Blood doping in athletes--detection of allogeneic blood transfusions by flow cytofluorometry

Athletes may undergo blood transfusion to increase their red cell mass and the oxygen carrying capacity of their blood in order to confer a competitive advantage. Allogeneic transfusions are normally mismatched at one or more minor blood group antigens. The most sensitive and accurate method known to detect this form of blood doping is flow cytometry. Low percentages of antigen-positive and antigen-negative red blood cells (RBCs) can be quantitated using suitable specific alloantibodies and careful analysis. By testing blood samples taken at various times, a reduction in the percentage of a minor population of RBCs will indicate transfusion has occurred.     

Neonatal red blood cell transfusions

Red blood cell and blood product transfusion in the fetus, neonate, and premature infant are often administered with poorly defined indications and unintentional adverse consequences. Products may be altered in an effort to limit potential adverse events or may be specially selected to meet the unique needs of a specific diagnosis. One area of particular concern to neonatologists is selection blood for small volume (5-15 mL/kg) transfusions in premature infants. For infants, use of red blood cells collected in anticoagulant-additive solutions and administered in small aliquots over the shelf life of the product to decrease donor exposure has supplanted the use of fresh red blood cells with each transfusion resulting in a donor exposure. The safety of this practice has been documented and procedures established to aid a transfusion service in making these products available. Less well established are the indications for transfusion in this population; hemoglobin or Hematocrit alone are likely insufficient unless clinical findings like oxygen desaturation, apnea, and bradycardia are part of the criteria used to define transfusion need. The comorbidities that increase oxygen demands in these infants, like bronchopulmonary dysplasia and increased oxygen consumption to accommodate growth, must be part of the decision to transfuse. Noninvasive methods or assays that will reflect the unique pathophysiology of oxygen delivery and peripheral oxygen offloading are needed.     

Current issues relating to the transfusion of stored red blood cells

The development of blood storage systems allowed donation and transfusion to be separated in time and space. This separation has permitted the regionalization of donor services with subsequent economies of scale and improvements in the quality and availability of blood products. However, the availability of storage raises the question of how long blood products can and should be stored and how long they are safe and effective. The efficacy of red blood cells was originally measured as the increment in haematocrit and safety began with typing and the effort to reduce the risk of bacterial contamination. Appreciation of a growing list of storage lesions of red blood cells has developed with our increasing understanding of red blood cell physiology and our experience with red blood cell transfusion. However, other than frank haemolysis, rare episodes of bacterial contamination and overgrowth, the reduction of oxygen-carrying capacity associated with the failure of some transfused cells to circulate, and the toxicity of lysophospholipids released from membrane breakdown, storage-induced lesions have not had obvious correlations with safety or efficacy. The safety of red blood cell storage has also been approached in retrospective epidemiologic studies of transfused patients, but the results are frequently biased by the fact that sicker patients are transfused more often and blood banks do not issue blood products in a random order. Several large prospective studies of the safety of stored red blood cells are planned.     

Scientific aspects of supplying blood to distant military theaters

PURPOSE OF REVIEW: Reduction in combat zone morbidity and mortality requires rapid delivery of safe blood products as an integral element of advanced trauma surgical care. This review of the current literature presents scientific aspects of supplying blood for rapid delivery to enhance survival and patient outcome in the combat zone. RECENT FINDINGS: Most deaths due to hemorrhage can be averted by transfusion during the first hour from injury; therefore, maintaining a dependable inventory of blood products in combat support hospitals is essential. Current casualty care in distant geographic locations involves rapid air evacuation to combat support hospitals or fleet hospitals, where massive transfusions may be required. Resuscitation by forward surgical teams utilizing red blood cells before air evacuation or in-flight has also been reported. To improve survival, these massive transfusions should be composed of not only red blood cells but also other blood components and plasma factors. SUMMARY: Rapid on-site combat casualty transfusion support requires specialized blood transport containers and transfusion practices not observed in noncombat settings, such as the mobile walking blood bank and a frozen blood program. Additionally, technology for improved transport containers, cell-free hemoglobin-based oxygen carriers, freeze-dried blood, and recombinant activated coagulation factor has attracted focused interest.     

