IV. PATHOPHYSIOLOGY

Review of Evidence for Abnormal von Willebrand Factor (vWF) Homeostasis

Normal vWF release and processing

vWF is synthesized in endothelial cells and stored in the Weibel-Palade bodies. After release, high shear stress causes the molecule to unfold. Then, it is cleaved by a plasma metalloproteinase (ADAMTS13) into smaller subunits which support platelet adhesion.

Pathologic changes

vWF Release and Lack of Processing in Acute TTP

Patients with TTP have a severe reduction in ADAMTS13. In many patients studied, this appears to be due to an autoantibody. In others, it may be a familial deficiency.  If IgG neutralizes ADAMTS13 creating a deficiency, the vWF molecule is not cleaved. Then, these unusually large vWF molecules, which are synthesized in endothelial cells and released into plasma, bind to platelets and cause aggregation in the microvascular vessels.

Note it takes 48-72 hours for bone marrow biopsy results to become available because the sample must first be decalcified. Gingival biopsies can be obtained and processed more quickly and sometimes are useful in the diagnosis of problem patients.