Real-world data of thrombotic microangiopathy management: The key role of ADAMTS13 activity and complement testing

Gavriilaki, Eleni; Koravou, Eudoxia-Evaggelia; Chatziconstantinou, Thomas; Kalpadaki, Christina; Printza, Nikoleta; Ximeri, Maria; Christoforidou, Anna; Karavalakis, George; Kaliou, Maria; Kalaitzidou, Vassiliki; Tassi, Iliana; Tzellou, Maria; Touloumenidou, Tasoula; Papalexandri, Apostolia; Παπαθανασίου, Μαρία; Syrigou, Antonia; Kioumi, Anna; Liga, Maria; Kaiafa, Georgia; Spyridonidis, Alexandros; Kapsali, Eleni; Kollios, Konstantinos; Μανδαλά, Ευδοκία; Vlachaki, Efthymia; Tsirigotis, Panagiotis; Papadaki, Eleni; Lalayanni, Chrysavgi; Anagnostopoulos, Αchilles

doi:10.1016/j.tru.2021.100043

Cited by 4 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several reasons may explain the increase of both ADAMTS-13 testing and non-TTP TMAs during the study period: (1) a growing awareness among physicians of the existence of TMAs and ADAMTS-13 testing [ 30 ]; (2) a better and unrestricted access to the test due to its inclusion in the province's official directory of medical tests [ 31 ]; (3) the requirement for the treating physician to exclude a diagnosis of TTP—i.e. to confirm a level of ADAMTS-13 activity level above 10%—in order to have access to the anti-C5 drug eculizumab for their patient with a suspected CM-TMA [ 32 ]; and (4) a true increase in non-TTP TMA. In recent years, new treatments for malignancies have become available, some of which are associated with an increased risk of TMA including vascular endothelial growth factor (VEGF) inhibitors and gemcitabine.…”

Section: Discussionmentioning

confidence: 99%

Incidence of thrombotic microangiopathies in Quebec: insight from a laboratory centralizing ADAMTS-13 testing

Merlen

Pépin

Barry

et al. 2022

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background Thrombotic microangiopathies (TMA) are serious medical conditions requiring a prompt diagnosis to adapt treatment. The determination of ADAMTS-13 activity enables discriminating thrombotic thrombocytopenic purpura (TTP) from other forms of TMA. The purpose of this study was to provide an estimate of the incidence of TTP and TMA in the Canadian Quebec province using data collected from a laboratory centralizing ADAMTS-13 testing for the whole province. Results From 2012 to 2019, 846 patients were evaluated for plasma ADAMTS-13 activity due to a suspicion of TMA. TTP was identified in 147 patients. Of these, 118 patients with a median age of 51.5 years and a male–female ratio of 1:1.4 had their first episode of TTP during the study period. The number of ADAMTS-13 tests performed and the number of patients with suspected TMA increased annually by 19% and 21% respectively. While the incidence of non-TTP TMA increased annually, that for TTP remained unchanged. This averaged 10.2 (95% CI 5.9–14.4) per million persons per year for suspected non-TTP TMA and 1.8 (95% CI 1.3–2.4) for confirmed TTP. The incidence rate of TMA other than TTP was higher in the age group 70–79 years (21.8; 95% CI 5.4–38.1) for females and in the age group 80–89 years (24.4; 95% CI 7.2–41.7) for males compared to other age groups. The incidence rate of TTP was higher in the age group 40–49 years (4.0; 95% CI 2.0–5.9) for women and in the age group 60–69 years (3.4; 95% CI 1.1–5.6) for men compared to other age groups. Conclusion The analysis of centralized data measuring ADAMTS-13 activity allowed us to adequately establish the incidence rate and demographic characteristics of TMA, particularly TTP, in Quebec. TTP incidence remained stable while suspected non-TTP TMA steadily increased from 2012 to 2019.

show abstract

Section: Discussionmentioning

confidence: 99%

Incidence of thrombotic microangiopathies in Quebec: insight from a laboratory centralizing ADAMTS-13 testing

