Fetomaternal Hemorrhage and Choriocarcinoma: A Case Report.

BACKGROUND: This case describes chronic anemia of a late preterm infant secondary to maternal-fetal hemorrhage and subsequent findings of maternal choriocarcinoma. CLINICAL FINDINGS: This infant was born at 35 6/7 weeks gestational age via cesarean section for non-reassuring fetal heart tones. The mother presented with decreased fetal movement and the biophysical profile was 4/8. Following delivery, the infant did not require respiratory support, was vigorous with extreme pallor, and had a hemoglobin of less than 5 on cord gas. PRIMARY DIAGNOSIS: Chronic anemia secondary to fetomaternal hemorrhage. INTERVENTIONS: The infant's initial hemoglobin was 2.4 and hematocrit was 8.1. The mother's Kleihauer-Betke test was elevated at 7%. The infant required a partial exchange transfusion following admission to the neonatal intensive care unit. Following the partial exchange transfusion, the infant began to experience increasing respiratory distress and required respiratory support. An echocardiogram showed severe persistent pulmonary hypertension of the neonate. The mother was subsequently diagnosed with choriocarcinoma. OUTCOMES: The infant fully recovered from chronic anemia and persistent pulmonary hypertension of the neonate and was discharged home with the mother. The infant required follow-up testing for choriocarcinoma outpatient. PRACTICE RECOMMENDATIONS: Newborns diagnosed with early chronic anemia should be evaluated, the cause investigated, and appropriate treatment considered. If the cause of blood loss is unknown, a maternal Kleihauer-Betke test should be considered. In this case, a partial exchange transfusion was performed to avoid cardiovascular volume overload, but another course of treatment could include small aliquots of packed red blood cell transfusions.

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.

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.

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.

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.

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.

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.

"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.

Can Exchange Transfusion Normalize Serum Levels of Copper, Zinc, and Magnesium in Severe Neonatal Hyperbilirubinemia?

BACKGROUND: Neonatal hyperbilirubinemia is a frequently encountered problem. Erythrocytes, especially reticulocytes are rich in copper (Cu) and magnesium (Mg) so its serum levels increase after hemolysis. Zinc (Zn) plays an important role in synthesis of some enzymes included in the bilirubin metabolism and may cause hemolysis. Exchange transfusion is the main treatment for severe neonatal hyperbilirubinemia but can exchange transfusion affect the previous trace elements. MATERIALS AND METHODS: We measured Cu, Zn, and Mg serum levels in full-term neonates admitted to neonatal intensive care unit of Minia University hospital with severe indirect hyperbilirubinemia before and after exchange transfusion. RESULTS: There were significant higher serum Cu and Mg and lower Zn serum levels in neonates with hyperbilirubinemia than controls and their levels were significantly normalized after exchange transfusion. Significant positive correlations between the total bilirubin levels and hemoglobin, Cu and Mg serum levels and significant negative correlations with Zn levels were present. There were no significant correlations between maternal and neonatal serum levels of any of them. CONCLUSIONS: Exchange transfusion can normalize the significant higher Cu and Mg and lower Zn serum levels in neonates with severe indirect hyperbilirubinemia which were not related to their maternal serum levels.

With a simple calculation, the fraction of platelets remaining can be used to estimate the residual hemoglobin S percentage in sickle cell disease patients undergoing automated red blood cell exchange.

OBJECTIVES: Automated red blood cell exchange (RBX) is an important treatment for patients with sickle cell disease (SCD). Although not specifically targeted for removal, platelets (PLTs) are collected along with red blood cells during RBX. We sought to determine whether the pre- and post- RBX PLT counts could be used to derive the post-procedure hemoglobin S% (HgbS%). METHODS: Using the pre- and post- RBX lab values of 59 SCD patients undergoing 112 RBX procedures over 1 year, we derived mathematical formulas which estimate the post-RBX HgbS% based on the pre-RBX HgbS%, the pre- and post- RBX PLT, and a correction factor. RESULTS: For patients with pre-RBX HgbS > 40%, the mathematically derived post-RBX HgbS% was statistically indistinguishable from the measured post-RBX HgbS%. CONCLUSIONS: Using a simple formula, pre- and post-RBX platelet counts can provide a rapid approximation of the measured post-RBX HgbS% in patients with SCD.

From total blood exchange to erythrocytapheresis and back to treat complications of sickle cell disease.

