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1.
Sci Rep ; 11(1): 4432, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627696

RESUMO

Cardiac injury is a common complication of the coronavirus disease 2019 (COVID-19), and is associated with adverse clinical outcomes. In this study, we aimed to reveal the association of cardiac injury with coagulation dysfunction. We enrolled 181 consecutive patients who were hospitalized with COVID-19, and studied the clinical characteristics and outcome of these patients. Cardiac biomarkers high-sensitivity troponin I (hs-cTnI), myohemoglobin and creatine kinase-myocardial band (CK-MB) were assessed in all patients. The clinical outcomes were defined as hospital discharge or death. The median age of the study cohort was 55 (IQR, 46-65) years, and 102 (56.4%) were males. Forty-two of the 181 patients (23.2%) had cardiac injury. Old age, high leukocyte count, and high levels of aspartate transaminase (AST), D-dimer and serum ferritin were significantly associated with cardiac injury. Multivariate regression analysis revealed old age and elevated D-dimer levels as being strong risk predictors of in-hospital mortality. Interleukin 6 (IL6) levels were comparable in patients with or without cardiac injury. Serial observations of coagulation parameters demonstrated highly synchronous alterations of D-dimer along with progression to cardiac injury. Cardiac injury is a common complication of COVID-19 and is an independent risk factor for in-hospital mortality. Old age, high leukocyte count, and high levels of AST, D-dimer and serum ferritin are significantly associated with cardiac injury, whereas IL6 are not. Therefore, the pathogenesis of cardiac injury in COVID-19 may be primarily due to coagulation dysfunction along with microvascular injury.


Assuntos
Transtornos da Coagulação Sanguínea/virologia , Traumatismos Cardíacos/virologia , Idoso , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/epidemiologia , /fisiopatologia , China/epidemiologia , Estudos de Coortes , Creatina Quinase Forma MB/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/epidemiologia , Traumatismos Cardíacos/fisiopatologia , Hemoglobinas/metabolismo , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Troponina I/sangue
2.
Am J Physiol Cell Physiol ; 320(3): C365-C374, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33471623

RESUMO

Factor XI (FXI) has been shown to bind platelets, but the functional significance of this observation remains unknown. Platelets are essential for hemostasis and play a critical role in thrombosis, whereas FXI is not essential for hemostasis but promotes thrombosis. An apparent functional contradiction, platelets are known to support thrombin generation, yet platelet granules release protease inhibitors, including those of activated FXI (FXIa). We aim to investigate the secretory and binding mechanisms by which platelets could support or inhibit FXIa activity. The presence of platelets enhanced FXIa activity in a purified system and increased coagulation Factor IX (FIX) activation by FXIa and fibrin generation in human plasma. In contrast, platelets reduced the activation of FXI by activated coagulation factor XII (FXIIa) and the activation of FXII by kallikrein (PKa). Incubation of FXIa with the platelet secretome, which contains FXIa inhibitors, such as protease nexin-II, abolished FXIa activity, yet in the presence of activated platelets, the secretome was not able to block the activity of FXIa. FXIa variants lacking the anion-binding sites did not alter the effect of platelets on FXIa activity or interaction. Western blot analysis of bound FXIa [by FXIa-platelet membrane immunoprecipitation] showed that the interaction with platelets is zinc dependent and, unlike FXI binding to platelets, not dependent on glycoprotein Ib. FXIa binding to the platelet membrane increases its capacity to activate FIX in plasma likely by protecting it from inhibition by inhibitors secreted by activated platelets. Our findings suggest that an interaction of FXIa with the platelet surface may induce an allosteric modulation of FXIa.


