A prospective, active haemovigilance study with combined cohort analysis of 19,175 transfusions of platelet components prepared with amotosalen-UVA photochemical treatment.

BACKGROUND AND OBJECTIVES: A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT(™) Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT-treated platelet components (PCT-PLT) administered across a broad patient population. MATERIALS AND METHODS: This open-label, observational haemovigilance programme of PCT-PLT transfusions was conducted in 21 centres in 11 countries. All transfusions were monitored for adverse events within 24 h post-transfusion and for serious adverse events (SAEs) up to 7 days post-transfusion. All adverse events were assessed for severity (Grade 0-4), and causal relationship to PCT-PLT transfusion. RESULTS: Over the course of 7 years in the study centres, 4067 patients received 19,175 PCT-PLT transfusions. Adverse events were infrequent, and most were of Grade 1 severity. On a per-transfusion basis, 123 (0.6%) were classified an acute transfusion reaction (ATR) defined as an adverse event related to the transfusion. Among these ATRs, the most common were chills (77, 0.4%) and urticaria (41, 0.2%). Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion (<0.1%). No case of transfusion-related acute lung injury, transfusion-associated graft-versus-host disease, transfusion-transmitted infection or death was attributed to the transfusion of PCT-PLT. CONCLUSION: This longitudinal haemovigilance safety programme to monitor PCT-PLT transfusions demonstrated a low rate of ATRs, and a safety profile consistent with that previously reported for conventional platelet components.

[Evolution of techniques for preparation of labile blood products (LBP): pathogen inactivation in LBP]. / Evolution des techniques de préparation des produits sanguins labiles (PSL): inactivation des pathogènes dans les PSL.

The techniques for inactivation of pathogens in labile blood products (LBP) would appear to be the new strategy which will permit us to increase transfusion safety in the face of the risks of transmission of pathogenic agents by LBP. Various methods are in the course of development or already validated and used in France. The latter only apply however to plasma or platelet concentrates. The mechanisms of action and the efficacy of inactivation and attenuation of pathogenic agents vary with the different techniques. Each of these constitutes a preparative procedure composed of unit steps which have to be fully mastered in order to ensure the quality and transfusion efficacy of the treated product.

[Platelet transfusion: products, indications, dose, threshold and efficacy]. / Transfusion de plaquettes: produits, indications, dose, seuil, efficacité

The quality of platelet concentrates had been greatly improved since the implementation of processing techniques based on the use of the buffy-coat in the years 1980. More recently, in the last 10 years, it is in the domain of safety that the greatest advances have been done, by the introduction of platelet additive solutions, on one hand, and by the progressive availability of pathogen reduction techniques, on the other hand. These developments in quality and safety of platelet components are important, as they lead to the conclusion that nowadays, apheresis platelet concentrates and pooled random donor platelet concentrates can be considered as equivalent, the only specific indication of the former being the care of HLA or HPA allo-immunized patients. This review covers the physiological basis of prophylactic and curative platelet transfusions, and the means to evaluate their efficacy. The main investigations that are necessary to perform in the event of an inefficient prophylactic transfusion are also mentioned. Platelet transfusion is an essential part of the transfusion support in case of central thrombocytopenia, and more indications in other medical and surgical situations are well defined. The vast majority of clinical situations in which platelet transfusions are indicated have been defined in the national guidelines published in 2003 by the AFSSAPS French authority, and are still fully valid today. Therefore, only some specific domains for which recent published data are questioning our present practices are discussed, such as the use of platelet concentrates in massive transfusion. Finally, three critical factors for establishing a coherent platelet transfusion strategy are developed: the transfusion trigger for prophylactic platelet transfusion, the platelet dose, and the impact of ABO compatibility between the product and the recipient.

[Automation in the preparation of labile blood products]. / Automatisation de la préparation des produits sanguins labiles.

The preparation of labile blood products in a blood bank is in permanent technological progress. Many operations, such as blood centrifugation, components separation, etc. are now performed by automated devices. A new generation of equipments is able to prepare blood products by reducing the number of manual operations. Therefore, buffy-coat platelet concentrate preparation and whole blood preparation can be prepared by these automated systems. Consequently, this directly impacts working conditions of employees, quality of blood products and process management.

An active haemovigilance programme characterizing the safety profile of 7437 platelet transfusions prepared with amotosalen photochemical treatment.