冰冻解冻去甘油红细胞研究进展

<正>冰冻解冻去甘油红细胞主要用于稀有血型血液及自体血液的长期保存,可减少输血反应,避免酸中毒、高钾血症及输血传播疾病,可杜绝因缺血引发的死亡事件,冰冻解冻去甘油红细胞制剂的作用是其他制剂所不能替代的,本文介绍冰冻解冻去甘油红细胞的研究进展。1冰冻解冻去甘油红细胞的应用范围目前冰冻解冻去甘油红细胞主要用途是:稀有血型患者的临床输血,Rh(D)阴性患者输血,其他稀有血型患者输血;自身输血,ABO亚型、孟买血     

Precautions surrounding blood transfusion in autoimmune haemolytic anaemias are overestimated

Background

It is very evident that many precautions are taken regarding transfusion of red blood cells in patients with autoimmune haemolytic anaemia. Frequently, considerable efforts are made to examine the indication and serological compatibility prior to transfusion in such patients. However, at times, this may unnecessarily jeopardize patients who urgently require a red blood cell transfusion.

Materials and methods

Thirty-six patients with warm-type autoimmune haemolytic anaemia were included in this study. All patients had reactive serum autoantibodies and required blood transfusion. Standard serological assays were employed for the detection and characterization of antibodies to red blood cells.

Results

A positive direct antiglobulin test was observed in all 36 patients, in addition to detectable antibodies in both the eluate and serum. Significant alloantibodies were detected in the serum samples of three patients (anti-c, anti-JK^a, and anti-E). In 32 patients, red blood cell transfusion was administered with no significant haemolytic transfusion reactions due to auto- and/or allo-antibodies. Due to overestimation of positive cross-matches three patients received no transfusion or delayed transfusion and died, and one patient died due to unrecognised blood loss and anaemia which was attributed to an ineffective red blood cell transfusion.

Discussion

Many of the reported recommendations regarding transfusion of red blood cells in autoimmune haemolytic anaemia are highly questionable, and positive serological cross-matches should not result in a delay or refusal of necessary blood transfusions.     

机洗冰冻红细胞在日常及突发事件中伤员救治的应用

目的:机器洗涤冰冻红细胞在日常和突发事件中的紧急抢救可行性。方法:选择日常及交通伤患者的大出血中冰冻红细胞输注,观察各种指标。结果:患者在输注冰冻红细胞后各项指标正常,效果明显,无输血反应。结论:冰冻红血细胞可应用于日常和紧急大出血的抢救。     

Utilization and quality of cryopreserved red blood cells in transfusion medicine

Cryopreserved (frozen) red blood cells have been used in transfusion medicine since the Vietnam war. The main method to freeze the red blood cells is by usage of glycerol. Although the usage of cryopreserved red blood cells was promising due to the prolonged storage time and the limited cellular deterioration at subzero temperatures, its usage have been hampered due to the more complex and labour intensive procedure and the limited shelf life of thawed products. Since the FDA approval of a closed (de) glycerolization procedure in 2002, allowing a prolonged postthaw storage of red blood cells up to 21 days at 2–6°C, cryopreserved red blood cells have become a more utilized blood product. Currently, cryopreserved red blood cells are mainly used in military operations and to stock red blood cells with rare phenotypes. Yet, cryopreserved red blood cells could also be useful to replenish temporary blood shortages, to prolong storage time before autologous transfusion and for IgA-deficient patients. This review describes the main methods to cryopreserve red blood cells, explores the quality of this blood product and highlights clinical settings in which cryopreserved red blood cells are or could be utilized.     

