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1.
Clin Appl Thromb Hemost ; 27: 10760296211042940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34693754

RESUMO

The world is in a hard battle against COVID-19. Endothelial cells are among the most critical targets of SARS-CoV-2. Dysfunction of endothelium leads to vascular injury following by coagulopathies and thrombotic conditions in the vital organs increasing the risk of life-threatening events. Growing evidences revealed that endothelial dysfunction and consequent thrombotic conditions are associated with the severity of outcomes. It is not yet fully clear that these devastating sequels originate directly from the virus or a side effect of virus-induced cytokine storm. Due to endothelial dysfunction, plasma levels of some biomarkers are changed and relevant clinical manifestations appear as well. Stabilization of endothelial integrity and supporting its function are among the promising therapeutic strategies. Other than respiratory, COVID-19 could be called a systemic vascular disease and this aspect should be scrutinized in more detail in order to reduce related mortality. In the present investigation, the effects of COVID-19 on endothelial function and thrombosis formation are discussed. In this regard, critical players, laboratory findings, clinical manifestation, and suggestive therapies are presented.


Assuntos
Coagulação Sanguínea , COVID-19/virologia , Células Endoteliais/virologia , Endotélio Vascular/virologia , SARS-CoV-2/patogenicidade , Trombose/virologia , Animais , COVID-19/sangue , COVID-19/patologia , COVID-19/fisiopatologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Interações Hospedeiro-Patógeno , Humanos , Transdução de Sinais , Trombose/sangue , Trombose/patologia , Trombose/fisiopatologia
2.
Hamostaseologie ; 41(5): 379-385, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34695854

RESUMO

In 2019 first reports about a new human coronavirus emerged, which causes common cold symptoms as well as acute respiratory distress syndrome. The virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe thrombotic events including deep vein thrombosis, pulmonary embolism, and microthrombi emerged as additional symptoms. Heart failure, myocardial infarction, myocarditis, and stroke have also been observed. As main mediator of thrombus formation, platelets became one of the key aspects in SARS-CoV-2 research. Platelets may also directly interact with SARS-CoV-2 and have been shown to carry the SARS-CoV-2 virus. Platelets can also facilitate the virus uptake by secretion of the subtilisin-like proprotein convertase furin. Cleavage of the SARS-CoV-2 spike protein by furin enhances binding capabilities and virus entry into various cell types. In COVID-19 patients, platelet count differs between mild and serious infections. Patients with mild symptoms have a slightly increased platelet count, whereas thrombocytopenia is a hallmark of severe COVID-19 infections. Low platelet count can be attributed to platelet apoptosis and the incorporation of platelets into microthrombi (peripheral consumption) and severe thrombotic events. The observed excessive formation of thrombi is due to hyperactivation of platelets caused by the infection. Various factors have been suggested in the activation of platelets in COVID-19, such as hypoxia, vessel damage, inflammatory factors, NETosis, SARS-CoV-2 interaction, autoimmune reactions, and autocrine activation. COVID-19 does alter chemokine and cytokine plasma concentrations. Platelet chemokine profiles are altered in COVID-19 and contribute to the described chemokine storms observed in severely ill COVID-19 patients.


Assuntos
Plaquetas/fisiologia , Plaquetas/virologia , COVID-19/sangue , Plaquetas/imunologia , COVID-19/complicações , COVID-19/imunologia , Quimiocinas/sangue , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Interações entre Hospedeiro e Microrganismos/imunologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Modelos Biológicos , Pandemias , Ativação Plaquetária/imunologia , Ativação Plaquetária/fisiologia , SARS-CoV-2/patogenicidade , Trombose/sangue , Trombose/etiologia
4.
Int J Mol Sci ; 22(18)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34576303

