ADAMTS13: origins, applications, and prospects

Abstract

ADAMTS13 is an enzyme that acts by cleaving prothrombotic von Willebrand factor (VWF) multimers from the vasculature in a highly regulated manner. In pathologic states such as thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies (TMAs), VWF can bind to the endothelium and form large multimers. As the anchored VWF chains grow, they provide a greater surface area to bind circulating platelets (PLTs), generating unique thrombi that characterize TTP. This results in microvasculature thrombosis, obstruction of blood flow, and ultimately end-organ damage. Initial presentations of TTP usually occur in an acute manner, typically developing due to an autoimmune response toward, or less commonly a congenital deficiency of, ADAMTS13. Triggers for TMAs that can be associated with ADAMTS13 deficiency, including TTP, have been linked to events that place a burden on hemostatic regulation, such as major trauma and pregnancy. The treatment plan for cases of suspected TTP consists of emergent therapeutic plasma exchange that is continued on a daily basis until normalization of PLT counts. However, a subset of these patients does not respond favorably to standard therapies. These patients necessitate a better understanding of their diseases for the advancement of future therapeutic options. Given ADAMTS13's key role in the cleavage of VWF and the prevention of PLT-rich thrombi within the microvasculature, future treatments may include anti-VWF therapeutics, recombinant ADAMTS13 infusions, and ADAMTS13 expression via gene therapy.

Cleavage by MMP‐13 renders VWF unable to bind to collagen but increases its platelet reactivity

“…Most MMPs, however, have many substrates and here we show that MMP‐13 can also cleave VWF under static conditions. This ability sets it apart from ADAMTS13, a circulating metalloproteinase which cleaves highly thrombotic ultra large VWF multimers into smaller fragments but only when the A2 domain of VWF is accessible under shear conditions . ADAMTS13 cleavage of unfolded VWF safeguards against the accumulation of ultra large VWF multimers and the subsequent formation of platelet aggregates that may occlude arterioles and capillaries .…”

vWFpp/ADAMTS13 ratio is a useful marker of postliver transplantation thrombotic microangiopathy: A pediatric case report

“…[8][9][10][11] However, the immediate accurate diagnosis of p-LT TMA can be extremely difficult for multiples reasons: There is no current widely available rapid diagnostic test in suspected cases, patients can develop only minimal hematologic disorder or organ involvement, and differential diagnosis is required to distinguish p-LT TMA from liver graft failure and disseminated intravascular coagulation. 3,12 It was the first case of TMA following living donor liver transplantation observed in the institution of Saint Luc in our cohort of more than 1000 operated children. This diagnosis F I G U R E 1 Trends in laboratory date in our patient.…”

“…TMA is a rare, life‐threatening, and not fully understood complication after liver transplantation that needs prompt treatment . However, the immediate accurate diagnosis of p‐LT TMA can be extremely difficult for multiples reasons: There is no current widely available rapid diagnostic test in suspected cases, patients can develop only minimal hematologic disorder or organ involvement, and differential diagnosis is required to distinguish p‐LT TMA from liver graft failure and disseminated intravascular coagulation …”

Trombotic Trombocytopenic Purpura Presenting With Headache And Agitation: Case Report

“…[9] Ateş, trombositopeni, hemolitik anemi, böbrek fonksiyon bozukluğu ve nörolojik fonksiyon bozukluğu bulgularından oluşan klasik TTP pentadına tanı için güvenilemez, çünkü vakaların sadece %50'sinde pentad görülür. [10] Hastamız iş kazası sonrası yanıkları nedeni ile antibiyotik kullandığı dönemde tedavisi sürerken gelişen ateş, baş ağrısı, ajitasyon nedeni ile acil servise getirilmişti. Tetkiklerinde anemi, trombositopeni, LDH yüksekliği ve kan periferik yaymasında şistositleri vardı.…”