Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia

Abstract

AbstractBackgroundCoagulopathy and associated bleeding and venous thromboembolism (VTE) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.ObjectivesTo evaluate the associations between biomarker levels and bleeding and VTE in acute leukemia patients.Patients/MethodWe examined plasma levels of activators, inhibitors and biomarkers of the coagulation and fibrinolytic pathways in patients ≥18 years with newly diagnosed acute leukemia compared to healthy controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and VTE in acute leukemia patients. The study included 358 patients with acute leukemia (29 acute promyelocytic leukemia [APL], 253 non-APL acute myeloid leukemia [AML] and 76 acute lymphoblastic leukemia [ALL]), and 30 healthy controls.ResultsPatients with acute leukemia had higher levels of extracellular vesicle (EV) tissue factor (TF) activity, phosphatidylserine-positive EVs, plasminogen activator inhibitor-1 (PAI-1), plasmin-antiplasmin complexes, cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared to healthy controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among the acute leukemia patients. There were 41 bleeding and 37 VTE events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (sHR 2.30, 95%CI 0.99-5.31) whereas high PAI-1 was associated with increased risk of VTE (sHR 3.79, 95%CI 1.40-10.28) in these patients.ConclusionsOur study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and VTE.EssentialsThe mechanisms of acute leukemia-associated bleeding and thrombosis have not been elucidated.We measured plasma biomarkers of coagulation and fibrinolysis in acute leukemia patients.Biomarkers of the coagulation and fibrinolytic pathways are altered in acute leukemia patients.EVTF activity is associated with bleeding, and PAI-1 is associated with VTE in acute leukemia.