Fibrinolysis is impaired in patients with primary immune thrombocytopenia

Theresa Schramm, Jasmin Rast, Dino Mehic, Stéphanie E Reitsma, Claire de Moreuil, Michael Fillitz, Peter Quehenberger, Bas de Laat, Alisa S Wolberg, Cihan Ay, Ingrid Pabinger, Johanna Gebhart*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Patients with primary immune thrombocytopenia (ITP) have an increased risk of thrombosis, which may be due to altered fibrinolysis. Objectives: To elucidate the clinical impact of delayed fibrinolysis in ITP patients. Methods: A turbidimetric clot formation and lysis assay and a fluorometric plasmin generation (PG) assay were performed, and levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), tPA-PAI-1 complexes, α2-antiplasmin, thrombin activatable fibrinolysis inhibitor, and D-dimer were assessed in 86 adult primary ITP patients and 78 healthy controls (HCs). Results: ITP patients showed significantly delayed clot formation, increased clot density, and prolonged clot lysis time (CLT) compared with HCs, with a median (IQR) CLT of 28.0 (13.7-34.7) minutes in patients and 17.3 (12.0-28.0) minutes in HCs, while in the PG assay, only the lag time was prolonged. In ITP patients compared with controls, PAI-1 was higher (1.2 [0.8-2.6] vs 1.1 [0.6-2.1] U/mL) and tPA antigen and activity were lower (tPA antigen: 2.6 [1.1-4.4] vs 3.7 [3.2-4.7] ng/mL; tPA activity ≤ 0 U/mL: 26% vs 7%). TPA-PAI-1 complex levels were positively associated with CLT in multiple linear regression analysis (β = 0.241; P = .019), whereas PG parameters were not associated with CLT. Six patients who developed thrombosis during follow-up had higher levels of tPA-PAI-1 complexes. Conclusion: Prolonged CLT and delayed onset of PG may indicate a hypofibrinolytic tendency in ITP patients, as also indicated by high PAI-1 and low tPA levels. No association was found between fibrinolytic potential and the bleeding phenotype, whereas higher tPA-PAI-1 complex levels were associated with prolonged CLT and increased in patients with future thrombosis.

Original languageEnglish
Pages (from-to)3209-3220
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume22
Issue number11
Early online date28 Aug 2024
DOIs
Publication statusPublished - Nov 2024

Keywords

  • clot lysis time
  • fibrinolytic test
  • immune thrombocytopenia
  • plasmin generation

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