Perfluorocarbon emulsions are being clinically evaluated as artificial oxygen carriers to reduce allogeneic blood transfusions or to improve tissue oxygenation. Perfluorocarbon emulsions are efficacious in animal experiments, and in humans they are well tolerated and at least as successful to reverse physiologic transfusion triggers than autologous blood. Perfluorocarbon emulsions may be used in the future in the concept of augmented acute normovolaemic haemodilution. In this concept relatively low preoperative haemoglobin levels are targeted during preoperative normovolaemic haemodilution and a perfluorocarbon emulsion is given to augment oxygen delivery during surgery when low endogenous haemoglobin levels are expected. The autologous blood is subsequently retransfused in the postoperative period when the patient's oxygenation is provided primarily by the endogenous haemoglobin. Additional uses of perfluorocarbon emulsions will include treatments of diseases with compromised tissue oxygenation such as cerebral or myocardial ischaemia, air embolism and emergency or trauma surgery as long as no allogeneic blood is available.
acute normovolaemic haemodilution; artificial oxygen carriers; blood conservation; blood transfusion; perfluorocarbon emulsion
Appropriate control of the affinity of haemoglobin for oxygen is fundamental to the efficient oxygenation of our tissues. Important modifiers of this relationship are pH, CO2 concentration and the intraerythrocytic level of 2,3-diphosphoglycerate (2,3-DPG). We have studied the influence of haemoglobin affinity on the radiosensitivity of the RIF-1 sarcoma in the mouse. Changes in haemoglobin affinity were induced by exposing donor mice to either 10% oxygen, normal air, or 100% oxygen for 48 h. Blood was drawn from these animals and exchanged transfused into tumour-bearing mice immediately before irradiation. Transfusion of blood from mice breathing 10% oxygen carried a lowered haemoglobin affinity and produced marked radiosensitization of the tumours in the recipients; transfusion with normal blood had no significant effect and transfusions from mice breathing 100% oxygen caused a small increase in radioresistance. Measurements of the level of 2,3-DPG in the blood of these groups showed higher concentrations in the oxygen-deprived animals than in controls but no significant change in animals exposed to 100% oxygen. These results demonstrate that alterations in haemoglobin affinity, probably resulting from changes in 2,3-DPG levels, can have a powerful influence on tumour radiosensitivity. We feel that this mechanism could have considerable clinical importance.
Transfusable fluids that may be used as alternatives to red blood cell transfusion offer the promise of preserving tissue perfusion and minimizing hypoxic cellular damage, and this promise may soon be fulfilled. Clinical testing of hemoglobin-based oxygen carriers has faced and met challenges involving molecular design, safety, efficacy, and regulatory requirements. Three leading candidates have emerged: two human (PolyHeme® and HemoLink™) and one bovine-based hemoglobin solution (Hemopure®). Because a survival benefit has been difficult to demonstrate, avoidance of allogeneic transfusion has been adopted as the standard efficacy end-point for these agents. An update on clinical trial status is provided, and the potential utility of hemoglobin-based oxygen carriers in surgery combined with intraoperative autologous donation is discussed.
blood substitutes; red blood cell transfusion; surgery
Anaemia is associated with inferior outcomes in critically ill patients. It is difficult to prevent and is treated commonly with the transfusion of packed red cells. However, transfusion to augment oxygen delivery has not been shown to consistently offer a survival advantage when the haemoglobin concentration exceeds 7 g/dL. Several studies point to inferior outcomes when patients are transfused. Observational studies have confirmed that critically ill patients have frequent blood draws as part of their routine daily care. Cumulatively large volumes of blood are frequently taken, which contribute significantly towards the development of anaemia. Reducing iatrogenic blood loss may reduce the risk of developing anaemia and possibly the need for transfusion. Blood conservation devices may help to achieve this goal. The integration of blood conservation devices into routine care has been relatively slow in critical care. This review summarises the current evidence base and confirms that blood conservation devices do reduce the volume of iatrogenic blood loss. In the most recent studies, these devices have been shown to reduce transfusion requirements even in those intensive care units that follow a restrictive transfusion strategy.
