ABSTRACT
BACKGROUND: Although the safety and therapeutic efficacy of COVID-19 convalescent plasma (CCP) has been extensively evaluated, the safety of CCP donation has not been explored in a multi-institutional context. STUDY DESIGN AND METHODS: Nine blood collection organizations (BCOs) participated in a multi-institutional donor hemovigilance effort to assess the safety of CCP donation. Donor adverse events (DAEs) were defined according to the Standard for Surveillance of Complications Related to Blood Donation, and severity was assessed using the severity grading tool. Multivariate analysis was performed to determine attributes associated with DAE severity. RESULTS: The overall DAE rate was 37.7 per 1000 donations. Repeat apheresis and apheresis-naïve donors experienced adverse event rates of 19.9 and 49.8 per 1000 donations, respectively. Female donors contributed 51.9% of CCP donations with a DAE rate of 49.4 per 1000 donations. The DAE rate for male donors was 27.4 per 1000 donations. Vasovagal reactions accounted for over half of all reported DAEs (51.1%). After adjustment, volume of CCP donated was associated with vasovagal reaction severity (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.5-17.1). Donor age and donation history were also associated with DAE severity. Considerable differences in DAE types and rates were observed across the participating BCOs despite the use of standardized hemovigilance definitions. CONCLUSION: The safety of CCP donation appears comparable to that of conventional apheresis plasma donation with similar associated risk factors for DAE types and severity.
Subject(s)
Blood Donors , Blood Safety , COVID-19/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Odds Ratio , Public Health Surveillance , Retrospective Studies , Severity of Illness Index , United States/epidemiology , Young AdultABSTRACT
BACKGROUND: Consensus definitions for transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) have recently been revised; however, pulmonary transfusion reactions remain difficult to diagnose. We hypothesized that N-terminal pro-brain natriuretic peptide (NT-proBNP) levels could have utility in the identification and classification of pulmonary transfusion reactions. STUDY DESIGN AND METHODS: We performed a secondary analysis of a case-control study of pulmonary transfusion reactions at four academic hospitals. We evaluated clinical data and measured NT-proBNP levels prior to and following transfusion in patients with TACO (n = 160), transfused acute respiratory distress syndrome (ARDS) [n = 51], TRALI [n = 12], TACO/TRALI [n = 7], and controls [n = 335]. We used Wilcoxon Rank-Sum tests to compare NT-proBNP levels, and classification and regression tree (CART) algorithms to produce a ranking of covariates in order of relative importance for differentiating TACO from transfused controls. RESULTS: Pre-transfusion NT-proBNP levels were elevated in cases of transfused ARDS and TACO (both P < .001) but not TRALI (P = .31) or TACO/TRALI (P = .23) compared to transfused controls. Pre-transfusion NT-proBNP levels were higher in cases of transfused ARDS or TRALI with a diagnosis of sepsis compared to those without (P < .05 for both). CART analyses resulted in similar differentiation of patients with TACO from transfused controls for models utilizing either NT-proBNP levels (AUC 0.83) or echocardiogram results (AUC 0.80). CONCLUSIONS: NT-proBNP levels may have utility in the classification of pulmonary transfusion reactions. Prospective studies are needed to test the predictive utility of pre-transfusion NT-proBNP in conjunction with other clinical factors in identifying patients at risk of pulmonary transfusion reactions.
Subject(s)
Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Respiratory Distress Syndrome , Transfusion-Related Acute Lung Injury , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/classification , Transfusion-Related Acute Lung Injury/blood , Transfusion-Related Acute Lung Injury/classificationABSTRACT
Risk assessments of transfusion-transmitted emerging infectious diseases (EIDs) are complicated by the fact that blood donors' demographics and behaviors can be different from the general population. Therefore, when assessing potential blood donor exposure to EIDs, the use of general population characteristics, such as U.S. travel statistics, may invoke uncertainties that result in inaccurate estimates of blood donor exposure. This may, in turn, lead to the creation of donor deferral policies that do not match actual risk. STUDY DESIGN AND METHODS: This article reports on the development of a system to rapidly assess EID risks for a nationally representative portion of the U.S. blood donor population. To assess the effectiveness of this system, a test survey was developed and deployed to a statistically representative sample frame of blood donors from five blood collecting organizations. Donors were directed to an online survey to ascertain their recent travel and potential exposure to Middle East respiratory syndrome coronavirus (MERS-CoV). RESULTS: A total of 7128 responses were received from 54 256 invitations. The age-adjusted estimated total number of blood donors potentially exposed to MERS-CoV was approximately 15 640 blood donors compared to a lower U.S. general population-based estimate of 9610 blood donors. CONCLUSION: The structured donor demographic sample-based data provided an assessment of blood donors' potential exposure to an emerging pathogen that was 63% larger than the U.S. population-based estimate. This illustrates the need for tailored blood donor-based EID risk assessments that provide more specific demographic risk intelligence and can inform appropriate regulatory decision making.
