Louis M. Katz

Red blood cell transfusion: A Clinical practice guideline from the AABB

DESCRIPTION Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children. METHODS These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. RECOMMENDATION 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). RECOMMENDATION 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

Emerging infectious disease agents and their potential threat to transfusion safety

BACKGROUND: Emerging infections have been identified as a continuing threat to human health. Many such infections are known to be transmissible by blood transfusion, while others have properties indicating this potential. There has been no comprehensive review of such infectious agents and their threat to transfusion recipient safety to date.

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.

Causes of Alternative Pathway Dysregulation in Dense Deposit Disease

BACKGROUND AND OBJECTIVES This study was designed to investigate the causes of alternative pathway dysregulation in a cohort of patients with dense deposit disease (DDD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Thirty-two patients with biopsy-proven DDD underwent screening for C3 nephritic factors (C3Nefs), factor H autoantibodies (FHAAs), factor B autoantibodies (FBAAs), and genetic variants in CFH. C3Nefs were detected by: ELISA, C3 convertase surface assay (C3CSA), C3CSA with properdin (C3CSAP), two-dimensional immunoelectrophoresis (2DIEP), and immunofixation electrophoresis (IFE). FHAAs and FBAAs were detected by ELISA, and CFH variants were identified by Sanger sequencing. RESULTS Twenty-five patients (78%) were positive for C3Nefs. Three C3Nef-positive patients were also positive for FBAAs and one of these patients additionally carried two novel missense variants in CFH. Of the seven C3Nef-negative patients, one patient was positive for FHAAs and two patients carried CFH variants that may be causally related to their DDD phenotype. C3CASP was the most sensitive C3Nef-detection assay. C3CASP and IFE are complementary because C3CSAP measures the stabilizing properties of C3Nefs, whereas IFE measures their expected consequence-breakdown of C3b. CONCLUSIONS A test panel that includes C3CSAP, IFE, FHAAs, FBAAs, and genetic testing for CFH variants will identify a probable cause for alternative pathway dysregulation in approximately 90% of DDD patients. Dysregulation is most frequently due to C3Nefs, although some patients test positive for FHAAs, FBAAs, and CFH mutations. Defining the pathophysiology of DDD should facilitate the development of mechanism-directed therapies.

Chagas disease and the US blood supply.

Purpose of review To describe new developments in blood-bank screening and management of patients with chronic Trypanosoma cruzi infection in the United States. Recent findings The first US Food and Drug Administration licensed serological test for T. cruzi blood screening went into widespread usage in January 2007. More than 500 confirmed T. cruzi-infected donations were detected by mid-June 2008. Until recently, drug therapy was recommended for acute and congenital infections, but seldom for chronic infections, which were believed to respond poorly. However, in the 1990s, efficacy was demonstrated in two placebo-controlled trials of benznidazole in children with chronic T. cruzi infection. In 2006, a nonrandomized, nonblinded trial demonstrated that benznidazole treatment may slow progression of cardiomyopathy and decrease mortality risk in infected adults. Summary Blood-bank screening will continue to detect T. cruzi-infected donors. Based on recent data, antitrypanosomal treatment is recommended for all acute and congenital T. cruzi infections, reactivated infection, and chronically infected children. In adults aged 19–50 years without advanced heart disease, treatment should generally be offered; management should be individualized for older adults. Less toxic, more effective drugs, a sensitive, specific assay for response to treatment, and improved healthcare access would promote more effective management.

The 2003 West Nile virus United States epidemic: the America's Blood Centers experience

BACKGROUND: A detailed assessment of West Nile virus (WNV) yield is needed to evaluate the effectiveness of the WNV nucleic acid amplification technology (NAT) screening implemented in 2003.

Allelic Variants of Complement Genes Associated with Dense Deposit Disease

The alternative pathway of the complement cascade plays a role in the pathogenesis of dense deposit disease (DDD). Deficiency of complement factor H and mutations in CFH associate with the development of DDD, but it is unknown whether allelic variants in other complement genes also associate with this disease. We studied patients with DDD and identified previously unreported sequence alterations in several genes in addition to allelic variants and haplotypes common to patients with DDD. We found that the likelihood of developing DDD increases with the presence of two or more risk alleles in CFH and C3. To determine the functional consequence of this finding, we measured the activity of the alternative pathway in serum samples from phenotypically normal controls genotyped for variants in CFH and C3. Alternative pathway activity was higher in the presence of variants associated with DDD. Taken together, these data confirm that DDD is a complex genetic disease and may provide targets for the development of disease-specific therapies.

It's time to phase in RHD genotyping for patients with a serologic weak D phenotype

