Eurobloodpack: a common European design for blood bag systems with integral leucodepletion filters.

Three EBA specified blood bag configurations ('Eurobloodpack') are described which are capable of meeting >80% of its member's requirements. These include a 'top-and-top' and two 'bottom-and-top' packs enabling aseptic, pre-donation collection of up to 40 ml of samples, 427.5-522.5 ml of whole blood and the preparation of an extensive range of blood components. Features currently beyond the scope of ISO standardisation have been controlled including: anticoagulant and additive volumes; collection needle and sampling system; transfer tubing; cross-match line; base label; leucodepletion filter performance; compatibility of access ports and transfusion sets. Eurobloodpack has significant advantages for blood services and blood bag manufacturers.

Skin contamination by radiopharmaceuticals and decontamination strategies.

The aim of the present study was to evaluate the percutaneous penetration of five common radiopharmaceuticals ((99m)Tc, (67)Ga, (125)I, (111)In and (51)Cr) and to evaluate the effect of decontamination by a detergent solution dedicated to hospital institutions for that purpose. The skin kinetic profiles were established by using the in vitro Franz cell method over 24h. The skin distribution in each skin layer was quantified after 6h exposure time and the efficacy of the detergent solution to remove radionuclides was evaluated also after 6h. The most striking result was the repartition into two classes of kinetic profiles: (125)I and (99m)Tc permeated quickly (∼60% of applied activity after 24h) while the 3 other radionuclides permeated slowly (from ∼2.75% for (67)Ga to ∼10% of applied activity for (111)In). The lag times, i.e. the time necessary to cross the skin varied from 20min for (99m)Tc to 5h for (51)Cr, which accumulated in skin compartments. Skin washings with the detergent solution were particularly efficient for this radionuclide, contrary to the others for which the washing procedure should be applied earlier. The permeation of ions was dependent on their chemical and physical forms and on their salting-in or salting-out effects (coordination state and Hofmeister series).

National French observatory of the quality of blood components for transfusion.

PURPOSE: Since 1998, prestorage leucoreduction of cellular blood components (BC) is mandatory in France. The French Blood Service needs to follow the data on the quality of the BC prepared by blood centers. This article gives an overview of the quality control (QC) data from 2001 to 2006. MATERIAL AND METHODS: QC data are submitted to a central data bank by each centre. The data are stratified according to preparation process for analysis of key performance criteria - residual leukocytes and haemoglobin or platelet content. BC preparation processes, methods for measuring haemoglobin and platelet content, and for counting residual leukocytes are those routinely employed by centers. RESULTS: The preparation process of red cell concentrates (RCC) influences the haemoglobin content: 57.6+/-6.8 g per unit versus 50.9+/-5.4 g per unit for whole blood or RCC filtration, respectively. Apheresis RCC exhibits a reduced variability (51.2+/-3.4 g per unit). For apheresis platelet concentrates, the median residual leukocyte count remains low for all separators (0.019-0.044 x 10(6)leukocytes per unit, in 2006). However, the percentage of units exceeding 1 x 10(6)leukocytes per unit is significantly higher with one separator (1.8% versus 0.8%, in 2006). For pooled buffy-coat derived platelets, we observed a significant increase in platelet recovery throughout the years (0.66-0.77 x 10(11)platelets per buffy-coat in 2001 and 2006, respectively). CONCLUSION: Our QC data show an overall compliance with the requirements for cellular BC. Our data bank is useful to inform on the performance of leucoreduced BC preparation processes carried out with market available devices.

Quality of leucoreduced red blood cell concentrates: 5 years of follow-up in France.

BACKGROUND: Since 1998, prestorage leucoreduction of all cellular blood components has been made mandatory in France. The French blood service needed to follow the data on the quality of the blood components prepared by blood centres. MATERIAL AND METHODS: Quality control (QC) data were submitted to a central data bank by each blood centre. The data were stratified by preparation method for analysis of key performance criteria - residual white blood cell (WBC) and total haemoglobin content. The red blood cell (RBC) preparation processes and the methods for measuring haemoglobin content and residual WBC count were those routinely employed by blood centres. Each year, more than 15,500 RBCs were tested. RESULTS: Red blood cells had a mean haemoglobin content between 53.6 and 54.9 g/unit depending on the year (2001 to 2005). The requirement of 40 g/unit was reached for about 99% of units. The haemoglobin content was influenced by the preparation process: 56.8 +/- 6.9 vs. 50.6 +/- 5.6 g/unit in average for whole blood filtration or RBC filtration, respectively. Apheresis RBCs exhibited a reduced variability (51.8 +/- 3.1 g/unit). The median residual WBC count remained low (0.046 to 0.057 x 10(6) WBCs/unit), and the percentage of RBC units exceeding the 1 x 10(6) WBCs/unit cut-off ranged from 1.5 to 0.6% depending on the year. A seasonal pattern was observed, with a significant increase (P < 0.001) of the median residual WBC count and of the percent of non-conforming units during the summer months. CONCLUSION: Our QC data suggest an overall compliance with the standard. Our data bank is useful to inform on the performance of leucoreduced RBC preparation processes carried out with market available devices.

