Thrombin Generation Profile in Various Lymphoma Sub-Groups and Its Augmentation by Andexanet Alfa

The prevalence of thrombosis in lymphoma patients is reportedly high and ranges from 3-10%. Vascular malfunction and inflammatory processes further contribute to the thrombotic activation process in these patients. Andexanet alfa (AA) is an antidote for factor Xa inhibitors and its usage has been reported with thrombotic complications. This study was designed to compare the effect of AA on the thrombin generation (TG) potential. Blood samples from 78 patients with confirmed diagnosis of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and Chronic lymphocytic leukemia (CLL) were collected from the University of Belgrade Clinic, Serbia. Normal human plasma (NHP) was used for referencing purposes. Individual samples were supplemented with AA at 100 ug/ml. TG studies were carried out using a commercially available fluorogenic substrate method. TG parameters such as peak thrombin (PT), lag time (LT) and area under the curve (AUC) were compiled. Cumulatively, lymphoma patients showed an increase in LT compared to NHP which decreases with AA. The PT and AUC levels were decreased compared to NHP and increases with AA. Upon sub-grouping of lymphoma patients, PT levels for all sub-groups were increased with AA. The AUC values increased for HL and NHL and decreased for CLL with AA. Variations in lag time were noted in all 3 sub-groups. Lymphoma represents a heterogenous group of patients where both the hypercoagulable state and inflammatory responses simultaneously occur. Increased thrombin generation in post AA supplemented samples suggest that the use of this agent may potentially be associated with thrombotic complications.