BACKGROUND: An active haemovigilance programme was implemented to survey adverse events (AE) associated with transfusion of platelets photochemically treated with amotosalen and ultraviolet A (PCT-PLT). The results of 5106 transfusions have already been reported. Here we report the results of an additional 7437 PCT-PLT transfusions. METHODS: The focus of this ongoing haemovigilance programme is to document all AEs associated with PCT-PLT transfusion. Data collected for AEs include: time of event after starting transfusion, clinical descriptions, vital signs, results from radiographs and bacterial cultures, event severity (Grade 0-4) and causal relationship to PCT-PLT transfusion. RESULTS: One thousand four hundred patients (mean 60 years, range 1-96) received PCT-PLT transfusions. The majority of the patients (53.4%) had haematology-oncology diseases and required conventional chemotherapy (44.8%) or stem cell transplantation (8.6%). Sixty-eight PCT-PLT transfusions were associated with AE. Acute transfusion reactions (ATR), classified as an AE possibly related, probably related, or related to PCT-PLT transfusions were infrequent (n = 55, 55/7437 = 0.7%) and most were of Grade 1 severity. Thirty-nine patients (39/1400 = 2.8%) experienced one or more ATRs. The most frequently reported signs/symptoms were chills, fever, urticaria, dyspnoea, nausea and vomiting. Five AEs were considered severe (> or = Grade 2); however, no causal relationship to PCT-PLT transfusion was found. Repeated exposure to PCT-PLT did not increase the likelihood of an ATR. No cases of transfusion-related acute lung injury and no deaths due to PCT-PLT transfusions were reported. CONCLUSIONS: Routine transfusion of PCT-PLT is well-tolerated in a wide range of patients. ATRs related to PCT-PLT transfusion were infrequent and most were of mild severity.

Use of random versus apheresis platelet concentrates.

The respective use of random (RPC) and apheresis (APC) platelet concentrates is highly heterogeneous among countries, ranging from 10 to 98% RPC in countries supposed to provide a similar transfusion service to patients. Moreover, when considering each country in the past 10 years, one can observe that some have changed their policy, switching from a majority of APC to RPC or vice versa. This presentation intends to analyse which factors may impact such decisions. For many years, the only available platelet component was a RPC obtained from whole blood donation by a two centrifugation steps process, the "platelet rich plasma" or PRP method. Since the beginning of the 1970s, APCs became available, with in fact many different techniques leading to many APCs that may not be equivalent. Since the end of the 1980s, a new method of RPC preparation was developed, using the buffy-coat (BC-PC), providing a blood component with highly preserved platelet functions as compared to RPCs prepared by the PRP technique. Finally, the use of each of these components either native, or leuco-reduced, or suspended in a storage solution, or processed with a pathogen inactivation technique adds new layers of complexity to compare them. Innumerable references can be found in the literature describing in vitro functional parameters of platelet concentrates. Although it is clear that BC-RPC retain much more their in vitro functions than PRP-RPC, indicating that no one should use the latter any more, it is much more difficult to distinguish differences between other PCs. Conversely, only a very few studies have been published related to a comparison of clinical efficacy of RPC versus APC, the endpoints being mainly CCI. Similarly to the in vitro studies, although RPC prepared with the PRP method show the lowest CCIs, no clear difference exists between "modern" RPC and APC. Another factor that may impact policy decision is the occurrence of adverse reactions in recipients. When considering only comparable data, for example leuco-reduced RPC versus leuco-reduced APC, there is now evidence that the latter is more associated with adverse reactions in recipients: data from hemovigilance in France show that, although no difference is noted for febrile non haemolytic transfusion reactions, nor for bacteria contamination, the incidence of allergic adverse reactions is about four times higher with APC as compared with RPC. Other aspects may impact the decision: the fact that using APC in place of RPC reduces the total donor exposure of patients was considered critical in some countries to reduce the risk of transmission of blood transmissible disease. Finally, the cost of the components, much higher for APC may be considered.

[Discovery of a chronic HVC infection without seroconversion in a blood donor in France during 28 months]. / Découverte d'une infection chronique par le VHC sans séroconversion chez un donneur de sang en France pendant 28 mois.