Evaluation of the potassium adsorption capacity of a potassium adsorption filter during rapid blood transfusion

The concentration of extracellular potassium in red blood cell concentrates (RCCs) increases during storage, leading to risk of hyperkalemia. A potassium adsorption filter (PAF) can eliminate the potassium at normal blood transfusion. This study aimed to investigate the potassium adsorption capacity of a PAF during rapid blood transfusion. We tested several different potassium concentrations under a rapid transfusion condition using a pressure bag. The adsorption rates of the 70‐mEq/l model were 76·8%. The PAF showed good potassium adsorption capacity, suggesting that this filter may provide a convenient method to prevent hyperkalemia during rapid blood transfusion.     

Variable leukocyte composition of red blood cell concentrates prepared in top-bottom systems: possible implications for pre-transplant blood transfusion

BACKGROUND AND OBJECTIVES: The beneficial effect of blood transfusion on kidney graft survival requires the presence of leukocytes in the transfusate, but a minimal dose has not been defined, nor has the role of individual leukocyte subsets been investigated. In the Netherlands, a standard pre-transplant blood transfusion consists of a buffy coat (BC)-depleted red blood cell concentrate (RBCC) containing a maximum of 1.2x10(9) residual leukocytes per unit. However, leukocyte subset composition is not standardized. MATERIALS AND METHODS: Using FACS analysis, this study compared the residual leukocyte composition of RBCCs produced by Compomat((R)) and Optipress((R)), two currently used top-bottom systems. Results: While the total leukocyte content of the RBCCs was equivalent in both press types (0.5x10(9)), the percentage of mononuclear cells (lymphocytes and monocytes) was significantly higher in the Compomat as compared with the Optipress system (p < 0. 0001), resulting in significantly higher numbers of transfused T cells, B cells, HLA-DR-positive cells, NK cells and stem cells. CONCLUSIONS: The leukocyte composition of a pre-transplant blood transfusion depends on the BC depletion method used; this might differentially affect the tolerizing or immunizing potential of a pre-transplant blood transfusion.     

Microcirculatory basis for the design of artificial blood

Artificial blood or blood substitutes are being developed using molecular solutions of modified free hemoglobin. When these products are used and the red blood cell mass is reduced below the transfusion trigger, there is a condition of extreme hemodilution which is characterized by a significant reduction of blood viscosity and NO production, reflex vasoconstriction, decreased functional capillary density, and impaired microvascular function. This combination of events may be lethal because decreased NO availability may also increase the intrinsic oxygen consumption of the tissue. Current developments in the understanding of the physiology of the microcirculation in extreme hemodilution, and the physical events associated with the substitution of red blood cells with molecular hemoglobin solutions show that a viable "artificial blood" can be obtained from a new formulation of the product, where viscosity is such that when introduced in the circulation the resulting viscosity of blood is close to normal, the dissociation curve is left shifted and the concentration of hemoglobin is in the range of 3-5 g Hb/dl. This formulation redistributes viscous losses in the circulation causing higher capillary pressure which maintains functional capillary density, a key parameter in tissue survival. Furthermore the increased plasma viscosity increases shear stress in the microcirculation, enhancing the production shear dependent vasodilators, thus counteracting the vasoconstrictor effects due to NO scavenging by free hemoglobin solutions. A principal feature of this formulation is that it maintains microvascular function when the transfusion trigger is passed and the circulation is subjected to extreme hemodilution.     

Kinetics of heat-damaged homologous red blood cells in patients with homozygous beta-thalassemia in relation to blood transfusion

The kinetics of heat-damaged homologous red blood cells (HDE) was studied prior to and 7-10 d following blood transfusion in 14 patients with homozygous beta-thalassemia. On the basis of our results, beta-thalassemic patients were classified into two distinct groups. In the first group the pretransfusion HDE extraction efficiency of the spleen was significantly lower than that of the second group and it increased dramatically following blood transfusion. On the contrary, the relatively higher pretransfusion HDE extraction efficiency of the patients of the second group showed a significant decrease after blood transfusion. These differences between the two groups of beta-thalassemics might be attributed to the different qualitative as well as quantitative alterations of the splenic vascular bed occurring in these patients during the course of their disease. Furthermore, there was convincing evidence that part of the HDE mixture was extracted by RES sites outside the spleen, a function which is also affected by blood transfusion.     