Assuntos
Plaquetas/metabolismo , Fator XIa/metabolismo , Adolescente , Precursor de Proteína beta-Amiloide/metabolismo , Sítios de Ligação/fisiologia , Coagulação Sanguínea/fisiologia , Feminino , Hemostasia/fisiologia , Humanos , Masculino , Trombina/metabolismo , Trombose/metabolismo
3.
Int J Mol Sci ; 21(24)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322373

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease associated with thrombotic complications. To elucidate pathogenic mechanisms, hemostatic disorders in RA were correlated with other laboratory and clinical manifestations. Hemostasis was assessed using relatively new complementary tests, the spatial growth of a plasma clot (Thrombodynamics assay), and contraction of whole blood clots. Platelet functionality was assessed with flow cytometry that quantified the expression of P-selectin and the fibrinogen-binding capacity of platelets before and after activation with a thrombin receptor-activating peptide. Parameters of fibrin clot growth and the kinetics of contraction of blood clots were significantly altered in patients with RA compared to the control group. In Thrombodynamics measurements, an increase in the clot growth rate, size, and optical density of plasma clots altogether indicated chronic hypercoagulability. The rate and extent of blood clot contraction in patients with RA was significantly reduced and associated with platelet dysfunction revealed by an impaired response to activation. Changes in the parameters of clot growth and contraction correlated with the laboratory signs of systemic inflammation, including hyperfibrinogenemia. These results confirm the pathogenic role of hemostatic disorders in RA and support the validity of fibrin clot growth and the blood clot contraction assay as indicators of a (pro)thrombotic state.


Assuntos
Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Fibrina/metabolismo , Trombose/metabolismo , Trombose/patologia , Adulto , Idoso , Coagulação Sanguínea/fisiologia , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/metabolismo , Adulto Jovem
4.
PLoS One ; 15(12): e0244792, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382840

RESUMO

Blood coagulation is central to myocardial ischemia and reperfusion (IR) injury. Studies on the light elicited circadian rhythm protein Period 2 (PER2) using whole body Per2-/- mice found deficient platelet function and reduced clotting which would be expected to protect from myocardial IR-injury. In contrast, intense light induction of PER2 protected from myocardial IR-injury while Per2 deficiency was detrimental. Based on these conflicting data, we sought to evaluate the role of platelet specific PER2 in coagulation and myocardial ischemia and reperfusion injury. We demonstrated that platelets from mice with tissue-specific deletion of Per2 in the megakaryocyte lineage (Per2loxP/loxP-PF4-CRE) significantly clot faster than platelets from control mice. We further found increases in infarct sizes or plasma troponin levels in Per2loxP/loxP-PF4-CRE mice when compared to controls. As intense light increases PER2 protein in human tissues, we also performed translational studies and tested the effects of intense light therapy on coagulation in healthy human subjects. Our human studies revealed that intense light therapy repressed procoagulant pathways in human plasma samples and significantly reduced the clot rate. Based on these results we conclude that intense light elicited PER2 has an inhibitory function on platelet aggregation in mice. Further, we suggest intense light as a novel therapy to prevent or treat clotting in a clinical setting.


Assuntos
Coagulação Sanguínea/fisiologia , Plaquetas/metabolismo , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteínas Circadianas Period/metabolismo , Fototerapia , Animais , Humanos , Luz , Masculino , Camundongos , Isquemia Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/sangue , Proteínas Circadianas Period/genética , Agregação Plaquetária/fisiologia , Proteômica
5.
Int J Mol Sci ; 21(21)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33153161

RESUMO

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.


Assuntos
Plaquetas/patologia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Eritrócitos/patologia , Ferritinas/sangue , Selectina-P/sangue , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Coagulação Sanguínea/fisiologia , Plaquetas/virologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/virologia , Eritrócitos/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Trombose/patologia , Trombose/virologia
6.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33004529

