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Jerard Seghatchian

Publications and source records attributed to Jerard Seghatchian.

At least 19 recordsLinked to original sources
PubMed2006

A new platelet storage lesion index based on paired samples, without and with EDTA and cell counting: comparison of three types of leukoreduced preparations.

Platelets derived from whole blood and diverse apheresis procedures come in contact with various artificial surfaces and undergo contact activation, sheer stress-induced shape changes, aggregation and microvesiculation during collection, processing and storage. These dynamic changes are qualitatively reflected in the log-normal platelet size distribution patterns seen, when using modern automated cell counters and can be measured quantitatively by counting the paired samples, without and with added EDTA, and calculating the differences (d) in platelet cellular indices (dPLT/dMPV/dPDW). Reporting the differences instead of the absolute values of cellular indices makes the measurements independent of basic principles used for cell counting (i.e. aperture-impedance or flow-optic). The measurements can be performed either in blood centres, hospital blood banks or nearby patient clinics equipped with a validated cell counter. At least three useful quality indices could be derived simultaneously from this procedure (accurate estimation of platelet yields using the value of the EDTA-containing sample); quantitative assessment of the % of reversible platelet aggregates, an age/pH/temperature-dependent degree of microvesiculation/apoptosis/PS exposure, based on the response to EDTA. This new set of indices correlate significantly with other conventional tests for platelet quality; hence, provide additional supportive evidence for confirming the low pH values and the subjective poor swirling data occasionally seen with stored PC. In the following study, the Sysmex SE 9000 was successfully employed for estimation of platelet cellular indices comparing the platelet storage lesion index of three types of leukoreduced platelet concentrates in current practice. The relationship between this in vitro response to clinical outcome remains to be established.

Blood Platelets↗
PubMed2006

Pathogen-reduction systems for blood components: the current position and future trends.

The current multi-layered interventional approaches to blood safety have dramatically reduced the risk of viral contamination of blood components. Nowadays most of the residual transfusion transmitted infections (TTI) occur as the result of the interval between the time the donor is infected and the moment at which tests are capable of detecting the agent, the so called "window period" which has been considerably reduced by the increased sensitivity of nucleic acid testing (NAT). However, the residual risk of bacterial contamination and the unexpected appearance of some other emerging pathogens, almost every five years, are still of major concern to the public, politicians, regulatory agencies and place immense pressures on the organisations responsible for the provision of safe blood and its components. In view of these bleak scenarios, the use of human blood as a raw biological source is inherently unsafe, and screening/testing alone cannot exclude all the potential human pathogens; hence we need to put in place some sort of safer alternatives and/or additional preventative safety measures. Recently, several substitutes (alternatives) to virtual blood components have been developed and tried. Moreover, various mechanical methods such as cell washing and leukofiltration have been implemented as additional preventative safety measures but with limited success in abrogating the risk of transfusion transmitted cell-associated agents. The most promising approaches, so far, are methods that target pathogen nucleic acids (Methylene blue; Psolaren and Riboflavin UV light treatment). These procedures have undergone considerable in vitro studies to ensure their extremely high safety margins in terms of toxicity to the cells or to the recipients. In essence, while the technology of targeting nucleic acid to stop viral proliferation is common to the above three strategies, in practice these procedures differ in terms of operational, physicochemical and biological characteristics; including the potential impacts of their metabolites and photo-adducts; their effects on the spectrum of pathogens affected and the log reductions in culture infective studies. Accordingly, any strategy that involves addition of an extraneous agent or physicochemical manipulation of blood must balance the benefits of pathogen reduction against the loss or alteration to the cells and plasma functional integrity, short and long term toxicity to the cells and to the recipients, as well as the risk to the personnel involved and the community at large. Moreover, it must be noted that each method will have a different profile of adverse reactions and may differ in terms of the risk to particularly vulnerable groups of patients, requiring in depth clinical trials, while taking into consideration the cost benefit of the final process. Newer diagnostic procedures must be in place to establish the storage stability of products that have undergone pathogen inactivation, in particular tests reflecting the release of platelet-derived cytokines, cellular apoptosis or microvesiculation and their role in immunosupressiveness. This overview aims to provide an update on the continual improvements in blood component safety, in particular using methods that target pathogen nucleic acid. Emphasis is placed on methylene blue light treatment (MBLT) and Intercept or Mirasol PRT systems for platelets and plasma. The status of pathogen reduction of whole blood and red cells is also highlighted, though the progress in this area has been virtually stopped after the finding of antibody development in the clinical trial.

