Evaluation of hematologic factors and bilirubin following exchange transfusion in neonatal hyperbilirubinemia.

INTRODUCTION: Exchange transfusion (ECT) is one of effective treatments for rapid reduction of the bilirubin serum levels. The main purpose of this study was to offer greater insights into the effects of ECT on the hematologic factors and bilirubin in neonatal hyperbilirubinemia. METHODS: This cross-sectional study was performed on 380 neonates over 35 gestational weeks, and 2-14 days old with a bilirubin of above 17 mg/dl who had undergone ECT at Ghaem Hospital of Mashhad in Iran from 2011 to 2021. Blood samples were examined before, immediately after, 6 h and 60 h after ECT for complete blood cell count (CBC), platelet count and bilirubin serum level analysis. RESULTS: In this study, the mean age of neonates was 5.21 ± 3.55 days with a mean birth weight of 2810 ± 710 gr. The mean platelet count (PLT), white blood cell (WBC) and the serum level of bilirubin were estimated at 260,000/mm2, 12,400/mm2, 23 mg/dl before ECT and 97,000/mm2, 7370//mm2 and 12.6 mg/dl immediately after ECT, respectively (P-value <0.001). CONCLUSION: The results indicated that the mean serum levels of bilirubin, platelets, and leukocytes dropped to 55%, 30%, and 60% of their baseline levels before ECT, respectively, but they all spiked after ECT.

Clinical Profile and Outcome Following Exchange Transfusion for Neonatal Jaundice in a Tertiary Care Centre.

INTRODUCTION: Phototherapy has reduced the need for exchange transfusion (ET) to manage jaundiced neonates. Hence there are concerns about increased risk of complication due to lack of opportunity to sustain skills in performing ET. We studied the complications and treatment outcomes of neonates treated for jaundice with ET. METHODOLOGY: A retrospective observational study was conducted from June 2013 to June 2020 in a tertiary care hospital in India. All neonates treated with ET for jaundice were included. RESULTS: Twenty-eight neonates underwent 31 ET during the study period. Their mean gestational age and birth weight were 37 weeks and 3200 g, respectively. Predisposing factor for jaundice observed were Coomb's positive status (11), hepatosplenomegaly suggesting hemolysis (3), cephalhematoma (2) and birth asphyxia (1). Abnormal neurological status before ET was seen in seven neonates. Adverse clinical events that happened during or within 8 h after ET were desaturation (4), tachycardia (3), tachypnea (2), bradycardia (2), shock (2) and temperature instability (2). One neonate developed acute kidney injury after ET and required peritoneal dialysis. Abnormal lab parameters observed during or within 8 h after ET were hypocalcemia (20), anemia (8), hypokalemia (7), hypernatremia (3), thrombocytopenia (3) and hyperkalemia (2). Post ET sepsis was seen in five neonates: two had only blood culture positive sepsis, two had bone and joint infection and one had liver abscess. CONCLUSION: The neonates undergoing ET are at high risk of developing complications which may be life threatening. Hence careful monitoring during the procedure is needed.

Exchange transfusion is a treatment done for newborn babies with severe jaundice. This procedure is done by removing baby's blood in small quantities and replacing it with donor's blood. This life-saving procedure is associated with many complications. We did this study to estimate the complications associated with this procedure in our newborn unit. Twenty-eight patients underwent exchange transfusion from June 2013 to June 2020 in our hospital. We found out that temperature disturbance, abnormal heart rate, abnormal breathing and fall in oxygen levels occurred during exchange transfusion. After the procedure blood circulation disturbances, low platelet count, low blood calcium levels and low blood potassium levels were commonly observed. One patient developed renal failure after the procedure and was treated with dialysis. Five patients developed infection after the procedure and were treated with antibiotics. Thus newborn patients undergoing exchange transfusion are at high risk of developing complications which may be life threatening. Hence careful monitoring during the procedure is needed to prevent these complications.

Pattern of serum bilirubin changes following double volume exchange blood transfusion in neonates at a tertiary health facility in Nigeria.