RESUMO

Novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has rapidly spread throughout the world, resulting in a pandemic with high mortality. There are no effective treatments for the management of severe COVID-19 and current therapeutic trials are focused on antiviral therapy and attenuation of hyper-inflammation with anti-cytokine therapy. Severe COVID-19 pneumonia shares some pathological similarities with severe bacterial pneumonia and sepsis. In particular, it disrupts the haemostatic balance, which results in a procoagulant state locally in the lungs and systemically. This culminates in the formation of microthrombi, disseminated intravascular coagulation and multi-organ failure. The deleterious effects of exaggerated inflammatory responses and activation of coagulation have been investigated in bacterial pneumonia and sepsis and there is recognition that although these pathways are important for the host immune response to pathogens, they can lead to bystander tissue injury and are negatively associated with survival. In the past two decades, evidence from preclinical studies has led to the emergence of potential anticoagulant therapeutic strategies for the treatment of patients with pneumonia, sepsis and acute respiratory distress syndrome, and some of these anticoagulant approaches have been trialled in humans. Here, we review the evidence from preclinical studies and clinical trials of anticoagulant treatment strategies in bacterial pneumonia and sepsis, and discuss the importance of these findings in the context of COVID-19.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/sangue , Pneumonia Bacteriana/sangue , Pneumonia Viral/sangue , Sepse/sangue , Biomarcadores/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia
7.
Clin Appl Thromb Hemost ; 26: 1076029620962853, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33074732

RESUMO

Thrombotic complications of the novel coronavirus (COVID-19) are a concerning aspect of the disease, due to the high incidence in critically ill patients and poor clinical outcomes. COVID-19 predisposes patients to a hypercoagulable state, however, the pathophysiology behind the thrombotic complications seen in this disease is not well understood. Several mechanisms have been proposed and the pathogenesis likely involves a host immune response contributing to vascular endothelial cell injury, inflammation, activation of the coagulation cascade via tissue factor expression, and shutdown of fibrinolysis. Treatments targeting these pathways may need to be considered to improve clinical outcomes and decrease overall mortality due to thrombotic complications. In this review, we will discuss the proposed pathophysiologic mechanisms for thrombotic complications in COVID-19, as well as treatment strategies for these complications based on the current literature available.


Assuntos
Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Trombofilia/etiologia , Infecções por Coronavirus/epidemiologia , Saúde Global , Humanos , Incidência , Pneumonia Viral/epidemiologia , Trombofilia/sangue , Trombofilia/epidemiologia
8.
Am J Pathol ; 190(10): 2146-2154, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745462

RESUMO

Patients with thalassemia exhibit an increased risk of thrombotic events that is augmented after splenectomy. Heparanase protein enhances cancer progression, angiogenesis, and inflammation; it also activates the coagulation system through direct interaction with tissue factor (TF). Additionally, erythropoietin, which is elevated in anemic patients, up-regulates heparanase expression via the Janus kinase 2 (JAK-2) pathway. This study aimed was to explore the heparanase profile in thalassemia. Coagulation factors were analyzed via immunostaining, enzyme-linked immunosorbent assay, and heparanase procoagulant activity assay. In spleen specimens of thalassemia major patients, a higher level of heparanase staining was observed compared with control spleens resected after trauma (P < 0.001). Higher heparanase levels, heparanase and TF procoagulant activity, and erythropoietin levels were found in the plasma of 67 thalassemia major patients compared with 29 control subjects. No difference was found in pediatric patients (23 of 67) compared with adults or splenectomized versus nonsplenectomized patients. Higher levels of heparanase, TF, TF pathway inhibitor, and TF pathway inhibitor-2 were observed in liver, spleen, heart, and kidney tissues of thalassemia intermedia mice (Hbbth3/+). These protein levels significantly reduced when mice were treated with the JAK-2 inhibitor ruxolitinib (P < 0.0001). In summary, heparanase levels are elevated in thalassemia, which may contribute to thrombotic phenomena in these patients. Inhibition of heparanase or the JAK-2 pathway may reduce thrombotic risk in thalassemia.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Glucuronidase/metabolismo , Janus Quinase 2/antagonistas & inibidores , Lipoproteínas/farmacologia , Trombose/tratamento farmacológico , Adulto , Animais , Humanos , Masculino , Camundongos Endogâmicos C57BL , Talassemia/tratamento farmacológico , Talassemia/metabolismo , Tromboplastina/metabolismo , Trombose/metabolismo , Adulto Jovem
9.
J Proteome Res ; 19(11): 4417-4427, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-32786691

