Fatal hemolytic disease of the newborn due to anti-B Isohemagglutinin: An unfamiliar presentation of a familiar disease.

BACKGROUND: Hemolytic disease of the newborn (HDN) occurs in approximately 1 out of 3000 live births. Severe presentations are atypical but must be recognized and treated rapidly to avoid life-threatening organ dysfunction. CASE PRESENTATION: Here we report an unusual case of neonatal ABO HDN that illustrates the enormous inflammatory potential of maternal-fetal blood group mismatch. Following an uneventful delivery notable only for HDN caused by maternal anti-B IgG, our patient developed shock, DIC, and renal failure. Despite numerous interventions, she experienced a rapid clinical decline and died 10 days after birth. Treatment with whole blood exchange and a monoclonal antibody directed at complement component 5 (eculizumab) were attempted late in the disease course but were unsuccessful. Importantly, this patient had several known risk factors for severe ABO HDN, including the pentad of a group O mother with a group B neonate, high newborn red blood cell B antigen expression, presence maternal anti-B isohemagglutinin in high titer, presence of a maternal IgG anti-B isohemagglutinin, and African ancestry. CONCLUSION: Clinicians should be aware of the potential for severe ABO HDN and consider earlier diagnostic workup and more aggressive therapy in patients with high-risk features.

Associations of donor, component, and recipient factors on hemoglobin increments following red blood cell transfusion in very low birth weight infants.

BACKGROUND: Anemia in very low birth weight (VLBW) infants is common and frequently managed with red blood cell (RBC) transfusions. We utilized a linked vein-to-vein database to assess the role of blood donors and component factors on measures of RBC transfusion effectiveness in VLBW infants. STUDY DESIGN AND METHODS: We linked blood donor and component manufacturing data with VLBW infants transfused RBCs between January 1, 2013 and December 31, 2016 in the Recipient Epidemiology Donor Evaluation Study-III (REDS III) database. Using multivariable regression, hemoglobin increments and subsequent transfusion events following single-unit RBC transfusion episodes were examined with consideration of donor, component, and recipient factors. RESULTS: Data on VLBW infants (n = 254) who received one or more single-unit RBC transfusions (n = 567 units) were linked to donor demographic and component manufacturing characteristics for analysis. Reduced post-transfusion hemoglobin increments were associated with RBC units donated by female donors (-0.24 g/dL [95% confidence interval (CI) -0.57, -0.02]; p = .04) and donors <25 years old (-0.57 g/dL [95% CI -1.02, -0.11]; p = .02). For RBC units donated by male donors, reduced donor hemoglobin levels were associated with an increased need for subsequent recipient RBC transfusion (odds ratio 3.0 [95% CI 1.3, 6.7]; p < .01). In contrast, component characteristics, storage duration, and time from irradiation to transfusion were not associated with post-transfusion hemoglobin increments. CONCLUSION: Donor sex, age, and hemoglobin levels were associated with measures of RBC transfusion effectiveness in VLBW infants. Mechanistic studies are needed to better understand the role of these potential donor factors on other clinical outcomes in VLBW infants.

The regional whole blood program in San Antonio, TX: A 3-year update on prehospital and in-hospital transfusion practices for traumatic and non-traumatic hemorrhage.

Low titer type O Rh-D + whole blood (LTO + WB) has become a first-line resuscitation medium for hemorrhagic shock in many centers around the World. Showing early effectiveness on the battlefield, LTO + WB is used in both the pre-hospital and in-hospital settings for traumatic and non-traumatic hemorrhage resuscitation. Starting in 2018, the San Antonio Whole Blood Collaborative has worked to provide LTO + WB across Southwest Texas, initially in the form of remote damage control resuscitation followed by in-hospital trauma resuscitation. This program has since expanded to include pediatric trauma resuscitation, obstetric hemorrhage, females of childbearing potential, and non-traumatic hemorrhage. The objective of this manuscript is to provide a three-year update on the successes and expansion of this system and outline resuscitation challenges in special populations.

