Fibrinolysis is impaired in patients with primary immune thrombocytopenia

Abstract

BackgroundPatients with primary immune thrombocytopenia (ITP) have an increased risk of thrombosis, which may be due to altered fibrinolysis. ObjectivesTo elucidate the clinical impact of delayed fibrinolysis in ITP patients. MethodsA 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, TAFI and D-Dimer were assessed in 86 adult primary ITP patients and 78 healthy controls (HC). ResultsITP patients showed significantly delayed clot formation, increased clot density, and prolonged clot lysis time (CLT) compared to HC with a median (IQR) CLT of 28.0 (13.7-34.7) minutes in patients and 17.3 (12.0-28.0) minutes in HC, while in PG only the lag time was prolonged. In ITP patients compared to 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=0.019), whereas PG parameters were not associated with CLT. Six patients, who developed thrombosis during follow-up, had higher levels of tPA-PAI-1 complexes. ConclusionProlonged 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.