Decreased total iron binding capacity upon intensive care unit admission predicts red blood cell transfusion in critically ill patients

IntroductionRed blood cell (RBC) transfusion is associated with poor clinical outcome in critically ill patients. We investigated the predictive value of biomarkers on intensive care units (ICU) admission for RBC transfusion within 28 days.MethodsCritically ill patients (n = 175) who admitted to our ICU with organ dysfunction and an expected stay of ≥ 48 hours, without hemorrhage, were prospectively studied (derivation cohort, n = 121; validation cohort, n = 54). Serum levels of 12 biomarkers (hemoglobin, creatinine, albumin, interleukin-6 [IL-6], erythropoietin, Fe, total iron binding capacity [TIBC], transferrin, ferritin, transferrin saturation, folate, and vitamin B12) were measured upon ICU admission, days 7, 14, 21 and 28.ResultsAmong the 12 biomarkers measured upon ICU admission, levels of hemoglobin, albumin, IL-6, TIBC, transferrin and ferritin were statistically different between transfusion and non-transfusion group. Of 6 biomarkers, TIBC upon ICU admission had the highest area under the curve value (0.835 [95% confidence interval] = 0.765–0.906) for predicting RBC transfusion (cut-off value = 234.5 μg/dL; sensitivity = 0.906, specificity = 0.632). This result was confirmed in validation cohort, whose sensitivity and specificity were 0.888 and 0.694, respectively. Measurement of these biomarkers every seven days revealed that albumin, TIBC and transferrin were statistically different between groups throughout hospitalization until 28 days. In validation cohort, patients in the transfusion group had significantly higher serum hepcidin levels than those in the non-transfusion group (P = 0.004). In addition, joint analysis across derivation and validation cohorts revealed that the serum IL-6 levels were higher in the transfusion group (P = 0.0014).ConclusionDecreased TIBC upon ICU admission has high predictive value for RBC transfusion unrelated to hemorrhage within 28 days.

引言
红细胞（Red Blood Cell, RBC）输注与重症患者的不良临床结局相关。本研究探讨了重症监护病房（Intensive Care Unit, ICU）入院时检测的生物标志物对28天内RBC输注的预测价值。
方法
本研究为前瞻性队列研究，纳入入住本院ICU、存在器官功能障碍、预计住院时长≥48小时且无出血的重症患者共175例，分为推导队列（n=121）与验证队列（n=54）。于ICU入院时及第7、14、21、28天检测12种生物标志物的血清水平，包括血红蛋白、肌酐、白蛋白、白细胞介素-6（Interleukin-6, IL-6）、促红细胞生成素、铁（Fe）、总铁结合力（Total Iron Binding Capacity, TIBC）、转铁蛋白、铁蛋白、转铁蛋白饱和度、叶酸及维生素B12。
结果
于ICU入院时检测的12种生物标志物中，输注组与非输注组患者的血红蛋白、白蛋白、IL-6、TIBC、转铁蛋白及铁蛋白水平存在统计学差异。在上述6种差异标志物中，ICU入院时检测的TIBC预测RBC输注的曲线下面积最高，为0.835（95%置信区间：0.765~0.906），其截断值为234.5 μg/dL，灵敏度为0.906，特异度为0.632。该结果在验证队列中得到验证，验证队列的灵敏度与特异度分别为0.888与0.694。每7天一次的生物标志物检测结果显示，白蛋白、TIBC及转铁蛋白在整个住院期间直至28天，两组间均存在统计学差异。在验证队列中，输注组患者的血清铁调素水平显著高于非输注组（P=0.004）。此外，对推导队列与验证队列的联合分析显示，输注组患者的血清IL-6水平更高（P=0.0014）。
结论
ICU入院时TIBC降低对28天内非出血相关RBC输注具有较高的预测价值。