Red blood cell rigidification during cyclosporin therapy: a possible early warning signal for adverse reactions
Red blood cell rigidification during cyclosporin therapy: a possible early warning signal for adverse reactions
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DOI：
10.1080/00365519850186049
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发表时间：
1998-12-01
影响因子：
2.1
通讯作者：
Vreeken, J
中科院分区：
文献类型：
--
作者：
Hardeman, MR;Meinardi, MMHM;Vreeken, J
在先前对肾移植患者的回顾性研究中，发现环孢素A（CsA）免疫抑制治疗与红细胞（RBC）变形能力受损相关。本研究的目的是在一项针对非移植患者的前瞻性研究中评价并证实CsA的使用与其对RBC变形性的影响之间可能存在的因果关系。12例银屑病患者在CsA（3 ~ 5 mg/d）治疗前、治疗后2、4、8、12和16周分别取血。红细胞变形性，表示为延伸指数（EI），用激光辅助光学旋转细胞分析仪（LORCA），一种新的ektacytometric仪器。用环孢菌素治疗16周后发现的EI的平均值+/- SD（0.570 +/- 0.008）显著（p < 0.001）低于治疗前的值（0.589 +/- 0.011）。在本研究中使用的CsA剂量的小范围内，无法建立剂量-反应关系。然而，无论剂量如何，治疗持续时间与EI降低之间均存在显著相关性（r= -0.55; p = 0.0001）。血液与环孢菌素的体外孵育不能再现这种作用，表明药物对RBC的直接作用不太可能。尽管CsA的使用剂量相对较低，但它会导致RBC变形性降低，这种作用在治疗过程中会增加。这表明，这种缓慢的，但不断增加，红细胞硬化起着重要的作用，在早期发病机制的不良肾毒性并发症经常与这种免疫抑制方案。
In a previous retrospective study with kidney-transplant patients, immunosuppressive treatment with Cyclosporin A (CsA) was found to be associated with impaired red blood cell (RBC) deformability. The aim of the present study was to evaluate and substantiate a possible causal relationship between the use of CsA and its effect on RBC deformability in a prospective study on non-transplant patients. Blood samples of 12 patients with psoriasis were taken before and after 2, 4, 8, 12 and 16 weeks of treatment with CsA (3 - 5 mg/day). Red cell deformability, expressed as Elongation Index (EI), was measured with the Laser-assisted Optical Rotational Cell Analyzer (LORCA), a new ektacytometric instrument. Mean values +/- SD for EI found after 16 weeks of treatment with cyclosporin (0.570 +/- 0.008) were significantly (p < 0.001) lower than the Value before treatment (0.589 +/- 0.011). A dose-response relation could not be established within the small range of CsA doses used in this study. Irrespective of the dose, however, a significant correlation (r= -0.55; p = 0.0001) between duration of treatment and decrease in EI was demonstrated. In vitro incubation of blood with cyclosporin was not able to reproduce this effect, suggesting that a direct effect of the drug on RBCs is unlikely. Despite its use in relatively low doses, CsA causes a reduction in RBC deformability, an effect that increases during the course of treatment. It is suggested that this slow, but continuously increasing, RBC rigidification plays a role in the early pathogenesis of the adverse nephrotoxic complications frequently associated with this immunosuppressive regimen.