Glenn Ramsey

Clinical practice guidelines from the AABB: Red blood cell transfusion thresholds and storage

Importance More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. Objective To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Evidence Review Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. Findings It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence). Conclusions and Relevance Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

Isohemagglutinins of Graft Origin after ABO-Unmatched Liver Transplantation

The increasing success of liver transplantation in recent years has provided an experimental model to study and document the hepatic synthesis of many plasma proteins.1–5 The normal hepatobiliary tract has not been regarded as a major source of antibody,6,7 aside from the enteric IgA secreted from plasma into the biliary tree.8 Liver transplantation affords the opportunity to study the production of antibody to red cells. Recipient ABO incompatibility to the donor (a mismatched transplant, e.g., a group A liver transplanted into a group B recipient), although not absolutely contraindicated in liver transplantation, is avoided when possible. However, ABO-unmatched transplants (defined as a group O liver transplanted into a non-group O recipient or a group A or B liver to an AB recipient) are used frequently. We report the short-term occurrence of anti-recipient ABO antibody after eight unmatched transplants. In five cases there was evidence of hemolysis. No such antibodies have been seen in over 180 ABO-matched transplants at our center. These antibodies were most probably produced by donor lymphocytes transplanted in or with the livers.

Guidelines for transfusion support in patients undergoing coronary artery bypass grafting

We have reviewed the impact of evolving issues in coronary artery bypass grafting (CABG) on transfusion support for these patients. Issues include increased awareness of transfusion risks, reappraisal of traditional indicators triggering transfusion, and evolving alternatives to homologous blood transfusion such as autologous blood and pharmacologic therapy. These issues have been prompted by programs, such as the National Institutes of Health Consensus Conferences, to provide physicians with guidelines for appropriate use of blood components. However, evidence suggests that transfusion practice in coronary artery bypass grafting procedures remains variable and does not take into account the results of recently published clinical studies. We have therefore developed guidelines and recommendations for transfusion support in patients undergoing coronary artery bypass grafting. In summary, they are the following. 1. Institutions with coronary artery bypass grafting programs should establish a multidisciplinary approach to use a combination of interventions designed to minimize homologous blood exposure. 2. Prophylactic transfusion of plasma and platelets are of no benefit and therefore carry an unnecessary risk to the patient. 3. Special request products such as designated blood donation from first-degree relatives should not be used because of the risk of transfusion-associated graft versus host disease. 4. For support of intravascular volume, crystalloids or colloids should be used because they do not have the potential to transmit infection.

Variation in the use of red blood cell transfusions. A study of four common medical and surgical conditions.

This study assessed variation in red cell transfusion practice among adult patients hospitalized with ulcer disease (ULCER), and those undergoing coronary artery bypass grafting (CABG), hip surgery (HIP), or total knee replacement (KNEE). The study design was a retrospective analysis of the 1989 MedisGroups Hospital Comparative Database, and the participants were adult patients presenting for their first admission with ULCER (N=4,664), CABG (N=6,812), HIP (N=4,131) or KNEE (N=3,042) in the MedisGroups Hospital Comparative Database. Outcome measures were whether a patient ws transfused, and the number of units transfused. Logistic regression was used to analyze the decision to transfuse, and linear regression to analyze the number of units transfused. In these analyses, patient characteristics, hospital characteristics, and unique hospital identity were used as independent variables. The percentage of patients transfused was ULCER 50%, CABG 81%, HIP 69%, and KNEE 51%. The range among hospitals in the percentage of patients transfused was ULCER 11% to 76%, CABG 51% to 100%, HIP 36% to 95%, and KNEE 9% to 97%. When only patient characteristics were entered in the linear regression analyses, the R2 values were ULCER 0.33, CABG 0.11, HIP 0.11, and KNEE 0.07. When hospital was added, the R2 increased to ULCER 0.38, CABG 0.29, HIP 0.19, and KNEE 0.20 (P < 0.0001 for the change for all analyses). The results of the logistic regression analyses of the probability of transfusion were similar. There is substantial interhospital variation in the proportion of patients transfused and number of units transfused in the four conditions studied. Patient demographic and clinical characteristics explain a substantial proportion of the variation in transfusion practices for ulcer patients, but little of the variation in the three surgical conditions.

