PARAMETERS OF THE FIBRINOLYTIC SYSTEM IN PATIENTS UNDERGOING BMT - ELEVATION OF PAI-1 IN VENOOCCLUSIVE DISEASE

Veno-occlusive disease (VOD) represents one of the more frequent and m ost severe complications after BMT. The pathophysiology of VOD is poor ly understood. To investigate a possible link between endothelial cell damage and VOD, tissue plasminogen activator (tPA) and its inhibitor (PAI-1) were measured in 32 patients as endothelial cell-derived param eters of the fibrinolytic system. A nearly fivefold increase (mean 103 .9 ng/ml, range 22.6-582.4 ng/ml, p<0.05) in PAI-1 levels was found in the four patients who developed VOD compared with patients without th is complication (mean 22.2 ng/ml, range 1.4-131.6 ng/ml). No significa nt difference was found in tPA levels between patient groups with or w ithout VOD or other complications following BMT, indicating a shift of the fibrinolytic balance towards hypofibrinolysis particularly in pat ients with VOD. We conclude that alterations of the fibrinolytic syste m occur in patients undergoing BMT. Hypofibrinolysis seems to be at le ast one factor in the pathogenesis of VOD and the determination of PAI -1 might be helpful for diagnosing the disease. Our data also may expl ain the reported successful treatment of VOD by recombinant tPA.