Administration Of Red Blood Cells Research Articles

Immunologic Responder Groups.

Abstract SCI-47Transfusion medicine has long recognized that there is significant variation in the human immune response to red blood cell (RBC) transfusions.1 All allogeneic RBC transfusions expose the recipient to multiple foreign antigens, but very few RBC transfusions induce a detectable humoral immune response. Using statistical analyses of antibody responses among transfused patient populations, we found that the response closely approximates a geometric distribution that would be predicted by a random memory-less (stochastic) process. These statistical analyses demonstrate that most patients fail to mount immune responses to RBC transfusions but a distinct group of patients, termed potential responders, is capable of mounting an immune response to blood transfusions. Potential responders comprise approximately 13% of the transfused population and this proportion does not depend on pathologic diagnoses, age, gender or racial group. The only group that has a higher rate of potential responders are pregnant women, but those patients have a second route of antibody exposure. Although the ability to immunologically respond to blood transfusions appears to be limited to the relatively small population of potential responders, even potential responders do not mount an immune response to most RBC transfusions. Additionally, the specific antibodies that patients make are not completely independent of each other. Indeed, patients who have made some specific antibodies are more likely to subsequently make one set of anti-erythrocyte antibodies and less likely to make another set of anti-erythrocyte antibodies. This suggests that the potential immune repertoire differs between patients and the difference in potential repertoire is not solely explained by the antigens expressed on the patients' erythrocytes. Moreover, the potential repertoire is influenced by the age of the patient. Younger patients have a more diverse immune response producing antibodies against a broad spectrum of RBC antigens. As patients get older, the immune response becomes more limited and usually only responds against the most immunogenic RBC antigens. In summary, these results suggest that potential responders to intravenous administration of RBCs comprise a genetically distinct group and that additional factors determine which transfusion will induce an immune response in potential responders. The factors that cause a person to be a potential responder and the factors that cause a potential responder actually respond to a specific transfusion are subjects of ongoing research. In the meantime, transfusion services may consider minimizing immunologic stimuli to patients who are clearly responders. 1. Higgins JM, Sloan SR. Stochastic modeling of human RBC alloimmunization: evidence for a distinct population of immunologic responders. Blood. 2008;112:2546-2553. DisclosuresNo relevant conflicts of interest to declare.

The German Haemovigilance System–reports of serious adverse transfusion reactions between 1997 and 2007

Data of the German Haemovigilance System were collected from 1997 to 2007 and assessed on the basis of pre-defined safety standards. Suspected cases of serious adverse reactions following transfusions reported to the Paul-Ehrlich-Institut were evaluated on the basis of national criteria, and the definitions of International Society of Blood Transfusion (ISBT) in compliance with defined causality criteria. The suspected cases were rated as confirmed and unconfirmed transfusion reactions. Assessment of causality took into consideration the clinical course of the adverse reaction and, if necessary, information about donation and manufacturing. Of the 5128 suspected serious adverse reactions, 1603 could be confirmed. Referring to the absolute figures, acute transfusion reactions (e.g. allergic reactions, hypotension and dyspnoea) were recorded most frequently, followed by transfusion-related acute lung injury (TRALI), haemolytic reactions, transfusion-related bacterial infections and virus infections. The majority of the 52 transfusion-related fatalities (14 each) were due to TRALI and acute transfusion reactions (mostly severe allergic reactions). Referred to the blood products administered, immune TRALI cases and TRALI-related fatal courses were most frequently reported after administration of fresh frozen plasma (FFP) (15/10(6) and 3.5/10(6) units, respectively), transfusion-related bacterial infections after administration of platelet concentrates (7/10(6) units), acute haemolytic transfusion reactions after administration of red blood cell concentrates (2.3/10(6)units) and acute transfusion reactions after administration of red blood cell or platelet concentrates (7.8/10(6) and 13/10(6) units, respectively). Despite the high safety standard required for blood products in Germany, there is still room for reducing the frequency of isolated cases of transfusion reactions by targeted action.

