Can Red Blood Cell and Platelet Transfusions Have a Pathogenic Role in Bronchopulmonary Dysplasia?

OBJECTIVE: To evaluate whether transfusions in infants born preterm contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We conducted a multihospital, retrospective study seeking associations between red blood cell or platelet transfusions and BPD. We tabulated all transfusions administered from January 2018 through December 2022 to infants born ≤29 weeks or <1000 g until 36 weeks postmenstrual age and compared those with BPD grade. We performed a sensitivity analysis to assess the possibility of a causal relationship. We then determined whether each transfusion was compliant with restrictive guidelines, and we estimated effects fewer transfusions might have on future BPD incidence. RESULTS: Eighty-four infants did not develop BPD and 595 did; 352 developed grade 1 (mild), 193 grade 2 (moderate), and 50 grade 3 (severe). Transfusions were given at <36 weeks to 7% of those who did not develop BPD, 46% who did, and 98% who developed severe BPD. For every transfusion the odds of developing BPD increased by a factor of 2.27 (95% CI, 1.59-3.68; P < .001). Sensitivity analyses suggested that transfusions might contribute to BPD. Fifty-seven percent of red blood cell transfusions and 68% of platelet transfusions were noncompliant with new restrictive guidelines. Modeling predicted that complying with restrictive guidelines could reduce the transfusion rate by 20%-30% and the moderate to severe BPD rate by ∼4%-6%. CONCLUSIONS: Transfusions were associated with BPD incidence and severity. Lowering transfusion rates to comply with current restrictive guidelines might result in a small but meaningful reduction in BPD rates.

Neonatal Thrombocytopenia: Factors Associated With the Platelet Count Increment Following Platelet Transfusion.

OBJECTIVE: To understand better those factors relevant to the increment of rise in platelet count following a platelet transfusion among thrombocytopenic neonates. STUDY DESIGN: We reviewed all platelet transfusions over 6 years in our multi-neonatal intensive care unit system. For every platelet transfusion in 8 neonatal centers we recorded: (1) platelet count before and after transfusion; (2) time between completing the transfusion and follow-up count; (3) transfusion volume (mL/kg); (4) platelet storage time; (5) sex and age of platelet donor; (6) gestational age at birth and postnatal age at transfusion; and magnitude of rise as related to (7) pre-transfusion platelet count, (8) method of enhancing transfusion safety (irradiation vs pathogen reduction), (9) cause of thrombocytopenia, and (10) donor/recipient ABO group. RESULTS: We evaluated 1797 platelet transfusions administered to 605 neonates (median one/recipient, mean 3, and range 1-52). The increment was not associated with gestational age at birth, postnatal age at transfusion, or donor sex or age. The rise was marginally lower: (1) with consumptive vs hypoproductive thrombocytopenia (P < .001); (2) after pathogen reduction (P < .01); (3) after transfusing platelets with a longer storage time (P < .001); and (4) among group O neonates receiving platelets from non-group O donors (P < .001). Eighty-seven neonates had severe thrombocytopenia (<20 000/µL). Among these infants, poor increments and death were associated with the cause of the thrombocytopenia. CONCLUSION: The magnitude of post-transfusion rise was unaffected by most variables we studied. However, the increment was lower in neonates with consumptive thrombocytopenia, after pathogen reduction, with longer platelet storage times, and when not ABO matched.

Platelet Transfusions in a Multi-Neonatal Intensive Care Unit Health Care Organization Before and After Publication of the PlaNeT-2 Clinical Trial.

OBJECTIVES: To evaluate whether implementing more restrictive neonatal intensive care unit (NICU) platelet transfusion guidelines following the Platelets for Neonatal Transfusion - Study 2 randomized controlled trial (transfusion threshold changed from 50 000/µL to 25 000/µL for most neonates) was associated with fewer NICU patients receiving a platelet transfusion, without adversely affecting outcomes. STUDY DESIGN: Multi-NICU retrospective analysis of platelet transfusions, patient characteristics, and outcomes during 3 years before vs 3 years after revising system-wide guidelines. RESULTS: During the first period, 130 neonates received 1 or more platelet transfusions; this fell to 106 during the second. The transfusion rate was 15.9/1000 NICU admissions in the first period vs 12.9 in the second (P = .106). During the second period, a smaller proportion of transfusions was administered when the platelet count was in the 50 000-100 000/µL range (P = .017), and a larger proportion when it was <25 000/µL (P = .083). We also saw a fall in the platelet counts that preceded the order for transfusion from 43 100/µL to 38 000/µL (P = .044). The incidence of adverse outcomes did not change. CONCLUSIONS: Changing platelet transfusion guidelines in a multi-NICU network to a more restrictive practice was not associated with a significant reduction in number of neonates receiving a platelet transfusion. The guideline implementation was associated with a reduction in the mean platelet count triggering a transfusion. We speculate that further reductions in platelet transfusions can safely occur with additional education and accountability tracking.