RESUMO

Thrombosis is a major comorbidity of obesity and type-2 diabetes mellitus (T2DM). Despite the development of numerous effective treatments and preventative strategies to address thrombotic disease in such individuals, the incidence of thrombotic complications remains high. This suggests that not all the pathophysiological mechanisms underlying these events have been identified or targeted. Non-esterified fatty acids (NEFAs) are increasingly regarded as a nexus between obesity, insulin resistance, and vascular disease. Notably, plasma NEFA levels are consistently elevated in obesity and T2DM and may impact hemostasis in several ways. A potentially unrecognized route of NEFA-mediated thrombotic activity is their ability to disturb Zn2+ speciation in the plasma. Zn2+ is a potent regulator of coagulation and its availability in the plasma is monitored carefully through buffering by human serum albumin (HSA). The binding of long-chain NEFAs such as palmitate and stearate, however, trigger a conformational change in HSA that reduces its ability to bind Zn2+, thus increasing the ion's availability to bind and activate coagulation proteins. NEFA-mediated perturbation of HSA-Zn2+ binding is thus predicted to contribute to the prothrombotic milieu in obesity and T2DM, representing a novel targetable disease mechanism in these disorders.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/sangue , Obesidade/metabolismo , Trombose/metabolismo , Zinco/sangue , Animais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Ácidos Graxos não Esterificados/metabolismo , Humanos , Obesidade/sangue , Obesidade/epidemiologia , Trombose/sangue , Trombose/epidemiologia , Zinco/metabolismo
5.
Cells ; 10(9)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34571872

RESUMO

There is increasing evidence for a link between inflammation and thrombosis. Following tissue injury, vascular endothelium becomes activated, losing its antithrombotic properties whereas inflammatory mediators build up a prothrombotic environment. Platelets are the first elements to be activated following endothelial damage; they participate in physiological haemostasis, but also in inflammatory and thrombotic events occurring in an injured tissue. While physiological haemostasis develops rapidly to prevent excessive blood loss in the endothelium activated by inflammation, hypoxia or by altered blood flow, thrombosis develops slowly. Activated platelets release the content of their granules, including ATP and ADP released from their dense granules. Ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39 dephosphorylates ATP to ADP and to AMP, which in turn, is hydrolysed to adenosine by ecto-5'-nucleotidase (CD73). NTPDase1/CD39 has emerged has an important molecule in the vasculature and on platelet surfaces; it limits thrombotic events and contributes to maintain the antithrombotic properties of endothelium. The aim of the present review is to provide an overview of platelets as cellular elements interfacing haemostasis and inflammation, with a particular focus on the emerging role of NTPDase1/CD39 in controlling both processes.


Assuntos
Antígenos CD/metabolismo , Apirase/metabolismo , Inflamação/complicações , Trombose/complicações , Animais , Humanos , Inflamação/sangue , Nucleotídeos/metabolismo , Ativação Plaquetária , Transdução de Sinais , Trombose/sangue
6.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34576172

RESUMO

Global data correlate severe vitamin D deficiency with COVID-19-associated coagulopathy, further suggesting the presence of a hypercoagulable state in severe COVID-19 patients, which could promote thrombosis in the lungs and in other organs. The feedback loop between COVID-19-associated coagulopathy and vitamin D also involves platelets (PLTs), since vitamin D deficiency stimulates PLT activation and aggregation and increases fibrinolysis and thrombosis. Vitamin D and PLTs share and play specific roles not only in coagulation and thrombosis but also during inflammation, endothelial dysfunction, and immune response. Additionally, another 'fil rouge' between vitamin D and PLTs is represented by their role in mineral metabolism and bone health, since vitamin D deficiency, low PLT count, and altered PLT-related parameters are linked to abnormal bone remodeling in certain pathological conditions, such as osteoporosis (OP). Hence, it is possible to speculate that severe COVID-19 patients are characterized by the presence of several predisposing factors to bone fragility and OP that may be monitored to avoid potential complications. Here, we hypothesize different pervasive actions of vitamin D and PLT association in COVID-19, also allowing for potential preliminary information on bone health status during COVID-19 infection.


