Associations between ABO non-identical platelet transfusions and patient outcomes-A multicenter retrospective analysis.

BACKGROUND: Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains controversial as to whether ABO non-identical platelet transfusions could potentially pose harm and/or have reduced efficacy. STUDY DESIGN AND METHODS: The large 4-year publicly available Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) database was used to investigate patient outcomes associated with ABO non-identical platelet transfusions. Outcomes included mortality, sepsis, and subsequent platelet transfusion requirements. RESULTS: Following adjustment for possible confounding factors, no statistically significant association between ABO non-identical platelet transfusion and increased risk of mortality was observed in the overall cohort of 21,176 recipients. However, when analyzed by diagnostic category and recipient ABO group, associations with increased mortality for major mismatched transfusions were noted in two of eight subpopulations. Hematology/Oncology blood group A and B recipients (but not group O) showed a Hazard Ratio (HR) of 1.29 (95%CI: 1.03-1.62) and intracerebral hemorrhage group O recipients (but not groups A and B) showed a HR of 1.75 (95%CI: 1.10-2.80). Major mismatched transfusions were associated with increased odds of receiving additional platelet transfusion each post-transfusion day (through day 5) regardless of the recipient blood group. DISCUSSION: We suggest that prospective studies are needed to determine if specific patient populations would benefit from receiving ABO identical platelet units. Our findings indicate that ABO-identical platelet products minimize patient exposure to additional platelet doses.

Transfusion practices for pediatric oncology and hematopoietic stem cell transplantation patients: Data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III).

BACKGROUND: To evaluate transfusion practices in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients. STUDY DESIGN AND METHODS: This is a multicenter retrospective study of children with oncologic diagnoses treated from 2013 to 2016 at hospitals participating in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III. Transfusion practices were evaluated by diagnosis codes and pre-transfusion laboratory values. RESULTS: A total of 4766 inpatient encounters of oncology and HSCT patients were evaluated, with 39.3% (95% confidence interval [CI]: 37.9%-40.7%) involving a transfusion. Red blood cells (RBCs) were the most commonly transfused component (32.4%; 95% CI: 31.1%-33.8%), followed by platelets (22.7%; 95% CI: 21.5%-23.9%). Patients in the 1 to <6 years of range were most likely to be transfused and HSCT, acute myeloid leukemia, and aplastic anemia were the diagnoses most often associated with transfusion. The median hemoglobin (Hb) prior to RBC transfusion was 7.5 g/dl (10-90th percentile: 6.4-8.8 g/dl), with 45.7% of transfusions being given at 7 to <8 g/dl. The median platelet count prior to platelet transfusion was 20 × 109 /L (10-90th percentile: 8-51 × 109 /L), and 37.9% of transfusions were given at platelet count of >20-50 × 109 /L. The median international normalized ratio (INR) prior to plasma transfusion was 1.7 (10-90th percentile: 1.3-2.7), and 36.3% of plasma transfusions were given at an INR between 1.4 and 1.7. DISCUSSION: Transfusion of blood components is common in hospitalized pediatric oncology/HSCT patients. Relatively high pre-transfusion Hb and platelet values and relatively low INR values prior to transfusion across the studied diagnoses highlight the need for additional studies in this population.

Transfusion Practices in Pediatric Cardiac Surgery Requiring Cardiopulmonary Bypass: A Secondary Analysis of a Clinical Database.