Subject(s)
Blood Donors , Blood Transfusion , Blood-Borne Infections/epidemiology , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Imported/epidemiology , Coronavirus Infections/epidemiology , Environmental Exposure , Risk Assessment/methods , Surveys and Questionnaires , Travel-Related Illness , Adolescent , Adult , Aged , Aged, 80 and over , Blood Banks , Blood Donors/statistics & numerical data , Blood-Borne Infections/blood , Blood-Borne Infections/prevention & control , Blood-Borne Infections/transmission , Communicable Diseases, Emerging/blood , Communicable Diseases, Emerging/prevention & control , Communicable Diseases, Emerging/transmission , Communicable Diseases, Imported/blood , Communicable Diseases, Imported/prevention & control , Communicable Diseases, Imported/transmission , Coronavirus Infections/blood , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Decision Making , Female , Humans , Male , Middle Aged , Middle East , Middle East Respiratory Syndrome Coronavirus , Sample Size , Sampling Studies , Transfusion Reaction/prevention & control , United States/epidemiology , Young AdultABSTRACT
BACKGROUND: Typically minor ABO incompatible platelet products are transfused without any incident, yet serious hemolytic transfusion reactions occur. To mitigate these events, ABO 'low titer' products are used for minor ABO incompatible transfusions. We sought to understand the role of IgM/IgG and complement activation by anti-A on extravascular hemolysis. METHODS: Samples evaluated included (i) Group O plasma from a blood donor whose apheresis platelet product resulted in an extravascular transfusion reaction, (ii) Group O plasma from 12 healthy donors with matching titers that activated complement (N = 6) or not (N = 6), and (iii) Group O sera from 10 patients with anti-A hemolysin activity. A flow cytometric monocyte erythrophagocytosis assay was developed using monocytes isolated by immunomagnetic CD14-positive selection from ACD whole blood of healthy donors. Monocytes were frozen at - 80 °C in 10% dimethyl sulfoxide/FBS and then thawed/reconstituted on the day of use. Monocytes were co-incubated with anti-A-sensitized fluorescently-labeled Group A1 + RBCs with and without fresh Group A serum as a source of complement C3, and erythrophagocytosis was analyzed by flow cytometry. The dependency of IgM/IgG anti-A and complement C3 activation for RBC erythrophagocytosis was studied. Anti-A IgG subclass specificities were examined for specific samples. RESULTS: The plasma and sera had variable direct agglutinating (IgM) and indirect (IgG) titers. None of 12 selected samples showed monocyte-dependent erythrophagocytosis with or without complement activation. The donor sample causing a hemolytic transfusion reaction and 2 of the 10 patient sera with hemolysin activity showed significant erythrophagocytosis (> 10%) only when complement C3 was activated. The single donor plasma and two sera demonstrating significant erythrophagocytosis had high IgM (≥ 128) and IgG titers (> 1024). The donor plasma anti-A was IgG1, while the patient sera were an IgG3 and an IgG1 plus IgG2. CONCLUSION: High anti-A IgM/IgG titers act synergistically to cause significant monocyte erythrophagocytosis by activating complement C3, thus engaging both Fcγ- and CR1-receptors.
Subject(s)
Blood Group Incompatibility , Transfusion Reaction , ABO Blood-Group System , Humans , Immunoglobulin G , Immunoglobulin MABSTRACT
BACKGROUND: Blood donors represent a healthy population, whose red blood cell (RBC) alloantibody persistence or evanescence kinetics may differ from those of immunocompromised patients. A better understanding of the biologic factors impacting antibody persistence is warranted, as the presence of alloantibodies may impact donor health and the fate of the donated blood product. METHODS: Donor/donation data collected from four US blood centers from 2012 to 2016 as part of the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) were analyzed. Clinically significant antibodies from blood donors with more than one donation who underwent at least one follow-up antibody screen after the initial antibody identification were included. Of 632,378 blood donors, 481 (128 males and 353 females) fit inclusion criteria. RESULTS: Antibody screens detected 562 alloantibodies, with 368 of 562 (65%) of antibodies being persistently detected and with 194 of 562 (35%) becoming evanescent. Factors associated with antibody persistence included antibody specificity, detection at the first donation, reported history of transfusion, and detection of multiple antibodies concurrently. Anti-D, C, and Fya were most likely to persist, while anti-M, Jka , and S were most frequently evanescent. CONCLUSIONS: These data provide insight into variables impacting the duration of antibody detection, and they may also influence blood donor center policies regarding donor recruitment/acceptance.
