Fibrinolysis is impaired in patients with primary immune thrombocytopenia
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.
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BibTeX
@article{schramm2026fibrinolysis,
title = {{Fibrinolysis is impaired in patients with primary immune thrombocytopenia}},
author = {Theresa Schramm and Jasmin Rast and Dino Mehic and Stéphanie E Reitsma and Claire de Moreuil and Michael Fillitz and Peter Quehenberger and Bas de Laat and Alisa S Wolberg and Cihan Ay and Ingrid Pabinger and Johanna Gebhart},
journal = {Journal of Thrombosis and Haemostasis},
year = {2026},
month = sep,
doi = {10.1016/j.jtha.2024.07.034},
url = {https://univ-brest.hal.science/hal-05745841v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Fibrinolysis is impaired in patients with primary immune thrombocytopenia
AU - Theresa Schramm
AU - Jasmin Rast
AU - Dino Mehic
AU - Stéphanie E Reitsma
AU - Claire de Moreuil
AU - Michael Fillitz
AU - Peter Quehenberger
AU - Bas de Laat
AU - Alisa S Wolberg
AU - Cihan Ay
AU - Ingrid Pabinger
AU - Johanna Gebhart
PY - 2026
DA - 2026/09/10
JO - Journal of Thrombosis and Haemostasis
DO - 10.1016/j.jtha.2024.07.034
UR - https://univ-brest.hal.science/hal-05745841v1
AB - 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.
SN - 1538-7933
SN - 1538-7836
ER -