Haemophilia & Bleeding Disorders in Children

Bleeding disorders in paediatrics split cleanly into two buckets: coagulation factor defects (deep bleeds, delayed, normal platelets — e.g. Haemophilia) and platelet/vessel defects (mucocutaneous bleeds, immediate — e.g. ITP, Von Willebrand disease). Getting this dichotomy right is the single most rewarding pattern for NEET PG, because almost every question is a screening-test plus clinical-pattern recognition exercise.

The two patterns of bleeding — the master framework

The first instinct on seeing a bleeding child should be to localise the defect to secondary haemostasis (coagulation) or primary haemostasis (platelet/vWF).

Feature	Coagulation defect (e.g. Haemophilia)	Platelet/vessel defect (e.g. ITP, vWD)
Site of bleed	Deep — joints (haemarthrosis), muscles, retroperitoneum	Superficial — skin, mucous membranes
Type of lesion	Large ecchymoses, deep haematoma	Petechiae, purpura, epistaxis, gum bleed
Timing after injury	Delayed (rebleed after initial clot)	Immediate
Bleeding after cuts	Minor	Persistent oozing
Menorrhagia	Uncommon	Common (vWD)
Inheritance	Often X-linked (Haem A/B)	Variable / acquired
Screening abnormality	↑ aPTT (or PT)	↑ Bleeding time / platelet count

High-yield: Petechiae = platelet problem; haemarthrosis = factor problem. Petechiae essentially never occur in pure Haemophilia, and haemarthrosis is rare in pure platelet disorders. This single discriminator answers a large fraction of stem-based questions.

Haemophilia — definition & classification

Haemophilia is an X-linked recessive inherited deficiency of a clotting factor of the intrinsic pathway.

• Haemophilia A — Factor VIII deficiency. Most common (≈80–85% of haemophilias). Incidence ~1 in 5000 male births.
• Haemophilia B (Christmas disease) — Factor IX deficiency. ~15–20%.
• Haemophilia C — Factor XI deficiency. Autosomal, common in Ashkenazi Jews; mild, usually only bleeds after surgery/trauma. Not X-linked — a frequent distractor.

Because it is X-linked recessive, affected males predominate; females are usually carriers. A carrier mother transmits to 50% of sons (affected) and 50% of daughters (carriers). An affected father gives the gene to all daughters (obligate carriers) and no sons. Symptomatic females are rare and occur via extreme lyonisation, Turner syndrome (45,XO), or homozygous/compound state.

Severity grading by factor level

Severity	Factor activity	Bleeding pattern
Severe	< 1% (<0.01 IU/mL)	Spontaneous haemarthrosis & muscle bleeds, often presents in infancy
Moderate	1–5%	Bleeding after minor trauma
Mild	5–40%	Bleeding only after major trauma/surgery; may present late

High-yield: Factor level <1% = severe; spontaneous bleeds. The clinical phenotypes of Haemophilia A and B are clinically indistinguishable — only the specific factor assay separates them.

Pathophysiology

Factors VIII and IX are essential cofactors/enzymes of the intrinsic (contact) pathway. The intrinsic tenase complex (FIXa + FVIIIa on phospholipid + Ca²⁺) activates FX. Loss of VIII or IX cripples thrombin generation, so a fibrin clot forms slowly and is unstable → delayed, recurrent deep bleeding. Platelet plug formation (primary haemostasis) is normal, so platelet count and bleeding time are normal — this is why superficial/petechial bleeding is absent.

The classic genetic lesion in severe Haemophilia A is the intron 22 inversion of the F8 gene (~40–45% of severe cases) — a tested molecular fact.

Clinical features of Haemophilia

• Often presents when the infant becomes mobile (crawling/walking) — first bleeds at 6–12 months.
• Haemarthrosis is the hallmark — knees > elbows > ankles. Repeated bleeds → target joint → chronic synovitis → haemophilic arthropathy and fixed deformity.
• Muscle haematomas — iliopsoas bleed (groin/flank pain, hip flexed, femoral nerve palsy) and calf/forearm bleeds (compartment syndrome, Volkmann contracture).
• Intracranial haemorrhage — leading cause of death; suspect after any head trauma.
• Prolonged bleeding after circumcision, dental extraction, intramuscular injections.
• Delayed bleeding after cord separation; cephalhaematoma at birth.
• Pseudotumour (encapsulated haematoma) — rare, chronic.

