Red cell requirements for intensive care units adhering to evidence-based transfusion guidelines

BACKGROUND: Anemia commonly complicates critical illness. Restrictive transfusion triggers are appropriate in this setting, but no large studies have measured red cell (RBC) requirements for intensive care patients when evidence-based transfusion guidelines are followed consistently. STUDY DESIGN AND METHODS: Data were recorded daily for 1023 of 1042 sequential admissions to 10 intensive care units (ICUs) over 100 days. The sample comprised 44 percent of all ICU admissions in Scotland during this period. RBC transfusions and the occurrence of clinically significant hemorrhage were recorded for every ICU day. Transfusion episodes were classified as either associated with or not associated with hemorrhage. Measures of RBC use were derived for the cohort and for Scotland with national audit data. RESULTS: A total of 39.5 percent (95% confidence interval [CI], 36.5%-42.5%) of admissions received transfusions. Eighteen percent of admissions received at least one transfusion associated with hemorrhage and 26 percent received at least one transfusion not associated with hemorrhage. The median (interquartile range) transfusion trigger in the absence of hemorrhage was 78 (73-78) g/L. The overall mean RBC use was 1.87 (95% CI, 1.79-1.96) units per admission or 0.34 (95% CI, 0.33-0.36) units per ICU-day. Forty-seven percent of RBCs administered were not associated with clinically significant hemorrhage. Mean RBC requirements for intensive care in Scotland were estimated to be 3950 (95% CI, 3780-4140) per million-adult-population per year. This represented 7 to 8 percent of the Scottish blood supply. CONCLUSIONS: Despite evidence-based transfusion practice, 40 percent of ICU patients receive transfusions, which account for 7 to 8 percent of the national blood supply.     

Plasma free fatty acid metabolism during storage of platelet concentrates for transfusion

New containers allow storage of platelet concentrates (PC) at 22 degrees C for up to 7 days, during which glycolytic and oxidative metabolism is vigorous. Recent evidence suggests that 85 percent of adenosine triphosphate regeneration is based on oxidative metabolism and that substrates other than glucose may be used. Because platelets can oxidize free fatty acids (FFA) as a possible source of energy during storage, the authors studied their availability, distribution, and turnover. Plasma FFA concentration was unchanged after 1 day of PC storage but significantly increased on Days 3, 5, and 7. Platelet-free plasma (PFP) stored under the same conditions as PC demonstrated a progressive increase in FFA, suggesting that some of the FFA accumulating in PC were derived from plasma rather than platelets. Indeed, during PC storage, plasma triglycerides decreased significantly, suggesting that they are a possible source of the increased levels of FFA found on Day 3 and thereafter. Thus, PC have a plasma FFA pool available continuously for oxidation during storage. Studies with radiolabeled palmitate suggested that FFA oxidation by platelets occurs during storage. The current findings show that plasma FFA could be a significant substrate for oxidative metabolism during storage of PC and that the oxidized FFA are replenished at least in part from plasma. These results may allow platelet storage to be improved, particularly in synthetic media.     

Red blood cell exchange transfusion in two patients with advanced erythropoietic protoporphyria

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare, autosomal dominant genetic disorder caused by the decreased or absent activity of ferrochelatase, the final enzyme in the heme biosynthetic pathway. This enzyme defect in peripheral blood progenitor cells leads to the accumulation of protoporphyrin deposits in multiple tissues. Plasmapheresis has been previously reported as an adjunctive therapy for patients with advanced hepatic EPP. Because the concentration of protoporphyrins is severalfold higher inside the red blood cell (RBC) compared to plasma, it was hypothesized that RBC exchange therapy might absorb excess protoporphyrins from the plasma and serve as an effective therapy to reduce protoporphyrin load in patients with advanced hepatic EPP. The effectiveness of RBC exchange plus hematin versus plasmapheresis plus hematin in two patients with advanced hepatic EPP is reported. STUDY DESIGN AND METHODS: Two patients with advanced hepatic EPP were treated with RBC exchange and plasmapheresis in the setting of recurrent disease in the graft (Patient 1) or preparation for liver transplantation (Patient 2). In vitro studies were performed to test transport of protoporphyrins from patients' plasma to normal RBCs. RESULTS: Compared with plasmapheresis, RBC exchange was more effective, for the duration of the therapy, in reducing blood levels of protoporphyrins. Liver function tests, however, showed only a modest improvement during therapy. In vitro extracellular protoporphyrin were rapidly adsorbed into normal RBCs. CONCLUSION: Neither RBC exchange nor plasmapheresis prevented progressive hepatic deterioration in advanced hepatic EPP despite a significant decrease in protoporphyrin levels.     

Indications for the transfusion of erythrocyte concentrates

Whole blood transfusions as usual are often not effective. The high fluid level overloads the circulatory system and the share of red blood corpuscles improves the hematocrit inconsiderably. On the contrary after application of erythrocyte suspension which has reducted volume the hematocrit increases and risks of the circulatory system will be prevented. Risks by means of whole-blood transfusions; advantages, indications, and production of erythrocyte concentrations are outlined.     

Current status of transfusion triggers for red blood cell concentrates.

Clinical practice guidelines on red blood cell transfusion (RBC) are based on expert opinion, animal studies and the few human trials available. Twelve randomized controlled trials on the benefits of RBC transfusions in humans have been published. In the absence of definitive outcome studies, numerous theoretical arguments have been put forward in favor or against the classic transfusion threshold of 100 g/l. However, data from randomized controlled trials suggest that overall morbidity (including cardiac) and mortality, hemodynamic, pulmonary and oxygen transport variables are not different between restrictive (transfusion threshold between 70 and 80 g/l) and liberal transfusion strategies and that a restrictive transfusion strategy is not associated with increased adverse outcomes. In fact, a restrictive strategy may be associated with decreased adverse outcomes in younger and less sick critical care patients. The majority of existing guidelines conclude that transfusion is rarely indicated when the hemoglobin concentration is greater than 100 g/l and is almost always indicated when it falls below a threshold of 60 g/l in healthy, stable patients or more in older, sicker patients. In anesthetized patients, this threshold should be modulated by factors related to the dynamic nature of surgery such as uncontrolled hemorrhage, microvascular bleeding, etc. Another important role of RBC relates to primary hemostasis and higher triggers may be appropriate in coagulopathic patients. RBC concentrates are administered to correct inadequate oxygen delivery and/or to sustain primary hemostasis. Reliable monitors of tissue oxygenation and hemostasis will be required to study the benefits (or lack thereof) of RBC transfusions. The quest for a universal transfusion trigger, i.e., one that would be applicable to patients of all ages under all circumstances, must be abandoned. All RBC transfusions must be tailored to the patient's needs, at the moment the need arises. In conclusion published recommendations are commensurate with existing knowledge and, unfortunately, their conclusions are limited. Future research and development should focus on the determination of optimal transfusion strategies in various patient populations and on reliable monitors to guide transfusion therapy.     

Clinical value of washed-platelet concentrates in patients with non- hemolytic transfusion reactions

In patients with severe allergic reactions to plasma proteins it is possible to observe such reactions to even the small quantity of plasma contained in platelet concentrates. A platelet washing solution was designed, and platelet concentrates for four such patients were washed before infusion. Transfusion reactions were completely eliminated by the washing procedure. Platelet recovery was equivalent to that of unwashed platelets, and hemostatic effectiveness of the infused platelet concentrates was evidenced by abrupt cessation of bleeding episodes, including purpura and hematuria. Platelet washing represents a valuable, rapid and simple approach to the problem patient with thrombocytopenia and severe reactions to plasma proteins.     

Red cell exchange transfusion for babesiosis in Rhode Island

We report four cases of clinically severe tick borne babesiosis treated with chemotherapy and adjunctive red cell exchange (RCE) at two Rhode Island hospitals from 2004 to 2007. All RCE procedures were performed using a Cobe Spectra device and were well tolerated without complications. The volume of allogeneic red cells used in the exchange was determined using the algorithm in the apheresis device with the input variables of preprocedure hematocrit, weight, height, an assumed allogeneic red cell hematocrit of 55 and a desired post procedure hematocrit of 27. The preprocedure level of parasitemia varied between 2.4% and 24% and the postprocedure level of parasitemia between 0.4 and 5.5% with an average overall percent reduction in parasitemia of 74%. Retrospectively, application of a new formula to calculate red cell mass appeared to correlate better with the percent reduction in parasitemia. Previous reports of RCE in babesiosis were reviewed. The reported reduction in parasitemia varied from 50% to >90%. Although a preprocedure level of parasitemia of 10% is sometimes used as a threshold for RCE in clinically severe babesiosis, this threshold does not have a firm empirical basis. No postprocedure desired level of parasitemia is indicated nor the mass of allogeneic red cells needed to achieve such a level. We conclude that current estimates of the dose of allogeneic red cells used in RCE are probably inaccurate, advocate a new formula to estimate this dose and suggest that a 90% reduction in parasitemia should be the minimally desired target of RCE in babesiosis. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Release of biologically active CD154 during collection and storage of platelet concentrates prepared for transfusion

Summary. Background: Millions of platelet transfusions are given each year. Transfusion reactions occur in as many as 30% of patients receiving unmodified platelet transfusions. The cause of some transfusion reactions remains unclear. The current paradigm suggests that platelet concentrates (PC) contain proinflammatory mediators that are released by white blood cells during collection, processing and storage. CD154 (CD40 ligand, CD40L) is a potent inflammatory mediator, normally sequestered inside the resting platelet, that is known to translocate to the platelet membrane and be shed into plasma in response to agonist activation. We hypothesized that platelet‐soluble CD154 (sCD154) is ‘spontaneously’ released by transfused platelets and plays a major role in transfusion reactions. Objectives: To determine the time course and biological properties of CD154 translocation and release during collection and storage of platelets for transfusion. Methods: We measured surface and sCD154 in platelets prepared by the platelet‐rich plasma method or apheresis by fluorescence‐activated cell sorting and enzyme‐linked immunosorbent assay, respectively. The specific biological activity of platelet sCD154 was assayed by stimulation of the CD154/CD40 pathway in known CD40‐positive cells with PC‐derived supernatants. Results and conclusions: We demonstrate that PCs prepared for transfusion have high levels of membrane‐bound CD154 and sCD154, with maximum levels being seen 72 h after platelet collection. Importantly, we show that platelet‐derived sCD154 potently stimulates CD40‐positive cells. We propose that platelet‐derived CD154 is a key ‘cytokine’ responsible for adverse reactions associated with platelet transfusions. Improved methods of platelet collection and/or storage, which limit CD154 expression, could reduce the risks of transfusion reaction.     

