A third form of thrombotic thrombocytopenic purpura?

Pathological Mechanisms and Novel Testing Methods in Thrombotic Thrombocytopenic Purpura

“…Recent reports have highlighted an additional potential mechanism resulting in TTP that is unrelated to the congenital deficiency of or antibodies to ADAMTS13. Changes in ADAMTS13 to a “closed” conformation have been linked to a non-immune form of TTP, in a proposed phenomenon of TTP of unknown pathophysiology, or uTTP ( Figure 1 ) [ 2 , 13 , 14 , 15 , 16 ]. In these cases, cTTP is not present, and antibodies to ADAMTS13 are not detected, leading to this third category [ 13 , 14 , 16 ].…”

“…Changes in ADAMTS13 to a “closed” conformation have been linked to a non-immune form of TTP, in a proposed phenomenon of TTP of unknown pathophysiology, or uTTP ( Figure 1 ) [ 2 , 13 , 14 , 15 , 16 ]. In these cases, cTTP is not present, and antibodies to ADAMTS13 are not detected, leading to this third category [ 13 , 14 , 16 ]. While the open conformation is linked to iTTP, non-immune uTTP patients present with closed ADAMTS13 [ 14 ].…”

“…Pregnant patients with uTTP show higher blood pressure than patients with other forms [ 15 ]. Lastly, ADAMTS13 is in the closed conformation in 86.4% of uTTP cases but only in 23.3% of iTTP cases [ 13 , 14 ].…”

“…Studies within the past decade have suggested Biomedicines 2024, 12, 621 2 of 11 laboratory measurements-most notably, immature platelet fraction (IPF) and absolute immature platelet count (A-IPC) tests may serve as complementary to ADAMTS13 testing, which for many institutions requires sending out testing to be performed at specialized reference laboratories, which is not ideal for a timely diagnosis [8][9][10][11][12]. Conversely, and with interesting implications for TTP pathophysiology, conformational changes in ADAMTS13 have been shown to contribute to the disease and may serve as a biomarker of disease progression or recurrence [13][14][15][16].…”