Assuntos
Plaquetas/imunologia , COVID-19/complicações , Osteoporose/imunologia , Trombose/imunologia , Deficiência de Vitamina D/imunologia , Vitamina D/metabolismo , Plaquetas/metabolismo , Remodelação Óssea/imunologia , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Retroalimentação Fisiológica , Humanos , Osteoporose/sangue , Ativação Plaquetária/imunologia , Contagem de Plaquetas , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Trombose/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações
7.
Front Immunol ; 12: 716361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34491250

RESUMO

Background: COVID-19 pathology is associated with exuberant inflammation, vascular damage, and activation of coagulation. In addition, complement activation has been described and is linked to disease pathology. However, few studies have been conducted in cancer patients. Objective: This study examined complement activation in response to COVID-19 in the setting of cancer associated thromboinflammation. Methods: Markers of complement activation (C3a, C5a, sC5b-9) and complement inhibitors (Factor H, C1-Inhibitor) were evaluated in plasma of cancer patients with (n=43) and without (n=43) COVID-19 and stratified based on elevated plasma D-dimer levels (>1.0 µg/ml FEU). Markers of vascular endothelial cell dysfunction and platelet activation (ICAM-1, thrombomodulin, P-selectin) as well as systemic inflammation (pentraxin-3, serum amyloid A, soluble urokinase plasminogen activator receptor) were analyzed to further evaluate the inflammatory response. Results: Increases in circulating markers of endothelial cell dysfunction, platelet activation, and systemic inflammation were noted in cancer patients with COVID-19. In contrast, complement activation increased in cancer patients with COVID-19 and elevated D-dimers. This was accompanied by decreased C1-Inhibitor levels in patients with D-dimers > 5 ug/ml FEU. Conclusion: Complement activation in cancer patients with COVID-19 is significantly increased in the setting of thromboinflammation. These findings support a link between coagulation and complement cascades in the setting of inflammation.


Assuntos
COVID-19/imunologia , Ativação do Complemento/imunologia , Inflamação/imunologia , Neoplasias/imunologia , SARS-CoV-2/imunologia , Trombose/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/sangue , COVID-19/virologia , Inativadores do Complemento/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Ativação Plaquetária/imunologia , Estudos Retrospectivos , SARS-CoV-2/fisiologia , Trombose/sangue , Adulto Jovem
8.
Clin Appl Thromb Hemost ; 27: 10760296211040110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34541935

RESUMO

Since the outbreak of Covid-19 in December, 2019, scientists worldwide have been committed to developing COVID-19 vaccines. Only when most people have immunity to SARS-CoV-2, COVID-19 can reduce even wholly overcome. So far, nine kinds of COVID-19 vaccines have passed the phase III clinical trials and have approved for use. At the same time, adverse reactions after COVID-19 vaccination have also reported. This paper focuses on the adverse effects of thrombosis and thrombocytopenia caused by the COVID-19 vaccine, especially the adenovirus-vector vaccine from AstraZeneca and Pfizer, and discusses its mechanism and possible countermeasures.


Assuntos
Adenoviridae/genética , Vacinas contra COVID-19/efeitos adversos , Vetores Genéticos , Trombocitopenia/induzido quimicamente , Trombose/induzido quimicamente , Vacinação/efeitos adversos , Anticorpos/sangue , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/imunologia , Humanos , Fator Plaquetário 4/imunologia , Medição de Risco , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/imunologia , Trombose/sangue , Trombose/imunologia
9.
J Thromb Thrombolysis ; 52(3): 708-714, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34519015

RESUMO

Coronavirus disease 2019 (Covid-19) is associated with a high incidence of venous and arterial thromboembolic events. Currently, there are no clinical or laboratory markers that predict thrombotic risk. Circulating immature platelets are hyper-reactive platelets, which are associated with arterial thrombotic events. The aim of this study was to assess whether the proportion of circulating immature platelets is associated with disease severity in Covid-19 patients. Patients admitted with Covid-19 disease were prospectively assessed. Immature platelet count (IPC) and immature platelet fraction (IPF) were measured at admission and at additional time points during the hospital course using the Sysmex XN-3000 auto-analyzer. A total of 136 consecutive patients with Covid-19 were recruited [mean age 60 ± 19 years, 49% woman, 56 (41%) had mild-moderate disease and 80 (59%) had severe disease at presentation]. The median IPF% was higher in patients with severe compared to mild-moderate disease [5.8 (3.9-8.7) vs. 4.2 (2.73-6.45), respectively, p = 0.01]. The maximal IPC value was also higher in patients with severe disease [15 (10.03-21.56), vs 10.9 (IQR 6.79-15.62), respectively, p = 0.001]. Increased IPC was associated with increased length of hospital stay. Patients with severe Covid-19 have higher levels of IPF than patients with mild-moderate disease. IPF may serve as a prognostic marker for disease severity in Covid-19 patients.


