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1.
Front Immunol ; 13: 862522, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464473

RESUMO

Lung injury may persist during the recovery period of COVID-19 as shown through imaging, six-minute walk, and lung function tests. The pathophysiological mechanisms leading to long COVID have not been adequately explained. Our aim is to investigate the basis of pulmonary susceptibility during sequelae and the possibility that prothrombotic states may influence long-term pulmonary symptoms of COVID-19. The patient's lungs remain vulnerable during the recovery stage due to persistent shedding of the virus, the inflammatory environment, the prothrombotic state, and injury and subsequent repair of the blood-air barrier. The transformation of inflammation to proliferation and fibrosis, hypoxia-involved vascular remodeling, vascular endothelial cell damage, phosphatidylserine-involved hypercoagulability, and continuous changes in serological markers all contribute to post-discharge lung injury. Considering the important role of microthrombus and arteriovenous thrombus in the process of pulmonary functional lesions to organic lesions, we further study the possibility that prothrombotic states, including pulmonary vascular endothelial cell activation and hypercoagulability, may affect long-term pulmonary symptoms in long COVID. Early use of combined anticoagulant and antiplatelet therapy is a promising approach to reduce the incidence of pulmonary sequelae. Essentially, early treatment can block the occurrence of thrombotic events. Because impeded pulmonary circulation causes large pressure imbalances over the alveolar membrane leading to the infiltration of plasma into the alveolar cavity, inhibition of thrombotic events can prevent pulmonary hypertension, formation of lung hyaline membranes, and lung consolidation.


Assuntos
COVID-19 , Lesão Pulmonar , Trombofilia , Trombose , Assistência ao Convalescente , COVID-19/complicações , Humanos , Lesão Pulmonar/etiologia , Alta do Paciente , SARS-CoV-2 , Trombofilia/etiologia , Trombose/etiologia
2.
J Pharm Pract ; 35(2): 205-211, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35484870

RESUMO

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) is associated with severe hypercoagulability. There is currently limited evidence supporting the routine use of therapeutic anticoagulation in the setting of COVID-19. OBJECTIVES: The primary objective was to compare the incidence of thromboembolic events in adult patients with COVID-19 treated with an unfractionated heparin (UFH) infusion versus prophylactic dose anticoagulation. Secondary objectives included exploration of the efficacy and safety of an UFH infusion through the evaluation of organ function and incidence of minor and major bleeding. METHODS: Retrospective observational cohort study with propensity score matching of COVID-19 patients who received an UFH infusion targeting an aPTT between 40 and 60 seconds. RESULTS: Fifty-six patients were included in this study. There was no difference in the composite of thromboembolic events comprised of venous thromboembolism, arterial thrombosis, and catheter-related thrombosis between the UFH and control group (17.9% vs. 3.6%, P = 0.19). There was a significant increase in median D-dimer concentrations from day 1 to day 7 in the control group (475 ng/mL [291-999] vs. 10820 ng/mL [606-21033], P = 0.04). Patients treated with UFH had a higher incidence of minor bleeding (35.7% vs. 0%, P < 0.005) and required more units of packed red blood cell transfusion (0.8 units ± 1.6 vs. 0 units, P = 0.01). CONCLUSION: Continuous infusion of UFH for patients with COVID-19 infection did not decrease the overall incidence of thromboembolic complications. UFH was associated with stabilization of D-dimer concentrations and increased rates of minor bleeding and transfusions.


Assuntos
COVID-19 , Trombofilia , Trombose , Tromboembolia Venosa , Adulto , Anticoagulantes , COVID-19/tratamento farmacológico , Hemorragia/induzido quimicamente , Heparina , Humanos , Estudos Retrospectivos , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Trombose/tratamento farmacológico , Trombose/epidemiologia , Trombose/etiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
3.
Thromb Res ; 213: 9-15, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35256195