Associations between blood donor sex and age, and outcomes of transfused newborn infants.

BACKGROUND: It is controversial whether the sex or age of red blood cell (RBC) donors affects mortality or morbidities of transfused newborn infants. We assessed these issues using a multi-year, multi-hospital database linking specific outcomes of neonatal transfusion recipients with RBC donor sex and age. STUDY DESIGN AND METHODS: We performed retrospective analyses of all neonates receiving ≥ one RBC transfusion during a 12-year period in all Intermountain Healthcare hospitals, matching mortality and specific morbidities of each transfusion recipient with the sex and age of each donor. RESULTS: There were 6396 RBC transfusions administered to 2086 infants in 15 hospitals. A total of 825 infants were transfused exclusively with RBC from female donors, 935 infants were transfused exclusively with RBC from male donors, and 326 infants were transfused with RBC from both female and male donors. No differences in baseline characteristics were identified among the three groups. Infants who received blood from both male and female donors had more RBC transfusions (5.3 ± 2.9 transfusions if received both male and female donor blood vs. 2.6 ± 2.2 if received blood from only one sex, mean ± SD, p < .001). We identified no significant differences in mortality or morbidities associated with the sex or the age of blood donors. Similarly, an analysis of matched vs. mismatched donor/recipient sex revealed no associations with death or neonatal morbidities. CONCLUSION: These data support the practice of transfusing newborn infants with RBC obtained from donors of either sex and regardless of donor age.

Neonatal Intensive Care Unit Patients Receiving More Than 25 Platelet Transfusions.

OBJECTIVE: A few patients in neonatal intensive care units (NICU) receive numerous platelet transfusions. These patients can become refractory, defined as transfusions of ≥10 mL/kg failing to increase the platelet count by at least 5,000/µL. Causes of, and best treatments for, platelet transfusion refractoriness in neonates have not been defined. STUDY DESIGN: Multi-NICU multiyear retrospective analysis of neonates receiving >25 platelet transfusions. RESULTS: Eight neonates received 29 to 52 platelet transfusions. All eight were blood group O. Five had sepsis, four were very small for gestational age, four had bowel resections, two Noonan syndrome, two had cytomegalovirus infection. All eight had some (19-73%) refractory transfusions. Many (2-69%) of the transfusions were ordered when the platelet count was >50,000/µL. Higher posttransfusion counts occurred after ABO-identical transfusions (p = 0.026). Three of the eight had late NICU deaths related to respiratory failure; all five survivors had severe bronchopulmonary dysplasia requiring tracheostomy for prolonged ventilator management. CONCLUSION: Neonates who are high users of platelet transfusions appear to be at high risk for poor outcomes, especially respiratory failure. Future studies will examine whether group O neonates are more likely to develop refractoriness and whether certain neonates would have a higher magnitude of posttransfusion rise if they received ABO-identical donor platelets. KEY POINTS: · Many of the platelet transfusions given in the NICU are given to a small subset of patients.. · Refractoriness to platelet transfusions is common among these very high recipients.. · Neonates who are high users of platelet transfusions appear to be at high risk for poor outcomes..

First report of transfusing low-titer cold-stored type O whole blood to an extremely-low-birth-weight neonate after acute blood loss.

BACKGROUND: Multiple reports suggest that cold-stored low-titer type O whole blood (LTOWB) is becoming a preferred transfusion product for resuscitating massive hemorrhage across trauma, obstetrical, and pediatric services. However, we know of no reports of using this product for emergency transfusion of newborn infants after acute severe hemorrhage. CASE REPORT: We report our experience with emergency transfusion of re-warmed LTOWB using a fluid warmer for the resuscitation of a hypotensive 25-week gestation neonate following acute and severe placental abruption. The transfusion was tolerated well, without evidence of hemolysis or other complications. CONCLUSIONS: This is the first report of which we are aware of transfusing warmed LTOWB to a preterm neonate. Our positive experience leads us to speculate that this product could have a role for neonates following acute severe blood loss.