Subject(s)
Blood Donors , Erythrocytes/immunology , Isoantibodies/blood , Adult , Antibody Specificity , Female , Humans , Kinetics , Male , Middle AgedABSTRACT
BACKGROUND: The provision of units with antigen-negative attributes is required for alloimmunized transfusion recipients and to avoid alloimmunization among patients on chronic transfusion support. Recent evidence confirms that the demand for antigen-typed units is increasing. STUDY DESIGN AND METHODS: A cloud-based search engine was designed by the blood center to find antigen-negative units. The service provided access to historical antigen information for units in hospital inventories. The hospital transfusion service was required to confirm the antigen phenotype. The results of 16 hospitals' use over 5 years were analyzed to determine trends and value of the service. The time commitment of the cloud-based query was compared to the hospital performing manual phenotyping with an outcome of at least one unit found with the desired antigen-negative attribute(s). RESULTS: Hospitals were located between 4 miles and 200 miles away from the blood center. A total of 6,081 queries were submitted over the 5 years, with an overall 50% success rate of finding at least one unit. Single antigen queries accounted for 67% of total searches, with two antigen queries and three or more antigen queries accounting for 24% and 9% of the units found, respectively. The cloud-based antigen query was most efficient for combined antigen frequencies <0.5 for two or more antigen-negative attributes. CONCLUSION: A cloud-based search engine provides hospitals with access to historical antigen information housed at the blood center. Future refinements may consider regulatory submission of a process to provide confirmed historical information through this cloud-based program.
Subject(s)
Cloud Computing , Databases, Factual , Inventories, Hospital/methods , Search Engine/methods , Tissue Donors/statistics & numerical data , HumansABSTRACT
CASE REPORT: A 45-year-old male presented in severe hypovolemic shock after a thoracoabdominal gunshot wound. The massive transfusion protocol (MTP) was activated and the patient was taken to the operating room. His major injuries included liver, small bowel, and right common iliac vein. Hemorrhage was stopped and a damage control laparotomy was completed. He received a total of 113 blood products. During his postoperative course he received a group B blood transfusion on Hospital Days 2 and 7 based on incorrect blood typing late in his massive transfusion and repeat testing on Day 4. RESULTS: He succumbed to multiple organ failure on Day 8. MTPs are standard in most trauma centers during which universal donor red blood cells are initially used. As hemorrhage is controlled, the patient undergoes a complete type and cross according to blood banking protocols. These typing results are used to continue transfusions once the MTP is no longer needed. In contacting other blood banks servicing Level I trauma centers, the policy of when to switch from universal donor blood to crossmatched blood is variable. CONCLUSION: Our case illustrates a potential blood typing problem that had a disastrous outcome. We identified changes in policy that will make MTPs safer.
