding.^[2]

Acquired coagulopathy risk factors: advanced age, pregnancy and the postpartum period, autoimmune disease (SLE, rheumatoid), lymphoproliferative and solid malignancy, sepsis and trauma (DIC), chronic liver disease, and anticoagulant therapy.^[6]

The mechanism — why haemophilia bleeds deep and VWD bleeds mucosal

The cascade is a thrombin-generation engine. The intrinsic tenase complex — factor IXa plus its cofactor VIIIa on the activated platelet surface — activates factor X, which drives the thrombin burst that turns fibrinogen into a cross-linked fibrin clot. Factor VIII and IX are the rate-limiting cofactors of secondary haemostasis. Lose either and the thrombin burst is weak and delayed, the clot is poorly cross-linked (factor XIII not activated) and unusually easy to lyse — hence the deep, rebleeding phenotype.^[1]

Von Willebrand factor has two jobs, and VWD is a double hit. First, the high-molecular-weight multimers bridge exposed subendothelial collagen to the platelet glycoprotein GPIb-IX-V receptor under high shear — the initiating step of primary haemostasis. Second, vWF is the plasma carrier and stabiliser of factor VIII, protecting it from clearance and extending its half-life from minutes to about 12 hours. So VWD gives mucocutaneous bleeding from failed adhesion plus a secondary factor VIII deficiency from loss of the carrier.^[2]

The subtypes map to distinct lesions: type 1 is a partial quantitative reduction; type 2A loses high-molecular-weight multimers; 2B is a gain-of-function that binds platelets spontaneously and causes thrombocytopenia (worsened by desmopressin); 2M has normal multimers but reduced function; 2N has a defective factor VIII binding site and mimics mild haemophilia A; type 3 is virtual absence of vWF, the severest form.^[2]

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How they present — deep bleeds versus mucocutaneous

Haemophilia A and B are clinically indistinguishable — they differ only in the deficient factor. Severity sets the tempo.^[1]

Haemarthrosis is the hallmark — bleeding into the knees, elbows and ankles (the target joints). The joint is swollen, warm, painful and held flexed; recurrent bleeds drive haemophilic arthropathy (synovial hypertrophy, cartilage destruction, fixed deformity), historically the leading cause of long-term disability. Intramuscular bleeds favour the iliopsoas (groin pain, hip held flexed, femoral nerve compression), the calf and forearm (compartment syndrome), and the gluteal region.^[1]

Intracranial haemorrhage is the most feared bleed and the leading cause of death in severe haemophilia, especially in neonates after instrumental delivery and in toddlers after minor head trauma. Any haemophilia patient with a headache, vomiting, altered consciousness, seizure or a head injury is treated empirically with factor to 100 percent before imaging.^[1]

VWD causes mucocutaneous bleeding — epistaxis, gum bleeding, easy bruising, prolonged bleeding after dental work, and, characteristically in women, heavy menstrual bleeding and postpartum haemorrhage. Type 3, with virtual absence of vWF, produces a severe haemophilia-like phenotype.^[2]

Everyone forgets the atypical presentations that examiners probe: mild haemophilia declaring only after surgery or a dental extraction; a symptomatic female carrier with menorrhagia (skewed X-inactivation); a neonate bleeding after heel-prick, circumcision or intramuscular vitamin K; acquired haemophilia in an elderly patient with no childhood history and dramatic soft-tissue bleeding; type 2N VWD masquerading as mild haemophilia A in a female.^[1]

The differential — and the mixing study that sorts it

A prolonged APTT with bleeding is not always haemophilia, and mucocutaneous bleeding is not always VWD. Name the mimic and the discriminator.^[1][2]

• Platelet disorders (ITP, Glanzmann, Bernard-Soulier) — petechiae and mucocutaneous bleeding with a normal PT and APTT. Glanzmann is a GPIIb/IIIa defect; Bernard-Soulier a GPIb defect.
• DIC — global consumption; both PT and APTT prolonged, low fibrinogen, raised D-dimer, thrombocytopenia, with a trigger.
• Liver disease — global factor deficiency; PT prolonged first, then APTT, with thrombocytopenia from hypersplenism.
• Vitamin K deficiency — factors II, VII, IX, X low; PT prolonged first (factor VII has the shortest half-life), responding to vitamin K in 6 to 12 hours.
• Acquired haemophilia A — an APTT that does not correct on mixing, a low factor VIII, a positive Bethesda assay, no childhood history.^[6]
• Factor XIII deficiency — normal PT and APTT with umbilical stump bleeding and recurrent miscarriage.^[1]