INTRODUCTION: exchange blood transfusion (EBT) is a form of massive transfusion useful in rapidly reducing serum bilirubin levels, but serum bilirubin levels frequently rebound within hours of completing the procedure, due to equilibration of extravascular bilirubin as well as on-going hemolysis. The study was carried out to determine the pattern of reduction in serum bilirubin levels following EBT among neonates with severe hyperbilirubinemia, as well as the factors contributing to this pattern, so as to establish evidence-based expectations following EBT. METHODS: a retrospective descriptive study covering a two-year period in a Nigerian tertiary hospital. Details of the EBT procedures, including serial serum bilirubin levels, were obtained from the hospital records of all newborn babies who had double volume EBT done for severe hyperbilirubinaemia during the study period. Data was analyzed using the statistical software SPSS version 21.0. RESULTS: the mean total serum bilirubin (TSB) before EBT in the 36 babies was 17.9 ± 6.3 mg/dl. The mean percentage decrease in TSB immediately following EBT was 44.3 ± 10.2%. Six hours after EBT, TSB levels had increased from the immediate post-EBT values by an average of 57.5 ± 32.2%. Twenty-four hours after the procedure, TSB values in most (87.1%) cases were still higher than the immediate post-EBT values, but lower than the pre-EBT values. Post-EBT anemia was recorded among 33.3% of the babies. CONCLUSION: EBT is effective in rapidly reducing serum bilirubin levels and preventing acute bilirubin encephalopathy in neonates with severe hyperbilirubinemia, despite the rebound increase that occurs in TSB values after the procedure.

Is it necessary to give calcium infusion during the exchange transfusion in newborns?

OBJECTIVES: We aimed to evaluate total serum calcium (TSC) and ionized serum calcium (ISC) levels and their effects on clinical outcomes in neonates underwent exchange transfusion (ET). METHOD: In this study, the data of newborn infants who underwent ET due to hyperbilirubinemia in a third level neonatal intensive care unit (NICU) were retrospectively analyzed. The patients were monitored by electrocardiogram during ET. Cardiac and respiratory rates, peripheral oxygen saturation, blood pressure values ​​and clinical findings as convulsion, tremor, hypertonia, laryngospasm, cyanosis and apnea were recorded in ET observation forms. The infants with no symptoms of hypocalcemia during the procedure were not routinely given IV calcium gluconate. TSC and ISC measured at the beginning, at the end and 24 h after the end of ET were evaluated retrospectively. RESULTS: Data of 36 newborn patients were evaluated. Median gestational age was 39 (35-40) weeks, mean birthweight was 2840 ± 841 (mean ± SD) grams. During the ET, desaturation was observed in five patients(13.9 %), sinus bradycardia in six(16.7 %), tachypnea in two(5.5 %), sinus tachycardia in one(2.8 %), and rare ventricular extrasystoles in one(2.8 %). Hypocalcaemia was not detected in any of the patients at the beginning of ET. Hypocalcemia was observed in two cases (5.5 %) at the end of ET. There was no statistically significant difference between the TSC and ISC levels at the beginning of ET, at the end and at the end of 24 h. CONCLUSION: As a result, routine intravenous (IV) calcium administration seems to be unnecessary provided that vital signs and neurological status are closely monitored during ET.

Safety and efficacy of low-titer O whole blood resuscitation in a civilian level I trauma center.

