Claudia S. Cohn

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.

A sequential treatment regimen with melatonin and all-trans retinoic acid induces apoptosis in MCF-7 tumour cells

Neoplastic events are marked by uncontrolled cell proliferation. One major focus of cancer research has been to identify treatments that reduce or inhibit cell growth. Over the years, various compounds, both naturally occurring and chemically synthesized, have been used to inhibit neoplastic cell proliferation. Two such oncostatic agents, melatonin and retinoic acid, have been shown to suppress the growth of hormone-responsive breast cancer. Currently, separate clinical protocols exist for the administration of retinoids and melatonin as adjuvant therapies for cancer. Using the oestrogen receptor (ER)-positive MCF-7 human breast tumour cell line, our laboratory has studied the effects of a sequential treatment regimen of melatonin followed by all-trans retinoic acid (atRA) on breast tumour cell proliferation in vitro. Incubation of hormonally responsive MCF-7 and T47D cells with melatonin (10(-9) M) followed 24 h later by atRA (10(-9) M) resulted in the complete cessation of cell growth as well as a reduction in the number of cells to below the initial plating density. This cytocidal effect is in contrast to the growth-suppressive effects seen with either hormone alone. This regimen of melatonin followed by atRA induced cytocidal effects on MCF-7 cells by activating pathways leading to apoptosis (programmed cell death) as evidenced by decreased ER and Bcl-2 and increased Bax and transforming growth factor beta 1 (TGF-beta1) expression. Apoptosis was reflected morphologically by an increase in the number of lysosomal bodies and perinuclear chromatin condensation, cytoplasmic blebbing and the presence of apoptotic bodies. The apoptotic effect of this sequential treatment with melatonin and atRA appears to be both cell and regimen specific as (a) ER-negative MDA-MB-231 and BT-20 breast tumour cells were unaffected, and (b) the simultaneous administration of melatonin and atRA was not associated with apoptosis in any of the breast cancer cell lines studied. Taken together, the results suggest that use of an appropriate regimen of melatonin and atRA should be considered for preclinical and clinical evaluation against ER-positive human breast cancer.

Transfusion reactions: prevention, diagnosis, and treatment

Blood transfusion is one of the most common procedures in patients in hospital so it is imperative that clinicians are knowledgeable about appropriate blood product administration, as well as the signs, symptoms, and management of transfusion reactions. In this Review, we, an international panel, provide a synopsis of the pathophysiology, treatment, and management of each diagnostic category of transfusion reaction using evidence-based recommendations whenever available.

Oxygen Therapeutics: Perfluorocarbons and Blood Substitute Safety

Current demands over the blood supply in developed and developing nations will compound over time. Red cell substitutes have a promising value proposition for transfusion services, because they hold the promise of increasing the availability of blood products and removing donor and contamination safety risks. In this article, the authors note that existing products suffer from critical shortcomings such as vasoactivity; they also point out that substitutes not based on human blood introduce potentially more complex safety hurdles. The authors discuss the attributes of an ideal blood substitute, and the mechanism and current status of perfluorocarbons; they also review the shortcomings of all oxygen therapeutic products in development today.

The direct antiglobulin test: a critical step in the evaluation of hemolysis.

The direct antiglobulin test (DAT) is a laboratory test that detects immunoglobulin and/or complement on the surface of red blood cells. The utility of the DAT is to sort hemolysis into an immune or nonimmune etiology. As with all tests, DAT results must be viewed in light of clinical and other laboratory data. This review highlights the most common clinical situations where the DAT can help classify causes of hemolysis, including autoimmune hemolytic anemia, transfusion‐related hemolysis, hemolytic disease of the fetus/newborn, drug‐induced hemolytic anemia, passenger lymphocyte syndrome, and DAT‐negative hemolytic anemia. In addition, the pitfalls and limitations of the test are addressed. False reactions may occur with improper technique, including improper washing, centrifugation, and specimen agitation at the time of result interpretation. Patient factors, such as spontaneous red blood cell agglutination, may also contribute to false results. Am. J. Hematol. 87:707–709, 2012.

A comparison of adverse reaction rates for PAS C versus plasma platelet units.

Plasma constituents have been implicated in some types of platelet (PLT) transfusion reactions. Leukoreduced apheresis PLTs stored in InterSol have 65% less plasma than apheresis PLTs stored in 100% plasma (PPs). This study compared transfusion reaction rates in InterSol PLTs (PLT additive solution [PAS] C) versus PPs.

International validation of a dithiothreitol (DTT)-based method to resolve the daratumumab interference with blood compatibility testing

Daratumumab (DARA) consistently interferes with routine blood bank serologic testing by directly binding to CD38 expressed on reagent red blood cells (RBCs). Treating RBCs with dithiothreitol (DTT) eliminates the DARA interference. We conducted an international, multicenter, blinded study aimed at validating the DTT method for use by blood bank laboratories worldwide.

Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival

Although hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic cell transplantation (alloHCT), its risk factors and effects on survival are not well known. We evaluated HC in a large cohort (n=1321, 2003–2012) receiving alloHCT from all graft sources, including umbilical cord blood (UCB). We compared HC patients with non-HC (control) patients and examined clinical variables at HC onset and resolution. Of these 1321 patients, 219 (16.6%) developed HC at a median of 22 days after alloHCT. BK viruria was detected in 90% of 109 tested HC patients. Median duration of HC was 27 days. At the time of HC diagnosis, acute GVHD, fever, severe thrombocytopenia and steroid use were more frequent than at the time of HC resolution. In univariate analysis, male sex, age <20 years, myeloablative conditioning with cyclophosphamide and acute GVHD were associated with HC. In multivariate analysis, HC was significantly more common in males and HLA-mismatched UCB graft recipients. Severe grade HC (grade III–IV) was associated with increased treatment-related mortality but not with overall survival at 1 year. HC remains hazardous and therefore better prophylaxis, and early interventions to limit its severity are still needed.

A data-driven approach to patient blood management

Patient blood management (PBM) has become a topic of intense interest; however, implementing a robust PBM system in a large academic hospital can be a challenge. In a joint effort between transfusion medicine and information technology, we have developed three overlapping databases that allow for a comprehensive, semiautomated approach to monitoring up‐to‐date red blood cell (RBC) usage in our hospital. Data derived from this work have allowed us to target our PBM efforts.

Transfusion Support Issues in Hematopoietic Stem Cell Transplantation

BACKGROUND Patients receiving hematopoietic stem cell transplantation require extensive transfusion support until red blood cell and platelet engraftment occurs. Rare but predictable complications may arise when the transplanted stem cells are incompatible with the native ABO type of the patient. Immediate and delayed hemolysis is often seen. METHODS A literature review was performed and the results from peer-reviewed papers that contained reproducible findings were integrated. RESULTS A strong body of clinical evidence has developed around the common complications experienced with ABO-incompatible hematopoietic stem cell transplantation. These complications are discussed and the underlying pathophysiology is explained. General treatment options and guidelines are enumerated. CONCLUSIONS ABO-incompatible hematopoietic stem cell transplantations are frequently performed. Immune-related hemolysis is a commonly encountered complication; therefore, health care professionals must recognize the signs of immune-mediated hemolysis and understand the various etiologies that may drive the process.