In vitro characteristics of cryopreserved platelet concentrates reconstituted by fresh frozen or lyophilized plasma.

BACKGROUND AND OBJECTIVES: Six percent dimethyl sulfoxide (DMSO) cryopreservation of platelet concentrates (PCs) allow longer storage of PCs but require time-consuming post-thaw washing. An alternative process based on removing supernatant before freezing has been implemented in several centres worldwide. We assessed the in vitro characteristics of cryopreserved PCs (CPPs) prepared according to this latest process using either French lyophilized plasma (FLyP) or fresh frozen plasma (FFP) for reconstitution. FLyP provides additional benefits to the process due to its logistical constraints and quick availability. MATERIALS AND METHODS: Apheresis PCs (n=16) and buffy coat PCs (n=16) were cryopreserved in 6% DMSO. After storage at -80°C, PCs were thawed and reconstituted with FFP or FLyP. Volume, residual leukocytes, total platelet counts (TPCs), post-thaw recovery, biochemical parameters, and DMSO concentration were assessed. Platelet functions were analysed by swirling index, viscoelastometric assay and CD62P quantification. RESULTS: After reconstitution, TPC was above 2.1011/CPs; recovery was 78±14% with no significant difference between FFP and FLyP. Glucose and lactate levels were not different between plasmas, whereas FLyP-CPPs exhibited a significant increase in LDH and significantly lower pH. Residual DMSO was 8±4G/L. Functional analysis revealed significant differences between FFP and FLyP-CPPs, with lower clot firmness and increased clot initiation. Activation of platelets was not higher in FLyP-CPPs. CONCLUSION: Preparing CPPs according to this "new" process fulfilled the French legal criteria regardless of the type of plasma. Differences highlighted between FFP-CPPs and FLyP-CPPs were unlikely to be of clinical relevance.

Iron-deficiency among blood donors: Donors' opinion on iron supplementation strategy.

BACKGROUND AND OBJECTIVES: Each donation of a single whole blood unit causes a 200-250mg iron loss. The main clinical manifestation of iron deficiency among blood donors is anemia, and every blood collection establishment must have measures in place to minimize and prevent iron depletion in blood donors, according to the European guidelines. However, iron deficiency without anemia is also associated with clinical manifestations. The management of iron deficiency is an acute issue; still, no consensus on its managements exists. One possibility is iron supplementation; however, the acceptability of such a measure is still unknown, so we asked donors' opinions on this topic. MATERIALS AND METHODS: Over a 2-month period, a questionnaire was voluntarily completed by blood donors at the French Military Blood Institute. Gender, age, number of donations in the last 12 months, and preference between iron supplementation and general practitioner consultation for management of iron deficiency were recorded. RESULTS: One thousand nine hundred and seventy-four questionnaires were returned. Donors between ages 18-50 represented 89% of respondents. Altogether, 49% declared that they would rather visit their general practitioner and 46% would rather receive iron supplementation. There were no significant differences correlated with gender or age. However, a higher number of prior donations was significantly associated with a preference for iron supplementation. Frequent female donors had an even stronger preference for iron supplementation. CONCLUSION: Our results showed that there are no strong objections to iron supplementation, which could be an acceptable option for frequent donors - the main population at risk for iron deficiency.

[From fibrogenesis towards fibrosis: Pathophysiological mechanisms and clinical presentations]. / De la fibrogenèse à la fibrose : mécanismes physiopathologiques et présentations cliniques.

Fibrogenesis is a universal and ubiquitous process associated with tissue healing. The impairment of tissue homeostasis resulting from the deregulation of numerous cellular actors, under the effect of specific cytokine and pro-oxidative environments can lead to extensive tissue fibrosis, organ dysfunction and significant morbidity and mortality. This situation is frequent in internal medicine, since fibrosis is associated with most organ insufficiencies (i.e. cardiac, renal, or hepatic chronic failures), but also with cancer, a condition with common pathophysiological mechanisms. Finally, fibrosis is a hallmark of numerous systemic autoimmune diseases such as connective tissue disorders (in particular systemic sclerosis), vasculitides, granulomatoses, histiocytoses, and IgG4-associated disease. Although the process leading to tissue fibrosis may be in part irreversible, new pharmacological approaches or cell therapies bring hope in the field of fibrotic conditions.

