Biomedical subjects
Publications and source records attributed to O Flesland.
During 2005 Norwegian Transfusion Medicine has faced some new problems, sought new solutions and gained strength. Interactions with the public and the health authorities have been important issues for consideration, which are discussed below.
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Important current issues in transfusion medicine in Norway are discussed. Current patient legislation specifically defines blood donors as patients, and blood and blood products are defined as drugs. Donor selection is controversial, especially deferral of all persons born in, or having lived for more than one year in areas with high prevalence of infections that are transmitted by blood. The threshold for becoming a blood donor is high, but registered donors donate frequently, e.g. 2,4 whole blood donations per year on average. Some blood banks have specialized in multicomponent aphereis technology, in particular collection of two units of red cells.
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BACKGROUND: Transferrin receptor mediates cellular uptake of iron, and the expression on cells reflects iron needs and erythropoietic activity. The results of measuring transferrin receptor in serum (sTfR) in blood donors are presented. STUDY DESIGN AND METHODS: Haemoglobin, serum-ferritin and sTfR were measured in 172 female and 174 male donors that had donated whole blood six or more times during the previous 3 years and in 96 female and 56 male new donors. RESULTS: Haemoglobin and sTfR were not significant different in new and repeat donors. New donors had significantly higher s-ferritin than repeat donors. Twenty donors had a Hb above the low limit for normal, but below the determined cut-off for donation. Only three of these had high sTfR and/or low serum-ferritin. Hence, of the total 492 donors 3.5% were below the Hb cut-off, but having Hb, s-ferritin and sTfR within normal ranges. 11.6% of new female donors belonged in this category. CONCLUSION: STfR is better than s-ferritin as a screening for iron deficiency. Most donors with low tissue iron neither have high sTfR, nor anaemia. There is probably no need to have a separate, higher than the lower normal range, requirement for Hb in donors. STfR measurements are probably most valuable in a setting where most donors are repeat donors.
Both red blood cells and platelets undergo lesions upon storage which affect their function and possibly their clinical outcome. Some of these lesions are reversible, others not. Improved additive solutions and leukocyte depletion can delay the appearance of storage lesions. In addition, cellular apoptosis leads to numerous mitochondrial and surface changes during storage which have the potential to induce immune suppression by tuning down the innate immune system. This overview highlights some laboratory and clinical aspects of red cell and platelet storage lesions.
The establishment of the Norwegian Fractionation Project (Project) was of major importance in preserving national self-sufficiency when plasma, cryoprecipitate and small batch factor IX-concentrates were replaced by virus inactivated products in the last part of the 1980s. Fractionation was performed abroad by contract with Octapharma after tenders on the European market. All Norwegian blood banks (>50) participated in the Project. Total yearly production was 50-60 tons of mainly recovered plasma. From 1993 solvent detergent (SD) treated plasma has replaced other plasma for transfusion. The blood banks paid for the fractionation and/or viral inactivation process, while the plasma remained the property of the blood banks and the final products were returned to the blood banks. The Project sold surplus products to other Norwegian blood banks and the majority of the coagulation factor concentrates to The Institute of Haemophilia and Rikshospitalet University Hospital. Both plasma and blood bank quality was improved by the Project. Clinical experience with the products has been satisfactory and self-sufficiency has been achieved for all major plasma proteins and SD plasma, but a surplus exceeding 3 years consumption of albumin has accumulated due to decreasing clinical use.The Project has secured high yields of the fractionated products and the net income from the produced products is NOK 1115 (140 Euros or US dollars) per litre plasma. An increasing surplus of albumin and the possibility of significant sales abroad of currently not fractionated IVIgG, could lead to a reorganisation of the Project from that of a co-ordinator to a national plasma handling unit. This unit could buy the plasma from the blood banks and have the plasma fractionated by contract after tender, before selling the products back for cost recovery. The small blood banks could produce plasma for products for the Norwegian market, while surplus products from the larger blood banks which are certified for delivery of plasma for fractionation of products to be consumed in the European Community, could be sold on the international market.
Plasma and red blood cell quality are affected both by citrate concentration and the levels of extracellular leukocyte and platelet derived substances, accumulated during storage of blood. The effect of leukocyte filtration on the storage stability of whole blood was therefore studied in blood collected in standard CPD and 0.5CPD (CPD with half strength citrate concentration). A total of 52 units, 12 of them with reduced citrate concentration, were leukocyte-filtered with Pall( whole blood filter (WBF1 or 3). No differences in leukocyte or platelet reduction were observed with the two citrate concentrations. However, with 0.5CPD a significantly longer filtration time and increased complement activation was observed. The effect of pre-storage leukocyte filtration on the plasma quality of whole blood was therefore only studied with standard CPDA1 anticoagulant solution (normal strength citrate concentration). Leukocyte filtration did not affect the von Willebrand factor concentration, while a small reduction (7%, p=0.04) in factor VIII (FVIII) concentration was observed. During storage, however, FVIII decreased more slowly in the filtered than in the unfiltered product, and, from day two, the FVIII content was significantly higher in the filtered product (46% versus 30% at 28 days, p<0.001). Factor V (FV) demonstrated a 16% reduction (p<0.001) upon filtration, followed by an additional 8% in the next 24 h and only a 4% reduction the next 27 days, while unfiltered products demonstrated a continuous reduction to 26% at 28 days. While the beta-thromboglobulin (beta-TG) concentration significantly increased (from 836 to 2483 IU/ml, p<0.001) during leukocyte filtration, no further increase was observed during storage. In contrast, unfiltered products demonstrated an increase to 5762 IU/ml (p<0.001) at 14 days, followed by a slight, not significant, reduction. This indicates platelet activation during filtration and explains a parallel reduction in FV. Filtration induced no increase in prothrombin fragment 1+2, while a slight increase was observed in some unfiltered products after 28 days of storage.Pre-storage leukocyte depletion thus improves the coagulation factor content of plasma in stored whole blood.
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In a prospective study of 16,756 consecutive blood donors, we found 54 donors (0.3%) to be anti-hepatitis C virus (HCV)-positive by a first-generation enzyme-linked immunosorbent assay. After retesting, 18 donors were confirmed positive or indeterminate by a second-generation recombinant immunoblot assay. Sixteen of these donors were found positive by a second-generation enzyme-linked immunosorbent assay, and 15 of these were positive by HCV polymerase chain reaction with two primer sets. Nine donors (50%) had a history of drug abuse. In 15 donors found positive by a second-generation enzyme-linked immunoblot assay liver biopsy specimens were taken after at least 6 months' follow-up. In all except one hepatitis C RNA-negative donor, histologic abnormalities were observed, even when alanine aminotransferase (ALAT) levels were continuously normal or only moderately elevated. The abnormalities were less pronounced in these donors (n = 5) than in donors with ALAT levels increased more than twice the upper normal limit (p < 0.05). In conclusion, we found the proportion of previous drug abusers in anti-HCV-positive blood donors to be high. We confirm that the presence of anti-HCV (second generation) usually, and HCV-RNA always, seems to indicate ongoing infection--also when ALAT levels are normal. Our study further suggests that low-activity hepatitis, evaluated by ALAT levels, may indicate a milder disease.
In a patient, at revisional Christiansen total hip arthroplasty, silver-impregnated bone cement was used as prophylaxis against deep infection. Five years later the patient developed serious neurological deficits, and the prosthesis was loose. The loose Christiansen prosthesis and the silver-impregnated bone cement were removed and a Charnley prosthesis inserted. Intra-operatively the concentration of silver in fluid drawn from the hip joint was assessed to be about 1000 times the normal serum reference value, and tissue samples from the acetabulum were densely impregnated with silver. During the following 2 years the serum concentration of silver decreased from more than 60 times to 20 times the normal; simultaneously the patient partially recovered from her grave muscle paralysis.
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Female blood donors with serum ferritin < or = 20 micrograms l-1 and haemoglobin > 120 g l-1 participated in an iron supplement study with two different low-dose supplements in a period without donations. Comparable non-donors served as controls. Serum ferritin, haemoglobin and transferrin were determined. Increases in serum ferritin and in haemoglobin, and decrease in transferrin were highly significant (p < 0.01) in both donor groups. In one of the non-donor groups the increase in serum ferritin and decrease in transferrin were highly significant (p < 0.01), while in the other only transferrin changed significantly (p < 0.03). The increases in serum ferritin and haemoglobin over a 5-month period were significantly higher among donors (p < 0.001) than among non-donors. We interpret the results to mean that the donors have a more efficient iron absorption.
Quality control of leucocyte depleted blood products has become a problem since the introduction of bedside leucocyte filtration. At our Blood Centre, this problem has been circumvented by testing a sample taken as the filtration is completed by sealing off a 10 cm piece of tubing just under the filter. We have tested four brands of erythrocyte filters, Pall RC100, Erypur Optima b, Sepacell R-200A and Sepacell R-500A(II) using two erythrocyte concentrates for each filter. We have tested two brands of thrombocyte filters, Pall PL100 with 6-8 thrombocyte concentrates, and Sepacell PL-5A with 2-6 concentrates. No transfusion should give more than 5 x 10(6) leucocytes. Pall PL100, Pall RC100 and Sepacell R-500A(II) met the criteria.
Serum ferritin levels were measured in 613 women and 376 men included in our Blood Donor Registry in 1990, prior to their first donation. The mean serum ferritin was 34 micrograms/l in females and 98 micrograms/l in males. For men less than 20 years of age mean serum ferritin was 52 micrograms/l which is significantly lower than for the other age groups. For women greater than or equal to 50 years of age mean serum ferritin was 61 micrograms/l, which is significantly higher than for the younger age groups. In 22% of the women and 1.3% of the men serum ferritin was less than 15 micrograms/l upon registration. Female blood donors with an initial serum ferritin of less than 10 micrograms/l had donated on average 1.2 times 11 to 23 months later, and 56% were temporarily or permanently deferred from donation. Females with an initial serum ferritin of between 30 and 39 micrograms/l had donated 2.5 times, and 26% were deferred.