Temporal Pattern of Transfusion and Its Relation to Rejection After Lung Transplantation

Blood transfusion has been shown to impact rejection after renal and cardiac transplantation, but it has not been studied after lung transplantation (LTx). In this study we assess: (1) patterns of transfusion, and (2) temporal interrelationships with histologic evidence of rejection. From July 1998 to January 2006, 326 of 331 patients undergoing LTx had available for study both time-related post-operative blood transfusion data and their series of transbronchial biopsy evaluations of perivascular rejection grade (Grades A0 to A4). Longitudinal temporal decomposition for ordinal variables was used to characterize prevalence of rejection grade and simultaneously assess the influence of (a) red blood cell (RBC), (b) platelet and (c) plasma administration. Although peri-operative transfusion was common, transfusions continued at a low, steady rate throughout the life of LTx patients; patients received a total of 2,841 RBC units through follow-up. Immediately after LTx, the prevalence of Grade A0 rejection was 51%, and this increased to 84% by 6 months. RBC transfusion between biopsies was associated with lower histologic grade of rejection (70%, 73% and 77% with Grade A0 for 0, 1 and 12 units, respectively; p = 0.009), and this was particularly evident early after LTx. Histologic grade was not influenced by platelets or plasma. Transfusion requirements are high and continue throughout life after LTx; causes and effective treatment of persistent anemia should be sought. RBC transfusion appears to have an immunosuppressive effect, particularly early after transplant.

Pure red cell aplasia associated with hemolytic anemia refractory to standard measures and resolved by rituximab in an elderly patient

Acquired pure red cell aplasia (PRCA) simultaneously associated with autoimmune hemolytic anemia (AIHA) has been very rarely described so far [1, 2]. We describe the case of an elderly woman, who was diagnosed as having idiopathic PRCA associated with AIHA which was unresponsive to two lines of immunosuppressive treatment and was then resolved by rituximab given as salvage therapy. A 68-year-old woman kept under our attention because of severe malaise, pallor and fatigue. Her past medical history was unremarkable; in particular, she denied any personal or familiar history of hereditary hemolytic anemia or autoimmune diseases. A past blood count had shown normal hemoglobin. Physical examination at admission was unremarkable, with the exception of pallor and mild jaundice; the patient did not present either spleen or liver enlargement. A comprehensive laboratory evaluation revealed no abnormalities other than those related to anemia and hemolysis. Indeed, severe normochromic and normocytic anemia (hemoglobin, Hb = 2.7 g/dl) was revealed. Reticulocytes were not detectable; white blood cell and platelet counts were normal. Increased indirect serum bilirubin, urinary urobilinogen and serum lactate dehydrogenase were present; serum haptoglobin was undetectable. Direct and indirect Coombs tests were positive. A warm-reactive antibody of the IgG isotype was eluted from the red blood cells (RBC). Serologic tests for parvovirus B19, HIV, Hepatitis virus, human cytomegalovirus, and Epstein-Barr virus were negative. Moreover, no clinical and/or laboratory signs of associated autoimmune disease were detected. Chest X-ray and total body CT scan showed normal findings. On the blood film, spherocytes and polychromasia were found. A bone marrow (BM) aspirate and a trephine biopsy demonstrated normal representation of myeloid and megakaryocytic precursors, but nearly absent erythroid precursors. Based on these findings, a diagnosis of AIHA combined to PRCA was made. Given the symptomatic anemia and the very low Hb levels, the patient received repeated administration of RBC concentrates. Methylprednisolone 2 mg/kg was given for 4 weeks without any benefit; equally ineffective was the concomitant treatment with cyclosporine-A (CSA) during the following 4 weeks. Therefore, in the light of reported experiences concerning the treatment of AIHA [3] and PRCA [2], the patient was offered rituximab as salvage therapy for which she gave her informed consent. Rituximab was administered intravenously at the dose of 375 mg/m as a 4-h infusion, once weekly for a total of four doses, without any adverse reaction or side effects (July 2007). Progressive increase of Hb levels and achievement of transfusion independence followed the rise in reticulocytes after the fourth dose of rituximab. Serum hemolytic parameters normalized, as well as the serologic finding of an auto-antibody also disappeared. A BM aspirate demonstrated no abnormal findings and, in particular, the full recovery of the erythroid matrix. The patient, 10 months after rituximab therapy, shows normal Hb and reticulocyte levels, and she is no longer received immunosuppressive therapy. Treatment of PRCA and of AIHA usually employs immunosuppressive drugs, mainly steroids and CSA, or immunomodulating agents [1]. However, conventional immunosuppressive treatments are often unsatisfactory for which rituximab has been successfully used as salvage therapy in the pediatric setting [2]. Our L. Scaramucci (&) P. Niscola M. Ales M. Giovannini A. Tendas L. Cupelli A. Siniscalchi D. Piccioni T. Dentamaro A. Perrotti P. de Fabritiis Hematology Unit, Sant’Eugenio Hospital, Piazzale dell’Umanesimo 10, 00144 Rome, Italy e-mail: scaramucci.laura@gmail.com