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.

Civilian walking blood bank emergency preparedness plan.

BACKGROUND: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. METHODS AND MATERIALS: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. RESULTS AND CONCLUSIONS: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.

Emergency-release blood transfusions after postpartum hemorrhage at the Intermountain Healthcare hospitals.

BACKGROUND: Most low-risk obstetric patients do not have crossmatched blood available to treat unexpected postpartum hemorrhage. An emergency-release blood transfusion (ERBT) program is critical for hospitals with obstetrical services. We performed a retrospective analysis of obstetrical ERBTs administered in our multihospital system. DESIGN AND METHODS: We collected data from the past 8 years at all Intermountain Healthcare hospitals on every ERBT after postpartum hemorrhage; logging circumstances, number and type of transfused products, and outcomes. RESULTS: Eighty-nine women received ERBT following 224,035 live births, for an incidence of 3.97 transfused women/10,000 births. The most common causally-associated conditions were: uterine atony (40%), placental abruption/placenta previa (16%), retained placenta (11%), and uterine rupture (5%). The mean number of total units transfused was 7.9 (range 1-76). The mean number of red blood cells (RBCs) transfused was 4.8, the median 4, and SD was ±4.4. Massive transfusion protocols (MTPs) for trauma recommend using a ratio of 1:1:1 or 2:1:1 of RBC:FFP:Platelets, however the ratios varied widely for postpartum hemorrhage. Only 1.5% received a 1:1:1 ratio and 7.5% received a 2:1:1 ratio. Nineteen percent (17/89) of women underwent hysterectomy, 7% (6/89) had uterine artery embolization, 36% (32/89) had an intensive care unit admission, and 1% (1/89) died. CONCLUSION: Emergency transfusion for postpartum hemorrhage occurred after 1/2500 births. Most women received less FFP and platelets than recommended for traumatic hemorrhage. A potentially better practice for postpartum hemorrhage would be a balanced ratio of blood products, transfusion of low-titer, group O, cold-stored, whole blood, or inclusion in a MTP.

Warming blood products for transfusion to neonates: In vitro assessments.

BACKGROUND: Blood products may be transfused into neonates at temperatures at or below room temperature. The benefits and risks of warming blood to 37°C are not defined in this population or with the equipment used in neonates. Physiologic warming might enhance product effectiveness or decrease transfusion-associated hypothermia. STUDY DESIGN AND METHODS: We utilized an in vitro model of neonatal transfusions, with a syringe pump, blood tubing, and 24-gauge catheter and compared current practice (cold products) vs an inline blood warmer. Transfusions were performed rapidly (30 minutes) and slower (120 minutes) to model emergent vs routine situations. We tested red blood cells, fresh-frozen plasma, apheresis platelets (PLTs), and cold-stored low-titer group O whole blood. We used infrared detectors and inline probes to measure temperatures at the origin and at the simulated patient. We assessed warmer-induced damage by measuring plasma hemoglobin and hematocrit (seeking hemolysis), fibrinogen (seeking activation of coagulation), and PLT count and TEG-MA (seeking PLT destruction or dysfunction). RESULTS: The cold-stored products were 4.2 ± 1.0°C (mean ± SD) at the origin and 21.5 ± 0.1°C at the patient. With the inline warmer, products were 37.8 ± 0.6°C at the warmer and 32.6 ± 1.7°C at the patient during a 30-minute infusion, but were 34.5 ± 2.1 with a foil sheath covering the terminal tubing. We found no warmer-induced damage using any metric. CONCLUSION: In simulated neonatal intensive care unit (NICU) transfusions, an inline blood warmer can deliver blood products at near-physiologic temperatures with no detected damage. We suggest in vivo testing of warmed NICU transfusions, assessing product effectiveness and hypothermia risk reduction.

Evaluating emergency-release blood transfusion of newborn infants at the Intermountain Healthcare hospitals.

