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.

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.

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.

Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload.

Children with sickle cell anemia (SCA) may be at risk of cerebral vasculopathy and strokes, which can be prevented by chronic transfusion programs. Repeated transfusions of packed red blood cells (PRBCs) is currently the simplest and most used technique for chronic transfusion programs. However, iron overload is one of the major side effects of this therapy. More developed methods exist, notably the apheresis of RBC (erythrapheresis), which is currently the safest and most efficient method. However, it is costly, complicated, and cannot be implemented everywhere, nor is it suitable for all patients. Manual exchange transfusions combine one or more manual phlebotomies with a PRBC transfusion. At the Reference Center of Sickle Cell Disease, we set up a continuous method of manual exchange transfusion that is feasible for all hospital settings, demands no specific equipment, and is widely applicable. In terms of HbS decrease, stroke prevention, and iron overload prevention, this method showed comparable efficiency to erythrapheresis. In cases where erythrapheresis is not available, this method can be a good alternative for patients and care centers.

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.

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%.

Routine administration of intravenous calcium during exchange blood transfusion for treatment of severe neonatal hyperbilirubinaemia: a systematic review of quantitative evidence protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to assess the effectiveness of intravenous calcium given during exchange blood transfusion (EBT) in neonates.More specifically, the objectives of the review are to determine whether: BACKGROUND: Neonatal hyperbilirubinaemia is an abnormally high level of bilirubin in the circulating blood, resulting in clinically visible icterus or jaundice. A serum bilirubin level above 5 mg per dL (86 µmol per L) is a frequently encountered problem worldwide and is a common reason for neonates to present to the emergency department.Unconjugated bilirubin is toxic to infants' brains when the concentration exceeds a certain level. An unconjugated serum bilirubin concentration at toxicity level is described as 'severe hyperbilirubinaemia'. The concentrations that define toxic level vary, depending on the gestational age of the neonates and fetal maturity.Severe hyperbilirubinaemia can cause encephalopathy if not promptly treated, with significant complications such as athetoid cerebral palsy, sensorineural hearing loss, paralysis of upward gaze, dental enamel dysplasia and death.Recent reports indicate that these conditions, though rare, are still occurring despite the availability of efficient methods for treatment of hyperbilirubinaemia and its prevention.These complications can be prevented if the level of bilirubin is reduced rapidly with exchange blood transfusion.Exchange blood transfusion (EBT) is the most rapid and effective method for lowering serum bilirubin concentrations, but it is rarely needed when intensive phototherapy is effective.In the presence of hemolytic disease, severe anaemia, or a rapid rise in the total serum bilirubin level (greater than 1 mg per dL per hour in less than six hours), EBT is the recommended treatment. EBT also removes partially hemolyzed and antibody-coated erythrocytes and which is then replaced with uncoated donor red blood cells. If intensive phototherapy fails to lower the bilirubin level, then EBT is always considered as the next line of treatment in any newborn with non-hemolytic jaundice.Complications of EBT can include hypocalcaemia, seizures and even death within 24 hours. The potential seriousness of these complications makes clinicians consider intensive phototherapy before EBT.However, the option of intensive phototherapy may not be feasible and could be quite ineffective in resource limited settings where the required facilities and electrical power supply are inadequate. Under these circumstances neonates with severe hyperbilirubinaemia will most likely be treated with EBT.Exchange transfusion of blood collected with acid-citrate-dextrose (ACD) containing bags may produce hypocalcaemia.To decrease the morbidity from chelation of divalent cations by citrate, routine administration of calcium gluconate during EBT was advocated,but tetany, convulsion and death may still occur when ACD blood is used.However, there are controversies about the effectiveness of intravenous calcium in reducing these calcium-related morbidities. A preliminary search for systematic reviews in MEDLINE, the Cochrane Library, Campbell Library and the Joanna Briggs Database of Systematic Reviews and Implementation Reports failed to identify any existing publications on this topic. As a result, this review will examine current quantitative evidence regarding the effectiveness of routine administration of intravenous calcium during EBT in the treatment of severe hyperbilirubinaemia, with specific aim to describe incidences of hypocalcaemia, seizures and deaths after such a transfusion.

Exchange transfusion in patients with Down syndrome and severe transient leukemia.

BACKGROUND: Among neonates with Down syndrome (DS) and transient leukemia (TL), hyperleukocytosis (white blood cell [WBC] count >100 × 10(9) /L) is associated with increased blood viscosity, respiratory failure due to pulmonary hypertension, multiorgan failure, and increased risk of early death. There have been no previous studies focusing on the effects of exchange transfusion (ExT) on WBC count, respiratory status, and other parameters in TL patients with hyperleukocytosis. METHODS: An observational retrospective study was carried out at a single center of all five DS neonates with TL, GATA1 mutations, and hyperleukocytosis, born at a median gestational age of 34 weeks (range, 30-38 weeks) with birthweight 2556 g (range, 1756-3268 g) during a 24 month study period between September 2011 and August 2013. All five neonates underwent ExT at a median age of 2 days (range, 0-5 days) before initiation of other cytoreductive therapy with cytarabine, which was carried out in two patients. RESULTS: All patients required respiratory support before ExT. After ExT, respiration status improved in all five patients: WBC count (mean) decreased by 85% from 143 × 10(9) /L to 21 × 10(9) /L. None developed tumor lysis syndrome. Three survived and two died: one hydrops fetalis neonate born at gestational week 30 died at age 5 days, and another died eventually from acute gastroenteritis 40 days after leaving hospital at the age of 155 days with complete remission. Two of the three surviving neonates developed acute megakaryocytic leukemia at age 90 days and 222 days. CONCLUSION: ExT was very effective in improving hyperleukocytosis and may have had favorable effects on respiration.