Assuntos
Plaquetas/virologia , COVID-19/virologia , SARS-CoV-2/patogenicidade , Trombose/virologia , Adulto , Idoso , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/terapia , Feminino , Mortalidade Hospitalar , Interações Hospedeiro-Patógeno , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Trombose/sangue , Trombose/diagnóstico , Fatores de Tempo
10.
Front Immunol ; 12: 688861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335591

RESUMO

Psoriasis (PsO) is a common T cell-mediated inflammatory disorder of the skin with an estimated prevalence of 2%. The condition manifests most commonly as erythematous plaques covered with scales. The aetiology of PsO is multifactorial and disease initiation involves interactions between environmental factors, susceptibility genes, and innate and adaptive immune responses. The underlying pathology is mainly driven by interleukin-17. In addition, various inflammatory mediators from specific T helper (TH) cell subsets, namely TH1, TH17, and TH22, are overexpressed in cutaneous lesions and may also be detected in the peripheral blood of psoriatic patients. Moreover, these individuals are also at greater risk, compared to the general population, of developing multiple comorbid conditions. Cardiovascular disease (CVD) has been recognised as a prominent comorbidity of PsO. A potential mechanism contributing to this association may be the presence of a hypercoagulable state in these individuals. Inflammation and coagulation are closely related. The presence of chronic, low-grade systemic inflammation may promote thrombosis - one of the major determinants of CVD. A pro-inflammatory milieu may induce the expression of tissue factor, augment platelet activity, and perturb the vascular endothelium. Altogether, these changes will result in a prothrombotic state. In this review, we describe the aetiology of PsO, as well as the pathophysiology of the condition. We also consider its relationship to CVD. Given the systemic inflammatory nature of PsO, we evaluate the potential contribution of prominent inflammatory mediators (implicated in PsO pathogenesis) to establishing a prothrombotic state in psoriatic patients.


Assuntos
Coagulação Sanguínea , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Psoríase/complicações , Pele/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Trombose/etiologia , Animais , Anti-Inflamatórios/uso terapêutico , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco de Doenças Cardíacas , Humanos , Prognóstico , Psoríase/sangue , Psoríase/tratamento farmacológico , Psoríase/imunologia , Medição de Risco , Pele/efeitos dos fármacos , Pele/imunologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Trombose/sangue , Trombose/tratamento farmacológico , Trombose/imunologia
11.
Ann Hematol ; 100(11): 2699-2706, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34383101

RESUMO

To assess the effects between MPL and JAK2V617F on the thrombosis risk and peripheral blood cell counts in patients with essential thrombocythemia (ET), we identified eligible studies from PubMed, Embase, and the Cochrane Library. Seven studies were ultimately included in this meta-analysis. All studies reported the peripheral blood cell counts of ET patients, and three of them reported the eligible thrombotic events. In comparing the effect of MPL versus JAK2V617F on thrombosis, 1257 ET patients (73 MPL + and 1184 JAK2V617F +) were included. MPL-positive (MPL +) ET patients had a higher risk of thrombosis than JAK2V617F-positive (JAK2V617F +) ET patients [RR = 1.80 (1.08-3.01), P = 0.025]. And 3453 ET patients (138 MPL + and 3315 JAK2V617F +) were included in the comparison of peripheral blood cell counts. Platelet counts of MPL + ET patients were higher than that of JAK2V617F + ET patients [WMD = 81.18 (31.77-130.60), P = 0.001]. MPL + ET patients had lower hemoglobin [WMD = - 11.66 (- 14.32 to - 9.00), P = 0.000] and white blood cell counts [WMD = - 1.01 (- 1.47 to - 0.56), P = 0.000] than JAK2V617F + ET patients. These findings indicate that the MPL mutation is a high-risk factor for thrombosis in ET patients, and it may be rational to include MPL mutation in the revised IPSET as a criterion for thrombosis prediction scores. And given the differences in peripheral blood, it is necessary to further study whether MPL + ET patients differ from JAK2V617F + ET patients in bleeding and survival.


