New insights into sinusoidal obstruction syndrome.

Background: Entry criteria included patients who developed sinusoidal obstruction syndrome (SOS) at a single centre from January 2000 to December 2011. Patients who underwent haemopoietic stem cell transplantation or actinomicyn-based chemotherapy for nephroblastoma were selected. The study group comprised five patients with SOS who were compared with a control group of seven patients without SOS.

Aim: To study the relationships between endothelial extracellular vesicles (EV) and plasminogen-activator inhibitor type 1(PAI-1) to assess their modification in the early phase of SOS.

Methods: Consecutive blood samples were tested for cell-derived EV, PAI-1 and coagulation parameters. Any statistically significant correlation between all datasets was searched.

Results: Antithrombin level and platelet count were statistically significantly reduced in SOS patients, suggesting a consumption status. PAI-1:Ag and PAI-1:act showed an inverse relationship with platelet counts (coef. -0.034, SE = 0.016; P = 0.041 and -0.052, SE = 0.019; P = 0.011 respectively). During follow up, PAI-1:Ag was inversely related to EV CD144+ (coef. -0.261, SE = 0.094; P = 0.007) and antithrombin (coef -0.509, SE = 0.175; P = 0.005). PAI-1:act showed an inverse association with EV CD144+ (coef.-0.251, SE = 0.121; P = 0.043), EV CD31+/CD41+ (coef. -0.004, SE = 0.002; P = 0.026) and antithrombin (coef. -0.470, SE = 0.220; P = 0.038). EV generated by rupture of gap junctions (EV CD144+) were increased in SOS patients and also showed a change over time.

Conclusion: This study demonstrates the existence of an ongoing procoagulant and hypofibrinolytic status in SOS, indicating a possible role for anticoagulant therapy. Moreover, these findings suggest a role for EV CD 144+, either alone or in combination with PAI-1, as a new biomarker for SOS.