vWFfrisetning

vWF fragmentation refers to the process by which the large multimeric protein von Willebrand factor (vWF) is cleaved into smaller pieces. vWF is a crucial protein in hemostasis, playing a vital role in platelet adhesion and aggregation, as well as acting as a carrier for coagulation factor VIII. Its large multimeric structure is essential for its function, allowing it to bind effectively to both collagen in the subendothelium and to activated platelets.

The fragmentation of vWF is primarily mediated by a metalloproteinase called ADAMTS13 (A Disintegrin And Metalloproteinase with Thrombospondin type 1 motif, member 13). ADAMTS13 cleaves vWF at specific sites within its A2 domain. This cleavage is a tightly regulated process. Under normal physiological conditions, ADAMTS13 generates a population of smaller vWF multimers that are still functional.

However, dysregulation of vWF fragmentation can have significant pathological consequences. If ADAMTS13 activity is severely deficient, large, uncleaved vWF multimers accumulate. These abnormally large multimers can lead to spontaneous platelet aggregation and the formation of microthrombi in small blood vessels, a hallmark of thrombotic thrombocytopenic purpura (TTP). Conversely, if vWF is excessively fragmented, its ability to mediate hemostasis may be impaired, potentially contributing to bleeding disorders. Therefore, the precise control of vWF fragmentation by ADAMTS13 is critical for maintaining vascular integrity and preventing both bleeding and clotting complications.