Helsinki University, Division of Anesthesiology, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Hematology, Coagulation Disorders Unit, Helsinki University Hospital, Helsinki, Finland, and Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Finland.
Division of Nephrology, Helsinki University Hospital, Helsinki, Finland.
Transfus Apher Sci. 2024 Jun;63(3):103918. doi: 10.1016/j.transci.2024.103918. Epub 2024 Mar 27.
Therapeutic plasma exchange (TPE), with solvent/detergent (S/D)-treated plasma as replacement fluid, is an extracorporeal blood purification technique with major impact on both coagulation and lipids. Our previous in vitro study showed that S/D-plasma enhances thrombin generation by lowering intact protein S (PS) levels.
To evaluate the impact of altered lipid balance on coagulation phenotype during heparin-anticoagulated TPE with S/D-plasma, and to investigate whether the lowered intact PS levels with concomitant procoagulant phenotype, are recapitulated in vivo.
Coagulation biomarkers, thrombin generation with Calibrated Automated Thrombogram (CAT), and lipid levels were measured before and after the consecutive 1st, 3rd and 5th episodes of TPE performed to six patients with Guillain-Barré syndrome or myasthenia gravis. The effects of in vitro dilution of S/D-plasma on thrombin generation were explored with CAT to mimic TPE.
Patients did not have coagulation disorders, except elevated FVIII. Intact PS, lipoproteins, especially LDL, Apolipoprotein CIII (ApoC3) and ApoB/ApoA1 ratio declined (p < 0.05). In contrast, VLDL and triglyceride levels stayed intact. CAT lag time shortened (p < 0.05). In vitro dilution of S/D plasma with co-transfused Ringer's lactate and 4% albumin partially reduced its procoagulant phenotype in CAT, which is mainly seen as peak thrombin, and modestly shortened lag time.
After the five settings of TPE using S/D-plasma in vivo, which associated with heparinization and reduced coagulation factor activities, our observations of declining natural anticoagulant intact PS and apolipoproteins refer to rebalance of the hemostatic and lipid profiles.
治疗性血浆置换（TPE）使用经溶剂/去污剂（S/D）处理的血浆作为置换液，是一种对凝血和脂质均有重大影响的体外血液净化技术。我们之前的体外研究表明，S/D 血浆通过降低完整蛋白 S（PS）水平来增强凝血酶生成。
评估在 S/D 血浆肝素抗凝 TPE 过程中脂质平衡改变对凝血表型的影响，并研究降低的完整 PS 水平与伴随的促凝表型是否在体内重现。
对 6 例吉兰-巴雷综合征或重症肌无力患者进行连续的第 1、3 和 5 次 TPE 治疗前后，分别测量凝血生物标志物、使用 Calibrated Automated Thrombogram（CAT）检测的凝血酶生成以及脂质水平。使用 CAT 体外稀释 S/D 血浆来模拟 TPE，以探索其对凝血酶生成的影响。
患者没有凝血障碍，除了 FVIII 升高。完整 PS、脂蛋白，特别是 LDL、载脂蛋白 CIII（ApoC3）和 ApoB/ApoA1 比值下降（p<0.05）。相反，VLDL 和甘油三酯水平保持不变。CAT 延迟时间缩短（p<0.05）。S/D 血浆与同时输注的林格氏乳酸盐和 4%白蛋白的体外稀释部分降低了其在 CAT 中的促凝表型，这主要表现为峰值凝血酶，并且适度缩短了延迟时间。
在体内使用 S/D 血浆进行五次 TPE 治疗后，与肝素化和凝血因子活性降低相关，我们观察到天然抗凝完整 PS 和载脂蛋白的下降，这反映了止血和脂质谱的重新平衡。