RESUMO

INTRODUCTION: Cardiovascular disease is the major cause of mortality in non-alcoholic fatty liver disease (NAFLD), a disease affecting one quarter of the world's population. Coagulation imbalance may be a contributing factor but is yet to be convincingly disclosed. AIM: To perform an extensive mapping of the hemostatic system; primary and secondary hemostasis and the fibrinolytic system in non-diabetic NAFLD patients. MATERIALS AND METHODS: Twenty-five non-diabetic, biopsy-proven NAFLD patients [12 simple steatosis; 13 non-alcoholic steatohepatitis (NASH)] investigated by a comprehensive panel of coagulation and fibrinolysis tests in a cross-sectional study. Fifty age- and sex-matched healthy persons served as controls for each of the dynamic analyses: platelet aggregation, thrombin generation, fibrin formation and lysis. Body composition, insulin resistance makers, and liver fat assessed by proton density magnetic resonance imaging were measured in the patients. RESULTS: Fibrinolytic function was impaired in simple steatosis [median 50% clot lysis time 1123 (min-max, 618-1967) s] and NASH [1448 (521-2618) s] compared to healthy controls [403 (184-1179) s] (p < 0.0001). Plasminogen activator inhibitor-1 (PAI-1) increased stepwise above reference interval from simple steatosis [54 (29-80) ng/ml] to NASH patients [109 (65-153) ng/ml; p = 0.03]. Impaired fibrinolysis correlated with hepatic fat fraction and insulin resistance; PAI-1 correlated with obesity and insulin resistance (ρ ≥ 0.42; p ≤ 0.04). Platelet aggregation, coagulation factors, natural anticoagulants, and thrombin generation were comparable to healthy controls and established reference intervals. CONCLUSIONS: NAFLD patients had impaired fibrinolysis without significant prothrombotic changes in coagulation. The impact of this abnormality on the increased cardiovascular risk remains to be investigated.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Trombofilia , Estudos Transversais , Tempo de Lise do Coágulo de Fibrina , Fibrinólise , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Inibidor 1 de Ativador de Plasminogênio , Trombina , Trombofilia/etiologia
4.
PLoS One ; 17(2): e0263238, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35180240

RESUMO

BACKGROUND: Envenomation by the European adder, Vipera berus berus (Vbb), is a medical emergency. The overall in vivo haemostatic effects of pro- and anticoagulant components in Vbb venom, and the downstream effects of cellular injury and systemic inflammation, are unclear. OBJECTIVES: To longitudinally describe the global coagulation status of dogs after Vbb envenomation and compare to healthy controls. A secondary aim was to investigate differences between dogs treated with and without antivenom. METHODS: Citrated plasma was collected at presentation, 12 hours (h), 24 h, 36 h and 15 days after bite from 28 dogs envenomated by Vbb, and from 28 healthy controls at a single timepoint. Thrombin generation (initiated with and without exogenous phospholipids and tissue factor), thrombin-antithrombin (TAT)-complexes and the procoagulant activity of phosphatidylserine (PS)-expressing extracellular vesicles (EVs), expressed as PS-equivalents, were measured. RESULTS: At presentation the envenomated dogs were hypercoagulable compared to controls, measured as increased thrombin generation, TAT-complexes and PS-equivalents. The hypercoagulability decreased gradually but compared to controls thrombin generation and PS-equivalents were still increased at day 15. The discrepancy in peak thrombin between envenomated dogs and controls was greater when the measurement was phospholipid-dependent, indicating that PS-positive EVs contribute to hypercoagulability. Lag time was shorter in non-antivenom treated dogs, compared to antivenom treated dogs <24 h after envenomation. CONCLUSIONS: Hypercoagulability was measured in dogs up to 15 days after Vbb envenomation. Dogs treated with antivenom may be less hypercoagulable than their non-antivenom treated counterparts. Thrombin generation is a promising diagnostic and monitoring tool for Vbb envenomation.


Assuntos
Antivenenos/uso terapêutico , Doenças do Cão/etiologia , Doenças do Cão/terapia , Fatores Imunológicos/uso terapêutico , Mordeduras de Serpentes/complicações , Trombofilia/etiologia , Trombofilia/veterinária , Viperidae , Animais , Antitrombina III , Estudos de Casos e Controles , Cães , Feminino , Inflamação/sangue , Inflamação/etiologia , Inflamação/terapia , Inflamação/veterinária , Estudos Longitudinais , Masculino , Peptídeo Hidrolases/sangue , Trombina/análise , Trombofilia/sangue , Trombofilia/terapia , Resultado do Tratamento , Venenos de Víboras/imunologia
5.
Viruses ; 14(2)2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35215822

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is currently developing into a rapidly disseminating and an overwhelming worldwide pandemic. In severe COVID-19 cases, hypercoagulability and inflammation are two crucial complications responsible for poor prognosis and mortality. In addition, coagulation system activation and inflammation overlap and produce life-threatening complications, including coagulopathy and cytokine storm, which are associated with overproduction of cytokines and activation of the immune system; they might be a lead cause of organ damage. However, patients with severe COVID-19 who received anticoagulant therapy had lower mortality, especially with elevated D-dimer or fibrin degradation products (FDP). In this regard, the discovery of natural products with anticoagulant potential may help mitigate the numerous side effects of the available synthetic drugs. This review sheds light on blood coagulation and its impact on the complication associated with COVID-19. Furthermore, the sources of natural anticoagulants, the role of nanoparticle formulation in this outbreak, and the prevalence of thrombosis with thrombocytopenia syndrome (TTS) after COVID-19 vaccines are also reviewed. These combined data provide many research ideas related to the possibility of using these anticoagulant agents as a treatment to relieve acute symptoms of COVID-19 infection.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/etiologia , Vacinas contra COVID-19/química , COVID-19/complicações , COVID-19/prevenção & controle , Nanopartículas/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/isolamento & purificação , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/classificação , Transtornos da Coagulação Sanguínea/prevenção & controle , Transtornos da Coagulação Sanguínea/virologia , Vacinas contra COVID-19/administração & dosagem , Síndrome da Liberação de Citocina/prevenção & controle , Síndrome da Liberação de Citocina/virologia , Humanos , Inflamação/etiologia , Inflamação/prevenção & controle , Nanopartículas/química , SARS-CoV-2/patogenicidade , Trombofilia/etiologia
7.
J Thromb Haemost ; 20(4): 845-856, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35068080

