Von Willebrand's Disease

📋 Key Information Summary

📋

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting approximately 1% of the general population, though clinically significant disease affects ~0.01%.
Type 1 VWD (partial quantitative deficiency of VWF) accounts for ~70–80% of cases; Type 2 (qualitative defects) ~15–20%; Type 3 (virtual absence of VWF) is rare (<5%).
Type 1 is autosomal dominant with variable penetrance; Types 2A, 2B, 2M are usually autosomal dominant; Type 2N and Type 3 are autosomal recessive.
The hallmark clinical presentation is mucocutaneous bleeding — epistaxis, menorrhagia, easy bruising, gingival bleeding, and prolonged bleeding post-procedure.
Initial investigations: FBC, blood film, APTT, PT/INR, fibrinogen, VWF antigen (VWF:Ag), VWF activity (VWF:GPIbM or VWF:RCo), Factor VIII:C, and VWF multimer analysis.
VWF:Ag/VWF:GPIbM ratio and multimer analysis distinguish Type 1 from Type 2 subtypes; factor VIII level helps identify Type 2N and Type 3.
DDAVP (desmopressin) is the first-line treatment for most Type 1 VWD and some Type 2 subtypes; perform a therapeutic trial to confirm individual response.
VWF-containing factor concentrates (e.g., Biostate®, Wilate®) are required for Type 3, severe Type 1, Type 2B, and DDAVP non-responders or refractory patients.
Tranexamic acid is an essential adjunct for mucocutaneous bleeding control, particularly for menorrhagia, dental procedures, and epistaxis.
Always avoid antiplatelet agents (aspirin, NSAIDs) as they worsen bleeding risk in VWD.
Pre-procedural haemostatic planning with a haematologist is essential; aim for VWF:RCo and FVIII:C ≥50 IU/dL for major surgery.
Iron deficiency is common due to chronic blood loss; monitor ferritin and treat with oral or IV iron as indicated.
Aboriginal and Torres Strait Islander peoples may face barriers to diagnosis and specialist access, particularly in remote communities; culturally safe care and point-of-care testing pathways should be prioritised.
Genetic counselling is recommended for affected families, particularly for autosomal recessive types (2N, 3).
Pregnancy in Type 1 VWD usually shows improvement in VWF levels in the third trimester; however, Type 2 and Type 3 patients require specialist management and postpartum haemorrhage risk remains.

Introduction & Australian Epidemiology

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, caused by quantitative deficiency or qualitative dysfunction of von Willebrand factor (VWF), a multimeric glycoprotein critical for platelet adhesion to damaged endothelium and stabilisation of coagulation factor VIII (FVIII) in the circulation. The prevalence of laboratory-diagnosed VWD is approximately 1% of the general population, though clinically significant bleeding occurs in only ~0.01% (1 in 10,000).

In Australia, the Australasian Society of Thrombosis and Haemostasis (ASTH) estimates that tens of thousands of Australians have some form of VWD, though many remain undiagnosed. The Royal Children's Hospital Melbourne and the Australian Bleeding Disorders Registry (managed by the National Blood Authority) are key centres for epidemiological data collection.

VWD affects males and females equally in its inheritance, though clinical presentation often differs by sex due to the haemostatic challenge of menstruation and childbirth. Women with heavy menstrual bleeding (HMB) are a particularly important diagnostic group, and delays in diagnosis remain common in Australia.

ℹ️

Australian prevalence: Mild Type 1 VWD likely affects ~1 in 100 Australians. Type 3 VWD affects approximately 1 in 1 million. The Haemophilia Foundation Australia (HFA) supports patients and families with all bleeding disorders including VWD.

Pathophysiology

Von Willebrand factor (VWF) is a large multimeric glycoprotein synthesised by vascular endothelial cells (stored in Weibel–Palade bodies) and megakaryocytes (stored in platelet α-granules). Its haemostatic functions include:

Platelet adhesion: VWF mediates initial platelet tethering and adhesion to exposed subendothelial collagen at sites of vascular injury, particularly under high shear stress in arterioles and capillaries.
Platelet aggregation: VWF binds platelet GPIbα on the glycoprotein Ib–IX–V complex, facilitating platelet plug formation.
FVIII stabilisation: VWF serves as the carrier protein for FVIII, protecting it from premature proteolytic degradation and extending its plasma half-life from ~2 hours to ~12 hours.