[Is GB virus C alias "hepatitis" G virus involved in human pathology?]. / Le virus GB-C ou virus << dit >> de l'hépatite G est-il impliqué en pathologie humaine?

GB virus-C alias "hepatitis" virus G was discovered in 1995 as a putative causative virus of non A-E hepatitis. It is a very common virus found in 1 to 5% of eligible blood donors in developed countries. Numerous studies over seven years led to the exclusion of its role as a significant etiological agent of hepatitis. Its in vivo replication site is still unknown. Its direct involvement in the induction of significant hepatic or extra-hepatic diseases could not be demonstrated. However, coinfections with other viruses may contribute to changes in the evolution of both liver disease (negatively) and HIV/AIDS (favourably). Today, no country has decided to screen GBV-C in blood donors. However, more studies are necessary before the absence of influence of GBV-C infection on human health in the context of other viral infections could be confirmed definitely. This article is a review of the literature on a possible involvement of GBV-C in pathologies whether associated or not to other infections.

Quality assessment of seven types of fresh-frozen plasma leucoreduced by specific plasma filtration.

BACKGROUND AND OBJECTIVES: A study was undertaken to determine plasma quality after specific filtration. MATERIALS AND METHODS: Seven types of plasma were tested, after filtration of plasma from filtered or non-filtered whole blood. Leucocyte counting was carried out after a 30-fold concentration of the sample. Twenty-nine parameters (including coagulation testing, proteins, coagulation factors and activation markers) were measured before and after filtration, and after 6 months of storage. RESULTS: After specific plasma filtration, the average residual leucocyte counts were less than 2250/l. In spite of small statistically significant changes in proteins, coagulation factors and complement activation, this study showed that plasma filtration did not alter plasma quality. After 6 months of storage at -30 degrees C, factor VIII recovery varied between 91 and 109%. Haemostasis parameters and activation markers remained within the normal range. CONCLUSIONS: Specific plasma filtration reduced the leucocyte number to < 104 leucocytes/l. The quality of plasma was not altered by the additional step of specific plasma filtration.

Quality control of leucoreduced cellular blood components in France.

BACKGROUND AND OBJECTIVES: Since 1 April 1998, all cellular blood components in France have been leucoreduced. The current French standard is < 1 x 10(6) white blood cells (WBC) per unit with a 95% confidence that at least 97% of units will meet this standard. MATERIALS AND METHODS: Quality control (QC) data for leucoreduced cellular blood components were collected from the 41 French blood centres over a 5-month period. Conformance to the standard was determined using a non-parametric approach. RESULTS: More than 98% of the 15 286 red cell concentrates and of the 2895 platelet concentrates tested had < 1 x 10(6) WBC per unit. One filtration device gave unsatisfactory results and its use was discontinued. CONCLUSION: This QC survey shows an overall compliance with the standard. The data illustrate the practical value of identifying devices or centres with consistent QC problems.

[Labile blood products and their preparation]. / Produits sanguins labiles et leur préparation.

Licensed labile blood components are put down on a regulatory list by the French Health Authority. They are prepared by the French National Blood Service and controlled according to regulatory and validated procedures. Depending on the origin of the blood, labile blood components are either homologous (donors) or autologous (from patients). Blood components (red cell concentrates, platelet concentrates and fresh frozen plasma) are processed within sterile closed disposable systems using either post-donation processing of whole blood or apheresis technology. All homologous blood components are leuco-reduced. Depending on specific settings, blood components could be washed, gamma irradiated or cryopreserved. Fresh frozen plasma is either "donor retested" after quarantine or viro-attenuated by solvent detergent treatment. Release is only allowed after a full conformity control of each blood component unit.

Prognostic factors for retinal vein occlusion: prospective study of 175 cases.

