Recommendations in the event of a suspected transfusion-related acute lung injury (TRALI).

The following recommendations, which aim at improving the clinical diagnosis ofTRALI and the laboratory investigations that can support it, were drawn up by a working group of the Superior Health Council. TRALI is a complication of blood transfusion that is both serious and underreported. Systematic reporting may help to develop preventive actions. Therefore, the Superior Health Council recommends that there should be a more stringent surveillance of patients who receive a blood component transfusion. The clinician should pay very close attention to any change in the patient's respiratory status (cf. dyspnoea and arterial desaturation), which should be notified systematically to the haemovigilance contact person in the hospital.

Adverse reactions and events related to musculoskeletal allografts: reviewed by the World Health Organisation Project NOTIFY.

PURPOSE: The use of bone and connective tissue allografts has grown rapidly and surpassed the use of autografts in many countries. Being of human origin, bone and tendon allografts carry the risk of disease transmission and complications have been reported. As part of the Project NOTIFY led by the World Health Organisation, an effort to improve recognition, reporting, tracking and investigation of adverse outcomes of allografts was initiated, achieving a comprehensive review of associated disease transmission and failures. Those involving the use of musculoskeletal allografts are reported here. A major objective is to involve orthopaedic surgeons in the improvement of the safe use of the musculoskeletal allografts. METHODS: We reviewed the medical literature, requested reports from surgeons in selected professional organisations and informally surveyed tissue bank organisations and selected tissue bank professionals to discover reported and unreported cases of adverse outcomes. We analysed each case to decide the likelihood that the complication was truly allograft related. RESULTS: The efficiency of the procedures involved in bone banking and bone and tendon allograft has improved significantly during the last three decades. The evolution of the incidence of reported adverse reactions and events reflects positively on the safety of transplanted tissues. Cases of bacterial and viral transmission by bone and tendon allografts occurred mainly with those that contained viable cells, were not processed to remove cells, or were not disinfected or sterilised. We documented cases of transmission of human immunodeficiency virus (HIV), hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), unspecified hepatitis, tuberculosis and other bacteria. Reporting of these adverse outcomes has led to corrective actions and has significantly improved the safety of allograft use. However, it is probable that not all cases have been reported and investigated. CONCLUSIONS: Considering the high quality standards achieved in many countries, the best approach for further improvement in the safety of allografts is through a systematic reporting of all serious adverse reactions and events in the context of a global biovigilance programme.

Recommended indications for the administration of polyclonal immunoglobulin preparations.

The following recommendations, which aim at standardising and rationalising the clinical indications for administering polyclonal immunoglobulins 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 use of immunoglobulins". The experts discussed the indications for immunoglobulin use, the'ideal'immunoglobulin preparation, its mechanisms of action, the practical issues involved in administering immunoglobulins and their potential side effects. The recommendations formulated by the experts were validated by the Superior Health Council working group with the purpose of harmonising immunoglobulin use in Belgium

Guidelines for the use of fresh frozen plasma.

Recommendations, which aim at standardising and rationalising clinical indications for the transfusion of fresh frozen plasma (FFP) in Belgium, were drawn up by a working group of the Superior Health Council. For this purpose the Superior Health Council organised an expert meeting devoted to "Transfusion Guidelines: Pathogen reduction, products and indications for the transfusion of plasma" in collaboration with the Belgian Haematological Society.The experts discussed the indications for the transfusion of FFP, pathogen reduction for FFP and the practical issues of administering FFP and plasma-derived concentrates. The recommendations formulated by the experts were validated by the working group with the purpose of harmonising FFP transfusion in Belgian hospitals.

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.

Guidelines for the transfusion of platelets.

Recommendations aiming at standardising and rationalising clinical indications for the transfusion of platelets 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 platelets" in collaboration with the Belgian Hematological Society. The experts discussed the indications for platelet transfusions, the ideal platelet concentrate and the optimal platelet transfusion therapy. The recommendations prepared by the experts were validated by the working group with the purpose of harmonising platelet transfusion in Belgian hospitals.

Mutation of the repeat number of the HPRTB locus and structure of rare intermediate alleles.

During routine paternity testing a mutation of a paternal allele at the HPRTB locus was observed. The opportunity was taken to analyse this mutation at a molecular level. The repeat sequence is flanked by an imperfect repeat sequence and this region could be involved in the mutation mechanism. For this reason, we also examined the structure of "intermediate" alleles. Sequencing confirmed the insertion of a perfect repeat motif and revealed a deletion of a dinucleotide some 50 nucleotides downstream from the repeat sequence for the intermediate alleles. It is likely that these intermediate alleles are rare biallelic deletion polymorphisms and are probably not involved in the mutation or variation mechanism of this locus.

The evolution of platelet procoagulant activity of remnant platelets in stored platelet concentrates prepared by the platelet-rich plasma method and the buffy coat method.

Platelets stored as concentrates are gradually activated (storage lesion), a process associated with changes in the expression of platelet procoagulant activity (PPCA). The aim of the present study was to evaluate the evolution of PPCA and the mean platelet volume (MPV) of stored platelets prepared according to the platelet-rich method (PRM) and the buffy coat method (BCM). Using the platelet factor 3 availability clotting test (PF3AT) on appropriately diluted concentrate samples, we found a decrease in PPCA expression of remnant platelets as a function of storage time (0.025 < p < 0.01 between day 1 and 7) in PRM-derived but not in BCM-derived platelet concentrates. Using the PF3AT reduction test we found a more important clotting time reduction in samples obtained from BCM than in samples obtained from PRM platelet concentrates, suggesting a higher PPCA expression of BCM platelets, not significant after 1 day but highly significant after 3 days (p < 0.0005) and after 7 days (p < 0.0005) of storage, as compared with PRM platelets. For both PRM and BCM concentrates there were no significant MPV changes as a function of storage time, but at any storage day the MPV of BCM concentrates was significantly higher (p < 0.0005) than the MPV of PRM concentrates. We conclude that the decrease of PPCA expression in PRM-derived concentrates as a function of storage time is in agreement with the gradual decrease of the platelet activation status in PRM concentrates during storage. There are probably several factors or variables causing platelets of BCM concentrates to express higher PPCA than those of PRM concentrates. Higher PPCA expression in BCM concentrates may be explained by an intrinsic platelet property, such as a difference in MPV between the two kinds of concentrates, or it may be related to an extrinsic factor such as different storage media, e.g., undiluted autologous plasma in PRM concentrates versus Plasmalyte A-diluted autologous plasma in BCM concentrates. Whether the difference in PPCA expression of remnant platelets in PRM and BCM concentrates is just an in vitro laboratory finding or may have consequences for the therapeutic efficiency of the concentrates is an interesting, still unresolved question.

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.

Possible implication of sterile connecting device in contamination of pooled platelet concentrates.

Considering the possibility that a pooled random donor platelet concentrate could become contaminated by welding with a sterile connecting device, we undertook a study to determine the influence of pooling on the contamination rate. As a control group, apheresis platelets were examined. Bacteriological testing was done with a sensitive CO2 detecting culture system, the BacT/ Alert. Out of 1105 pooled platelet concentrates prepared by the buffy coat method, 15 (1.4%) were confirmed as contaminated, all with Staphylococcus epidermidis and two with a second bacterial species, i.e. Staphylococcus capitis and Propionibacterium acnes, respectively. Median detection time by the BacT/Alert was 23 h. Twelve pools of five units were contaminated, which is significantly more than the three contaminated pools of four units. On the other hand, the reuse of the welding wafers proved not be a risk factor for contamination. One welded tubing segment of a contaminated platelet concentrate failed the air leakage test, an incident which was 73 times more frequent than with the sterile platelet concentrates. We found five pooled platelet concentrates containing Staphylococci from which no bacteria could be grown from the individual buffy coats that had been pooled. We suggest the contamination here to have occurred after separation of the buffy coat from the whole blood, possibly during the welding process. Finally, none out of 378 apheresis platelet concentrates was contaminated. All our observations highlight the potential risk for contamination when making pooled platelet concentrates with a sterile connecting device. For this type of transfusion product, we advocate bacteriological screening of all units before release. The incubation time for the sterility test should, however, be limited to 36 h, if logistical problems with the availability of platelets are to be avoided.

A multicenter evaluation of the routine use of a new white cell-reduction apheresis system for collection of platelets.

BACKGROUND: Residual white cells (WBCs) cause serious side effects in platelet transfusion. An in-line WBC-reduction system based on fluidized particle bed technology was recently developed as a modification of an existing plateletpheresis system. STUDY DESIGN AND METHODS: In an investigational phase, three flow profiles were evaluated using prototype software in five centers, each using their standard conditions. In the confirmatory phase, the released software was tested in three centers. WBCs were counted in two full Nageotte grids (dilution 1-in-5). RESULTS: With the prototype software, WBC levels were always below 1 x 10(6) per procedure (median, 25,000/procedure; n = 314). One profile proved to be superior to the other two with respect to platelet yield and residual WBCs, and it was incorporated in the released WBC-reduction system, together with a built-in process control. Median residual WBCs in these WBC-reduction system components not rejected by the process control were 19,000 per procedure (n = 211/225 total), with 99.5 percent of the platelet components having less than 1 x 10(6) WBCs. CONCLUSION: The protocol selected in the initial phase, now available as a WBC-reduction system, results in platelet concentrates with very low residual WBC levels. This satisfies even the most stringent criteria for WBC reduction in platelets, without the platelet loss typically seen with conventional fiber filtration.