VPB0634 - Veno-occlusive disease in pediatric patients after stem cell transplant is associated with impaired fibrinolysis

Background: Hepatic veno-occlusive disease is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis and prompt initiation of defibrotide - the only approved therapy - is important to a successful treatment of VOD. Because of the severity of this disease, an early diagnosis is important to start treatment of VOD as soon as possible. Currently, no predictive biomarker exists to monitor disease progression or therapy responsiveness.

Aims: In this prospective study, we systematically analyze the viscoelastic changes in coagulation system with a focus on plasmin resistance in HSCT patients.

Methods: 54 pediatric patients with leukemia or other hemato-oncological disease who received HSCT with a high risk of VOD were included in this prospective study. Whole blood samples were investigated using a viscoelastic test system to assess coagulation and fibrinolysis. Additionally immunoassays for factors of the fibrinolysis system were performed.

Results: Significantly elevated resistance to clot lysis and longer time of lysis after adding tissue plasminogen activator were observed in blood samples from VOD patients compared to non-VOD HSCT patients. Plasma levels of plasminogen activator inhibitor 1 are still in evaluation but seems to be significantly higher in plasma samples from clinical diagnosed VOD patients.

Conclusion(s): Our data support the hypothesis that VOD is associated with impaired fibrinolysis in blood. It’s assumed that fibrinolytic inhibitors are elevated leading to an increased resistance to clot lysis. Further investigations are following. Thromboelastography could be useful to investigate VOD early in patients after HSCT.