Luzzatto Guido, Cella Giuseppe, Messina Chiara, Randi Maria Luigia, Sbarai Alessandra, Zanesco Luigi
Department of Medical and Surgical Science, Chair of Hematology, Padova University Medical School, Italy.
Med Pediatr Oncol. 2003 Jan;40(1):9-12. doi: 10.1002/mpo.10145.
Endothelial cells and leukocytes intimately interact in inflammation and coagulation processes, so that dysregulation of their function may lead to both cellular damage and thrombosis, which may occur as complications of bone marrow transplantation (BMT). Partially conflicting evidence about endothelial markers and their relationships with clinical complications after BMT has been reported in the literature. Since almost all studies were carried out in adults, we evaluated some recent available markers of endothelial cell function in pediatric patients undergoing stem cell transplantation (SCT) for acute leukemia.
We studied the variation in circulating serum endothelial-selectin (ES), leukocyte-selectin (LS), thrombomodulin (TM), von Willebrand factor (vWF), nitrate + nitrite (NO(2) (-)/NO(3) (-)), endothelin-1 (EN), and tissue factor (TF) in 21 pediatric patients undergoing SCT for acute leukemia.
ES and LS significantly lowered following SCT and returned to pre-SCT levels 4 weeks after the procedure. NO(2) (-)/NO(3) (-) markedly increased following SCT. Also, TM and vWF increased, although such changes did not reach statistical significance. EN and TF did not appreciably change. A strong correlation was observed between white blood cell (WBC) count and both ES and LS, as well as between such selectins. TM significantly correlated with both selectins and NO(2) (-)/NO(3) (-). The pre-conditioning levels of TM and vWF in patients undergoing major complications, considered altogether, were significantly lower and higher, respectively, than in uncomplicated patients. NO(2) (-)/NO(3) (-) levels 3 and 4 weeks post-SCT were significantly lower in patients suffering from veno occlusive disease. Both selectins were significantly higher in allo- than in auto-transplanted patients 4 weeks after SCT.
Our data support the hypothesis of severe endothelial damage after conditioning and SCT, particularly allogeneic. However, the increase in TM, which has strong anticoagulant properties, and metabolites of NO, involved also in protective actions, may reflect regeneration of the anti-thrombotic endothelial function. This could take place after transitory functional impairment, rather than pure endothelial damage.
内皮细胞和白细胞在炎症和凝血过程中密切相互作用，因此它们功能的失调可能导致细胞损伤和血栓形成，这可能作为骨髓移植（BMT）的并发症出现。文献中报道了关于内皮标志物及其与BMT后临床并发症关系的部分相互矛盾的证据。由于几乎所有研究都是在成人中进行的，我们评估了接受急性白血病干细胞移植（SCT）的儿科患者中一些最新可用的内皮细胞功能标志物。
我们研究了21例接受急性白血病SCT的儿科患者循环血清中内皮选择素（ES）、白细胞选择素（LS）、血栓调节蛋白（TM）、血管性血友病因子（vWF）、硝酸盐+亚硝酸盐（NO₂⁻/NO₃⁻）、内皮素-1（EN）和组织因子（TF）的变化。
SCT后ES和LS显著降低，并在术后4周恢复到SCT前水平。SCT后NO₂⁻/NO₃⁻显著增加。此外，TM和vWF增加，尽管这种变化未达到统计学意义。EN和TF没有明显变化。观察到白细胞（WBC）计数与ES和LS之间以及这些选择素之间存在强相关性。TM与两种选择素和NO₂⁻/NO₃⁻均显著相关。总体而言，发生主要并发症的患者中TM和vWF的预处理水平分别显著低于和高于未发生并发症的患者。发生静脉闭塞性疾病的患者在SCT后3周和4周时NO₂⁻/NO₃⁻水平显著较低。SCT后4周，同种异体移植患者的两种选择素均显著高于自体移植患者。
我们的数据支持预处理和SCT后，尤其是同种异体移植后存在严重内皮损伤的假设。然而，具有强抗凝特性的TM增加以及同样参与保护作用的NO代谢产物增加，可能反映了抗血栓形成内皮功能的再生。这可能发生在短暂的功能损害之后，而不是单纯的内皮损伤。