BACKGROUND: Military experience has shown low-titer O whole blood (LTOWB) to be safe and beneficial in the resuscitation of hemorrhaging trauma patients. However, few civilian centers use LTOWB for trauma resuscitation. We evaluated the early experience and safety of a LTOWB program at a level 1 civilian trauma center. METHODS: We retrospectively reviewed our trauma registry from January 2018 to June 2020 for patients admitted in shock (defined as ≥1 of the following: heart rate, >120 beats per minute; systolic blood pressure, <90 mm Hg; or shock index, >0.9) who received blood products within 24 hours. Patients were grouped by resuscitation provided: LTOWB (group 1), component therapy (CT; group 2), and LTOWB-CT (group 3). Safety, outcomes, and variables associated with LTOWB transfusion and mortality were analyzed. RESULTS: 216 patients were included: 34 in Group 1, 95 in Group 2, and 87 in Group 3. Patientsreceiving LTOWB were more commonly male (p<0.001) and had a penetrating injury (p=0.005). Groups 1 and 3 had higher median ISS scores compared to Group 2 (19 and 20 vs 17; p=0.01). Group 3 received more median units of blood product in the first 4h (p<0.001) and in the first 24h (p<0.001). There was no difference between groups in 24h mortality or transfusion-related complications (all p>0.05). Arrival ED SBP was associated with LTOWB transfusion (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.95-1.00, p=0.03). ED lactate was independently associated with 24h mortality. (OR 1.27, CI 1.02-1.58, p=0.03). LTOWB transfusion was not associated with mortality (p=0.49). Abstract. CONCLUSION: Severely injured patients received LTOWB-CT and more overall product units but had similar 24 h mortality when compared with the LTOWB or CT groups. No increase in transfusion-related complications was seen after LTOWB transfusion. Low-titer O whole blood should be strongly considered in the resuscitation of trauma patients at civilian centers. LEVEL OF EVIDENCE: Retrospective, therapeutic, level IV.

Therapeutically-rational exchange (T-REX) of Gerbich-negative red blood cells can be evaluated in Papua New Guinea as "a rescue adjunct" for patients with Plasmodium falciparum malaria.

"Conventional exchange transfusion"-that delivers nondescript "standard issue" units of red blood cells (RBCs)-is used worldwide to rescue dying Plasmodium falciparum (Pf) malaria patients. Recently, exchanging special malaria-resistant RBCs (T-REX) has been recommended to prevent random delivery of malaria-susceptible RBCs that promote Pf infection. Fortunately, Papua New Guinea (PNG) is well positioned to help optimize exchange as "a rescue adjunct" because (a) Gerbich-negative (GN) RBCs that resist Pf invasion are prevalent in PNG; (b) with international support, PNG has conducted outstanding malaria research; (c) PNG's scientists feel studies of GN RBCs can advance malaria therapeutics; and (d) with blood-bank support, evaluating exchange of GN RBCs is feasible in PNG. An exchange-transfusion study of GN RBCs might attract international sponsorship given the threat of expanding drug-resistance as well as growing recognition that advancing transfusion medicine and expanding blood donation could especially help Pf-infected children-immediately.

Safety profile of high molecular weight polymerized hemoglobins.

BACKGROUND: Hemoglobin (Hb)-based oxygen (O2 ) carriers (HBOCs) are being developed as alternatives to red blood cells and blood when these products are unavailable. Clinical trials of previous HBOC generations revealed side effects, including hypertension and vasoconstriction, that were not observed in preclinical studies. Large molecular weight (MW) polymerized bovine Hb (PolybHb) represents a new class of HBOC with promising results. We evaluated the safety profile of PolybHb after an exchange transfusion (ET) in guinea pigs (GPs). This study compares changes in indices of cardiac, inflammatory, and organ function after ET with high (R-state) and low (T-state) O2 affinity PolybHb with high MW. STUDY DESIGN AND METHODS: Guinea pigs underwent a 20% ET with PolybHb. To assess the implication of PolybHb ET on the microcirculation, hamsters instrumented with a dorsal window chamber were subjected to a similar volume ET. RESULTS: T and R-state PolybHb did not induce significant alterations in cardiac function. T-state PolybHb induced mild vasoconstriction shortly after transfusion, while R-state did not have acute effects on microvascular tone. CONCLUSION: Large MW PolybHbs were found to be safe and efficacious in increasing O2 carrying capacity and the O2 affinity of the PolybHb did not affect O2 delivery or extraction by tissues in relevant preclinical models. In conclusion, these results suggest that both T-state and R-state PolybHb are safe and do not impair O2 delivery. The results are encouraging and support further evaluation of high MW PolybHbs and their future feasibility compared to allogenic blood in a trauma model.

Blood exchange transfusion in viral hepatitis in a small infant: a case report.