Subject(s)
Blood Group Incompatibility , Erythrocyte Transfusion , Multiple Organ Failure , Shock , Transfusion Reaction , Wounds, Gunshot , Blood Group Incompatibility/blood , Blood Group Incompatibility/therapy , Humans , Male , Middle Aged , Multiple Organ Failure/blood , Multiple Organ Failure/therapy , Shock/blood , Shock/therapy , Transfusion Reaction/blood , Transfusion Reaction/therapy , Wounds, Gunshot/blood , Wounds, Gunshot/therapyABSTRACT
BACKGROUND: Blood for transfusion is lifesaving and essential to many elements of modern medical practice. The global blood supply relies on volunteer blood donors. Apheresis is increasingly used to collect blood and requires anticoagulant to prevent extracorporeal coagulation. Citrate, the standard apheresis anticoagulant, chelates ionized calcium with consequent perturbations of serum calcium, parathyroid hormone, vitamin D, and markers of bone remodeling in donors. Cross-sectional studies of bone mineral density (BMD) among apheresis donors exhibit conflicting results. METHODS: The longitudinal, randomized, controlled ALTRUYST trial (NCT02655055) was undertaken to determine whether BMD declined following high frequency apheresis blood donation over 1â¯year. The study was powered at 80% to detect the primary outcome of a 3% decline in BMD. Subjects new to apheresis agreed to make ≥20 apheresis donations in a one-year period and were randomized to treatment (high frequency apheresis) or control (no apheresis). Dual-energy x-ray absorptiometry was performed before and after participation. Two-sided t-test and multivariable logistic regression were used to assess outcomes. FINDINGS: Mean lumbar spine BMD did not change during the study among control donors (-0.002â¯g/cm2, 95%CI [-0.020, 0.016], pâ¯=â¯0.78), or among donors in the apheresis arm (mean changeâ¯=â¯0.007â¯g/cm2, 95%CI [-0.005, 0.018], pâ¯=â¯0.24). Mean total hip BMD did not change for control donors (mean changeâ¯=â¯0.002â¯g/cm2, 95%CI [-0.006, 0.009], pâ¯=â¯0.63) or apheresis donors (-0.004â¯g/cm2, 95%CI [-0.10, 0.002], pâ¯=â¯0.16). Tests for differences in proportions of donors with change in BMD exceeding the least significant change at the lumbar spine in either a positive [8 apheresis (31%), 4 control (27%), pâ¯=â¯0.78] or negative direction [4 apheresis (15%), 5 control (33%)] were statistically non-significant (pâ¯=â¯0.18). Proportional increases [0 apheresis (0%), 1 control (7%), pâ¯=â¯0.18] and decreases [3 apheresis (12%), 1 control (14%)] were also not significantly different at the total hip (pâ¯=â¯0.61). INTERPRETATION: ALTRUYST is the first longitudinal trial to demonstrate that apheresis blood collection guidelines in the United States adequately protect the skeletal health of male volunteer blood donors. FUNDING: Marquette University and the BloodCenter Research Foundation.
ABSTRACT
BACKGROUND: Little information exists on red blood cell (RBC) alloimmunization in healthy US blood donors, despite the potential significance for donors themselves, blood recipients, and the blood center. STUDY DESIGN AND METHODS: Donor/donation data were sourced from the Recipient Epidemiology and Donor Evaluation Study-III, which contains information from four US blood centers during 2012 through 2016. Multivariable logistic regression was used to assess prevalence of positive antibody screen by donor demographics, blood type, parity, and transfusion history. RESULTS: More than 2 million units were collected from 632,378 donors, with 0.51% of donations antibody screen positive and 0.77% of donors having at least one positive antibody screen. The most common antibody specificities were D (26.4%), E (23.8%), and K (21.6%). Regression analysis indicated that increasing age, female sex, D-negative status, and history of transfusion and pregnancy were positively associated with a positive antibody screen. Prior transfusion history was most strongly associated with a positive antibody screen, with donors reporting a prior transfusion having a higher adjusted odds ratio (3.9) of having a positive antibody screen compared to donors reporting prior pregnancy (adjusted odds ratio, 2.0). Though transfusion was a more potent immune stimulus for RBC alloantibody formation than pregnancy, the sheer number of previously pregnant donors contributed to pregnancy being a risk factor for the majority of clinically significant RBC alloantibodies detected in females. CONCLUSION: These findings on prevalence of and risk factors for RBC antibodies may have implications for future medical care of donors and for operations at blood centers.
Subject(s)
Blood Donors , Erythrocytes/immunology , Isoantibodies/immunology , Adolescent , Adult , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Pregnancy , Prevalence , Risk Factors , Young AdultABSTRACT
BACKGROUND: Acute splenic sequestration crisis is a complication of sickle cell disease (SCD) occurring when intrasplenic red blood cell (RBC) sickling prevents blood from leaving the spleen, causing acute splenic enlargement. Although typically seen in young children, it has been reported in older children with hemoglobin (Hb)SC disease, eventually resulting in functional asplenia. Ceftriaxone is a frequently used antibiotic of choice for children with SCD, because of its efficacy against invasive pneumococcal disease. CASE REPORT: We report a case of a 9-year-old female with HbSC disease, who had a fatal reaction after receiving a dose of ceftriaxone in the outpatient clinic for fever. Her Hb level decreased abruptly from 9.3 to 2.3 mg/dL. RBC clumps with no visible hemolysis were observed in the postreaction sample. Autopsy examination revealed marked splenomegaly with acute congestion and sickled cells in the spleen and liver. Serologic testing revealed a positive direct antiglobulin test with polyspecific antibody, anti-C3, and anti-C3d, but negative with anti-immunoglobulin G. Ceftriaxone-dependent RBC antibodies were detected in her serum and RBC eluate when tested in the presence of the drug. CONCLUSION: We report a new presentation of ceftriaxone-induced drug reaction in a patient with SCD mimicking an acute splenic sequestration crisis. Review of the literature for cases of ceftriaxone-induced drug reactions in pediatric patients revealed nine previously reported cases of ceftriaxone-induced immune hemolytic anemia in children with SCD since 1995, but none with an initial presentation suggestive of acute splenic sequestration crisis.
Subject(s)
Anemia, Hemolytic, Autoimmune/chemically induced , Ceftriaxone/adverse effects , Erythrocytes/immunology , Hemoglobin SC Disease/complications , Splenomegaly/chemically induced , Anemia, Hemolytic, Autoimmune/blood , Autoantibodies/blood , Autoantibodies/immunology , Child , Fatal Outcome , Female , Humans , Liver/pathology , Spleen/pathology , Splenomegaly/pathologyABSTRACT
OBJECTIVES: Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload. DESIGN: Case-control study. SETTING: Four tertiary care hospitals. PATIENTS: We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery, pretransfusion diuretic use, and plasma transfusion-the latter especially in females. Compared with matched controls, transfusion-associated circulatory overload cases were more likely to require mechanical ventilation (71% vs 49%; p < 0.001), experienced longer intensive care and hospital lengths of stay following transfusion, and had higher mortality (21% vs 11%; p = 0.02) even after adjustment for other potentially confounding variables. CONCLUSIONS: Despite restrictive transfusion practice, transfusion-associated circulatory overload remains a frequent complication of transfusion and is an independent risk factor for in-hospital morbidity and mortality. In addition to cardiovascular and renal risk factors, plasma transfusion was associated with transfusion-associated circulatory overload after controlling for other covariates. Additional research is needed to examine the benefit of reduced erythrocyte or plasma exposure in patients at high risk for transfusion-associated circulatory overload.
Subject(s)
Critical Illness/therapy , Transfusion Reaction/epidemiology , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Case-Control Studies , Critical Illness/epidemiology , Critical Illness/mortality , Diuretics , Female , Hospital Mortality/trends , Humans , Kidney Diseases/epidemiology , Male , Middle Aged , Pulmonary Edema , Risk Factors , Severity of Illness Index , Sex Factors , Tertiary Care Centers , Transfusion Reaction/mortalityABSTRACT
BACKGROUND: Blood transfusion is one of the most common medical procedures during hospitalization in the United States. To understand the benefits of transfusion while mitigating potential risks, a multicenter database containing detailed information on transfusion incidence and recipient outcomes would facilitate research. STUDY DESIGN AND METHODS: The Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) program has developed a comprehensive transfusion recipient database utilizing data from hospital electronic health records at 12 participating hospitals in four geographic regions. Inpatient and outpatient data on transfusion recipients from January 1, 2013 to December 31, 2014 included patient age, sex, ethnicity, primary diagnosis, type of blood product provided, issue location, pretransfusion and post-transfusion hemoglobin (Hgb), and hospital outcomes. Transfusion incidence per encounter was calculated by blood product and various patient characteristics. RESULTS: During the 2-year study period, 80,362 (12.5%) inpatient encounters involved transfusion. Among inpatients, the most commonly transfused blood products were red blood cells (RBCs; 10.9% of encounters), followed by platelets (3.2%) and plasma (2.9%). Among patients who received transfusions, the median number of RBC units was one, the pretransfusion Hgb level was 7.6 g/dL, and the Hgb increment per unit was 1.4 g/dL. Encounter mortality increased with patient age, the number of units transfused, and the use of platelet or plasma products. The most commonly reported transfusion reaction was febrile nonhemolytic. CONCLUSION: The database contains comprehensive data regarding transfusion use and patient outcomes. The current report describes an evaluation of the first 2 years of a planned, 4-year, linked blood donor-component-recipient database, which represents a critical new resource for transfusion medicine researchers.