Critical care; Blood conservation devices; Anaemia; Transfusion
Orthopaedic patients frequently require blood transfusions to treat peri-operative anemia. Research in the area of hemoglobin substitutes has been of great interest since it holds the promise of reducing the reliance on allogeneic blood transfusions. The three categories of hemoglobin substitutes are (1) cell-free, extracellular hemoglobin preparations made from human or bovine hemoglobin (hemoglobin-based oxygen carriers or HBOCs); (2) fluorine-substituted linear or cyclic carbon chains with a high oxygen-carrying capacity (perfluorocarbons); and (3) liposome-encapsulated hemoglobin. Of the three, HBOCs have been the most extensively studied and tested in preclinical and clinical trials that have shown success in diminishing the number of blood transfusions as well as an overall favorable side-effect profile. This has been demonstrated in vascular, cardiothoracic, and orthopaedic patients. HBOC-201, which is a preparation of cell-free bovine hemoglobin, has been approved for clinical use in South Africa. These products may well become an important tool for physicians treating peri-operative anemia in orthopaedic patients.
Hemoglobin substitute; HBOC; HBOC-201; Perfluorocarbons
Homozygous sickle cell carriers have an increased perioperative mortality. Some indications may justify an exchange blood transfusion to reduce the proportion of haemoglobin S. The advantages of general blood transfusion in a perioperative setting have not been proven and thus remain controversial. It is not clear whether reducing the proportion of haemoglobin S minimizes perioperative complications or whether patients with sickle cell disease in a stable clinical condition benefit from an exchange blood transfusion in a perioperative setting.
We report the case of two Angolan children aged 10 and 11 respectively, of African origin with sickle cell anaemia who underwent surgery to treat chronic necrosis, fistula of the bones and bone destruction. This presentation describes the perioperative course, including general anaesthesia. A partial exchange blood transfusion decreased S-haemoglobin levels from 81% to 21% and simultaneously treated the anaemia.
There is a consensus that imbalances in homoeostasis, including operative procedures, can cause a critical exacerbation of sickle cell disease. The case presented here illustrates a strategy for successfully managing sickle cell disease in the perioperative period to minimize its complications. It is important for the anaesthesiologist to carefully manage pulmonary gas exchange and to ensure sufficient tissue perfusion, balanced fluid resuscitation and normothermia, while keeping in mind the level of organ impairment in order to prevent an acute exacerbation of sickle cell disease.
We performed a partial exchange blood transfusion due to the following factors: high haemoglobin S-fraction, anaemia, operating procedure at several sites, and difficult management of body temperature. Esmarch ischemia is an established tool for preventing uncontrolled blood loss. There is no known contraindication for this, but attention must be paid to prevent uncontrolled tissue ischemia and acidosis. The use of regional anaesthesia should be considered for postoperative pain management.
Background: Peripheral fractional oxygen extraction (FOE) may be a better indicator of the need for transfusion than the haemoglobin concentration (Hb) because it is a measure of the adequacy of oxygen delivery to meet demand. A randomised controlled trial of the use of peripheral FOE to guide the need for blood transfusions in preterm infants was carried out to test this hypothesis.
Method: Infants less than 1500 g birth weight who were stable and less than 2 weeks old were randomised to receive transfusions guided by either a conventional protocol based on Hb (conventional group) or a protocol based on measurements of peripheral FOE made by near infrared spectroscopy (NIRS group). Measurements of Hb and FOE were made on all infants from randomisation until discharge. The primary outcome measures were number of transfusions received, rate of weight gain, and postmenstrual age at discharge.
Results: Thirty seven infants were randomised to each group. Birth weight (median, range) (1200, 1004–1373 v 1136, 1009–1285 g) and Hb (median, range) at randomisation (160, 149–179 v 155, 145–181 g/l) did not differ between the two groups. The total number of transfusions given to the NIRS group was 56 and to the conventional group 84. The median number of transfusions per infant, the median volume of blood transfused to each group, and the total number of donors to which infants were exposed were similar in the two groups. Infants transfused according to the conventional protocol were more likely to be transfused earlier and at a higher Hb than those transfused in the NIRS group. Infants in the conventional group spent a significantly shorter period than those in the NIRS group with Hb < 100 g/l. Of the 56 transfusions given to the NIRS group, 33 (59%) were given because of clinical concerns rather than because of high FOE. There was no difference in the rate of weight gain, rate of linear growth, postmenstrual age at discharge, or the incidence of chronic lung disease or retinopathy of prematurity.
Conclusions: FOE measurements failed to identify many infants felt by clinicians to require blood transfusion. This may have been because clinicians relied on conventional indicators of transfusion that are vague and non-specific, or a peripheral FOE of 0.47 alone may not be a sensitive enough predictor of the need for transfusion. This requires further study.
Malaria is an annual killer of over one million people globally and its essential co-morbidity is anaemia. Cord blood, because of its rich mix of foetal and adult haemoglobin, high platelet and WBC counts, hypo-antigenic nature, altered metabolic profile and high affinity for oxygen as well as its anti-malarial effect, is an ideal choice in malaria with anaemia, necessitating blood transfusion.
This paper presents an alternative protocol for fresh whole blood/packed cell transfusion from the hospital's biological waste resources, i.e., the placenta, after the birth of a healthy baby from a healthy mother. This collected blood was routinely transfused to patients admitted in our hospital with severe anaemia in the background of confirmed malaria. 94 units of placental umbilical cord whole blood were collected after lower uterine caesarean section (LUCS) from consenting mothers (from 1st April 1999 to April 2005), and safely transfused to 39 informed, consenting patients (age varying from 8 to 72 years). The collected volume of cord blood from each placenta (Unit) varied from 52 ml to 143 ml, with a mean packed cell volume of 48.9 ± 4.1 SD and a mean haemoglobin concentration of 16.4 Gm percent ± 1.6 Gm percent SD. The blood was immediately transfused after following the standard adult blood transfusion protocol of screening and cross-matching between the donor and the recipient. On occasion, the collected cord blood was preserved in the refrigerator, if no volunteer was readily available, and transfused within 72 hours of collection.
Cord blood transfusion was tested on twenty two patients infected with Plasmodium falciparum and 17 patients with Plasmodium vivax. For inclusion in this study, the patient's plasma haemoglobin had to be 8 gm percent or less (the pre-transfusion haemoglobin in the malaria-infected patients in this series varied from 5.4 gm/dl to 7.9 gm/dl). The rise of haemoglobin within 72 hours of two units of freshly collected cord blood transfusion was 0.5 gm/dl to 1.6 gm/dl. Each patient received two to six units of freshly collected cord blood transfusion (two units at a time), depending on availability and compatibility. No clinical immunological or non-immunological reaction has been encountered in this series.
Properly screened cord blood is safe for transfusion, in victims of severe malarial anaemia who need transfusion support.
Traditional wisdom is that wound healing is directly related to haemoglobin level in the blood; therefore blood transfusion is given in anaemic patients to raise the haemoglobin level for better wound healing.
Evaluation of wound healing in the form of split thickness skin graft take was done in 35 normovolaemic anaemic patients (haemoglobin level of < 10 gm/ dl) and compared with control group (patients with haemoglobin level of 10 or > 10 gm/ dl).
There was no statistically significant difference in mean graft take between the two groups.
It is not mandatory to keep haemoglobin level at or >10 g/dL or PCV value at or >30% for skin graft take, as mild to moderate anaemia per se does not cause any deleterious effect on wound healing; provided perfusion is maintained by adequate circulatory volume. Prophylactic transfusion to increase the oxygen carrying capacity of the blood for the purpose of wound healing is not indicated in asymptomatic normovolemic anaemic patients (with haemoglobin levels greater than 6g/dL) without significant cardiovascular or pulmonary disease.