Relationship of the time of storage and transfusion reactions to platelet concentrates from buffy coats

BACKGROUND: Transfusion reactions to platelet concentrates prepared from buffy coats (BC-PCs) were reviewed to determine the effect of some variables of BC-PC preparation and storage: time of BC storage before BC-PC preparation (1-2 days); time of BC-PC storage before transfusion (1-5 days); no white cell reduction versus laboratory and bedside BC-PC white cell reduction. STUDY DESIGN AND METHODS: A multiple linear logistic regression model was used by which the relative effect of one variable is expressed as the relative risk of transfusion reaction against a baseline level (1-day storage, no white cell reduction). RESULTS: During the 14 months of study, a total of 2707 BC-PC transfusions were given to 192 patients; 37 reactions (1.4%) were reported in 25 patients (13%). The transfusion reactions were febrile, nonhemolytic in 23 cases; allergic in 5; febrile and allergic in 2; and other in 7. The relative risk of transfusion reaction to BC-PCs prepared from BCs stored for 2 days was 1.98 times that to BC-PCs prepared from BCs stored for 1 day (p = 0.07). The relative risk of transfusion reaction of 5-day-old BC-PCs was 10.7 times that of 1-day- old BC-PCs (p = 0.001). The relative risk of transfusion reactions of BC-PCs white cell-reduced in the laboratory and at the bedside were 0.65 (p = 0.3) and 1.87 (p = 0.1) times, respectively, that of non- white cell-reduced BC-PCs. CONCLUSION: Time of storage seems to be an important variable associated with BC-PC transfusion reaction.     

Red cell transfusion trigger-avoiding the highs and the lows

<正>One of the most vexing problems in AIHA is handling the acute situation where all blood is incompatible and the patient has severe,worsening anemia. Since the panagglutinin in the patient's serum typically reacts with all donor red cells,crossmatching donor blood is a difficult and time consuming process and probably of little benefit. The most pressing problem in a patient with previous pregnancies or transfusions is detecting alloantibody which may be hidden by the autoantibody. Sophisticated immunohematology laboratories can use a combination of procedures including differential adsorption and warm autoadsorption to identify underlying alloantibodies.     

Red blood cell transfusion in patients with subarachnoid hemorrhage: a multidisciplinary North American survey

Introduction  

Anemia is associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). It remains unclear whether this association can be modified with more aggressive use of red blood cell (RBC) transfusions. The degree to which restrictive thresholds have been adopted in neurocritical care patients remains unknown.     

Red cell transfusion therapy in the critical care setting

According to our own experience and published reports the frequency of red cell transfusion in intensive care units is in the range of 0.2 to 0.4 units per patient per day and is dependent upon the local strategy, the patients involved and the kind of surgery performed. The rationale for red cell transfusion is to maintain or restore the oxygen carrying capacity of the blood to avoid tissue hypoxia which occurs when oxygen delivery drops below a certain critical value. Besides bleeding, phlebotomy is also a significant source of blood loss in critically ill patients. According to several recent reviews and consensus articles there is no basis for a fixed indicator for transfusion, such as a haemoglobin concentration of < 100 gL-1. The decision to transfuse has to be made according to the patients individual status. The major adaptive mechanism in response to acute anaemia is an increase in cardiac output and hence blood flow to tissues. As a consequence even moderate degrees of acute anaemia may not be tolerated by patients with cardiac disease, whilst marked anaemia carries a considerable risk of ischaemia in patients with brain lesions or cerebral arterial stenoses. In critically ill patients it has been postulated that supply dependency of oxygen consumption occurs over a wide range of oxygen delivery, far above the critical values of oxygen delivery seen under normal conditions. Maximising oxygen delivery was therefore formulated as a goal in these patients. However, whether pathological supply dependency of oxygen delivery really exists in critically ill patients is still under discussion and recent studies found no benefit in maximising oxygen delivery to this patient group. However, individualised triggers for red blood cell transfusion are adequate for critically ill patients considering their co-morbidities and severity of disease. Finally, the decision to transfuse must also take into account the potential risks (infectious and non-infectious), as well as benefits for the individual patient. In the future, the level of transfusions may be reduced by using blood sparing techniques such as blood withdrawal in closed systems, bedside microchemistry, intravascular monitors, or autotransfusion of drainage blood in intensive care units.     

Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion

BACKGROUND: Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients.
STUDY DESIGN AND METHODS: A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO- and D-matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage-leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity.
RESULTS: Sixty-five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations.
CONCLUSION: This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD patients.