The HCV-RNA screening technique developed by the French Fractionation and Biotechnology Laboratory singled out in March 1998 a case of positive HCV-RNA viremia in a blood donor without any anti-HCV antibody. That donor was a 46-year-old woman who had made 54 donations of blood products from 1988 to 1997. She had no history of blood transfusion, no history of hepatitis and no life-style risk factor. Clinical examination was normal. Liver tests (serum alanine amino transferases, gamma glutamyl transpeptidase , alkaline phosphatase, bilirubin , prothrombin and albumin) were normal. Total blood count was normal. Lymphocyte count was normal as well as in vitro functional analysis of lymphocytes (stimulation with different antigens). All screening HCV Elisa tests and immunoblot System available on the French market were unable to detect anti-HCV antibodies. Quantification of serum HCV-RNA (Amplicor Monitor Roche) showed 294,000 copies/mL and HCV genotype 1b determination was performed using Innolipa assay. Further examination of the HCV genotype by direct sequencing of the PCR product showed a classical 1b genotype sequence. The hemovigilance inquiry identified 25 labile products distributed since 1988. Analyzing the records of the recipients that have so far been traced and identified revealed three periods: 1997 to 1995: three recipients were found to be positive for anti-HCV antibodies; two are now cured of hepatitis C. In one recipient, direct sequencing after specific PCR of the hypervariable region coding for the envelope domain showed 100% homology with the donor; 1993 to 1990: four recipients were identified and traced without contamination; in 1988: three of four blood product recipients were anti-HCV negative without HCV-RNA viremia. The forth carried anti-HCV antibodies and genotype 1b HCV-RNA but had a history of multiple surgery. Alter et al. [4] and Bush et al. [5] have previously suggested the possibility of a chronic, immunologically silent state of infection. The case described herein, is the first evidence for this hypothesis. Indeed, the donor has not yet seroconverted 28 months after viremia was discovered. This blood donor was identified by HCV-RNA screening of plasma products. The identification of the same sequence in a recipient of blood from this donor clearly establishes the transmission of the virus by transfusion. The prevalence of such cases of infectious silent chronic HCV carriers has to be determined and the mechanisms responsible for the absence of antibody production need to be clarified.

Corrosion susceptibility of titanium covered by dental cements.

OBJECTIVES: The aim of this study is to determine the influence of acidic fluorinated cements (as glass ionomer (GI) cements) on the passivation of titanium, using electrochemical investigations. METHODS: We realized experimental electrodes that associate titanium and dental cements. Polarization resistance of titanium electrodes has been determined for uncovered metal and electrodes covered with three dental cements. Student's t-tests proved the reproducibility. We also compared successive voltammograms for uncovered titanium and GI covered titanium. RESULTS: Correct passivation was observed with zinc eugenate, but fluorinated GI or zinc phosphate coverage increased the corrosion susceptibility. SIGNIFICANCE: However there is no evidence of titanium depassivation when covered with cement. No clinical contraindication can be held.

[Biomechanical study of the vasomotor system of the arterial smooth muscle after long-term cryopreservation of a human arterial graft at two different temperatures -80 and -150C]. / Etude biomécanique et de la vasomotricité du muscle lisse artériel après cryocongélation de longue durée de greffon artériel humain à deux températures différentes -80 degrees et -150 degrees C.

We conducted two parallel studies on cryopreserved arterial homografts: a biomechanical study based on traction tests and a functional study coupled with a histology examination. Twenty-four arterial segments from 6 donors (2 iliac and 2 superficial femoral segments per donor) were cryopreserved at -150 degrees C and -80 degrees C. Cryopreservation lasted at least 6 months. Lengthening at rupture, the Young elasticity module, and rupture stress were calculated from the traction test. Results were significantly different depending on the preservation temperature. The functional properties of the cryopreserved arterial grafts were evaluated by studying the vasomotricity capacity of the vascular smooth muscle (VSM) and the endothelium. The expected results (direct contracture of VSM induced by PHE and endothelial dependent relaxation of VSM induced by ACH) were measured on fresh arteries. Cryopreserved arteries showed no response to physiological doses of PHE and ACH, whatever the preservation temperature. In one-third of the cases, a lower amplitude vasoconstriction was obtained using nonphysiological doses of PHE; there was no relaxation with ACH.

[Evaluation of the cost of autologous erythrocyte concentrates in a hospital]. / Evaluation du coût pour un établissement de santé des concentrés de globules rouges autologues.

This study evaluated the cost of autologous and homologous blood products. The cost effectiveness of the transfusion therapy was not evaluated. To compare the different products, the cost of one gram of transfused haemoglobin was calculated. Acute normovolaemic haemodilution is the most economical technique. Intraoperative autologous transfusion without washing is the most expensive. All blood products from the autologous techniques, except the latter, were less expensive than homologous red cells.