Deficiency or dysfunction of VWF therefore leads to two pathological consequences: impaired primary haemostasis (manifesting as mucocutaneous bleeding) and reduced FVIII levels (which may cause a secondary coagulation defect resembling mild haemophilia A). The degree of clinical bleeding depends on the severity of VWF reduction, the presence of dysfunctional VWF multimers, and the associated FVIII level.

Types & Inheritance

VWD is classified into three major types, with further subdivision of Type 2 into four subtypes (2A, 2B, 2M, 2N). Accurate typing is essential for guiding management decisions.

Type	Mechanism	VWF:Ag	VWF:GPIbM / RCo	FVIII:C	Multimers	Inheritance
Type 1	Partial quantitative deficiency of VWF	↓	↓ (proportionate)	↓ or low-normal	Normal pattern	AD (variable penetrance)
Type 2A	Decreased high-molecular-weight (HMW) multimers; defective secretion or increased ADAMTS13 proteolysis	↓ or N	↓↓ (disproportionate)	↓ or N	Absent HMW multimers	AD
Type 2B	Enhanced binding to GPIb → loss of HMW multimers and possible thrombocytopaenia	↓ or N	↓↓ (disproportionate)	↓ or N	Absent HMW; enhanced platelet agglutination with ristocetin	AD
Type 2M	Decreased platelet-dependent function despite normal multimer distribution	N or ↓	↓↓ (disproportionate)	N or ↓	Normal pattern	AD
Type 2N	Defective FVIII binding; mimics mild haemophilia A	N	N	↓↓	Normal pattern	AR
Type 3	Virtual absence of VWF (homozygous or compound heterozygous null alleles)	Absent / <3 IU/dL	Absent	<10 IU/dL	Absent	AR

⚠️

DDAVP caution in Type 2B: Desmopressin is generally contraindicated in Type 2B VWD because it may paradoxically worsen thrombocytopaenia and enhance platelet aggregation via release of abnormal VWF. Use VWF-containing concentrates instead.

Type 1 — Partial Quantitative Deficiency (~70–80% of VWD)

Type 1 is the most common form and is inherited in an autosomal dominant pattern with variable penetrance and expressivity. VWF levels may range from ~20–50 IU/dL (mild) to <10 IU/dL (severe). Blood group O individuals have ~25% lower baseline VWF levels, which can confound diagnosis. VWF:Ag and VWF:RCo are reduced proportionately, and multimer analysis shows a normal distribution.

Phenotypic expression can be influenced by ABO blood group, age, stress, exercise, inflammation, and hormonal status (e.g., pregnancy, oral contraceptives). Patients with Type 1 VWD are typically excellent responders to DDAVP.

Type 2 — Qualitative Defects (~15–20% of VWD)

Type 2 VWD is subdivided into four functional variants. In all Type 2 subtypes, there is a discrepancy between VWF antigen level and functional activity (VWF:RCo/VWF:Ag ratio <0.7 is a key diagnostic clue).

Type 2A: The most common qualitative subtype. Characterised by loss of high-molecular-weight (HMW) multimers due to either defective intracellular processing or enhanced ADAMTS13-mediated proteolysis. Results in impaired platelet adhesion. Usually autosomal dominant.
Type 2B: Gain-of-function mutations in the GPIbα-binding domain of VWF lead to spontaneous binding to platelets. HMW multimers are consumed, and thrombocytopaenia may occur, especially during physiological stress, pregnancy, or infection. The RIPA (ristocetin-induced platelet aggregation) assay shows increased sensitivity.
Type 2M: Loss-of-function mutations that impair VWF binding to platelet GPIb without affecting multimer assembly. Multimer pattern is normal but function is reduced. Autosomal dominant.
Type 2N: Mutations in the FVIII-binding site of VWF lead to failure to stabilise FVIII, resulting in low FVIII:C with normal VWF levels. This subtype mimics mild haemophilia A and is autosomal recessive. A specific FVIII binding assay or genetic testing is needed to differentiate from haemophilia A in males, and can be critical for genetic counselling.