^[1]

The discriminator line: the mixing study is the single most powerful first step. Corrects — it is a deficiency (haemophilia, VWD). Does not correct — it is an inhibitor (acquired haemophilia, lupus anticoagulant). ^[1]

The bedside round

The focused examination has three jobs — characterise active bleeding, document chronic damage, and protect the distal neurovascular status of any limb bleed.^[1]

Look for the swollen, warm, flexed joint (haemarthrosis); the tender, tense compartment (intramuscular bleed with compartment-syndrome risk); groin pain with a flexed hip and femoral nerve signs (iliopsoas haematoma). Then document the chronic damage — target joints, fixed flexion deformities, muscle wasting, synovial thickening. Examine distal pulses and nerves for every limb bleed; the dangers are compartment syndrome and nerve compression (femoral, median, posterior tibial). Fundoscopy and a neurological exam are mandatory if intracranial bleeding is suspected.^[1]

Named bedside phenomena worth knowing: the target joint (three or more bleeds into the same joint in six months — a marker for prophylaxis escalation); iliopsoas haemorrhage (inguinal mass, hip held flexed, femoral nerve palsy — easily mistaken for appendicitis or a psoas abscess); and the airway-threatening parapharyngeal or retropharyngeal haematoma, a true emergency.^[1]

The bleeding assessment tool (BAT) endorsed by the ISTH quantifies the lifetime bleeding history. A high score (4 or more in adult males, 6 or more in adult females) favours VWD or a platelet disorder over haemophilia.^[2]

Investigations — APTT, mixing, factor assays, the vWF panel, Bethesda

First-line coagulation screen is the entry point and the discriminator:^[1][2]

• APTT prolonged in haemophilia (when factor VIII or IX falls below about 30 percent) and variably in VWD; PT, thrombin time and platelet count NORMAL.
• Mixing study — corrects in a factor deficiency (haemophilia, VWD, rare factor deficiencies) and does NOT correct with an inhibitor (acquired haemophilia, lupus anticoagulant).^[1]

Specific factor assays confirm and grade severity: factor VIII for haemophilia A, factor IX for B (severe under 1 percent, moderate 1 to 5 percent, mild over 5 percent). Both must be sent before any factor replacement blurs the picture.^[1]

The von Willebrand panel — the four tests that define VWD and its subtype: vWF antigen (quantity); vWF activity / ristocetin cofactor (vWF:RCo) or the newer GP1bM assay (function); factor VIII (often low because vWF stabilises it); and vWF multimer analysis to subtype the type 2 variants. Interpret in light of blood group (group O lowers vWF by about 25 percent) and the acute-phase response (vWF rises with inflammation, surgery, pregnancy — a normal result during an acute illness can mask VWD, so repeat when the patient is well).^[2]

The inhibitor screen (Bethesda assay) is mandatory in all newly diagnosed haemophilia and whenever bleeding escalates despite adequate factor. A titre of 0.6 Bethesda units (BU) per mL or higher defines a positive inhibitor. Low-responding inhibitors (under 5 BU/mL) may be transient; high-responding inhibitors (5 BU/mL or higher) persist and rise on re-exposure.^[1]

^[1]

The acute bleed — factor first, investigate after

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^{[9] [10] [16] [25]}

An acute bleed in known haemophilia is treated first and investigated after. The cardinal error is to wait for a factor level or a scan before treating — emergency management is immediate factor replacement based on the suspicion of a bleed rather than the confirmation of one.^[11]

Dosing to full replacement: in the emergency department, the doses that achieve factor levels of 100 percent are 50 units per kilogram of factor VIII and 100 units per kilogram of factor IX.^[11] Practical targets:^[11]

