Transfusion

BACKGROUND: Blood utilization has long been suspected to consume more health care resources than previously reported. Incomplete accounting for blood costs has the potential to misdirect programmatic decision making by health care systems. Determining the cost of supplying patients with blood transfusions requires an in‐depth examination of the complex array of activities surrounding the decision to transfuse.

STUDY DESIGN AND METHODS: To accurately determine the cost of blood in a surgical population from a health system perspective, an activity‐based costing (ABC) model was constructed. Tasks and resource consumption (materials, labor, third‐party services, capital) related to blood administration were identified prospectively at two US and two European hospitals. Process frequency (i.e., usage) data were captured retrospectively from each hospital and used to populate the ABC model.

RESULTS: All major process steps, staff, and consumables to provide red blood cell (RBC) transfusions to surgical patients, including usage frequencies, and direct and indirect overhead costs contributed to per‐RBC‐unit costs between $522 and $1183 (mean, $761 ± $294). These exceed previously reported estimates and were 3.2‐ to 4.8‐fold higher than blood product acquisition costs. Annual expenditures on blood and transfusion‐related activities, limited to surgical patients, ranged from $1.62 to $6.03 million per hospital and were largely related to the transfusion rate.

CONCLUSION: Applicable to various hospital practices, the ABC model confirms that blood costs have been underestimated and that they are geographically variable and identifies opportunities for cost containment. Studies to determine whether more stringent control of blood utilization improves health care utilization and quality, and further reduces costs, are warranted.

BACKGROUND: The purpose of this study was to assess current practices in blood management in elective orthopedic surgery in Europe.

STUDY DESIGN AND METHODS: For this 225‐center prospective survey, data were collected on 3996 patients. Actual perioperative blood loss was compared to preoperative estimates. Differences in Hb levels and other outcome variables for patients receiving allogeneic versus autologous transfusions were evaluated. The probability of allogeneic transfusion based on selected predictor variables was estimated.

RESULTS: A total of 2640 (67%) hip and 1305 (33%) knee arthroplasty patients were evaluated. Estimated blood loss (median, 750 mL) was significantly lower than computed blood loss (median, 1944 mL). A total of 2762 (69%) patients received transfusions, including 1393 (35%) autologous‐only and 1024 (25%) allogeneic‐only. The probability of allogeneic transfusion decreased with increasing baseline Hb, but differentially so for men and women. Transfusion triggers were Hb levels of 8.93 ± 1.83 g per dL for allogeneic transfusions, and 21 percent of these occurred when the Hb level was greater than 10 g per dL. Autologous blood transfusion was associated with a significantly lower rate (1%) of wound infections than allogeneic blood transfusion (4.2%).

CONCLUSION: Accurate assessment of preoperative Hb levels, better estimation of perioperative blood loss, efficient use of autologous blood, adherence to transfusion guidelines, and pharmacologic alternatives contribute to effective and comprehensive blood and anemia management.

For many years, an association between ABO histo‐blood group and risk of thrombosis has been recognized. Blood group non‐O (A, B, and AB) individuals have consistently been found to demonstrate increased incidence of both arterial and venous thrombotic disease, compared to group O individuals. This increased risk is attributable to the fact that ABO blood group influences plasma levels of a coagulation glycoprotein named von Willebrand factor (VWF). VWF levels are 25 percent higher in non‐O compared to group O individuals. The mechanism by which ABO group determines plasma VWF levels has not been determined. ABO(H) carbohydrate antigenic determinants, however, are expressed on the N‐linked glycan chains of circulating plasma VWF. This review will focus on the carbohydrate structures of VWF and recent studies suggesting that subtle variations in these structures (particularly differences in ABO blood group antigen expression) may have clinically significant effects on VWF proteolysis and clearance.

A method is described which permits dilute red cell suspensions (1/32%) to be used in plastic microtiter plates for detecting hemagglutinins at unusually high dilutions. The use of suitable additives to the hemagglutination mixture enables excellent settling patterns and a high sensitivity to be obtained. Direct agglutination, inhibition, enzyme promoted agglutination, and Coombs tests can all be performed. Quantitative studies demonstrate the discriminatory powers of the technic. The method may be useful for economizing in the consumption of reagents in blood grouping.

Mesenchymal stem cells (MSCs) have recently generated great interest in the fields of regenerative medicine and immunotherapy due to their unique biologic properties. In this review we attempt to provide an overview of the current clinical status of MSC therapy, primarily focusing on immunomodulatory and regenerative or tissue repair applications of MSCs. In addition, current manufacturing is reviewed with attention to variation in practices (e.g., starting material, approach to culture and product testing). There is considerable variation among the 218 clinical trials assessed here; variations include proposed mechanisms of action, optimal dosing strategy, and route of administration. To ensure the greatest likelihood of success in clinical trials as the field progresses, attention must be given to the optimization of MSC culture.

