Fujii Yoshinari, Nagaya Satomi, Seo Atsunobu, Kanazawa Yuji, Oba Taisei, Morishita Eriko
Faculty of Health and Medical Sciences, Hokuriku University, Kanazawa, JPN.
Clinical Laboratory Science, Graduate School of Medical Science, Kanazawa University, Kanazawa, JPN.
Cureus. 2024 Dec 4;16(12):e75117. doi: 10.7759/cureus.75117. eCollection 2024 Dec.
Introduction Hemodialysis (HD) therapy is a crucial treatment for patients with renal failure but can impact the hemodynamics of antithrombin (AT), a protein essential for regulating hemostasis and preventing thrombosis. Reduced AT activity can lead to thrombus formation at unusual sites and increase the risk of recurrent venous thromboembolism. The loss of AT during HD or hemodiafiltration (HDF) through leakage or adsorption onto dialysis membranes has not been fully investigated, and its effects on AT hemodynamics remain unclear. We aimed to elucidate the mechanisms underlying AT activity reduction due to dialysis, with the goal of developing dialysis protocols that preserve AT activity and reduce the risk of vascular access-related thrombosis. Methods AT activity and antigen levels were measured before and after dialysis therapy in 24 patients undergoing maintenance dialysis at Itaya Clinic (HD, 12; HDF, 12). AT antigen levels in dialysis effluent were also measured to analyze the effects of dialysis on AT hemodynamics. Additionally, immunofluorescence staining of dialysis membranes was used to semi-quantitatively assess the amount of AT adsorbed onto the membrane. Results AT activity and antigen levels in patients undergoing HD were significantly lower than those in healthy participants but increased following dialysis. A negative correlation was found between dialysis vintage (history of heparin use) and predialysis AT activity. AT leakage and adsorption were significantly greater with HDF than with HD. However, no correlation was observed between AT leakage and activity or antigen levels before and after dialysis. Conclusions AT activity and antigen levels were decreased in patients on HD, with long-term heparin use suggested as a contributing factor. Additionally, AT leakage was observed during HDF therapy, indicating that dialysis-related AT leakage may contribute to decreased AT activity and antigen levels. Therefore, regular measurement of AT activity is recommended for patients with HD. If AT activity decreases, treatment adjustments, such as switching to HD therapies that minimize AT leakage and adsorption, should be considered.
引言 血液透析（HD）疗法是肾衰竭患者的关键治疗手段，但会影响抗凝血酶（AT）的血流动力学，AT是一种调节止血和预防血栓形成所必需的蛋白质。AT活性降低会导致在异常部位形成血栓，并增加复发性静脉血栓栓塞的风险。HD或血液透析滤过（HDF）过程中AT通过透析膜渗漏或吸附而损失的情况尚未得到充分研究，其对AT血流动力学的影响仍不清楚。我们旨在阐明透析导致AT活性降低的机制，以期制定出能保留AT活性并降低血管通路相关血栓形成风险的透析方案。方法 对伊谷诊所24例接受维持性透析的患者（HD组12例；HDF组12例）在透析治疗前后测量AT活性和抗原水平。还测量了透析流出液中的AT抗原水平，以分析透析对AT血流动力学的影响。此外，采用透析膜免疫荧光染色半定量评估吸附在膜上的AT量。结果 HD患者的AT活性和抗原水平显著低于健康参与者，但透析后有所升高。透析龄（肝素使用史）与透析前AT活性呈负相关。HDF导致的AT渗漏和吸附明显高于HD。然而，透析前后AT渗漏与活性或抗原水平之间未观察到相关性。结论 HD患者的AT活性和抗原水平降低，长期使用肝素是一个促成因素。此外，在HDF治疗期间观察到AT渗漏，表明透析相关的AT渗漏可能导致AT活性和抗原水平降低。因此，建议对HD患者定期测量AT活性。如果AT活性降低，应考虑调整治疗，如改用能将AT渗漏和吸附降至最低的HD治疗方法。