• Joint or muscle bleed — treat early with factor replacement and rest the joint for four to five days; paracetamol for pain; ice therapy may help although its role remains debated.^[22]
• Intracranial haemorrhage, major trauma or major surgery — give factor immediately to achieve 100 percent activity (factor VIII 50 units per kilogram; factor IX 100 units per kilogram).^[11] Central nervous system bleeding affects 3 to 8 percent of haemophilia patients and is a major cause of mortality and morbidity; in suspected intracranial haemorrhage factor VIII replacement is performed prior to radiological examinations and consultations, and the objective thereafter is to bring factor levels to normal limits through treatment and follow-up.^[12]
• Life-threatening or airway-threatening bleeding — full-dose factor replacement stratified by bleeding severity: patients without inhibitors receive factor VIII concentrate, while those with inhibitors preferably receive recombinant activated factor VII.^[25]
• Mild haemophilia A with a minor bleed or a dental procedure — desmopressin and antifibrinolytic agents may avoid factor concentrate altogether, provided desmopressin response has been documented.^[18][15]

Adjuncts: rest, ice and paracetamol-based analgesia for joint bleeds; use medications that impair platelet function — including aspirin — cautiously if at all; take precautions with intramuscular injections (schedule them after factor cover). Tranexamic acid is approved for short-term use in haemophilia, including prevention of dental-procedure bleeding and treatment of menorrhagia, and a tranexamic acid mouthwash effectively controls gingival bleeding during dental scaling.^{[22][15][20][21]}

Haemophilia prophylaxis — emicizumab changes everything

The principle of prophylaxis is to prevent spontaneous bleeds — and the arthropathy they cause — before they start. Primary prophylaxis started after the first joint bleed and/or before the age of 2 is the evidence-based, first-choice treatment in severe haemophilia, and prophylaxis (factor VIII concentrate or subcutaneous emicizumab) is standard for severe disease and for moderate or mild disease with frequent bleeding.^[17][15]

Emicizumab is a subcutaneous bispecific antibody that bridges activated factor IX and factor X, replacing the function of missing activated factor VIII. It is approved for haemophilia A with and without factor VIII inhibitors: four weekly loading doses of 3 mg per kilogram are followed by maintenance of 1.5 mg/kg once weekly, 3 mg/kg every two weeks, or 6 mg/kg every four weeks.^[9] With inhibitors, once-weekly emicizumab cut the annualised bleeding rate to 2.9 from 23.3 events — an 87 percent reduction versus no prophylaxis — and 79 percent below previous bypassing-agent prophylaxis.^[8] Without inhibitors, 1.5 mg/kg weekly or 3 mg/kg every two weeks cut the rate by 96 and 97 percent versus no prophylaxis, and by 68 percent versus previous factor VIII prophylaxis.^[3]

Prophylactic factor VIII — regular concentrate infusions prevent bleeds and arthropathy; in resource-limited settings low-dose schedules of twice or three times weekly remain effective.^[24] Desmopressin is for mild haemophilia A with a documented response, with antifibrinolytics for minor bleeding episodes and surgical procedures.^[18] Haemophilia B follows the same principle — regular factor IX replacement as prophylaxis or on-demand therapy.^[1]

Gene therapy — a functional cure for selected adults

AAV-vector gene therapy is a licensed option in haemophilia A and has completed phase 3 evaluation in haemophilia B:^[15][7]

• Valoctocogene roxaparvovec for haemophilia A — a single IV infusion of an AAV5 vector carrying a B-domain-deleted factor VIII gene. The phase 3 GENEr8-1 trial showed the mean factor VIII activity at one year had risen by 41.9 IU/dL, with annualised factor VIII concentrate use down 98.6 percent and treated bleeding down 83.8 percent.^[4] At two years the annualised treated bleeding rate remained 84.5 percent below baseline, and transgene-derived factor VIII declined gradually with first-order kinetics (modelled half-life of about 123 weeks).^[5]
• Etranacogene dezaparvovec for haemophilia B — a single infusion of an AAV5 vector expressing the factor IX Padua variant. In the phase 3 HOPE-B trial, factor IX activity increased by a mean of 36.2 percentage points at six months and 34.3 points at 18 months, the annualised bleeding rate fell from 4.19 to 1.51, and benefit persisted in participants with pre-existing AAV5 neutralising antibody titres under 700.^[7]

