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1.
Clin Hematol Int ; 3(3): 77-82, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34820612

RESUMO

The use of convalescent plasma (CP) from individuals recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a promising therapeutic modality for the coronavirus disease 2019 (COVID-19). CP has been in use for at least a century to provide passive immunity against a number of diseases, and was recently proposed by the World Health Organization for human Ebola virus infection. Only a few small studies have so far been published on patients with COVID-19 and concomitant hematological malignancies (HM). The Italian Hematology Alliance on HM and COVID-19 has found that HM patients with COVID-19 clinically perform more poorly than those with either HM or COVID-19 alone. A COVID-19 infection in patients with B-cell lymphoma is associated with impaired generation of neutralizing antibody titers and lowered clearance of SARS-CoV-2. Treatment with CP was seen to increase antibody titers in all patients and to improve clinical response in 80% of patients examined. However, a recent study has reported impaired production of SARS-CoV-2-neutralizing antibodies in an immunosuppressed individual treated with CP, possibly supporting the notion of virus escape, particularly in immunocompromised individuals where prolonged viral replication occurs. This may limit the efficacy of CP treatment in at least some HM patients. More recently, it has been shown that CP may provide a neutralising effect against B.1.1.7 and other SARS-CoV-2 variants, thus expanding its application in clinical practice. More extensive studies are needed to further assess the use of CP in COVID-19-infected HM patients.

7.
Vox Sang ; 116(6): 617-627, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33634867

RESUMO

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.


Assuntos
Policitemia Vera , Trombose , Humanos , Janus Quinase 2/genética , Biologia Molecular , Mutação , Policitemia Vera/diagnóstico , Policitemia Vera/genética , Policitemia Vera/terapia
9.
Medicina (Kaunas) ; 56(12)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33287459

RESUMO

The demand of platelet transfusions is steadily growing worldwide, inter-donor variation, donor dependency, or storability/viability being the main contributing factors to the current global, donor-dependent platelet concentrate shortage concern. In vitro platelet production has been proposed as a plausible alternative to cover, at least partially, the increasing demand. However, in practice, such a logical production strategy does not lack complexity, and hence, efforts are focused internationally on developing large scale industrial methods and technologies to provide efficient, viable, and functional platelet production. This would allow obtaining not only sufficient numbers of platelets but also functional ones fit for all clinical purposes and civil scenarios. In this review, we cover the evolution around the in vitro culture and differentiation of megakaryocytes into platelets, the progress made thus far to bring the culture concept from basic research towards good manufacturing practices certified production, and subsequent clinical trial studies. However, little is known about how these in vitro products should be stored or whether any safety measure should be implemented (e.g., pathogen reduction technology), as well as their quality assessment (how to isolate platelets from the rest of the culture cells, debris, microvesicles, or what their molecular and functional profile is). Importantly, we highlight how the scientific community has overcome the old dogmas and how the new perspectives influence the future of platelet-based therapy for transfusion purposes.


Assuntos
Megacariócitos , Trombopoese , Plaquetas , Diferenciação Celular , Humanos , Transfusão de Plaquetas
11.
Transfus Apher Sci ; 59(5): 102934, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32948465

RESUMO

This communication provides a compilation on aspects of COVID-19 infection control measures, describes the potential role of therapeutic plasma exchange to reduce fatality rates, addresses precautions concerning dexamethasone pharmacotherapy and updates the current status on the availability of vaccines. As part of passive immunotherapy, it focuses on various blood derivatives. These include coronavirus neutralising antibodies extracted from different sources to be administered as a pure hyper concentrate intramuscularly or for upgrading and standardising the specific potency of high affinity antibodies. These processes are intended to compose standardised pooled bioproducts of corona convalescent plasma/cryosupernatant that are pathogen inactivated for additional safety by well-established UV technologies. For the best practice of optimising plasma exchange, hyper concentrate NAb should be added to the cryosupernatant, which contains some of the active principles of corona convalescent plasma. The cryosupernatant apart from the high molecular weight viscous part of cold insoluble proteins that are removed, is equivalent to CCP, but makes it safer for general application. Such a bioproduct is often used routinely for substitution therapy of thrombotic thrombocytopaenic purpura. Alternative resources of large-scale specific coronavirus antibodies warrant further exploration such as cadaveric donations. The early uses of therapeutic plasma exchange and low molecular weight heparin, for any clinical trial in development is warranted, in order to interdict the intense inflammatory/kinin driven cascade. Because coronavirus positive patients are highly prone to thrombosis, thromboprophylaxis is necessary, even some time after recovery guided by the laboratory data.


Assuntos
Corticosteroides/uso terapêutico , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/terapia , COVID-19/epidemiologia , Ensaios Clínicos como Assunto , Humanos , Imunização Passiva , SARS-CoV-2/fisiologia
12.
Transfus Apher Sci ; 59(5): 102940, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32950375

RESUMO

Stem cell therapy is a relatively novel field of investigation, 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 a patient's blood cells, now a widely established procedure for many oncologic and non-oncologic diseases. Innovative cell-based therapies are being developed to replace, regenerate or repair injured, absent, or diseased tissues and organs. However, cell therapy bioproducts are based on their inherent biological features such as proliferation, migratory, capability, plasticity, and capacity of self-renewal, posing serious challenges during such bioproduct development. The extraordinary promise of stem cells for future treatments of otherwise intractable diseases has raised great hope and expectations in patients, advocates, physicians, and researchers alike. However, despite thousands of scientific publications and research programs, increased efforts need to be put into the identification of the factors involved, biological mechanisms and materials that affect safety/ efficacy, and into the design of cost-effective methods for the harvesting, expansion, manipulation and purification of the cells.


Assuntos
Substitutos Sanguíneos/metabolismo , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células-Tronco/metabolismo , Medicina Transfusional/métodos , Humanos
13.
Transfus Apher Sci ; 59(5): 102942, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32943325

RESUMO

Extracellular vesicles (EVs) have been shown to be involved in various physiological and pathophysiological processes. With respect to Transfusion Medicine, the accumulation of EVs in blood products during hypothermic storage is an indicator of the storage lesion and reportedly correlates with adverse effects after transfusion, including but not limited to immunomodulation, activation of coagulation, endothelial activation, and others. To optimally reduce such an impact on blood product quality degradation and improve post-transfusion outcomes, better methods for detection, enumeration, characterisation by size and phenotype, and functional involvement of EVs in different pathophysiological and physiological processes are required. Currently, Imaging Flow Cytometry (IFC) technology provides the most comprehensive assessment of EV subsets in different body fluids. The unique ability of IFC to detect EVs of 20 nm size by registration of a single pixel of fluorescence signal makes this approach highly promising for comprehensive studies of EVs. In this review, we will focus on the recent breakthrough and advantages of using the ImageStreamX MKII IFC platform for the detection and characterisation of EVs and its future prospects for routine application of IFC in Transfusion Medicine.


Assuntos
Vesículas Extracelulares/metabolismo , Citometria de Fluxo/métodos , Medicina Transfusional/métodos , Humanos
14.
Transfus Apher Sci ; 59(5): 102933, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32919879

RESUMO

COVID-19 convalescent plasma (CCP) therapy involves the use of circulating antibodies administration from recovered COVID 19 patients as a practical strategy to provide immediate passive immunity in susceptible recipients in need. Global concern over the potential for "second" or "third" waves of infection to occur before effective vaccines or drug therapies are available has many looking at other biological sources for large-scale production of neutralizing SARS-CoV-2 antibodies. This report summarizes some of the novel strategies for developing alternative safe sources of therapeutic autologous antibodies from COVID -19 infected patients, and provides some original thoughts on how to rapidly implement a safe passive immunity in those COVID-19 patients who are most in need of intervention. COVID-19 antibodies can be isolated or delivered using a number of other techniques including: plasmapheresis, plasma cryoprecipitate reduced (cryosupernatant), antibody hyperconcentrates and advanced cell-based delivery systems. While these proposed technological options may, in some cases, be theoretical, the growing concern over the rapid spread of the SARS-CoV-2 virus has prompted many to pursue innovative and creative solutions to reduce the mortality and morbidity resulting from the current global pandemic. A comparative analysis of various strategies currently in use deserved exploring and this highlighted separately as the essential part of this concise theme.


Assuntos
COVID-19/terapia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , Sistemas de Liberação de Medicamentos , Humanos , Plasmaferese , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia
16.
Transfus Apher Sci ; 59(5): 102941, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32958397

RESUMO

A shortage of blood during the pandemic outbreak of COVID-19 is a typical example in which the maintenance of a safe and adequate blood supply becomes difficult and highly demanding. So far, human RBCs have been produced in vitro using diverse sources: hematopoietic stem cells (SCs), embryonic SCs and induced pluripotent SCs. The existing, even safest core of conventional cellular bioproducts destined for transfusion have some shortcoming in respects to: donor -dependency variability in terms of hematological /immunological and process/ storage period issues. SCs-derived transfusable RBC bioproducts, as one blood group type for all, were highly complex to work out. Moreover, the strategies for their successful production are often dependent upon the right selection of starting source materials and the composition and the stability of the right expansion media and the strict compliance to GMP regulatory processes. In this mini-review we highlight some model studies, which showed that the efficiency and the functionality of RBCs that could be produced by the various types of SCs, in relation to the in-vitro culture procedures are such that they may, potentially, be used at an industrial level. However, all cultured products do not have an unlimited life due to the critical metabolic pathways or the metabolites produced. New bioreactors are needed to remove these shortcomings and the development of a new mouse model is required. Modern clinical trials based on the employment of regenerative medicine approaches in combination with novel large-scale bioengineering tools, could overcome the current obstacles in artificial RBC substitution, possibly allowing an efficient RBC industrial production.


Assuntos
Transfusão de Sangue , Eritrócitos/citologia , Células-Tronco Hematopoéticas/citologia , Linhagem Celular , Ensaios Clínicos como Assunto , Humanos
18.
Transfus Apher Sci ; 59(4): 102861, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32636115

RESUMO

Culture of blood cells, mainly erythrocytes, at industrial levels complying with cGMP regulations, aim to make them available, at large scale, any time and everywhere, when needed for transfusion, or laboratory applications. Understanding how blood cells differentiate and develop in-vivo, and mechanisms of differentiation and growth factors, has opened newer strategies for in-vitro culture from multipotent stem cells or immortalized lines. This offers interesting perspectives for obtaining such cultured bioproduct cells for medical applications. In addition, many attempts for preparing platelets in-vitro from megakaryocyte culture have been reported. Nevertheless, the quantities of functional viable platelets obtained are still not sufficient to envisage transfusion applications. Other strategic approaches concern culture of organoids, which can synthesize functional blood proteins, but still significant scale-up of yield needs to be addressed. Finally, considerable advances have been made in culturing specific lymphocytes for personalized immunotherapy of some cancer patients with highly promising results in certain applications. This concise mini report focuses on the progress made in these directions, and attempts are made to describe some newer perspectives.


Assuntos
Técnicas de Cultura de Células/métodos , Eritrócitos/metabolismo , Organoides/metabolismo , Humanos
20.
Transfus Apher Sci ; 59(4): 102862, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32620410

RESUMO

Blood transfusion, using the safest conventional blood bioproducts, is an irreplaceable part of substitution therapy. It is considered the most essential supportive clinical intervention aimed to restore the health of patients in need. Nevertheless, numerous unresolved problems are still associated with current blood substitution therapy. To alleviate our dependency on blood donors, many investigators have been focusing on the quest for stem cell-derived blood cells in line with major developments in the field of regenerative medicine. The main objective is to provide a safe and highly standardized universal cultured red cell concentrate [CRBC] for all clinical applications, regardless of blood groups. Currently, we are close to overcoming some of the main obstacles in culturing cells. This concise report is a prelude to the immortalized cell lines that are ready for in vivo clinical trials. It is only through the sharing of experimental ideas and knowledge-based strategies that we will be able to achieve such an enormous task and better understand ''the one for all concept'' of CRBCs and their universal usage in all clinical settings.


Assuntos
Transfusão de Sangue/métodos , Transfusão de Eritrócitos/métodos , Eritrócitos/metabolismo , Humanos
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