What are the mechanisms of acquired von Willebrand syndrome?¶
Answer: Multiple mechanisms, none very well understood. Unlike acquired hemophilia A (AHA), acquired von Willebrand syndrome (AvWS) occurs most of the time with an underlying disorder, and some disorders act through overlapping mechanisms.
Increased plasma clearance of VWF — the main route:
- Antibodies — MGUS, multiple myeloma, SLE: anti-VWF antibodies form immune complexes that are cleared by the reticuloendothelial system (RES).
- Adsorption onto cell surfaces — high-molecular-weight (HMW) multimers bind cells and are then cleared:
- tumor cells in lymphoproliferative disease and solid cancers; in MGUS, aberrant GPIb expression on abnormal plasma cells drives selective binding;
- platelets in essential thrombocythemia and other myeloproliferative neoplasms (MPNs) — the platelet count is inversely related to the plasma HMW-multimer defect.
- Shear stress — LVADs and valvular disease: HMW multimers sheared by mechanical stress and by ADAMTS13-mediated proteolysis.
- Increased proteolysis — MPNs may also lower VWF through increased plasma proteolysis.
Decreased synthesis — hypothyroidism.
An illustrative case: lymphoma-associated AvWS responsive to splenectomy — the likely mechanism was VWF antibody-mediated inhibition and/or VWF adsorption onto platelets sequestered in the spleen or onto the massive number of tumor cells.
Source: Acquired von Willebrand syndrome: focused for hematologists