Type 3 — Virtual Absence of VWF (<5% of VWD)

Type 3 VWD is the most severe form, inherited in an autosomal recessive pattern. Patients have virtually undetectable VWF:Ag (<3 IU/dL) and FVIII:C levels usually <10 IU/dL. Clinical features include severe mucocutaneous bleeding, haemarthroses, and soft-tissue haematomata resembling moderate-to-severe haemophilia A. Patients do not respond to DDAVP and require VWF-containing concentrates for haemostasis.

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Anti-VWF alloantibodies: Patients with Type 3 VWD are at risk of developing neutralising anti-VWF alloantibodies (approximately 5–10%), which can cause anaphylaxis with concentrate infusion and render replacement therapy ineffective. Monitor for anaphylactic reactions and check for inhibitors if poor response to concentrates.

Clinical Features — Mucocutaneous Bleeding

The hallmark of VWD is mucocutaneous bleeding due to defective primary haemostasis. Symptoms vary by VWD type and severity but share common features:

Mild

Type 1 (mild) / Type 2M

Occasional epistaxis, easy bruising, prolonged bleeding post-dental extraction. May go undiagnosed until haemostatic challenge.

Often diagnosed incidentally or after surgical bleeding

Moderate

Type 2A / 2B / Type 1 (severe)

Frequent epistaxis (>5 min, >5 episodes/year), heavy menstrual bleeding (HMB), prolonged bleeding from cuts, postpartum haemorrhage, GI bleeding, haematomata.

May require pre-procedural haemostatic cover

Severe

Type 3 / Type 2N (low FVIII)

Severe mucocutaneous AND deep tissue bleeding: haemarthroses, muscle haematomata, intracranial haemorrhage (rare), severe postpartum haemorrhage. FVIII:C <10 IU/dL.

Requires specialist haematology centre, lifelong management

Common Clinical Manifestations

Symptom	Prevalence	Clinical Notes
Epistaxis	~60–70%	Most common presenting symptom; often recurrent from childhood
Heavy menstrual bleeding (HMB)	~50–90% of women	Leading cause of iron deficiency; may be first presentation in adolescence
Easy/prolonged bruising	~50–60%	Spontaneous ecchymoses, particularly on limbs
Prolonged bleeding post-procedure	~40–50%	Dental extraction, tonsillectomy, circumcision, surgery
Postpartum haemorrhage	~20–40%	Primary and secondary PPH; VWF levels fall postpartum
Gingival bleeding	~30–40%	Spontaneous or post-brushing; respond well to tranexamic acid mouthwash
GI bleeding	~10–15%	May be occult; angiodysplasia more common in Type 2A
Haemarthroses / muscle haematomata	Type 3 only	Due to very low FVIII:C levels (<10 IU/dL)

ℹ️

Bleeding Assessment Tool (ISTH-BAT): The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool is validated for evaluating bleeding symptoms in VWD. A score ≥4 (adults) or ≥3 (children) is considered abnormal and should prompt VWD testing. This is available via haematology referral in Australian centres.

Investigations

Diagnosis of VWD requires a combination of clinical history, family history, and a panel of specialised laboratory tests. Testing should be performed when the patient is well and not acutely bleeding, as VWF levels are elevated by stress, inflammation, pregnancy, and oral contraceptive use.

Initial Screening Tests

Essential

Full Blood Count (FBC)

MBS Item 65070. Check platelet count (may be low in Type 2B). May show microcytic anaemia from chronic blood loss.

Essential

APTT (Activated Partial Thromboplastin Time)

MBS Item 65090. Prolonged when FVIII:C is reduced (Type 2N, Type 3, some severe Type 1). Normal in mild Type 1.

Essential

PT/INR

MBS Item 65080. Usually normal in VWD; helps exclude coagulopathy.

Essential

Fibrinogen

MBS Item 65100. To exclude hypofibrinogenaemia as a cause of bleeding.

Specialised VWD Diagnostic Panel

Specialist

VWF Antigen (VWF:Ag)

Quantitative measurement of VWF protein level by immunological assay. Normal range: 50–150 IU/dL. Low in Types 1, 2A, 2B, 3. Normal in Type 2M, 2N.