We report a case of blood exchange transfusion to treat acute liver failure following hepatitis B infection at the Infectious Disease Department of Children's Hospital No.2 in Ho Chi Minh City, Vietnam. A 3.5-month old baby boy was admitted to the hospital with a presentation of progressively worsening jaundice for the past one month. The patient was diagnosed with hepatitis B infection with a positive HBV DNA quantitative assay. Plasma exchange was indicated in view of progressive liver failure and gradually increasing hepatic coma. However, it was impossible to perform plasmapheresis in this case because the patient was small (in terms of age and weight) and there was no suitable plasma exchange filter. Accordingly, the patient was treated with 3 times of blood exchange transfusion in combination with an antiviral drug, lamivudine. After each blood exchange transfusion, the biochemical values (bilirubin, liver enzymes, and coagulation profile) gradually improved and he was discharged after 1 month of treatment. Blood exchange transfusion is an effective procedure for managing acute liver failure, where plasma exchange is not possible while waiting for the recovery of liver functions or liver transplantation.

Educational strategy for the development of skills in exchange transfusion: a randomized clinical trial protocol.

BACKGROUND: Exchange transfusion is a highly complex procedure that requires high levels of expertise. Trainee paediatricians do not have adequate training in exchange transfusion because opportunities to perform this procedure in practice are scarce. This protocol seeks to compare two educational interventions for exchange transfusion that allow students to develop competencies to perform the technique in an appropriate and safe way. METHODS/DESIGN: This is a randomized parallel single-blind clinical trial with allocation by simple randomization to the educational intervention (simulation or a digital didactic environment). Students from the paediatric specialization who volunteer to participate will be included. A practical evaluation of the procedure will be performed through a simulated scenario using a standardized clinical case. The main outcome is defined as the result of evaluation using the Objective Structured Clinical Examination; superior performance will be defined when the percentage is greater than or equal to 85%, and non-superior performance will be defined when the result is less than 84%. The chi-square independence test or the Fisher exact test will be used to evaluate the effect of the interventions. Multivariate analysis will be performed using a non-conditional logistic regression model. Stata 15® software will be used. DISCUSSION: Exchange transfusion is a procedure that requires expertise to achieve adequate outcomes. The inclusion of new educational strategies, such as simulation and digital didactic environments, is seen as a training option that can improve performance in clinical skills, reduce adverse events and increase the level of trust. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04070066. Registered on 28 August 2019. https://clinicaltrials.gov.

"Dual-gene" malaria-resistance: Therapeutically-rational exchange (T-REX) of group-O sickle trait and group-O C-traittrait red blood cells can be evaluated in Benin and Nigeria.

BACKGROUND: Using indicators of disease severity, clinicians can predict which Plasmodium falciparum (Pf) malaria patients being treated with artesunate or quinine are likely to die despite these drugs. Effective "rescue adjuncts" are needed when drugs alone are inadequate. "Therapeutically-rational exchange" (T-REX) of special malaria-resistant red blood cells (RBCs) has been proposed to optimize adjunctive exchange transfusion. METHODS: Studies were reviewed that (1) quantified how group-O status and "sickle-trait" (HbAS) and "C-trait" (HbAC) hemoglobins affect Pf mortality, risk of thrombosis, or birth outcomes for women with pregnancy associated malaria (PAM), (2) reported prevalences of "dual-gene" malaria-resistant RBCs, or (3) reflected the level of exchange-transfusion and malaria-related expertise in Benin and Nigeria. RESULTS: Data show that the malaria- and thrombosis-resistance of RBCs depend on specific genes and the patient's clinical status and medical history. In malaria-endemic Benin and Nigeria, prevalences of "dual-gene" malaria-resistant group-O HbAS and group-O HbAC RBCs are substantial, and both malaria- and exchange-related expertise are outstanding. CONCLUSIONS: T-REX of "dual-gene" malaria-resistant RBCs is feasible in Benin and Nigeria and warrants evaluation as a rescue adjunct for 3 subsets of Pf-malaria patients. For therapeutic use, group-O HbAS RBCs are likely to be more effective than non-O HbAS RBCs for Pf-infected patients who (1) have a history of thrombosis or (2) are taking birth-control hormones while group-O HbAC RBCs may substantially improve birth outcomes for women with PAM. Studies suggest it is prudent to assume - until proven otherwise - that T-REX of "dual-gene" malaria-resistant RBCs can improve ("personalize") rescue of these patient subsets.

