Haemostasis Laboratory, CHU, Grenoble, France.
Therex, TIMC-IMAG, CNRS UMR5525, Grenoble, France.
J Clin Apher. 2020 Sep;35(5):444-452. doi: 10.1002/jca.21825. Epub 2020 Aug 17.
ABO- or HLA-incompatible kidney transplantation is possible thanks to pretransplant antibody-depletion achieved by extracorporeal-treatment modalities. These methods induce depletion of some plasma proteins and may also impact on proteins involved in hemostasis.
To determine the impact of one session of immunoadsorption (IA) alone or combined with membrane filtration (MF) on clotting factors and natural anticoagulants, we performed a prospective, observational study on 13 patients waiting for HLA-/ABO-incompatible kidney transplants. Plasma hemostasis parameters were measured before and immediately after a first session of IA alone in six patients and of IA + MF in seven patients.
IA alone induced depletion of fibrinogen and factor XIII (FXIII) whereas IA + MF caused greater depletion of all high-molecular-weight hemostatic proteins (fibrinogen, FV, FVIII, FXI, FXIII, von-Willebrand factor [VWF]). After an IA session, median reductions were 30% for fibrinogen and 43% for FXIII compared to baseline values. After a session of IA + MF, median decreases were 70% for fibrinogen, 54% for FV, 56% for FVIII, 37% for FXI, 78% for FXIII, and 62% for VWF. Noticeably, levels of low-molecular-weight factors (<100 kDa) were far less decreased than high-molecular-weight proteins with IA + MF, except for protein S and the tissue factor pathway inhibitor, which are known to be partially physiologically bound to high-molecular-weight molecules.
IA and IA + MF induced significant depletion of some proteins implicated in the hemostatic process; however, IA + MF resulted in stronger modifications to hemostasis parameters than IA alone. This may have potential clinical implications regarding bleeding risk, and particularly depletion of fibrinogen and FXIII.
由于体外治疗模式实现了移植前抗体耗竭,因此可以进行 ABO 或 HLA 不相容的肾移植。这些方法可耗竭一些血浆蛋白,并且可能还会影响到参与止血的蛋白。
为了确定单次免疫吸附(IA)单独或与膜过滤(MF)联合应用对凝血因子和天然抗凝剂的影响,我们对 13 名等待 HLA-/ABO 不相容肾移植的患者进行了一项前瞻性、观察性研究。在 6 名患者中,我们在单独进行单次 IA 前和之后立即测量了 13 名患者的血浆止血参数,在 7 名患者中,我们在进行 IA+MF 后测量了这些参数。
IA 单独应用可导致纤维蛋白原和因子 XIII(FXIII)耗竭,而 IA+MF 则导致所有高分子量止血蛋白(纤维蛋白原、FV、VIII、FXI、FXIII、血管性血友病因子[VWF])的耗竭更为严重。与基线值相比,IA 治疗后纤维蛋白原的中位数降低了 30%,FXIII 的中位数降低了 43%。IA+MF 治疗后,纤维蛋白原的中位数降低了 70%,FV 的中位数降低了 54%,VIII 的中位数降低了 56%,FXI 的中位数降低了 37%,FXIII 的中位数降低了 78%,VWF 的中位数降低了 62%。值得注意的是,除了已知部分与高分子量分子生理性结合的蛋白 S 和组织因子途径抑制剂外,IA+MF 对低分子量因子(<100 kDa)的降低程度远低于高分子量蛋白。
IA 和 IA+MF 诱导了一些参与止血过程的蛋白质的显著耗竭;然而,IA+MF 引起的止血参数变化比 IA 单独应用更为强烈。这可能对出血风险具有潜在的临床意义,尤其是对纤维蛋白原和 FXIII 的耗竭。