OBJECTIVES: To describe blood component usage in transfused children with congenital heart disease undergoing cardiopulmonary bypass surgery across perioperative settings and diagnostic categories. DESIGN: Datasets from U.S. hospitals participating in the National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III were analyzed. SETTING: Inpatient admissions from three U.S. hospitals from 2013 to 2016. PATIENTS: Transfused children with congenital heart disease undergoing single ventricular, biventricular surgery, extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eight hundred eighty-two transfused patients were included. Most of the 185 children with single ventricular surgery received multiple blood products: 81% RBCs, 79% platelets, 86% plasma, and 56% cryoprecipitate. In the 678 patients undergoing biventricular surgery, 85% were transfused plasma, 75% platelets, 74% RBCs, and 48% cryoprecipitate. All 19 patients on extracorporeal membrane oxygenation were transfused RBCs, plasma, and cryoprecipitate, and 18 were transfused platelets. Intraoperatively, patients commonly received all three components, while postoperative transfusions were predominantly single blood components. Pretransfusion hemoglobin values were normal/low-normal for age for all phases of care for single ventricular surgery (median hemoglobin 13.2-13.5 g/dL). Pretransfusion hemoglobin values for biventricular surgeries were higher intraoperatively compared with other timing (12.2 g/dL vs 11.2 preoperative and postoperative; p < 0.0001). Plasma transfusions for all patients were associated with a near normal international normalized ratio: single ventricular surgeries median international normalized ratio was 1.3 postoperative versus 1.8 intraoperative and biventricular surgeries median international normalized ratio was 1.1 intraoperative versus 1.7 postoperative. Intraoperative platelet transfusions with biventricular surgeries had higher median platelet count compared with postoperative pretransfusion platelet count (244 × 109/L intraoperative vs 69 × 109/L postoperative). CONCLUSIONS: Children with congenital heart disease undergoing cardiopulmonary bypass surgery are transfused many blood components both intraoperatively and postoperatively. Multiple blood components are transfused intraoperatively at seemingly normal/low-normal pretransfusion values. Pediatric evidence guiding blood component transfusion in this population at high risk of bleeding and with limited physiologic reserve is needed to advance safe and effective blood conservation practices.

The epidemiology of platelet transfusions: an analysis of platelet use at 12 US hospitals.

BACKGROUND: Using the Recipient and Donor Epidemiology Study-III (REDS-III) recipient and donor databases, we performed a retrospective analysis of platelet use in 12 US hospitals that were participants in REDS-III. STUDY DESIGN AND METHODS: Data were electronically extracted from participating transfusion service and blood center computer systems and from medical records of the 12 REDS-III hospitals. All platelet transfusions from 2013 to 2016 given to patients aged 18 years and older were included in the analysis. RESULTS: There were 28,843 inpatients and 2987 outpatients who were transfused with 163,719 platelet products (103,371 apheresis, 60,348 whole blood derived); 93.5% of platelets were leukoreduced and 72.5% were irradiated. Forty-six percent were transfused to patients with an International Classification of Diseases, 9th/10th Revision (ICD-9/10) diagnosis of leukemia, myelodysplastic syndrome (MDS), or lymphoma. The general ward and the intensive care unit (ICU) were the most common issue locations. Only 54% of platelet transfusions were ABO identical; and 60.6% of platelet transfusions given to Rh-negative patients were Rh positive. The most common pretransfusion platelet count range for inpatients was 20,000 to 50,000/µL, for outpatients it was 10,000 to 20,000/µL. Among ICU patients, 35% of platelet transfusion episodes had a platelet count of greater than 50,000/µL; this was only 8% for general ward and 2% for outpatients. The median posttransfusion increment, not corrected for platelet dose and/or patient size, ranged from 12,000 to 20,000/µL for inpatients, and from 17,000 to 27,000/µL for outpatients. CONCLUSIONS: These data from one of the largest reviews of platelet transfusion practice to date provide guidance for where to focus future clinical research studies and platelet blood management programs.

Contemporary Risk Factors and Outcomes of Transfusion-Associated Circulatory Overload.

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.

The first reported case of concurrent trimethoprim-sulfamethoxazole-induced immune hemolytic anemia and thrombocytopenia.

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.

Practical approaches and costs for provisioning safe transfusions during anti-CD38 therapy.

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.

Use and Future Investigations of Recombinant and Plasma-Derived Coagulation and Anticoagulant Products in the Neonate.

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.

A multicenter study of plasma use in the United States.