Exchange transfusion as a life-saving intervention in three patients with different haematological malignancies with severe hyperleukocytosis where leukapheresis was not available.

Hyperleukocytosis is a rare but potentially serious complication of haematological malignancies. It is usually treated with rehydration, prevention of tumour lysis syndrome and the administration of cytotoxic therapy. Leukapheresis may be life-saving in emergency cases. In this article we describe how, in a resource-limited setting where leukapheresis was not available, manual exchange transfusion was utilised as a life-saving intervention in three patients with different haematological malignancies complicated by hyperleukocytosis. Further we outline the procedure that was carried out and evaluated possible complications associated with this rarely used practice.

Exanguinotransfusión parcial en un paciente con anemia falciforme homocigota sometido a cirugía cardíaca con circulación extracorpórea: reporte de caso / Partial exchange transfusion in a patient with homozygous sickle cell disease undergoing heart surgery with cardiopulmonary bypass: a case report

En pacientes con anemia falciforme, el circuito de circulación extracorpórea promueve la polimerización de la hemoglobina y la formación de drepanocitos. La exanguinotransfusión reduce los niveles circulantes de hemoglobina S. Reportamos el manejo de un niño con anemia falciforme homocigótica que requirió cirugía de cierre de comunicación interauricular. Se realizó exanguinotransfusión parcial intraoperatoria disminuyendo los niveles de hemoglobina S de 89 por ciento a 23 por ciento. La circulación extracorpórea fue conducida en normotermia utilizando cardiología fría, realizando el procedimiento quirúrgico en paro sinusal.

In patients with sickle cell anemia, the extracorporeal circulation circuit promotes the polymerization of hemoglobin and sickle cell formation. Exchange transfusion reduces circulating levels of hemoglobin S. We report the management of a child with homozygous sickle cell anemia who required surgical closure of atrial septal defect. Partial intraoperative exchange transfusion was performed that decreased hemoglobin S levels from 89 percent to 23 percent. Cardiopulmonary bypass was conducted at normothermia with cold blood cardioplegia and the surgical procedure was performed in sinus arrest.

Acute lymphoblastic leukemia with hyperleukocytosis, sinus pauses, and hypoxemic respiratory failure in an infant.

A 5-month-old female infant presented with new-onset acute lymphoblastic leukemia and hyperleukocytosis with white blood cell count of 352 × 10(9) cells/L. She developed sinus pauses and hypoxemic respiratory failure. A manual single volume exchange blood transfusion was done with complete resolution of sinus pauses and hypoxemia.

Exchange transfusion before cardiopulmonary bypass in sickle cell disease.

Cardiac operations in patients with sickle cell disease present the surgical team with many challenges. We describe a method of complete intraoperative exchange transfusion in the operating room that reduces the hemoglobin S (Hb S) level to less than 5%, without preoperative exchange transfusions. Plasma and platelet fractions separated intraoperatively from the patient's native red cell mass were used, in addition to hemoconcentration while on cardiopulmonary bypass, to effectively reduce the red cell and clotting factor transfusion requirements after the procedure. The technique is useful in reducing transfusion requirements, avoiding cardiovascular stress associated with exchange transfusion before the operation, and can be used in urgent situations.

Partial-exchange blood transfusion: an effective method for preventing mortality in a child with propofol infusion syndrome.

Here we describe a case of propofol-related infusion syndrome (PRIS) in a child with malignant refractory status epilepticus treated with partial-exchange blood transfusion (PEBT), an innovative method of resuscitation that has the potential to reduce the mortality rate associated with this syndrome. Our patient is a 4-year-old boy with malignant status epilepticus associated with bacterial meningitis. Propofol was used because of persistent seizure activity refractory to adequate doses of phenytoin, phenobarbital, levetiracetam, and midazolam infusion at 0.7 mg/kg per hour. Propofol was escalated from 0.6 mg/kg per hour to an electroencephalogram-burst-suppressing dose of 15.6 mg/kg per hour. Signs of PRIS were noticed after 48 hours on propofol. The severe bradycardia responded only to infusions of calcium gluconate. PEBT corrected all the cardiac abnormalities and returned enough hemodynamic stability to permit continuous veno-venous hemodialysis for renal failure and removal of toxins. PEBT is a safe and innovative option for correcting the metabolic abnormalities that result in cardiac dysfunction, which is typically the most serious and usually terminal event in PRIS. When done with small aliquots, it avoids the severe hemodynamic instability that is usually a hindrance with hemodialysis, continuous veno-venous hemodialysis, and extracorporeal membrane oxygenation, which are other methods of supporting these children during the crisis that are mentioned in the literature.