Rational and design of the T-STORHM Study: A prospective randomized trial comparing fresh whole blood to blood components for acutely bleeding trauma patients.

Massive hemorrhage remains the main cause of preventable death in combat settings and is also the main cause of year loss in developing countries. The management of these patients relies on blood transfusion and surgery. Time is a key factor, related to survival. Recent events highlight the need to be more efficient in the transfusion supply during terror attacks or mass casualties in civilian settings. Blood components therapy with a 1:1:1 ratio is associated with a decrease of mortality but encounters many logistic issues in those circumstances. Whole blood provides in one bag all the blood components in physiologic proportions with minimal amount of additive solution. Whole blood has been implemented in military as well as civilian settings worldwide. However, direct comparisons with component therapy in prospective clinical trials are scarce. Here we present the rational and the design of the T-STORHM (Trauma-Sang TOtal dans les Hémorragies Massives) trial. This prospective randomized multicentric clinical trial will test low titer group O whole blood to components therapy in the in-hospital management of trauma patients with massive hemorrhage. Sample size calculation, primary and secondary endpoints as trial blood products preparations are discussed. The trial is expected to start in 2019 in 6 civilians and military trauma centers. The French Military Health Service is promoting the study in collaboration with the French transfusion public service (Établissementfrançaisdusang).

The plasma supply in France.

Contrary to economically comparable countries, France has had a versatile policy to process and manufacture therapeutic plasma, and to apply safety measures. This has principally affected the origin of plasma (whole blood supernatant versus apheresis), and the application or not of a chemical process. At the time being, the civilian and Army Forces blood establishments produce more than 99% of the plasma issued for patients in need; safety means consist in a large part of quarantine and, to a lesser extent, to a pathogen reduction technology process (Amotosalen-HCl-UVA). The blood establishments ship plasma to the national manufacturer of blood derivatives. Plasma in France is strictly within the Voluntary Non-Remunerated pathway with no breach to this principle to be expected for both labile components and source plasma. The constant hemovigilance allows reflection to make policies evolving, with respect to safety measures particularly to reduce cases of allergy.

Vox Sanguinis International Forum on the use of prehospital blood products and pharmaceuticals in the treatment of patients with traumatic haemorrhage.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high­quality research in this area to guide optimal resuscitation strategies.

Air-drop blood supply in the French Army.

BACKGROUND: Haemorrhagic shock remains the leading cause of preventable death in overseas and austere settings. Transfusion of blood components is critical in the management of this kind of injury. For French naval and ground military units, this supply often takes too long considering the short shelf-life of red blood cell concentrates (RBCs) and the limited duration of transport in cooling containers (five to six days). Air-drop supply could be an alternative to overcome these difficulties on the condition that air-drop does not cause damage to blood units. METHODS: After a period of study and technical development of packaging, four air-drops at medium and high altitudes were performed with an aircraft of the French Air Force. After this, one air-drop was carried out at medium altitude with 10 RBCs and 10 French lyophilised plasma (FLYP). A second air-drop was performed with a soldier carrying one FLYP unit at 12 000 feet. For these air-drops real blood products were used, and quality control testing and temperature monitoring were performed. RESULTS: The temperatures inside the containers were within the normal ranges. Visual inspection indicated that transfusion packaging and dumped products did not undergo deterioration. The quality control data on RBCs and FLYP, including haemostasis, suggested no difference before and after air-drop. DISCUSSION: The operational implementation of the air-drop of blood products seems to be one of the solutions for the supply of blood products in military austere settings or far forward on battlefield, allowing safe and early transfusion.

Early and repeated use of plasma for the management of Ebola patients: Reflection around a case.

In December 2013, the most widespread epidemic of Ebola virus disease began in Guinea and continued for over 2 years. At the request of the Guinean state, France deployed a military field hospital to treat Ebola infected healthcare workers. From January to July 2015, our center supported 26 healthcare workers suffering from Ebola virus disease. Despite an individualized care and optimal treatment, the fatality rate remained high at 30.7%. Improved therapies are required to reduce mortality risk in Ebola virus disease. We report the case of a patient admitted to the hospital on the 4th day after onset, who survived despite several clinical and biological predictors of fatal outcome. We transfused plasma at a high dose and spread over time. This innovative therapeutic approach was based on our clinical experience of Ebola patients' management, literature review and knowledge of plasma ability to restore coagulation disorders and endotheliopathy. Even without any bleeding sign, coagulopathy and endothelial permeability disorders participate in hypovolemia and fatal multi-system organ failure. Early intake of therapeutic plasma at repeated doses seems to reduce the endothelial permeability and coagulation disorders related to Ebola virus disease.

