Guidelines for the transfusion of red cells.

The following recommendations, which aim at standardising and rationalising clinical indications for the transfusion of red cells in Belgium, were drawn up by a working group of the Superior Health Council. To this end, the Superior Health Council organised an expert meeting devoted to "Guidelines for the transfusion of red cells" in collaboration with the Belgian Hematological Society. The experts discussed the indications for red cell transfusions, the ideal red cell concentrate, the practical issues of administering red cells, and red cell transfusions in patients in a critical condition. The recommendations formulated by the experts were validated by the working group with the purpose of harmonising red cell transfusion in Belgian hospitals.

Histamine synthesis by white cells during storage of platelet concentrates.

OBJECTIVES: To resolve the question whether histamine, like some cytokines, is actively synthesized during storage of platelet concentrates. METHODS: We prepared conventional buffy coat platelet concentrates and stored them in the usual way at 22 degrees C. Disodium cromoglycate was added to one series, saline to the controls. Samples were taken at intervals, to be tested for histamine and interleukin-6 (IL-6). RESULTS: The plasma histamine level increased from a median of 1.02 ng/ml (range 0.11-3.27) to 12.9 ng/ml (range 4.30-32.9) whereas the total histamine content of the platelet concentrates remained unchanged during the 5-day storage period. In contrast, the total content of IL-6 increased rapidly. CONCLUSION: Histamine is not synthesized during storage of platelets, whereas IL-6 is. The addition of disodium cromoglycate, a substance that inhibits granulocyte activation, had no effect on the release of histamine or on the total histamine content at various storage times.

Higher prevalence of parvovirus B19 in Belgian as compared to Tunisian blood donors: differential implications for prevention of transfusional transmission.

Serious anaemia can be induced by human parvovirus B19 (HPV) infection in immuno-compromised patients or subjects with an haemolytic disorder. Routine inactivation procedures are insufficient to neutralize the virus, but screening for HPV is an effective means to avoid transmission by transfusion of blood components. In the present study, we have compared for the first time the IgG and IgM seroprevalence in a North African (Tunisian) and Western European (Belgian) population of blood donors. The prevalence of HPV-specific IgM was less than 2% in both populations, pointing to the absence of an epidemic. The prevalence HPV IgG was significantly (p < 0.01) higher in Belgium (74%) than in Tunisia (65%), without any relationship with age or sex. This finding may suggest a south-north gradient of this infectious disease. Since the presence or absence of HPV-specific antibodies does not preclude transfusional transmission, screening for the virus itself should be done to avoid iatrogenic infection in HPV-naive subjects at risk. In view of the different transfusion policies in Belgium and Tunisia, a strategy for each of both countries is proposed.

Febrile reactions to platelet transfusion: the effect of increased interleukin 6 levels in concentrates prepared by the platelet-rich plasma method.

BACKGROUND: A relation between febrile reactions to platelet transfusion and high cytokine levels in platelet concentrates (PCs) was found previously. The levels of cytokines such as interleukin (IL)-6 are related to the while cell content of the PC during storage. Therefore, early removal of white cells should prevent reactions. STUDY DESIGN AND METHODS: This prospective study was set up to compare methods for the preparation of random PCs, the platelet-rich plasma method (PRP-PCs), which results in a high white cell content, and the buffy coat method (BC-PCs), which results in a low white cell content, with regard to the frequency and severity of reactions to platelet transfusion and the IL-6 level of the PC. IL-6 was chosen because it is the major mediator of the acute-phase response. White cells were reduced in all PCs before transfusion. RESULTS: Platelet transfusions (n = 584) in 64 patients were studied. An overall reaction frequency of 7.2 percent was observed. Transfusion reactions were seen predominantly in patients who received PRP-PCs (PRP-PCs: 9.3% vs. BC-PCs: 2.7%, p = 0.007). Allergic reactions were limited to transfusions of PRP-PCs. The following PRP-PC characteristics were significantly correlated with febrile transfusion reactions: IL-6 level (p < 0.0001), initial white cell count (p = 0.001), and storage time (p = 0.02). In this group, reactions were less frequent in patients receiving pretransfusion medication (p < 0.001). In the PRP-PC group, IL-6 content (p = 0.01) and initial white cell count (p = 0.04) were also significantly correlated with allergic reactions, which indicated that these or associated factors might have an effect on the outcome of this type of reaction. CONCLUSION: Febrile reactions are highly correlated with IL-6 levels in PCs. The low white cell content of BC-PCs is associated with undetectable IL-6 levels and a reduced frequency of febrile as well as allergic reactions in recipients. The BC method is the preferable one for the production of random-donor PCs.

Effect of prestorage leukocyte removal on the cytokine levels in stored platelet concentrates.

The effect of the prestorage removal of leukocytes from platelet concentrates (PC) on the cytokine levels during its storage was studied. Two methods for leukocyte removal were examined: filtration and preparation of the PC by the buffy coat method. Cytokine levels were measured at various storage times. Highly increased levels of tumor necrosis factor-alpha (TNF-alpha; 120 +/- 131 ng/l) and interleukin 6 (IL-6; 988 +/- 494 ng/l) were found after a 5-day storage in the control group, whereas no increased levels were found in filtered PC (TNF-alpha 14 +/- 4 ng/l, IL-6 < 4 ng/l) or in buffy coat PC (TNF-alpha 8 +/- 2 ng/l, IL-6 < 4 ng/l). Furthermore an effect of the pooling of buffy coats or PC on the cytokine levels was not found. Transfusion of PC containing high levels of IL-6 and TNF-alpha has been associated with febrile transfusion reactions in the recipient and therefore the prestorage leukocyte removal might prevent these febrile transfusion reactions. The preparation of buffy coat PC, through its simplicity, seems to be the method of choice.