BACKGROUND: The prognosis of retinal vein occlusion is highly unpredictable because nonischemic types may convert into ischemic types within the first months. This study was designed to identify epidemiologic characteristics of the different types of retinal vein occlusion, their visual outcome, and their prognostic factors. METHODS: The authors analyzed prospectively the data from patients who have had retinal vein occlusion with complete medical and biologic examination, including fluorescein angiography, and a 1-year follow-up. RESULTS: One hundred seventy-five retinal vein occlusion eyes consisted of 120 central retinal vein occlusions (CRVO), 7 hemicentral occlusions, and 48 branch occlusions. In initially nonischemic CRVO eyes, retinal ischemia developed in 54%. The study of prognostic factors in the CRVO group showed that older age, male sex, and the number of risk factors (systemic vascular risk factors and glaucoma) were correlated with a poor visual outcome and with the development of retinal ischemia, as well as baseline visual acuity, initial extent of retinal ischemia, and rheologic findings (hematocrit, fibrinogen, and erythrocyte aggregation levels). Logistic regression underlined the prognostic role of sex, the number of risk factors, erythrocyte aggregation, and initial clinical features. Persistent macular edema was shown to be associated with hyperlipidemia and cardiovascular history, and inversely correlated to glaucoma. CONCLUSION: Because clinical characteristics of CRVO may worsen, the authors' results provide a basis to predict visual outcome by taking into account epidemiologic and rheologic findings. A careful follow-up of these patients is recommended.

[Value of an extensive biological study in venous or arterial thromboses]. / Intérêt d'une exploration biologique approfondie au cours des thromboses veineuses ou artérielles.

OBJECTIVES: The aim of this work is to study the signification of an extensive biological evaluation in patients with "unexplained" thrombosis. We studied 78 patients with more than one arterial and/or venous thromboembolic event. METHODS: Fifty-four patients were admitted for unexplained deep venous thrombosis (group I, n = 19, 9 men and 10 women) and/or arterial thrombosis (group II, n = 35, 21 men and 14 women). A third group (group III) included 24 patients (13 men, 11 women) known to have a pathologic state which can lead to a thrombotic event. RESULTS: The patients in both groups I and II had, more often than normal subjects, a high level of homocysteinemia (26% vs 3%, p < 0.001), anti-beta 2 glycoprotein 1 (18.5% vs 3%, p < 0.001) and antiphospholipid antibodies (13% vs 3%, p < 0.02). We also found a significant association between an increase of erythrocytic aggregation and arterial thrombosis (group II). In the third group, for both arterial (n = 14) and venous (n = 10) thrombosis, we found a high level of anticardiolipin antibodies (25% vs 3%, p < 0.001), anti-beta 2 glycoprotein 1 antibodies (12.5% vs 3%, p < 0.05) and abnormal erythrocytic aggregation (16.5% vs 3%, p < 0.01). In these 3 groups the other studied parameters (Lp(a), platelet aggregation, cryoglobulin, cryofibrinogen, antinuclear antibodies, anticytoplasm antibodies, plasma and urine immunoelectrophoresis, protein C, protein S, antithrombin III, plasminogen) were not different from levels observed in normal subjects. CONCLUSION: An extensive biological analysis, including plasma homocystein level, anticardiolipin antibodies, anti-beta 2 glycoprotein 1 antibodies and a study of the erythrocytic aggregation would appear to be of value in patients presenting recurrent arterial or venous thromboembolic events. Specific therapy can be applied in case of abnormal results continued anticoagulant therapy for anticardiolipin and anti-beta 2 glycoprotein 1 antibodies, and a vitamin therapy for increased homocysteinemia.

Increasing erythrocyte aggregability with the progressive grades of chronic venous insufficiency: importance and mechanisms.

Erythrocyte aggregation (EA) has appeared as the most interesting parameter among rheological measurements in chronic venous insufficiency (CVI). We therefore conducted two different kinds of studies to provide further information about the distribution and mechanisms of EA in CVI. We first analysed EA values in 67 patients, classified according to 3 evolutive groups: 27 patients suffering only from subjective symptoms of venous disease (grade 1), 19 patients with varicosis and sapheno-femoral incompetence (grade 2), 21 patients with varicosis and trophic skin changes (grade 3). EA values were also measured in 22 healthy controls. Analysis of EA was performed for equal concentrations of fibrinogen and adjusted for age. EA was significantly higher in CVI. The aggregation index, related to the kinetics of aggregates formation, rose significantly even from grade 1 while compared to controls and rose further with the evolutive grades. The same trend was found with the partial dissociation threshold (i.e. red cells aggregates cohesion). As the measurements were performed at standardized hematocrit and the results expressed after fibrinogen levels adjustment, this suggests the involvement of other factors. We subsequently investigated whether red cells from CVI patients aggregate more than those of controls when suspended in the same medium. The results showed that a cellular factor is unlikely to be involved, and that an interaction between red cells and plasma proteins other than fibrinogen could also explain the increased EA in CVI.

