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1.
Orv Hetil ; 161(37): 1545-1553, 2020 09.
Artigo em Húngaro | MEDLINE | ID: mdl-32894734

RESUMO

Human red blood cell concentrate and platelet suspension are unstable preparations, therefore, they are not part of the international pharmaceutical market for biological and economic reasons. Consequently, they cannot be replaced by external sources. Human allogeneic erythrocyte and platelet preparations should therefore be considered as part of the common national wealth. The amount of transfused red blood cell concentrate has been declining in countries with advanced health systems in recent years. The changes were initially driven by the spread of the concept and practice of liberal and restrictive transfusion triggers. A complex, thoughtful system of perioperative blood utilization, the Patient Blood Management has later emerged, and a paradigm shift in the delivery of life-threatening perioperative bleeding has developed. At the same time, clinical practitioners are facing a new challenge of reducing willingness to donate blood worldwide. The rationalization of the use of human red blood cell concentrate and platelet suspension is essential in Hungary. As a health care measure, the currently rigidly earmarked financial resources available for allogeneic preparations and stable factor concentrates for the treatment of life-threatening haemorrhages need to be changed to be interoperable. The perioperative blood use could additionally be reduced by the widespread dissemination of the Patient Blood Management requiring complex coordinated educational interdisciplinary and logistical work. Orv Hetil. 2020; 161(37): 1545-1553.


Assuntos
Transfusão de Sangue , Transfusão de Eritrócitos , Plaquetas , Hemorragia , Humanos , Hungria
2.
Nat Commun ; 11(1): 4034, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788576

RESUMO

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency with severe platelet abnormalities and complex immunodeficiency. Although clinical gene therapy approaches using lentiviral vectors have produced encouraging results, full immune and platelet reconstitution is not always achieved. Here we show that a CRISPR/Cas9-based genome editing strategy allows the precise correction of WAS mutations in up to 60% of human hematopoietic stem and progenitor cells (HSPCs), without impairing cell viability and differentiation potential. Delivery of the editing reagents to WAS HSPCs led to full rescue of WASp expression and correction of functional defects in myeloid and lymphoid cells. Primary and secondary transplantation of corrected WAS HSPCs into immunodeficient mice showed persistence of edited cells for up to 26 weeks and efficient targeting of long-term repopulating stem cells. Finally, no major genotoxicity was associated with the gene editing process, paving the way for an alternative, yet highly efficient and safe therapy.


Assuntos
Edição de Genes , Terapia Genética , Células-Tronco Hematopoéticas/metabolismo , Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/terapia , Animais , Plaquetas/metabolismo , Sistemas CRISPR-Cas/genética , Linhagem da Célula , Códon/genética , Feminino , Loci Gênicos , Células HEK293 , Transplante de Células-Tronco Hematopoéticas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Macrófagos/metabolismo , Masculino , Camundongos , Testes de Mutagenicidade , Células Mieloides/metabolismo , Linfócitos T/metabolismo , Síndrome de Wiskott-Aldrich/patologia , Proteína da Síndrome de Wiskott-Aldrich/genética
3.
BMC Infect Dis ; 20(1): 580, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762658

RESUMO

BACKGROUND: Dengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage. METHODS: In this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC). RESULTS: A total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases. CONCLUSION: Thrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.


Assuntos
Plaquetas/metabolismo , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/epidemiologia , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Difosfato de Adenosina/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Colágeno/metabolismo , Dengue/virologia , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/diagnóstico , Humanos , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Agregação Plaquetária , Contagem de Plaquetas , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
4.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(4): 750-754, 2020 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-32773814

