Transfusion immunomodulation — the case for leukoreduced and (perhaps) washed transfusions

Abstract

During the last three decades, a growing body of clinical, basic science and animal model data has demonstrated that blood transfusions have important effects on the immune system. These effects include: dysregulation of inflammation and innate immunity leading to susceptibility to microbial infection, down-regulation of cellular (T and NK cell) host defenses against tumors, and enhanced B cell function that leads to alloimmunization to blood group, histocompatibility and other transfused antigens. Furthermore, transfusions alter the balance between hemostasis and thrombosis through inflammation, nitric oxide scavenging, altered rheologic properties of the blood, immune complex formation and, no doubt, several mechanisms not yet elucidated. The net effects are rarely beneficial to patients, unless they are in imminent danger of death due to exsanguination or life threatening anemia. These findings have led to appeals for more conservative transfusion practice, buttressed by randomized trials showing that patients do not benefit from aggressive transfusion practices. At the risk of hyperbole, one might suggest that if the 18th and 19th centuries were characterized by physicians unwittingly harming patients through venesection and bleeding, the 20th century was characterized by physicians unwittingly harming patients through current transfusion practices. In addition to the movement to more parsimonious use of blood transfusions, an effort has been made to reduce the toxic effects of blood transfusions through modifications such as leukoreduction and saline washing. More recently, there is early evidence that reducing the storage period of red cells transfused might be a strategy for minimizing adverse outcomes such as infection, thrombosis, organ failure and mortality in critically ill patients particularly at risk for these hypothesized effects. The present review will focus on two approaches, leukoreduction and saline washing, as means to reduce adverse transfusion outcomes.

Interrelationship of preoperative anemia, intraoperative anemia, and red blood cell transfusion as potentially modifiable risk factors for acute kidney injury in cardiac surgery: a historical multicentre cohort study

“…43,44 Erythropoietin stimulating agents may also be used to correct preoperative anemia, thereby avoiding intraoperative anemia and RBC transfusion, 42 but the risk-benefit of this intervention in cardiac surgery has not been elucidated. 45 Other potential options that are currently undergoing evaluation include optimizing oxygen delivery by modifying pump flow; 46 washing of blood to remove the pro-inflammatory molecules, free hemoglobin, and iron that accumulate in the supernatant during storage; 47 haptoglobin therapy to scavenge the free hemoglobin that can be present after CPB and blood transfusion; 48 and prophylactic RBC transfusion one to two days before surgery in patients with preoperative anemia. 49 This latter Relative risks and confidence intervals derived from the Poisson regression model presented in Table 3 and represent each category's adjusted risk of AKI relative to patients who have none of the risk factors approach has been postulated to ''reduce the risk of AKI by reducing the severity of anemia, reducing the need for RBC transfusions, allowing time for the transfused blood to recover from the deleterious changes that they undergo during storage, and allowing time for the kidneys to recuperate from the harmful effects of transfused blood before they are exposed to other renal insults'' during surgery.…”

Blood Transfusions After Pediatric Cardiac Operations: A North American Multicenter Prospective Study

“…Despite their undoubted life-saving potential, RBC transfusions have come under intense scrutiny in recent years due to the inherent risks associated with their use. These include transfusion-transmitted infections [19] and noninfectious serious hazards of transfusion such as transfusion-related acute lung injury [20], transfusion-mediated immunomodulation [21,22], and transfusion-associated circulatory overload [23]. The overall complication rate of transfusion is considerably higher in children than in adults [24]: Stainsby and colleagues [25] reported in 2008 that the incidence rate of adverse outcome was 18:100,000 RBC units issued for children aged younger than 18 years and 37:100,000 for infants younger than 12 months compared with 13:100,000 for adults.…”

Frequency and Specificity of Red Blood Cell Alloimmunization in Chilean Transfused Patients

“…In our study, the units transfused are non-leukoreduced, only neonatal and hematooncology patients received some leukoreduced hemocomponents. Recently, has been signed that leukoreduction and saline washing of the RBC concentrates may be an effective way to minimize immune effects in transfused patients [22]. Currently, universal leukoreduction has been adopted as quality policy in our hospital.…”