Candidate selection: GENEr8-1 enrolled adult men with severe haemophilia A (factor VIII 1 IU/dL or lower) without pre-existing anti-AAV5 antibodies or a history of inhibitors; HOPE-B was effective regardless of pre-existing AAV5 neutralising antibodies.^[4][7]

VWD management — subtype-driven

Type 1 (and selected type 2) — the guidelines recommend a desmopressin trial to determine therapy, so response is documented before it is relied on; desmopressin and antifibrinolytics cover minor bleeding and procedures, while severe bleeding needs VWF-increasing treatment.^[2][16]

Types 2 and 3 — treatment guidelines recommend a von Willebrand factor/factor VIII concentrate (for example Haemate-P) for type 2 or 3 VWD undergoing surgery, and for type 1 patients who are unresponsive to desmopressin or in whom it is contraindicated; in surgical trials the median loading dose ranged from 42.6 to 61.2 units of VWF ristocetin cofactor activity per kilogram, depending on the procedure.^[14]

Tranexamic acid is adjunctive across the subtypes — approved for short-term haemophilia use including prevention of dental-procedure bleeding, with a mouthwash effective for dental work — and heavy menstrual bleeding in VWD is managed with hormonal therapies, alone or combined with antifibrinolytics and VWF-increasing treatment.^[20][21][16]

^[1]

Inhibitors — the biggest complication

Inhibitors — neutralising IgG antibodies to factor VIII (less often IX) — develop in 20 to 30 percent of children with severe haemophilia A (1 to 5 percent of haemophilia B), risk concentrated in the first 50 exposure days. They render standard factor replacement ineffective and are the single most important determinant of morbidity and mortality after severity.^[1][6]

Acute bleeding with an inhibitor is treated with bypassing agents:^[10]

• Recombinant activated factor VII (rFVIIa) — a typical regimen is 90 micrograms per kilogram repeated every 3 hours if needed; in a Bayesian meta-regression this resolved 88 percent of joint bleeds by 24 hours and 95 percent by 36 hours.^[13]
• Activated prothrombin complex concentrate (aPCC, FEIBA) — a typical regimen is 75 units per kilogram repeated every 12 hours if needed (62 percent of joint bleeds resolved by 24 hours in the same model, which favoured rFVIIa at 12 to 36 hours).^[13]
• Emicizumab provides effective prophylaxis in patients with inhibitors — once-weekly dosing cut the annualised bleed rate by 87 percent in HAVEN 1.^[8]

Eradication: immune tolerance therapy is the established approach to eradicating inhibitors in congenital haemophilia.^[15] Acquired haemophilia is treated with bypassing agents — recombinant activated factor VII, activated prothrombin complex concentrate or recombinant porcine factor VIII — plus immunosuppression with corticosteroids, cyclophosphamide or rituximab, alone or in combination; the median time to remission is five weeks.^[10]

The rare factors — and why factor XIII fools everyone

• Factor XI deficiency (haemophilia C) — common in Ashkenazi Jews (carrier frequency up to 8 percent); bleeding is disproportionate to the factor level and is provoked at sites of high fibrinolytic activity (mouth, tonsils, urinary tract). First-line is tranexamic acid, then fresh frozen plasma or factor XI concentrate for major bleeding. The APTT is prolonged, PT normal.^[1]
• Factor VII deficiency — the commonest of the rare factor deficiencies; PT prolonged, APTT normal. Treat with recombinant activated factor VII 15 to 30 microgram/kg.
• Factor XIII deficiency — PT and APTT are both normal (the clot forms but is not cross-linked and is fragile). Hallmarks: umbilical stump bleeding in neonates, delayed bleeding, recurrent miscarriage, intracranial bleeding. Treat with factor XIII concentrate monthly.^[1]
• Fibrinogen disorders — afibrinogenaemia (prolonged PT, APTT and thrombin time) and dysfibrinogenaemia (some variants cause thrombosis). Treat with cryoprecipitate or fibrinogen concentrate.^[1]

