vWFMultimeren

Von Willebrand factor multimeres (vWF multimers) refer to the different-sized assemblies of von Willebrand factor (VWF) circulating in blood. VWF is produced by endothelial cells and megakaryocytes and released into plasma as multimers that range from small to ultra-large high-molecular-weight forms. The multimer distribution is biologically important because the hemostatic activity of VWF increases with multimer size, particularly the high-midelity, high-molecular-weight multimers.

Structure and processing: A VWF monomer is about 275-280 kDa and contains multiple domains, including A1, A2, and A3. Subunits are linked by disulfide bonds to form large multimers. In the circulation, ultra-large multimers are cleaved by the metalloprotease ADAMTS13 in the A2 domain to generate a normal distribution of smaller, active multimers. The multimeric state is influenced by shear forces, with unfolding under high shear exposing binding sites that promote platelet adhesion.

Function: VWF mediates platelet adhesion to damaged subendothelium by binding to the platelet GPIb-IX-V complex (via the A1 domain) and to exposed collagen (via the A3 domain). It also serves as a carrier for factor VIII, protecting it from proteolysis. The presence of large multimers enhances initial platelet plug formation, while regulated cleavage prevents excessive thrombus formation.

Clinical relevance: Abnormal VWF multimer distribution is central to von Willebrand disease (VWD) and to acquired von Willebrand syndromes; multimer analysis by electrophoresis helps classify VWD subtypes. In thrombotic thrombocytopenic purpura (TTP), deficient ADAMTS13 leads to accumulation of ultra-large multimers and microvascular thrombosis. Laboratory assessment includes VWF antigen, ristocetin cofactor activity, collagen-binding assays, and multimer analysis. Therapy may involve desmopressin, vWF concentrates, or plasma exchange in specific conditions.