Salat C, Holler E, Reinhardt B, Kolb H J, Seeber B, Ledderose G, Mittermueller J, Duell T, Wilmanns W, Hiller E
Department of Hematology and Oncology, Med. Klinik III Klinikum Grosshadern, Munich, Germany.
Bone Marrow Transplant. 1994 Nov;14(5):747-50.
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.
静脉闭塞性疾病(VOD)是骨髓移植(BMT)后较为常见且最为严重的并发症之一。VOD的病理生理学机制目前尚不清楚。为了研究内皮细胞损伤与VOD之间可能存在的联系,我们检测了32例患者的组织纤溶酶原激活物(tPA)及其抑制剂(PAI-1),将其作为纤溶系统中内皮细胞衍生的参数。结果发现,与未发生该并发症的患者(平均22.2 ng/ml,范围1.4 - 131.6 ng/ml)相比,发生VOD的4例患者的PAI-1水平几乎增加了五倍(平均103.9 ng/ml,范围22.6 - 582.4 ng/ml,p < 0.05)。在接受BMT后有或无VOD或其他并发症的患者组之间,tPA水平未发现显著差异,这表明纤溶平衡向低纤溶状态转变,尤其是在VOD患者中。我们得出结论,接受BMT的患者会发生纤溶系统改变。低纤溶似乎至少是VOD发病机制中的一个因素,测定PAI-1可能有助于诊断该疾病。我们的数据还可能解释了重组tPA对VOD的成功治疗报道。