Acquired coagulopathies

• Acquired haemophilia A — neutralising autoantibodies to factor VIII, typically in older patients with comorbidities and no previous bleeding history; the presentation is an isolated prolonged APTT and the Nijmegen-modified Bethesda assay detects the inhibitor. Treat bleeds with bypassing agents and eradicate the antibody with corticosteroids, cyclophosphamide or rituximab.^[10][6]
• A prolonged APTT before an invasive procedure — never ignore it: roughly 10 percent of acquired haemophilia patients present without any bleeding.^[10]

The subtypes that bite

• Severe haemophilia A in a child — primary prophylaxis started before age 2 (after the first joint bleed, or before any) is the evidence-based first-choice treatment to prevent arthropathy; subcutaneous emicizumab spares the venous-access problems of frequent factor infusions in small children. Take precautions with intramuscular injections and aspirin-containing medicines.^[17][15]
• Type 3 VWD behaves like severe haemophilia — prophylaxis should be considered in those with more severe bleeding, using VWF replacement.^[16]
• Acquired haemophilia in the elderly — spontaneous, often severe bleeding with no childhood history, an isolated prolonged APTT, and autoantibodies on the Bethesda assay; look for the underlying autoimmune or neoplastic trigger.^[10][6]

When it goes wrong — complications and the traps that cost marks

Disease complications: haemophilic arthropathy (the leading long-term morbidity, prevented by primary prophylaxis); intracranial haemorrhage (the leading cause of death — factor to 100 percent before imaging); compartment syndrome from intramuscular bleeds; airway compromise from parapharyngeal haematomas.^[1]

Treatment complications: inhibitor formation in 20 to 30 percent of severe haemophilia A; transfusion-transmitted infection (the historical hepatitis C and HIV catastrophe of plasma-derived factor in the 1970s and 1980s — modern recombinant, viral-inactivated products are safe); thrombosis from repeated bypassing agents or from the dangerous combination of emicizumab plus activated prothrombin complex concentrate (never combine them).^[1]

The classic pitfalls: ^[1]

• Delaying factor replacement to await levels or imaging in a suspected intracranial bleed.
• Intramuscular injections, aspirin or NSAIDs in a haemophilia patient.
• Giving desmopressin in type 2B VWD (worsens thrombocytopenia) or without a prior DDAVP trial.
• Relying on the APTT alone — factor XIII deficiency, mild haemophilia and type 2N VWD can present with a normal APTT.
• Failing to screen for an inhibitor when bleeding escalates on adequate factor.
• Missing acquired haemophilia in an elderly patient with new bleeding — the mixing study is the discriminator.^[1]

Prognosis and disposition

With modern prophylaxis — emicizumab, recombinant factor and gene therapy — life expectancy in severe haemophilia is now near-normal in high-income countries, a transformation from the 1970s when most severe haemophilia patients died before 20. The determinants of outcome are severity, the presence and titre of inhibitors, access to comprehensive care, and adherence to prophylaxis.^[1]

Disposition from the emergency department depends on the bleed. A joint or muscle bleed gets a single factor dose, RICE, analgesia and next-day review. An ICH, airway bleed, iliopsoas or compartment bleed mandates admission with sustained factor cover above 50 to 100 percent for 7 to 14 days. A new inhibitor or acquired haemophilia needs haematology admission for bypassing therapy, eradication and investigation of the trigger. Every patient benefits from a comprehensive haemophilia treatment centre.^[6]

Special populations

• Neonates and delivery — suspect haemophilia in a male neonate with unusual bleeding; circumcision of at-risk males should wait until haemophilia is excluded or covered with factor concentrate; take precautions with intramuscular injections (including neonatal vitamin K). For a fetus potentially affected with a bleeding disorder, avoid fetal scalp clips and operative vaginal delivery, and consider caesarean delivery for an affected male neonate to reduce the risk of neonatal intracranial haemorrhage.^[15][19]
• Pregnancy and the peripartum — obtain clotting factor levels in the third trimester and plan delivery at a centre with haemostasis expertise if levels do not meet the minimum threshold (for example under 50 percent for von Willebrand factor, factor VIII or factor IX); haemostatic agents include factor concentrates, desmopressin and tranexamic acid; monitor affected women for delayed postpartum bleeding. The VWD guidelines address neuraxial anaesthesia during labour and delivery and postpartum management specifically.^[19][2]
• The elderly — acquired haemophilia A with no previous bleeding history, an isolated prolonged APTT, and an underlying autoimmune or neoplastic trigger.^[10][6]
• Surgery and dentistry — plan with haematology: VWF/FVIII concentrate dosing aims to raise and maintain both VWF and factor VIII at haemostatic levels through surgery and afterwards; a tranexamic acid mouthwash can cover dental work; a patient on emicizumab still needs factor-based cover for surgery and invasive procedures.^[14][21][25]