BACKGROUND: An emergency-release blood transfusion (ERBT) protocol (uncrossmatched type O-negative red blood cells, AB plasma, AB platelets) is critical for neonatology practice. However, few reports of emergency transfusions are available. We conducted an ERBT quality improvement project as a basis for progress. STUDY DESIGN AND METHODS: For each ERBT in the past 8 years, we logged indications, products, locations and timing of the transfusions, and outcomes. RESULTS: One hundred forty-nine ERBTs were administered; 42% involved a single blood product, and 58% involved two or more. The incidence was 6.25 ERBT per 10,000 live births, with a higher rate (9.52 ERBT/10,000) in hospitals with a Level 3 neonatal intensive care unit (NICU) (p < 0.001). Seventy percent of ERBTs were administered in a NICU and 30% in a delivery room, operating room, or emergency department. Indications were abruption/previa (32.2%), congenital anemia (i.e., fetomaternal hemorrhage; 15.4%), umbilical cord accident (i.e., velamentous insertion; 15.0%), and bleeding/coagulopathy (12.8%). Fifty-eight percent of those with hemorrhage before birth did not have a hemoglobin value reported on the umbilical cord gas; thus, anemia was not recognized initially. None of the 149 ERBTs were administered using a blood warmer. The mortality rate of recipients was 35%. CONCLUSION: Based on our findings, we recommend including a hemoglobin value with every cord blood gas after emergency delivery to rapidly identify fetal anemia. We also discuss two potential improvements for future testing: 1) the use of a warming device for massive transfusion of neonates and 2) the use of low-titer group O cold-stored whole blood for massive hemorrhage in neonates.

First report of using low-titer cold-stored type O whole blood in massive postpartum hemorrhage.

BACKGROUND: In cases of massive hemorrhage in the US military, improved outcomes have been reported with the use of warm, fresh whole blood transfusions. Cold-stored low-titer type O whole blood (LTOWB) has become the preferred product for resuscitation of severe bleeding in deployed surgical units. Reports of LTOWB use in civilian trauma are becoming more frequent. CASE REPORT: We report our experience with emergency transfusion of LTOWB for a woman with massive postpartum hemorrhage. The patient had two previous cesarean section deliveries at term without complications. With her third elective cesarean section at term, blood loss during surgery was not excessive, but 3 to 4 hours later she had an estimated blood loss of 3600 mL. Despite measures to control the hemorrhage, she rapidly became hypotensive and tachycardic, and our massive transfusion protocol (MTP) was activated. The transfusion service had very recently incorporated LTOWB into Trauma Pack 1 of the MTP. She received two LTOWB units, after which her hemorrhaging ceased, blood pressure normalized, and she became alert. One hour later she received one unit of fresh frozen plasma and one unit of red blood cells (RBCs). The following morning she received one unit of crossmatched RBCs, for a hematocrit of 20.7%. She was discharged home on Day 4, and she remains healthy. CONCLUSIONS: This is the first report of which we are aware of massive postpartum hemorrhage treated using LTOWB. Our positive experience leads us to speculate that this approach could have a role in massive obstetric hemorrhage.

Fatal Sepsis Associated with Bacterial Contamination of Platelets - Utah and California, August 2017.

During August 2017, two separate clusters of platelet transfusion-associated bacterial sepsis were reported in Utah and California. In Utah, two patients died after platelet transfusions from the same donation. Clostridium perfringens isolates from one patient's blood, the other patient's platelet bag, and donor skin swabs were highly related by whole genome sequencing (WGS). In California, one patient died after platelet transfusion; Klebsiella pneumoniae isolates from the patient's blood and platelet bag residuals and a nontransfused platelet unit were matched using WGS. Investigation revealed no deviations in blood supplier or hospital procedures. Findings in this report highlight that even when following current procedures, the risk for transfusion-related infection and fatality persists, making additional interventions necessary. Clinicians need to be vigilant in monitoring for platelet-transmitted bacterial infections and report adverse reactions to blood suppliers and hemovigilance systems. Blood suppliers and hospitals could consider additional evidence-based bacterial contamination risk mitigation strategies, including pathogen inactivation, rapid detection devices, and modified screening of bacterial culture protocols.

Bilirubin levels and phototherapy use before and after neonatal red blood cell transfusions.