BACKGROUND: Detailed information regarding plasma use in the United States is needed to identify opportunities for practice improvement and design of clinical trials of plasma therapy. STUDY DESIGN AND METHODS: Ten US hospitals collected detailed medical information from the electronic health records for 1 year (2010-2011) for all adult patients transfused with plasma. RESULTS: A total of 72,167 units of plasma were transfused in 19,596 doses to 9269 patients. The median dose of plasma was 2 units (interquartile range, 2-4; range 1-72); 15% of doses were 1 unit, and 45% were 2 units. When adjusted by patient body weight (kg), the median dose was 7.3 mL/kg (interquartile range, 5.5-12.0). The median pretransfusion international normalized ratio (INR) was 1.9 (25%-75% interquartile range, 1.6-2.6). A total of 22.5% of plasma transfusions were given to patients with an INR of less than 1.6 and 48.5% for an INR of 2.0 or more. The median posttransfusion INR was 1.6 (interquartile range, 1.4-2.0). Only 42% of plasma transfusions resulted in a posttransfusion INR of less than 1.6. Correction of INR increased as the plasma dose increased from 1 to 4 units (p < 0.001). There was no difference in the INR response to different types of plasma. The most common issue locations were general ward (38%) and intensive care unit (ICU; 42%). CONCLUSION: This large database describing plasma utilization in the United States provides evidence for both inadequate dosing and unnecessary transfusion. Measures to improve plasma transfusion practice and clinical trials should be directed at patients on medical and surgical wards and in the ICU where plasma is most commonly used.

Trends in red blood cell transfusion and 30-day mortality among hospitalized patients.

BACKGROUND: Blood conservation strategies have been shown to be effective in decreasing red blood cell (RBC) utilization in specific patient groups. However, few data exist describing the extent of RBC transfusion reduction or their impact on transfusion practice and mortality in a diverse inpatient population. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study using comprehensive electronic medical record data from 21 medical facilities in Kaiser Permanente Northern California. We examined unadjusted and risk-adjusted RBC transfusion and 30-day mortality coincident with implementation of RBC conservation strategies. RESULTS: The inpatient study cohort included 391,958 patients who experienced 685,753 hospitalizations. From 2009 to 2013, the incidence of RBC transfusion decreased from 14.0% to 10.8% of hospitalizations; this change coincided with a decline in pretransfusion hemoglobin (Hb) levels from 8.1 to 7.6 g/dL. Decreased RBC utilization affected broad groups of admission diagnoses and was most pronounced in patients with a nadir Hb level between 8 and 9 g/dL (n = 73,057; 50.8% to 19.3%). During the study period, the standard deviation of risk-adjusted RBC transfusion incidence across hospitals decreased by 44% (p < 0.001). Thirty-day mortality did not change significantly with declines in RBC utilization in patient groups previously studied in clinical trials nor in other subgroups. CONCLUSIONS: After the implementation of blood conservation strategies, RBC transfusion incidence and pretransfusion Hb levels decreased broadly across medical and surgical patients. Variation in RBC transfusion incidence across hospitals decreased from 2010 to 2013. Consistent with clinical trial data, more restrictive transfusion practice did not appear to impact 30-day mortality.

Population-based screening for anemia using first-time blood donors.

Anemia is an important public health concern. Data from population-based surveys such as the National Health and Nutrition Examination Survey (NHANES) are the gold standard, but are obtained infrequently and include only small samples from certain minority groups. We assessed whether readily available databases of blood donor hemoglobin values could be used as a surrogate for population hemoglobin values from NHANES. Blood donor venous and fingerstick hemoglobin values were compared to 10,254 NHANES 2005-2008 venous hemoglobin values using demographically stratified analyses and ANOVA. Fingerstick hemoglobins or hematocrits were converted to venous hemoglobin estimates using regression analysis. Venous hemoglobin values from 1,609 first time donors correlated extremely well with NHANES data across different ages, genders, and demographic groups. Cigarette smoking increased hemoglobin by 0.26-0.59 g/dL depending on the intensity. Converted fingerstick hemoglobin from 36,793 first time donors agreed well with NHANES hemoglobin (weighted mean hemoglobin of 15.53 g/dL for donors and 15.73 g/dL for NHANES) with similar variation in mean hemoglobin by age. However, compared to NHANES, the larger donor data set showed reduced differences in mean hemoglobin between Blacks and other races/ethnicities. Overall, first-time donor fingerstick hemoglobins approximate US population data and represent a readily available public health resource for ongoing anemia surveillance.