RESUMO

OBJECTIVE: To compare the blood parameters related to erythrocyte and platelet between baseline and 3 months after initial periodontal therapy in patients with both type 2 diabetes mellitus and chronic periodontitis (DM-P). METHODS: According to the International Symposium on Classification of Periodontal Diseases and Conditions in 1999 and the diagnostic criteria of type 2 diabetes mellitus proposed by the World Health Organization in 1999, 35 patients with DM-P were recruited. All the participants received initial periodontal therapy, including oral hygiene instruction, scaling, and root planning provided by one senior periodontist. Original diet, exercise, and medication for blood glucose control were unchanged for all the participants. At baseline and 3 months after initial periodontal therapy, the clinical periodontal parameters, including probing depth (PD), bleeding index (BI) and clinical attachment loss (CAL); erythrocyte-related indexes, including red blood cell (RBC) count, hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), RBC volume distribution width (RDW); platelet-related indexes, including platelet (PLT) count, mean platelet volume (MPV), platelet distribution width (PDW), plateletocrit (PCT) were measured and compared. RESULTS: Compared with baseline, the periodontal parameters, including PD [(3.370±0.601) mm vs. (2.729±0.431) mm], BI [2.160 (1.550~3.410) vs. 1.420 (1.000~2.970)] and CAL [(3.307±1.577) mm vs. (2.990±1.587) mm], were significantly reduced (P < 0.001) three months after the initial periodontal therapy; the erythrocyte-related indexes, including RBC count [(4.727±0.392)×1012/L vs. (4.825±0.394)×1012/L, P=0.010], HGB [(145.886±11.792) g/L vs. (149.200±12.979) g/L, P=0.007] and HCT [43.40% (37.50%~48.50%) vs. 43.80% (38.50%~53.20%), P=0.003], were significantly increased three months after the initial periodontal therapy; PLT count [(216.714±61.900)×109/L vs. (205.886±62.051)×109/L, P=0.016] was significantly reduced 3 months after the initial periodontal therapy. CONCLUSIONS: The initial periodontal therapy can significantly improve blood parameters related to RBC and PLT, which might decrease the risk of vascular complications in DM-P patients.


Assuntos
Periodontite Crônica , Diabetes Mellitus Tipo 2 , Plaquetas , Eritrócitos , Hematócrito , Humanos
5.
Int J Mol Sci ; 21(15)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731360

RESUMO

Along with cancer, cardiovascular and cerebrovascular diseases remain by far the most common causes of death. Heart attacks and strokes are diseases in which platelets play a role, through activation on ruptured plaques and subsequent thrombus formation. Most platelet agonists activate platelets via G protein-coupled receptors (GPCRs), which make these receptors ideal targets for many antiplatelet drugs. However, little is known about the mechanisms that provide feedback regulation on GPCRs to limit platelet activation. Emerging evidence from our group and others strongly suggests that GPCR kinases (GRKs) are critical negative regulators during platelet activation and thrombus formation. In this review, we will summarize recent findings on the role of GRKs in platelet biology and how one specific GRK, GRK6, regulates the hemostatic response to vascular injury. Furthermore, we will discuss the potential role of GRKs in thrombotic disorders, such as thrombotic events in COVID-19 patients. Studies on the function of GRKs during platelet activation and thrombus formation have just recently begun, and a better understanding of the role of GRKs in hemostasis and thrombosis will provide a fruitful avenue for understanding the hemostatic response to injury. It may also lead to new therapeutic options for the treatment of thrombotic and cardiovascular disorders.


Assuntos
Quinases de Receptores Acoplados a Proteína G/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Trombose/metabolismo , Plaquetas/metabolismo , Humanos , Ativação Plaquetária
6.
BMC Infect Dis ; 20(1): 609, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811463

RESUMO

BACKGROUND: Ratios of different immune cell populations (i.e., monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios) have been studied as a means of predicting future tuberculosis (TB) disease risk or to assist in the diagnosis of incident TB disease. No studies to-date, however, have evaluated the potential of these ratios to predict or assist in the diagnosis of incident TB infection - the first step in the natural history of TB disease. METHODS: In this prospective study, we evaluated the complete blood count (CBC)-derived metrics of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) as predictors of future TB infection risk or aids in the diagnosis of TB infection among 145 Tanzanian adolescents enrolled in the DAR-901 vaccine trial, using paired CBCs and interferon-gamma release assays (IGRAs) obtained at 0, 60 and 720 days after study enrollment. RESULTS: At baseline, there were no significant differences between study participants who remained persistently IGRA negative throughout the study period and those who subsequently converted to IGRA positive with respect to MLR (0.18 vs 0.17, p = 0.10), NLR (0.88 vs 1.02, p = 0.08), or PLR (115 vs 120, p = 0.28). Similarly, no significant differences were noted with respect to MLR, NLR, and PLR between IGRA converters and time-matched negative controls at the time of IGRA conversion. With respect to other blood cell measures, however, there were modest but significant differences between IGRA negatives and IGRA converters with respect to red blood cell count (4.8 vs 4.6 ×  106 cells/mcL, p = 0.008), hemoglobin (12.6 vs 12.3 g/dL, p = 0.01), and hematocrit (38.8 vs 37.8%, p = 0.005). CONCLUSIONS: In contrast to prior studies that have suggested that the ratios of different immune cell populations are associated with development of TB disease, our present findings do not demonstrate an association between these ratios and the development of TB infection. However, decreased red blood cell measures were associated with the subsequent development of TB infection, suggesting either that dysregulation of iron metabolism may play a role in TB pathogenesis or that following TB infection, iron dysregulation may precede IGRA positivity. TRIAL REGISTRATION: Clinicaltrials.gov NCT02712424 . Date of registration: March 14, 2016.


Assuntos
Contagem de Células Sanguíneas/métodos , Plaquetas , Linfócitos , Monócitos , Neutrófilos , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Feminino , Humanos , Incidência , Testes de Liberação de Interferon-gama , Masculino , Estudos Prospectivos , Tanzânia/epidemiologia , Tuberculose/sangue , Tuberculose/microbiologia
7.
Adv Biol Regul ; 77: 100735, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32773098

RESUMO

The novel Corona virus infection (Covid-19) first identified in China in December 2019 has rapidly progressed in pandemic leading to significant mortality and unprecedented challenge for healthcare systems. Although the clinical spectrum of Covid-19 is variable, acute respiratory failure and systemic coagulopathy are common in severe Covid-19 patients. Lung is an important target of the SARS-CoV-2 virus causing eventually acute respiratory distress syndrome associated to a thromboinflammatory state. The cytokinic storm, thromboinflammation and pulmonary tropism are the bedrock of tissue lesions responsible for acute respiratory failure and for prolonged infection that may lead to multiple organ failure and death. The thrombogenicity of this infectious disease is illustrated by the high frequency of thromboembolic events observed even in Covid-19 patients treated with anticoagulation. Increased D-Dimers, a biomarker reflecting activation of hemostasis and fibrinolysis, and low platelet count (thrombocytopenia) are associated with higher mortality in Covid-19 patients. In this review, we will summarize our current knowledge on the thromboembolic manifestations, the disturbed hemostatic parameters, and the thromboinflammatory conditions associated to Covid-19 and we will discuss the modalities of anticoagulant treatment or other potential antithrombotic options.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/complicações , Coagulação Intravascular Disseminada/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Insuficiência Respiratória/complicações , Doença Aguda , Biomarcadores/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Plaquetas/virologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Interações Hospedeiro-Patógeno , Humanos , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/virologia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/virologia , Análise de Sobrevida
8.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(8): 1025-1030, 2020 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-32794673

RESUMO

Objective: To identify a more popularized preparation protocol of leukocytes-rich platelet-rich plasma (L-PRP) for higher tolerance rate. Methods: The peripheral blood samples of 76 volunteers (45.0 mL/case) were mixed with 5 mL sodium citrate injection for blood transfusion, and L-PRP was prepared by twice centrifugations. All blood samples were divided into three groups according to the parameters of twice centrifugation: experimental group A (12 cases, 400× g, 10 minutes for the first time and 1 100× g, 10 minutes for the second time), experimental group B (27 cases, 800× g, 10 minutes for the first time and 1 100× g, 10 minutes for the second time), and control group (37 cases, 1 360× g, 10 minutes for the first time and 1 360× g, 10 minutes for the second time). The platelet recovery rate and platelet and leukocyte enrichment coefficient of L-PRP in each group were calculated and compared. Results: After removal of abnormal blood samples (platelet recovery rate was more than 100% or white thrombus), the remaining 55 cases were included in the statistical analysis, including 10 cases in experimental group A, 21 cases in experimental group B, and 24 cases in control group. The platelet enrichment coefficient and platelet recovery rate of experimental group B were significantly higher than those of experimental group A and control group ( P<0.05); there was no significant difference between experimental group A and control group ( P>0.05). There was no significant difference in leukocyte enrichment coefficient between experimental groups A, B, and control group ( P>0.05). Conclusion: The preparation quality of PRP is affected by various factors, including centrifugal force, centrifugal time, temperature, and operation process, etc. Twice centrifugation (800× g, 10 minutes for the first time and 1 100× g, 10 minutes for the second time) is an ideal and feasible centrifugation scheme, which can obtain satisfactory platelet recovery rate and enrichment coefficient with thicker buffy coat, which can reduce the fine operation requirements for operators, improve the fault tolerance rate and generalization.


Assuntos
Plasma Rico em Plaquetas , Plaquetas , Centrifugação , Humanos , Leucócitos
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1240-1244, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798405

RESUMO

OBJECTIVE: To explore the clinical significance of platelet closure time (PCT) in patients with multiple myeloma (MM). METHODS: Peripheral blood samples of 50 newly diagnosed MM patients treated in our hospital from July 2018 to November 2019 and 34 healthy persons underuent physical at the same time were collected. PCT induced by collagen/epinephrine (CEPI) and collagen/adenosinediphosphate (CADP) in peripheral blood were detected by PFA-200,and the clinical data included age, sex, leukocyte count, hemoglobin level, platelet count and level of serum creatinine, cystatin c, blood calcium, ß2-microglobulin (ß2-MG), bone marrow plasma cells, light chain protein, as well as the MM types, ISS stage of patients were collected. RESULTS: The level of PCT in MM patients was significantly higher than that in healthy persons; the level of PCT were significantly increased with the increasing of ISS stage in newly diagnosed MM patients; After chemotherapy with bortezomib/dexamethasone (BD), the level of PCT in 15 patients who were responded to the treatment was significantly lower than those before treatment. CONCLUSION: The platelet closure time is abnormal in MM patients, moreover, relates to the progress of the disease. It has an important clinical significance for the evaluation of diagnostic stage and therapeutic efficacy evaluation of MM patients.


Assuntos
Mieloma Múltiplo , Plaquetas , Medula Óssea , Bortezomib , Humanos , Contagem de Plaquetas
10.
Medicine (Baltimore) ; 99(27): e20888, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629679

RESUMO

This study aims to identify prognostic value of neutrophil-to-lymphocyte ratio (NLR) in early miscarriages. A total of 260 pregnant women with vaginal spotting were recruited from the Department of Obstetrics and Gynecology of the Kyung Hee Medical Center from January 1, 2011, and December 31, 2018. Venous samples were obtained from the women for measurements of platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and NLR. All the patients were in < 14 gestational weeks of their pregnancy. Eighty-four patients were excluded because of incomplete data, loss of follow-up, and serious medical diseases. We enrolled 176 women for analysis and divided them into two groups. Group 1 included 104 women with threatened abortion; and group 2, 72 women with missed abortion. A significant difference in NLR was found between the groups (p = 0.001; P < .01). The multivariate analysis also revealed that NLR was the only prognostic factor of early miscarriage (odd ratio [OR], 0.732; 95% confidence interval [CI], 0.612-0.881, P = .001). The area under the Receiver-operating characteristic of NLR for distinguishing between the missed and threatened abortion groups was 0.792, and the best cutoff value was 5.72 (P < .05).


Assuntos
Aborto Espontâneo/sangue , Linfócitos/metabolismo , Neutrófilos/metabolismo , Adulto , Plaquetas/metabolismo , Feminino , Humanos , Monócitos/metabolismo , Gravidez , Prognóstico , Estudos Retrospectivos
11.
Anticancer Res ; 40(7): 3947-3952, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620636

RESUMO

AIM: This study aimed to evaluate plateletcrit (PCT) and platelet distribution width-to-PCT ratio (PDW/PCT) as potential prognostic biomarkers in patients with breast cancer. PATIENTS AND METHODS: Information of 337 patients was retrospectively reviewed. The Cox regression proportional hazards model was used to evaluate the prognostic value of PCT and PDW/PCT compared to the platelet distribution width-to-platelet count ratio (PDW/P) and red cell distribution width-to-platelet count ratio (RDW/P). RESULTS: Large tumor size (p<0.01), lymph node involvement, and increased PDW/P, RDW/P, and PDW/PCT (p<0.05) were significantly associated with inferior disease-free survival (DFS) according to the univariate analysis. The multivariate analysis showed that large tumor size (p<0.01) and increased PDW/PCT (p<0.05) were significant prognostic factors for poor DFS. CONCLUSION: To our knowledge, this is the first report to show that PDW/PCT is a significant prognostic factor for patients with breast cancer. Therefore, it might be an attractive biomarker providing additional prognostic information for these patients.


Assuntos
Plaquetas/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
13.
PLoS One ; 15(7): e0235392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726315

RESUMO

Platelets upregulate the generation of thrombin and reinforce the fibrin clot which increases the incidence risk of venous thromboembolism (VTE). However, the role of platelets in the pathogenesis of venous cardiovascular diseases remains hard to quantify. An experimentally validated model of thrombin generation dynamics is formulated. The model predicts that a high platelet count increases the peak value of generated thrombin as well as the endogenous thrombin potential (ETP) as reported in experimental data. To investigate the effects of platelets density, shear rate, and wound size on the initiation of blood coagulation, we calibrate a previously developed model of venous thrombus formation and implement it in 3D using a novel cell-centered finite-volume solver. We conduct numerical simulations to reproduce in vitro experiments of blood coagulation in microfluidic capillaries. Then, we derive a reduced one-equation model of thrombin distribution from the previous model under simplifying hypotheses and we use it to determine the conditions of clotting initiation on the platelet count, the shear rate, and the plasma composition. The initiation of clotting also exhibits a threshold response to the size of the wounded region in good agreement with the reported experimental findings.


Assuntos
Coagulação Sanguínea/fisiologia , Plaquetas/fisiologia , Modelos Teóricos , Contagem de Plaquetas/métodos , Testes de Coagulação Sanguínea , Plaquetas/metabolismo , Fibrina/metabolismo , Humanos , Agregação Plaquetária/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Resistência ao Cisalhamento/fisiologia , Trombina/metabolismo , Tromboplastina/metabolismo , Trombose/metabolismo , Trombose/fisiopatologia , Veias/metabolismo , Veias/fisiologia
14.
Clin Rheumatol ; 39(9): 2529-2543, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32654082

RESUMO

The pathogenesis of Coronavirus disease 2019 (COVID-19) is gradually being comprehended. A high number of thrombotic episodes are reported, along with the mortality benefits of heparin. COVID-19 can be viewed as a prothrombotic disease. We overviewed the available evidence to explore this possibility. We identified various histopathology reports and clinical case series reporting thromboses in COVID-19. Also, multiple coagulation markers support this. COVID-19 can be regarded as a risk factor for thrombosis. Applying the principles of Virchow's triad, we described abnormalities in the vascular endothelium, altered blood flow, and platelet function abnormalities that lead to venous and arterial thromboses in COVID-19. Endothelial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS) with the release of procoagulant plasminogen activator inhibitor (PAI-1), and hyperimmune response with activated platelets seem to be significant contributors to thrombogenesis in COVID-19. Stratifying risk of COVID-19 thromboses should be based on age, presence of comorbidities, D-dimer, CT scoring, and various blood cell ratios. Isolated heparin therapy may not be sufficient to combat thrombosis in this disease. There is an urgent need to explore newer avenues like activated protein C, PAI-1 antagonists, and tissue plasminogen activators (tPA). These should be augmented with therapies targeting RAAS, antiplatelet drugs, repurposed antiinflammatory, and antirheumatic drugs. Key Points • Venous and arterial thromboses in COVID-19 can be viewed through the prism of Virchow's triad. • Endothelial dysfunction, platelet activation, hyperviscosity, and blood flow abnormalities due to hypoxia, immune reactions, and hypercoagulability lead to thrombogenesis in COVID-19. • There is an urgent need to stratify COVID-19 patients at risk for thrombosis using age, comorbidities, D-dimer, and CT scoring. • Patients with COVID-19 at high risk for thrombosis should be put on high dose heparin therapy.


Assuntos
Infecções por Coronavirus/sangue , Endotélio Vascular/metabolismo , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/sangue , Trombofilia/sangue , Trombose/sangue , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticoagulantes/uso terapêutico , Betacoronavirus/metabolismo , Plaquetas , Viscosidade Sanguínea , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Endotélio Vascular/fisiopatologia , Produtos de Degradação da Fibrina e do Fibrinogênio , Fibrinogênio/metabolismo , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Humanos , Pandemias , Inibidor 1 de Ativador de Plasminogênio/sangue , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/uso terapêutico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Índice de Gravidade de Doença , Trombofilia/etiologia , Trombofilia/metabolismo , Trombose/tratamento farmacológico , Trombose/etiologia , Ativador de Plasminogênio Tecidual/sangue , Ativador de Plasminogênio Tecidual/uso terapêutico
15.
Nat Commun ; 11(1): 3569, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678083

RESUMO

The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative individuals show markedly increased proliferation and higher reticulocyte yields, suggesting an important regulatory role for EMP3 in erythropoiesis and control of cell production. Our data establish MAM as a new blood group system and demonstrate an interaction of EMP3 with the cell surface signalling molecule CD44.


Assuntos
Antígenos de Grupos Sanguíneos/genética , Proliferação de Células , Células Eritroides/citologia , Glicoproteínas de Membrana/genética , Antígenos de Grupos Sanguíneos/química , Antígenos de Grupos Sanguíneos/metabolismo , Plaquetas/metabolismo , Células Cultivadas , Membrana Eritrocítica/metabolismo , Células Eritroides/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/metabolismo , Modelos Moleculares , Mutação , Fenótipo , Ligação Proteica , Sequenciamento Completo do Exoma
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(3): 388-392, 2020 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-32616137

RESUMO

Platelets are non-nuclear blood cells that are widely involved in physiological and pathological processes.Their main role is to participate in hemostasis and thrombosis.Toll-like receptors(TLRs)are innate immune receptors.Platelets express multiple TLRs and can promote thrombosis by recognizing ligand-induced platelet activation and aggregation.This article reviews the relationship between platelets/TLR and thrombosis and the roles of TLRs in the development of thrombotic diseases.


Assuntos
Plaquetas , Trombose , Hemostasia , Humanos , Ativação Plaquetária , Receptores Toll-Like
17.
Rinsho Ketsueki ; 61(6): 628-633, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32624536

RESUMO

Since induced pluripotent stem (iPS) cell-derived blood products can be produced from any individual, they are expected to complement current transfusion products. However, a main problem is how to produce 10 U platelet preparations. Therefore, we established an immortalized megakaryocyte cell line (imMKCL) from iPS cells. We also found that turbulent flow was an essential physical factor for platelet generation in vivo. This knowledge enabled us to obtain 100 billion functional platelets from imMKCL using an 8 L bioreactor. We propose that the enhanced platelet production in the bioreactor occurs due to the turbulent flow that promoted the release of stress-induced cytokines.


Assuntos
Plaquetas , Reatores Biológicos , Células-Tronco Pluripotentes Induzidas , Megacariócitos , Trombopoese
18.
Blood Adv ; 4(13): 2967-2978, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32609845

RESUMO

Thrombocytopenia is a common complication of influenza virus infection, and its severity predicts the clinical outcome of critically ill patients. The underlying cause(s) remain incompletely understood. In this study, in patients with an influenza A/H1N1 virus infection, viral load and platelet count correlated inversely during the acute infection phase. We confirmed this finding in a ferret model of influenza virus infection. In these animals, platelet count decreased with the degree of virus pathogenicity varying from 0% in animals infected with the influenza A/H3N2 virus, to 22% in those with the pandemic influenza A/H1N1 virus, up to 62% in animals with a highly pathogenic A/H5N1 virus infection. This thrombocytopenia is associated with virus-containing platelets that circulate in the blood. Uptake of influenza virus particles by platelets requires binding to sialoglycans and results in the removal of sialic acids by the virus neuraminidase, a trigger for hepatic clearance of platelets. We propose the clearance of influenza virus by platelets as a paradigm. These insights clarify the pathophysiology of influenza virus infection and show how severe respiratory infections, including COVID-19, may propagate thrombocytopenia and/or thromboembolic complications.


Assuntos
Plaquetas/virologia , Vírus da Influenza A/patogenicidade , Influenza Humana/complicações , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/metabolismo , Trombocitopenia/etiologia , Animais , Plaquetas/metabolismo , Plaquetas/patologia , Modelos Animais de Doenças , Furões , Interações Hospedeiro-Patógeno , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H1N1/fisiologia , Vírus da Influenza A Subtipo H3N2/patogenicidade , Vírus da Influenza A Subtipo H3N2/fisiologia , Virus da Influenza A Subtipo H5N1/patogenicidade , Virus da Influenza A Subtipo H5N1/fisiologia , Vírus da Influenza A/fisiologia , Influenza Humana/metabolismo , Influenza Humana/patologia , Influenza Humana/virologia , Infecções por Orthomyxoviridae/complicações , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Trombocitopenia/metabolismo , Trombocitopenia/patologia , Trombocitopenia/virologia , Internalização do Vírus
19.
Int J Mol Sci ; 21(14)2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32708334

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.


Assuntos
Plaquetas/metabolismo , Infecções por Coronavirus/patologia , Células Endoteliais/metabolismo , Eritrócitos/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Selectina-P/metabolismo , Pneumonia Viral/patologia , Fator de von Willebrand/metabolismo , Betacoronavirus , Síndrome da Liberação de Citocina/patologia , Humanos , Pandemias , Sistemas Automatizados de Assistência Junto ao Leito , Medicina de Precisão/métodos , Trombocitopenia/patologia , Trombose/patologia
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