Assuntos
Contagem de Células Sanguíneas , Janus Quinase 2/genética , Mutação , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Trombose/etiologia , Humanos , Mutação de Sentido Incorreto , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Trombocitemia Essencial/sangue , Trombocitemia Essencial/complicações , Trombose/sangue , Trombose/epidemiologia
12.
Nutr Metab Cardiovasc Dis ; 31(10): 2904-2911, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34344545

RESUMO

BACKGROUND AND AIMS: Low serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients. METHODS AND RESULTS: Multicenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4-41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71-12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37-0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS -0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30-9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99-14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02-18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21-10.80, p = 0.022) were associated with AEs. CONCLUSION: Low SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.


Assuntos
Hipoalbuminemia/sangue , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Albumina Sérica Humana/análise , Trombose/etiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hospitalização , Humanos , Hipoalbuminemia/complicações , Hipoalbuminemia/diagnóstico , Hipoalbuminemia/mortalidade , Itália , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Trombose/sangue , Trombose/diagnóstico , Trombose/mortalidade , Resultado do Tratamento
13.
Diabetes Metab Syndr ; 15(5): 102240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34403950

RESUMO

AIMS: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients. METHODS: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied. RESULTS: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively. CONCLUSIONS: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability.


Assuntos
COVID-19/diagnóstico , Taxa de Filtração Glomerular/fisiologia , Plasma/química , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , COVID-19/sangue , COVID-19/fisiopatologia , COVID-19/terapia , Estudos de Coortes , Complicações do Diabetes/sangue , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/terapia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Admissão do Paciente/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Trombose/sangue , Trombose/diagnóstico , Trombose/etiologia , Trombose/fisiopatologia , Equilíbrio Hidroeletrolítico/fisiologia
14.
Eur Rev Med Pharmacol Sci ; 25(15): 5063-5069, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34355379

RESUMO

OBJECTIVE: Vaccine-induced immune thrombocytopenia (VITT) is a new syndrome occurring primarily in healthy young adults, with a female predominance, after receiving the first dose of ChAdOx1 nCoV-19 vaccine. We describe VITT syndrome characterized by severe thrombosis and thrombocytopenia found in our patient, with fatal outcome. CASE REPORT: A 58-year-old man, after 13 days from the first administration of ChAdOx1 nCoV-19 vaccine (AstraZeneca), presented with abdominal pain, diarrhea and vomitus. Laboratory tests revealed a severe thrombocytopenia, low fibrinogen serum levels and marked increase of D-dimer serum levels. The patient quickly developed a multiple organ failure, till death, three days after the hospital admission. RESULTS: At histology, in the lungs, interalveolar septa appeared thickened with microthrombi in the capillaries and veins. Interalveolar septa appeared thickened and showed vascular proliferation. Thrombi were detected in the capillaries of glomerular tufts. In the hearth, thrombi were observed in veins and capillaries. In the liver, voluminous fibrin thrombi were diffusely observed in the branches of the portal vein. Microthrombi were also found in the vasa vasorum of the wall of abdominal aorta. In the brain, microthrombi were observed in the capillaries of the choroid plexuses. Diffuse hemorrhagic necrosis was observed in the intestinal wall with marked congestion of the venous vessels. CONCLUSIONS: In our patient, the majority of data necessary for a VITT final diagnosis were present: thrombocytopenia and thrombosis in pulmonary, portal, hepatic, renal and mesenteric veins, associated with a marked increase of D-dimer serum levels. The finding of cerebral thrombosis in choroid plexuses, is a new finding in VITT. These features are suggestive for a very aggressive form of VITT.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Púrpura Trombocitopênica Idiopática/etiologia , Trombose/etiologia , Aorta/patologia , COVID-19/sangue , Vacinas contra COVID-19/administração & dosagem , Plexo Corióideo/patologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Íleo/patologia , Rim/patologia , Fígado/patologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Púrpura Trombocitopênica Idiopática/sangue , Trombose/sangue
15.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445311