RESUMO

Over 5 million people around the world have tested positive for the beta coronavirus SARS-CoV-2 as of May 29, 2020, a third of which are in the United States alone. These infections are associated with the development of a disease known as COVID-19, which is characterized by several symptoms, including persistent dry cough, shortness of breath, chills, muscle pain, headache, loss of taste or smell, and gastrointestinal distress. COVID-19 has been characterized by elevated mortality (over 100 thousand people have already died in the US alone), mostly due to thromboinflammatory complications that impair lung perfusion and systemic oxygenation in the most severe cases. While the levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) have been associated with the severity of the disease, little is known about the impact of IL-6 levels on the proteome of COVID-19 patients. The present study provides the first proteomics analysis of sera from COVID-19 patients, stratified by circulating levels of IL-6, and correlated to markers of inflammation and renal function. As a function of IL-6 levels, we identified significant dysregulation in serum levels of various coagulation factors, accompanied by increased levels of antifibrinolytic components, including several serine protease inhibitors (SERPINs). These were accompanied by up-regulation of the complement cascade and antimicrobial enzymes, especially in subjects with the highest levels of IL-6, which is consistent with an exacerbation of the acute phase response in these subjects. Although our results are observational, they highlight a clear increase in the levels of inhibitory components of the fibrinolytic cascade in severe COVID-19 disease, providing potential clues related to the etiology of coagulopathic complications in COVID-19 and paving the way for potential therapeutic interventions, such as the use of pro-fibrinolytic agents. Raw data for this study are available through ProteomeXchange with identifier PXD020601.


Assuntos
Proteínas Sanguíneas/análise , Proteínas do Sistema Complemento/análise , Infecções por Coronavirus , Interleucina-6/sangue , Pandemias , Pneumonia Viral , Proteoma/análise , Adulto , Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Feminino , Hemólise , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Proteômica
10.
Intern Emerg Med ; 15(8): 1369-1373, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32748128

RESUMO

The overflow of studies in the recent literature on COVID-19 often gives provisional or contradictory results and therefore deserves pauses of reflection and reconsideration. In fact, knowledges of pathophysiology of this new disease are still in development and hence originate discussions and interpretations. Regarding the role of blood coagulation and fibrinolysis, these mechanisms should be considered as crucial especially in severe cases. It is proposed to consider two distinct phenotypes of thrombotic manifestations: the current "thromboembolic type" also occurring in other kinds of sepsis, and the diffuse micro-thrombotic type, prevailing in the lungs but sometimes extending to other organs. Both types can induce severe disease and are potentially lethal. The micro-thrombotic pattern, more specific for COVID-19, results from a massive activation of coagulation strictly coupled with a hyper-intense inflammatory and immune reaction. This results in widespread occlusive thrombotic micro-angiopathy with destruction of alveoli and obstructive neoangiogenesis. The involvement of fibrinolysis, often neglected, confers a double faceted process of activation/inhibition, finally conducive to a fibrinolytic shutdown that reinforces persistence of micro-thrombi. Considering these peculiar mechanisms, it seems evident that both prophylactic and therapeutic effects of current anti-thrombotic drugs cannot be taken for granted and need therefore new specific and rigorous controlled trials.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Fibrinólise/efeitos dos fármacos , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Coagulação Sanguínea/fisiologia , Fibrinólise/fisiologia , Humanos , Pandemias , Terapia Trombolítica/métodos
11.
J Mol Cell Cardiol ; 147: 74-87, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32827510