Merlen

Pépin

Barry

et al. 2022

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…Deficiency in the activity of plasma ADAMTS13 (<10%) is typical in thrombotic thrombocytopenic purpura (TTP) [51]. Despite the identification of mutations in the ADAMTS13 gene, the activity of ADAMTS13 was between 43 and 50% in the whole group of patients, excluding the diagnosis of TTP [49,52]. CFHR5 is part of a complement factor H (CFH) gene cluster, located on chromosome 1, encoding a protein that can bind to complement component 3 b (C3b), acting as an alternative complement pathway regulator [53]).…”

Section: Genetic Susceptibility To Hsct-tmamentioning

confidence: 99%

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Evangelidis,

Kalmoukos

et al. 2024

CIMB

Self Cite

View full text Add to dashboard Cite

Hematopoietic stem cell transplantation (HSCT) remains a cornerstone in the management of patients with hematological malignancies. Endothelial injury syndromes, such as HSCT-associated thrombotic microangiopathy (HSCT-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (SOS/VOD), and capillary leak syndrome (CLS), constitute complications after HSCT. Moreover, endothelial damage is prevalent after immunotherapy with chimeric antigen receptor-T (CAR-T) and can be manifested with cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Our literature review aims to investigate the genetic susceptibility in endothelial injury syndromes after HSCT and CAR-T cell therapy. Variations in complement pathway- and endothelial function-related genes have been associated with the development of HSCT-TMA. In these genes, CFHR5, CFHR1, CFHR3, CFI, ADAMTS13, CFB, C3, C4, C5, and MASP1 are included. Thus, patients with these variations might have a predisposition to complement activation, which is also exaggerated by other factors (such as acute graft-versus-host disease, infections, and calcineurin inhibitors). Few studies have examined the genetic susceptibility to SOS/VOD syndrome, and the implicated genes include CFH, methylenetetrahydrofolate reductase, and heparinase. Finally, specific mutations have been associated with the onset of CRS (PFKFB4, CX3CR1) and ICANS (PPM1D, DNMT3A, TE2, ASXL1). More research is essential in this field to achieve better outcomes for our patients.

show abstract

“…At the time of publication of the first research evaluating the PLASMIC score, few institutions were testing for ADAMTS-13 in-house. Therefore, the PLASMIC score had more utility in the setting of evaluating a patient within the first few days after presenting with signs/ symptoms of TMA/TTP without the availability of rapid ADAMTS-13 activity results [20][21][22][23]. In this study, we evaluated our 14-year experience of patients referred to the apheresis service with the clinical suspicion of TTP.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies: Lessons learned from a 14‐year retrospective study

et al. 2022

View full text Add to dashboard Cite

Introduction Thrombotic thrombocytopenic purpura (TTP) is a clinical thrombotic microangiopathy (TMA) syndrome defined by the pentad of symptoms. Therapeutic plasma exchange with plasma replacement is an ASFA Category I modality that can reduce morbidity and mortality if initiated early. We describe a 14‐year review of patients referred for plasma exchange with a suspected diagnosis of TTP. Methods For 70 patients referred for urgent plasma exchange, clinical, therapeutic, and laboratory data were retrospectively analyzed, and the diagnosis was determined. Results Fifteen of the patients were diagnosed with TTP based upon ADAMTS‐13 activity with the other 51 patients having other non‐TTP TMA diagnoses. The mortality rate was significant for both TTP and non‐TTP TMAs. PLASMIC scores were also calculated retrospectively and were noted to have limited value. TMA is a diagnostic challenge and encompasses different syndromes with similar presentations. Conclusion Determining an accurate diagnosis, including prompt ADAMTS‐13 testing, makes it possible to initiate appropriate therapy for the multiple different TMAs that can be seen in clinical practice.

show abstract

Real-world data of thrombotic microangiopathy management: The key role of ADAMTS13 activity and complement testing

Cited by 4 publications

References 14 publications

Incidence of thrombotic microangiopathies in Quebec: insight from a laboratory centralizing ADAMTS-13 testing

Incidence of thrombotic microangiopathies in Quebec: insight from a laboratory centralizing ADAMTS-13 testing

Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill

Evaluation of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies: Lessons learned from a 14‐year retrospective study

Contact Info

Product

Resources

About