Increased tumor necrosis factor alpha (TNF alpha), interleukin 1, and interleukin 6 (IL-6) levels in the plasma of stored platelet concentrates: relationship between TNF alpha and IL-6 levels and febrile transfusion reactions.

Increased interleukin 6 (IL-6) levels were found in 8 of 12 platelet concentrates (PCs) after 3 days of storage and in 10 of 12 PCs after 5 and 7 days of storage. Most of the PCs with an increased IL-6 level also showed increased tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) levels. Levels of IL-6 increased by 3 log10 over the base level during storage. Increased levels were found when the PC white cell count exceeded 3 x 10(9) per L. A linear correlation was found among the levels of TNF alpha, IL-1 beta, IL-1 alpha, and IL-6 in the PCs (r > 0.885). Comparison of the TNF alpha, IL-1 beta, and IL-6 levels in samples taken at various storage times indicates that the increased levels are the result of an active synthesis and release of interleukins during storage. In a second part of the study, 45 transfusions of white cell-reduced PCs were studied. Six transfusions were complicated by a febrile reaction. These reactions were related to high levels of IL-6 and TNF alpha in the PCs (p < 0.0001). These cytokines are known as endogenous pyrogens. These findings indicate that transfusion reactions might be due to the intravenous administration of plasma with high cytokine levels and might not always result from an antigen-antibody reaction.

The mechanism of white cell reduction by synthetic fiber cell filters.

The mechanism of white cell (WBC) retention by synthetic fiber-based WBC filters was studied. Filters were made of nonwoven fleece prepared from polyester, surface-modified polyester, or polypropylene fibers. Human platelet concentrates were filtered through experimental filters consisting of 8 to 54 layers of nonwoven fleece with mean pore sizes from 7.3 to 14.2 microns. Filters made of fleece of smaller pore size removed WBCs less effectively than filters with larger-pore fleece. Retention of lymphocytes and granulocytes gradually dropped to 0 percent as increasing loads were applied to the filters. The maximal retention capacity for these cell types (i.e., the number of cells retained when "saturating" numbers of WBCs were applied) was proportional to the number of layers of filter material used. Platelet retention did not correlate with WBC retention. Depth filtration, rather than mechanical sieving, seems to be the principal means of WBC removal by nonwoven fiber filters. A low initial number of WBCs in the component to be filtered is important for successful WBC filtration.

Linkage analysis of distal hereditary motor neuropathy type II (distal HMN II) in a single pedigree.

We describe a six generation family affected with the autosomal dominant form of distal hereditary motor neuropathy type II (distal HMN II). The distal HMN shows similarities with the hereditary motor and sensory neuropathies type I and II (HMSN I and HMSN II) or Charcot-Marie-Tooth disease type 1 and 2 (CMT 1 and CMT 2) and with some proximal HMN or spinal muscular atrophies (SMA). Gene loci have been assigned to chromosomes 1q, 17p, and 19q for CMT 1 and to chromosome 5q for recessive SMA. In this study we excluded all four regions for the presence of distal HMN II, indicating that this neuropathy is genetically different from CMT 1 and recessive SMA.

Exopeptidases in human platelets: an indication for proteolytic modulation of biologically active peptides.

The determination in human platelets of four exopeptidases--aminopeptidase P, dipeptidyl peptidase IV, carboxypeptidase N, and angiotensin converting enzyme--by means of fluorometric or liquid chromatography techniques was carried out. The results obtained show that the specific activities of dipeptidyl peptidase IV, carboxypeptidase N, and angiotensin converting enzyme in intact and disrupted platelets are small compared to their specific activities in serum. However, for aminopeptidase P the specific activity of this enzyme is much higher in platelets than in serum. This suggests that circulating platelets may have a significant role as scavengers for circulating peptides containing bonds susceptible for aminopeptidase P.

A seroepidemiological survey of HTLV-I/HTLV-II in selected Belgian populations.

A preliminary survey of the prevalence of HTLV-I antibody during 1987 and 1988 in Belgium revealed no positive results among selected blood donors who sided for some length of time in areas where HTLV-I/HTLV-II is endemic (n = 270), in development-aid workers (n = 145), or in missionaries (n = 35) serving in developing countries. Among foreign groups, African students (n = 212), and political refugees (n = 311), HTLV-I/HTLV-II antibodies were detected and confirmed in 3 cases. Limited data from 1987 and 1988 suggest that HTLV-I/HTLV-II poses no major public health problem in Belgium.

Binding of serum ferritin to concanavalin A in patients with malignancy.

The percentage non-glycosylated, tissue type ferritin was measured in the serum of 30 cancer patients and 11 normal subjects, as well as in 10 tumour cytosols. As expected, in normal subjects the larger part of serum ferritin corresponded to glycosylated ferritin, and in tumour cytosols the larger part corresponded to non-glycosylated ferritin (tissue ferritin). In all but one cancer patients a significant part of the protein did not bind to Con A, thus behaving as tissue ferritin. The findings obtained suggest release of tissue type, non-glycosylated, ferritin by damaged cells or through abnormal secretion. This relative increase of the non-glycosylated ferritin fraction appears to be very frequently present in cancer, although not specific for it. Assaying for Con A binding may prove to be valuable in the study of malignant disease, and therefore deserves further investigation.