LAB DIAGNOSIS OF VON WILLEBRAND DISEASE

LAB DIAGNOSIS OF VON WILLEBRAND DISEASE
  • It is the most common mucocutaneous inherited bleeding disorder described first by Erik Von willebrand (Finnish professor in 1926).
  • It has autosomal dominant inheritance found in approximately 1% of population.
  • It results due to germline mutations which cause either structural or quantitative abnormalities of von Willebrand Factor (vWF) leading to decreased adhesion by platelets to injured vessel wall causing impaired primary hemostasis.
Clinical Features:
  • Mostly patient presents with mucocutaneous bleed
  • Common presentations are
    • Epistaxis (Nasal bleed)
    • Menorrhagia (Heavy, prolonged menstrual periods)
    • Gastro intestinal bleeding
    • Easy bruising 
    • Bleeding after surgery (especially involving mucus
      membranes)
    •  Prolonged or excessive bleeding after dental procedures
    •  Prolonged bleeding after delivery of a baby
    •  May vary in each person from time to time, throughout life depending on type of von Willebrand disease
Laboratory diagnosis:
  • CBC to rule out thrombocytopenia as a cause of mucocutaneous bleeding.
  • PT and APTT to assess coagulation system.
  • Standard vWD test panel includes 3 stages.
    • Quantitative VWF test by employing enzyme immunoassay or automated latex immune assay methodology.
    • vWF activity test which determines the factors ability to bind to platelets. vWF function is assessed by Ristocetin agglutination test
      • This assay is performed by mixing the patients plasma with formalin fixed platelets and Ristocetin, a small molecule that binds and activate VWF. 
      • Ristocetin induces multivalent VWF multimers to bind platelet glycoprotein –Ib-1X and form interplatelet” bridges” 
      • The resulting clumping (agglutination) of platelets is measured in a device called an aggregometer.
      • Degree to which patient plasma promotes ristocetin dependent platelet aggulatination reflects the vWF activity of the sample.
    • vWF multimer analysis by sodium doclecy sulphate polyacrylamide gel electophoresis to further differentiate between vWD subtypes 2A & 2B.

References
  1. Elaine M. Keohane, Larry J Smith, Jeanine M. Walenga. Rodaks Haematology: Clinical Principles and Applications. Fifth edition
  2. Vinay kumar, Abul K.Abbas, Jon C. Aster. Robbins and Cotran. Pathologic Basis of Disease. 9th edition
  3. Shirish M.Kawthalkar. Essentials of Haematology. Second edition