RESUMO

BACKGROUND: Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitudinal follow-up of cardiac injury, inflammation and coagulation markers in relation to disease severity and outcome. METHODS: We retrospectively assessed 2068 patients with laboratory-confirmed COVID-19 between January 29 and April 1, 2020 at Tongji Hospital in Wuhan, China. We defined cardiac injury as an increase in high sensitivity cardiac troponin-I (hs-cTnI) above the 99th of the upper reference limit. We explored the dynamics of elevation in hs-cTnI and the relationship with inflammation (interleukin [IL]-6, IL-8, IL-10, IL-2 receptor, tumor necrosis factor-α, C-reactive protein) and coagulation (d-dimer, fibrinogen, international normalized ratio) markers in non-critically ill versus critically ill patients longitudinally and further correlated these markers to survivors and non-survivors. RESULTS: Median age was 63 years (first to third quartile 51-70 years), 51.4% of whom were women. When compared to non-critically ill patients (N = 1592, 77.0%), critically ill (defined as requiring mechanical ventilation, in shock or multiorgan failure) patients (N = 476, 23.0%), had more frequent cardiac injury on admission (30.3% vs. 2.3%, p < 0.001), with increased mortality during hospitalization (38.4% vs. 0%, p < 0.001). Among critically ill patients, non-survivors (N = 183) had a continuous increase in hs-cTnI levels during hospitalization, while survivors (N = 293) showed a decrease in hs-cTnI level between day 4 and 7 after admission. Specifically, cardiac injury is an independent marker of mortality among critically ill patients at admission, day 4-7 and 8-14. Consistent positive correlations between hs-cTnI and interleukin (IL)-6 on admission (r = 0.59), day 4-7 (r = 0.66) and day 8-14 (r = 0.61; all p < 0.001) and d-dimer (at the same timepoints r = 0.54; 0.65; 0.61, all p < 0.001) were observed. A similar behavior was observed between hs-cTnI and most of other biomarkers of inflammation and coagulation. CONCLUSIONS: Cardiac injury commonly occurs in critically ill COVID-19 patients, with increased levels of hs-cTnI beyond day 3 since admission portending a poor prognosis. A consistent positive correlation of hs-cTnI with IL-6 and d-dimer at several timepoints along hospitalization could suggest nonspecific cytokine-mediated cardiotoxicity.


Assuntos
Infecções por Coronavirus/patologia , Citocinas/sangue , Traumatismos Cardíacos/patologia , Pneumonia Viral/patologia , Troponina I/sangue , Idoso , Betacoronavirus , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/sangue , Estado Terminal , Feminino , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/diagnóstico , Humanos , Inflamação , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Prognóstico , Estudos Retrospectivos
12.
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
13.
Intern Emerg Med ; 15(8): 1375-1387, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32653981

RESUMO

The acute respiratory illnesses caused by severe acquired respiratory syndrome corona Virus-2 (SARS-CoV-2) is a global health emergency, involving more than 8.6 million people worldwide with more than 450,000 deaths. Among the clinical manifestations of COVID-19, the disease that results from SARS-CoV-2 infection in humans, a prominent feature is a pro-thrombotic derangement of the hemostatic system, possibly representing a peculiar clinicopathologic manifestation of viral sepsis. The severity of the derangement of coagulation parameters in COVID-19 patients has been associated with a poor prognosis, and the use of low molecular weight heparin (LMWH) at doses registered for prevention of venous thromboembolism (VTE) has been endorsed by the World Health Organization and by Several Scientific societies. However, some relevant issues on the relationships between COVID-19, coagulopathy and VTE have yet to be fully elucidated. This review is particularly focused on four clinical questions: What is the incidence of VTE in COVID-19 patients? How do we frame the COVID-19 associated coagulopathy? Which role, if any, do antiphospolipid antibodies have? How do we tackle COVID-19 coagulopathy? In the complex scenario of an overwhelming pandemic, most everyday clinical decisions have to be taken without delay, although not yet supported by a sound scientific evidence. This review discusses the most recent findings of basic and clinical research about the COVID-associated coagulopathy, to foster a more thorough knowledge of the mechanisms underlying this compelling disease.