Patterns of Autologous Blood Use in Elective Orthopedic Surgery: Does the Availability of Autologous Blood Change Transfusion Behavior?

We studied the orthopedic surgery service at our institution to determine whether the mere availability of autologous blood (AB) affected transfusion practice. As a group, patients who had AB available received an average of 1.11 fewer red cell units per hospitalization than did patients with only homologous blood (HB) available. At every transfusion episode, those patients having AB available received fewer red cell units than did patients without AB available. Predeposit of autologous red cells was effective in protecting 77.6% of patients from HB exposure. The availability of autologous red cells resulted in an overall more conservative approach to transfusion.     

Kinetics of heat-damaged homologous red blood cells in patients with homozygous ß-thalassemia in relation to blood transfusion

The kinetics of heat-damaged homologous red blood cells (HDE) was studied prior to and 7–10 d following blood transfusion in 14 patients with homozygous ß-thalassemia. On the basis of our results, ß-thalassemic patients were classified into two distinct groups. In the first group the pretransfusion HDE extraction efficiency of the spleen was significantly lower than that of the second group and it increased dramatically following blood transfusion. On the contrary, the relatively higher pretransfusion HDE extraction efficiency of the patients of the second group showed a significant decrease after blood transfusion. These differences between the two groups of ß-thalassemics might be attributed to the different qualitative as well as quantitative alterations of the splenic vascular bed occurring in these patients during the course of their disease. Furthermore, there was convincing evidence that part of the HDE mixture was extracted by RES sites outside the spleen, a function which is also affected by blood transfusion.     

Long-term survival after colorectal surgery associated with buffy-coat-poor and leucocyte-depleted blood transfusion: a follow-up study

A Danish clinical trial showed that transfusion with leucocyte-depleted red blood cells reduces postoperative infectious complications compared with cells without buffy-coat. However, the effect on long-term outcome is unknown. We followed up the 142 cancer patients transfused with buffy-coat-poor red cells, the 118 transfused with leucocyte-depleted blood, and the 329 who were not transfused, until 2003. After 7 years' follow-up, survival for those with leucocyte-depleted blood transfusion (46 [41%]) was not significantly different from transfusion of blood without buffy-coat (59 [45%], p=0.51). Although survival is reduced by blood transfusion, it does not differ between the two transfusion regimens.     

Exchange Transfusions with Frozen Blood

Abstract. On 15 newborn infants, 31 exchange transfusions were performed, 11 with previously frozen red blood cells resuspended in albumin-electrolyte-glucose solution, 4 with previously frozen red blood cells resuspended in fresh frozen plasma and 16 with ACD blood.
Good clinical effects were obtained in all cases and no untoward clinical reactions were noticed. More pronounced decreases in vB pH and vB standard bicarbonate were noted after exchange transfusions with frozen blood than after ACD blood transfusions. Small and unimportant changes of plasma electrolytes were recorded following exchange transfusions with frozen blood. The P-haemoglobin concentrations were higher in the frozen blood than in the ACD blood, resulting in an increase of P-haemoglobin following exchange transfusion with frozen blood.
The wash-out effect of the frozen blood was indicated by a reduction of platelets, fibrinogen and IgG during the exchange transfusions to 20% of the original value. Furthermore, a decrease in coagulation capacity was observed as revealed by considerable changes in TT and APTT values.
For newborn infants with suspected or manifest coagulation disorders and for newborn infants needing more than one exchange transfusion, frozen, thawed and washed red blood cells should be resuspended in fresh or fresh frozen plasma when used as transfusion blood.     