Red cell aggregability increases with the severity of venous insufficiency.

Several studies have suggested the presence of hemorheological abnormalities in venous insufficiency. The present prospective study was carried out to determine whether the increase in hemorheological disturbances parallels the evolution of the disease. Patients were recruited among ambulant outpatients and classified in 3 evolution stages of venous insufficiency according to the clinical and functional examination. Once a certain number of patients were included, the following successive inclusions were made in order to match for age and sex, in the other stages of venous insufficiency, the previously included patients. Since blood rheology is frequently altered in hypertension, diabetes and several other vascular pathologies, patients with those pathologies were not included. Sixty nine patients with venous insufficiency and 23 healthy subjects were tested, making up twenty three matching sets. Red blood cell (RBC) aggregation and disaggregation were assessed with the SEFAM erythroaggregameter on blood samples adjusted to 40% hematocrit. Statistical analysis showed a significant difference for the aggregation index (p = 0.0001), disaggregation shear rate (p = 0.0001) and fibrinogen (p = 0.006) between the 4 groups. Aggregability parameters increased gradually with the evolution of the disease, while the fibrinogen rise was significant only when varicose veins were present (stages 2 and 3). This progressive rise in RBC aggregability with the aggravation of venous insufficiency, by superimposing to the haemodynamic deficit, is likely to induce the formation of RBC aggregates in vivo, to perpetuate venous stasis and to contribute to the development of severe skin damages.

A randomized, double-masked study on the treatment of retinal vein occlusion with troxerutin.

Hemorheologic factors probably play a role in the pathogenesis and prognosis of retinal vein occlusion. Accordingly, we designed a prospective, randomized, double-masked study to evaluate the effect of troxerutin, a rheologic drug, on retinal vein occlusion. Fifty-three patients were included, 27 with central retinal vein occlusion and 26 with branch retinal vein occlusion. They were randomly assigned for treatment with either troxerutin or a placebo. All subjects were similar in age, gender, associated diseases, hemorheologic values, and clinical severity of the retinal vein occlusion. At the end of follow-up, members of the troxerutin-treated group, as compared with the placebo group, showed significant improvement in visual acuity (P = .03), macular threshold (P = .01), retinal circulation times (P = .04), and macular edema (P = .05). Furthermore, they had diminished progression of ischemia (P = .05) and decreased red blood cell aggregability (P = .006) when compared with the controls. These encouraging preliminary results obtained with a rheologic treatment attest to the pathogenic role of blood viscosity in retinal vein occlusion and suggest that a large-scale randomized study should be conducted.

Elevated erythrocyte aggregation in patients with central retinal vein occlusion and without conventional risk factors.

BACKGROUND: Retinal venous circulation is characterized by the combination of a low flow state and a high vascular resistance, which would make it particularly dependent on blood viscosity. Erythrocyte aggregation is the chief determinant of blood viscosity at low shear rates. Recent studies have demonstrated increased erythrocyte aggregation in many systemic vascular disorders and also in retinal vein occlusion. METHODS: To assess the possible role of abnormal hemorheologic findings in the pathogenesis of central retinal vein occlusion (CRVO), the authors retrospectively studied erythrocyte aggregation and hematocrit and fibrinogen levels in 33 patients with CRVO and without any known risk factors (diabetes, hypertension, smoking, hyperlipidemia, cardiovascular disease, glaucoma). Erythrocyte aggregation was assessed with a light back-scattering method. Results were compared with those of a group of 33 age- and sex-matched controls. RESULTS: Eleven (33%) of the 33 patients with CRVO had abnormal hemorheologic findings. Erythrocyte aggregation was highly significantly increased in the CRVO group when compared with the control group (P < 0.0001), as was the hematocrit level (P < 0.05). In addition, the proportion of patients with abnormal blood rheologic tests was greater (50%) in the subgroup of patients who initially had nonischemic CRVO that worsened into an ischemic CRVO during the follow-up. CONCLUSION: These data suggest that abnormal hemorheologic findings could affect the pathogenesis of CRVO, and perhaps be predictive of an aggravation. The latter hypothesis needs to be confirmed in a larger, prospective study.

Red blood cell aggregability in patients with a history of leg vein thrombosis: influence of post-thrombotic treatment.

