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J Seghatchian

Publications and source records attributed to J Seghatchian.

At least 73 records · Page 4Linked to original sources
PubMed1997

Platelet therapy: current opinions on laboratory and clinical aspects.

The rapid development in blood component technologies has lead to production of various types of platelet concentrates which are highly heterogenous in terms of cellular content, subpopulation of platelet and leucocytes and in vitro characteristics and storage stability. This emphasizes the need for a stringent in-process validation and statistical process control to ensure that optimal process efficiency and platelet functional integrity are continuously attained and maintained throughout the 5 days shelf life. Several unresolved issues such as development of cytokines and microparticles, some with immunomodulatory effects; fears of bacterial contamination of leucodepleted platelets, in particular in storage media; lack of progress in reduction of some unquantified risk of all types of transfusion transmitted infection (TTI), still remain the focus of current interest. While some processing results recently succeeded in killing both viruses and bacteria through a recently developed viral inactivation and filtration process, nevertheless much still remains to be elucidated in respect to long term effects of such treatments. Apart from development of purer products to reduce transfusion reactions, some complimentory alternatives to platelet transfusion are becoming available, which in the near future, may influence the demand for platelet support.

Clinical Laboratory Techniques↗
PubMed1997

Are cytokines in platelet concentrates responsible for febrile transfusion reactions?

In recent years, several studies have identified the leukocyte content and the age of the blood components as dominant factors in febrile transfusion reactions (FTRs). At present, extensive efforts are being made to reduce adverse effects by implementation and/or introduction of new methods for leuko-depletion of blood components and by studying the mechanisms responsible for these phenomena. A recent approach has been the evaluation of cytokines in platelet concentrates and this issue has been addressed with some detail in this review. Comparative data currently available on levels of cytokines in the different platelet concentrates is provided along with the functional role of the detected cytokines in including adverse reactions.

Cytokines↗
PubMed1997

Quality is a matter of mind: proposed quality improvement through the implementation of best practice.

In the past two decades, blood component, production and transfusion therapy have undergone considerable changes in terms of preparation of purer and safer products. This has led to a real improvement in their clinical effectiveness and prevention of untoward effects. With new developments in "tailor made" products it becomes imperative to establish a system of Quality Management in blood transfusion, similar to those of pharmaceutical manufacturers of blood products. Such a system must be comprehensive to embody all aspects of monitoring from donors to recipients, including validation processes using "state of the art" methodology and technology. To achieve overall acceptability, such a quality system must be simple, reliable and practical. We propose a quality improvement programme through the implementation of 6 pointers of quality which lend themselves to both harmonization and standardization programmes in all blood centres.

Blood Cell Count↗
PubMed1994

Effect of filtration, storage and platelet suspension media on platelet indices.

We describe a new approach for assessing filtration-induced changes in cellular indices of platelet concentrates at the beginning and the end of storage, using pairs of identical packs. The results revealed that post-filtered products did not store as well as their counterparts. Filtration did not induce any significant changes on aggregation as determined by spontaneous aggregation nor was there a disparity between leucocyte peroxidase/basophil count. We recommend filtration on day 2 which causes minimal loss of platelets and less change in the mean platelet volume.

Blood Platelets↗
PubMed1991

Interaction of heparinoids with platelets: comparison with heparin and low molecular weight heparins.

Heparin interacts with platelets to impair collagen-induced aggregation and adhesion to collagen. Low molecular weight heparin and heparinoids have little or no inhibitory activity in these platelet-collagen interactions. Thrombin-induced aggregation of platelets is inhibited by any of the glycosaminoglycans that will block the action of thrombin on fibrinogen. However, heparin is a much more potent inhibitor than low molecular weight heparins or heparinoids at equigravimetric concentrations in these reactions. The inhibition of ristocetin or asialo-von Willebrand factor aggregation of platelets is partially blocked by high dose heparin but not by low molecular weight heparin or heparinoids. The heparin-induced IgG antibody, produced to a heparin-platelet complex, aggregates platelets strongly in the presence of heparin, less strongly in the presence of low molecular weight heparins and pentosan polysulfate and not at all with dermatan sulfate or the pentasaccharide. Heparan sulfate does interact with platelets and this antibody, which is of interest because of the heparan sulfate on endothelial cells. Clinical information to date suggests a low incidence of heparin antibodies in patients receiving only low molecular weight heparin of the depolymerized type. Whether long-term clinical use of low molecular weight heparins, heparan sulfate, and dermatan sulfate will give rise to specific antibodies that would cause a similar problem as heparin remains to be seen.

Autoantibodies↗
PubMed1989

In vitro studies of the interaction of heparin, low molecular weight heparin and heparinoids with platelets.

Heparin, low molecular weight heparins, and heparinoids were studied for their ability to inhibit the aggregation of platelets by various agonists and for their ability to adhere to collagen. Heparin was a very effective inhibitor of aggregation with collagen and with ristocetin as it was with adhesion to collagen. The heparinoids showed little effect on aggregation or adhesion. Heparan sulfate and pentosan polysulfate did show slight inhibitory activity against collagen aggregation and adhesion and both interacted with the antibody induced by heparin therapy. It is of interest that dermatan sulfate and the pentasaccharide were almost inert in these experiments, and are unlikely to induce bleeding by inhibition of platelet function. It is highly probable that interference with the interaction of von Willebrand factor with platelets and collagen is a major mechanism for bleeding in the heparinized patient.