Anaemia; skin graft take; wound healing
Most healthy humans have a haemoglobin concentration of 12 to 15 g/dL and most intensivists now transfuse packed red blood cells for haemoglobin <7 g/dL. Higher haemoglobin is associated with improved intermediate and clinical outcomes after subarachnoid hemorrhage (from ruptured brain aneurysm) or neurotrauma. An observational study in a recent issue shows that higher haemoglobin was associated with better functional outcomes in patients with spontaneous intracerebral haemorrhage; few patients received a packed red blood cell transfusion, so it is not known if that treatment is better than the disease. The mechanism of anaemia's purported impact on outcome is unclear, although altered metabolism in brain tissue that is sensitive to reduced oxygen delivery is plausible. These data may intensify the differences of opinion between intensivists: whether neurologic patients are better served by higher haemoglobin and potentially by more packed red blood cell transfusion, or simply need to be studied more in prospective clinical trials, remains unclear.
Severe anaemia requiring emergency blood transfusion is a common complication of malaria in children. To ensure access for urgent blood transfusion, the World Health Organization has developed clear guidelines with haemoglobin thresholds prevent unwarranted transfusion,. Few studies have reported outcome and haematological recovery of children with severe malaria where transfusion practice complies with WHO recommendations.
A prospective observational study of survivors of severe and complicated malaria transfused in accordance with WHO guidelines. Children were invited for review at one month post-discharge. Non-attendees were traced in the community to ascertain survival.
Outcome was assessed in 213 survivors. Those transfused were younger, had a higher base deficit, mean lactate levels and a higher prevalence of respiratory distress. As expected mean admission haemoglobin (Hb) was significantly lower amongst transfused [5.0 g/dL SD: 1.9] compared to non-transfused children [8.3 g/dL SD: 1.7] (p < 0.001). At discharge mean Hb was similar 6.4 g/dL [SD: 1.5] and 6.8 g/dL [SD: 1.6] respectively (p = 0.08), most children remained moderately to severely anaemic. At one month follow up 166 children (78%) returned, in whom we found no differences in mean Hb between the transfused (10.2 g/dL [SD: 1.7]) and non-transfused (10.0 g/dL [SD: 1.3]) survivors (p = 0.25). The major factors affecting haematological recovery were young age (<24 months) and concomitant malaria parasitaemia; Hb being 8.8 g/dL [SD: 1.5] in parasitaemic individuals compared with 10.5 g/dL [SD: 1.3] in those without (p < 0.001).
This data supports the policy of rational use of blood transfusion, as proposed in the WHO guidelines, for children with anaemia in areas where access to emergency transfusion is not guaranteed. We have provided empirical data indicating that transfusion does not influence superior recovery in haemoglobin concentrations and therefore cannot be justified on this basis alone. This may help resolve the disparity between international policy and current clinical practice. Effective anti-malarial treatment at discharge may prevent reoccurrence of anaemia.
To avoid unnecessary blood transfusions, physiologic transfusion triggers, rather than exclusively hemoglobin-based transfusion triggers have been suggested. The objective of this study was to determine systemic and microvascular effects of using a perfluorocarbon-based oxygen carrier (PFCOC) to maintaining perfusion and oxygenation during extreme anemia.
The hamster (weight 55-65 g) window chamber model was used. Two isovolemic hemodilution steps were performed using 10% hydroxyethyl starch at normoxic conditions to hematocrit of 19% (5.5 gHb/dl), point where the transfusion trigger was reached. Two additional hemodilution exchanges using the PFCOC (Oxycyte™, Synthetic Blood International, Inc. Costa Mesa, CA) and increasing fraction of inspired oxygen to 1.0 were performed to reduce hematocrit to 11% (3.8 gHb/dl) and 6% (2.0 gHb/dl), respectively. No control group was used in the study, as this level of hemodilution is lethal with conventional plasma expanders. Systemic parameters, microvascular perfusion, functional capillary density and oxygen tensions across the microvascular network were measured.