Specialist

VWF Activity — VWF:GPIbM or VWF:RCo (Ristocetin Cofactor)

Functional VWF assay measuring platelet-dependent activity. VWF:GPIbM is the newer automated method replacing the less reproducible VWF:RCo. Key ratio: VWF:GPIbM/VWF:Ag <0.7 suggests Type 2 VWD.

Specialist

Factor VIII Coagulant Activity (FVIII:C)

MBS Item 65130. Low in Type 2N, Type 3, and severe Type 1. Critical for treatment planning and monitoring.

Specialist

VWF Multimer Analysis

Electrophoretic analysis of VWF multimer distribution. Available at specialised reference laboratories (e.g., Royal Prince Alfred Hospital, Melbourne Haemophilia Centre). Distinguishes Type 1 (normal pattern) from Type 2A/2B (absent HMW multimers).

Specialist

Ristocetin-Induced Platelet Aggregation (RIPA)

Platelet function test using low-dose ristocetin. Enhanced in Type 2B (platelet agglutination at low ristocetin concentrations). Reduced in Type 2A, 2M.

Specialist

VWF:FVIII Binding Assay

Specific test for Type 2N VWD. Measures the ability of patient VWF to bind exogenous FVIII. Differentiates Type 2N from mild haemophilia A, which is critical for genetic counselling.

Genetic Testing

VWF gene sequencing (locus 12p13.31) is available through specialised laboratories in Australia, including through the Australian Genomics Health Alliance. It is most useful for:

Confirming diagnosis when laboratory results are ambiguous
Distinguishing Type 2N VWD from mild haemophilia A
Family studies and genetic counselling for recessive types
Predicting DDAVP response in borderline cases

⚠️

Pitfall — ABO blood group: Blood group O individuals have ~25% lower VWF:Ag and VWF:RCo levels than group A, B, or AB. A VWF level of 35 IU/dL in a group O patient may represent a normal variant rather than Type 1 VWD. Always consider ABO group when interpreting VWF levels.

DDAVP Trial

A therapeutic trial with desmopressin (DDAVP) is recommended for all newly diagnosed Type 1 patients and select Type 2 patients (not Type 2B). This confirms individual responsiveness:

Protocol: DDAVP 0.3 μg/kg IV infusion over 20–30 minutes (or 300 μg intranasal for adults >50 kg)
Measure: VWF:Ag, VWF:RCo/GPIbM, and FVIII:C at baseline, 1 hour, and 4 hours post-DDAVP
Adequate response: ≥3-fold rise in VWF:RCo and FVIII:C to ≥50 IU/dL
Monitor: Hyponatraemia risk (fluid restrict post-infusion), tachyphylaxis with repeated dosing

Risk Stratification & Severity Scoring

Severity assessment guides the intensity of haemostatic cover and the setting of management:

Low Risk

Mild Type 1 (VWF:Ag 30–50 IU/dL)

Infrequent bleeding symptoms; may not require prophylactic treatment. Antifibrinolytics alone may suffice for minor procedures.

Setting: GP management with haematology backup

Moderate Risk

Type 1 (VWF:Ag <30), Type 2A, 2M

Recurrent mucocutaneous bleeding, HMB, post-procedural bleeding. Requires DDAVP or concentrates for haemostatic cover.

Setting: Haematologist-led management, pre-procedural planning

High Risk

Type 2B, Type 2N, Type 3

Severe bleeding, thrombocytopaenia risk (2B), deep tissue haemorrhage, inhibitor risk (Type 3). Requires concentrates, may need immunotolerance if inhibitors develop.

Setting: Tertiary haemophilia comprehensive care centre

Procedure-Related Risk

Procedure Risk	Examples	Target VWF:RCo / FVIII:C	Duration
Minor	Dental extraction, skin biopsy, minor endoscopy	≥50 IU/dL	Single dose often sufficient + tranexamic acid
Moderate	Tonsillectomy, colonoscopy with polypectomy, arthroscopy	≥50–70 IU/dL	3–5 days
Major	Abdominal surgery, joint replacement, caesarean section	≥80–100 IU/dL (peak), maintain ≥50 IU/dL	7–14 days

Management

Management of VWD involves both on-demand treatment of bleeding episodes and prophylactic cover for procedures. Three main pharmacological agents are used, often in combination.