Absence of acute adverse in vitro effects on aged AS-1 red blood cells and thawed plasma after prolonged exposure to 13.56-MHz radio energy.

BACKGROUND: There is growing interest in radio frequency identification (RFID) technology for tracking blood products to improve productivity and safety in the transfusion medicine supply chain. We conducted a limited study to assess the temperature and biologic effects after extreme exposure to 13.56-MHz RF radiation on aged red blood cells (aRBCs) nearing their 42-day life and three types of thawed plasma (TP). STUDY DESIGN AND METHODS: Using a Food and Drug Administration-approved limit test protocol, test units of both aRBCs and three types of TP were subjected to high levels of RF energy for an extended duration to assess worst-case effects compared to minimally exposed control units. Three replications were performed for each product type. RESULTS: Hemolysis after 23 to 25 hours of RF energy exposure was less than 0.3% for all test and control aRBC units and well within the 1% or less acceptance criterion. Both biologic test and temperature increase results were within acceptance criteria and consistent with earlier tests on 6- to 9-day RBCs, with no detectable acceleration in cellular degradation of aRBCs. Nine different plasma coagulation factors were evaluated and, with one explainable exception, all showed less than 20% change in their measured test versus control values, meeting the acceptance criteria. The relative temperature increase between test and control units never exceeded the 1.5°C acceptance criterion for RBCs and 4°C for plasma. CONCLUSION: Use of 13.56-MHz RFID technology is unlikely to have any significant temperature or biologic effects on aRBC and plasma units under normal operating conditions.

Absence of acute adverse in-vitro effects on AS-1 RBCs and whole blood-derived platelets following prolonged exposure to 13.56 MHz radio energy.

BACKGROUND: There is growing interest in radio frequency identification (RFID) technology application for tracking blood products to achieve higher productivity and safety in the transfusion medicine supply chain. We have conducted a limited study to assess the temperature and biological effects of 13.56 MHz RF radiation on RBCs and whole blood-derived platelets (WBDP) under extreme exposure conditions. STUDY DESIGN AND METHODS: Using an FDA-approved protocol, test units of both RBC and WBDP were subjected to approximately 100 watts of RF energy for an extended duration (23-25 h) to assess worst-case effects. Three replications of the test were performed. RESULTS: Hemolysis after 23-25 hours of RF energy exposure was 0.09% and 0.05%, respectively, for TEST and CONTROL RBC units and well within the ≤1% limit in the FDA-approved acceptance criteria. For WBDP units, the mean pH of TEST and CONTROL units were 7.27 and 7.19, respectively, following 23-25 hours of RF energy exposure, and well above the ≥6.2 acceptance limit. Further, there was no detectable acceleration in cellular degradation of RBC and WBDP products. While there was minimal temperature rise, the relative temperature increase between TEST and CONTROL units never exceeded the 1.5°C acceptance criterion. CONCLUSIONS: 13.56 MHz-based RFID technology is unlikely to have any significant temperature or biological effects on RBC and WBDP units under the normal operating conditions (a maximum of 4 watts RF power exposure for about 20 nonconsecutive minutes for RFID tracking during the life of the blood product).

Splenic rupture in a parental donor undergoing peripheral blood progenitor cell mobilization.

Peripheral blood progenitor cells (PBPCs) are now widely used as a source of progenitor cells for allogeneic transplantation. Recombinant human granulocyte colony-stimulating factor is used to mobilize PBPCs for collection by leukapheresis. Although side effects of mobilization are generally benign, adverse effects have been reported. The authors present a case of spontaneous splenic rupture, without splenomegaly, in a parental donor undergoing PBPC mobilization, review the literature regarding this adverse event, and explore issues regarding donor safety.