RESUMO

BACKGROUND: Hemostasis evaluation in chronic kidney disease (CKD) is critical for optimal management of thrombotic and bleeding events. Standard coagulation screens are inadequate for predicting coagulopathy in CKD. OBJECTIVE: To evaluate hemostasis parameters in patients with different stages of CKD using novel coagulation assays. PATIENTS/METHODS: Cross-sectional study of 30 healthy controls (HC) and 120 CKD patients (10 Stage 2, 20 Stage 3, 20 Stage 4, 20 Stage 5 not requiring renal replacement therapy, 20 transplant, 10 newly started on hemodialysis [HD], 20 established on HD). Standard laboratory tests were performed in addition to rotational thromboelastometry (ROTEM), multiple electrode aggregometry (MEA), thrombin generation assays, D-dimer, and markers of thrombogenesis (thrombin-antithrombin [TAT]), fibrinolysis, and endothelial activation (intercellular adhesion molecule-1 [ICAM-1]). RESULTS: D-dimer, TAT, and ICAM-1 concentrations were significantly higher in patients with CKD than HC (P < .01). ROTEM maximum clot firmness was significantly higher in patients than in HC (P < .01). In CKD Stage 5 patients (pre-HD and started HD) adenosine diphosphate and thrombin receptor activating peptide MEA tests were significantly lower than HC indicating platelet aggregation defect (P < .05). Multivariate analysis confirmed the direct effect of estimated glomerular filtration rate (eGFR) in the variance of ROTEM and MEA tests. Endogenous thrombin potential and peak thrombin were not statistically different between groups, but Stage 5 CKD patients had prolonged lag time (7.91 vs. 6.33, P < .001) and time to thrombin peak (10.8 vs. 9.5, P < .05) compared to HC. CONCLUSIONS: Patients with CKD exhibit features of concomitant hypercoagulability measured by ROTEM and platelet dysfunction measured with MEA. eGFR was an independent determinant of platelet dysfunction and hypercoagulability.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Trombofilia , Testes de Coagulação Sanguínea , Estudos Transversais , Feminino , Hemostasia , Humanos , Molécula 1 de Adesão Intercelular , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Tromboelastografia , Trombina , Trombofilia/diagnóstico , Trombofilia/etiologia
8.
J Appl Lab Med ; 7(3): 794-802, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35060606

RESUMO

BACKGROUND: One of the most complex risk factors for the laboratory assessment of thrombophilia is Protein S (PS). The testing algorithm for PS employs the plasma-based assays of free PS antigen, total PS antigen, and PS activity creating a complex diagnostic scheme that can lead to misdiagnosis if incorrectly used, and a potential waste of resources and money. CONTENT: This paper compares the recently published evidence-based algorithm from the International Society for Hemostasis and Thrombosis (ISTH) with several commonly performed nonevidence-based testing schemes, to demonstrate the efficiency of the evidence-based algorithm for diagnostic efficiency with improved patient care and increased cost savings for the laboratory. SUMMARY: Significant savings (31%-60%) can be realized when the evidence-based algorithm is used in place of other testing modalities of initial PS activity testing (31%) or testing with all 3 assays simultaneously (60%). This study utilizing the PS testing evidence-based algorithm as part of a thrombophilia evaluation demonstrates that the appropriate testing methods can be used to limit wasteful practices while achieving the maximum level of information in this time of limited resources and need for increase monetary savings.


Assuntos
Proteína S , Trombofilia , Algoritmos , Análise Custo-Benefício , Humanos , Proteína S/metabolismo , Fatores de Risco , Trombofilia/diagnóstico , Trombofilia/etiologia , Trombofilia/metabolismo
9.
J Hepatol ; 76(5): 1090-1099, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35066090