First-Line Agents

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Desmopressin (DDAVP)

Minirin® · Desmopressin Sandoz® · DDAVP® · Vasopressin analogue

Mechanism Stimulates release of stored VWF and FVIII from endothelial Weibel–Palade bodies via V2 receptor

Indications Type 1 VWD (first-line), some Type 2A, Type 2M. NOT for Type 2B (contraindicated) or Type 3 (no VWF to release)

IV dose 0.3 μg/kg in 50 mL 0.9% NaCl IV over 20–30 minutes

Intranasal dose (adults) 300 μg (one spray of 150 μg per nostril) — Stimate® or equivalent

Paediatric intranasal <50 kg: 150 μg (single nostril). <2 years: generally IV route preferred

SC/IM dose 0.3 μg/kg SC or IM if IV access unavailable

Duration of effect Peak at 30–60 min; effect lasts 6–8 hours. Repeat every 12–24 hours for up to 3–4 doses; tachyphylaxis with prolonged use

Renal adjustment Use with caution; increased hyponatraemia risk in renal impairment. Monitor sodium closely

Key precautions Fluid restrict to 500 mL in first 12 hours post-dose. Monitor for hyponatraemia, especially in children <2 years and elderly. Avoid repeated dosing >3–4 days

PBS status ✔ PBS General Benefit

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Tranexamic Acid

Cyklokapron® · Generic · Antifibrinolytic (lysine analogue)

Mechanism Inhibits plasminogen activation and fibrinolysis, stabilising clot formation at mucosal sites

Oral dose (adult) 1 g PO TDS (or 13 mg/kg TDS); max 4 g/day

IV dose (adult) 1 g IV over 10 minutes TDS, or 1 g loading then 1 g over 8 hours

Paediatric dose Oral: 15–25 mg/kg TDS (max 1 g per dose). IV: 10 mg/kg TDS

Mouthwash 5% tranexamic acid solution, 10 mL swilled for 2 minutes TDS for gingival/oral bleeding

Indications Mucocutaneous bleeding: menorrhagia, epistaxis, dental procedures, oral surgery, GI bleeding. Can be combined with DDAVP

Renal adjustment eGFR 30–59: reduce to 50% dose. eGFR <30: avoid or use with extreme caution; seizure risk at high doses

Contraindications Active thromboembolic disease, subarachnoid haemorrhage (risk of cerebral oedema), severe renal impairment

PBS status ✔ PBS General Benefit

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VWF-Containing Factor Concentrates

Biostate® · Wilate® · Humate-P® · VWF/FVIII replacement

Mechanism Exogenous VWF and FVIII replacement; provides functional VWF for platelet adhesion and FVIII stabilisation

Indications Type 3 VWD, Type 2B, DDAVP non-responders, DDAVP contraindicated, severe bleeding not controlled by DDAVP, major surgery

Biostate® dose 40–80 IU/kg IV loading; maintenance 20–40 IU/kg every 12–24 hours. Dose based on VWF:RCo recovery target

Wilate® dose 40–60 IU/kg IV loading for bleeding/surgery. Contains VWF:RCo and FVIII:C in 1:1 ratio

Monitoring Check VWF:RCo and FVIII:C 15–30 minutes post-infusion (peak), then pre-dose (trough). Adjust dosing to maintain target levels

Key caution Monitor for thrombotic risk with repeated dosing; FVIII can accumulate over time. Check FVIII:C at 24 and 48 hours with prolonged use

PBS status ✔ Authority Required (via National Blood Authority)

Additional Agents & Adjuncts

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Aminocaproic Acid

Generic · Antifibrinolytic (alternative to tranexamic acid)

Adult dose 4–5 g PO/IV loading, then 1 g PO/IV hourly (max 30 g/day)

Use Alternative antifibrinolytic when tranexamic acid unavailable or contraindicated

PBS status ⚠ Not PBS-listed for VWD

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Combined Oral Contraceptive Pill (for HMB)

Ethinylestradiol/levonorgestrel · Various · Hormonal therapy

Use First-line hormonal management for HMB in VWD; raises endogenous VWF levels via oestrogen effect