Postinjury Life Threatening Coagulopathy: Is 1:1 Fresh Frozen Plasma: Packed Red Blood Cells the Answer?

Recent military experience suggests that immediate 1:1 fresh frozen plasma (FFP); red blood cells (RBC) for casualties requiring >10 units packed red blood cells (RBC) per 24 hours reduces mortality, but no clinical trials exist to address this issue. Consequently, we reviewed our massive transfusion practices during a 5-year period to test the hypothesis that 1:1 FFP:RBC within the first 6 hours reduces life threatening coagulopathy. We queried our level I trauma center's prospective registry from 2001 to 2006 for patients undergoing massive transfusion. Logistic regression was used to evaluate the independent effect of FFP:RBC in 133 patients who received >10 units RBC in 6 hours on (1) Coagulopathy (international normalized ratio [INR] >1.5 at 6 hours), controlling for our previously described risk factors predictive of coagulopathy, as well as RBC, FFP, and platelet administration (2) Death (controlling for all variables plus age, crystalloids per 24 hours, INR >1.5 at 6 hours). Overall mortality was 56%; 50% died from acute blood loss in the operating room. Over 80% of the RBC transfusions were completed in the first 6 hours: (Median RBC: 18 units) Median FFP:RBC survivors, 1:2, nonsurvivors: 1:4. (p < 0.001) INR >1.5 at 6 hours occurred in 30 (23%); 81% died. Regarding mortality, logistic regression showed significant variables (p < 0.05) included: RBC per 6 hours (OR = 1.248, 95%CI: 1.957-53.255), INR at 6 hours >1.5 (OR = 10.208, 95% CI: 1.957-53.255), ED temperature <34 degrees C (OR = 15.491, 95% CI 1.376-174.396), and age >55 years (OR = 40.531, CI 5.315-309.077). The adjusted OR for FFP:RBC ratio including the quadratic term was found to follow a U-shaped association (quadratic term estimate 0.6737 +/- 0.0345, p = 0.0189). Although our data suggest that 1:1 FFP:RBC reduced coagulopathy, this did not translate into a survival benefit. Our findings indicate that the relationship between coagulopathy and mortality is more complex, and further clinical investigation is necessary before recommending routine 1:1 in the exsanguinating trauma patient.

How often should a red blood cell administration set be changed while a patient is being transfused? A commentary and review of the literature

Current recommendations vary with regard to the frequency of change of a red blood cell (RBC) administration set. A full review was undertaken to evaluate the recommendations for how often a RBC administration set should be changed while a patient is being transfused. Comprehensive searches of Medline, Embase, Cinahl, the Cochrane Library, handsearching of transfusion journals, guidelines and websites and contact with administration set manufacturers identified 32 relevant papers: 11 clinical updates; 11 guidelines; 5 manufacturer data sheets; 3 standards; 1 Department of Health report and 1 expert opinion. Recommendations varied widely across papers. There was no pattern in recommendation by paper type, date or country of origin. Recommendations were based on change of RBC administration set either after a given number of hours or number of RBC units. The recommendations varied widely and ranged from 4 to 48 h and from 'every unit' to 'several units'. The most frequent recommendations were change of RBC administration set after 12 h or 4 units. Methodological quality of the included papers is poor. There is no formal evidence base on which to support current recommendations or challenge the current British Committee for Standards in Haematology guideline. Targeted research aimed at establishing an evidence base may be warranted and would need to document other variables that can impact frequency of change, including type of filter, age of blood and duration of RBC transfusion.

Cardiac Arrests Associated with Hyperkalemia During Red Blood Cell Transfusion: A Case Series

Transfusion-associated hyperkalemic cardiac arrest is a serious complication of rapid red blood cell (RBC) administration. We examined the clinical scenarios and outcomes of patients who developed hyperkalemia and cardiac arrest during rapid RBC transfusion. We retrospectively reviewed the Mayo Clinic Anesthesia Database between November 1, 1988, and December 31, 2006, for all patients who developed intraoperative transfusion-associated hyperkalemic cardiac arrest. We identified 16 patients with transfusion-associated hyperkalemic cardiac arrest, 11 adult and 5 pediatric. The majority of patients underwent three types of surgery: cancer, major vascular, and trauma. The mean serum potassium concentration measured during cardiac arrest was 7.2 +/- 1.4 mEq/L (range, 5.9-9.2 mEq/L). The number of RBC units administered before cardiac arrest ranged between 1 (in a 2.7 kg neonate) and 54. Nearly all patients were acidotic, hyperglycemic, hypocalcemic, and hypothermic at the time of arrest. Fourteen (87.5%) patients received RBC via central venous access. Commercial rapid infusion devices (pumps) were used in 8 of 11 (72.7%) of the adult patients, but RBC units were rapidly administered (pressure bags, syringe pumped) in all remaining patients. Mean resuscitation duration was 32 min (range, 2-127 min). The in-hospital survival rate was 12.5%. The pathogenesis of transfusion-associated hyperkalemic cardiac arrest is multifactorial and potassium increase from RBC administration is complicated by low cardiac output, acidosis, hyperglycemia, hypocalcemia, and hypothermia. Large transfusion of banked RBCs and conditions associated with massive hemorrhage should raise awareness of the potential for hyperkalemia and trigger preventative measures.

Impact of splenectomy on surgical outcome in patients with cancer of the distal esophagus and gastro-esophageal junction

We aim to determine the effect of splenectomy on clinical outcome in patients with cancer of the distal esophagus and gastro-esophageal junction (GEJ) after a curative intended resection. From January 1991 to July 2004, 210 patients underwent a potentially curative gastroesophageal resection with an extended nodal dissection. The study group was divided into: group I with splenectomy, consisting of 66 patients (31.4%), and group II without splenectomy, of 144 patients. Splenectomy was performed for oncological reasons. Medical records were reviewed retrospectively. Postoperative complications occurred in 27 patients (40.9%) in group I and in 68 patients (47.2%) in group II (P = 0.4). The overall mortality was not significantly different between both groups (P = 0.7). There was a higher administration of red blood cells during surgery (P < or = 0.001), increased operating room (OR) time (P < or = 0.001) and longer intensive care unit (ICU) stay (P = 0.01) in group I. Independent prognostic factors for survival were outcome of surgery, nodal metastases, gender, complications and ICU stay. Sepsis was a strong prognostic factor among the complications. The 1 and 2-year survival was significantly higher in group II; 75% and 67% (P = 0.032) compared to 69% and 56% (P = 0.017) in group I, respectively. However, the 5-year survival was not different in both groups (29% in group I and 60% in group II, P = 0.191). Splenectomy had no marked effect on mortality and morbidity after curative resection of esophageal cancer. Splenectomy had a significant increase in blood transfusions with prolonged OR time and ICU stay and decreased short-term survival.

Changes in red blood cell transfusion practice during the past two decades: a retrospective analysis, with the Mayo database, of adult patients undergoing major spine surgery

Others have reported significant changes in red blood cell (RBC) transfusion practice during the past two decades during knee, hip, prostate, and carotid surgery. Similar data for patients undergoing major spine surgery, however, are not available. After institutional review board approval, adult patients undergoing elective major spine surgery were stratified into one of two transfusion-related groups: 1) 1980 to 1985 (i.e., before human immunodeficiency virus screening, early practice group; n = 699) or 2) 1995 to 2000 (i.e., late practice group; n = 610). Patients in the late practice group were older, had greater numbers of preoperative coexisting diseases (e.g., hypertension, cardiac dysrhythmias, coronary artery disease, prior myocardial infarction, diabetes mellitus, renal disease, cerebrovascular disease, and asthma), and were exposed to longer operations (p < 0.01 for each variable). Over time, allogeneic RBC administration significantly decreased, whereas autologous and intraoperative autotransfusion significantly increased. Compared to the early practice group, all perioperative Hb concentrations were significantly lower than the late practice group, yet no significant difference in major morbidity or mortality was observed between groups. In this retrospective analysis, significantly lower acceptable perioperative Hb concentrations were observed in older patients having substantially worse baseline comorbidity and exposed to longer major spine operations, without significant change in the incidence of perioperative morbidity or mortality.

Administration of Fludarabine-Loaded Autologous Red Blood Cells in Simian Immunodeficiency Virus-Infected Sooty Mangabeys Depletes pSTAT-1-Expressing Macrophages and Delays the Rebound of Viremia after Suspension of Antiretroviral Therapy

A major limitation of highly active antiretroviral therapy is that it fails to eradicate human immunodeficiency virus (HIV) infection due to its limited effects on viral reservoirs carrying replication-competent HIV, including monocytes/macrophages (M/M). Therefore, therapeutic approaches aimed at targeting HIV-infected M/M may prove useful in the clinical management of HIV-infected patients. In previous studies, we have shown that administration of fludarabine-loaded red blood cells (RBC) in vitro selectively induces cell death in HIV-infected M/M via a pSTAT1-dependent pathway. To determine the in vivo efficacy of this novel therapeutic strategy, we treated six naturally simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) with either 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) only, fludarabine-loaded RBC only, or PMPA in association with fludarabine-loaded RBC. The rationale of this treatment was to target infected M/M with fludarabine-loaded RBC at a time when PMPA is suppressing viral replication taking place in activated CD4+ T cells. In vivo administration of fludarabine-loaded RBC was well tolerated and did not induce any discernible side effect. Importantly, addition of fludarabine-loaded RBC to PMPA delayed the rebound of viral replication after suspension of therapy, thus suggesting a reduction in the size of SIV reservoirs. While administrations of fludarabine-loaded RBC did not induce any change in the CD4+ or CD8+ T-cell compartments, we observed, in chronically SIV-infected SMs, a selective depletion of M/M expressing pSTAT1. This study suggests that therapeutic strategies based on the administration of fludarabine-loaded RBC may be further explored as interventions aimed at reducing the size of the M/M reservoirs during chronic HIV infection.

EARLY COAGULOPATHY AND MASSIVE TRANSFUSION (MT) IN CIVILIAN TRAUMA AND COMBAT CASUALTIES

Objective: Current ATLS standard of normotensive resuscitation results in disproportionate crystalloid to packed red blood cell (PRBC) administration. Recent studies advocate earlier fresh frozen plasma (FFP) based on the premise that patients are coagulopathic prior to MT. The purpose of the study was to compare civilian and military trauma patients who required MT (>10 U PRBC). Methods: Research databases from a regional Level I US Trauma center and a Combat Support Hospital were reviewed. Patient demographic and resuscitative variables were compared. Data are expressed as mean ± SD, * P < 0.05. Results: The combat cohort was younger, but both cohorts had high injury severity score (ISS) and similar survival. Admission hemoglobin concentration ([Hb]), temperature (T), base deficit (BD), and International Normalized Ratio (INR) were similar. Admission INR indicated moderate to severe coagulopathy. Civilian patients received care consistent with ATLS guidelines, receiving isotonic crystalloid to PRBC in a 3:1 ratio and FFP administration delayed until after 6 units PRBC. Combat casualties received colloid in the field followed by isotonic crystalloid to PRBC in a 2:1 ratio and similar FFP transfusion. Following resuscitation, INR remained elevated in both cohorts. Conclusion: Consistent with recent literature, combat and civilian trauma patients were coagulopathic prior to MT. Moreover, current military and civilian MT practice does not correct this coagulopathy. Based on this study, the civilian population appears to be an appropriate model for the evaluation of more aggressive haemostatic shock resuscitation.Table