In 2014, the College of American Pathologists (CAP) Transfusion Medicine Resource Committee (TMRC) reported the results of a survey of more than 3100 laboratories concerning their policies and procedures for testing serological weak D phenotypes and administration of Rh immune globulin (RhIG).1 Among the findings of this survey is the observation that there is a lack of standard practice in the United States for interpreting the RhD type when a serological weak D phenotype is detected. In some laboratories, an individual with a serological weak D phenotype, especially if a blood donor, is interpreted to be RhD-positive. In the same or other laboratories, especially if a serological weak D phenotype is detected in a female of child-bearing potential, the individual is likely to be managed as RhD-negative for transfusions and, if pregnant, considered a candidate for RhIG. Also, the performance characteristics of serological typing methods for RhD vary. For patients, including pregnant women, the majority of laboratories have policies and procedures that do not use the indirect antiglobulin (weak D) test, thereby avoiding detection of a serological weak D phenotype so that the RhD type will be interpreted to be RhD-negative. Other laboratories typically perform a weak D test for the same category of patients. For blood donors and newborns, it is standard practice for laboratories to have policies and procedures for RhD typing to ensure that serological weak D phenotypes are detected and interpreted as RhD-positive.1 The goal of these RhD typing practices is to protect RhD-negative persons from inadvertent alloimmunization to the D antigen by exposure to RhD-positive RBCs, including RBCs expressing a serological weak D phenotype. Although there has not been a recent prospective study in the United States, it is estimated that current RhD typing practice, together with contemporary obstetrical practices for administration of antepartum and postpartum RhIG, is 98.4 to 99 percent successful in preventing RhD alloimmunization and RhD hemolytic disease of the fetus/newborn.2 However, there are unwarranted consequences associated with the practice of not determining the RHD genotype of persons with a serological weak D phenotype, including unnecessary injections of RhIG and transfusion of RhD-negative RBCs -- always in short supply -- when RhD-positive RBCs could be transfused safely. CAP’s TMRC reviewed the current status of RHD genotyping and proposed that selective integration of RHD genotyping in laboratory practices could improve the accuracy of RhD typing results, reduce unnecessary administration of RhIG in women with a serological weak D phenotype, and decrease unnecessary transfusion of RhD-negative RBCs to recipients with a serological weak D phenotype.1 In response to the findings of the CAP TMRC survey, AABB and CAP convened a Work Group on RHD Genotyping and charged it with developing recommendations to clarify clinical issues related to RhD typing in persons with a serological weak D phenotype. As an initial step for formulating recommendations, the Work Group reviewed the current state of molecular science of RHD, including more than 140 publications covering background;1-12 D variants with anti-D;13-29 molecular basis of serological weak D phenotypes;30-92 reviews, editorials and commentaries;93-129 technical resources;130-142 and standards and guidelines.143-149 This Commentary summarizes the proceedings and recommendations of the Work Group.

Audiovisual touch‐screen computer‐assisted self‐interviewing for donor health histories: results from two years experience with the system

BACKGROUND:  The donor history interview is an important aspect of blood safety, in part designed to identify unsuitable donors who may present a risk to blood recipients. There is evidence from behavioral science literature that use of computer‐assisted interviewing may be superior to face‐to‐face (FTF) and paper techniques in eliciting sensitive behavioral information of interest to blood collection facilities.

Emerging infectious agents and the nation's blood supply: responding to potential threats in the 21st century

In the early 1990s, the Department of Health and Human Services (DHHS) asked the Institute of Medicine (IOM) to assess how the government, the private sector, and other stakeholders had responded to the human immunodeficiency virus (HIV) epidemic and its impact on blood safety. In its executive summary published in TRANSFUSION,1 the IOM Committee to Study HIV Transmission Through Blood and Blood Products noted that although stakes were high, decisions had to be made under a cloud of uncertainty and that responses were slowed by imprecise and incomplete knowledge, personal and institutional biases, and ultimately by failures in leadership. Emphasizing that blood safety is a shared responsibility, the IOM Committee issued 14 recommendations related to structure and policy including the designation of a Blood Secretary Director by DHHS, the establishment of a Blood Safety Council by the US Public Health Service (PHS), and several recommendations to the Federal agencies involved in the evaluation of an infectious threat, in particular, the Food and Drug Administration (FDA). Since then, these recommendations have been implemented and the blood safety community (blood collectors, blood safety experts, and relevant Federal agencies) has responded to other emerging infectious disease (EID) threats, such as West Nile virus (WNV) and most recently the xenotropic murine leukemia virus–related virus (XMRV). Responding to any new threat entails assessing the risk to the blood supply and recipients’ health; evaluating how best to manage and/or control each potential risk; and communicating this information to blood donors, recipients, physicians, and the general public. Although the FDA has the regulatory authority to develop guidance documents and new regulations in response to EID threats based on available data, the challenge of generating that data and responding to potential risks requires concerted and coordinated actions by the multiple PHS agencies (Centers for Disease Control and Prevention [CDC], FDA, National Institutes of Health [NIH]) and by the broader transfusion medicine community (AABB and blood providers). It is therefore incumbent upon the transfusion medicine professionals to collect and provide robust data in a timely manner to policymakers to inform their decision process, as well as take an active role in risk communication. All stakeholders must recognize what they can do and provide leadership and timely research and risk assessments. In so doing, they must take a hard look at their responses and learn lessons from history. Such a process does not involve a confirmation or criticism of what has been done in previous responses to potential threats to the blood supply, but an assessment of how responses can be improved for future threats. In the aftermath of the recent XMRV investigation and the inevitable occurrence of future infectious threats, the National Heart, Lung, and Blood Institute (NHLBI) convened an expert task force charged with evaluating how lessons from previous EID blood safety threat assessments could be used to optimize future response strategies. The task force was asked to review and discuss responses to past epidemics and recent EIDs and to consider: What worked? What could have worked better? What data are necessary to assess blood safety risk? Who needs to be engaged in the evaluation of risk; that is, who are the stakeholders? What methods and/or processes need to be in place and when? What resources, infrastructure, and capacity are needed? How best to train future experts? And how can a scientific culture be encouraged that encourages cooperation? In a first session, responses to earlier epidemics were examined, followed by a discussion on responses to recent agents of concern, including an in-depth look at the latest potential threat, XMRV. A general overview of other agents of potential concerns (the horizon) ensued followed by a general discussion on lessons learned and consideration of future strategies. This report summarizes the results of these discussions.