At 6% hematocrit, the PFCOC maintained mean arterial pressure, cardiac output, systemic oxygen delivery and consumption. As hematocrit was lowered from 11% to 6%, functional capillary density, calculated microvascular oxygen delivery and consumption decreased, and oxygen extraction ratio was close to 100%. Peripheral tissue oxygenation was not predicted by systemic oxygenation.
PFCOC in conjunction with hyperoxia was able to sustain organ function, and partially provide systemic oxygenation during extreme anemia over the observation period. The PFCOC can work as a bridge until red blood cells are available for transfusion, or where additional oxygen is required, notwithstanding possible limitations in peripheral tissue oxygenation.
Beta thalassaemia is an autosomal recessive inherited blood disorder which results in abnormal formation of Haemoglobin molecule and ineffective erythropoiesis. Patients need to be dependent on habitual blood transfusion and on unaffordable exorbitant therapies for continued existence. It has been hypothesized that if the level of foetal Haemoglobin increases, it compensates the need of adult Haemoglobin and hence, ameliorates clinical symptoms associated with beta thalassaemia major. Illation from previous studies has proved that reactivation of foetal Haemoglobin with the aid of natural compounds is a better alternative therapy for patients of beta thalassaemia because of its cost effectiveness and occurrence in natural eatables. Piceatannol, a naturally occurring stilbene, is less studied compound in comparison to resveratrol, but it shows a wide range of biological activities. This article has mainly focused on piceatannol and its application as a foetal Haemoglobin inducer in future.
Beta thalassaemia; Foetal Haemoglobin inducer; Piceatannol; Stilbene
Reviewed here are recent attempts to produce protein-based artificial oxygen carriers (“blood substitutes”). Most of these involve chemical or physical modifications on hemoglobin, although a recent line of research using hemerythrin instead of hemoglobin is also described. The focus is set on the extent to which these modifications alter the redox reactivity of the proteins, and on ways in which this can be done systematically and purposefully, within the framework of a working hypothesis where redox side-reactions hold an important role in the physiological outcome of experimental transfusions with artificial oxygen carriers.
hemoglobin; blood substitute; oxidative stress
Blood loss during total joint arthroplasty strongly influences the time to recover after surgery and the quality of the recovery. Blood conservation strategies such as pre-operative autologous blood donation and post-operative cell salvage are intended to avoid allogeneic blood transfusions and their associated risks. Although widely investigated, the real effectiveness of these alternative transfusion practices remains controversial.
Materials and methods
The surgery reports of 600 patients undergoing total joint arthroplasty (312 hip and 288 knee replacements) were retrospectively reviewed to assess transfusion needs and related blood management at our institute. Evaluation parameters included post-operative blood loss, haemoglobin concentration measured at different time points, ASA score, and blood transfusion strategies.
Autologous blood donation increased the odds of receiving a red blood cell transfusion. Reinfusion by a cell salvage system of post-operative shed blood was found to limit adverse effects in cases of severe post-operative blood loss. The peri-operative net decrease in haemoglobin concentration was higher in patients who had predeposited autologous blood than in those who had not.
The strengths of this study are the high number of cases and the standardised procedures, all operations having been performed by a single orthopaedic surgeon and a single anaesthesiologist. Our data suggest that a pre-operative autologous donation programme may often be useless, if not harmful. Conversely, the use of a cell salvage system may be effective in reducing the impact of blood transfusion on a patient’s physiological status. Basal haemoglobin concentration emerged as a useful indicator of transfusion probability in total joint replacement procedures.
