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BASICS

  • vWD: lifelong bleeding disorder due to quantitative or qualitative vWF defects.
  • vWF: large glycoprotein facilitating platelet adhesion and carrying factor VIII (FVIII).
  • Common clinical signs: mucocutaneous bleeding, bleeding during childbirth/dental procedures, easy bruising, menorrhagia.
  • Inherited forms: autosomal dominant (most), autosomal recessive (less common).
  • Acquired von Willebrand disease (AvWD) is rare.

EPIDEMIOLOGY

  • Most common inherited bleeding disorder.
  • Prevalence: 109 to 2,200 per 100,000 in general population.
  • Equal frequency in males and females; women diagnosed more often due to menstrual/pregnancy bleeding.
  • AvWD prevalence estimated up to 0.1%.

ETIOLOGY AND PATHOPHYSIOLOGY

  • vWF released from endothelial cells and platelet Ξ±-granules.
  • Binds subendothelial collagen, facilitates platelet adhesion via GP1b receptor (primary hemostasis).
  • Carrier protein for FVIII; vWF deficiency causes decreased FVIII and defective secondary hemostasis.
  • Types of inherited vWD:
  • Type 1: mild-moderate quantitative deficiency (70-80% cases).
  • Type 2: qualitative defects with subtypes:
    • 2A: loss of high/intermediate molecular weight multimers.
    • 2B: gain-of-function mutation increases platelet binding, leading to thrombocytopenia.
    • 2M: defective platelet binding without multimer loss.
    • 2N: defective FVIII binding, low FVIII levels.
  • Type 3: severe, near absence of vWF and FVIII (1-5% cases).
  • Platelet-type vWD (pseudo-vWD): gain-of-function in platelet GP1b receptor; mimics 2B.
  • AvWD caused by autoimmune, cardiovascular, hematologic diseases, tumors, or medications.

GENETICS

  • vWF gene on chromosome 12.
  • Type 1 mostly autosomal dominant with variable expressivity; rare recessive cases.
  • Types 2A, 2B, 2M: autosomal dominant.
  • Type 2N and type 3: autosomal recessive inheritance.

RISK FACTORS

  • Inherited: positive family/personal bleeding history.
  • Acquired: lymphoproliferative/myeloproliferative disorders, autoimmune diseases, high shear vascular states.

ASSOCIATED CONDITIONS

  • Blood type O associated with 25-30% lower vWF levels; type 1 diagnosed more in type O individuals.

DIAGNOSIS

History

  • Family/personal bleeding history is critical.
  • Common bleeding sites: oral mucosa, gingiva, endometrium, GI tract.

Physical Exam

  • Evaluate mucocutaneous bleeding.

Differential Diagnosis

  • Congenital thrombocytopenias.
  • Platelet function defects.
  • Coagulation factor deficiencies.
  • Acquired inhibitors.

Laboratory Tests

  • CBC, PT/INR, PTT, fibrinogen, peripheral smear initially.
  • vWF antigen (vWF:Ag) – quantity of vWF.
  • vWF activity (Ristocetin cofactor assay, vWF:RCo) – function.
  • FVIII level (FVIII:C).
  • Multimeric analysis not routine in initial workup.

TREATMENT

General Measures

  • Minor bleeding often does not require treatment.
  • Prophylaxis before surgeries/dental procedures recommended.

First Line

  • Desmopressin (DDAVP): induces vWF release from endothelium; trial dosing to test response.
  • Factor replacement therapy with vWF/FVIII concentrates for more severe disease or DDAVP nonresponders.
  • Platelet transfusion in platelet-type vWD.
  • Monitor FVIII levels to prevent thromboembolism.

Second Line

  • Hormonal contraceptives for menorrhagia.
  • Platelets adjunctively for uncontrolled bleeding.
  • IV immunoglobulin in select acquired cases.

ADMISSION AND NURSING

  • Mechanical VTE prophylaxis preferred in low thrombotic risk patients.
  • Consider chemoprophylaxis with caution in high thrombotic risk if vWF levels preserved.

ONGOING CARE

  • Hematologist consultation before invasive procedures.
  • Avoid aspirin and NSAIDs.
  • Repeat labs if bleeding pattern changes in moderate-severe cases.

PATIENT EDUCATION

PROGNOSIS

  • Normal life expectancy in most.
  • Bleeding risk greatest in major trauma.
  • 15% may experience major bleeding over 4 years, mostly GI bleeds requiring hospitalization.

COMPLICATIONS

  • Development of alloantibodies to vWF after multiple transfusions.

REFERENCES

  1. Du P, Bergamasco A, Moride Y, et al. Von Willebrand disease epidemiology, burden of illness and management: a systematic review. J Blood Med. 2023;14:189-208.

ICD10

  • D68.0 Von Willebrand's disease

Clinical Pearls

  • vWD is the most common inherited bleeding disorder in adults.
  • Treat recurrent bleeding in all types; minor events may not require prophylaxis.
  • First-line therapies: DDAVP, factor replacement, antifibrinolytics, recombinant factor VIIa.