High-yield: A boy with recurrent painful, swollen knee (haemarthrosis) and a normal platelet count is Haemophilia until proven otherwise. Avoid IM injections and aspirin/NSAIDs.

Diagnosis & investigation of choice

Screening (step 1): PT, aPTT, platelet count, bleeding time.

• aPTT is prolonged (intrinsic pathway).
• PT is normal (extrinsic pathway intact).
• Platelet count, bleeding time, and thrombin time are normal.

Mixing study (step 2): Patient plasma + normal plasma. In factor deficiency, aPTT corrects. If it does not correct → a factor inhibitor (e.g. anti-FVIII antibody or lupus anticoagulant).

Confirmation / investigation of choice (step 3): Specific factor assay — Factor VIII activity (Haemophilia A) or Factor IX activity (Haemophilia B). This both confirms the diagnosis and grades severity.

Diagnostic flow:

Prolonged aPTT, normal PT → mixing study corrects → FVIII assay low → Haemophilia A → (if FVIII normal) check FIX → low = Haemophilia B

High-yield: aPTT ↑, PT normal, platelets normal, BT normal → think Haemophilia. The investigation of choice for diagnosis and typing is the specific factor assay.

A key cross-check: vWF deficiency also lowers FVIII (vWF carries and stabilises VIII), so a low FVIII with prolonged BT and abnormal platelet function should redirect you to von Willebrand disease, not Haemophilia A.

Management & drug of choice

The principle is factor replacement to a target level appropriate to the bleed.

• Haemophilia A → recombinant or plasma-derived Factor VIII concentrate.
  • 1 IU/kg of FVIII raises plasma level by ~2%. Half-life ~8–12 h.
• Haemophilia B → Factor IX concentrate.
  • 1 IU/kg of FIX raises level by ~1%. Half-life ~18–24 h.

Target levels: minor bleed/haemarthrosis ~30–50%; major bleed/surgery/intracranial ~80–100%.

High-yield: For mild Haemophilia A, the drug of choice (when level rise is modest, e.g. minor bleed/pre-procedure) is DDAVP (desmopressin) — it releases stored endogenous FVIII and vWF from endothelium (Weibel-Palade bodies), raising levels 2–4 fold. DDAVP does NOT work in Haemophilia B (no stored FIX). Watch for hyponatraemia (antidiuretic effect) — caution under 2 years.

Adjuncts:

• Antifibrinolytics — tranexamic acid / epsilon-aminocaproic acid for mucosal & dental bleeds. Avoid in haematuria (clot retention/ureteric obstruction).
• Prophylaxis — regular factor (or modern non-factor therapy) in severe disease to prevent arthropathy.
• Emicizumab — a bispecific antibody bridging activated FIX and FX, mimicking FVIII; subcutaneous prophylaxis for Haemophilia A, effective even with inhibitors.
• Inhibitor management — bypassing agents: activated prothrombin complex concentrate (aPCC/FEIBA) or recombinant FVIIa; immune tolerance induction for eradication.
• Local measures: rest, ice, compression, elevation (RICE), splinting; hepatitis B vaccination; avoid IM injections, aspirin, NSAIDs.

Mnemonic — "8 = 2, 9 = 1": each IU/kg of Factor VIII raises level by 2%; Factor IX by 1%.

Complications of Haemophilia

• Haemophilic arthropathy — chronic disabling joint disease (most important long-term morbidity).
• Inhibitor (alloantibody) development — more common in Haemophilia A; renders factor ineffective; suspect when bleeds stop responding.
• Transfusion-transmitted infection — historically HIV/HCV (now minimised with recombinant products).
• Compartment syndrome, Volkmann ischaemic contracture, femoral nerve palsy from muscle bleeds.
• Intracranial haemorrhage — top cause of bleeding death.
• Pseudotumour.

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Immune (Idiopathic) Thrombocytopaenic Purpura — ITP

ITP is the most common cause of acute-onset thrombocytopaenia in an otherwise well child, classically 1–4 weeks after a viral illness or vaccination (peak age 2–6 years).