total hip arthroplasty; total knee arthroplasty; pre-operative autologous blood donation; post-operative blood cell salvage system; blood management
The physiological anaemia experienced by preterm babies is exacerbated by common care practices such as early clamping of the umbilical cord at birth and gradual exsanguination by phlebotomy for laboratory monitoring. The need for subsequent transfusion with red blood cells can be reduced by delaying cord clamping for 30–60 s in infants who do not require immediate resuscitation. The need for transfusions can be further reduced by limiting phlebotomy losses, providing good nutrition, and using standard guidelines for transfusion based on haemoglobin or haematocrit. What those guidelines should be is not clear. Analysis of two recent large clinical trials comparing restrictive and liberal transfusion guidelines leads to several conclusions. Restrictive transfusion guidelines may reduce the number of transfusions given, but there is no reduction in donor exposures if a single-donor transfusion programme is used. There is some evidence that more liberal transfusion guidelines may help to prevent brain injury, but information on the impact of transfusion practice on long-term outcome is lacking. Until further guidance emerges, transfusion thresholds lower than those used in the two trials should not be used, as there is no evidence that lower thresholds are safe.
Transfusion of allogeneic blood products is given for correction of coagulation deficits and for the improvement in oxygen-carrying capacity or delivery. Blood transfusion has become safer following the advancement in blood testing using state-of-the-art viral assays; however, there continues to exist a variety of noninfectious transfusion risks that still remain and that cannot be entirely eliminated. Research is now directed towards understanding these lesser-known, but serious transfusion-related complications. This purpose of this review is to discuss a serious noninfectious cause of acute lung injury, transfusion-related acute lung injury (TRALI), which occurred in 2 recent cases in the intensive care unit, and to review the current literature of this syndrome.
Adult/etiology/immunology; blood transfusion/adverse effects; neutrophils/immunology; respiratory distress syndrome
The purpose of our study was to determine the effectiveness of a postoperative autologous blood reinfusion system as an alternative to homologous, banked blood transfusions in total knee arthroplasty. We carried out a prospective randomised controlled study on 60 patients having unilateral total knee replacements. In all these patients, the same surgical team applied the same surgical technique, and all patients followed the same rehabilitation program. In 30 of these patients (group A), a reinfusion system of unwashed salvaged blood was applied, and they were supplemented postoperatively with banked blood transfusions when required. A control group of 30 patients (group B), in whom standard suction drains were used, received one unit of homologous banked blood transfusion intraoperatively and additional blood transfusions postoperatively when required. The administration of banked blood transfusion was determined by the haemoglobin value (<9 mg/dl) and/or clinical signs (blood pressure, pulse, etc.). The values of haemoglobin, haematocrit and platelets were recorded preoperatively and the first, fifth and 15th postoperative days, respectively. Five patients of group A required nine units of homologous blood (0.3 units/patient) postoperatively. Ten patients of group B required an additional 15 banked blood units postoperatively (in total 45 banked blood units for group B; 1.5 units/patient). In the study group, the total homologous blood requirements were reduced by 80%, while the postoperative blood requirements were reduced by 50%. There was no significant difference in the postoperative haematocrit and haemoglobin values between the two groups. The cost of the blood management in the study group was reduced by 36%. The use of an autologous blood reinfusion system reduces highly effectively the demands of homologous banked blood transfusion in total knee arthroplasty.
