Parameters of the fibrinolytic system in patients undergoing BMT: elevation of PAI-1 in veno-occlusive disease.
Veno-occlusive disease (VOD) represents one of the more frequent and most severe complications after BMT. The pathophysiology of VOD is poorly 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 parameters 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 this complication (mean 22.2 ng/ml, range 1.4-131.6 ng/ml). No significant difference was found in tPA levels between patient groups with or without VOD or other complications following BMT, indicating a shift of the fibrinolytic balance towards hypofibrinolysis particularly in patients with VOD. We conclude that alterations of the fibrinolytic system occur in patients undergoing BMT. Hypofibrinolysis seems to be at least one factor in the pathogenesis of VOD and the determination of PAI-1 might be helpful for diagnosing the disease. Our data also may explain the reported successful treatment of VOD by recombinant tPA.
Salat
C
C
Department of Hematology and Oncology, Med. Klinik III Klinikum Grosshadern, Munich, Germany.
Holler
E
E
Reinhardt
B
B
Kolb
H J
HJ
Seeber
B
B
Ledderose
G
G
Mittermueller
J
J
Duell
T
T
Wilmanns
W
W
Hiller
E
E
D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000293:injuries / Q000503:physiopathology; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006487:Hemostasis; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator