260 results on '"Seghatchian, Jerard"'
Search Results
2. Spotlights on the trends in performance assessment of qualitative in vitro diagnostic medical devices in transfusion medicine.
- Author
-
Pereira, Paulo and Seghatchian, Jerard
- Subjects
- *
BLOOD transfusion , *MEDICAL equipment , *MEDICAL laboratories , *CONFORMANCE testing - Abstract
For reliable clinical decisions in transfusion medicine, assessing the performance of qualitative tests performed in medical laboratories is critical. When false results are reported, these can lead to an adverse reaction to blood components. Good performance assessment practices are essential for this kind of scenario, and they still remain as one of the many unmet high-priority challenges in this area. This paper aims to provide an overview of the current trends in this field. A review of the IFCC-IUPC. qualitative vocabulary was carried out, and a particular focus was given to the evaluation protocols CLSI EP12-A3 and Eurachem AQA, such as the European Union Regulation for class D in vitro diagnostic medical devices. There is a consistency between the current protocols and recognized performance assessment principles, which are mandatory in transfusion service labs. We believe that a revised imprecision interval approach and models based on emerging qualitative test types may prove beneficial in the long run. It is also important to emphasize the uncertainty of proportions to mitigate the risk of misclassification. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Editorial commentary.
- Author
-
Seghatchian, Jerard
- Published
- 2024
- Full Text
- View/download PDF
4. Polycythaemia vera: molecular genetics, diagnostics and therapeutics.
- Author
-
Putter, Jeffrey S. and Seghatchian, Jerard
- Subjects
- *
MOLECULAR genetics , *GENETIC mutation , *THERAPEUTICS , *JUVENILE diseases , *GENETICS , *SOMATIC mutation , *POLYCYTHEMIA vera - Abstract
Polycythaemia vera is one of several classical myeloproliferative neoplasms that may occur in a juvenile onset or late‐onset adult forms. It is linked to specific genetic mutations that cause a deleterious elevation in the patient's red cell mass. The discourse on genetics includes an exposé on the molecular biology of the disease and how a shared JAK2 V617F mutation can co‐exist among three distinct neoplasms. Concepts of genetics and immunology help define the origin and behaviour of the disease: the tracking of allele burdens of mutations (genetic dosage), the timing or order of acquired mutations, the import of bystander mutations and the onco‐inflammatory response; all theories are invoked to explain the progression of disease severity and potential transformational leukaemia. The World Health Organization's diagnostic criteria are accessed to focus on the subtleties of the Hb laboratories and sifting through the challenging listing of differential diagnoses that mimic PV, and our report includes an overview of manual and automated phlebotomy (erythrocytapheresis) procedures, enumerating their clinical indications, significance of temporary phlebotomy resistance and optimizing safety/ efficacy, quality and cost. Stratification of low and high‐risk disease distinguishes when to commence chemo‐cytoreductive therapy in the high‐risk patient to prevent thrombotic complications. Drug resistance is circumvented by artfully switching drugs or using novel drug designs. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
5. Facts and challenges on global deployment of vaccines for the Immunotherapy of the evolving SARS Cov-2 variants, from the UK perspectives.
- Author
-
Seghatchian, Jerard
- Subjects
- *
ANGIOTENSIN converting enzyme , *INFECTION , *VACCINES - Published
- 2021
- Full Text
- View/download PDF
6. Editorial commentary – A snapshot on the role of newer technologies identifying variability in donor red cell storage stability and its implications on recipients' clinical outcome.
- Author
-
Seghatchian, Jerard
- Subjects
- *
ERYTHROCYTES , *STORAGE - Published
- 2023
- Full Text
- View/download PDF
7. Reflections on current status of blood transfusion transplant viral safety in UK/Europe and on novel strategies for enhancing donors/recipients healthcare in promising era of advanced cell therapy/regenerative medicine.
- Author
-
Seghatchian, Jerard
- Subjects
- *
REGENERATIVE medicine , *BLOOD transfusion , *CELLULAR therapy , *MEDICAL care , *BLOOD products , *BLOOD transfusion reaction , *HYDROGELS in medicine - Abstract
In this report, a personal view is provided on the current achievements and challenges with unresolved issues regarding the viral and transfusion safety of blood in the UK and Europe. Advances in plasma fractionation processes and the use of alternative strategies to reshape treatment of bleeding disorders are also explored. The relationships between the cellular storage lesion and transfusion outcomes using newer tools such as -omics are explored. The use of some newer developments in the promising areas of diagnosis, development, and research [DDR] strategies for improving healthcare of both donors and recipients are discussed using the current transfusion transplant practices in the UK as an example. Other key sections include: a concise presentation of the "Big Six Parameters" for enhancing the safety of transfusion / transplant practice; surmounting the unresolved issues of blood viral safety and food borne diseases, the circulatory role of the donor-gut microbiome in transfusion-induced immunomodulation, and the use of extracellular vesicles [EV] in routine aspects of the cell lesion and in the clinical performance of red cells. These topics are discussed together with the concept of using cell microparticles in drug delivery and the promising role of novel blood products such as serum eye drops and platelet lysates in regenerative medicine. It is hoped that the information conveyed in this overview would be of educational value and serve the transfusion/ transplant services and those involved in related clinical-DDR strategies worldwide and cultivate future talents capable of serving patients. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
8. Revisiting the activated protein C-protein S-thrombomodulin ternary pathway: Impact of new understanding on its laboratory investigation.
- Author
-
Amiral, Jean and Seghatchian, Jerard
- Subjects
- *
MEMBRANE proteins , *PROTEIN S , *PROTEIN C , *ACTIVATED protein C resistance , *PROTEIN S deficiency , *PLASMINOGEN activator inhibitors - Abstract
Although suspected conceptually in the 60 s, Protein C and Protein S activities in hemostasis were investigated and reported from the mid-80 s, followed by the discovery of Thrombomodulin, an endothelial cell membrane associated protein, playing the most important heamostatic role. These 3 proteins act in regulating thrombogenesis and protecting against thrombo-embolic events. When blood is activated, any trace of circulating thrombin is captured by Thrombomodulin in the microcirculation, making thrombin become an anticoagulant through its capacity to activate Protein C to Activated Protein C, which operates as a sentinel in blood coagulation, in the form of a complex with free Protein S, to block any new blood activation site, and more especially circulating activated Factors V and VIII. Protein S not only acts as the Activated Protein C cofactor, but also as the cofactor of Tissue Factor Pathway Inhibitor. In addition, it has some functions in the complement pathway through its binding to C4b-BP. Another capability of activated protein C is to lower fibrinolytic activity, as the Activated Protein C Inhibitor is also known as Plasminogen Activator Inhibitor 3. The Protein C-Protein S system becomes less efficient in the presence of mutated Factor V (Factor V-Leiden or other variants), which is resistant to its inactivating effect. Other pathologies linked to this system concern the development of allo- or auto-antibodies to Protein S or to thrombin, which can generate severe thrombotic complications in affected patients. Some antithrombotic drugs have originated from this regulatory system. Protein C or Protein S concentrates are used for treating deficient patients. Activated Protein C (especially in patients with sepsis) or Thrombomodulin are proposed as antithrombotic medications. Most importantly, congenital or acquired Protein C or Protein S deficiencies are associated with severe recurrent thrombotic events. From the clinical standpoint most of the patients are heterozygous, as homozygosity is almost incompatible with life in the absence of a continuous and efficient treatment. Laboratory investigation of this highly complex system involves many different specialized assays for measuring these 3 proteins' activities, their antigenic content or their genetic sequence. The Protein S in-vitro anticoagulant activity is weak and contrasts with its high antithrombotic role in-vivo, showing that diagnostic assays have not yet succeeded in reproducing all the natural mechanisms for evidencing the anticoagulant role of Protein S. This paradoxal notion is discussed and illustrated in this manuscript as well is a revisit of the major characteristics and pathophysiological functions of the Protein C-Protein S-Thrombomodulin system; the associated pathologies; and the main laboratory tools available for clinical diagnosis. In respect to future perspectives, we also focused on developing more significant and relevant assays, especially for Protein S, thanks to the understanding of its biological roles. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
9. What's happening CAR T cell immunotherapy.
- Author
-
Seghatchian, Jerard
- Subjects
- *
T cells , *IMMUNOTHERAPY , *CHIMERIC antigen receptors - Published
- 2023
- Full Text
- View/download PDF
10. An invite for evidence-based insights and expert viewpoints on blood donor recruitment and retention.
- Author
-
Seghatchian, Jerard
- Subjects
- *
BLOOD donors - Published
- 2023
- Full Text
- View/download PDF
11. Passive immunotherapy, for the management of over 65 ages against the evolving fast spreading SARS CoV-2 variants infection.
- Author
-
Seghatchian, Jerard
- Subjects
- *
MEDICAL personnel , *IMMUNOTHERAPY , *IMMUNIZATION of children , *INFECTION , *COVID-19 , *CONVALESCENT plasma , *COVID-19 pandemic - Abstract
As the one shot is probably sufficient, as there is some level of antibodies against the virus exist in people who were already infected and with one shot, they basically develop the level of antibodies that most people get with two shots of vaccine; b] Is the infection has primed the immune system and the on shot vaccine is effectively boosting those existing immune responses? This concept is also supported by a new trial on Moderna' vaccine, using the same vaccination principle, than the Pfizer vaccine, indicating that that a single dose is effective after 2 months of vaccination. However, in support of the UK decision it should be mentioned that the one dose of Pfizer/BioNTech's COVID-19 vaccine is 51% effective at preventing both symptomatic and asymptomatic SARS-CoV-2 infection and this level of efficacy meets the WHO acceptance criteria for the useful vaccine to be equal or over 50% efficacy. [Extracted from the article]
- Published
- 2021
- Full Text
- View/download PDF
12. The contact system at the crossroads of various key patho- physiological functions: Update on present understanding, laboratory exploration and future perspectives.
- Author
-
Amiral, Jean and Seghatchian, Jerard
- Subjects
- *
DRUG side effects , *DRUGS , *BLOOD coagulation , *MOLECULAR weights , *NATURAL immunity - Abstract
The contact system initiates the intrinsic pathway of coagulation and is started by Factor XII activation, which then activates prekallicrein to kallicrein and Factor XI to Factor XIa and, in the presence of high molecular weight kininogen, forms a "contact phase activation loop", that amplifies Factor XII activation. FXII deficiency is not associated with bleeding tendencies, but when the blood clots, the thrombus is less dense, thus favoring antithrombotic protection. Activated Factor XII inhibition emerges as an efficient target for preventing thrombo-embolic diseases without inducing a hemorrhagic risk. Activated Factor XII exhibits other activities, in that it can activate complement and provoke inflammation, contributing to innate immunity. It also stimulates fibrinolysis through uPA activation from scu-PA. Among the other components of the contact phase, Factor XI has a more important role in coagulation pathways and can directly activate FX, FVIII and FV, in a FIX independent pathway. Its deficiency is associated with a mild bleeding diathesis ("pseudo-hemophilia" or hemophilia C), with a variable incidence among kindreds. Recently, the occurrence of thrombotic events the same day following infusion of immunoglobulin concentrates has been demonstrated to be caused by the presence of trace amounts of activated Factor XI, pointing out the key role of this factor for thrombogenicity. Prekallicrein can be activated at the endothelial surface in the presence of high molecular weight kininogen, whose cleavage generates bradykinins and contributes to vessel tonicity and inflammation. The contact phase, through its activation loop, is then an important physiological system, which can initiate and regulate various biological functions and is at the crossroads of various biological activities. Many of the body's physiological functions are intimately linked between them, making the global approach of special usefulness for understanding the interactions which can result from any abnormality of one of them. New pharmaceutical drugs targeting a defined activity need to be investigated for all the possible interferences or side effects. In this article we aim to present and summarize the present understanding of contact phase system activation and regulation, its involvement in various physiological functions, and the laboratory tools for its exploration. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
13. Donor health assessment – When is blood donation safe?
- Author
-
Nissen-Meyer, Lise Sofie H. and Seghatchian, Jerard
- Subjects
- *
BLOOD products , *BLOOD transfusion , *UNIVERSITY hospitals , *DRUG utilization , *BLOOD donors - Abstract
Abstract Blood donation is a highly regulated practice in the world, ensuring the safety and efficacy of collected blood and its components whether used as irreplaceable parts of modern transfusion medicine, as a therapeutic modality or additional support to other clinical therapies. In Norway blood donation is regulated by governmental regulations ("Blodforskriften") and further instructed by national guidelines, "Veileder for transfusjonstjenesten" [1], providing an aid for assessment of donor health. This concise review touches upon: definitions of donor health and disease; some important pitfalls; and the handling of some common and less common pathophysiological conditions; with an example from the Blood center of Oslo University Hospital, Norway's largest blood center. I also comment on some medications used by a number of blood donors, although wounds, ulcers and surgery are not included. Considering the panorama of conditions blood donors can suffer from, blood donation can never be completely safe for everybody, as zero risk does not exist, but it is our task through donor evaluation to identify and reduce risk as much as possible. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
14. The use of thromboelastography (TEG) in massively bleeding patients at Haukeland University Hospital 2008–15.
- Author
-
Saeveraas, Snorre Brundtland, Seghatchian, Jerard, Sivertsen, Joar, and Hervig, Tor
- Subjects
- *
UNIVERSITY hospitals , *BLOOD products , *MEDICAL needs assessment , *BLOOD transfusion , *COAGULATION - Abstract
Abstract Thromboelastography (TEG) has been part of the assessment of patients receiving massive transfusion (MT) at Haukeland university hospital (HUH) since 2007. However, the test has been used inconsistently, and in general, the value of the test in evaluation of patients with critical bleeding is still debated, although it has been suggested that the TEG-guided treatment decreases blood usage. This single-centre retrospective study examines the use of TEG and discusses its place as part of assessing MT patients. The study focuses on the amount of blood product transfused in TEG-tested and non-TEG tested patients and whether TEG assisted coagulation therapy has affected mortality compared to conventional coagulation tests (CCTs). The study is based on the data from the massive transfusion study (MTS) 2002-15. 241 MT patients were identified, and they were grouped into patients assessed with TEG and patients who did not get this evaluation. In a sub-analysis, the patients with the initially (first TEG-test) 30 best and 30 worst TEG curves were defined based on normal ranges for the parameters R-time, α-angle, Maximal Amplitude (MA) and lysis after 30 min (LY). Survival rate and blood product usage were compared between these groups and between TEG and non-TEG patients. 111 patients were tested with TEG and 130 were not. The patients with highly pathological TEG curves (worst) have significantly higher mortality than the 30 normal-TEG patients (best) after 24 h (p < 0.001), 5 days (p < 0.05) and 30 days (p < 0.05). The best group had significantly lower mortality than the non TEG-group (p < 0.001). The difference in mortality between TEG and non-TEG patients overall was not statistically significant (p = 0.679). The TEG patients received more blood transfusions than non-TEG patients, (p < 0.001) and the patients with the worst TEG curves received the highest number of blood components. The use of TEG is debated in patients with critical bleeding. This study shows that TEG-testing is variably used in the assessment of massively bleeding patients at Haukeland University Hospital. 43.2% of 241 patients receiving massive transfusion packs were tested by TEG. When we compared the patients with the 30 best TEG curves with the 30 worst curves, there was a significantly better survival in the "best" group – without any significant difference in blood component usage. This study was not designed to provide causal information, but despite the limitations, the study indicates that the role of TEG in this patient group should be further evaluated. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
15. Immunohematologic issues in ABO-incompatible allogeneic hematopoietic stem cell transplantation.
- Author
-
Akkök, Çiğdem Akalın and Seghatchian, Jerard
- Subjects
- *
STEM cell transplantation , *IMMUNOHEMATOLOGY , *HEMOLYSIS & hemolysins , *GRAFT versus host disease , *IMMUNOLOGIC diseases , *GRAFT versus host reaction - Abstract
Abstract It is a conceptual paradox to perform allogeneic hematopoietic stem cell transplantations across the ABO blood group border, when we, on the other hand, put so much effort into preventing ABO-incompatible transfusions. In clinical practice though it is still controversial whether ABO-incompatible allogeneic hematopoietic stem cell transplant have detrimental effects on patient outcomes in view of overall survival, non-relapse mortality, and graft-versus-host disease. However, the number of ABO-incompatible transplantations will probably continue to increase, unless solid evidence about contraindications can be presented. In the meantime, all necessary measures to reduce the acute hemolysis risk have to be taken regarding graft manipulation and correct selection of ABO group blood components for transfusion. In addition the immunohematologic challenges dealing with gradual ABO group shift have to be handled. These puzzling but exciting issues are addressed briefly in this What's Happening manuscript. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
16. An update on evidence based diagnostic and confirmatory testing strategies for heparin induced thrombocytopenia using combined immunological and functional assays.
- Author
-
Amiral, Jean and Seghatchian, Jerard
- Subjects
- *
HEPARIN , *THROMBOCYTOPENIA , *BLOOD platelet disorders , *GRAY platelet syndrome , *ANTICOAGULANTS , *HEMATOLOGIC agents - Abstract
Abstract This manuscript aims to provide a concise review on current diagnostic/ confirmatory strategies of Heparin Induced Thrombocytopenia (HIT) with the combined use of immunological / functional assays in addition to the clinical probability. Laboratory diagnosis of HIT is of primordial importance as the related complications could become rapidly severe and life-threatening and can provoke limb amputation in some cases. The first action in the presence of HIT suspicion is to withdraw heparin and to initiate an alternative anticoagulant. Whilst vitamin K antagonists are not appropriate, anticoagulant options include Fondaparinux, Sodium Danaparoid, DOACs, Argatroban, and Bivalirudin. However, if HIT is excluded, patients can benefit again from the high therapeutic and antithrombotic efficacy of this drug, which remains superior to all the substitutive anticoagulant treatments. HIT is suspected in the presence of a platelet count drop > 50% on 2 successive counts, or a platelet count < 100 G/L, and of a significant clinical probability (4 Ts score). Testing patients' plasma is required for establishing the diagnosis. Laboratory investigation involves first the immunological measurement of heparin dependent IgG antibodies (mainly targeted to Heparin-Platelet Factor 4 complexes). When positive, a functional assay for platelet activation, performed at a low and high heparin concentration, allows confirming this disease. In any case, if the immuno-assay is negative, HIT can be excluded with a high probability, and heparin can be continued (if clinical examination favors this decision). Conversely, the higher the IgG antibody concentration is (and affinity), the higher is the probability of developing HIT. The functional assay has now become for confirming the platelet activation capacity of antibodies, and therefore confirming the presence of HIT. Up to now, the gold reference method for testing antibody-dependent platelet activation is the C14-Serotonin Release Assay, available only in very few laboratories working with radio-isotopes. A simple, sensitive, and accurate flow cytometry assay becomes now available to all clinical sites, and it can be easily used for testing the capacity of heparin dependent-antibodies to activate platelets, at low heparin concentration. This technique can be performed in any laboratory equipped with a flow cytometer and can make the HIT confirmation diagnosis rapidly available, which introduces a great improvement for management of patients with HIT. We believe that an evidence–based update on this topic is timely and well warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
17. What's happening editorial commentary: Immunological impacts CD71+RBC subpopoulation present in stored blood and validation of a new irradiation system for off-line EPC.
- Author
-
Seghatchian, Jerard
- Subjects
- *
IRRADIATION - Published
- 2023
- Full Text
- View/download PDF
18. T-cell lymphocytopenia: An omnipresent predictor of morbidity and mortality in consequence of SARS-CoV disease and influenza A infections.
- Author
-
Putter, Jeffrey S. and Seghatchian, Jerard
- Subjects
- *
LYMPHOPENIA , *SARS virus , *CYTOKINE release syndrome , *INFLUENZA , *VIRUS diseases , *BLOOD coagulation factors , *T cells - Abstract
[Display omitted] • An update on lymphocytopenia induced by severe SARS-CoV disease and influenza A infections. • Apoptosis and sequestration are reportedly amongst two principal modes of CD4+/CD8+ leukodepletion. • A novel "Index Severity Score" of infection was classified in conjunction with depleted T -cell counts. • A total T -cell threshold of <=560 cell/uL, a predictor of advanced infection, escalated mortality; and a tool guiding clinical trials of new therapeutics. • Future research in progress to identify quantifiable relationships between T -cell counts, cytokines, inflammatory and coagulation markers in conjunction with disease severity. We proposed T -cell lymphocytopenia as a strategic predictor of serious coronavirus and influenza infections. Our preeminent goal was to determine whether a degree of T -cell lymphopenia would identify a distinct threshold cell count to differentiate between severe and non-severe infections. We codified an Index Severity Score to exploit an association between T -cell cytopenia and the grade of disease activity. A T -cell count of 560 cells/uL or below signified a trend towards advanced disease. (1.) The T -cell threshold > 560 cells/uL discriminated 85.7 % specificity of the lesser viral infections and <=560 cells/uL identified 100 % sensitivity of severe infections or death. (2.) The positive predictive value of this threshold test was 92.9 %. (3.) T -cell apoptosis and sequestration are two of the primary mechanisms of T -cell lymphodepletion. (4.) There is potential for the T -cell threshold at <=560 cells/uL to become a standard to differentiate disease severity. (5.) The T-cell threshold should be tested further against flow cytometry of CD4+, CD8+ counts of individual patients. (6.) Future research should explore correlations between the T -cell threshold, medical outcomes of treatment, Cytokine Release Syndromes, cytokine levels, inflammatory and coagulation markers. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
19. Reflection on passive immunotherapy in those who need most: some novel strategic arguments for obtaining safer therapeutic plasma or autologous antibodies from recovered COVID‐19 infected patients.
- Author
-
Lanza, Francesco and Seghatchian, Jerard
- Subjects
- *
COVID-19 , *IMMUNOTHERAPY , *PLASMAPHERESIS , *EBOLA virus disease , *COVID-19 pandemic - Abstract
Reflection on passive immunotherapy in those who need most: some novel strategic arguments for obtaining safer therapeutic plasma or autologous antibodies from recovered COVID-19 infected patients The COVID-19 pandemic is an emerging new human disease, for which no vaccines, or monoclonal antibodies (mAbs) or drugs, are currently available for therapy. In fact, critically ill COVID-19 patients as well as those in early phases of the disease might be excellent candidates for passive immunotherapy, and for further randomized clinical trials for addressing its clinical usefulness in various patient subcategories. [Extracted from the article]
- Published
- 2020
- Full Text
- View/download PDF
20. Pediatric red cell and platelet transfusions.
- Author
-
Akkök, Çiğdem Akalın and Seghatchian, Jerard
- Subjects
- *
ERYTHROCYTES , *BLOOD platelets , *BLOOD transfusion , *THALASSEMIA , *CHILD patients - Abstract
The aim of pediatric transfusions should be based on the concept of avoiding unnecessary transfusions without jeopardizing the patient safety and providing correct blood components when there are well founded indications to transfuse. Despite considerable efforts from transfusion services to increase transfusion safety, transfusions are still associated with preventable and unpreventable adverse effects that may, in the worst case, have severe and fatal consequences. Transfusions to pediatric patients constitute a small proportion of all transfusions but have higher incidence of adverse events compared to adults. Pediatric transfusions consist of intrauterine transfusions, top-up transfusions to neonates and young children, exchange transfusions in the management of hemolytic disease of newborn (HDN), in addition to sickle cell crisis, chronic transfusion therapy in thalassemia patients, massive transfusion in trauma, HLA- and HPA-compatible platelets in immunized patients and neonates with fetal neonatal alloimmune thrombocytopenia (FNAIT). Packed red cells (PRCs) and platelet (PLT) concentrates are the most utilized blood components and will be reviewed here. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
21. Emerging stem cell based strategies for treatment of childhood diseases.
- Author
-
Sniecinski, Irena and Seghatchian, Jerard
- Subjects
- *
STEM cells , *CELLULAR therapy , *REGENERATIVE medicine , *IMMUNOTHERAPY , *MEDICAL ethics - Abstract
Cell therapy is an important regenerative medicine approach, in which either differentiated cells or stem cells capable of differentiation are transplanted into an individual with the objective of yielding specific cell types in the damaged tissue and consequently restoring its function. The most successful example of cell therapy is hematopoietic stem cell transplantation, leading to regeneration of patient’s blood cells, now a widely established procedure for many hematopoietic diseases. Development of cellular therapies for other tissues then followed in the footsteps of the hematopoietic experience. Nowadays, there are numerous ongoing clinical trials using various types of stem cells and some of them become approved cell-based products for use by patients. The aim of this review is to highlight some of advances and challenges of cell-based therapies including: • New trends in HSCT. • Clinical applications of new biopharmaceuticals and cell sources. • New frontiers in regenerative and gene therapies. • Broadening perspectives for adoptive immunotherapy. • Collaboration between medical science, health care providers, governing bodies and biopharmaceutical industry. • Challenging global issues; accessibility to effective therapy, concerted effort to coordinate regulation processes, ethical concerns and financial costs. • Future dynamics of regenerative medicine including ethical, financial and global issues associated with these developments. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
22. Concluding commentary on current trends to enhance the clinical safety of pediatric transfusion, focusing on prevention of untoward complications of HSC transplantation & newer strategies for improving the standards of safety/quality of stem cells expansion for cellular therapy
- Author
-
Sniecinski, Irena and Seghatchian, Jerard
- Subjects
- *
ADVERSE health care events , *ARTIFICIAL intelligence , *BLOOD transfusion , *PHOTODYNAMIC therapy , *IMMUNOTHERAPY - Abstract
Clinical practice and related diagnostic, development and research [DDR] strategies in pediatric transfusion and transplantation cover a broad range of multidisciplinary studies, performed by many professionals involved in this most challenging clinical field [ 1 ]. This commentary on the current position and future perspectives in pediatric transfusion field is aimed to highlight major unresolved transfusion complications in pediatric patients, namely red blood cell and platelet alloimmunisation, and new ones such as nosocomial infection, thrombosis and multi-organ failure. Some other safety related issues issues in clinical management of neonates/young infants with urgent medical conditions, requiring immediate transfusion or apheresis treatment, especially, those resulting from hematopoietic stem cell transplantation (HSCT), have been addressed. Pediatric HSCT has evolved along with its growth and progress in adult population. New sources of stem cells, and greater donor options including apheresis donation by identical or haploidentical young children, new immunosuppressive drug and cell therapy regimens for prevention and treatment of transplantation related graft versus host disease (GVHD), recent developments in gene and immune cell as well as regenerative therapies, requiring implementation of advanced laboratory methods designed for efficient and safe HSC cell engineering are also discussed. Finally, the use of novel blood components, obtained from allogeneic cord bloods or platelet concentrates in successful treatment of ulcerative lesions in inherited or acquired conditions and in expansion of stem cells, as the growth media clinical grade supplement will be presented. Management of these new and challenging clinical situations in pediatric patients requires an integrated approach involving many specialties with overall goal of improving treatment outcome and quality of life. This only could be accomplished by adhering to existing practice standards in current practices and timely developing guidelines for new clinical applications. It is hoped that this commentary on the pediatric theme, by bridging the gap from bench to bedside and bringing the input from the prospective clinical trials back to laboratories provides a step forward to help in educational aspects of better understanding the specifics of pediatric patient care more fitting for the future interventional treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
23. Usefulness of chromogenic assays for potency assignment and recovery of plasma-derived FVIII and FIX concentrates or their recombinant long acting therapeutic equivalents with potential application in treated pediatric hemophiliac patients.
- Author
-
Amiral, Jean and Seghatchian, Jerard
- Subjects
- *
CHROMOGENIC compounds , *PHARMACOKINETICS , *HEMOPHILIACS , *RECOMBINANT drugs , *IMMUNOGLOBULINS - Abstract
On demand and prophylaxis usage of FVIII/ FIX concentrates for the therapeutic management of hemophilia has greatly changed quality of life, and healthy life span of affected patients. Availability of recombinant therapeutic FVIII and FIX products, and of their long-acting variants, further improves the treatment constraints, and progressively permits to hemophiliacs to have an almost normal way of life. Unlimited amounts of recombinant or engineered substitutive products become available, and open new avenues for extending the benefits of prophylaxis to all hemophiliac patients, not only in economically advanced territories, but also in emerging and developing countries, worldwide. Pharmacokinetics of injected products can be variable among treated patients, and dependent on age. In addition, patient medical status, existing diseases, and the nature of joint damages can impact protective effect of substitutive products, and risks associated to way of life and activity. Product requirements and half-life of infused products are therefore patient specific. Monitoring recoveries of injected products thus provide useful information for the most appropriate treatment adjustment. FVIII and FIX measurements in plasma of treated patients helps to establish the optimal interval between injections for each treated patient, and the overall therapeutic cost. Due to the high variability from reagent to reagent, and the different behavior from plasma derived products, clotting methods are not ideal for recombinant and long-acting products. They require to be performed only in association with a drug specific calibrator. They are not recommended for patients’ survey, due to the high variety of reagents available. Chromogenic assays (2-stage methods) offer a standard reactivity to all available FVIII or FIX products in drugs, whether the way they are obtained, or in plasma. In a subset of treated patients, inhibitory antibodies to FVIII or FIX develop and can be measured with inhibition assays (Bethesda units), or by Elisa. Unfortunately, FVIII or FIX substitutive therapies cannot be used in patients with inhibitors, and alternative clinical management is requested, such as the use of FEIBA or FVIIa for their bypassing activity. A new treatment is being introduced in the form of a bispecific antibody (Emicizumab) targeted to both FIXa and FX, and which allows activating FX by FIXa without the need for FVIII. Some chromogenic assays (Biophen FVIII), designed with human proteins, offer the possibility to measure the activity and recovery of this new drug. Chromogenic methods are then useful for establishing potency of therapeutic products or monitoring recovery and kinetics in treated patients, through plasma measurements. Availability of International Standards for FVIII and FIX, in concentrates or plasma, allows harmonization of assay results. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
24. Statistical control of the production of blood components by control charts of attribute to improve quality characteristics and to comply with current specifications.
- Author
-
Pereira, Paulo, Seghatchian, Jerard, Caldeira, Beatriz, Xavier, Sandra, and de Sousa, Gracinda
- Subjects
- *
STATISTICAL process control , *BLOOD transfusion , *QUALITY control charts , *DONOR blood supply , *GAUSSIAN distribution - Abstract
Statistical process control (SPC) is closely related to good quality control practices in the manufacturing process. One of the primary goals is to detect unnatural patterns, allowing the production service to control the conformity of the blood components produced. Despite being recommended by national and international standards, its exercise is not uniform, and sometimes the methodology used is misinterpreted as SPC. When the input data has a Gaussian distribution, control charts for variables are proposed. However, when the data distribution is not normal, control charts for attributes are suggested. This article presents and discusses four statistical procedures for the control of attributes using p -, np -, u -, and c -charts. An empirical demonstration shows these models are reliable for in routine use in the Blood Establishment quality control, as also suggests the use when the control charts for variables are inapplicable. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
25. Revisiting antithrombin in health and disease, congenital deficiencies and genetic variants, and laboratory studies on α and β forms.
- Author
-
Amiral, Jean and Seghatchian, Jerard
- Subjects
- *
ANTITHROMBINS , *HUMAN genetic variation , *BLOOD coagulation , *ESTERASES regulation , *BLOOD circulation - Abstract
Antithrombin [AT] is the main inhibitor for activated plasma coagulation serine esterases, inhibiting thrombin, Factors Xa and IXa, but also Factors XIIa, XIa, VIIa, kallicrein, and plasmin. Its activity is highly enhanced by heparin, through binding to the pentasaccharide sequences, for inhibition of all coagulation proteases, except thrombin, which inhibition requires its additional binding to the heparin polysaccharide chain. However, AT is the major inhibitor of thrombin in the blood circulation. Congenital or acquired deficiencies of AT expose affected patients to an increased risk of developing unprovoked and recurrent thrombo-embolic diseases. Antithrombin can be measured with various laboratory techniques, by either immunological or functional methods. Earlier, a radial immunodiffusion immunoassay allowed measurement of the protein antigenic content. Functional assays are mainly designed with Anti-Thrombin or Anti-Factor Xa chromogenic methods and are useful for detecting genetic molecular mutations with decreased inhibitory activity and contributed to study the conformational changes of antithrombin and its variants, which potentially regulate the activity of this serine protease inhibitor. These assays are not equivalent in terms of diagnosing protein abnormalities, associated with increased thrombotic incidence, and they have variable performance for reflecting impaired antithrombin binding capacity for heparin, reduced progressive inhibition of serine proteases, or accelerated switch rates to the latent and less active forms. A small proportion of AT (<10%) is present in blood in the β-form, with a lower oligosaccharide content, a lower Molecular Weight, a higher binding rate to endothelial glycosaminoglycans, and a higher anticoagulant activity, hence requiring specific laboratory methods for its measurement. The β-AT form is then of critical importance for controlling blood activation by tissue injury and preventing development of thrombo-embolic diseases. This article reviews the performance characteristics of the currently available assays, and their usefulness for monitoring the use of AT concentrates in intensive care units, disseminated intravascular coagulation or severe infections, to restore the anticoagulant protective effect of heparin by supplementing the requested AT concentration. The issues of automation, harmonization and standardization are also revisited and discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
26. Statistical methods to the control of the production of blood components: principles and control charts for variables.
- Author
-
Pereira, Paulo, Seghatchian, Jerard, Caldeira, Beatriz, Xavier, Sandra, and De Sousa, Gracinda
- Subjects
- *
QUALITY control charts , *HEMAPHERESIS , *BLOOD transfusion , *PLASMAPHERESIS - Abstract
General quality control good practices require the control of the production of blood components using statistical techniques, such as mandatory by the European Commission Directives and the American Association of Blood Banks standards. Sometimes, the control procedure is exclusively in favor of the compliance verification with specifications per individual component or to compute the number of defective parts usually on a monthly basis. However, this is a critical restriction to detect unnatural patterns such as to guarantee that the production has a non-significance chance to manufacturing nonconforming components. Therefore, a crucial issue in Blood Establishments is the application of a reliable statistical process control methodology to assure products reliable and consistent to specifications. Statistical principles and control charts for variables are reviewed, discussed and recommended, based on current good practices. The empirical data demonstrate the consistency of these models on blood establishment routine. A flowchart to select the type of control chart is suggested. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
27. Sampling methods to the statistical control of the production of blood components.
- Author
-
Pereira, Paulo, Seghatchian, Jerard, Caldeira, Beatriz, Santos, Paula, Castro, Rosa, Fernandes, Teresa, Xavier, Sandra, de Sousa, Gracinda, and de Almeida e Sousa, João Paulo
- Subjects
- *
BLOOD products , *BLOOD sampling , *STATISTICAL process control , *ROBUST statistics - Abstract
The control of blood components specifications is a requirement generalized in Europe by the European Commission Directives and in the US by the AABB standards. The use of a statistical process control methodology is recommended in the related literature, including the EDQM guideline. The control reliability is dependent of the sampling. However, a correct sampling methodology seems not to be systematically applied. Commonly, the sampling is intended to comply uniquely with the 1% specification to the produced blood components. Nevertheless, on a purely statistical viewpoint, this model could be argued not to be related to a consistent sampling technique. This could be a severe limitation to detect abnormal patterns and to assure that the production has a non-significant probability of producing nonconforming components. This article discusses what is happening in blood establishments. Three statistical methodologies are proposed: simple random sampling, sampling based on the proportion of a finite population, and sampling based on the inspection level. The empirical results demonstrate that these models are practicable in blood establishments contributing to the robustness of sampling and related statistical process control decisions for the purpose they are suggested for. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
28. Spotlight on the impact of transfusion support, the detrimental influence of blood donation microbiomes on hematological immune-related toxicities, and the sustained efficacy and survival outcomes of immune checkpoint inhibitors' treated cancer patients.
- Author
-
Seghatchian, Jerard
- Subjects
- *
IMMUNE checkpoint inhibitors , *SURVIVAL rate , *CANCER patients , *IPILIMUMAB - Published
- 2023
- Full Text
- View/download PDF
29. Spotlight on SARS CoV-2 infection inducing autoimmunity, through the formation of autoantibody to self hemostatic components or to host cells, often leading to severe thrombotic or bleeding events.
- Author
-
Seghatchian, Jerard
- Subjects
- *
SARS-CoV-2 , *CELL anatomy , *AUTOANTIBODIES , *AUTOIMMUNE diseases , *AUTOIMMUNITY , *HEMORRHAGE - Published
- 2023
- Full Text
- View/download PDF
30. Autoimmune complications of COVID-19 and potential consequences for long-lasting disease syndromes.
- Author
-
Amiral, Jean and Seghatchian, Jerard
- Subjects
- *
ANGIOTENSIN converting enzyme , *COVID-19 pandemic , *AUTOIMMUNE diseases , *COVID-19 , *SARS-CoV-2 Omicron variant - Abstract
The latest WHO report determined the increasing diversity within the CoV-2 omicron and its descendent lineages. Some heavily mutated offshoots of BA.5 and BA.2, such as BA.4.6, BF.7, BQ.1.1, and BA.2.75, are responsible for about 20% of infections and are spreading rapidly in multiple countries. It is a sign that Omicron subvariants are now developing a capacity to be more immune escaping and may contribute to a new wave of COVID-19. Covid-19 infections often induce many alterations in human physiological defense and the natural control systems, with exacerbated activation of the inflammatory and homeostatic response, as for any infectious diseases. Severe activation of the early phase of hemostatic components, often occurs, leading to thrombotic complications and often contributing to a lethal outcome selectively in certain populations. Development of autoimmune complications increases the disease burden and lowers its prognosis. While the true mechanism still remains unclear, it is believed to mainly be related to the host autoimmune responses as demonstrated, only in some patients suffering from the presence of autoantibodies that worsens the disease evolution. In fact in some studies the development of autoantibodies to angiotensin converting enzyme 2 (ACE2) was identified, and in other studies autoantibodies, thought to be targeting interferon or binding to annexin A1, or autoantibodies to phospholipids were seen. Moreover, the occurrence of autoimmune heparin induced thrombocytopenia has also been described in infected patients treated with heparin for controlling thrombogenicity. This commentary focuses on the presence of various autoantibodies reported so far in Covid-19 diseases, exploring their association with the disease course and the durability of some related symptoms. Attempts are also made to further analyze the potential mechanism of actions and link the presence of antibodies with pathological complications. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
31. The microbiome and transfusion in cancer patients.
- Author
-
Goubran, Hadi, Seghatchian, Jerard, Radosevic, Julia, Ragab, Gaafar, and Burnouf, Thierry
- Subjects
- *
CANCER immunotherapy , *ABO blood group system , *BLOOD microbiology , *BLOOD transfusion , *IMMUNOSUPPRESSION - Abstract
Our microbiota is determined by many variables including ABO blood groups. The microbiota is not only confined to the gut and skin but is also recoverable from blood of healthy donors. The microbiota shape our immune system through cross reactivity with antigens, the expression of direct molecular patterns, the release of cytokines, the effects on nutrients and micronutrients and even through an interplay with epigenetics. It is likely, therefore, that a donor's microbiota could alter the antigenicity of blood and its components and potentially contribute to transfusion-related immune modulation [TRIM]. It could also potentially transmit infections. The recipient's microbiome contributes, on the other hand, to the tolerance to transfused blood, or to the development of transfusion reactions. Cancer patients are a particularly vulnerable population, often immunosuppressed with a significantly altered microbiota. They are more at risk for transmission of “dormant” bacteria via blood transfusion. Furthermore, chemotherapy and radiation induce mucositis that likely results in significant translocation of gut microbiota and abnormal immune reactions to transfused blood. It is therefore relevant to revisit transfusion thresholds and consider transfusion-saving strategies in cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
32. Transfusion and alternatives therapeutic support for oncology patients with hematological problems: “Are we doing more harm than benefit”?
- Author
-
Seghatchian, Jerard and Goubran, Hadi
- Subjects
- *
CANCER treatment , *BLOOD transfusion , *ALTERNATIVE medicine , *IMMUNOREGULATION , *HEALTH outcome assessment - Published
- 2017
- Full Text
- View/download PDF
33. Reflections on multiple strategies to reduce transfusion in cancer patients: A joint narrative.
- Author
-
Goubran, Hadi, Seghatchian, Jerard, Prokopchuk-Gauk, Oksana, Radosevic, Julia, Sabry, Waleed, Iqbal, Nayyer, and Burnouf, Thierry
- Subjects
- *
BLOOD transfusion , *THROMBOCYTOPENIA treatment , *ANEMIA treatment , *BLOOD coagulation , *CANCER patients - Abstract
Transfusion of red blood cells, platelets and plasma is widely used in the management of anemia and coagulopathy in cancer patients undergoing surgery, chemotherapy, and radiation. The decision to transfuse should not be made lightly as exposure to transfused blood, whether from an allogeneic or even autologous source, is not without risk and the long-term effect of blood transfusion on cancer outcomes remains questionable. Recognition of anemia associated with nutritional deficiency should be promptly corrected while avoiding the use of erythropoiesis stimulating agents. Minimizing blood loss and the prompt control of bleeding, coupled with a restrictive transfusion strategy, seem to be a reasonable approach that does not appear to be associated with long-term sequelae. Limiting platelet transfusion to patients with severe hypo-proliferative thrombocytopenia, and implementation of local hemostatic measures, together with the use of fractionated coagulation factor concentrates, as an alternative to frozen plasma transfusion, may reduce the exposure of cancer patients to potentially harmful thrombogenic and pro-inflammatory cellular microparticles. This joint narrative highlights current opinions for minimizing blood usage in patients with cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
34. Transfusion challenges in hematology oncology and hematopoietic stem cell transplant – Literature review and local experience.
- Author
-
Elemary, Mohamed, Seghatchian, Jerard, Stakiw, Julie, Bosch, Mark, Sabry, Waleed, and Goubran, Hadi
- Subjects
- *
CANCER treatment , *HEMATOPOIETIC stem cell transplantation , *BLOOD transfusion , *HEMATOLOGICAL oncology , *JEHOVAH'S Witnesses , *MEDICAL care - Abstract
Transfusion medicine plays a vital role in the supportive care of patients receiving therapy for hematology, oncology and hematopoietic stem cell transplants (HSCT). With advances in therapy with more intensive chemotherapy or radiotherapy, patients usually develop cytopenias and need frequent transfusion support with packed red blood cells, granulocyte transfusion or platelets to support them until they recover from the effect of therapy. HSCT poses unique challenges for transfusion medicine, since transplant recipients may require substantial transfusion support due to cytopenias associated with toxic medications, decreased marrow reserve, infection or their malignancy. Transfusion support has many complications, mainly immune mediated and infectious complications. Jehovah's Witness patients deny transfusions of blood products as a therapeutic option and, consequently, management of their disease with chemotherapy and stem cell transplant after myeloablative therapy is quite challenging. This review describes the challenges of transfusion support in managing hemato-oncology and stem cell transplant patients and highlights a local experience in transplanting two Jehovah's Witness patients. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
35. Taming the immune system through transfusion in oncology patients.
- Author
-
Kormi, Seyed Mohammad Amin and Seghatchian, Jerard
- Subjects
- *
CANCER immunotherapy , *BLOOD transfusion , *CANCER patients , *CANCER immunology , *IMMUNE response - Abstract
Blood transfusion is a clinical replacement therapy with many successes with some benefit and, also, some harm. Cancer is a multifaceted disease potentially associated with the immune system's weakness where the cancerous tumor cells escape from the immune system. Allogeneic blood transfusion, through five major mechanisms including the lymphocyte-T set, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), natural killer cells (NKCs), and dendritic cells (DCs) can help the recipient's defense mechanisms. On the other hand, the role for each of the listed items includes activation of the antitumor CD8+ cytotoxic T lymphocytes (CD8+/CTL), temporal inactivation of Tregs, inactivation of the STAT3 signaling pathway, the use of bacteria to enhance the antitumor immune response and cellular immunotherapy. The above issues are concisely addressed in this manuscript based on a literature survey on this topic carried out by the first author. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
36. Monitoring of anticoagulant therapy in cancer patients with thrombosis and the usefulness of blood activation markers.
- Author
-
Amiral, Jean and Seghatchian, Jerard
- Subjects
- *
CARDIOVASCULAR disease treatment , *THROMBOSIS , *THROMBOSIS diagnosis , *ANTICOAGULANTS , *CANCER patients , *CANCER invasiveness , *DISEASES - Abstract
Thrombotic diseases caused by cancer progression have been reported as one of the major causes of cancer associated morbidity and mortality along with cancer invasiveness and infectious complications. Moreover, anticoagulant therapy with heparin and heparin-like drugs, or vitamin K antagonists, or the Direct Oral Anticoagulants, is seeing an extended application in cancer patients and offers prolonged life expectancy to oncology patients for whom blood activation and thrombotic events have a variable incidence, depending on cancer type. Laboratory tools are highly useful for identifying patients at thrombotic risk through the measurement of blood activation markers and selecting those appropriate for anticoagulant therapy. Among the pathological markers, DDimer or Extracellular Vesicles have the highest diagnostic value in these pathological conditions. Global assays are useful for dosage adjustment, such as assessing either an induced anticoagulant effect or the measurement of drug activity. Various assays are also developed such as platelet aggregometry techniques for evaluating drug induced- aggregates or methods allowing measurement of the drug activity to its targeted coagulation factors such as: heparin to thrombin or Factor Xa; DOACs to Thrombin or Factor Xa (Dabigatran to thrombin and DiXaIs, Rivaroxaban, Apixaban, and Edoxaban, to Factor Xa). Such explorative techniques help to find the right dosage adjustment to protect patients from developing thrombosis without exposing them bleeding. It also permits exploration of unexpected drug behavior in treated patients, to check the right adherence to therapy in long-term anticoagulant protocols, and prevention of bleeding in patients with impaired renal or hepatic function. Complementary use of blood activation markers brings additional information on the curative effects of the anticoagulant therapy, and allows identification of pro-thrombotic activity in the clinically silent state. These issues are concisely addressed below. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
37. Red blood cell transfusion in surgical cancer patients: Targets, risks, mechanistic understanding and further therapeutic opportunities.
- Author
-
Tzounakas, Vassilis L., Seghatchian, Jerard, Grouzi, Elissavet, Kokoris, Styliani, and Antonelou, Marianna H.
- Subjects
- *
RED blood cell transfusion , *ONCOLOGIC surgery , *CANCER patients , *CANCER treatment , *CANCER risk factors , *CANCER-related mortality - Abstract
Anemia is present in more than half of cancer patients and appears to be an independent prognostic factor of short- and long-term adverse outcomes. It increases in the advanced period of cancer and perioperatively, in patients with solid tumors who undergo surgery. As a result, allogeneic red blood cell (RBC) transfusion is an indispensable treatment in cancer. However, its safety remains controversial, based on several laboratory and clinical data reporting a linkage with increased risk for cancer recurrence, infection and cancer-related mortality. Immunological, inflammatory and thrombotic reactions mediated by the residual leukocytes and platelets, the stored RBCs per se , the biological response modifiers and the plasticizer of the unit may underlie infection and tumor-promoting effects. Although the causality between transfusion and infection has been established, the effects of transfusion on cancer recurrence remain confusing; this is mainly due to the extreme biological heterogeneity that characterizes RBC donations and cancer context. In fact, the functional interplay between donation-associated factors and recipient characteristics, including tumor biology per se , inflammation, infection, coagulation and immune activation state and competence may synergistically and individually define the clinical impact of each transfusion in any given cancer patient. Our understanding of how the potential risk is mediated is important to make RBC transfusion safer and to pave the way for novel, promising and highly personalized strategies for the treatment of anemia in surgical cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
38. Hitchhiker's guide to the red cell storage galaxy: Omics technologies and the quality issue.
- Author
-
D’Alessandro, Angelo and Seghatchian, Jerard
- Subjects
- *
ERYTHROCYTES , *BLOOD banks , *BLOOD transfusion , *ANTICOAGULANTS , *LYSOSOMAL storage diseases - Abstract
Red blood cell storage in the blood bank makes millions of units of available for transfusion to civilian and military recipients every year. From glass bottles to plastic bags, from anticoagulants to complex additives, from whole blood to leukocyte filtered packed red blood cells: huge strides have been made in the field of blood component processing and storage in the blood bank during the last century. Still, refrigerated preservation of packed red blood cells under blood bank conditions results in the progressive accumulation of a wide series of biochemical and morphological changes to the stored erythrocytes, collectively referred to as the storage lesion(s). Approximately ten years ago, retrospective clinical evidence had suggested that such lesion(s) may be clinically relevant and mediate some of the untoward transfusion-related effects observed especially in some categories of recipients at risk ( e.g. massively or chronically transfused recipients). Since then, randomized clinical trials have failed to prospectively detect any signal related to red cell storage duration and increased morbidity and mortality in several categories of recipients, at the limits of the statistical power of these studies. While a good part of the transfusion community has immediately adopted the take-home message “if it isn’t broken, don’t fix it” ( i.e. no change to the standard of practice should be pursued), decision makers have been further questioning whether there may be room for further improvements in this field. Provocatively, we argue that consensus has yet to be unanimously reached on what makes a good quality marker of the red cell storage lesion and transfusion safety/efficacy. In other words, if it is true that “you can’t manage what you can’t measure”, then future advancements in the field of transfusion medicine will necessarily rely on state of the art analytical omics technologies of well-defined quality parameters. Heavily borrowing from Douglas Adam's imaginary repertoire from the world famous “Hitchhiker's guide to the galaxy”, we briefly summarize how some of the principles for intergalactic hitchhikers may indeed apply to inform navigation through the complex universe of red cell storage quality, safety and efficacy. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
39. Blood derived products in pediatrics: New laboratory tools for optimizing potency assignment and reducing side effects.
- Author
-
Amiral, Jean and Seghatchian, Jerard
- Subjects
- *
PEDIATRICS , *BLOOD products , *BLOOD coagulation , *RECOMBINANT proteins , *HEMAPHERESIS , *PATIENTS - Abstract
Neonates and children can develop rare bleeding disorders due to congenital/acquired coagulation Factor deficiencies, or allo-immune/autoimmune complications, or can undergo surgeries at high haemorrhagic risk. They then need specialized transfusion of blood components/products, or purified blood extracted products or recombinant proteins. Blood-derived therapies conventionally used for management of affected infants with genetic/acquired deficiencies, bleeding problems (coagulation Factor reduced or missing) or thrombotic disorders (reduced or missing anticoagulant proteins) pose some additional risks. These remedial therapies can cause tolerance when used very early in life and, sometimes needed, repeatedly. The introduction of recombinant proteins has allowed manufacturers to produce large amounts of the proteins usually present at very low concentration in blood. This has also changed the risk pattern of plasma-extracted products, especially in terms of continual reduction of viral transmission. Many efforts have been made over these past decades to reduce the risks associated with the use of all these products in terms of viral and bacterial safety, as well as immune disorders but they are not the objective of this article. Other associated side effects are the presence of undesired activities in blood products, which can produce thrombotic events or adverse reactions. The progressive introduction of blood derived products has greatly improved the prognosis and quality of life of affected patients. This concerns whole blood, but also blood cell concentrates, mainly platelets and red blood cells, plasma, while the blood extracted products are increasingly replaced by recombinant proteins. All these therapeutic products, i.e. blood extracted drugs, improve health and quality of life for hemophiliac's A or B, or patients with auto/allo-immune thrombocytopenias or with rare bleeding disorders, and those with thrombotic events occurring in childhood, which are mainly due to Protein C or Protein S deficiencies (congenital or acquired). Progress in analytical methods and biotechnology allow better control of the manufacturing processes for all blood derived or plasma extracted products and recombinant proteins, and contribute to improved manufacturing processes to minimize the occurrence of side effects. These adverse events can be due to the aging of the blood cell concentrate with release of their granule content, and generation of EVs, which can produce anaphylactic reactions and risk of thrombosis, but also to the presence of activated coagulation Factors in purified products, such as Factor Xia as recently identified in immunoglobulin concentrates. Characterization and measurement of contaminant products is of special usefulness during product preparation and for optimization of manufacturing processes for purified extracted products, but also for recombinant proteins. The pharmaceutical industry introduces these new methods for validating manufacturing processes, or for quality control assessments. The objective is first to warrant the full quality and safety of the lots produced, and assure the highest efficacy with the lowest risks when used in patients. For cell concentrates and fresh blood, storage conditions are critical and measurement of analytes such as EVs or Annexin V allows evaluation of quality of each individual transfused pouch. In addition to all the rules around viral and bacterial transmission risk, and immune tolerance, our available laboratory methods contribute to reducing the side effects of blood cell concentrates and derived plasma products, as well as those of the therapeutic recombinant proteins. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
40. Factual reflections and recommendations on extracorporeal photopheresis in pediatrics.
- Author
-
Sniecinski, Irena and Seghatchian, Jerard
- Subjects
- *
HEMODIALYSIS , *HEMAPHERESIS , *PEDIATRICS , *GRAFT versus host disease , *HEMATOPOIETIC stem cells , *PATIENTS - Abstract
One of the biggest challenges in evaluating available literature on extracorporeal photopheresis (ECP) practices in pediatric patients is the marked heterogeneity of approaches to the patient evaluation, procedural aspects and apheresis product analysis. These issues are most relevant in ECP management in children with graft versus host disease (GVHD) after hematopoietic stem cell transplantation. Extracorporeal photopheresis in pediatric patients is considered relatively safe with few adverse effects reported from retrospective or observational studies. Careful patient eligibility assessment for ECP procedures and close monitoring while on ECP therapy is still required by transfusion medicine and pediatric specialists. Particular attention is necessary considering the rapidly changing clinical status of children with graft versus host disease after hematopoietic stem cell transplantation, focusing on hemodynamic compromise, hematologic and metabolic disturbances. This is a review of the approaches to some of the safety issues in long-term ECP therapy in low-weight pediatric patients. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
41. Extracellular vesicle characteristics in stored red blood cell concentrates are influenced by the method of detection.
- Author
-
Almizraq, Ruqayyah J., Seghatchian, Jerard, Holovati, Jelena L., and Acker, Jason P.
- Subjects
- *
EXOSOMES , *PHOSPHOLIPIDS , *BLOOD products , *BLOOD transfusion , *IMMUNOMODULATORS - Abstract
Extracellular vesicles (EVs), including microvesicles and exosomes, are small phospholipid vesicles (≤1 μm in diameter) that are present in blood products, accumulate during storage, and have a potential transfusion-related immunomodulatory role. Knowledge of EVs in stored blood products is limited due to the challenges and difficulties in detecting these heterogeneous submicron-sized vesicles. The aim of this study was to assess the impact of different approaches to characterize EVs in stored RBC products. Quantification and size-profiling of EVs in leukoreduced red cell concentrates (RCCs) were examined on day 3, 7, 21, and 42 of storage using tunable resistive plus sensing (TRPS), flow cytometer (FC), and dynamic light scatting (DLS) methods. Using the TRPS method, the concentration of EVs < 200 nm significantly increased throughout storage ( p < 0.05). This change in exosome concentration was not detectable with FC or DLS due to limitations in their ability to resolve particles <200 nm and/or accurately determine EV concentration. Both the TRPS and FC demonstrate that the concentration of EVs ≥ 200 nm significantly increases in RCCs by day 42/43 compared to EVs present on day 3 ( p < 0.001). As the DLS measures the average size of particles in suspension, only an increase in the zeta-average size was observed during storage. EV size and concentration in RBC products is significantly influenced by the length of storage. Overall, this study shows that combining technologies may be important to improve the characterization and study of EVs in stored RCCs. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
42. Hepatitis E virus: Emerging from the shadows in developed countries.
- Author
-
Dalton, Harry R. and Seghatchian, Jerard
- Subjects
- *
HEPATITIS E virus , *PREGNANCY complications , *THIRD trimester of pregnancy , *GENOTYPES ,DISEASES in adults - Abstract
Following the discovery of HEV in the 1980s, it became apparent that HEV is endemic in a number of developing countries in Asia, Africa and Mexico. In these geographical settings HEV is spread oral faecally by HEV genotypes (gt) 1 and 2, which are obligate human pathogens. Infection occurs oro-faecally, often as a result in the breakdown of fragile sanitary infrastructure allowing drinking water supplies to become contaminated with human sewage. Hepatitis E usually causes a self-limiting hepatitis in young adults with sporadic cases and occasional dramatic outbreaks involving hundreds or thousands of cases. Clinically the illness is indistinguishable from hepatitis A, except in pregnant women where the mortality is 20–25%. Death occurs in the third trimester from fulminant hepatic failure and obstetric complications such as eclampsia, with very high associated foetal loss. For the best part of 20 years hepatitis E was considered as an imported disease in developed countries, and was only seen in travellers returning from endemic developing countries. We got this very badly wrong: HEV gt3 was ‘hiding in the shadows’ in humans, pigs, and other animals. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
43. Insights into red blood cell storage lesion: Toward a new appreciation.
- Author
-
Antonelou, Marianna H. and Seghatchian, Jerard
- Subjects
- *
RED blood cell transfusion , *CYTOMETRY , *BLOOD donors , *BIOMARKERS , *QUALITY control - Abstract
Red blood cell storage lesion (RSL) is a multifaceted biological phenomenon. It refers to deterioration in RBC quality that is characterized by lethal and sub-lethal, reversible and irreversible defects. RSL is influenced by prestorage variables and it might be associated with variable clinical outcomes. Optimal biopreservation conditions are expected to offer maximum levels of RBC survival and acceptable functionality and bioreactivity in-bag and in vivo ; consequently, full appraisal of RSL requires understanding of how RSL changes interact with each other and with the recipient. Recent technological innovation in MS-based omics, imaging, cytometry, small particle and systems biology has offered better understanding of RSL contributing factors and effects. A number of elegant in vivo and in vitro studies have paved the way for the identification of quality control biomarkers useful to predict RSL profile and posttransfusion performance. Moreover, screening tools for the early detection of good or poor “storers” and donors have been developed. In the light of new perspectives, storage time is not the touchstone to rule on the quality of a packed RBC unit. At least by a biochemical standpoint, the metabolic aging pattern during storage may not correspond to the currently fresh/old distinction of stored RBCs. Finally, although each unit of RBCs is probably unique, a metabolic signature of RSL across storage variables might exist. Moving forward from traditional hematologic measures to integrated information on structure, composition, biochemistry and interactions collected in bag and in vivo will allow identification of points for intervention in a transfusion meaningful context. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
44. Extracellular vesicles in transfusion-related immunomodulation and the role of blood component manufacturing.
- Author
-
Almizraq, Ruqayyah J., Seghatchian, Jerard, and Acker, Jason P.
- Subjects
- *
IMMUNOREGULATION , *BLOOD products , *IMMUNE system , *BIOMARKERS , *BLOOD transfusion - Abstract
There is an emerging interest in the risks posed by the ability of blood transfusion to modulate the immune system of recipients. Observational trials suggest that RBC transfusions may be associated with increased morbidity and mortality, however studies demonstrating the deleterious consequences of transfusion-related immunomodulation have had conflicting results. Efforts to understand the biological mechanisms responsible for TRIM are under way, and are focusing on the role that the extracellular vesicles (EVs) that accumulate in a red cell concentrate (RCC) during storage may play. EVs are heterogeneous submicron-sized vesicles that vary in size, composition and surface biomarkers. The biophysical and biochemical parameters of EVs reflect their mechanism of formation and cell sources. RCCs have been shown to contain a mixed population of EVs and not all EVs in RCC are solely from the constituent RBCs. The concentration of the different EVs (the RBC EVs and the non-RBC EVs), their composition, as well as their effects on the quality of the blood product vary depending on the manufacturing methods used to produce the RCC units. This article will review current evidence of the role of extracellular vesicles in transfusion-related immunomodulation and will discuss the impact that different methods used to collect, manufacture and store blood have on the composition and characteristics of EVs in RCCs. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
45. Drug delivery by erythrocytes: “Primum non nocere”.
- Author
-
Villa, Carlos H., Seghatchian, Jerard, and Muzykantov, Vladimir
- Subjects
- *
ERYTHROCYTES , *DRUG delivery systems , *NANOCARRIERS , *PHARMACOKINETICS , *BIOCOMPATIBILITY - Abstract
Red blood cells (RBCs) are naturally capable of transporting diverse cargoes throughout the circulatory system, both loaded to their surface or within their inner volume. Starting largely from the 1970s, diverse approaches for encapsulation into, and surface coupling onto, RBCs have been investigated as potential drug delivery systems. In the last decade, these efforts have yielded diverse strategies to load drugs and nanocarriers to RBCs, and to optimize their pharmacokinetics, distribution, and effects in the body. Several formulations of donor RBCs encapsulated with enzymes and drugs are currently undergoing clinical trials for treatment of oncologic and neurologic conditions. Newer approaches include design of drugs with an affinity to circulating RBCs, encapsulation into RBCs using membrane permeating compounds, and design of hybrid drug delivery systems combining synthetic components with fragments of RBC membranes. Notwithstanding the growing enthusiasm and optimism in RBC drug delivery, in this article we discuss potentially problematic issues of this biomedical concept, especially impairment of biocompatibility of the carrier RBCs, and other adverse and unintended effects. Rigorous and systematic analysis of the cautionary aspects described in this article should be further developed and extended in order to soberly gauge the risk/benefit balance of any given RBC-based drug delivery application. While there is little doubt that RBC drug delivery will ultimately flourish, focusing research efforts on approaches that are unlikely to cause adverse effects in patients will help to sooner bring this day. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
46. Measurement of extracellular vesicles as biomarkers of consequences or cause complications of pathological states, and prognosis of both evolution and therapeutic safety/efficacy.
- Author
-
Amiral, Jean and Seghatchian, Jerard
- Subjects
- *
BIOMARKERS , *EXTRACELLULAR matrix , *BLOOD products , *IMMUNOREGULATION , *MEDICAL care , *STATISTICAL sampling - Abstract
Utility of EVs, as biomarkers of cause or consequence of various pathological complications, and prognosis of blood components' therapy in terms of safety/efficacy and their potential associated hazards, primed by EVs involvements in pro-inflammatory, immunomodulatory and activations of both pro/anti-coagulatory and others associated pathways, as well as various cellular cross talks, are highlighted as the fundamental. Today EVs are becoming the “buzz” words of the current diagnosis, development and research [DDR] strategies, with the aim of ensuring safer therapeutic approaches in the current clinical practices, also incorporating their potential in long term cost effectiveness in health care systems. The main focus of this manuscript is to review the current opinions in some fundamental areas of EVs involvements in health and diseases. Firstly, our goal is highlighting what are EVs/MVs/MPs and how are they generated in physiology, pathology or blood products; classification and significance of EVs generated in vivo; followed by consequences and physiological/pathological induced effects of EVs generation in vivo. Secondly, specific cell origin EVs and association with malignancy; focus on EVs carrying TF and annexin V as a protective protein for harmful effects of EVs, and associations with LA; and incidence of anti-annexin V antibodies are also discussed. Thirdly, utility of EVs is presented: as diagnostic tools of disease markers; prognosis and follow-up of clinical states; evaluation of therapy efficacy; quality and risk assessment of blood products; followed by the laboratory tools for exploring, characterizing and measuring EVs, and/or their associated activity, using our own experiences of capture based assays. Finally, in perspective, the upcoming low volume sampling, fast, reliable and reproducibility and friendly use laboratory tools and the standardization of measurement methods are highlighted with the beneficial effects that we are witnessing in both wound healing and tissue remodeling, with an expected blockbuster status EVs as future therapeutic directions. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
47. Unresolved clinical aspects and safety hazards of blood derived- EV/MV in stored blood components: From personal memory lanes to newer perspectives on the roles of EV/MV in various biological phenomena.
- Author
-
Seghatchian, Jerard and Amiral, Jean
- Subjects
- *
BLOOD products , *BLOOD cells , *MEGAKARYOCYTES , *APOPTOTIC bodies , *BIOACTIVE compounds - Abstract
Blood cells generate heterogeneous populations of vesicles that are delivered, as small-specialized packages of highly active cell fragments in blood circulation, having almost similar functional activities, as the mother cells. These so called extracellular vesicles are the essential part of an energy-dependent natural apoptotic process; hence their beneficial and harmful biological functions cannot be ignored. Evidence is accumulating, that cellular derived vesicles, originate from all viable cells including: megakaryocytes, platelets, red blood cells, white blood cells and endothelial cells, the highest in proportions from platelets. Shedding can also be triggered by pathological activation of inflammatory processes and activation of coagulation or complement pathways, or even by shear stress in the circulation. Structurally, so called MV/EV appear to be, sometimes inside-out and sometimes outside-in cell fragments having a bilayered phospholipid structure exposing coagulant-active phosphatidylserine, expressing various membrane receptors, and they serve as cell-to-cell shuttles for bioactive molecules such as lipids, growth factors, microRNAs, and mitochondria. Ex vivo processing of blood into its components, embodying centrifugation, processing by various apheresis procedures, leukoreduction, pathogen reduction, and finally storage in different media and different types of blood bags, also have major impacts on the generation and retention of MV content. These artificially generated small, but highly liable packages, together with the original pool of MVs collected from the donor, do exhibit differing biological activities, and are not inert elements and should be considered as a parameter of blood safety in haemovigilance programmes. Harmonization and consensus in sampling protocols, sample handling, processing, and assessment methods, in particular converting to full automation, are needed to achieve consensual interpretations. This review focuses on some of our past personal studies on the role of MV/EV focusing on characterization of platelet storage lesion and platelet therapy that shows the highest transfusion hazards [up to 25%], and loss of 25% platelet efficacy after various leukoreduction and validated platelet pathogen reduction treatments. The planned paths for the future of EV/MV involvement in immunological and viral/ non-viral transfusion hazards are also discussed. Whilst considerable advances made on the characterization of EV/MV, but disparity still exists between various surrogate markers, showing some subtle differences in the levels of MV/ EV & BRMs in platelet preparations, and the clinical outcome showing platelets derived by all current technologies are equivalents in vivo. One possible reason for such a disparity may be relatedto the fact that MVs, being the end products of apoptotic cells, have little specificity and clear rapidly from circulation [<6 h in thrombocytopoenia]. This makes their clinical usefulness rather short lived. The recent findings that pegylating smaller subsets of EV increases its circulatory life from <15 minutes to approximately about one hour is highly promising, in particular, for drug delivery on specific sides. Hence a promising clinical utility of EV/MV continues, as a journey without end, indeed. This manuscript is based mainly on the selected key readings listed below. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
48. Update on extracellular vesicles inside red blood cell storage units: Adjust the sails closer to the new wind.
- Author
-
Antonelou, Marianna H. and Seghatchian, Jerard
- Subjects
- *
ERYTHROCYTES , *EXTRACELLULAR matrix , *CIRCULATING anticoagulants , *MOLECULAR pathology , *DRUG side effects - Abstract
Release of vesicles from cells is a universal biological system, an adaptive cellular response to endogenous or external physiological or stressful stimuli and a genius means for intercellular, inter-organ and even inter-organism communication. These secreted vesicles that are collectively designated extracellular vesicles (EVs) have increasingly attracted the interest of cell biologists due to their imaginable interactions with every piece of the known biological systems in both health and disease states. Although EVs isolation and characterization are challenges, owing to their particular physicochemical features and complex biology, recent technological innovation has offered better understanding and inevitably, driven the revision of previously established theories on them. However, a crucial question remains unsolved: the physiological relevance of EVs in vivo . Since membrane vesiculation is an integral part of red blood cell (RBC) aging and homeostatic machinery and a prominent feature of RBC storage lesion, the characterization of storage EVs and their probable clinical relevance with the therapeutic or adverse effects of transfusions are extremely important targets in the research fields of transfusion biology and medicine. The scientists involved should transfer nascent knowledge and state-of-the-art technological tools in the packed RBC unit in order to: (i) update the inventory of biochemical and biophysical features of storage EVs; (ii) gain insight into the molecular pathways/signals underlying their generation; and (iii) clarify their dependence on blood donor, storage strategies and analytical variations, in order to step forward on understanding their interactions with stored or recipient target cells. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
49. Big things from small packages: The multifaceted roles of extracellular vesicles in the components quality, therapy and infection.
- Author
-
Petrik, Juraj and Seghatchian, Jerard
- Subjects
- *
BLOOD plasma , *IMMUNOREGULATION , *BLOOD products , *ERYTHROCYTES , *BLOOD platelets - Published
- 2016
- Full Text
- View/download PDF
50. Spotlight on the impacts of transfusion on patients with Autoimmune Rheumatic Diseases.
- Author
-
Seghatchian, Jerard
- Subjects
- *
BLOOD transfusion , *RHEUMATISM , *AUTOIMMUNE diseases - Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.