Fetomaternal hemorrhage: Evidence from a multihospital healthcare system that up to 40% of severe cases are missed.

BACKGROUND: We previously reported fetomaternal hemorrhage (FMH) in 1/9160 births, and only one neonatal death from FMH among 219,853 births. Recent reports indicate FMH is not uncommon among stillbirths. Consequently, we speculated we were missing cases among early neonatal deaths. We began a new FMH initiative to determine the current incidence. METHODS: We analyzed births from 2011 to 2020 where FMH was diagnosed. We also evaluated potential cases among neonates receiving an emergent transfusion just after birth, whose mothers were not tested for FMH. RESULTS: Among 297,403 births, 1375 mothers were tested for FMH (1/216 births). Fourteen percent tested positive (1/1599 births). Of those, we found 25 with clinical and laboratory evidence of FMH adversely affecting the neonate. Twenty-one received one or more emergency transfusions on the day of birth; all but two lived. We found 17 others who received an emergency transfusion on the day of birth where FMH was not tested for, but was likely; eight of those died. The 42 severe (proven + probable) cases equate to 1/7081 births. We judged that 10 of the 42 had an acute FMH, and in the others it likely had more than a day before birth. CONCLUSIONS: We estimate that we fail to diagnose >40% of our severe FMH cases. Needed improvements include (1) education to request maternal FMH testing when neonates are born anemic, (2) education on false-negative FMH tests, and (3) improved FMH communications between neonatology, obstetrics, and blood bank.

Efficacy and safety of fibrinogen concentrate for perioperative prophylaxis of bleeding in adult, adolescent, and pediatric patients with congenital fibrinogen deficiency: FORMA-02 and FORMA-04 clinical trials.

BACKGROUND: Congenital fibrinogen deficiency (CFD) is a rare coagulation disorder placing patients at increased bleeding risk. Human fibrinogen concentrate (HFC) represents current standard of care for fibrinogen replacement in CFD, however, limited data are available on HFC for prophylactic administration before/during surgery. Here, we report results and dosing considerations for HFC treatment in perioperative bleeding management in adult, adolescent, and pediatric patients with CFD. STUDY DESIGN AND METHODS: FORMA-02/FORMA-04 were multinational, prospective, open-label, uncontrolled Phase 3 HFC efficacy/safety studies for surgical bleeding prophylaxis in adult/adolescent (≥12 years) and pediatric patients (<12 years) respectively. HFC dosing was calculated to achieve pre-established target fibrinogen plasma levels. Overall hemostatic efficacy was assessed as success/failure by an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) according to objective criteria. RESULTS: Twelve patients (≥12 years, N = 9; <12 years, N = 3) received HFC for surgical prophylaxis (15 surgeries; 13 minor, 2 major). Eleven minor surgeries in patients aged ≥12 years required a median of 1 infusion (range; 1-5), with a mean (±SD) dose of 93.50 mg/kg [±41.43] and two minor surgeries in patients <12 years required 1 infusion (91.55 mg/kg [±23.40]). The major surgery in an adult patient required eight infusions (225.3 mg/kg total dose). The major surgery in a pediatric patient required six infusions (450.4 mg/kg). All surgeries were rated successful by the IDMEAC. DISCUSSION: In adults/adolescents and pediatric patients with fibrinogen deficiency, HFC treatment for hemostatic management during/after minor and major surgery was successful, with efficacy comparable across the different age groups.

Pediatric resident knowledge of transfusion medicine: Results from the BEST-TEST3 international education needs assessment.