Neonatal exchange transfusion: Experience in Korea.

BACKGROUND: Exchange transfusion (ET) is an established, efficacious, and reliable practice for severe neonatal hyperbilirubinemia, hemolytic disease of the newborn, and neonatal sepsis. This study assessed the indications and clinical outcomes of ET performed in a tertiary hospital in Korea. MATERIALS AND METHODS: We studied 64 ET sessions performed on 23 neonates between March 1999 and March 2018. ET was performed based on estimated double volume exchange transfusion using fresh red blood cells and fresh frozen plasma. Patients' clinical information, including demographic data and ET indication, and laboratory data were collected pre- and post-ET. RESULTS: The most common ET indication was hyperbilirubinemia with hemolytic anemia due to non-ABO maternal blood group discrepancies. In three preterm babies, ETs were performed for severe anemia, leukocytosis, and hyperkalemia cases. Before ET, the patients showed slightly high WBC counts, low hemoglobin levels, and low platelet counts. After ET, blood examination revealed normal WBC counts, increased hemoglobin levels, and decreased platelet counts (all P < 0.001). Bilirubin levels decreased immediately after ET (P < 0.001). Electrolyte and C-reactive protein levels showed no significant changes after ETs. Adverse events occurred in 11 (47.8 %) patients; the most common were hypoxemia and hypotension. One infant experienced cardiorespiratory arrest due to hypercalcemia and was successfully resuscitated. No one died within 24 h of ET. However, five infants showed hyperbilirubinemia aggravation. CONCLUSIONS: ET is an effective treatment modality for leukocytosis and hyperbilirubinemia with low mortality but involves common adverse events post-ET. This report provides an overview of current ET practices in Korea.

Pathology's historic 2019 incoming residents: Why "the internationalization of pathology" may markedly advance transfusion medicine and cellular therapeutics.

OBJECTIVES: This study had two objectives: (1) to determine if, in the United States of America (US), the proportion of non-US citizen international medical graduates (non-US IMGs) entering pathology residencies had increased (again) in 2019 and (2) to assess how this multi-year trend might impact transfusion medicine in the US. METHODS: The most recent (2019) "National Resident Matching Program" (NRMP) data were analyzed. To assess potential future impact, using controversies related to Plasmodium falciparum (Pf) malaria, conflicting US and non-US perspectives were reviewed. Differences between published US and non-US views were identified regarding, for example, the value of Pf-resistant ("variant") red blood cells (RBCs) and exchange transfusions. RESULTS: Year 2019 is the first year non-US IMGs were the largest group to fill residency-training positions for a major US specialty via the "Main Residency Match." Also notable, US and non-US views were found to differ markedly regarding (1) the value and safety of Pf-resistant RBC variants and exchange transfusions, and (2) the threat of drug-resistant Pf-malaria parasites. Non-US clinicians and researchers seem more concerned about Pf-malaria, and their interest in cellular therapies seems greater and more optimistic. CONCLUSIONS: In 2019, the historically high proportion of non-US IMGs among incoming pathology residents dramatically highlights the steady demographic shift that began years ago: "the internationalization of pathology" in the US. Fortunately, a review of publications related to exchange transfusion, Pf-malaria, and variant RBCs suggests non-US IMGs may markedly promote and advance cell therapies such as therapeutically-rational exchange (T-REX) of disease-resistant RBCs.

[Severe neonatal anemia due to fetomaternal hemorrhage: an ilustrative case]. / Anemia neonatal grave secundaria a transfusion feto-materna: a proposito de un caso.

Fetomaternal transfusion (FMT) is defined by the transfer of fetal blood into the maternal circulation. The incidence of massive FMT is estimated to be approximately 0.2-0.9 % of births. Although a number of etiologies have been associated with FMT, most causes remain unidentified and the pregnancy is usually asymptomatic. The most frequent symptom is the decrease in fetal movements (26 %) in relation to severe anemia. Several diagnostic modalities for FMT are described (Kleihauer stain, flow cytometry). We describe a case of a newborn with chronic anemia secondary to FMT who, after treatment with transfusions of red blood cells, presented volume overload and clinical worsening as a complication. In this case, our patient needed exchange transfusion for definitive improvement without disability.

