II. Physiology

  1. Von Willebrand Factor synthesis
    1. Vascular endothelium
    2. Megakaryocytes
  2. Von Willebrand Factor release
    1. Platelet activation
    2. Endothelial cells
  3. Von Willebrand Factor activity
    1. Binds factor VIII in circulation (prolongs Factor VIII half-life)
      1. Releases factor VIII in response to bleeding
      2. Factor VIII in turn is a Cofactor in the conversion of Factor IX to IXa in the initrinsic Clotting Pathway to form thrombin
    2. Bridges exposed collagen and platelets when vascular injury occurs
      1. Von Willebrand Factor mediates platelet adhesion
      2. Von Willebrand Factor is a large protein that binds damaged vasculature and traps, binds platelets to form a platelet plug
        1. Analogous to 6-pack plastic ring holder that traps wildlife
    3. Von Willebrand Factor deficiency
      1. Results in delayed platelet plug formation
      2. Results in mucocutaneous bleeding

III. Labs

  1. Normal VWF range: 50-200 IU/dl

IV. Causes: Decreased VWF Levels or function

  1. Von Willebrand Deficiency
  2. Type O Blood (25% lower VWF than other blood types)
  3. Acquired Von Willebrands Deficiency
    1. Hypothyroidism (causes decreased VWF Synthesis)
    2. Wilms Tumor and lymphoproliferative disorders are associated with tumor cell binding to VWF resulting in VWF Deficiency
    3. Conditions with antibodies to VWF
      1. Lymphoproliferative disorders
      2. Monoclonal Gammopathy
      3. Systemic Lupus Erythematosus
    4. Conditions that alter VWF conformation via shearing resulting in increased proteolysis
      1. Ventricular Septal Defect
      2. Aortic Stenosis
      3. Hypertrophic Cardiomyopathy
      4. Primary Pulmonary Hypertension
      5. Left Ventricular Assist Device
    5. Conditions with significant Thrombocythemia
      1. Essential Thrombocythemia
      2. Polycythemia Vera
      3. Myeloproliferative disorders
    6. Medications
      1. Ciprofloxacin
      2. Valproic Acid
      3. Griseofulvin
  4. References
    1. Kumar (2002) Mayo Clin Proc 77(2): 181-7 [PubMed]

V. Causes: Falsely increased VWF Levels

  1. Inflammatory Conditions
  2. Pregnancy

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