Pathophysiology

Autoantibodies (usually IgG against platelet GPIIb/IIIa or GPIb/IX) coat platelets → splenic macrophage clearance → isolated thrombocytopaenia. It is a type II hypersensitivity / autoimmune process; in children, usually post-infectious and self-limiting.

Clinical features

• Sudden petechiae, purpura, bruising, epistaxis in a well-looking child.
• No hepatosplenomegaly, no lymphadenopathy, no pallor (their presence should prompt a hunt for leukaemia/aplastic anaemia).
• Serious bleeding (especially intracranial haemorrhage, ~0.1–0.5%) is rare but feared.

Investigations

• Platelet count low (often <20,000–30,000/µL), frequently with large platelets on smear.
• Normal Hb and WBC; normal smear otherwise.
• PT and aPTT normal.
• ITP is a diagnosis of exclusion — bone marrow shows normal or increased megakaryocytes (done if atypical features, before steroids in some protocols, or if treatment fails).

High-yield: Isolated thrombocytopaenia in a well child after a viral illness, with NO hepatosplenomegaly/lymphadenopathy, with large platelets and normal Hb/WBC = ITP. Marrow shows increased megakaryocytes.

Management

Driven by bleeding severity, not the platelet number alone.

Scenario	Approach
No/minor bleeding (skin only)	Observation — most children recover spontaneously
Significant mucosal bleeding	IVIG or corticosteroids (± anti-D in Rh+ non-splenectomised)
Life-threatening/ICH	Platelet transfusion + IVIG + IV steroids (methylprednisolone) ± emergency measures
Chronic (>12 months) / refractory	Splenectomy, rituximab, TPO-receptor agonists (eltrombopag, romiplostim)

High-yield: Acute childhood ITP is usually self-limiting — observation is appropriate for the well child with only cutaneous signs. First-line drug therapy when needed = IVIG (fastest rise) or corticosteroids. Acute (<3 mo), persistent (3–12 mo), chronic (>12 mo) is the current terminology — chronicity is more common in older children/adolescents.

Differentiate from TTP (pentad: fever, microangiopathic haemolytic anaemia, thrombocytopaenia, renal, neuro — ADAMTS13 deficiency) and HUS (diarrhoea-associated, E. coli O157:H7, renal failure) — both have schistocytes and haemolysis, unlike ITP.

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Von Willebrand Disease — vWD

The most common inherited bleeding disorder overall (much commoner than Haemophilia, though often mild). Mostly autosomal dominant.

Function of vWF

1. Bridges platelets to subendothelial collagen (via GPIb) → adhesion.
2. Carries and stabilises Factor VIII in circulation.

Hence vWD causes a platelet-type bleeding pattern (mucocutaneous, menorrhagia) plus a variably low FVIII.

Subtypes

Type	Defect	Notes
Type 1	Partial quantitative deficiency	Most common (~75%); mild; AD
Type 2	Qualitative (dysfunctional vWF) — subtypes 2A, 2B, 2N, 2M	2B: gain-of-function binds platelets → thrombocytopaenia; 2N mimics Haemophilia A (defective FVIII binding)
Type 3	Near-complete absence	Severe, autosomal recessive; very low FVIII, can mimic Haemophilia

Clinical & lab features

• Easy bruising, epistaxis, gum bleeding, menorrhagia, prolonged post-surgical/dental bleeding.
• Bleeding time / PFA-100 prolonged; aPTT may be mildly prolonged (low FVIII); platelet count usually normal (low in 2B).
• Investigations: vWF antigen (vWF:Ag), vWF activity (ristocetin cofactor, vWF:RCo), FVIII level, and ristocetin-induced platelet aggregation (RIPA).

High-yield: Ristocetin aggregates platelets only in the presence of normal vWF — so RIPA is reduced/absent in vWD but corrects with normal plasma. Exception: Type 2B shows INCREASED response to low-dose ristocetin. Ristocetin is the keyword that flags vWD.

Management

• DDAVP — drug of choice for Type 1 (releases endothelial vWF). Avoid in Type 2B (worsens thrombocytopaenia).
• vWF-containing FVIII concentrate (e.g. Humate-P) for Type 3, severe bleeds, or DDAVP-unresponsive types.
• Antifibrinolytics (tranexamic acid) for mucosal bleeds; oestrogens/OCPs for menorrhagia.