La transfusión feto-materna es el paso de eritrocitos fetales a la circulación materna. Cuando es masiva, tiene una incidencia aproximada del 0,2-0,9 %. Generalmente, se desconoce el agente desencadenante, pero, en ocasiones, se pueden identificar factores de riesgo. En el embarazo, suele ser asintomática; el síntoma más frecuente es la disminución de los movimientos fetales (el 26 %) en relación con la anemia grave. Se diagnostica mediante la detección de hemoglobina fetal en la sangre materna (test de Kleihauer o citometría de flujo). Se presenta a un recién nacido con anemia crónica secundaria a la transfusión fetomaterna, que, después del tratamiento con transfusión de concentrado de hematíes, tuvo como complicación síntomas de sobrecarga de volumen y empeoramiento clínico. Tras la realización de una exanguinotransfusión, evolucionó favorablemente, sin secuelas.

Changes in total serum bilirubin during phototherapy in late preterm and term infants with non-haemolytic hyperbilirubinemia.

BACKGROUND: There is no standardized method for total serum bilirubin (TSB) monitoring during phototherapy for neonatal hyperbilirubinemia and national guidelines give heterogeneous indications. AIM: To assess the hypothesis that TSB values do not exceed exsanguino-transfusion (EXT) threshold during phototherapy and that it is possible to decrease its monitoring frequency in jaundiced infants. STUDY DESIGN: We carried out a prospective observational study in which changes in TSB during phototherapy for non-haemolytic hyperbilirubinemia were recorded in a cohort of late preterm and term infants. TSB values after 6, 12, 18, and 24 h of phototherapy were compared to the EXT threshold matched to infants' gestational and postnatal age according to the specific nomogram of the Italian Society of Neonatology guidelines. RESULTS: We studied 105 infants who started phototherapy at a mean age of 89 ±â€¯37 h when mean TSB was 17.1 ±â€¯2.5 mg/dL. We found that TSB decreased during phototherapy and the difference between mean TSB and EXT threshold progressively increased during phototherapy; TSB exceeded EXT threshold in none of our patients (0%). CONCLUSIONS: Our study demonstrates that differences between mean TSB and EXT threshold increased during phototherapy in late preterm and term infants with non-haemolytic hyperbilirubinemia; in none of our patients TSB exceeded EXT threshold. Our findings support the possibility of safely decreasing TSB monitoring during phototherapy, thus limiting noxious painful stimuli in neonates.

Optimizing exchange transfusion for patients with severe Babesia divergens babesiosis: Therapeutically-Rational Exchange (T-REX) of M antigen-negative and/or S antigen-negative red blood cells should be evaluated now.

Babesia divergens is an intraerythrocytic parasite, which is the major cause of babesiosis in Europe. For years, clinicians have been publishing stunning case reports that describe how some - but not all - conventional red blood cell (RBC) exchange transfusions have saved the lives of severely ill babesiosis patients. Due to markedly different patient outcomes, clinicians agree that new treatments and additional studies are needed. Here we argue that we should evaluate "therapeutically-rational exchange" (T-REX) in which the RBCs used to replace Babesia-parasitized RBCs are special disease-resistant RBC genetic variants (instead of the nondescript, "standard issue" RBCs used in conventional exchanges). T-REX seems prudent because with conventional exchange only some units of "standard issue" RBCs may be disease-resistant, while other units may not protect or may even promote disease. The random selection of RBCs for conventional RBC exchange may explain why clinical outcomes can vary dramatically. Fortunately, researchers have found that M antigen-negative (M-) and S antigen-negative (S-) RBCs resist invasion by B. divergens. Thus, we recommend evaluating T-REX of RBC variants that are B. divergens invasion-resistant: RBCs that are (1) M-, (2) S-, or (3) both M- and S-. By using only Babesia-resistant RBCs, T-REX eliminates the risk of unintentionally infusing Babesia-susceptible RBCs that might increase the severity of babesiosis. Because the T-REX variation of the conventional RBC exchange procedure is feasible, safe, and biologically plausible, we feel T-REX of Babesia-resistant RBCs should now be evaluated.