Adenosine Diphosphate↗
PubMed1978

Microheterogeneity in thrombin standards.

Potency estimations of thrombin have been performed using clotting and synthetic substrates in parallel assays. The International Standard and the Nordic Standard of thrombin have both been used as references. Divergencies in estimated unitage necessitated a study on possible heterogeneities in the standard preparations presented in this paper.

Animals↗
PubMedDate not supplied

The values of synthetic substrates in the improvement of diagnostic tests for haemostatic function.

The accumulated evidence suggests that synthetic substrates measure a similar biological expression as their natural counterpart with, in some cases, a better precision and simplicity of operation. Proteolytic enzymes are involved in a variety of physiological and pathological processes extending from blood coagulation to the release of specific enzymes from certain cells and bacteria. The variation in the level of these proteases, and their inhibitors in plasma or in cells, will be an excellent indicator of any malfunction in the particular system. Excellent agreement between these new generation tests and other conventional methods particularly in measuring fibrinolytic components is seen, and the assay time is cut from hours to a matter of minutes using a reaction rate analyser. Some discrepancy in the estimated potency was observed between methods used for the assay of thrombin, FVIII and several other clotting factors and their inhibitors. There has been methodological improvement and, in some cases, the cause of discrepancy has been revealed. Nevertheless, greater emphasis should still be given to standardization problems. It is, therefore, suggested that until the problems of standardization of various assay methods are resolved and the complications due to non-specificity in chromogenic methods and non-selectivity in clotting tests are overcome, the ratio of amidolytic to clotting activities should be included in the request for potency estimations and in the diagnostic assessment. Whether or not the use of substrates should be complementary or supplementary is left to individual centres according to their particular circumstances.

Aniline Compounds↗
PubMedDate not supplied

Evaluation of Cobe Trima for the collection of blood components with particular reference to the in vitro characteristics of the red cell and platelet concentrates and the clinical responses to transfusion.

This study evaluated Cobe Trima for donor and operational acceptability, the quality and storage stability of the blood components collected, and the clinical responses to transfusion. The study was carried out in 2 phases; phase 1 assessed the efficiency of red cells and platelet collection, and the characteristics of the components collected before and after storage. Phase 2 was an evaluation of operational issues and the in vitro characteristics of the red cells and platelet concentrates at the time of transfusion in respect to their cellular content, and leucocyte (interleukin IL-6 and IL-8) and platelet-derived (Rantes) cytokine levels. Cytokine levels were also measured in the donors before and after the collection procedure and in patients both before and after transfusion. The clinical responses to a small number of transfusions were assessed. The Cobe Trima was found to be straightforward to use by the operators, although additional operator training was required to manage occasional uncertainty with alarm messages. It was acceptable to the donors except for the occurrence of citrate reactions in 3/6 donors in phase 1; this problem persisted in phase 2 (6/15 donors), and needs to be addressed in the future. All blood components met UK product specifications apart from 2 platelet concentrates, 2 red cell concentrates, and one unit of FFP; the red cell and platelet concentrates had good storage characteristics. The 2 procedures, which resulted in low platelet yields, were due to occlusion of the plasma line; the method for installation of the harness has been subsequently modified to prevent this. 2 red cell concentrates showed haemolysis; the reason for this was not established. The Factor VIII level was satisfactory in plasma and the cellular content was low. The responses to 12 platelet transfusions were expected as in a group of haematology patients, and no immediate adverse effects were reported with any of the transfusions. Leucocyte-associated (IL-8 and IL-6) and platelet-associated (Rantes) cytokine levels were not elevated in donor samples taken before or after the collection procedure, or in the red cell and platelet concentrates at the time of issue. Pre- and post-transfusion IL-8 levels were raised in one patient with non-immune platelet refractoriness, and normal in 2 patients with excellent or almost satisfactory responses to platelet transfusions raising the question as whether IL-8 could be used as a laboratory marker for non-immune platelet refractoriness due to infection.

Blood Component Removal↗
PubMedDate not supplied

Current position on preparation and quality of leucodepleted platelet concentrates for clinical use.

Double dose leucodepleted PC without filtration is considered to be the most cost-effective way of preparing leucodepleted PC in a reasonable time. The procedure lends itself to a multicomponent system and production of hyperconcentrate and dry platelets, with < 10-15 ml plasma in final product and viral inactivation without considerable loss of in vitro platelet functions. Platelet concentrates obtained by various procedures are highly heterogeneous, even if a standard protocol is used for the preparation. Therefore, standard/standardisation in both production and testing procedures remain a challenging area in order to obtain comparative results. Attention needs to be focused on growing and complex technical features of preparation and on the use of new filter material in terms of biocompatibility and the related effects of activated factors on function of platelets and leucocytes. Both the production process and storage containers appear to contribute to various cellular lesion and generation of some biological response modifiers such as complements, cytokines and microparticles. In this respect it is relevant to adopt a multiparameter analysis for the validation of platelet quality as some markers of platelet storage lesion have different affinity to various surfaces, leading to false under estimation. Further development work is still needed in preparation and usage of dry platelet, platelet alternative and bacterially safe products. The underlying conditions of the transfused patients is also an important issue in this respect, it is interesting to note that patients with high IL8 levels have a substantially lower platelet recovery.

Annexin A5↗