Erythrocytapheresis is an important procedure in the management of certain complications of sickle cell disease, including acute stroke, stroke prevention, acute chest syndrome, and multiorgan failure. Erythrocytapheresis in sickle cell disease simply entails the removal of the patient's red blood cells containing the abnormal sickle hemoglobin and replacing them with normal red blood cells carrying normal hemoglobin. In these procedures, the patient's plasma is not exchanged but is returned to the patient. Several studies have demonstrated that the plasma of patients with sickle cell disease contains several components that increase blood viscosity and initiate or promote vaso-occlusion. These factors include increased levels of globulins, especially immunoglobulin G, acute-phase reactants, fibrinogen, coagulation factors, inflammatory mediators, and heme in the steady state and increase further during painful crises. This may explain why, in certain complications of sickle cell disease, such as acute chest syndrome, hepatic crisis, and priapism, erythrocytapheresis by itself may not be effective despite repetitive cycles of red blood cell exchange. The use of therapeutic plasma exchange in addition to erythrocytapheresis in these situations seems to be useful in resolving them more efficiently. The role of therapeutic plasma exchange in the management of certain complications of sickle cell disease needs further evaluation. This commentary addresses the role of therapeutic plasma exchange in the management of complications of sickle cell disease.

A 5-year cost analysis of automated red cell exchange transfusion for the management of recurrent painful crises in adult patients with sickle cell disease.

The painful vaso-occlusive crisis is the most common acute manifestation of sickle cell disease resulting in poor quality of life and high utilisation of hospital facilities. The main disease modifying strategy is treatment with hydroxycarbamide. For patients intolerant or who fail hydroxycarbamide, chronic transfusions are an alternative. Automated red cell exchange transfusion (ARCET) are more effective in lowering rapidly the HbS level while avoiding iron overload. As they require specialised equipment and specially trained staff while utilising higher volumes of blood, there have been concerns regarding the costs involved. We retrospectively analysed data on 23 patients who have been on a regular programme for 1-5 years and found that their utilisation of hospital services reduced by 20%, 48%, 58%, 71%, and 79% after 1, 2, 3, 4 and 5 years respectively. The overall mean annual cost of care per patient was £9702 and £2378 higher than baseline after the 1st and 2nd years of ARCET respectively and then reduced by £5486, £8317, and £14,664 after the 3rd, 4th and 5th year of ARCET respectively indicating that ARCET leads to cost savings to health services in the medium to long term due to reduction in hospital attendance of these patients.

Effectiveness of red blood cell exchange, partial manual exchange, and simple transfusion concurrently with iron chelation therapy in reducing iron overload in chronically transfused sickle cell anemia patients.

BACKGROUND: Chronic transfusion therapy (CTT) is indicated for stroke prevention in children with sickle cell anemia (SCA) and is complicated by iron overload and alloimmunization. CTT is performed by simple transfusion (ST), partial manual exchange (PME), or erythrocytapheresis (RCE). Although small case series have demonstrated RCE in combination with iron chelation therapy stabilizes and/or decreases ferritin, there are no reports comparing the effect of ST, PME, and RCE on liver iron concentration (LIC). CTT modality effect on serum ferritin and LIC were compared in SCA patients on iron chelation, with hemoglobin (Hb)S goal of 30%. STUDY DESIGN AND METHODS: Medical records of SCA patients on CTT and deferasirox (≥25 mg/kg/day) were retrospectively reviewed. Mean HbS%, change in ferritin and LIC, and alloimmunization rate were determined for each CTT group. RESULTS: Twenty-eight patients were included; six crossed over (one from ST to PME, one from ST to PME then to RCE, three from ST to RCE, and one from PME to RCE) to include 36 transfusion modality intervals. Median pretransfusion HbS% levels were 32.7% (ST), 36.2% (PME), and 34.7% (RCE; p = 0.732). Median ferritin changes were +15 (-17 to +45), +38 (+24 to +105), and -91 (-141 to -48) ng/mL/month (p = 0.003), and median LIC changes (available in 22 patient transfusion modality intervals) were +1.3 (-1.6 to +4.3), +2.3 (-6.5 to +8.9), and -5.7 (-10.7 to -0.5) mg/g/year (p = 0.024) in ST, PME, and RCE, respectively. There was no significant difference in alloimmunization rate between ST/PME and RCE groups. CONCLUSION: We recommend RCE plus chelation as an effective method for reducing iron overload, while maintaining HbS at 30% to 35%.

Comparison of automated erythrocytapheresis versus manual exchange transfusion to treat cerebral macrovasculopathy in sickle cell anemia.

BACKGROUND: Chronic exchange transfusion is effective for primary and secondary prevention of stroke in children with sickle cell anemia (SCA). Erythrocytapheresis is recognized to be the most efficient approach; however, it is not widely implemented and is not suitable for all patients. The aim of our study was to compare automated exchange transfusion (AET) with our manual method of exchange transfusion and, in particular, to evaluate the efficacy, safety, and cost of our manual method. STUDY DESIGN AND METHODS: Thirty-nine SCA children with stroke and/or abnormal findings on transcranial Doppler were included in the study. We retrospectively analyzed 1353 exchange sessions, including 333 sessions of AET and 1020 sessions of manual exchange transfusion (MET). RESULTS: Both methods were well tolerated. The median decrease in hemoglobin (Hb)S per session was 21.5% with AET and 18.8% with our manual method (p < 0.0001) with no major increase in red blood cell consumption. Iron overload was well controlled, even with the manual method, with a median (interquartile range) ferritin level of 312 (152-994) µg/L after 24 months of transfusions. The main differences in annual cost relate to equipment costs, which were 74 times higher with the automated method. CONCLUSION: Our study shows that continuous MET has comparable efficacy to the automated method in terms of stroke prevention, decrease in HbS, and iron overload prevention. It is feasible in all hospital settings and is often combined with AET successively over time.