OBJECTIVES: To determine the proportion of patients who received a blood transfusion after joint replacement, and to devise a simple method to ensure patients were transfused based on strict clinical and haematological need. DESIGN: Prospective audit over 2 years. PATIENTS AND METHODS: The study group was 151 patients who underwent total hip and knee arthroplasty in a typical district general hospital (Kettering) over a 2-year period. They were divided into three consecutive groups. Current practice was audited (producing the first group of 62 patients) and transfusion rates were compared to regional figures. Local guidelines were drawn up. A form was introduced on which the indications for any transfusion had to be documented prior to transfusion of the blood. This was designed to encourage transfusion only on strong clinical grounds or an haemoglobin (Hb) level < 8 g/dl. Transfusion practice was then re-audited (producing the second group of 44 patients) to assess whether practice had improved. A year later, all relevant staff were reminded by letter of the guidelines. The process was then re-audited (producing the third group of 45 patients) again to determine whether practice remained improved or not. RESULTS: In the first audit (current practice) of 62 patients, the overall transfusion rate was 71%, with a higher rate in the hip replacement group (84%) ordered mainly by anaesthetic staff. Ward staff were reluctant not to transfuse patients whose Hb level fell below 10 g/dl. In the second audit, the transfusion rate fell by nearly 50% to 37%, with almost identical figures for knee and hip replacement. In the third audit of 45 patients, a year later, the transfusion rate was 40% overall. CONCLUSIONS: Patients were being transfused routinely, generally without good clinical evidence of benefit to the patient. The audit process was successful in instituting change for the better in blood transfusion practice for elective joint replacement. The improved practice can be largely maintained provided staff are regularly reminded of appropriate guidelines and encouraged to transfuse for clinical need only. For absolute adherence to guidelines, we would recommend a compulsory form system be introduced for transfusion in the per-operative period, to ensure blood transfusion is only given when absolutely necessary.
Editor's Highlight: The development of hemoglobin-based oxygen carriers (HBOCs) as a replacement for whole-blood transfusions has been impeded by their systemic toxicity. This paper presents data from a series of HBOCs, demonstrating one candidate that meets predetermined safety criteria. This approach may allow the development of an acceptable blood substitute for human use.
Hemoglobin (Hb)-based oxygen carriers (HBOCs) are being developed as resuscitative fluids for use in multiple medical applications and in lieu of blood transfusion. However, cardiovascular, central nervous system, and renal adverse events have largely impeded progress. This has prompted a need to evaluate novel down selection approaches for HBOCs prior to in-depth preclinical and clinical safety testing. In the present study, polymerized bovine Hbs (PolybHbs) were prepared with increasing ratios of glutaraldehyde to bovine Hb (10:1, 20:1, 30:1, and 40:1). The optimal PolybHb candidate selection was based on a priori determined in vivo response to include a long circulating PolybHb with no measurable renal exposure, minimal cardiovascular response, limited oxidation to metHb in vitro, or in circulation and absence of acute end organ toxicity. Guinea pigs were dosed via a 50% blood for PolybHb exchange transfusion. Data suggested that the 30:1 preparation exhibited maximum circulatory exposure (AUC0–∞) with the lowest level of oxidation (plasma metHb formation) and minimal (< 10%) blood pressure elevation. Additionally, the 30:1 preparation was absent renal iron deposition as well as abnormal glomerular/tubular histopathology or serum creatinine elevation. Clearance pathways predominantly followed those consistent with endogenous Hb clearance based pathways. Therefore, data confirmed the ability to select a single PolybHb from a small library of HBOCs based on a priori determined characteristics. Moreover, the approach to down selection described could be applied to enhance the early predictability of human safety for this class of biological therapeutics to optimize for specific indications.
hemoglobin; polymerized hemoglobin; red blood cell substitute; transfusion medicine; oxygen therapeutic; pharmacokinetics/pharmacodynamics; toxicity
Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a fixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient’s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a “one-by-one” administration schedule. Evidence-based clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within well-constructed protocols will offer better prospects for blood conservation in selected IBD patients undergoing elective surgery.
Anaemia; Blood transfusion; Autologous blood transfusion; Inflammatory bowel diseases; Risk assessment
The use of blood transfusion was examined in 476 patients who underwent curative surgery for large bowel cancer. Of these patients, 128 were not transfused while 348 received a total of 1174 units of blood. A patient was considered over-transfused if the predischarge haemoglobin was more than 12 g/dl. Using this criteria and accepting that single unit transfusions should be avoided, transfusion could have been avoided in 30% of the patients and a total of 377 units were given unnecessarily. Major under-transfusion did not occur; no patient being discharged with a haemoglobin of less than 9 g/dl. This study shows that blood transfusion is overused and the reasons for its use rarely recorded. In view of the morbidity related to transfusion, it is suggested that surgeons and anaesthetists reappraise their transfusion policy and the first step in this must be to record the reason for transfusion.