[Rheologic and cytologic study of autologous blood collected with Cell Saver 4 during cesarean]. / Etude rhéologique et cytologique du sang autologue recueilli par le "Cell Saver 4" au cours de césarienne.

Intra-operative autologous transfusion has been frequently used in vascular and traumatic surgery for about ten years. The technique would be justified in other procedures when intra-operative bleeding is significant and the quality of retrieved blood is satisfactory. We have studied the potential use of intra-operative autologous transfusion during caesarean section of 15 parturients. The quality of autologous blood (at different stages of the procedure) was assessed after being recovered and washed by "Cell Saver 4" (Haemonetics). Blood quality was assessed through 1) measuring the following: erythrocyte deformability with Erythrometer and Hemorheometer; blood and plasma viscosities; ATP, 2.3 DPG and plasma hemoglobin rates; and RBC morphology through SEM; 2) bacterial detection and identification; 3) detection of foetal cells which could create immunological disturbances if reinjected into the mother. The results showed: 1) little variation in RBC deformability properties with ATP and 2.3 DPG rates which, apart from a slight decrease, remained within the normal range; 2) a 20 fold increase in plasma hemoglobin persisting, despite successive washes, in 80% of cases; 3) positive Staphylococcus epidermidis hemoculture clinically irrelevant in the reinjectable bag in 90% of cases; 4) close to 1% foetal cells in the reinjectable bag in 20% of cases; 5) 8% abnormal cells as seen on SEM (Stage I echinocytes) and a slight swelling of the RBCs, which could account for their fragility. These preliminary results show that intraoperative autologous transfusion could be used in obstetrical surgery, provided that certain precautions are taken to minimize the aforesaid drawbacks.

Prevention of HLA immunization with leukocyte-poor packed red cells and platelet concentrates obtained by filtration.

HLA immunization is a common complication of transfusion therapy in 30% to 60% of oncohematologic patients. Evidence shows that leukocytes present in cellular blood products are the main component involved in the occurrence of HLA immunization, and several studies showed that leukocyte-poor blood products are less able to induce it. However, leukocyte-poor platelet concentrates obtained by conventional techniques, ie, centrifugation, frequently have a high level of remaining leukocytes. Cotton wool filter Imugard IG 500 can be used to obtain leukocyte-poor cellular blood products. The technique is easy to perform, even in an emergency, and can be used with either packed RBCs or platelet concentrates. Means of 97%, 92%, and 76% elimination of leukocytes are obtained for packed RBCs, pooled standard platelet concentrates, and single-donor platelet concentrates, respectively. Patients were randomized to receive either standard (control group) or filtered (leukocyte-poor group) blood products. Of 112 randomized patients, 69 were evaluable, 35 in the control group and 34 in the leukocyte-poor group. Both groups are comparable according to age, diagnosis, sex ratio, previous transfusions, and pregnancies. There is a significant difference in regard to the HLA immunization rate (31.4% in the control v 11.7% in the leukocyte-poor group, P less than .05) and frequency of refractoriness to platelet transfusions (46.6% v 11.7%, P less than .05). We conclude that this filtration technique can be an efficient means to reduce the HLA immunization rate in polytransfused oncohematologic patients.

A new method for monitoring the sterility of blood donation.

Sterility of blood products is a cardinal contributor to patient safety. Bacteriologic controls of stable products comply with strict regulations, but legislation imposes only limited constraints in the case of perishable products, such as packed red cells (RBCs) or fresh-frozen plasma (FFP). Therefore, it is essential to monitor the sterility of aseptic donations from uninfected donors. Such bacteriologic monitoring can now be carried out through a tertiary bag (containing a soybean casein culture medium) connected to the classical double-pack system. This system does not jeopardize the sterility of the whole system, as the connection is tightly stoppered by a membrane. After the blood drawing, this tertiary bag is filled with 5 ml of blood, and separated from the rest of the system. It is then incubated for 3 days at 30 degrees C and for 14 days at 22 degrees C, to test for eventual bacteriologic or fungal contamination. In order to check the feasibility of this technique, we studied 76 blood drawings in the control laboratory of the blood center, and the results confirm the value of this system.

Standardization of blood product preparation by means of a "centrifugation index".

A centrifugation index for blood product preparation is proposed. This index, calculated from the domain of ultracentrifugation, is most applicable to describe the effects of centrifugation of large volumes than the relative centrifugal force and centrifugation time commonly used. The value of such an index is illustrated by the calculation of the minimum centrifugation time required for the preparation of platelet-poor plasma with seven different centrifuges.