Transfusion

BACKGROUND:  Parvoviridae are small nonenveloped viruses that are known to be highly resistant to physico‐chemical treatments. Because low pH is frequently applied to process intermediates or final products, the impact of such conditions on the human erythrovirus B19 (B19V) and the mouse parvovirus (mice minute virus, MMV) was assessed, which is often used as a model for B19V. Owing to the lack of a suitable cultivation and/or detection system for B19V no such data exist so far.

STUDY DESIGN AND METHODS:  Virus inactivation was monitored by decrease of infectivity and loss of capsid integrity. Infectious B19V was quantified by dete‐ction of virus‐specific messenger RNA from Ku812Ep6 cells. To measure capsid integrity, endonucleases were added after exposure to low pH and the encapsidated (endonuclease‐protected) virus DNA was quantified by real‐time PCR.

RESULTS:  B19V was inactivated greater than 5 log after 2 hours at pH 4, whereas MMV was resistant over 9 hours. Infectivity data strongly correlated with data obtained by the endonuclease assay. Capsid disintegra‐tion was observed in immunoglobulin G as well as in different albumin solutions. Temperature and pH showed concerted impact on B19V capsid disintegration.

CONCLUSION:  Our data show that B19V is much more vulnerable toward low pH conditions than MMV. Together with the previously reported susceptibility of B19V toward wet heat conditions, low pH is the second treatment where erythrovirus B19V is less resistant than viruses from the parvovirus genus.

BACKGROUND: Blood is a costly and scarce resource. We report on a systematic review of the literature to estimate the cost of a 2‐unit red blood cell (RBC) transfusion in Western Europe.

STUDY DESIGN AND METHODS: Medline was searched for studies about the cost of RBC transfusion in Europe. Data extracted included authors, country, year of data, cost perspective, cost types, cost elements, units examined, study design, study population, and cost of a 2‐unit blood transfusion. The population‐weighted mean cost per 2 units of transfused blood was calculated.

RESULTS: Six studies met inclusion and exclusion criteria and reported data from the United Kingdom, Sweden, Switzerland, Austria, and France. Methodology used to derive cost estimates differed across the studies. The population‐weighted mean cost of transfusing 2 units of blood was €877.69.

CONCLUSION: The estimated cost of transfusing 2 units of RBCs in Western Europe is significant. Differences in methodology were partially diffused by aggregation of prior estimates into a population‐weighted mean. Future cost studies should follow the Cost of Blood Consensus Conference (COBCON) recommendation to apply activity‐based costing methods.

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.

Frequent blood transfusions are necessary in aplastic anemia because of decreased hematopoietic function. In order to maintain the hemoglobin level and to decrease the need for blood transfusion, human ceruloplasmin was used for the treatment of 73 patients with aplastic anemia. A marked beneficial effect was obtained in 16 cases. The treatment was moderately effective in 17 cases, slightly effective in eight cases, and ineffective in 32 cases. The usual dose of ceruloplasmin was 15 mg/day, but it was varied according to symptoms. Side effects were minimal when ceruloplasmin was administered by slow intravenous injection.

BACKGROUND: Individuals donating whole blood 13 times in a 2‐year period without development of iron deficiency anemia (superdonors) are a self‐selected population that is deferred for low hematocrit (Hct) level less frequently than other donors.

STUDY DESIGN AND METHODS: Iron metabolism was assessed in 138 superdonors through a questionnaire and measurement of Hct, serum ferritin, serum hepcidin, and serum growth differentiation factor 15 (GDF15). Genetic testing for HFE and JAK‐2 mutations was also performed.

RESULTS AND CONCLUSIONS: Iron deficiency (ferritin level, <30 µg/L) is present in more than 60 percent of superdonors. Behaviors altering iron status included casual use of iron supplements in males, but not in females, and cigarette smoking that produced increased Hct associated with decreased ferritin. The striking biochemical characteristic of superdonors is greatly decreased serum hepcidin, consistent with their need to absorb maximal amounts of dietary iron to replace that lost from blood donation. GDF15 is normal in most superdonors, indicating that GDF15 overexpression arising from the expanded erythroid pool necessary to replace donated red cells is not the biochemical mechanism for the decreased serum hepcidin. Mutations in JAK‐2 were not found, indicating that undiagnosed polycythemia vera is not a common cause for successful repeated blood donation by superdonors. Mutations in HFE associated with hemochromatosis were present in superdonors at the same frequency as the normal population. However, superdonors heterozygous for the H63D mutation in HFE had significantly decreased hepcidin : ferritin ratios demonstrating for the first time that the heterozygous state for HFE mutations is associated with alterations in hepcidin expression.

BACKGROUND: Current blood transfusion standards in Canada and the United States permit transfusion of ABO‐nonidentical platelets when ABO‐identical platelets are not available. This practice increases the availability of platelets, a component in chronic shortage in Ontario, Canada because of the 5‐day shelf‐life. The impact of transfusing ABO‐nonidentical platelets on patient outcomes is unknown.

STUDY DESIGN AND METHODS: A retrospective review of 1721 patients who had cardiovascular surgery between November 1989 and December 1999 and who had also received a platelet transfusion perioperatively was conducted. The impact of platelet and plasma incompatibility on clinical outcomes was analyzed.

RESULTS: The analysis included 1691 patients who were divided into two groups according to the compatibility of the first platelet transfusion received: ABO‐identical platelet transfusion (n = 1008) and ABO‐nonidentical platelet transfusion (n = 683). The only difference in baseline characteristics between the two groups was that there were more urgent cases in the ABO‐identical platelet transfusion group (p = 0.04). There were no significant differences in mortality at 30 days (10% for both groups, p = NS) or in postoperative length of stay (median, 7.0 days for both groups, p = NS). No significant differences were found with respect to the use of blood components, indices of bleeding, incidence of infection, or platelet CCIs.

CONCLUSION: Transfusion of ABO‐nonidentical platelets in patients undergoing cardiovascular surgery is not associated with an adverse impact on patient outcome.

BACKGROUND: Immune thrombocytopenia (ITP) is a bleeding disorder characterized by antibody‐opsonized platelets (PLTs) being prematurely destroyed by macrophages in the reticuloendothelial system. T helper (Th) cells and different Th cytokines play an important role in the pathophysiology of ITP. As immunomodulators, adipose‐derived mesenchymal stem cells (ADSCs) regulate Th cells and show therapeutic effects in autoimmune diseases. However, it is not clear how ADSCs affect ITP. In this study, we explored the specific effects of ADSCs on ITP in mice.

STUDY DESIGN AND METHODS: BALB/c mice were randomly divided into three groups: normal controls, ITP controls, and ITP with ADSC transplantation. PLT levels were monitored by an automatic blood cell counter, and the cytokines interferon‐γ (IFN‐γ); interleukin (IL)‐2, ‐4, ‐10, and ‐17; and transforming growth factor‐β1 (TGF‐β1) were analyzed by enzyme‐linked immunosorbent assays.

RESULTS: Compared to the untreated ITP mice, the PLT level of the ITP mice significantly increased after ADSC treatment. In the ADSC group, IFN‐γ, IL‐2, and IL‐17 significantly decreased, while IL‐4, IL‐10, and TGF‐β1 increased.

CONCLUSION: These findings constitute the first experimental evidence that ADSCs are efficacious in improving PLT levels and reducing the related Th cytokines mediating proinflammatory response in ITP mice, which may provide a scientific basis for using ADSCs as a new therapy for ITP.

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.