Subject(s)
Blood Donors , Blood Transfusion/statistics & numerical data , Databases as Topic , Transfusion Reaction/epidemiology , Demography , Fever/etiology , Humans , United States/epidemiologyABSTRACT
BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) and drug-induced immune thrombocytopenia (DIIT) are rare but dangerous complications of pharmacotherapy that may be underrecognized in hematopoietic stem cell transplant (HSCT) patients due to overlap of signs and symptoms with those of more common disease processes. CASE REPORT: A 61-year-old woman with NK-cell deficiency and GATA-2-associated myelodysplastic syndrome, status post-recent allogeneic HSCT (Day +58), presented with 3 days of acute-onset severe back pain, muscle cramps, and increasingly dark urine. She was found to be anemic, thrombocytopenic, and in acute renal failure. On admission, the direct antiglobulin test was positive for complement (C3) only. After careful review of her medication list, the possibility of DIIHA was raised. She had started taking trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jiroveci pneumonia prophylaxis 24 days prior on a weekend dose schedule. Serologic tests on peripheral blood samples were performed using standard methods. Drug studies were performed at an immunohematology reference laboratory. RESULTS: The patient's serum showed hemolysis of donor red blood cells in the presence of TMP-SMX and also TMP-SMX-induced platelet antibodies. The patient was treated with transfusions, hemodialysis, and immunosuppressive agents. Her clinical condition improved and she was discharged after 8 days in stable condition. CONCLUSION: This case describes the first reported concurrent DIIHA and DIIT due to TMP-SMX-induced antibodies in an HSCT patient. DIIHA and DIIT can present a diagnostic challenge in the setting of intermittent medication dosing.
Subject(s)
Anemia, Hemolytic/chemically induced , Thrombocytopenia/chemically induced , Trimethoprim, Sulfamethoxazole Drug Combination/toxicity , Anemia, Hemolytic/complications , Anemia, Hemolytic/diagnosis , Anemia, Hemolytic/therapy , Blood Transfusion , Female , Humans , Immunosuppressive Agents/therapeutic use , Middle Aged , Renal Dialysis , Thrombocytopenia/complications , Thrombocytopenia/diagnosis , Thrombocytopenia/therapy , Transfusion Reaction , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic useABSTRACT
BACKGROUND: Anti-CD38 therapy causes interference with both the direct and the indirect antiglobulin tests. We describe the experience from an Immunohematology Reference Laboratory and model cost options for providing safe transfusions. STUDY DESIGN AND METHODS: Phenotyping, genotyping, and antibody identification orders were retrospectively reviewed in the setting of anti-CD38 therapy. The data were used to model the added cost of transfusion support. Four approaches were evaluated: 1) thiol-treated reagent red blood cells (RRCs) in antibody investigations with K- red blood cell (RBC) transfusions, 2) patient phenotyping or 3) genotyping with antigen-matched RBC transfusions, and 4) a combination of interval thiol-treated RRC antibody investigations with genotype antigen-matched RBC transfusions. RESULTS: Sixty-two patients were identified as receiving anti-CD38 therapy. Thiol-treated RRC antibody investigations (28/62 patients) were favored over genotyping (23/62) and combination testing (11/62). Patient phenotyping failed to detect useful antigen information on eight patients: seven Fyb silencing mutations and one partial e. A thiol-treated RRC antibody investigation was the least expensive testing method for the first transfusion, but four- and five-antigen-matched RBC transfusions were equal in cost within five and 21 transfusion events, respectively. CONCLUSION: Genotyping provided a more accurate antigen status than phenotyping patient RBCs. Patients requiring long-term transfusion support benefit from antigen matching when matching less than four antigens. Ultimately, the decision to genotype or use thiol-treated RRC antibody investigations will vary for each hospital blood bank.
Subject(s)
ADP-ribosyl Cyclase 1/immunology , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Blood Transfusion/methods , Erythrocyte Transfusion/methods , Adult , Aged , Aged, 80 and over , Blood Donors , Erythrocytes/metabolism , Female , Genotype , Humans , Male , Middle Aged , Multiple Myeloma/therapy , Phenotype , Platelet Transfusion , Retrospective StudiesABSTRACT
Minor ABO-mismatched transfusions are a common occurrence, although infrequent transfusion reactions occur. We sought to investigate the regulation of complement C3 activation induced by anti-A. In vitro complement C3 activation was observed with 10 of 30 group O samples and correlated with immunoglobulin M (IgM) anti-A titers. We developed an in vitro paroxysmal nocturnal hemoglobinuria (PNH) model of hemolysis in which group A1 red blood cells (RBCs) were chemically treated with 2-aminoethylisothiouronium (AET) to alter regulators of complement C3 activation. Intravascular hemolysis was simulated by incubating an IgG nonhemolytic group O plasma (titer = 32) with A1 RBCs. IgG was detected on the RBCs, but hemolysis was observed with AET-treated RBCs only. When treated and untreated RBCs were tested together (1:4), we determined that the failure to observe C3b/d deposition on RBCs was due to the complete hemolysis of the AET-treated minor RBC population. A group O patient with a 9% CD59-deficient PNH clone was sensitized with an IgM anti-I. Hemolysis, with a weak positive direct antiglobulin test (DAT) resulting from C3b/d, was observed after incubation with fresh AB serum. Flow cytometry showed an 86% reduction of the PNH clone. Our work indicates that the transfusion of minor ABO-mismatched plasma could cause hemolysis with a negative DAT C3b/d. We propose that the presence of a PNH clone is 1 possible cause of unexplained anemia for recipients of ABO-mismatched product. This work suggests that other acquired or inherited defects of decay-accelerating factor and membrane inhibitor of reactive lysis could be responsible for infrequent but clinically important hemolysis after ABO-mismatched transfusions.