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Key differentials at a glance

Disorder	Inheritance	PT	aPTT	Platelets	BT/PFA	Discriminator
Haemophilia A/B	X-linked recessive	N	↑	N	N	Factor assay; haemarthrosis
von Willebrand	AD (mostly)	N	N/↑	N (↓ in 2B)	↑	Ristocetin; mucosal bleed
ITP	Acquired/autoimmune	N	N	↓	↑	Isolated low platelets, well child
Vitamin K deficiency / HDN	Acquired	↑	↑	N	N	Both PT & aPTT ↑; neonate
DIC	Acquired	↑	↑	↓	↑	↓ fibrinogen, ↑ D-dimer, sick child
Bernard-Soulier	AR	N	N	↓ (giant platelets)	↑	GPIb defect; absent ristocetin agg, no correction
Glanzmann thrombasthenia	AR	N	N	N	↑	GPIIb/IIIa defect; absent aggregation to all agonists except ristocetin

High-yield: Both PT and aPTT prolonged with normal platelets in a neonate not given vitamin K = Haemorrhagic Disease of the Newborn (factors II, VII, IX, X). Prevent with IM vitamin K at birth.

High-yield: Distinguish Bernard-Soulier (absent ristocetin aggregation, NOT corrected by normal plasma because the platelet receptor GPIb is missing) from vWD (absent ristocetin aggregation that IS corrected by adding normal plasma/vWF).

Recently asked / exam angle

• aPTT prolonged, PT normal, mixing study corrects → factor deficiency; if it does not correct → inhibitor (this two-step logic is a recurring single-best-answer theme).
• "1 IU/kg FVIII raises level by 2%; 1 IU/kg FIX raises by 1%" — direct dosage calculation MCQs.
• DDAVP works in mild Haemophilia A and vWD Type 1 but not in Haemophilia B or vWD Type 2B/3 — a favourite trap.
• Ristocetin as the keyword for vWD; Type 2B = increased low-dose ristocetin response with thrombocytopaenia.
• ITP management is bleeding-driven: observation for the well child; IVIG/steroids for significant bleeding; avoid platelet transfusion unless life-threatening.
• Identify the iliopsoas bleed (hip flexion, femoral nerve palsy) and the contraindication to IM injections / aspirin in Haemophilia.
• Intron 22 inversion of F8 in severe Haemophilia A; Haemophilia B = Christmas disease; Haemophilia C = Factor XI, autosomal, Ashkenazi Jews.
• Carrier-pedigree genetics: affected father → all daughters carriers, no sons affected.

Rapid revision

1. Haemophilia A = Factor VIII, Haemophilia B (Christmas) = Factor IX; both X-linked recessive, clinically identical.
2. aPTT ↑, PT normal, platelets & BT normal = Haemophilia; investigation of choice = specific factor assay.
3. Factor level <1% = severe (spontaneous haemarthrosis).
4. Mixing study corrects → deficiency; doesn't correct → inhibitor.
5. DDAVP for mild Haemophilia A & vWD Type 1; useless in Haemophilia B; avoid in vWD 2B.
6. Dose rule: VIII → 2% per IU/kg, IX → 1% per IU/kg.
7. Avoid IM injections, aspirin, NSAIDs; tranexamic acid for mucosal bleeds but not in haematuria.
8. ITP = post-viral, isolated thrombocytopaenia in a well child, large platelets, marrow shows ↑ megakaryocytes; usually self-limiting → observe.
9. ITP first-line drug = IVIG or steroids; platelet transfusion only for life-threatening bleed.
10. vWD = most common inherited bleeding disorder; mucocutaneous + menorrhagia; ristocetin is the keyword; Type 1 most common, Type 3 severe (AR).
11. vWF stabilises FVIII → low vWF gives low FVIII (can mimic Haemophilia; vWD 2N especially).
12. Both PT & aPTT ↑ in a neonate = Haemorrhagic Disease of Newborn → prevent with IM vitamin K; intracranial haemorrhage is the leading bleeding-death in Haemophilia.