RESUMO

BACKGROUND: Today there are many devices that can be used to study blood clotting disorders by identifying abnormalities in blood platelets. The Total Thrombus Formation Analysis System is an automated microchip flow chamber system that is used for the quantitative analysis of clot formation under blood flow conditions. For several years, researchers have been using a tool to analyse various clinical situations of patients to identify the properties and biochemical processes occurring within platelets and their microenvironment. METHODS: An investigation of recent published literature was conducted based on PRISMA. This review includes 52 science papers directly related to the use of the Total Clot Formation Analysis System in relation to bleeding, surgery, platelet function assessment, anticoagulation monitoring, von Willebrand factor and others. CONCLUSION: Most available studies indicate that The Total Thrombus Formation Analysis System may be useful in diagnostic issues, with devices used to monitor therapy or as a significant tool for predicting bleeding events. However, T-TAS not that has the potential for diagnostic indications, but allows the direct observation of the flow and the interactions between blood cells, including the intensity and dynamics of clot formation. The device is expected to be of significant value for basic research to observe the interactions and changes within platelets and their microenvironment.


Assuntos
Coagulação Sanguínea , Plaquetas/fisiologia , Dispositivos Lab-On-A-Chip/normas , Microfluídica/métodos , Trombose/sangue , Plaquetas/metabolismo , Humanos , Microfluídica/instrumentação , Trombose/diagnóstico
16.
J Trauma Acute Care Surg ; 91(2): 331-335, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397954

RESUMO

OBJECTIVES: As thromboelastography (TEG) becomes the standard of care in patients with hemorrhagic shock (HS), an association between concomitant traumatic brain injury (TBI) and coagulopathy by TEG parameters is not well understood and is thus investigated. METHODS: Retrospective analysis of trauma registry data at a single level 1 trauma center of 772 patients admitted with head Abbreviated Injury Scale (AIS) score of 3 and TEG studies between 2014 and 2017. Patients were stratified to moderate-severe TBI by head AIS scores of 3 and 4 (435 patients) and critical TBI by head AIS score of 5 (328 patients). Hemorrhagic shock was defined by base deficit of 4 or shock index of 0.9. Statistical analysis with unpaired t tests compared patients with critical TBI with patients with moderate-severe TBI, and patients were grouped by presence or absence of HS. A comparison of TBI data with conventional coagulation studies was also evaluated. RESULTS: In the setting of HS, critical TBI versus moderate-severe TBI was associated with longer R time (p = 0.004), longer K time (p < 0.05), less acute angle (p = 0.001), and lower clot strength and stability (maximum amplitude [MA]) (p = 0.01). Worse TBI did not correlate with increased fibrinolysis by clot lysis measured by the percentage decrease in amplitude at 30 minutes after MA (p = 0.3). Prothrombin time and international normalized ratio failed to demonstrate more severe coagulopathy, while partial thromboplastin time was found to correlate with severity of TBI (p = 0.01). In patients with critical TBI, the presence of HS correlated with a statistically significant worsening of all parameters (p < 0.05) except for clot lysis measured by the percentage decrease in amplitude at 30 minutes after MA (LY-30). CONCLUSION: Thromboelastography demonstrates that, with and without hemorrhagic shock, critical TBI correlates with a significant worsening of traumatic coagulopathy in comparison with moderate/severe TBI. In HS, critical TBI correlates with impaired clot initiation, impaired clot kinetics, and impaired platelet-associated clot strength and stability versus parameters found in moderate-severe TBI. Hemorrhagic shock correlates with worse traumatic coagulopathy in all evaluated patient groups with TBI. Conventional coagulation studies underestimate TBI-associated coagulopathy. Traumatic brain injury-associated coagulopathy is not associated with fibrinolysis. LEVEL OF EVIDENCE: Prognostic/epidemiological, level IV; prognostic/epidemiological, level III.