ABSTRACT
Although congenital bleeding disorders can manifest in the newborn period, the most common causes of bleeding and thrombosis in neonates are acquired conditions. Factor concentrates are used for specific diagnoses (hemophilia with inhibitors, specific factor deficiency, von Willebrand disease) and approved indications, and increasingly for off-label indications (bleeding in surgery cardiopulmonary bypass, extracorporeal membrane oxygenation). We will review the approved indications for factor products in the neonate and discuss the evidence and rationale for off-label use of factor products in management of bleeding and thrombosis in the neonate.
Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Recombinant Proteins/therapeutic use , Factor VIII/therapeutic use , Factor VIIa/therapeutic use , Hematology/methods , Hematology/trends , Hemophilia A/drug therapy , Hemorrhage/drug therapy , Humans , Infant, Newborn , Infant, Premature , Thrombosis/therapy , von Willebrand Diseases/drug therapyABSTRACT
BACKGROUND: Prevalence estimates of the serious hazards of transfusion vary widely. We hypothesized that the current reporting infrastructure in the United States fails to capture many transfusion reactions and undertook a multicenter study using active surveillance, data review, and adjudication to test this hypothesis. STUDY DESIGN AND METHODS: A retrospective record review was completed for a random sample of 17% of all inpatient transfusion episodes over 6 months at four academic tertiary care hospitals, with an episode defined as all blood products released to a patient in 6 hours. Data were recorded by trained clinical research nurses, and serious reactions were adjudicated by a panel of transfusion medicine experts. RESULTS: Of 4857 transfusion episodes investigated, 1.1% were associated with a serious reaction. Transfusion-associated circulatory overload was the most frequent serious reaction noted, being identified in 1% of transfusion episodes. Despite clinical notes describing a potential transfusion association in 59% of these cases, only 5.1% were reported to the transfusion service. Suspected transfusion-related acute lung injury/possible transfusion-related acute lung injury, anaphylactic, and hypotensive reactions were noted in 0.08, 0.02, and 0.02% of transfusion episodes, respectively. Minor reactions, including febrile nonhemolytic and allergic, were noted in 0.62 and 0.29% of transfusion episodes, respectively, with 30 and 50% reported to the transfusion service. CONCLUSION: Underreporting of cardiopulmonary transfusion reactions is striking among academic, tertiary care hospitals. Complete and accurate reporting is essential to identify, define, establish pathogenesis, and mitigate/treat transfusion reactions. A better understanding of the failure to report may improve the accuracy of passive reporting systems.