BACKGROUND: Transfusions are a common intervention within pediatrics and require unique considerations to optimize patient care. Poor knowledge of evidence-based transfusion practice can lead to misuse of transfusion therapy and harm. While there have been assessments of transfusion medicine knowledge of physicians caring for adult patients, there is little data regarding pediatricians. STUDY DESIGN AND METHODS: Using a published transfusion medicine knowledge exam for internal medicine physicians as a backbone, pediatric transfusion medicine experts, using an iterative process, developed a pediatric-specific examination. Pilot testing and Rasch analysis, a method used in high-stakes testing, was used to validate the exam. The exam and a previously validated survey on transfusion medicine training, attitudes, and perceived ability were administered to pediatric residents. Analysis consisted of descriptive statistics as well as comparisons of exam scores based on survey responses. RESULTS: 330 pediatric residents from 19 sites in 6 countries participated in the study. The vast majority (91%) of residents had obtained blood product consent. The mean exam score was 37.1% (range 9.5%-71.4%) with no statistical differences based on amount or perceived quality of transfusion medicine education or perceived ability. DISCUSSION: A rigorously validated exam has now been developed that can be used to assess pediatric transfusion medicine knowledge. A large international group of pediatric residents performed poorly on the exam demonstrating a pressing need for improved transfusion medicine education to ensure safe and appropriate administration of blood components to infants and children.

Transfusion-associated hyperkalemia in pediatric population: Prevalence, risk factors, survival, infusion rate, and RBC unit features.

BACKGROUND: Hyperkalemia is a rare life-threatening complication of red blood cell (RBC) transfusion. Stored RBCs leak intracellular potassium (K+) into the supernatant; irradiation potentiates the K+ leak. As the characteristics of patients and implicated RBCs have not been studied systematically, a multicenter study of transfusion-associated hyperkalemia (TAH) in the pediatric population was conducted through the AABB Pediatric Transfusion Medicine Subsection. STUDY DESIGN: The medical records of patients <18 years old were retrospectively queried for hyperkalemia occurrence during or ≤12 h after the completion of RBC transfusion in a 1-year period. Collected data included patient demographics, diagnosis, medical history, timing of hyperkalemia and transfusion, mortality, and RBC unit characteristics. RESULTS/FINDINGS: A total of 3777 patients received 19,649 RBC units during the study period in four facilities. TAH was found in 35 patients (0.93%) in 37 occurrences. The patient median age and weight were 1.28 years and 9.80 kg, respectively. All patients had multiple serious comorbidities. There were 79 RBC units transfused in the TAH events; 62% were irradiated, and the median age of the units was 10 days. The median total RBC volume transfused ≤12 h before TAH was 24% of patient estimated total blood volume, and the median infusion rate (IR) was19.6 ml/kg/h. Mortality rate within 1 day after the TAH event was 20%. CONCLUSIONS: The prevalence of TAH in children was low; however, the 1-day mortality rate was 20%. Patients with multiple comorbidities may be at higher risk for TAH. The IR was higher for patients who had TAH than the IR threshold for safe transfusion.

Estimating Tanzania's National Met and Unmet Blood Demand From a Survey of a Representative Sample of Hospitals.

Estimating blood demand to determine collection goals challenges many low-income countries. We sampled Tanzanian hospitals to estimate national blood demand. A representative sample based on probability proportional to size sampling of 42 of 273 (15%) Tanzanian transfusing hospitals was selected. Blood bank registers, patient medical records, and blood component disposition records were reviewed prospectively from June to September 2013 to determine the number of components requested and the number and proportion issued, not issued due to nonavailability, and not issued for other reasons. Data were estimated for an annual national estimate. Of an estimated 278 371 components requested in 2013, 6648 (2.4%) were not issued due to nonavailability, 34 591 (12.4%) were not issued for other reasons, and 244 535 (87.8%) were issued. Of these 278 371 components, 86 753 (31.2%) were requested by adult medical, 74 499 (26.8%) by pediatric medical, and 57 312 (20.6%) by obstetric units. In these 3 units, the proportion of units not issued due to nonavailability was 1.8%. Private (4.1%) and large (6%) hospitals had the largest proportion of units not issued because of nonavailability. Of 244 535 issued components, 91 690 (37.5%) were collected, tested, and issued from blood banks that are not part of the Tanzania National Blood Transfusion Services (TNBTS). Nearly 98% of blood component demand was met. However, a large portion of the blood supply for the hospitals came from non-TNBTS blood banks. TNBTS could increase availability of safe blood through assuring the quality of donor selection and donation testing at non-TNBTS blood banks.