ArticleBlood advances2022
Relative hypercoagulation induced by suppressed fibrinolysis after tisagenlecleucel infusion in malignant lymphoma.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Clinical practice guidelines for management of disseminated intravascular coagulation in Japan 2024. Part 2: hematologic malignancy.International journal of hematology · 2025Guideline
- Endotheliopathy in CAR T-Cell Therapy: Mechanistic Insights into the VWF/ADAMTS13 Axis and the Angiopoietin-Tie2 Pathway.TH open : companion journal to thrombosis and haemostasis · 2026Review
- Digital Biomarkers of Cytokine Release Syndrome: Scoping Review and Ontology Development of the Role and Relevance of Digital Measures Using a Mixed Methods Approach.Journal of medical Internet research · 2025Article
- Article
- CAR T-cell toxicities: from bedside to bench, how novel toxicities inform laboratory investigations.Blood advances · 2024Review
- Cardiovascular toxicities associated with bispecific T-cell engager therapy.Journal for immunotherapy of cancer · 2024Article
- IL-10 plus the EASIX score predict bleeding events after anti-CD19 CAR T-cell therapy.Annals of hematology · 2023Article
- Early prediction of cytokine release syndrome by measuring phosphate and magnesium levels following chimeric antigen receptor T cell therapy.Blood cell therapy · 2023Article
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy has facilitated progress in treatment of refractory/relapsed diffuse large B-cell lymphoma (DLBCL). A well-known adverse event after CAR-T therapy is cytokine release syndrome(CRS). However, the etiology and pathophysiology of CRS-related coagulopathy remain unknown. Therefore, we conducted a prospective cohort study to comprehensively analyze coagulation/ fibrinolysis parameters present in peripheral blood of adult DLBCL patients treated with tisagenlecleucel in a single institution. Samples were collected from 25 patients at 3 time points: before lymphocyte-depletion chemotherapy and on days 3 and 13 after CAR-T infusion. After infusion, all patients except 1 experienced CRS, and 13 required the administration of tocilizumab. A significant elevation in the plasma level of total plasminogen activator inhibitor 1 (PAI-1), which promotes the initial step of coagulopathy (mean, 22.5 ng/mL before lymphocyte-depletion and 41.0 on day 3, P = .02), was observed at the onset of CRS. Moreover, this suppressed fibrinolysis-induced relatively hypercoagulable state was gradually resolved after CRS remission with normalization of total PAI-1 to preinfusion levels without any organ damage (mean values of soluble fibrin: 3.16 µg/mL at baseline, 8.04 on day 3, and 9.16 on day 13, P < .01; and mean PAI-1: 25.1 ng/mL on day 13). In conclusion, a hypofibrinolytic and relatively hypercoagulable state concomitant with significant total PAI-1 elevation was observed at the onset of CRS even in DLBCL patients with mild CRS. Our results will facilitate understanding of CRS-related coagulopathy, and they emphasize the importance of monitoring sequential coagulation/fibrinolysis parameters during CAR-T therapy.
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