This study determined the effects of serial, normovolemic, stepwise exchange transfusions with either 6% human serum albumin (HSA) or the hemoglobin-based oxygen carrier, HBOC-201, on tissue oxygenation of the heart, brain and kidney in intact anaesthetized pigs. Exchange transfusions to 10%, 30% and 50% of the pigs total blood volume were completed at a withdrawal rate of 1.0 ml/kg/min followed by an infusion rate of 0.5 ml/kg/min of HBOC-201 or iso-oncotically matched 6% HSA. Measurements included invasive systemic hemodynamic (blood pressures, left ventricular end diastolic pressure [LVEDP]), hematolic (hemoglobin, hematocrit, methemoglobin), acid-base (pH, pCO2) and biochemistry (serum lactate) measurements. Brain and kidney tissue oxygenation (tPO2) were determined by electron paramagnetic resonance (EPR) and heart tPO2 by O2 sensitive fiber optic probe. The main results demonstrated that tPO2 after HBOC-201 remained stable despite significant decreases in hematocrit and changing hemodynamics. In vivo tPO2 measurements (heart tPO2 average ≥ 22 mm Hg; brain tPO2 average ≥ 8 mmHg; and kidney tPO2 average ≥10 mmHg) were maintained in all groups at all times. Blood pressures were 20–30 mm Hg higher after HBOC-201 compared to HSA controls. Heart rate and LVEDP were not different among treatment groups. In conclusion, the administration of HBOC-201 maintained tPO2 in three vital organs after profound hemodilution.
Blood substitutes; HBOC-201; tissue oxygenation; isovolemic; resuscitation; brain; heart; kidney
The effects of red blood cell transfusion on the incidences of apnoea, bradycardia, tachycardia and oxygen desaturation over periods of 72 hours before and after transfusion were assessed in 25 infants with a gestational age of < or = 32 weeks (mean (SEM) 29.2 (0.4) weeks, birthweight 1170 (73) g; postnatal age at transfusion 39 (4) days). During transfusion haemoglobin rose from 78 (2) g/l to 117 (2) g/l. Significant decreases were observed in daily frequencies of apnoeas longer than 15 seconds (median from 2.7 to 0.9 events a day), tachycardias of more than 200 beats per minute (from 34 to 25 events per day), bradycardias below 100 beats per minute (from 65 to 12 events per day) and 80 beats per minute (from 8.4 to 3.3 events per day). Oxygen saturation improved in 20 of the infants. Transfusion improves cardiorespiration in preterm infants for several days.
To evaluate the outcomes of patients with gastric cancer bleeding who had been treated with palliative radiotherapy with haemostatic intent.
Methods and materials:
Fifty-two gastric cancer patients aged 52–92 years (median 78 years) with active bleeding or anaemia resulting from inoperable gastric cancer were treated with short-course radiotherapy. Responses to radiotherapy treatment were evaluated based on the changes of haemoglobin level, number of transfusions received before and after radiotherapy, and overall median survival.
Thirty-nine (75%) patients received single 8 Gy fraction, and 13 (25%) patients received 20 Gy in five daily fractions. The need for transfusion was evaluable in 44 patients, and the response rate was 50%, with less requirement for blood transfusions within four weeks of radiotherapy. There was also an increase in mean haemoglobin level (0.66 ± 1.12 g/dl, p < 0.01) after radiotherapy in 35 evaluable patients. The overall median survival (calculated from last day of treatment to date of death) was 160 days (95% CI of 119–201 days), making actuarial 12-month survival 15%.
Palliative short-course radiotherapy is a reasonably effective treatment that can provide durable palliation of bleeding in gastric cancer.
bleeding; gastric cancer; haemostasis; palliative; radiotherapy