Potentially life-threatening coagulopathy associated with simultaneous reduction in coagulation and fibrinolytic function in pediatric acute leukemia after hematopoietic stem-cell transplantation.

The pathogenesis of sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) is poorly understood, and limited information is available on global hemostatic function in HSCT. We assessed changes in coagulation and fibrinolysis using a simultaneous thrombin and plasmin generation assay (T/P-GA) during HSCT. Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) using T/P-GA in six pediatric acute leukemia patients treated with HSCT were compared to normal plasma. In the SOS case, the ratios of T-EP and P-Peak to normal were simultaneously decreased at four weeks post-HSCT (Pre; ~1.1/1.1-1.4, Week+4; 0.14/0.0084, respectively). Similarly, in the TMA patient, both ratios were decreased at 3 weeks and recovered after 8 weeks (Pre; 1.2/~0.95, Week+3; 0.59/0.22, Week+8; 1.2/0.64-0.85). In the other patients, when SOS/TMA was not evident, the T/P-GA data remained within normal limits. These findings suggest that the simultaneous reduction of coagulation and fibrinolytic function in patients developing SOS/TMA can lead to a life-threatening coagulopathy. Further research is warranted to clarify global hemostatic function after HSCT to establish optimal supportive therapy for these critical clinical disorders of hemostasis.