The evidence and regional differences

^[1]

Regional deltas. In high-income regions, emicizumab is first-line prophylaxis for severe haemophilia A and gene therapy is being deployed. In India and South Asia, cost is the dominant constraint — plasma-derived factor VIII and IX remain widely used, emicizumab access is expanding but not universal, prophylaxis uptake is lower and arthropathy remains common in adults. The historical HIV and hepatitis C cohort from the 1970s and 1980s persists everywhere.^[1]

Controversies the exam may probe: the durability of gene therapy (factor VIII levels decline gradually; re-dosing is blocked by pre-formed anti-AAV antibodies); whether emicizumab monotherapy suffices for surgery (it does not — additional factor is required); and the place of non-factor rebalancing therapies (fitusiran, anti-TFPI agents).^[1]

The mantra, and the mnemonic

^{[1] [9] [10] [11] [13]}

The mantra: Factor first and investigate after — for an intracranial bleed, factor to 100 percent before the scan.^[1]

Ward-round test — three stems, thirty seconds each

Stem 1 — the boy with the swollen knee (answer)ShowHide

A 4-year-old with a painful flexed knee, easy bruising and a maternal uncle who died of bleeding. APTT prolonged, PT and platelets normal, mixing study corrects. What is the diagnosis, the confirmatory test, and the first treatment step? Model: This is haemophilia (A or B — clinically identical). A prolonged APTT with a normal PT that corrects on mixing indicates a factor deficiency rather than an inhibitor; confirm with factor VIII and factor IX activity assays, which also grade severity (severe disease means factor activity under 1 IU/dL).^[23][17] Treat the acute bleed with immediate factor replacement on suspicion — rest the joint, paracetamol for pain, and caution with intramuscular injections and aspirin-like drugs.^[11][22][15] Long-term, severe disease gets prophylaxis — subcutaneous emicizumab (approved with and without inhibitors) or regular factor VIII.^[9]

Stem 2 — the head injury that cannot wait for the scan (answer)ShowHide

A 3-year-old with severe haemophilia A falls off a bed and vomits. He is drowsy. The registrar wants a CT head before any treatment. What do you do? Model: Do not wait for imaging. Emergency management of haemophilia is immediate factor replacement based on suspicion rather than confirmation, and in intracranial haemorrhage factor VIII replacement is performed prior to radiological examinations and consultations.^[11][12] Central nervous system bleeding affects 3 to 8 percent of haemophilia patients and is a major cause of mortality and morbidity. The dose achieving 100 percent factor activity is 50 units per kilogram of factor VIII; thereafter the objective is to hold factor levels in the normal range through treatment and follow-up.^[12][11]

Stem 3 — the elderly man with new bruising (answer)ShowHide

A 78-year-old presents with dramatic spontaneous bruising and a thigh haematoma. He has no childhood or family history of bleeding. APTT prolonged, PT and platelets normal — but the mixing study does NOT correct. What is this, and what is the next test? Model: This is acquired haemophilia A — neutralising autoantibodies against factor VIII in a patient with no previous bleeding history; the presentation is an isolated prolonged APTT due to factor VIII deficiency. The next test is the Nijmegen-modified Bethesda assay for the inhibitor (with a factor VIII activity level). Treat acute bleeds with bypassing agents — recombinant activated factor VII, activated prothrombin complex concentrate or recombinant porcine factor VIII — and eradicate the antibody with immunosuppression: corticosteroids, cyclophosphamide or rituximab (median time to remission five weeks). Search for the underlying trigger.^[10]

References25ShowHide

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