BACKGROUND: Our previous retrospective study suggested that red blood cell (RBC) transfusion of preterm neonates can be associated with an increase in bilirubin, but this has not been tested prospectively. STUDY DESIGN AND METHODS: We studied neonates before and after RBC transfusions, recording serial bilirubin levels and whether they qualified for phototherapy. Because lysed RBCs release plasma-free hemoglobin (Hb), a precursor to bilirubin, we also measured plasma free Hb and bilirubin from the donor blood. RESULTS: We studied 50 transfusions given to 39 neonates. Gestation ages of transfused neonates, at birth, were 26 (24-29) weeks (median [interquartile range]); birthweights were 750 (620-1070) g. The study transfusion was given on Day of Life 9.9 (3.4-19.2). In 20% (10/50) phototherapy was being administered at the beginning of and during the transfusion. In these patients neither the 4- to 6- nor the 24- to 36-hour-posttransfusion bilirubin levels were significantly higher than before transfusion. However, in 30% of the others (12/40) phototherapy was started (or restarted) after the transfusion and 15% had a posttransfusion bilirubin increase of at least 2.5 mg/dL. These neonates received donor blood with a higher plasma-free Hb (p < 0.05). CONCLUSIONS: Neonates commonly qualify for phototherapy after transfusion. A minority (15% in this series) have a posttransfusion bilirubin increase of at least 2.5 mg/dL. We speculate that neonates qualifying for a RBC transfusion, who are judged to be at high risk for bilirubin-induced neurotoxicity, might benefit from checking their serum bilirubin level after the transfusion and providing donor blood with low plasma-free Hb levels.

Reference intervals for common coagulation tests of preterm infants (CME).

BACKGROUND: Fresh-frozen plasma (FFP) is sometimes administered to nonbleeding preterm neonates who are judged to be at risk for bleeding because they have abnormal coagulation tests. The benefits/risks of this practice are not well defined. One limitation to progress is lack of reference intervals for the common coagulation tests, thus limiting precision about whether coagulation tests are indeed abnormal. STUDY DESIGN AND METHODS: In a sequential observational study, fetal blood was drawn at preterm birth (≤ 34 weeks) from the umbilical vein near the placenta. Fibrinogen, prothrombin time, activated partial thromboplastin time, D-dimer, platelet (PLT) count, and mean PLT volume were measured. Reference intervals were constructed using 5th and 95th percentile values. Associations were then sought between abnormal coagulation values at birth and bleeding problems identified during the first week. RESULTS: Coagulation tests were drawn at 175 preterm deliveries and the results were organized into reference intervals by gestational age. No abnormal coagulation value, either alone or in combination, predicted hemorrhage (intraventricular, gastrointestinal, or pulmonary) during the first week. However, fibrinogen exceeding the 95th percentile was associated with evidence of in utero infection/inflammation (correlations with elevated C-reactive protein, p<0.01, and elevated immature to total neutrophil ratio, p<0.001). CONCLUSIONS: Abnormal coagulation values at preterm birth do not predict bleeding during the first week. This suggests to us that bleeding in the days after preterm birth is not generally the result of in utero coagulopathy. These findings bring into question the value of coagulation screening of nonbleeding preterm infants and prophylactic FFP administration to those with abnormal values.

Association, among very-low-birthweight neonates, between red blood cell transfusions in the week after birth and severe intraventricular hemorrhage.

BACKGROUND: Previous reports describe a statistical association, among very-low-birthweight (VLBW, <1500 g) neonates, between red blood cell (RBC) transfusion in the first days after birth and development of severe intraventricular (brain) hemorrhage (IVH). STUDY DESIGN AND METHODS: We hypothesized that after we established a neonatal intensive care unit (NICU) transfusion management program in 2009, a decrease in early (first week after birth) RBC transfusion rate and a decrease in the incidence of severe IVH occurred concomitantly. RESULTS: During a 9-year period 2716 VLBW neonates were admitted to our NICUs. In 2004, 58% of VLBW neonates received one or more RBC transfusions during the first week. After a transfusion compliance program was established in 2009, this rate declined, reaching 25% by 2012. In parallel, the severe IVH rate also declined, from 17% in 2004 to 8% in 2012 (R(2) = 0.73). IVH occurred in 27% of those who received a RBC transfusion during the first week versus less than 2% of those with no early transfusion (p < 0.001). The decrease in IVH rate occurred exclusively among neonates born in an Intermountain Healthcare perinatal center and not among those initially cared for in an "outside" hospital and subsequently transported to an Intermountain NICU. CONCLUSIONS: It remains unclear whether transfusing VLBW neonates during the first days after birth is a proximate cause of IVH. However, the present report is consistent with previous studies showing that successful efforts to reduce early RBC transfusions is associated with a decrease in the incidence of severe IVH.