Hemoglobin‐Based Oxygen Carriers in Trauma Care: Scientific Rationale for the US Multicenter Prehosptial Trial

The greatest need for blood substitutes worldwide is in patients with unanticipated acute blood loss, and trauma is the most likely scenario. The blood substitutes reaching advanced clinical trials today are red blood cell (RBC) substitutes derived from hemoglobin. The hemoglobin-based oxygen carriers (HBOCs) tested currently in advanced clinical trials are polymerized hemoglobin solutions. In the USA, the standard approach to restoring oxygen delivery for hemorrhagic shock has been crystalloid administration to expand intravascular volume, followed by stored RBCs for critical anemia. Allogeneic RBCs, however, may have adverse immunoinflammatory effects that increase the risk of postinjury multiple organ failure (MOF). Phase II in hospital clinical trials, as well as in vitro and in vivo work, suggest that resuscitation with an HBOC--in lieu of stored RBCs--attenuates the systemic inflammatory response invoked in the pathogenesis of MOF. Specifically, an HBOC has been shown to obviate stored RBC-provoked polymorphonuclear neutrophil (PMN) priming, endothelial activation, and systemic release of interleukins (IL) 6, 8, and 10. In a 2-event rodent study of shock-induced PMN-mediated acute respiratory distress syndrome (ARDS), the simulated prehospital administration of an HBOC markedly attenuated lung injury. Based on this background and work by others, we have initiated a US multicenter prehospital trial in which severely injured patients with major blood loss [systolic blood pressure (SBP)<or=90 mmHg] are randomized to initial field resuscitation with crystalloid versus HBOC. During the hospital phase, the control group is further resuscitated with stored RBCs whereas the study group receives HBOC (up to 6 units) in the first 12 hours. The primary study endpoint is decreased 30-day mortality, and secondary endpoints include reductions in administration of allogeneic RBCs and uncrossmatched RBCs; avoiding circulating hemoglobin levels<5 g/dl; and decreased ARDS and MOF. To date, >500 injured patients have been enrolled in this multicenter trial, and the final interim analyses support the original target of 720.

Use of a Blood Gas Analyzer to Measure Blood Hemoglobin During Liver Transplantation: A Study of 935 Paired Samples

IVER TRANSPLANTATION is associated with significant blood loss and frequent variations in blood hemoglobin concentrations. The administration of red blood cells (RBC) under strict rules supported by the hemoglobin values is an important strategy to reduce blood consumption. The rapidity of the analytic response is important for an appropriate transfusion policy. In general, blood gas analyzers measure hemoglobin concentrations accurately and are contiguous to operating rooms, contrary to standard Coulter analyzers, which are usually located in central hospital laboratories. The use of blood gas analyzers to measure hemoglobin has the advantage of rapidity, as there is no time wasted in transport. Additionally, a reduction in laboratory samples has economic advantages and spares patient blood. Some previous studies compared blood gas analyzers with standard laboratory Coulter analyzers, 1,2 however, as far we know, this was never done specifically in liver transplantation, in young children, at low levels of hemoglobin, or with high levels of bilirubin, factors which could influence the results. We performed this study with the purpose of evaluating the accuracy of a blood gas analyzer to measure hemoglobin in these specific conditions.

Red Blood Cell Transfusions in Patients Undergoing Lower Extremity Artery Bypass Surgery

