Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpura

Abstract

Immune-mediated thrombotic thrombocytopenic purpura is characterized by severe thrombocytopenia and microangiopathic hemolytic anemia. It is primarily caused by immunoglobin G type autoantibodies against ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. However, reliable markers predictive of patient outcomes are yet to be identified. Seventy-three unique patients with a confirmed diagnosis of immune-mediated thrombotic thrombocytopenic purpura between April 2006 and December 2017 were enrolled from the Univeristy of Alabama at Birmingham Medical Center. Clinical information, laboratory values, and a panel of special biomarkers were collected and/or determined. The results demonstrated that the biomarkers associated with endothelial injury (e.g. von Willebrand factor antigen and collagen-binding activity), acute inflammation (e.g. human neutrophil peptides 1-3 and histone/deoxyribonucleic acid complexes), and activation of the complement alternative pathway (e.g. factors Bb and iC3b) were all significantly increased in patients with acute immune-mediated thrombotic thrombocytopenic purpura compared to those in the healthy controls who did not have a hematological disease; moreover, failure to normalize platelet counts within 7 days or failure to markedly reduce serum lactate dehydrogenase by day 5, low total serum protein or albumin, and high serum troponin levels were also predictive of mortality; so were the prolonged activated partial thromboplastin time, high fibrinogen, and elevated serum lactate dehydrogenase, Bb, and sC5b-9 on admission. These results may help to stratify patients for more intensive management; the findings may also provide a framework for future multicenter studies to identify valuable prognostic markers for immune-mediated thrombotic thrombocytopenic purpura.

A modified PLASMIC score including the lactate dehydrogenase/the upper limit of normal ratio more accurately identifies Chinese thrombotic thrombocytopenic purpura patients than the original PLASMIC score

“…In order to solve this difficulty, many doctors and scientists had tried to use available clinical data to predict TTP, such as the Bentley score, Coppo score, the PLASMIC score, and so on . Among the scores, the PLASMIC score has proved to be practical and effective, which was validated in some studies .…”

Histone-induced thrombotic thrombocytopenic purpura in adamts13−/− zebrafish depends on von Willebrand factor

“…Lysine-rich histone induces a more severe and persistent TTP phenotype in a13 -/than wt zebrafish: Plasma histone/DNA complexes are significantly elevated in patients with acute thrombotic microangiopathy (TMA) including iTTP. (29,40) When zebrafish were challenged with a single dose of lysine-rich histone, a significant drop in the number of total, immature, and mature thrombocytes within 24 to 48 hours was observed in both wt and a13 -/zebrafish. As shown, in wt zebrafish the number of total ( Fig.…”

Efficacy and safety of open‐label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study

“…This allows unrestrained vWF‐mediated platelet adhesion in the microvasculature, which, if left untreated, is fatal in >90% of cases . Although daily therapeutic plasma exchange (TPE) and immunosuppression has improved patient outcomes, acute mortality is still ~10% to 20%, and patients are at risk for irreversible organ damage . In addition, 30%‐50% of patients experience disease exacerbations (platelet count <150 × 10 9 /L after initial recovery and within 30 days of last TPE), which may require rehospitalization and resumption of TPE, and puts patients at risk for thrombotic events and death associated with active disease.…”