Red blood cell transfusion and increased length of storage are not associated with deep vein thrombosis in medical and surgical critically ill patients: a prospective observational cohort study

Abstract

IntroductionWith prolonged storage times, cell membranes of red blood cells (RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'. Storage lesions may promote inflammation and thrombophilia when transfused. In trauma patients, RBC transfusion was an independent risk factor for deep vein thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or more units were transfused. The objective of this study was to determine if RBC transfusions or RBC storage age predicts incident DVT in medical or surgical intensive care unit (ICU) patients.MethodsUsing a database which prospectively enrolled 261 patients over the course of 1 year with an ICU stay of at least 3 days, we analyzed DVT and RBC transfusions using Cox proportional hazards regression. Transfusions were analyzed with 4 thresholds, and storage age using 3 thresholds. DVTs were identified by twice-weekly proximal leg ultrasounds. Multivariable analyses were adjusted for 4 significant DVT predictors in this population (venous thrombosis history, chronic dialysis, platelet transfusion and inotropes).ResultsOf 261 patients, 126 (48.3%) had at least 1 RBC transfusion; 46.8% of those transfused had ≥ 5 units in ICU. Patients receiving RBCs were older (68.8 vs 64.1 years), more likely to be female (47.0 vs 30.7), sicker (APACHEII 26.8 vs 24.4), and more likely to be surgical (21.4 vs 8.9) (P < 0.05). The total number of RBCs per patient was 1-64, mean was 6.3 (SD 7.5), median was 4 (IQR 2,8). In univariate analyses, there was no association between DVT and RBC exposure (1 day earlier, 3 days earlier, 7 days earlier, or ever) or RBC storage (≤ 7 or > 7 days, ≤ 14 or > 14 days, ≤ 21 or > 21 days). Among patients transfused, no multivariable analyses showed that RBC transfusion or storage age predicted DVT. Trends were counter to the hypothesis (e.g., RBC storage for ≤ 7 days suggested a higher DVT risk compared to > 7 days (HR 5.3; 95% CI 1.3-22.1).ConclusionsWe were unable to detect any association between RBC transfusions or prolonged red cell storage and increased risk of DVT in medical or surgical ICU patients. Alternate explanations include a lack of sufficient events or patients' interaction, between patient groups, a mixing of red cell storage times creating differential effects on DVT risk, and unmeasured confounders.

Relationship between red cell storage duration and outcomes in adults receiving red cell transfusions: a systematic review

“…Moreover, these results were challenged by a prospective study of 261 medico-surgical ICU patients in which there was no association between the age of transfused RBCs and the occurrence of DVT [85]. Leal-Noval and coworkers found no association between duration of storage of transfused RBCs and postoperative myocardial infarction [55].…”

Age of red blood cells and transfusion in critically ill patients

“…Three reports have especially studied the impact of RBC age on acute lung injury (ALI) or short-term pulmonary function in critically ill patients and did not find any difference [50,54,62]. Similarly, no effect of age of blood on deep vein thrombosis, ICU LOS, and mortality was found in two recent studies of ICU patients [56,57]. All of these studies were small and likely underpowered.…”

Co-enrollment of critically ill patients into multiple studies: patterns, predictors and consequences

“…Multivariable analyses documented that neither red blood cell transfusion nor storage age predicted DVT in medical-surgical patients. Trends were counter to findings in trauma (for example, red blood cells stored for ≤ 7 days had a higher associated DVT risk compared to > 7 days (hazard ratio 5.3; 95% CI 1.3 TO 22.1)) [15]. Based on inconclusive research evidence, the PROTECT and ABLE Steering Committees affirmed co-enrollment into these trials.…”