Assuntos
Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/complicações , Choque Hemorrágico/sangue , Tromboelastografia , Escala Resumida de Ferimentos , Testes de Coagulação Sanguínea , Lesões Encefálicas Traumáticas/patologia , Humanos , Escala de Gravidade do Ferimento , Coeficiente Internacional Normatizado , Modelos Logísticos , Estudos Retrospectivos , Choque Hemorrágico/etiologia , Trombose/sangue , Trombose/etiologia , Centros de Traumatologia
17.
Arterioscler Thromb Vasc Biol ; 41(10): 2523-2537, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34348487

RESUMO

Objective: Roxadustat is a new medication for the treatment of renal anemia. EPO (erythropoietin)-the current treatment standard-has been reported to enhance platelet activation and production. However, to date, the effect of roxadustat on platelets is unclear. To address this deficiency, herein, we have evaluated the effect of roxadustat on platelet production and function. Approach and Results: We performed several mouse platelet functional assays in the presence/absence of in vitro and in vivo roxadustat treatment. Both healthy and 5/6 nephrectomized mice were utilized. The effect of roxadustat on platelet function of healthy volunteers and chronic kidney disease patients was also evaluated. For platelet production, megakaryocyte maturation and proplatelet formation were assayed in vitro. Peripheral platelet and bone marrow megakaryocyte counts were also determined. We found that roxadustat could not stimulate washed platelets directly, and platelet aggregation, spreading, clot retraction, and P-selectin/JON/A exposure were similar with or without in vitro or in vivo roxadustat treatment among both healthy and 5/6 nephrectomized mice. In vivo mouse thrombosis models were additionally performed, and no differences were detected between the vehicle and roxadustat treatment groups. EPO, which was considered a positive control in the present study, promoted platelet function and production as reported previously. Megakaryocyte maturation and proplatelet formation were also not significantly different between control mice and those treated with roxadustat. After receiving roxadustat for 14 days, no difference in the peripheral platelet count was observed in the mice. Conclusions: Administration of roxadustat has no significant impact on platelet production and function.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Eritropoetina/farmacologia , Glicina/análogos & derivados , Hematínicos/farmacologia , Isoquinolinas/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Trombopoese/efeitos dos fármacos , Trombose/sangue , Animais , Plaquetas/metabolismo , Estudos de Casos e Controles , Modelos Animais de Doenças , Eritropoetina/toxicidade , Glicina/farmacologia , Glicina/toxicidade , Hematínicos/toxicidade , Humanos , Isoquinolinas/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etiologia , Trombose/etiologia
18.
Curr Opin Hematol ; 28(5): 323-330, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34267080

RESUMO

PURPOSE OF REVIEW: Preeclampsia is a common complication of pregnancy and contributes significantly to maternal and fetal morbidity and mortality. A protective hypercoagulable state is often developed during late pregnancy and can evolve into a prothrombotic state in patients with preeclampsia. The underlying mechanism of this prothrombotic transition remains poorly understood. We discuss recent progress in understanding the pathophysiology of preeclampsia and associated prothrombotic state. RECENT FINDINGS: The hypercoagulable state developed during pregnancy is initiated by placental factors and progresses into the prothrombotic state in preeclampsia when the placenta is subjected ischemic and oxidative injuries. The cause of the preeclampsia-induced prothrombotic state is multifactorial, involving not only placental factors but also maternal conditions, which include genetic predisposition, preexisting medical conditions, and conditions acquired during pregnancy. Endotheliopathy is the primary pathology of preeclampsia and contributes to the prothrombotic state by inducing the dysregulation of coagulation, platelets, and adhesive ligands. SUMMARY: Patients with preeclampsia often develop a severe prothrombotic state that predisposes them to life-threatening thrombosis and thromboembolism during and after pregnancy. Early recognition and treatment of this prothrombotic state can improve maternal and infant outcomes of preeclampsia patients.