Association of neonatal red blood cell transfusion with increase in serum bilirubin.

BACKGROUND: It is not clear whether red blood cell (RBC) transfusions typically increase a neonate's total serum bilirubin (TSB) level or if so by how much. STUDY DESIGN AND METHODS: In this retrospective analysis, from 2009 through 2012, we collected TSB measurements before and after transfusions, recording blood types of mothers, neonates, and blood donors and whether phototherapy was used before, during, or after transfusion. RESULTS: Of 7272 neonates admitted during this period, 658 (9%) received 2597 RBC transfusions. TSB levels were drawn before and after 431 transfusions, 255 of which did not have phototherapy at the time the transfusion was administered. The mean increase in TSB was 2.2 mg/dL (95% confidence interval, 1.9-2.5 mg/dL). Seven percent of all transfusions and 12% of transfusions to very-low-birthweight (VLBW) infants (<1500 g) were followed by a TSB increase of at least 5 mg/dL. Transfusions with "universal donor" blood (O-) resulted in a higher TSB increase (p < 0.0001), but the magnitude was clinically insignificant (0.3 mg/dL). Older blood (days since donor draw) did not generate significantly higher posttransfusion TSB levels (p = 0.092). A focused study of the 10 neonates with the highest TSB increases revealed that six were unexplained other than transfusion related. CONCLUSIONS: We describe an association between RBC transfusion and TSB elevation, but we recognize that this does not establish a cause-and-effect relationship. However, the observation that an increase of at least 5 mg/dL occurs after 12% of transfusions to VLBW neonates suggests to us that clinicians will want to evaluate jaundice, or measure bilirubin, on VLBW neonates after transfusion.

Erythrokinetic mechanism(s) causing the "late anemia" of hemolytic disease of the fetus and newborn.

A transfusion-requiring "late anemia" can complicate the management of neonates convalescing from hemolytic disease of the fetus and newborn (HDFN). This anemia can occur in any neonate after HDFN but is particularly prominent in those who received intrauterine transfusions and/or double-volume exchange transfusions. Various reports describe this condition as occurring based on ongoing hemolysis, either due to passive transfer of alloantibody through breast milk or persistence of antibody not removed by exchange transfusion. However, other reports describe this condition as the result of inadequate erythrocyte production. Both hypotheses might have merit, because perhaps; (1) some cases are primarily due to continued hemolysis, (2) others are primarily hypoproductive, and (3) yet others result from a mixture of these two mechanisms. We propose prospective collaborative studies that will resolve this issue by serially quantifying end-tidal carbon monoxide. Doing this will better inform the assessment and treatment of neonates recovering from HDFN.

Low-Titer Type O Whole Blood for Transfusing Perinatal Patients after Acute Hemorrhage: A Case Series.

Objective Acute and massive blood loss is fortunately a rare occurrence in perinatal/neonatal practice. When it occurs, typical transfusion paradigms utilize sequential administration of blood components. However, an alternative approach, transfusing type O whole blood with low anti-A and anti-B titers, (LTOWB) has recently been approved and utilized in trauma surgery. Study Design Retrospective analysis of all perinatal patients who have received LTOWB after acute massive hemorrhage at the Intermountain Medical Center. Results LTOWB was the initial transfusion product we used to resuscitate/treat 25 women with acute and massive postpartum hemorrhage and five infants with acute hemorrhage in the first hours/days after birth. We encountered no problems obtaining or transfusing this product and we recognized no adverse effects of this treatment. Conclusion Transfusing LTOWB to perinatal patients after acute blood loss is feasible and appears at least as safe a serial component transfusion. Its use has subsequently been expanded to multiple hospitals in our region as first-line transfusion treatment for acute perinatal hemorrhage. Key Points Low-titer type O whole blood (LTOWB) was our initial transfusion product for 30 perinatal patients with acute hemorrhage. Twenty-five of these were obstetrical patients and five were neonatal patients. We encountered no problems with, or adverse effects from LTOWB in any of these patients. LTOWB transfusions to women were ten days since donor draw (interquartile range, 8-13) and to neonates was six days (5-8).

Neonatal and Obstetrical Outcomes of Pregnancies Complicated by Alloimmunization.

BACKGROUND AND OBJECTIVES: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. METHODS: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. RESULTS: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. CONCLUSIONS: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.