Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura

Antibodies, Journal Year: 2025, Volume and Issue: 14(1), P. 24 - 24

Published: March 10, 2025

Autoantibodies to ADAMTS13 are at the center of pathology immune-mediated thrombotic thrombocytopenic purpura. These autoantibodies can be either inhibitory (enzymatic function) or non-inhibitory, resulting in protein depletion. Under normal physiologic conditions, antibodies generated response foreign antigens, which include infectious agents; however, these may times cross-react with self-epitopes. This is one possible mechanisms mediating formation anti-ADAMTS13 autoantibodies. The process known as “antigenic mimicry” responsible for development that recognize and bind cryptic epitopes ADAMTS13, disrupting its enzymatic function over ultra large von Willebrand factor multimers, forming seeds platelet activation microthrombi formation. In particular, specific amino acid sequences lead conformational structures recognized by Generation occur more frequently among patients a genetic predisposition. Conformational changes between open closed states also constitute critical change driving interactions their generation. Nowadays, there growing understanding role play pathology. knowledge, especially functional qualitative differences sequence specificity such antibodies, make targeted therapeutic agents treat disease. review aims present what against how structure result

Language: Английский

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Prospective Study of ADAMTS13 and von Willebrand Factor’s Role in the Prediction of Outcomes in Acute Ischemic Stroke

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(7), P. 2470 - 2470

Published: April 4, 2025

Background: In this prospective study, the prognostic role of ADAMTS13 activity and von Willebrand (VWF) antigen (VWF: Ag) levels in ischemic stroke outcomes was investigated. Methods: Patients diagnosed with acute were prospectively enrolled while samples for VWF: Ag level measurements collected upon their admission to our unit. The National Institutes Health Stroke Scale (NIHSS) score estimated at discharge. modified Rankin scale neurologic disability (Rankin) based on patient's history before onset, during (RankinAdm), discharge (RankinDis). Results: 29 patients a median age 82.5 (51, 92) included. univariate analysis, associated platelet values same time point (r = 0.12, p 0.01) 0.439, 0.04), previous 0.9176, 0.031), glucose 0.64, 0.049). Associations between ADAMTS13/VWF: Ratio RankinDis 0.3253, 0.03), change RankinAdm 0.1589, 0.014) identified. Additionally, correlated 0.0072, Conclusions: These markers might be useful as biomarkers prediction poor after stroke.

Language: Английский

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Thrombotic Thrombocytopenic Purpura in Pediatric Patients

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1038 - 1038

Published: April 25, 2025

Thrombotic thrombocytopenia purpura is a serious disease that can involve complex symptomatology, prolonged hospitalization, and high risk of mortality if treatment delayed. This rare, but it even rarer among pediatric patients. Even though was first described 100 years ago, the earliest documented case patient. The last three decades have seen discovery pathological mechanisms responsible for its clinical presentation. Symptoms/signs characteristic microangiopathic hemolytic anemia with significant characterize vast majority Its pathology centers on accumulation ultra-large von Willebrand factor multimers due to an enzyme deficiency prevents their breakdown. Currently, in patients, two forms are known: congenital mutation enzyme’s gene immune-mediated depletion or neutralization secondary autoantibody formation. With advent therapeutic plasma exchanges, immunosuppression, and, more recently, TTP-specific nanobody, there reason optimism does not necessarily equate bad outcome. Thus, aim this review contrast patients while presenting them context pathologic mechanisms, diagnosis, treatment.

Language: Английский

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Thrombosis in Paroxysmal Nocturnal Hemoglobinuria (PNH): From Pathogenesis to Treatment

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12104 - 12104

Published: Nov. 11, 2024

Paroxysmal Nocturnal Hemoglobinuria (PNH) constitutes a rare bone marrow failure syndrome characterized by hemolytic anemia, thrombotic events (TEs), and aplasia of variable degrees. Thrombosis is one the major clinical manifestations disease, affecting up to 40% individuals with PNH. Venous thrombosis more prevalent, mainly unusual sites, such as intrabdominal hepatic veins. TEs might be first manifestation Complement activation, endothelial dysfunction, hemolysis, impaired bioavailability nitric oxide, activation platelets neutrophils are implicated in pathogenesis PNH patients. Moreover, vicious cycle involving coagulation cascade, complement system, inflammation cytokines, interleukin-6, established. inhibitors, eculizumab ravulizumab (C5 inhibitors), have revolutionized care patients C5 inhibitors should initiated thrombosis, while they constitute great prophylactic measure for those individuals. Anticoagulants, warfarin low-molecular-weight heparin, and, selected cases, direct oral anticoagulants (DOACs) used combination who develop TEs. Novel considered an alternative treatment option, especially extravascular or breakthrough hemolysis when terminal administered.

Language: Английский

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