Anti-Infective Agents↗
PubMed2006

What's happening - Scotblood 2006 advances in immunetolerance, information technology, microarrays and pathogen inactivation in transfusion medicine.

This commentary on Scotblood meeting aimed to provide a highlight on four areas of new development in blood transfusion medicine, based on the abstracts provided by the invited speakers. Dr. Jerard Seghatchian would like to express his sincere thanks to Prof. Robin Fraser, Chairman of the Scotblood Organising Committee, and Dr. Hagop Bessos, chairman of the Scotblood Programme Sub-Committee, for inviting him to attend this event and providing him with the essential material for this report.

Blood Transfusion↗
PubMed2006

The Mirasol PRT system for pathogen reduction of platelets and plasma: an overview of current status and future trends.

The safety of blood transfusion is still threatened by contamination of blood products with a variety of pathogens such as viruses, bacteria and parasites. A novel pathogen reduction process for platelets and plasma products, the Mirasol PRT system, has been developed and is under clinical evaluation for its efficacy and safety. The Mirasol PRT process is based on riboflavin photochemistry. This manuscript reviews current progress and future trends.

Blood Component Transfusion↗
PubMed2006

The combined effect of platelet storage media and intercept pathogen reduction technology on platelet activation/activability and cellular apoptosis/necrosis: Lisbon-RBS experience.

Platelets are known to undergo shape change, activation, a release reaction and apoptosis/necrosis during processing and storage, all of which are collectively known as the platelet storage lesion. Any additional processing may have some deleterious impact on platelet activability and functional integrity, which need to be investigated. This preliminary investigation was undertaken to establish the combined effects of standard platelet storage media and the intercept pathogen reduction technology on platelet activation and activability during 7 day storage, using buffy-coat derived platelets in standard storage media containing 35% plasma (N=24). P-selectin (CD62p) expression, a classical marker of platelet activation, and phosphatidylserine (PS) exposure on the platelet surface membrane, a hallmark of cellular necrosis/apoptosis, were both measured by flow cytometry. The results reveal significant increases in activation, from an average of 22.7% on day 1 before treatment to 31.6% on day 2 after treatment and 58.7% at the end of storage. Concomitantly, the basal expression of PS was slightly increased from 1.9% to 2.8% at day 2 after treatment and 7.3% at the end of storage. However, the functional reserve of platelets during storage, which reflects their capability to undergo activation and the release reaction when platelets were challenged with either calcium ionophore or thrombin, was relatively well maintained. These preliminary data confirm the earlier data on the use of intercept, and for the first time, based on the assessment of platelet functional integrity, suggest that platelet functional reserve is relatively well maintained, with little change in the formation of apoptotic cells.

Apoptosis↗
PubMed2006

The effects of leukodepletion on the generation and removal of microvesicles and prion protein in blood components.

BACKGROUND: Universal leukodepletion (LD) has been implemented in the United Kingdom to reduce the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease. If LD causes microvesiculation of blood cells, however, potentially infectious membrane-associated prion could reach the final products. STUDY DESIGN AND METHODS: We have measured microvesicles (MV) derived from red cells (RBC-MV), platelets (PLT-MV), and white blood cells (WBC-MV) and cellular prion protein (PrP(c)) in blood components produced by four whole-blood, five RBC, three PLT, and two plasma LD filters and three plateletpheresis techniques. RESULTS: RBC-MV and PLT-MV were either unaltered or reduced by all processes, with PLT-MV reduced 10-fold by RBC LD and greater than 300-fold by plasma LD. WBC-MV were reduced or unchanged by RBC and PLT LD and reduced by plasma LD. Whole-blood filtration appeared to increase MVs derived from granulocytes, but the load in the final components was comparable to that in processed RBCs in additive solution. PrP(c) was reduced by whole-blood, RBC, and plasma LD and unchanged by PLT techniques. There were differences between various filters and techniques, which were generally minor compared to the overall effects. CONCLUSION: These findings suggest no detrimental effects of LD processes in terms of generation of MVs or PrP(c) release.

Blood Component Transfusion↗
PubMed2005

Platelet storage lesion: an update on the impact of various leukoreduction processes on the biological response modifiers.

