Thrombosis and hemostasis “enthusiasts” reveal coagulation-related complications encountered in pediatric oncology treatment: Thrombosis or bleeding symptoms?

Abstract

The association between coagulation (C) and fibrinolysis (F) potentials is such that thrombosis occurs when coagulation is predominant, and bleeding occurs when the opposite is true. In other words, a balance between C and F is crucial. Coagulopathy encountered in pediatric oncology includes sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA); however, its pathogenesis is not well understood. We developed a novel thrombin–plasmin generation assay (T/P-GA) that can simultaneously measure comprehensive C/F potential because hemostatic balance may offer a window into the pathophysiology of such coagulopathies. In SOS, a simultaneous decrease in thrombin generation and plasmin generation (PG) was found immediately before the onset of the disease, confirming that both C/F potentials were reduced. The same was true for TMA brought on by hematopoietic cell transplantation, and C/F potential improved as the condition improved. PG was increased in patients with metastasis of pediatric solid tumors, indicating a relationship between metastasis and fibrinolysis. When L-asparaginase was administered, PG in acute lymphoblastic leukemia considerably decreased, and in the last stages of induction therapy, a relative procoagulant state was seen. It has also been reported that the level of “total plasminogen activator inhibitor-1”, a fibrinolysis inhibitory factor, is increased in cases of the coagulopathy associated with cytokine release syndrome in chimeric antigen receptor-modified T-cell therapy for adult malignant lymphoma, and pathological analysis utilizing T/P-GA is warranted in novel immunotherapy. Therefore, it is anticipated that the pathological analysis of different coagulation disorders based on the balance of C/F potential will help develop a safe and efficient cancer treatment.