The purpose of this study was to search predictors of red blood cell transfusions in peripheral vascular surgical patients. All the patients who undergone infrainguinal bypass surgery at Helsinki University Hospital in the year 2000 were included. Of 266 records 261 (98%) were available for data review. Multiple stepwise regression model was created to identify independent predictors of blood use. 174 (67%) of the patients received red blood cell transfusion. The lowest measured mean (SD) haemoglobin was 94 (11) g/l intraoperatively and 92 (+/- 10) g/l on the first two postoperative days. The median (range) number of units was 3 (1-19). Multivariate analysis showed that high age (p = 0.019), small body surface area (p = 0.017), low preoperative haemoglobin (p < 0.001), blood loss (p < 0.001), long lasting surgery (p<0.001), reoperation (p=0.018), femoro-distal reconstruction (p=0.048) and chronic obstructive pulmonary disease (p = 0.023) increased the risk to receive red blood cell transfusion. The frequent use of antithrombotic medication (72% of the patients) did not significantly increase red blood cell administration. The generous use of red blood cells despite relative safe haemoglobin levels indicates a need for a standardized multidisciplinary transfusion strategy in this patient population. Otherwise, most of the predictors for red blood cell administration were nonmodifiable.

Memory Antibody Responses of Broiler and Leghorn Chickens as Influenced by Dietary Vitamin E and route of Sheep Red Blood Cell Administration

Influences of dietary levels of vitamin E fed to hens and their progeny, and routes of SRBC inoculation on antibody responses of diverse populations of chickens were studied. Populations were a commercial broiler sire line (C), 2 commercial broiler dam lines (A and B), and Leghorn lines selected for high (H) or low (L) antibody response to SRBC. Dams from lines A and B were fed diets supplemented with either 10 or 300 IU/kg of vitamin E, whereas dams from lines H and L received only the diet with 10 IU of vitamin E/kg. Progeny from matings of C males with A and B females as well as H and L females mated to males from their respective lines were hatched on the same day and fed diets supplemented with either 10 or 300 IU/kg of vitamin E. Breeders were the same age and eggs were incubated in the same machine. Chicks were inoculated on d 14 intravenously with 0.1 mL of a 0.5% suspension of SRBC or intramuscularly with 0.1 mL of a 25% suspension of SRBC. Antibody response was measured 6 and 14 d later. Chicks received a booster i.m. inoculation of 0.1 mL of 25% SRBC on d 28. Titers were again measured 6 and 14 d later. Level of vitamin E fed to dams did not affect progeny BW or plasma vitamin E levels. Although titers were higher following i.v. than i.m. inoculation, the degree of difference varied among stocks. Dietary vitamin E level interacted with inoculation route with a greater response to the higher than lower level of vitamin E for i.v., but there was no difference for i.m. There were stock × level of vitamin E and stock × route of inoculation interactions for secondary responses to SRBC inoculation. Stock rankings after the first inoculation were not predictive of the rankings after the second inoculation. The 30-fold increase in dietary level of vitamin E resulted in >12-fold differences in plasma levels of vitamin E. Overall, there was a stock-dependent influence of dietary vitamin E on growth and humoral antibody response.

Cancer-Related Anemia

Anemia has a high prevalence in patients with cancer. Its frequency and severity depend on tumor type, tumor stage, duration of disease, and treatment status. The etiology of cancer-related anemia is multifactorial and includes myelotoxicity of treatment, bone marrow infiltration, impaired erythropoietin production, blood loss, and the anemia of chronic disease. Anemia affects health-related quality of life (QOL) and may impact on tolerance or even outcome of anticancer therapy. Despite its high prevalence and impact on QOL, anemia is often under-recognized and under-treated. Treatment should correct etiologic factors, whenever possible. Symptomatic treatments are red blood cell transfusions and administration of erythropoietic growth factors. Transfusions result in rapid improvement of anemia-related symptoms but are usually only given to patients with moderate to severe anemia. Administration of epoetins (epoetin alfa, epoetin beta) or darbepoetin alfa increases hemoglobin levels, reduces the need for blood transfusions, and improves QOL in patients with cancer-related anemia. Trials determining the exact association of anemia with both response to chemo(radio)therapy and survival are ongoing. Physicians should be aware of the clinical relevance of and treatment options for anemia in cancer patients.