[Haemovigilance and blood safety in overseas military]. / Hémovigilance et sécurité transfusionnelle en opération extérieure.

The French military blood institute (FMBI) is the only military blood supplier in France. FMBI operates independently and autonomously under the Ministry of Defense's supervision, and accordingly, to the French, European and NATO technical and safety guidelines. FMBI is in charge of the collection, preparation and distribution of blood products to supply transfusion support to armed forces, especially during overseas operations. In overseas military, a primary physician is responsible for haemovigilance in permanent relation with an expert in the FMBI to manage any adverse reaction. Additionally, traceability of delivered or collected blood products during overseas operation represents a priority, allowing an appropriate management of transfusion inquiries and assessment of practices aiming to improve and update procedures and training. Transfusion safety in overseas operation is based on regular and specific training of people concerned by blood supply chain in exceptional situation.

[Assessment of malaria screening management in blood donation control in the French Military Blood Institute]. / Évaluation de la stratégie de dépistage du paludisme en qualification biologique du don au CTSA.

The French Military Blood Institute is responsible for the entire blood supply chain in the French Armed Forces. Considering, the high exposition rate of military to malaria risk, blood donation screening of plasmodium infection must be as efficient as possible. The main aim of our study was to assess our malaria testing strategy based on a single Elisa test compared with a two-step strategy implying immunofluorescence testing as confirmation test. The second goal was to describe characteristic of malaria Elisa positive donors. We conducted a prospective study: every malaria Elisa positive test was implemented by immunofluorescence testing and demographical data were recorded as usual by our medical software. We showed a significant risk of malaria ELISA positive tests among donor born in endemic area and we estimate the number of abusively 3-year rejected donors. However, based on our estimations, the two-step strategy is not relevant since the number of additionally collected blood products will be low.

An 8-year survey of strains identified in blood cultures in a clinical haematology unit.

The aim of our study was to determine the epidemiological profile and the antibiotic susceptibility of bacteria and fungi identified from blood cultures in the patients of the clinical haematology unit. A retrospective study was carried out over an 8-year period (2003-2010) in the clinical haematology unit of the Percy Military Medical Center. During this period, we collected 723 isolates: Gram-negative bacilli (70.8%) and Gram-positive cocci (18.7%). The four most commonly isolated species were Escherichia coli (18.5%), Pseudomonas aeruginosa (14.8%), Stenotrophomonas maltophilia (6.2%) and Staphylococcus epidermidis (5.4%). The rate of methicillin-resistant Staphylococcus aureus was 6.45% and that of coagulase-negative staphylococci 61.2%. No resistance to glycopeptides was observed. In E. coli, as in the Klebsiella-Enterobacter-Serratia group, a 27% resistance to fluoroquinolones was observed. Concerning P. aeruginosa, the phenotypes were distributed over penicillinase (23.4%) and cephalosporinase (13.1% were resistant to ceftazidime). The impermeability rate of imipenem was 9.3%. The aggressiveness and duration of haematological treatments explains why infections remain one of the main complications of neutropenia. The emergence of new or unusual bacteria is highly likely. Antibiotic selective pressure and long periods of hospitalization could explain the emergence of multiresistant bacteria. As a consequence, epidemiological surveillance is indispensable.

[Therapeutic plasmas available worldwide]. / Les plasmas thérapeutiques dans le monde.

Therapeutic plasma is a current product; French guidelines were reviewed in 2012. Connections between more or less closed countries are frequent, during relief disasters as well as in war settings. This is associated with the increasing use of plasma in the management of casualties. Additionally, The real possibility of lack of plasma supply in some countries provides a fundamental interest of the knowledge of foreign blood supply organizations. We present here the main divergences and mutual point between plasmas available worldwide. We present the main characteristics of each product.