Currently, platelet concentrates are produced either from pooled buffy which are leukoreduced during processing, by various types of WBC removal filters and several apheresis technologies, which are leukocyte-reduced during collection with or without filtration. It is therefore important to define the impact of various leukocyte-removal processes on the acceleration of platelet storage of lesion and cellular apoptosis/necrosis. This overview briefly highlights the effects of exposure to artificial surfaces, during apheresis leukoreduction processes and platelet storage bags on the development of the platelet storage lesion that may contribute to transfusion reactions. The results obtained from three plateletpheresis technologies are compared with data from a "like with like" study on buffy-coat-derived platelet concentrates, using three types of platelet filter/pack assemblies. Emphasis is placed on the combined preparative methods and storage bags on generation/removal of: kallikrein/kinin; activated complement, leukocytes and platelet-derived cytokines and the development of cellular injuries, measured by the release of Annexin V. There was no systematic evidence of significant cellular fragmentation caused by filtration, but the combined preparative methods and storage bags appears to have some impact on the rate of release of soluble HLA. Moreover, large variability was observed between and within groups, in terms of various laboratory markers of biocompatibility and major biological response modifiers, indicating that much still remains to be done on various aspects of quality improvement to fully abrogate platelet concentrates associated transfusion reactions.

Annexin A5↗
PubMed2005

What's happening: an overview of potential adverse reactions associated with apheresis technology.

The current status of potential adverse reactions associated with the use of apheresis technology is reviewed, focussing on three main areas: adverse events related to component collection, progenitor cells collection and therapeutic apheresis. Based on available information it is believed that apheresis technologies are safe and increasingly used in transfusion medicine, including in auto-transfusion and different types of therapy. Occasionally, however, for various donor/patient and operational reasons, mild or moderate adverse reactions do occur. The majority of these reactions are related to vascular access and anticoagulants used, which can be mostly eliminated with calcium/magnesium administration. The reactions associated with therapeutic apheresis are more frequent (6.75%) than the multi-components and stem cell collections. Most of these reactions are generally mild and only 0.89% has been classified as severe. A national registry of donor adverse reactions as well as a planned haemovigilance system may prove helpful in identifying the potential causes which might be associated with either to donor/donation and/or with a particular technology or procedure.

Calcium↗
PubMed2005

Red cell storage lesion: the potential impact of storage-induced CD47 decline on immunomodulation and the survival of leucofiltered red cells.

Red blood cells undergo major biochemical and biomechanical changes during storage that could effect their post transfusion performance. Biochemical effects include changes in 2,3-diphosphoglycerate (2,3-DPG), ATP, and calcium levels, as well as metabolic modulation and release of Annexin V, a cytosolic component of blood cells, as a global marker of cellular injury and fragmentation. Biomechanical changes include alterations in cellular membrane, shape changes, phospholipid content, phospholipid asymmetry, and antigenic markers. Although the extent of these changes under various storage conditions has been well documented, their clinical effects remain unclear. In the current era of universal leucodepletion, the immunomodulatory effects of some essential markers such as CD47 and phosphatidyl serine become the focus of interest as highlighted in this manuscript.

Antigens, CD↗
PubMed2005

The influence of methylene blue light treatment and methylene blue removal filter on fibrinogen activity states and fibrin polymerisation indices.

BACKGROUND/OBJECTIVE: Methylene blue light treatment (MBLT) is efficient in inactivating viruses in plasma. However, it may cause alterations in clotting factors, especially fibrinogen (Fg). The true mechanism of such a selective alteration is poorly understood, The effects of MBLT and MB removal filters (MBRF) on Fg concentration, functional activity and fibrin polymerisation were studied. DESIGN: Apheresis plasma collected by Haemonetic MCS Plus (n=10) was split into two equal aliquots. Both were leukofiltered and virally inactivated in a standardized fashion, using Theraflex MB-Plasma Photodynamic viral inactivation Macopharma method. One of the pair was subsequently processed, using Blueflex MBRF to remove residual MB and its by-products. Control plasma samples were obtained after filtration but before MBLT. Samples were also obtained after MBLT and MBRF. All samples were analyzed for the Fg activity, Fg antigen, thrombin clotting time (TT), and alterations fibrin polymerisation indices. RESULTS: After MBLT, mean Fg concentration increased slightly (2%) whereas functional activity decreased by 31%, as compared to control samples. Mean TT prolonged by 6s after MBLT, with no further changes after MBRF. A similar trend was observed using RT. Both thrombin and reptilase triggered fibrin polymerisation were delayed and the polymerisation curves slopes were decreased slightly, with concomitant changes in fibrin opacity in samples from MBLT and MBRF as compared to control. Comparison is made for the first time with a similar changes observed in dysfibrinogenemia. CONCLUSION: MBLT resulted in about 30% decrease in Fg activity but a slight modification in fibrin polymerisation indices, with no additional alteration subsequent to MBRF. These in vitro changes are similar to those seen in plasma from patients with dysfibrinogenemia, which are usually without clinical significance.