BACKGROUND: As clinical diagnosis of heparin‐associated thrombocytopenia (HAT) is often difficult, confirmation by sensitive laboratory assays is desirable.

STUDY DESIGN AND METHODS: The sensitivity of the heparin‐induced platelet activation (HIPA) test and the platelet aggregation test (PAT) was prospectively compared by using the sera of 209 patients with the putative diagnosis of HAT. Both assays were performed concomitantly with platelets of the same four donors using a different combination of donors from day to day. Further, all sera were assessed with a platelet factor 4 (PF4)/heparin enzyme‐linked immunosorbent assay (ELISA).

RESULTS: Positive results were obtained with 33 percent of sera in the PF4/heparin ELISA, with 33.5 percent of sera in the HIPA test, and with 11.5 percent of sera in the PAT. The PF4/heparin ELISA and the HIPA test showed no difference in sensitivity (p = 0.27 by McNemar's test) and were more sensitive than PAT (p < 10(‐8) by McNemar's test). However, they recognized different patient cohorts. Nine HIPA‐indeterminate and 12 HIPA‐negative sera were positive in the PF4/heparin ELISA. Eight of the nine indeterminate sera caused platelet activation with high heparin concentrations in the HIPA test. Eleven of the 12 negative sera contained no IgG, but 9 contained IgM and 2 contained IgA HAT antibodies. Four sera that were indeterminate in the PF4/heparin ELISA and 18 sera that were negative were positive in the HIPA test. None of the sera that were positive in the PAT was missed in the HIPA test, but two of those were negative in the PF4/heparin ELISA. All sera were assessed with four low‐molecular‐weight heparins and a low‐molecular‐ weight heparinoid in the HIPA test with platelets from the same four donors. Low‐molecular‐weight heparin caused platelet activation with positive sera in 98 percent of tests, and the heparinoid did so in 10 percent; in a further 12.8 percent, crossreactivity to the low‐ molecular‐weight heparinoid could not be excluded.

CONCLUSION: The majority of HAT antibodies react with a PF4/heparin complex, but there is strong evidence that other antigens are involved in some patients. The HIPA test and the PF4/heparin ELISA are sensitive for diagnosing HAT, and they complement one another.

ĐỀ CƯƠNG: Bằng chứng rõ ràng từ các động vật nhiễm bệnh trong thực nghiệm và bằng chứng không đầy đủ từ con người nhiễm bệnh tự nhiên cho thấy rằng máu có thể chứa nồng độ thấp của tác nhân gây bệnh Creutzfeldt-Jakob (CJD), tuy nhiên, các thành phần máu chưa bao giờ được xác định là nguyên nhân gây ra CJD ở con người.

THIẾT KẾ VÀ PHƯƠNG PHÁP NGHIÊN CỨU: Các thành phần máu và các phân đoạn huyết tương đã được chế biến từ máu của chuột mà trước đó đã bị nhiễm một chủng có khả năng lây nhiễm bệnh não bọt ở người (TSE). Các thử nghiệm sinh học khả năng lây nhiễm được thực hiện trên chuột khỏe mạnh, và não của tất cả các động vật thử nghiệm chết trong quá trình thí nghiệm đã được kiểm tra để tìm protein kháng proteinase.

The serologic reactivity and epidemiology associated with different hepatitis C virus (HCV) variants were investigated in a cohort of 113 anti‐HCV‐positive donors. In Scotland, HCV type 1 accounted for one‐ half of all infections; 40 percent of subjects were infected with HCV type 3, and the remainder were infected with type 2. Reactivity with the NS‐4‐encoded antigens in the first‐generation anti‐c100 assay was absent in 68 percent of donors infected with types 2 and 3, as compared with 10 percent for those infected with type 1. Even when combined with surrogate marker testing, first‐generation tests would have failed to detect 12 percent of HCV‐infected blood donors. The age distribution, incidence of past infection with hepatitis B virus, and reported risk factors were similar in donors infected with types 1 and 3 (mean ages were 31.9 and 29.9; 18 and 17.5% were positive for antibody to hepatitis B core antigen; and 47 and 48% had past intravenous drug abuse). However, the distributions of alanine aminotransferase levels were significantly different in those infected with type 3 (abnormally raised in 83%) and those infected with type 1 (55% abnormal alanine aminotransferase; p < 0.05) or type 2 (60%; p < 0.01) and those who were nonviremic (8%; p < 0.0001). These data suggest that HCV type 1 is the most common HCV infection in blood donors and that infection with HCV type 3 may be associated with more severe liver disease, because of more recent infection or because of a greater inherent pathogenicity of type 3 variants.

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions toRBCsin the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high‐energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affectRBCmorphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long‐storedRBCsand promote the rapid clearance of up to one‐fourth of long‐storedRBCsfrom the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of storedRBCshave observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects.