Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
NHS Blood and Transplant, Bristol, UK.
J Clin Apher. 2022 Dec;37(6):534-543. doi: 10.1002/jca.22008. Epub 2022 Aug 24.
Therapeutic plasma exchange (TPE) is used for several chronic conditions with little evidence on the efficacy and safety of different choice of replacement fluid. Measurement of haemostasis, particularly in vitro thrombin generation, could play a role in determining the immediate efficacy of different fluid replacement.
To determine the impact of different TPE replacement fluid regimens on haemostatic assays.
Prospective observational multi-centre cohort study in adult patients 18 years and older evaluating haemostatic changes between four different TPE regimens: (1) 5% human albumin solution (Alb) only, (2) 50:50 mix of 5% Alb + modified gelatin, (3) 70:30 mix of 5% Alb and normal saline (NS), and (4) solvent-detergent, virus-inactivated fresh frozen plasma (FFP) (either alone or combined with other fluids). Twenty-one haemostasis variables were analysed (procoagulant, anticoagulant and fibrinolytic factors) pre and post TPE sessions, including in vitro thrombin generation. Linear mixed modelling and canonical discriminant analyses were used to examine the effect of TPE fluid type on haemostatic variables.
A total of 31 patients with up to 5 TPE sessions each (131 sessions in total) were enrolled. Out of 21 markers analysed using linear mixed modelling, the main effects of fluid type were found to be significant for 19 markers (P < 0.05), excluding plasminogen activator inhibitor-1 antigen and thrombin-anti-thrombin. Multivariate Analysis of Variance showed significant differences between the fluid types (Wilks' lambda = 0.07; F = 5.50; P < 0.0001) and this was supported by a canonical discriminant analysis, which identified the 4 most discriminating markers for fluid types as thrombin generation (lag-time, time-to Peak), fibrinogen and Factor V. In our analyses, the effect of FFP on haemostasis was significantly greater compared with other fluid types. Of the non-FFP fluids, 5% Alb + NS had a lower effect on haemostasis compared to other fluid types (Alb and modified gelatin + 5% Alb).
Thrombin generation and fibrinogen discriminated better the effect of different TPE fluids on haemostasis and should be considered as potential markers to evaluate the immediate haemostatic effect of TPE procedures. The use of NS as a TPE replacement fluid had a distinctive impact on thrombin generation and fibrinogen responses compared to other non-FFP fluids.
治疗性血浆置换（TPE）用于多种慢性疾病，但对于不同替代液选择的疗效和安全性证据甚少。止血的测量，特别是体外凝血酶生成，可以在确定不同液体替代物的即时疗效方面发挥作用。
确定不同 TPE 替代液方案对止血检测的影响。
这是一项在 18 岁及以上成年患者中进行的前瞻性观察性多中心队列研究，评估了四种不同 TPE 方案之间的止血变化：（1）仅 5%人白蛋白溶液（Alb）；（2）5% Alb 和改良明胶 50:50 混合液；（3）5% Alb 和生理盐水（NS）70:30 混合液；（4）溶剂/去污剂，病毒灭活新鲜冷冻血浆（FFP）（单独或与其他液体联合使用）。在 TPE 前后分析了 21 项止血变量（促凝、抗凝和纤维蛋白溶解因子），包括体外凝血酶生成。线性混合模型和典型判别分析用于研究 TPE 液类型对止血变量的影响。
共纳入 31 例患者，每位患者接受多达 5 次 TPE 治疗（共 131 次）。通过线性混合模型分析的 21 个标记物中，有 19 个标记物（P<0.05）的液型主效应显著，不包括纤溶酶原激活物抑制剂-1 抗原和凝血酶-抗凝血酶。多变量方差分析显示液型之间有显著差异（Wilks' lambda=0.07；F=5.50；P<0.0001），典型判别分析也支持这一点，该分析确定了液型的 4 个最具判别力的标记物为凝血酶生成（lag-time、time-to Peak）、纤维蛋白原和因子 V。在我们的分析中，FFP 对止血的影响明显大于其他液型。在非 FFP 液型中，5% Alb+NS 对止血的影响低于其他液型（Alb 和改良明胶+5% Alb）。
凝血酶生成和纤维蛋白原更好地区分了不同 TPE 液对止血的影响，应考虑作为评估 TPE 过程即时止血效果的潜在标记物。与其他非 FFP 液型相比，NS 作为 TPE 替代液使用对凝血酶生成和纤维蛋白原反应有独特的影响。