Assuntos
Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Tromboembolia Venosa/etiologia , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Coagulação Intravascular Disseminada/etiologia , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia
14.
Stroke ; 51(8): 2347-2354, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32646335

RESUMO

BACKGROUND AND PURPOSE: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. METHODS: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. RESULTS: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). CONCLUSIONS: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Reperfusão/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reperfusão/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Trombectomia/métodos , Terapia Trombolítica/métodos , Resultado do Tratamento
15.
Rev Col Bras Cir ; 47: e20202595, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32490891

RESUMO

The New Coronavirus Epidemic (2019-nCoV), discovered in the city of Wuhan, China, in December 2019, presents mainly with pulmonary pneumonia that is preceded by fever, cough and myalgia. However, as the disease spread globally and the number of hospitalizations increased exponentially, it was noted that most serious patients hospitalized by COVID-19 have laboratory changes worthy of attention, such as lymphopenia, neutrophilia, increased time of prothrombin and increased levels of D-dimer. Due to these changes proving to be crucial for the mortality and morbidity rates in this subset of infected people, several studies focusing on the pathophysiology, mainly hematological, of the disease appear every day. Deepening these studies, several published works have shown SarsCoV-2 infection to the installation of a prothrombotic state in hospitalized patients, which leads to the potential occurrence of thrombotic or arterial events in this cohort. Thus, in order to understand how the departments of Angiology and Vascular Surgery are acting in the context of the COVID-19 pandemic, this work aims to gather studies that reveal from protocols applied in vascular services in the current situation, until to the role of vascular surgeons and angiologists in the clinical and surgical management of patients infected or not, as a way of helping and clarifying this specialty during the context of a pandemic due to the new coranavirus. For the selection of works, the following search criteria were used: "Coronavirus and venous thrombosis", "Coronavirus and thrombosis", "COVID-19 and venous thrombosis" and "COVID-19 Coronavirus and thrombosis".


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Embolia Pulmonar/virologia , Tromboembolia/virologia , Coagulação Sanguínea/fisiologia , Protocolos Clínicos , Infecções por Coronavirus/fisiopatologia , Humanos , Pneumonia Viral/fisiopatologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Tromboembolia/diagnóstico , Tromboembolia/terapia , Procedimentos Cirúrgicos Vasculares/métodos , Procedimentos Cirúrgicos Vasculares/normas
16.
Int J Mol Med ; 46(3): 903-912, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32588061

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) is a novel ß coronavirus that is the etiological agent of the pandemic coronavirus disease 2019 (COVID­19) that at the time of writing (June 16, 2020) has infected almost 6 million people with some 450,000 deaths. These numbers are still rising daily. Most (some 80%) cases of COVID­19 infection are asymptomatic, a substantial number of cases (15%) require hospitalization and an additional fraction of patients (5%) need recovery in intensive care units. Mortality for COVID­19 infection appears to occur globally between 0.1 and 0.5% of infected patients although the frequency of lethality is significantly augmented in the elderly and in patients with other comorbidities. The development of acute respiratory distress syndrome and episodes of thromboembolism that may lead to disseminated intravascular coagulation (DIC) represent the primary causes of lethality during COVID­19 infection. Increasing evidence suggests that thrombotic diathesis is due to multiple derangements of the coagulation system including marked elevation of D­dimer that correlate negatively with survival. We propose here that the thromboembolic events and eventually the development of DIC provoked by SARS­CoV­2 infection may represent a secondary anti­phospholipid antibody syndrome (APS). We will apply both Baconian inductivism and Cartesian deductivism to prove that secondary APS is likely responsible for coagulopathy during the course of COVID­19 infection. Diagnostic and therapeutic implications of this are also discussed.


Assuntos
Síndrome Antifosfolipídica/patologia , Infecções por Coronavirus/patologia , Coagulação Intravascular Disseminada/patologia , Pneumonia Viral/patologia , Tromboembolia/patologia , Trombose/patologia , Síndrome Antifosfolipídica/imunologia , Antivirais/uso terapêutico , Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Coagulação Intravascular Disseminada/imunologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Pandemias , Fosfolipídeos/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Tromboembolia/imunologia
17.
J Pediatr ; 221S: S29-S36, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32482231

RESUMO

This post hoc study of a plasma proteomic database investigated hemostatic proteins in the context of developmental hemostasis. Twenty-seven hemostatic proteins changed expression with age, and the hemostatic profile of neonates was unique. Appreciating developmental hemostasis through proteomics may lead to more personalized medicine for hospitalized children.