PBS status ✔ PBS General Benefit

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Iron Replacement

Ferrous sulphate / Ferinject® (IV ferric carboxymaltose) · Iron supplementation

Oral dose Ferrous sulphate 325 mg PO daily (elemental iron ~105 mg); take on empty stomach with vitamin C

IV dose Ferinject® (ferric carboxymaltose) 500–1000 mg IV as single infusion if oral intolerant or ferritin severely depleted

Monitoring Ferritin, transferrin saturation, FBC every 3–6 months in chronic blood loss

PBS status ✔ PBS General Benefit (oral). IV iron: Authority Required if oral intolerant

⚠️

Avoid: Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) impair platelet function and worsen mucocutaneous bleeding. Paracetamol is the preferred analgesic. If NSAIDs are essential, use at the lowest dose for the shortest duration with haematology advice.

Management Algorithm by VWD Type

1

Type 1 (mild–moderate)

First-line: DDAVP (if trial positive). Adjunct: tranexamic acid for mucocutaneous bleeding. VWF concentrates for DDAVP failure or major surgery.

2

Type 2A / 2M

DDAVP trial (may have partial response). VWF concentrates for major haemostatic challenges. Tranexamic acid as adjunct.

3

Type 2B

DDAVP generally contraindicated (worsens thrombocytopaenia). First-line: VWF-containing concentrates. Platelet transfusion if severe thrombocytopaenia with bleeding.

4

Type 2N

DDAVP usually ineffective (VWF is normal; FVIII binding is defective). VWF concentrates with combined FVIII. Recombinant FVIII may also be used.

5

Type 3

DDAVP ineffective (no VWF to release). VWF-containing concentrates are the only option. Consider prophylactic regimen in severe recurrent bleeding. Monitor for inhibitors.

Monitoring

VWF and FVIII levels: Monitor VWF:Ag, VWF:RCo/GPIbM, and FVIII:C at baseline and annually in stable patients; more frequently during treatment for acute bleeding or surgery.
Post-DDAVP levels: Measure 1 and 4 hours post-DDAVP to confirm response; repeat with each therapeutic course if using intermittently.
Post-concentrate levels: VWF:RCo and FVIII:C at 15–30 minutes post-infusion (peak recovery) and pre-dose (trough). Adjust dosing to maintain targets.
FVIII accumulation: With repeated VWF concentrate dosing, FVIII:C can rise above target (risk of thrombosis). Monitor daily FVIII:C during prolonged treatment courses.
Iron studies: Ferritin, transferrin saturation, and FBC every 3–6 months if chronic blood loss; more frequently if symptomatic anaemia.
Sodium: Serum sodium 12–24 hours post-DDAVP, especially in children, elderly, and those receiving repeated doses.
Inhibitor screen: Consider VWF inhibitor testing in Type 3 patients who show poor response to concentrate therapy or experience anaphylaxis during infusion.
Bleeding diary: Encourage patients to maintain a bleeding symptom diary for ongoing clinical assessment and treatment adjustment.

Special Populations

🤰 Pregnancy

Type 1 VWD: VWF and FVIII levels typically rise 2–3 fold by the third trimester due to oestrogen-mediated stimulation. Many women reach normal levels. However, levels fall rapidly postpartum — risk of secondary PPH (day 1–30) is significant.

Type 2 VWD: VWF levels may rise but dysfunctional protein persists. Type 2B: thrombocytopaenia may worsen. Cover with VWF concentrates at delivery.

Type 3 VWD: No improvement in VWF levels during pregnancy. Requires VWF concentrates at delivery and postpartum. Neuraxial anaesthesia only if VWF:RCo ≥50 IU/dL.

Postpartum: Monitor VWF:RCo and FVIII:C for 2–4 weeks postpartum. Consider prophylactic tranexamic acid for 2–3 weeks. All women with VWD should deliver at a centre with haematology and transfusion support.

👶 Paediatrics

Diagnosis: VWF levels are physiologically low at birth and do not reach adult levels until 6 months of age. Delay definitive testing until after 6 months (ideally >2 years) if possible.

DDAVP: IV dose: 0.3 μg/kg. Intranasal: 150 μg for <50 kg. Children <2 years have higher risk of hyponatraemia — restrict fluids closely, monitor sodium 12–24 hours post-dose.