Replacement of Massive Blood Loss

Treatment of massive blood loss has experienced major changes during the recent decade. The transition towards pure component therapy has been the most significant issue, which has compelled the clinician to revise some of their basic strategics in treatment of massively bleeding patients. The importance of adequate volume resuscitation with crystalloids and colloids is still unrefutable, but the therapy of hemorrhagic derangements has changed. Plasma-poor red cells (RC) are now commonly used instead of whole blood (WB) or packed red blood cells (PRBC) to correct oxygen carrying capacity during massive blood loss. As the plasma content of RC is minimal, deficit of plasma and coagulation factors develops earlier than during transfusion of WB and PRBC. Hypofibri- nogenemia develops first followed by other coagulation factor deficits and later by thrombocytopenia. Therefore the use of fresh frozen plasma (FFP) is the primary intervention to treat abnormal bleeding encountered in the replacement of massive blood loss with RC. As the development of thrombocytopenia is a highly individual phenomenon, the transfusion of platelets should be guided by repeatedly determined platelet counts.     

Autologous blood salvage in the era of patient blood management

Almost 150 years after the first autologous blood transfusion was reported, intraoperative blood salvage has become an important method of blood conservation. The primary goal of autologous transfusion is to reduce or avoid allogeneic red blood cell transfusion and the associated risks and costs. Autologous salvaged blood does not result in immunological challenge and its consequences, provides a higher quality red blood cell that has not been subjected to the adverse effects of blood storage, and can be more cost‐effective than allogeneic blood when used for carefully selected surgical patients. Cardiac, orthopaedic and vascular surgery procedures with large anticipated blood loss can clearly benefit from the use of cell salvage. There are safety concerns in cases with gross bacterial contamination. There are theoretical safety concerns in obstetrical and cancer surgery; however, careful cell washing as well as leucoreduction filters makes for a safer autologous transfusion in these circumstances. Further studies are needed to determine whether oncologic outcomes are impacted by transfusing salvaged blood during cancer surgery. In this new era of patient blood management, where multimodal methods of reducing dependence on allogeneic blood are becoming commonplace, autologous blood salvage remains a valuable tool for perioperative blood conservation. Future studies will be needed to best determine how and when cell salvage should be utilized along with newer blood conservation measures.     

Perioperative blood transfusion and solid tumour recurrence

Evidence regarding the association of blood transfusions with recurrence of solid tumours is largely conflicting. This is perhaps unsurprising given the retrospective nature of the studies performed to date, the complexity of the disease and its treatment, and variations in local transfusion practices. Nonetheless, new data demonstrating that transfusions of whole blood, as opposed to red cell concentrates, are associated with earlier cancer recurrence are most readily explained by a cause and effect relationship. There is a growing literature documenting previously unforeseen immunologic consequences of homologous blood transfusion. These possible clinical consequences include earlier cancer recurrence and increased susceptibility to infection with bacteria and viruses. The questions raised in this review can be answered conclusively only by controlled prospective studies. For the present the prudent clinician will select red blood cells rather than whole blood for transfusion, employ autologous transfusions whenever feasible, and recognize that blood transfusion is a therapy with considerable benefits, but also considerable risks.     

Liquid-stored red blood cells for transfusion. A status report

Blood transfusion in a modern sense means the transfusion of red cells, when necessary supplemented by other components. The demand for plasma and plasma fractions and for platelets for therapeutic use has had an influence on the technique for preparing red cells. Automated devices have made it possible to perform collection as well as separation under more standardized conditions. Improved techniques for storage of red cells have prolonged the shelf life somewhat but most of the available methods disregard the rapid loss of 2,3-diphosphoglycerate and the accompanying increase in oxygen affinity. Methods are available which reduce the number of contaminating leukocytes to low levels, but information is still incomplete as to the degree of depletion actually needed.