Reversible aggregation of red blood cells (RBC) plays an important role in determining blood flow properties, and it is this aggregation which increases blood viscosity at low shear rates. The structure and sites of venous thrombi, as well as the fact that stasis is a major predisposing factor in venous thrombosis, suggest a strong association between vein thrombosis, slow blood flow and increased blood viscosity. RBC aggregation and disaggregation were measured (SEFAM erythroaggregameter, France) in 54 patients with a history of unexplained leg vein thrombosis. Results were compared to those of controls classified according to age. Increased RBC aggregability was observed in 41% of the patients, and the mean values indicated a significant elevation of RBC aggregability in patients when compared with controls (P < 0.05). Subgroups were compared to study the influence of thrombus recurrence and thrombosis type (deep versus superficial vein thrombosis) on the aggregation parameters. No significant difference was found between these subgroups. The use of compression stockings and veinotropic drugs tended to reduce the abnormalities in RBC aggregability (P < 0.05). An increase in RBC aggregability and in the shear resistance of RBC aggregates, by predisposing to circulatory stasis, is likely to contribute to the evolution and complications of leg vein thrombosis.

[Erythrocyte aggregation and clinical course stages of venous insufficiency of the legs]. / Agrégation érythrocytaire et stades d'évolution de l'insuffisance veineuse des membres inférieurs.

A double vicious circle at the venule and capillary level had already been pointed out by J. Dormandy and G. Nash as a pathophysiologic mechanism of rheological disorders associated with venous insufficiency of the lower limbs. Afterwards, such disorders were found by many authors when ex vivo analysis were performed on venous insufficient patients. However the time of their onset and their evolution in the course of the disease remain unknown. We studied red cell aggregation and plasma fibrinogen in 67 patients depending on the evolutive stage: 1st stage: isolated functional disorders, 2nd stage: trunk varicose vein linked to ostial incompetence, 3rd stage: trunk varicose vein linked to ostial incompetence with chronic trophic skin changes. The results showed that red cell aggregation and fibrinogen values are increased with the severity of the diseases. The rheological parameters increase when compared to controls from the first stage. Within the studied population, we avoided skewed results due to age and fibrinogen level by covariance analysis. Therefore recorded differences were practically linked with erythrocyte aggregability. Thus, red cell aggregation appears to be both an aggravating factor and a severity marker of the disease, proving the relevance of a rheological treatment in the lower limb insufficiency.

[Increase of erythrocyte disaggregation shear rate in arterial hypertension]. / Augmentation de la contrainte de cisaillement de désagrégation érythrocytaire dans l'hypertension artérielle.

Aggregation index and critical disaggregation shear rate (which represent the minimum shear rate necessary to break up the aggregates) have been measured for 21 hypertensive and 17 normotensive subjects by a laser technique (erythro-aggregameter SEFAM). A simultaneous measurement of blood viscosity by a Couette viscometer with coaxial cylinders at different shear rate allowed the calculation of critical disaggregation shear stress by the product of critical disaggregation shear rate and blood viscosity. The comparison of the results of normotensive and hypertensive subjects showed a higher aggregation index (22%, p less than 0.0001), critical disaggregation shear rate (19%, p less than 0.002) and critical disaggregation shear stress (29%, p less than 0.004) in hypertensive patients. These alterations might play an important role on development of cardiovascular complication in hypertensive subjects.

[Erythrocyte aggregation in vascular disease. Influence++ of hypertension]. / Agrégation erythrocytaire en pathologie vasculaire. Influence de l'hypertension.

In vascular diseases, when the vasomotor reserve is exhausted, microcirculation is strongly dependent on blood fluidity. For patients with vascular disorders, it was therefore decided to evaluate red blood cells (RBC) aggregation and disaggregation (SEFAM erythro-aggregometer) which are important factors determining blood viscosity in low flow areas. Our results show that, in essential hypertension (EH), RBC aggregation is significantly increased (+15%), and disaggregation is decreased (-20%). The highest frequency of troubles was found in EH. This observation led to exclusion of EH subjects in all the other studied pathological groups. When EH is excluded from a group of 70 patients with cerebrovascular disorders (CVD), we did not observe significant changes in RBC aggregation. However, in essential and post-thrombotic venous insufficiency there remains a significant increase in RBC aggregation (+10%) and a decrease in disaggregation (-13%). In diabetes, disaggregation is more disabled than for controls (-16%). In all these pathologies presence of EH magnifies the abnormalities, or makes them appear like in CVD. This study underlines the critical importance of taking the influence of hypertension into consideration when evaluating RBC aggregation in vascular pathology. The increase in RBC aggregability and in the shear resistance of the aggregates, when present in vascular pathology, is likely to add a burden to the circulatory system already hindered by a deficient vasomotor regulation system.