Assuntos
Envelhecimento/sangue , Proteínas Sanguíneas/fisiologia , Hemostasia/fisiologia , Proteômica , Adulto , Coagulação Sanguínea/fisiologia , Plaquetas/fisiologia , Criança , Pré-Escolar , Células Endoteliais/fisiologia , Feminino , Fibrinólise/fisiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Adulto Jovem
18.
Cleve Clin J Med ; 87(8): 461-468, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32409435

RESUMO

Severe COVID-19 illness is associated with intense inflammation, leading to high rates of thrombotic complications that increase morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory findings of severe COVID-19- associated coagulopathy. Prophylaxis against venous thromboembolism is paramount for all hospitalized patients, with more aggressive prophylaxis and screening recommended for patients with D-dimer levels above 3.0 µg/mL. Point-of-care ultrasonography is the imaging method of choice for patients at high risk, as it entails minimal risk of exposing providers to the virus.


Assuntos
Anticoagulantes/farmacologia , Betacoronavirus , Transtornos da Coagulação Sanguínea , Infecções por Coronavirus , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Monitorização Fisiológica/métodos , Pandemias , Pneumonia Viral , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/terapia , Testes de Coagulação Sanguínea/métodos , Quimioprevenção/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Humanos , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Trombose/etiologia , Trombose/prevenção & controle
19.
Monaldi Arch Chest Dis ; 90(2)2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32425013

RESUMO

Latest evidences from literature suggest that SARS-CoV-2 disease 2019 (COVID-19) is commonly complicated with coagulopathy and that disseminated intravascular coagulation is present in the majority of deceased patients. Particularly, conventional coagulation parameters appear to be significantly altered in patients with poor prognosis. A wide-ranging cross- talk between coagulative haemostasis and inflammation, as well as the activation of coagulation cascade during viral infections, are well established. Another important evidence which may explain coagulation disorders in COVID-19 is the increase of thrombus formation under conditions of hypoxia. Despite the exact pathophysiological mechanism of coronavirus-induced thromboembolism needs to be further investigated, this finding suggests that it is good practice to assess the risk of thrombosis in COVID-19 patients to improvethe clinical management in terms of anticoagulation therapy. Anticoagulants, mainly low-molecular-weight heparin (LMWH), should be tailored in patients meeting sepsis induced coagulopathy (SIC) criteria or with markedly elevated D-dimer. In this context, further studies are needed to optimise the decision making in therapeutic approach.


Assuntos
Transtornos da Coagulação Sanguínea/virologia , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Betacoronavirus/isolamento & purificação , Coagulação Sanguínea/fisiologia , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/epidemiologia , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia
20.
Med Sci (Paris) ; 36(4): 348-357, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32356711

RESUMO

Cardiovascular diseases are the leading cause of deaths in the world. Platelets play a major role in the occurrence of these diseases and the development of antiplatelet drugs is a priority in the fight against cardiovascular diseases-associated mortality. Aspirin and thienopyridine-based P2Y12 inhibitors are the main drugs currently used. These molecules target the initiation of platelets activation and are responsible for a moderate inhibitory action. Other antiplatelet agents, as glycoprotein (GP) IIb/IIIa antagonists, inhibit platelet aggregation independently of initial activation-associated pathways, but are responsible for increased hemorrhagic events. Regarding each antiplatelet agent's specific characteristics, the prescription of these drugs must take into account the type of cardiovascular event, the age of the patient, the past medical history, and the potential hemorrhagic adverse events. Thus, there is a need for the development of new molecules with a more targeted effect, maintaining optimal efficiency but with a reduction of the hemorrhagic risk, which is the principal limitation of these treatments.


Assuntos
Terapia de Alvo Molecular/tendências , Inibidores da Agregação de Plaquetas/uso terapêutico , Terapias em Estudo/tendências , Aspirina/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Hemorragia/induzido quimicamente , Humanos , Terapia de Alvo Molecular/métodos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Fatores de Risco , Terapias em Estudo/métodos
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