Assuntos
Predisposição Genética para Doença , Pré-Eclâmpsia , Trombose , Plaquetas/metabolismo , Feminino , Humanos , Placenta/metabolismo , Adesividade Plaquetária , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/genética , Gravidez , Proteínas da Gravidez/sangue , Proteínas da Gravidez/genética , Trombose/sangue , Trombose/genética
19.
Nutr Metab Cardiovasc Dis ; 31(9): 2716-2723, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34218987

RESUMO

BACKGROUND AND AIMS: Postprandial responses are influenced not only by the type and amount of fat ingested, but also lipid droplet size distribution. However, little research has investigated the impact of differential lipid size distributions within a mixed-macronutrient meal context on postprandial vascular health. Therefore, we examined whether manipulating the lipid droplet size distribution within a mixed-macronutrient meal impacts vascular-inflammatory and thrombotic parameters. METHODS AND RESULTS: In a randomised and counterbalanced fashion, sixteen adults (8 males; age 34 ± 7 years; BMI of 25.3 ± 4.5 kg/m2) completed three separate fasted morning-time feeding challenges, each separated by a minimum washout of 7-days. On each occasion, test-meals matched for carbohydrate and protein content differing only in fat amount and the lipid droplet size distribution were administered, such that participants consumed (1) a low-fat meal (LF) with negligible fat content, (2) an emulsified-high-fat meal with a fine lipid droplet size (FE), or (3) an emulsified-high-fat meal with a coarse lipid droplet size (CE). Periodic blood samples were retrospectively analysed for plasma triglycerides, tumour necrosis factor alpha (TNFα), tissue factor (TF), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1). Triglyceride concentrations increased rapidly overtime under FE (P-time<0.05); this rise was attenuated under CE (P-time>0.05) and was comparable to LF (P-condition>0.05). Similarly, FE induced a significant rise in TNFα, TF, fibrinogen, and PAI-1 (P-time<0.05); these parameters remained unchanged under LF and CE (P-time>0.05). CONCLUSION: A high-fat mixed-macronutrient meal with a larger lipid droplet size distribution ameliorates the associated rise in vascular-inflammatory and thrombotic parameters. TRIAL REGISTRATION: ISRCTN88881254.


Assuntos
Coagulação Sanguínea , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Mediadores da Inflamação/sangue , Inflamação/prevenção & controle , Gotículas Lipídicas , Período Pós-Prandial , Trombose/prevenção & controle , Adulto , Biomarcadores/sangue , Gorduras na Dieta/administração & dosagem , Inglaterra , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Trombose/sangue , Trombose/etiologia , Fatores de Tempo
20.
Curr Rheumatol Rep ; 23(8): 65, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-34218350

RESUMO

PURPOSE OF REVIEW: COVID-19 patients have a procoagulant state with a high prevalence of thrombotic events. The hypothesis of an involvement of antiphospholipid antibodies (aPL) has been suggested by several reports. Here, we reviewed 48 studies investigating aPL in COVID-19 patients. RECENT FINDINGS: Prevalence of Lupus Anticoagulant (LA) ranged from 35% to 92% in ICU patients. Anti-cardiolipin (aCL) IgG and IgM were found in up to 52% and up to 40% of patients respectively. Anti-ß2-glycoprotein I (aß2-GPI) IgG and IgM were found in up to 39% and up to 34% of patients respectively. Between 1% and 12% of patients had a triple positive aPL profile. There was a high prevalence of aß2-GPI and aCL IgA isotype. Two cohort studies found few persistent LA but more persistent solid phase assay aPL over time. aPL determination and their potential role is a real challenge for the treatment of this disease.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , COVID-19/imunologia , Trombose/imunologia , Anticorpos Anticardiolipina/imunologia , Proteína C-Reativa/imunologia , COVID-19/sangue , COVID-19/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Inibidor de Coagulação do Lúpus/imunologia , SARS-CoV-2 , Índice de Gravidade de Doença , Trombose/sangue , Trombose/etiologia , beta 2-Glicoproteína I/imunologia
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