Maloney James P, Ambruso Daniel R, Voelkel Norbert F, Silliman Christopher C
Departments of Pulmonary Sciences and Critical Care Medicine, University of Colorado at Denver, USA ; Department of Medicine, University of Colorado at Denver, USA.
Department of Pediatrics, University of Colorado at Denver, USA ; Department of Pathology, University of Colorado at Denver, USA ; University of Colorado School of Medicine; the Center for Cancer and Blood Disorders, Children's Hospital Colorado, USA ; Bonfils Blood Center, University of Colorado at Denver, USA.
J Pulm Respir Med. 2014;4. doi: 10.4172/2161-105X.1000212.
The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors.
Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak.
There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak.
Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products.
血小板和血浆输注时非溶血性输血反应的发生率最高。其中一些反应的特征是内皮渗漏，尤其是输血相关急性肺损伤（TRALI）。血液制品储存期间污染白细胞分泌的炎症介质浓度升高可能导致此类反应，但血小板分泌的介质也可能起作用。我们推测血小板储存会导致内皮通透性介质血管内皮生长因子（VEGF）积累，并且血管内给予外源性VEGF会导致其与肺受体广泛结合。
对单采白细胞去除术采集的单供者血小板单位在储存5天期间进行采样。通过酶联免疫吸附测定法（ELISA）测定离心后上清液中的VEGF蛋白含量，并对污染白细胞中VEGF的潜在贡献进行定量。使用离体灌注大鼠肺研究血管内给予放射性标记VEGF的摄取情况，以及未标记VEGF对肺渗漏的影响。
VEGF呈时间依赖性释放入血小板浓缩物的血浆部分（第1天为62±9 pg/ml，第5天为149±23 pg/ml；均值±标准误，p<0.01，n = 8），且排除了污染白细胞的影响。外源性125I-VEGF与肺血管系统紧密且特异性结合，肺灌注液中的未标记VEGF导致血管渗漏。
单供者血小板浓缩物储存期间VEGF浓度升高是由于血小板分泌或解体，而非白细胞污染。这些浓度的外源性VEGF迅速与其在肺血管中的受体结合。在较高VEGF浓度下，VEGF会导致未损伤肺的血管渗漏。这些数据进一步证明VEGF可能导致与血小板制品相关的TRALI中肺通透性增加。
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