Subject(s)
Risk Management/statistics & numerical data , Transfusion Reaction/epidemiology , Blood Safety/methods , Humans , Incidence , Retrospective Studies , Tertiary Care Centers , Transfusion Medicine/methodsABSTRACT
BACKGROUND: When problems with compatibility arise, transfusion services often use time-consuming serological tests to identify antigen-negative red cell units for safe transfusion. New methods have made red cell genotyping possible for all clinically relevant blood group antigens. We did mass-scale genotyping of donor blood and provided hospitals with access to a large red cell database to meet the demand for antigen-negative red cell units beyond ABO and Rh blood typing. METHODS: We established a red cell genotype database at the BloodCenter of Wisconsin on July 17, 2010. All self-declared African American, Asian, Hispanic, and Native American blood donors were eligible irrespective of their ABO and Rh type or history of donation. Additionally, blood donors who were groups O, A, and B, irrespective of their Rh phenotype, were eligible for inclusion only if they had a history of at least three donations in the previous 3 years, with one donation in the previous 12 months at the BloodCenter of Wisconsin. We did red cell genotyping with a nanofluidic microarray system, using 32 single nucleotide polymorphisms to predict 42 blood group antigens. An additional 14 antigens were identified via serological phenotype. We monitored the ability of the red cell genotype database to meet demand for compatible blood during 3 years. In addition to the central database at the BloodCenter of Wisconsin, we gave seven hospitals online access to a web-based antigen query portal on May 1, 2013, to help them to locate antigen-negative red cell units in their own inventories. FINDINGS: We analysed genotype data for 43,066 blood donors. Requests were filled for 5661 (99.8%) of 5672 patient encounters in which antigen-negative red cell units were needed. Red cell genotyping met the demand for antigen-negative blood in 5339 (94.1%) of 5672 patient encounters, and the remaining 333 (5.9%) requests were filled by use of serological data. Using the 42 antigens represented in our red cell genotype database, we were able to fill 14,357 (94.8%) of 15,140 requests for antigen-negative red cell units from hospitals served by the BloodCenter of Wisconsin. In the pilot phase, the seven hospitals identified 71 units from 52 antigen-negative red cell unit requests. INTERPRETATION: Red cell genotyping has the potential to transform the way antigen-negative red cell units are provided. An antigen query portal could reduce the need for transportation of blood and serological screening. If this wealth of genotype data can be made easily accessible online, it will help with the supply of affordable antigen-negative red cell units to ensure patient safety. FUNDING: BloodCenter of Wisconsin Diagnostic Laboratories Strategic Initiative and the NIH Clinical Center Intramural Research Program.
Subject(s)
Blood Banks/organization & administration , Blood Group Antigens/genetics , Blood Grouping and Crossmatching , Erythrocytes/classification , Genotyping Techniques , Blood Donors , Genotype , Humans , Polymorphism, Single Nucleotide , WisconsinABSTRACT
BACKGROUND: When problems with compatibility beyond ABO and D arise, currently transfusion services search their inventories and perform time-consuming serologic testing to locate antigen-negative blood. These clinically important blood group antigens can be detected reliably by red cell genotyping, which is a technology whereby DNA-based techniques are used to evaluate gene polymorphisms that determine the expression of blood group antigens. We introduced mass-scale genotyping and measured availability of genotyped blood. STUDY DESIGN AND METHODS: All non-Caucasian donors qualified for genotyping along with donors who had a history of repeat donation. Mass-scale red cell genotyping, performed on an electronic interfaced open array platform, was implemented to screen blood donors for 32 single-nucleotide polymorphisms that predicted 42 blood group antigens. Genotype screening results were confirmed by phenotyping, when needed for antigen-negative transfusion, before release of the red blood cell (RBC) unit. RESULTS: Approximately 22,000 donors were red cell genotyped within 4 months and a total of 43,066 donors in 4 years. There were 463 discordances (0.52% of 89,596 genotypes with a phenotype). Among the 307 resolved discordances, approximate equal numbers represented historical serologic or genotyping discrepancies (n = 151 and n = 156, respectively). In the final year of the study, a mean of 29% of the daily inventory had a genotype. CONCLUSIONS: Red cell genotyping of blood donors using an electronic interface created a large and stable supply of RBC units with historical genotypes. The database served the needs of antigen-negative blood requests for a large regional blood center and allowed us to abandon screening by serology.
Subject(s)
Erythrocytes/metabolism , Blood Donors , Blood Group Antigens/genetics , Blood Grouping and Crossmatching/methods , Erythrocytes/classification , Genotype , Humans , Polymorphism, Single Nucleotide/geneticsABSTRACT
BACKGROUND: The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request. STUDY DESIGN AND METHODS: At the 12 Level 1 trauma centers participating in PROPPR, blood components transfused and delivery times were tabulated, with a focus on universal donor (UD) plasma management. The adequacy of site plans was assessed by comparing the bedside blood availability times to study goals and the new American College of Surgeons guidelines. RESULTS: Eleven of 12 sites were able to consistently deliver 6 units of thawed UD plasma to their trauma-receiving unit within 10 minutes and 12 units in 20 minutes. Three sites used blood group A plasma instead of AB for massive transfusion without complications. Approximately 4700 units of plasma were given to the 680 patients enrolled in the trial. No site experienced shortages of AB plasma that limited enrollment. Two of 12 sites reported wastage of thawed AB plasma approaching 25% of AB plasma prepared. CONCLUSION: Delivering UD plasma to massively hemorrhaging patients was accomplished consistently and rapidly and without excessive wastage in high-volume trauma centers. The American College of Surgeons Trauma Quality Improvement Program guidelines for massive transfusion protocol UD plasma availability are practicable in large academic trauma centers. Use of group A plasma in trauma resuscitation needs further study.