A T-cell-dependent humoral immune response is preserved during the administration of the nerve agent pre-treatment pyridostigmine bromide in a murine model

Immune regulation, either via the autonomic nervous system or by a proposed “non-neuronal” cholinergic system, suggests that the immune system may be susceptible to perturbation by compounds affecting cholinergic function. Here, the current UK and US nerve agent pre-treatment, pyridostigmine bromide (PB) and the related anti-acetylcholinesterase (AChE) compounds physostigmine (PHY) and BW284c51 were tested for their ability to affect mouse splenocyte function in vitro. In addition, PB, at a dose equivalent to that received during pre-treatment for nerve agent poisoning, was tested for its effect on a T-cell-dependent humoral response to antigen in vivo in the mouse. None of the anti-AChEs tested affected concanavalin A (Con A)-, anti-CD3- or lipopolysaccharide LPS-driven splenocyte proliferation, in vitro, at concentrations expected to give effective nerve agent pre-treatment. However, higher concentrations (>100 μM) particularly of PHY caused some inhibition of the proliferative responses. In vivo, PB or saline was administered via 28-day mini-osmotic pumps to give a 25–40% inhibition of whole blood AChE in the PB-treated animals. During PB or saline administration, primary and secondary doses (i.p.) of sheep red blood cells (SRBC) were given and the humoral response determined by monitoring anti-SRBC IgM and IgG levels. Splenocytes isolated from the experimental animals were also examined for their proliferative and cytokine responses to stimulation. No remarkable effects of PB were seen during the period of AChE inhibition on the humoral immune response. However, a modest elevation in IL-2 and IFNγ in Con A-stimulated lymphocytes was seen in PB-treated animals following pump removal. Overall these data suggest that, in vivo, the SRBC stimulated T-cell-dependent immune response is unaffected by the administration of PB at pre-treatment doses.

Case 1–2003 The use of intraoperative echocardiography during insertion of ventricular assist devices

Transesophageal echocardiography (TEE) assists in the intraoperative decision-making process during cardiac anesthesia and cardiac surgery. Mechanical ventricular support may be necessary to support the circulatory system temporarily or serve as a bridge to heart transplantation. A left ventricular assist device (LVAD) is most commonly used.1 Biventricular failure necessitates the use of an LVAD along with a right ventricular assist device (RVAD) to form a biventricular assist device (BIVAD) (Fig 1). TEE plays a vital role in evaluating effective mechanical assistance of the circulation.1-3 This case describes a BIVAD placement in a patient and shows the roles and limitations of TEE in this scenario.

Risk markers for thrombocytopenia in critically ill patients: a prospective analysis.

To identify independent risk markers for thrombocytopenia in critically ill patients. Prospective, observational study. Eleven-bed intensive care unit-coronary care unit (ICU-CCU) in a community hospital. Three hundred sixty-two consecutive patients meeting inclusion criteria during 1 year. Potential risk marker data were collected on admission to the ICU-CCU and for the period before development of thrombocytopenia (defined as two or more consecutive platelet counts < 150 x 10(3)/mm3 obtained at least 12 hours apart), or for the duration of ICU-CCU stay if thrombocytopenia did not develop. Thrombocytopenia developed in 68 patients (18.8%). Multivariate logistic regression analyses identified patients at risk on admission, but the predictive, potential of the regression model improved when all risk marker exposures during the ICU-CCU stay were considered. Independent risk markers included fresh frozen plasma administration, sepsis, musculoskeletal diagnosis, pulmonary artery catheter insertion, gastrointestinal diagnosis, packed red blood cell administration, and nonsurgical respiratory diagnosis. Higher admission platelet count and aspirin administration were associated with a lower risk of thrombocytopenia. Heparin administration was not identified as a risk marker, and no patient developed heparin-induced thrombocytopenia with thrombosis. Patients with thrombocytopenia had longer ICU-CCU and hospital stays, and higher ICU-CCU and hospital mortality than those without thrombocytopenia. Development of thrombocytopenia in critically ill patients is associated with specific diagnoses, packed red cell and fresh frozen plasma transfusions, pulmonary artery catheter insertion, and admission platelet count.

Red blood cells: an analysis of risk versus benefit

The value of red blood cell administration to increase oxygen carrying capacity is obvious to all clinicians. Nevertheless, there has never been a prospective, randomized, controlled study documenting the efficacy or conclusively defining the indications for red blood cell use. Considering the risks associated with allogeneic blood, careful consideration must be given before the administration of each unit of blood product.