Red cell alloimmunization in multitransfused HLA‐typed patients

The authors studied retrospectively the formation of clinically significant red cell (RBC) alloantibodies in 958 HLA‐typed, multiply transfused patients receiving kidney (603 patients) or liver (263 patients) transplants or plateletpheresis transfusions (92 patients). RBC alloantibodies were found in 91 (9.5%) of these patients and multiple antibodies in 35 (3.7%). Rh (D, C, c, and E) antibodies accounted for 49 percent of the total and Kell antibodies for 31 percent. Antibodies were found in 15 percent of apheresis recipients and in 8.6 percent of renal and 9.5 percent of liver transplantation patients. No association was found between any HLA‐A, HLA‐B, or HLA‐DR phenotype and the presence of RBC alloantibodies, either in general or when analyzed according to the specific antibody. Renal transplant patients with RBC alloantibodies were somewhat more broadly HLA‐ alloimmunized than were those without RBC alloantibodies. Patient gender did not affect these results. The authors concluded that the immune response to RBC alloantigens is independent of HLA type but is associated with an increased level of HLA antibody formation.

Red cell antibody problems in 1000 liver transplants

Liver transplant patients frequently require large amounts of blood. The frequency and nature of their red cell (RBC) antibody problems were examined. Records were reviewed in 496 adults and 286 children undergoing 1000 consecutive transplants. Twenty‐two percent of adults and 14 percent of children had RBC alloantibodies. Antibodies of potential clinical significance were found before transplant in 6.3 percent of adults and 1.0 percent of children; despite immunosuppression, they appeared 1 to 5 weeks after transplant in an additional 7.5 and 5.2 percent respectively. These antibodies probably represented secondary immune responses. Of 58 transplant patients with prior potentially significant antibodies, 8 required 7 to 110 units of antigen‐untyped blood after 8 to 28 units of antigen‐negative blood; of these patients, one had subsequent hemolysis. Positive direct antiglobulin tests in 24 percent of adults and 10 percent of children were most often thought to be due to nonspecific adsorption of IgG. Anti‐recipient ABO antibodies developed in 22 of 60 (37%) evaluable ABO‐unmatched grafts; 13 cases had associated hemolysis. In all, 36 percent of adults and 20 percent of children had diverse RBC antibody problems. Resolution of these problems is an important part of the laboratory support necessary for a liver transplantation program.

Loss of red cell alloantibodies over time

The loss of red cell alloantibodies over time was analyzed in 160 patients with 209 antibodies retested 1 to 60 months after initial identification. The mean follow‐up consisted of 3.6 specimens taken over 18 months. Twenty‐nine percent of clinically significant and 72 percent of clinically insignificant antibodies were not detected on at least one follow‐up screening. Anti‐Jka and anti‐C were lost in 59 and 45 percent of cases, respectively. No significant differences in overall antibody loss were found according to sex, diagnosis, or the presence of multiple antibodies. Patients under 20 years of age may be more likely to lose significant antibodies. Pretransfusion review of previous records is vital for the prevention of delayed hemolytic transfusion reactions, because of the high number of clinically significant antibodies that are undetected in subsequent routine screening.

Alloimmunization in sickle cell anemia in the era of extended red cell typing.

Red blood cell (RBC) transfusion remains an essential part of the management of patients with sickle cell disease (SCD). Alloimmunization is a major complication of transfusions. Extended RBC typing is advocated as a means to reduce alloimmunization in SCD. Our goal was to assess alloimmunization among individuals with SCD at our center since implementing extended RBC typing.

Long‐term follow‐up testing of red cell alloantibodies

Background: In previous studies, 29 to 34 percent of potentially hemolytic red cell antibodies were not detected after short‐term follow‐ up.

Catastrophic multiple organ ischemia due to an anti-Pr cold agglutinin developing in a patient with mixed cryoglobulinemia after treatment with rituximab.

Cold agglutinin disease occurring with cryoglobulinemia is a rare occurrence. Here, we report a patient with mixed cryoglobulinemia that was treated with rituximab and, after response, developed an anti‐Pr cold agglutinin that manifested with hemolysis and microvascular occlusion causing mesenteric ischemia and cerebral infarction. Unlike previous reports of patients with cryoglobulinemia and cold agglutinin disease, our patient did not have a detectable cryoprecipitate when his cold agglutinin manifested. Am. J. Hematol, 2009.