Blood Preservation↗
PubMed2005

What's happening? The expanding role of apheresis platelet support in neonatal alloimmune thrombocytopenia: current status and future trends.

Despite some unresolved problems that may be associated with platelet transfusion, such as alloimmunisation, refractoriness, bacterial contamination, and the potential side effects related to the development of some biological response modifiers during storage, platelet therapy remains the most effective treatment for the management and prevention of severe thrombocytopenia and hemorrhage [Seghatchian J, Snyder EL, Krailadsiri P, editors. Platelet therapy: current status and future trends. Amsterdam, The Netherlands: Elsevier; 2000]. This appears to be particularly the case in neonatal alloimmune thrombocytopenia (NAIT), which arises due to an incompatibility of the platelet specific antigens between the pregnant mother and her baby. Over 80% of severe NAIT cases in the Caucasian population occur when the mother and baby differ in their HPA-1 epitope (HPA-1a negative and positive respectively) leading, in 10% of cases, to the production of anti-HPA-1a which can cross the placenta and cause NAIT in utero or post-partum. Anti-HPA-5b is the second most cause of NAIT, although severe cases occur only after the first pregnancy. Clinical manifestations of NAIT vary from mild (petechia and bruises) to severe (intracranial haemorrhage with possible death or life long morbidity). A recent study in Scotland indicated that the cost per case of severe NAIT detected during screening of pregnant women, where anti-HPA-1a is detected for the first time, would amount to $98,771 [Turner M, Bessos H, et al. Prospective epidemiological study of the outcome and cost effectiveness of antenatal screening to detect neonatal alloimmune thrombocytopenia (NAIT) due to anti-HPA-1a. Transfusion, in press. Yet, unlike the case with Rhesus hemolytic disease of the new born, the cost-effectiveness of HPA-1 screening in NAIT remains unresolved, as does the most optimal mode of treatment. Therefore, in the absence of a consensus on the screening and optimal management of NAIT, the availability and provision of HPA-1a/5b negative apheresis platelets based on current practice (transfusionguidelines.org.uk) appear to be a clinically effective treatment in NAIT. In that vein, an increasing number of blood transfusion centres are screening blood donors in order to secure panels of donors for the prompt provision of HPA-1a/5b negative apheresis platelets. However, evidence is also accumulating that while platelets derived from various apheresis technologies currently in use may be equivalent in terms of cellular contents (thus meeting specifications), they may differ in terms of the platelet storage lesion, microvesiculation and the development of platelet-derived cytokines and some other biological response modifiers [Seghatchian J. Platelet storage lesion: the influence of various leukoreduction procedures on generation/retention of some biological response modifiers, microvesiculation, distribution of membrane-bound/soluble Prion and the rate of HLA-CLASS1 release. Trans Apher Sci, in press. This manuscript summarises strategy and progress both in the improvement of apheresis platelet quality and provision in NAIT.

Antigens, Human Platelet↗
PubMed2004

What is happening? Are the current acceptance criteria for therapeutic plasma adequate?

The main objective of this overview is to highlight the impact of new developments in the processing of plasma, on the quality, safety and efficacy fresh frozen plasma (FFP). Based on the currently available information, it is suggested that current guidelines need an urgent review to include more relevant criteria of acceptability for therapeutic plasma. Moreover additional streamlining of FFP production, using selective donor panel, will improve the uniformity of therapeutic plasma and lower the potential risks of transfusion reactions.

Animals↗
PubMed2004

Bacterial contamination in blood components and preventative strategies: an overview.

Bacterial contamination of blood and its cellular components remains an unresolved problem in transfusion medicine and is considered to be the most common microbiological cause of transfusion associated morbidity and mortality. This is because contaminated units may contain large numbers of virulent bacteria as well as endotoxins that are considered to be fatal to the recipient. Accordingly, measures have been proposed to prevent or at least control the potential risk of transfusion associated bacteria infections. Broadly, these approaches include: bacterial avoidance; bacterial growth inhibition and bacterial load reduction by leucofiltration/viral inactivation. Unfortunately, none of the current approaches alone or in combination have received overall acceptance in terms of operational practice and safety/efficacy. Considerable effort has also been directed towards improving bacterial detection in order to provide a scientific basis for the lengthening of the shelf life of liquid stored platelets, without affecting, to a large extent their safety/efficacy. These issues have been highlighted in this overview on the current status and future trends.

Bacterial Infections↗