Lehner Georg Franz, Harler Ulrich, Feistritzer Clemens, Haller Viktoria Maria, Hasslacher Julia, Bellmann Romuald, Joannidis Michael
Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Department of Internal Medicine V - Haematology and Oncology, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Ann Intensive Care. 2017 Sep 4;7(1):89. doi: 10.1186/s13613-017-0312-3.
Microvesicles (MV) are extracellular vesicles known to be associated with cellular activation and inflammation. Hemofiltration is an effective blood purification technique for patients with renal failure and possibly also eliminates inflammatory mediators in the setting of sepsis. On the other hand, proinflammatory stimuli are induced by blood contacting the artificial membrane during extracorporeal blood purification. In chronic dialysis patients a systemic increase in MV has been described. The aim of the study was to investigate whether hemofilter passage of blood in continuous veno-venous hemofiltration (CVVH) alters MV composition and levels in critically ill patients with sepsis.
Pre- and postfilter bloods as well as ultrafiltrate samples from intensive care unit patients with severe sepsis were obtained during CVVH with regional citrate anticoagulation. MV subtypes in blood were analyzed by high-sensitivity flow cytometry. Additionally, tissue factor (TF) levels and MV-associated TF activities as well as MV activities were quantified. All parameters were corrected for hemoconcentration applied during CVVH.
Twelve patients were analyzed. A significant increase in presumably mostly leukocyte-derived CD31+/CD41- MV (1.32 (1.09-1.93)-fold [median (25th-75th quartiles)], p = 0.021) was observed post- to prefilter, whereas platelet-derived MV as well as AnnexinV-binding MV were unaltered. Increments of AnnexinV+, CD42b+ and CD31+/CD41- MV post- to prefilter correlated with filtration fraction (FF) (all p < 0.05). Significant reductions in MV activity [0.72 (0.62-0.84)-fold, p = 0.002] and TF level [0.95 (0.87-0.99)-fold, p = 0.0093] were detected postfilter compared to prefilter. No MV activity was measurable in ultrafiltrate samples.
Despite clearing a fraction of small PS-exposing MV CVVH does not eliminate larger MV. Concurrently, CVVH induces the release of CD31+/CD4- MV that indicate leukocyte activation during hemofilter passage in septic patients. Increments of several MV subtypes within the hemofilter correlate with FF, which supports common recommendations to keep FF low. A fraction of TF is being cleared by CVVH via ultrafiltration.
微泡（MV）是已知与细胞活化和炎症相关的细胞外囊泡。血液滤过是治疗肾衰竭患者的一种有效的血液净化技术，并且可能在脓毒症时也能清除炎症介质。另一方面，体外血液净化过程中血液与人工膜接触会诱导促炎刺激。在慢性透析患者中，已观察到MV的全身性增加。本研究的目的是调查在连续性静脉-静脉血液滤过（CVVH）中血液通过血液滤过器是否会改变脓毒症重症患者的MV组成和水平。
在采用局部枸橼酸盐抗凝的CVVH过程中，获取重症监护病房严重脓毒症患者的滤器前和滤器后血液以及超滤液样本。通过高灵敏度流式细胞术分析血液中的MV亚型。此外，对组织因子（TF）水平、与MV相关的TF活性以及MV活性进行定量。所有参数均针对CVVH期间应用的血液浓缩进行校正。
分析了12例患者。观察到滤器后推测主要源自白细胞的CD31+/CD41- MV显著增加（1.32（1.09 - 1.93）倍[中位数（第25 - 7�四分位数）]，p = 0.021），而源自血小板的MV以及膜联蛋白V结合MV未改变。滤器后膜联蛋白V阳性、CD42b阳性和CD31+/CD41- MV的增加与滤过分数（FF）相关（所有p < 0.05）。与滤器前相比，滤器后检测到MV活性[0.72（0.62 - 0.84）倍，p = 0.002]和TF水平[0.95（0.87 - 0.99）倍，p = 0.0093]显著降低。在超滤液样本中未检测到MV活性。
尽管CVVH清除了一部分暴露磷脂酰丝氨酸的小MV，但并未消除较大的MV。同时，CVVH诱导CD31+/CD4- MV的释放，这表明脓毒症患者血液滤过器通过期间白细胞被激活。血液滤过器内几种MV亚型的增加与FF相关，这支持了将FF保持在低水平的常见建议。一部分TF通过CVVH经超滤清除。