A palliative care approach in treating patients with sickle cell disease using exchange transfusion.

The authors present a case report of an adult patient with sickle cell disease (SCD), who required frequent hospitalizations for sickle cell vaso-occlusive painful crisis as well as management of complications that resulted from treatment. The patient demonstrated clinical improvement after initiating palliative exchange transfusions of packed red blood cells (PRBCs) once every 4 weeks. They also promptly addressed their physical and psychosocial issues of care. The author described that because the patient was started on chronic exchange transfusions, there was a significant decrease in hospitalizations and emergency department (ED) visits. They saw a major improvement in the quality of life of this patient. The review of medical literature did not reveal any clear-cut guidelines for palliative chronic exchange transfusion for painful vaso-occlusive crisis in adult patients. This case review highlights the usefulness of this palliative model of care. The burden and benefits of chronic exchange transfusion always need to be weighed carefully.

Severe iron intoxication treated with exchange transfusion.

An 18-month-old previous healthy girl who had ingested 442 mg elemental iron/kg was admitted to a paediatric intensive care unit. The child was treated with gastric lavage, whole bowel irrigation and intravenous deferoxamine. After 2 h of standard therapy serum iron had risen threefold to 1362 microg/dl (244 micromol/l). The child was treated with exchange transfusion (ET; 52 ml/kg) and serum iron fell to 134 microg/dl (24 micromol/l). The patient made an uncomplicated recovery. ET should be considered in severe iron poisoning when standard therapy is inadequate.

Mitral valve replacement in a patient with sickle cell disease using perioperative exchange transfusion.

Sickle cell disease is a genetic hemoglobinopathy in which a significant number of red blood cells carry hemoglobin-S as opposed to normal red blood cells that contain hemoglobin-A. Under certain conditions such as hypoxia, acidosis, and hypothermia, the red blood cells containing hemoglobin-S will sickle, leading to occlusion of the microvasculature. As such, patients with sickle cell disease present unique challenges during heart surgery using cardiopulmonary bypass (CPB). After conducting a literature review, we discovered that the exact hemoglobin-S level for conducting cardiac surgery with CPB is not known. However, a hemoglobin-S level < 30% is considered safe for conducting CPB. The following case report will discuss these challenges and present a patient with sickle cell disease undergoing a mitral valve repair. Management of this patient involved exchange transfusions both preoperatively and intraoperatively.

Perioperative management of sickle cell disease in paediatric cardiac surgery.

In sickle cell disease, cardiopulmonary bypass may induce red cell sickling. Partial exchange transfusion reduces the circulating haemoglobin S level. We report the management of a child with sickle cell disease who required surgical closure of a ventricular septal defect. Preoperative exchange transfusion of 50% of the total blood volume was performed with fresh packed red cells over three days. Further exchange transfusion was performed as cardiopulmonary bypass commenced. The haemoglobin S level was reduced from 76% to 37%. The blood removed from the patient during the exchanges was processed allowing storage and re-infusion of the patient's plasma and platelets. Combined preoperative and intraoperative exchange transfusions, instead of a single stage 50% volume exchange, was effective and potentially avoids larger haemodynamic effects. Cardiopulmonary bypass was conducted at normothermia and cold cardioplegia was avoided (fibrillatory arrest was used during the surgical repair).

O2-binding albumin thin films: solid membranes of poly(ethylene glycol)-conjugated human serum albumin incorporating iron porphyrin.

Poly(ethylene glycol) (PEG)-conjugated human serum albumin (HSA) incorporating the tetrakis(alpha,alpha,alpha,alpha-o-amidophenyl)porphinatoiron(II) derivative (FeP) [PEG(HSA-FeP)] is a unique plasma protein-based O2 carrier as a red blood cell substitute. The aqueous solution of PEG(HSA-FeP) [mw of PEG: 2-kDa (PEG2) or 5-kDa (PEG5)] was evaporated on a glass surface to produce a red-colored solid membrane. Scanning electron microscopy observations revealed that the PEG2(HSA-FeP) membrane consisted of two parts: (i) a surface layer made of a fibrous component (10 microm thickness), and (ii) a bottom layer of an amorphous phase (5 microm thickness). The condensed solution provided a thick membrane (70 microm), which also has the amorphous bottom layer. On the other hand, the PEG5(HSA-FeP) produced homogeneous membrane made of the fibrous component. The FeP active sites in the solid membrane formed very stable O2-adduct complexes at 37 degrees C with a half-lifetime of 40 h. The O2-binding affinity of the PEG2(HSA-FeP) membrane (P1/2 = 40 Torr, 25 degrees C) was 4-fold lower than that in aqueous solution, which is kinetically due to the low association rate constant. The membrane was soluble again in water and organic solvents (ethanol and chloroform) without deformation of the secondary structure of the protein. The addition of hyaluronic acid gave a free-standing flexible thin film, and it can also bind and release O2 as well. These O2-carrying albumin membranes with a micrometer-thickness would be of significant medical importance for a variety of clinical treatments.