Irene Cortés-Puch

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes.

Transfusion of older stored blood worsens outcomes in canines depending on the presence and severity of pneumonia

In experimental pneumonia we found that transfused older blood increased mortality and lung injury that was associated with increased in vivo hemolysis and elevated plasma cell‐free hemoglobin (CFH), non–transferrin‐bound iron (NTBI), and plasma labile iron (PLI) levels. In this study, we additionally analyze identically treated animals that received lower or higher bacterial doses.

Transfusion of recently donated (fresh) red blood cells (RBCs) does not improve survival in comparison with current practice, while safety of the oldest stored units is yet to be established: a meta-analysis.

Preclinical studies generated the hypothesis that older stored red blood cells (RBCs) can increase transfusion risks. To examine the most updated and complete clinical evidence and compare results between two trial designs, we assessed both observational studies and randomized controlled trials (RCTs) studying the effect of RBC storage age on mortality.

More on the Age of Transfused Red Cells.

Since publication of their article, the authors report no further potential conflict of interest. 1. O’Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Hepatology 2010;51:307-28. 2. Singal AK, Salameh H, Singal A, et al. Management practices of hepatitis C virus infected alcoholic hepatitis patients: a survey of physicians. World J Gastrointest Pharmacol Ther 2013;4:16-22. 3. Verbeke L, Roskams T, Verslype C, et al. Ductular bilirubinostasis predicts the evolution to acute-on-chronic liver failure in patients suspected with severe alcoholic steatohepatitis. Hepatology 2014;60:Suppl 1:778A. abstract. 4. Katoonizadeh A, Laleman W, Verslype C, et al. Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 2010;59:1561-9. 5. Petts G, Lloyd K, Vergis N et al. Utility of liver biopsy in the diagnosis of alcoholic hepatitis from the Steroids or Pentoxifylline in Alcoholic Hepatitis (STOPAH) clinical trial. Hepatology 2015;62:Suppl 2:776A. abstract.

In a canine pneumonia model of exchange transfusion, altering the age but not the volume of older red blood cells markedly alters outcome.

Massive exchange transfusion of 42‐day‐old red blood cells (RBCs) in a canine model of Staphylococcus aureus pneumonia resulted in in vivo hemolysis with increases in cell‐free hemoglobin (CFH), transferrin‐bound iron (TBI), non–transferrin‐bound iron (NTBI), and mortality. We have previously shown that washing 42‐day‐old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7‐day‐old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs.

Hypothalamic-pituitary-adrenal axis in lethal canine Staphylococcus aureus pneumonia.

The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life-supportive measures. Treatment with dexamethasone, a glucocorticoid, but not desoxycorticosterone, a mineralocorticoid, improves outcome in this model. Total and free cortisol, adrenocorticotropic hormone (ACTH). and aldosterone levels, as well as responses to exogenous ACTH were measured serially. At 10 h after the onset of infection, the acute HPA axis stress response, as measured by cortisol levels, exceeded that seen with high-dose ACTH stimulation but was not predictive of outcome. In contrast to cortisol, aldosterone was largely autonomous from HPA axis control, elevated longer, and more closely associated with survival in early septic shock. Importantly, dexamethasone suppressed cortisol and ACTH levels and restored ACTH responsiveness in survivors. Differing strikingly, nonsurvivors, sepsis-induced hypercortisolemia, and high ACTH levels as well as ACTH hyporesponsiveness were not influenced by dexamethasone. During septic shock, only serial measurements and provocative testing over a well-defined timeline were able to demonstrate a strong relationship between HPA axis function and prognosis. HPA axis unresponsiveness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.

Transfused older stored red blood cells improve the clinical course and outcome in a canine lethal hemorrhage and reperfusion model.

In canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell‐free hemoglobin (CFH) and non–transferrin‐bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury and mortality. It is unknown if in shock without infection transfusion of older RBCs will result in similar adverse effects.

In vivo reduction of cell‐free methemoglobin to oxyhemoglobin results in vasoconstriction in canines

Cell‐free hemoglobin (Hb) in the vasculature leads to vasoconstriction and injury. Proposed mechanisms have been based on nitric oxide (NO) scavenging by oxyhemoglobin (oxyHb) or processes mediated by oxidative reactions of methemoglobin (metHb). To clarify this, we tested the vascular effect and fate of oxyHb or metHb infusions.

Parenteral irons versus transfused red blood cells for treatment of anemia during canine experimental bacterial pneumonia: INTRAVENOUS IRON VS. TRANSFUSED RBCs

No studies have been performed comparing intravenous (IV) iron with transfused red blood cells (RBCs) for treating anemia during infection. In a previous report, transfused older RBCs increased free iron release and mortality in infected animals when compared to fresher cells. We hypothesized that treating anemia during infection with transfused fresh RBCs, with minimal free iron release, would prove superior to IV iron therapy.

Risks of restrictive red blood cell transfusion strategies in patients with cardiovascular disease (CVD): a meta-analysis: Restrictive RBC transfusion triggers with CVD

To evaluate the risks of restrictive red blood cell transfusion strategies (haemoglobin 7–8 g dL−1) in patients with and without known cardiovascular disease (CVD).