Exchange Transfusion in the Treatment of Neonatal Septic Shock: A Ten-Year Experience in a Neonatal Intensive Care Unit.

Septic shock, occurring in about 1% of neonates hospitalized in neonatal intensive care unit (NICU), is a major cause of death in the neonatal period. In the 1980s and 90s, exchange transfusion (ET) was reported by some authors to be effective in the treatment of neonatal sepsis and septic shock. The main aim of this retrospective study was to compare the mortality rate of neonates with septic shock treated only with standard care therapy (ScT group) with the mortality rate of those treated with ScT and ET (ET group). All neonates with septic shock admitted to our NICU from 2005 to 2015 were included in the study. Overall, 101/9030 (1.1%) neonates had septic shock. Fifty neonates out of 101 (49.5%) received one or more ETs. The mortality rate was 36% in the ET group and 51% in the ScT group (p = 0.16). At multivariate logistic regression analysis, controlling for potentially confounding factors significantly associated with death (gestational age, serum lactate, inotropic drugs, oligoanuria), ET showed a marked protective effect (Odds Ratio 0.21, 95% Confidence Interval: 0.06-0.71; p = 0.01). The lack of observed adverse events should encourage the use of this procedure in the treatment of neonates with septic shock.

Mortality increases after massive exchange transfusion with older stored blood in canines with experimental pneumonia.

Two-year-old purpose-bred beagles (n = 24) infected with Staphylococcus aureus pneumonia were randomized in a blinded fashion for exchange transfusion with either 7- or 42-day-old canine universal donor blood (80 mL/kg in 4 divided doses). Older blood increased mortality (P = .0005), the arterial alveolar oxygen gradient (24-48 hours after infection; P ≤ .01), systemic and pulmonary pressures during transfusion (4-16 hours) and pulmonary pressures for ~ 10 hours afterward (all P ≤ .02). Further, older blood caused more severe lung damage, evidenced by increased necrosis, hemorrhage, and thrombosis (P = .03) noted at the infection site postmortem. Plasma cell­free hemoglobin and nitric oxide (NO) consumption capability were elevated and haptoglobin levels were decreased with older blood during and for 32 hours after transfusion (all P ≤ .03). The low haptoglobin (r = 0.61; P = .003) and high NO consumption levels at 24 hours (r = −0.76; P < .0001) were associated with poor survival. Plasma nontransferrin-bound and labile iron were significantly elevated only during transfusion (both P = .03) and not associated with survival (P = NS). These data from canines indicate that older blood after transfusion has a propensity to hemolyze in vivo, releases vasoconstrictive cell-free hemoglobin over days, worsens pulmonary hypertension, gas exchange, and ischemic vascular damage in the infected lung, and thereby increases the risk of death from transfusion.

In a canine pneumonia model of exchange transfusion, altering the age but not the volume of older red blood cells markedly alters outcome.

BACKGROUND: Massive exchange transfusion of 42-day-old red blood cells (RBCs) in a canine model of Staphylococcus aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin-bound iron (TBI), non-transferrin-bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7-day-old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs. STUDY DESIGN AND METHODS: Two-year-old purpose-bred infected beagles were transfused with increasing volumes (5-10, 20-40, or 60-80 mL/kg) of either 42- or 7-day-old RBCs (n = 36) or 80 mL/kg of either unwashed or washed RBCs with increasing storage age (14, 21, 28, or 35 days; n = 40). RESULTS: All volumes transfused (5-80 mL/kg) of 42-day-old RBCs resulted in alike (i.e., not significantly different) increases in TBI during transfusion as well as in CFH, lung injury, and mortality rates after transfusion. Transfusion of 80 mL/kg RBCs stored for 14, 21, 28, and 35 days resulted in increased CFH and NTBI in between levels found at 7 and 42 days of storage. However, washing RBCs of intermediate ages (14-35 days) does not alter NTBI and CFH levels or mortality rates. CONCLUSIONS: Preclinical data suggest that any volume of 42-day-old blood potentially increases risks during established infection. In contrast, even massive volumes of 7-day-old blood result in minimal CFH and NTBI levels and risks. In contrast to the extremes of storage, washing blood stored for intermediate ages does not alter risks of transfusion or NTBI and CFH clearance.