Abstract
BackgroundFerritin is the major iron storage protein and an acute phase reactant. Hyperferritinemia is frequently seen in the critically ill where it has been hypothesized that not only underlying conditions but also factors such as transfusions, hemodialysis and extracorporeal life support (ECLS) lead to hyperferritinemia. This study aims to investigate the influence of transfusions, hemodialysis, and ECLS on hyperferritinemia in a multidisciplinary ICU cohort.MethodsThis is a post-hoc analysis of a retrospective observational study including patients aged ≥ 18 years who were admitted to at least one adult ICU between January 2006 and August 2018 with hyperferritinemia ≥ 500 μg/L and of ≥ 14 days between two ICU ferritin measurements. Patients with hemophagocytic lymphohistiocytosis (HLH) were excluded. To identify the influence of transfusions, hemodialysis, and ECLS on ferritin change, multivariable linear regression analysis with ferritin change between two measurements as dependent variable was performed.ResultsA total of 268 patients was analyzed. Median duration between measurements was 36 days (22–57). Over all patients, ferritin significantly increased between the first and last measurement (p = 0.006). Multivariable linear regression analysis showed no effect of transfusions, hemodialysis, or ECLS on ferritin change. Changes in aspartate aminotransferase (ASAT) and sequential organ failure assessment (SOFA) score were identified as influencing factors on ferritin change [unstandardized regression coefficient (B) = 2.6; (95% confidence interval (CI) 1.9, 3.3); p < 0.001 and B = 376.5; (95% CI 113.8, 639.1); p = 0.005, respectively]. Using the same model for subgroups of SOFA score, we found SOFA platelet count to be associated with ferritin change [B = 1729.3; (95% CI 466.8, 2991.9); p = 0.007]. No association of ferritin change and in-hospital mortality was seen in multivariable analysis.ConclusionsThe present study demonstrates that transfusions, hemodialysis, and ECLS had no influence on ferritin increases in critically ill patients. Hyperferritinemia appears to be less the result of iatrogenic influences in the ICU thereby underscoring its unskewed diagnostic value.Trial registrationThe study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.
Highlights
Ferritin is the major iron storage protein located in hepatocytes and the reticulo-endothelial system
Multivariable linear regression analysis showed no effect of transfusions, hemodialysis, or extracorporeal life support (ECLS) on ferritin change
Changes in aspartate aminotransferase (ASAT) and sequential organ failure assessment (SOFA) score were identified as influencing factors on ferritin change [unstandardized regression coefficient (B) = 2.6; (95% confidence interval (CI) 1.9, 3.3); p < 0.001 and B = 376.5;; p = 0.005, respectively]
Summary
Ferritin is the major iron storage protein located in hepatocytes and the reticulo-endothelial system. Mortality was increased in critically ill patients with hyperferritinemia [7,8] Among this patient population, high levels of ferritin have been detected [8]. In patients with end-stage renal disease requiring hemodialysis, severely elevated ferritin levels of > 400000 μg/L have been detected [12]. Both hemolysis caused by osmotic and shear stress in the extracorporeal circuit [13] as well as pro-inflammatory immune reactivity triggered by dialysis membranes and catheters [14] might account for this effect. The impact of PRBC transfusion, hemodialysis, and ECLS on ferritin levels and their diagnostic accuracy in critically ill patients remains unclear. This study aims to investigate the influence of transfusions, hemodialysis, and ECLS on hyperferritinemia in a multidisciplinary ICU cohort
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