ADAMTS13, a disintegrin and metalloproteinase with thrombospondin type 1 motifs, 13, is a plasma metalloprotease crucial for normal hemostasis. It cleaves von Willebrand factor (VWF), processing VWF multimers to prevent their interaction with platelets and subsequent microvascular thrombosis [2,3]. ADAMTS13 is mainly synthesized by hepatic stellate cells and is involved in regulating thrombogenesis, as well as having roles in down-regulating inflammation, angiogenesis, and extracellular matrix degradation [5].

In congenital thrombotic thrombocytopenic purpura (TTP), which results from severe hereditary deficiency of ADAMTS13, a phase 3 trial found that prophylaxis with recombinant ADAMTS13 led to no acute TTP events, while 1 event occurred with standard therapy. Thrombocytopenia was less frequent with recombinant ADAMTS13, and adverse events related to the trial drug were fewer. ADAMTS13 activity reached approximately 100% of normal levels with recombinant ADAMTS13 prophylaxis [1]. In acquired immune thrombotic thrombocytopenic purpura (iTTP), autoantibody-mediated deficiency of plasma ADAMTS13 occurs. Plasma ADAMTS13 exists in multiple conformations, and inhibitory antibodies in iTTP mainly bind the spacer domain, while antibodies binding distal C-terminal domains may activate it [3].

In conclusion, ADAMTS13 is essential for normal hemostasis by regulating VWF-platelet interactions. Studies on ADAMTS13, especially in the context of TTP, have shown its significance in preventing microvascular thrombosis. Understanding ADAMTS13's function and regulation, as well as the development of recombinant ADAMTS13 treatments, provides important insights for the treatment of TTP and potentially other thrombotic diseases [1,2,3,4,5].

References:

1. Scully, Marie, Antun, Ana, Cataland, Spero R, Zhang, Pinghai, Wang, Linda T. . Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura. In The New England journal of medicine, 390, 1584-1596. doi:10.1056/NEJMoa2314793. https://pubmed.ncbi.nlm.nih.gov/38692292/

2. Papakonstantinou, Anna, Kalmoukos, Panagiotis, Mpalaska, Aikaterini, Koravou, Evaggelia-Evdoxia, Gavriilaki, Eleni. 2024. ADAMTS13 in the New Era of TTP. In International journal of molecular sciences, 25, . doi:10.3390/ijms25158137. https://pubmed.ncbi.nlm.nih.gov/39125707/

3. Halkidis, Konstantine, Zheng, X Long. 2022. ADAMTS13 conformations and mechanism of inhibition in immune thrombotic thrombocytopenic purpura. In Journal of thrombosis and haemostasis : JTH, 20, 2197-2203. doi:10.1111/jth.15822. https://pubmed.ncbi.nlm.nih.gov/35842925/

4. Plautz, William E, Raval, Jay S, Dyer, Mitchell R, Zuckerbraun, Brian S, Neal, Matthew D. 2018. ADAMTS13: origins, applications, and prospects. In Transfusion, 58, 2453-2462. doi:10.1111/trf.14804. https://pubmed.ncbi.nlm.nih.gov/30208220/

5. Feng, Yun, Li, Xueyin, Xiao, Juan, Chen, Xi, Chen, Suhua. 2016. ADAMTS13: more than a regulator of thrombosis. In International journal of hematology, 104, 534-539. doi:. https://pubmed.ncbi.nlm.nih.gov/27696191/