Tranexamic acid: 15–25 mg/kg PO TDS (max 1 g per dose). IV: 10 mg/kg TDS. Avoid in neonates with renal immaturity.

Immunisation: Subcutaneous or intramuscular injection with firm pressure for ≥5 minutes post-vaccination. Use the smallest gauge needle appropriate. Avoid NSAIDs as antipyretics post-vaccination.

👴 Elderly

Diagnosis: VWF levels increase with age, which can mask a previously low VWF level. A history of lifelong bleeding symptoms is key to diagnosis in older patients.

DDAVP: Use with caution; hyponatraemia risk is higher. Check serum sodium post-infusion. Avoid in patients with uncontrolled hypertension or heart failure.

Anticoagulants: Patients on anticoagulants or antiplatelets require careful haemostatic balancing. Haematology co-management is essential.

🩺 Renal Impairment

DDAVP: Higher risk of water retention and hyponatraemia. Use with close sodium monitoring; fluid restrict strictly. Consider reduced dose or alternative therapy.

Tranexamic acid: eGFR 30–59: reduce dose by 50%. eGFR <30: avoid or use with extreme caution due to accumulation and seizure risk.

VWF concentrates: No renal adjustment required; preferred agent in renal impairment.

🫁 Hepatic Impairment

Consideration: Liver disease may independently alter VWF metabolism and coagulation. Acquired von Willebrand syndrome should be considered in liver disease with new-onset bleeding.

DDAVP: May be less effective if hepatic VWF stores are depleted. VWF concentrates preferred in decompensated liver disease.

🛡️ Immunocompromised

General: Infection and inflammation can raise VWF levels (acute phase reactant), potentially masking VWD severity. Monitor levels when inflammation resolves.

HIV/hepatitis: VWF concentrates carry a theoretical infection risk despite modern viral inactivation; recombinant products may be preferred in some settings.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Prevalence & data gaps

There is limited epidemiological data on VWD prevalence specifically in Aboriginal and Torres Strait Islander peoples. However, the known burden of chronic disease and barriers to specialist access suggest significant underdiagnosis. Iron deficiency anaemia is highly prevalent and may mask underlying bleeding disorders.

Remote access

Specialist haematology services and VWD-specific testing (VWF:Ag, VWF:GPIbM, multimer analysis) are primarily available in metropolitan centres. Patients in remote and very remote communities may need to travel hundreds of kilometres or rely on telehealth consultations. Royal Flying Doctor Service (RFDS) can facilitate access for urgent needs.

Diagnostic delays

Heavy menstrual bleeding and recurrent epistaxis in Aboriginal and Torres Strait Islander women may be dismissed or treated symptomatically without investigation for underlying bleeding disorders. Culturally safe screening and awareness among primary care providers is essential.

Cultural considerations

Menstruation and reproductive health may be sensitive topics requiring gender-matched clinicians and culturally appropriate communication. Engage Aboriginal Health Workers and Liaison Officers as part of the care team. Yarning and storytelling approaches may support understanding of chronic conditions.

Medication access

DDAVP and tranexamic acid are PBS-listed and generally accessible via community pharmacies. However, VWF concentrates are supplied through the National Blood Authority and typically administered in hospital settings, which may be inaccessible in remote areas. Ensure adequate supply planning for patients returning to remote communities post-procedure.

Comorbidities

Higher rates of iron deficiency, chronic kidney disease, and cardiovascular disease in Aboriginal and Torres Strait Islander populations may complicate VWD management. Tranexamic acid dosing requires renal function monitoring. NSAID avoidance is especially important given concurrent renal and cardiovascular risks.

Actionable steps

1. Consider VWD in any Aboriginal or Torres Strait Islander patient with unexplained mucocutaneous bleeding or iron deficiency. 2. Use telehaematology services for initial assessment and diagnostic planning. 3. Partner with local Aboriginal Community Controlled Health Organisations (ACCHOs) for follow-up and medication support. 4. Advocate for inclusion in national bleeding disorder registries.

📚 References

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8. Haemophilia Foundation Australia. Von Willebrand Disease: A Guide for Patients and Families. Melbourne: HFA; 2022.
9. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework 2020 summary report. Canberra: AIHW; 2020.
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