RESUMO

BACKGROUND & AIMS: It has been suggested that the ratio of procoagulant factor VIII to anticoagulant protein C (FVIII/PC) reflects the hemostatic equilibrium. Moreover, FVIII/PC predicted decompensation/death in a small study not accounting for portal hypertension severity. We investigated (i) the prognostic value of FVIII/PC (outcome-cohort) and (ii) whether FVIII/PC reflects the hypercoagulable state (assessed by thrombomodulin-modified thrombin generation assay [TM-TGA]) or the risk of bleeding/thrombotic events in patients undergoing hepatic venous pressure gradient (HVPG) measurement during follow-up. METHODS: (i) The outcome-cohort comprised 576 patients with evidence of advanced chronic liver disease (liver stiffness measurement ≥10 kPa and/or HVPG ≥6 mmHg). (ii) TM-TGA-cohort patients (n = 142) were recruited from the prospective VIenna CIrrhosis Study (VICIS: NCT03267615). RESULTS: (i) FVIII/PC significantly increased across clinical stages (p <0.001) as well as HVPG (p <0.001) and MELD score (p <0.001) strata and remained independently associated with decompensation/liver-related death (adjusted hazard ratio 1.06; 95% CI 1.01-1.11; p = 0.013), even after multivariable adjustment. It was also associated with acute-on-chronic liver failure (ACLF) development (adjusted hazard ratio 1.10; 95% CI 1.02-1.19; p = 0.015) in patients with decompensated cirrhosis. (ii) FVIII/PC showed a weak positive correlation with endogenous thrombin potential (Spearman's ρ = 0.255; p = 0.002), but this association disappeared after adjusting for the severity of liver disease. FVIII/PC was not associated with the development of bleeding (p = 0.272) or thrombotic events (p = 0.269). However, FVIII/PC correlated with biomarkers of different pathophysiological mechanisms that promote liver disease progression. CONCLUSION: FVIII/PC provides prognostic information regarding hepatic decompensation/death and ACLF, independently of established prognostic indicators. However, this is not evidence that hypercoagulability drives disease progression, as the correlation between FVIII/PC and thrombin generation is confounded by liver disease severity and FVIII/PC was not associated with thrombosis. Therefore, FVIII/PC does not reflect coagulation and results from previous studies on FVIII/PC require re-interpretation. CLINICAL TRIAL NUMBER: NCT03267615 (in part). LAY SUMMARY: A balanced coagulation system is essential for preventing bleeding episodes and blood clot formation (thrombosis). Blood of patients with advanced liver disease may have increased coagulation potential, possibly promoting the worsening of liver disease via thrombosis in the blood vessels of the liver. The ratio between the results of 2 blood tests (procoagulant factor VIII to anticoagulant protein C) has been suggested to reflect these increases in coagulation potential. Our study demonstrates, on the one hand, that this ratio is a versatile predictor of the development of complications of cirrhosis, yet on the other hand, that it is unrelated to coagulation.


Assuntos
Insuficiência Hepática Crônica Agudizada , Trombofilia , Insuficiência Hepática Crônica Agudizada/complicações , Anticoagulantes , Progressão da Doença , Fator VIII/metabolismo , Humanos , Cirrose Hepática/complicações , Estudos Prospectivos , Proteína C/metabolismo , Trombina , Trombofilia/diagnóstico , Trombofilia/etiologia
10.
Ren Fail ; 44(1): 34-42, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35094650

RESUMO

INTRODUCTION: Thrombosis of fistula occurs most frequently in end-stage kidney disease (ESKD) patients receiving hemodialysis. However, the role of thrombophilia in arteriovenous fistula (AVF) failure has not been well established. Hence, this study was aimed at assessing the roles of hereditary and acquired thrombophilic factors in association with AVF failure among patients with ESKD undergoing hemodialysis. METHODS: A cross-sectional study was conducted on 100 ESKD patients, of whom 50 patients with well-functioning AVFs with no fistula failures earlier were enrolled as Group 1, and 50 patients who have had AVF failure were enrolled as Group 2. The hereditary factors as factor V Leiden, factor XIII, prothrombin, and methylene tetrahydrofolate reductase and the acquired factors as lipoprotein (a), fibrinogen, homocysteine, and anticardiolipin antibodies IgG and IgM were studied. RESULTS: Among the hereditary factors, no statistically significant difference was observed in relation to factor V Leiden and Prothrombin (p > 0.05). However, for factor XIII and methylene tetrahydrofolate reductase, a statistically significant difference was observed between patients with well-functioning AVFs and patients who have had AVF failure (p < 0.05). We found a statistically significant increase in all the acquired factors in patients who have had AVF failure in comparison with patients with well-functioning AVFs (p < 0.001). Association between ABO blood groups and thrombophilic factors showed significant association between factor V Leiden, anticardiolipin antibody IgG and IgM and ABO blood groups (p < 0.05), whereas none of the other thrombophilic factors showed significant association (p > 0.05). CONCLUSION: Thus, our study suggests significant role of acquired factors in causing AVF failure.


Assuntos
Sistema ABO de Grupos Sanguíneos , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Trombofilia/etiologia , Adulto , Fístula Arteriovenosa/etiologia , Estudos Transversais , Fator V/análise , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombofilia/genética , Trombose/etiologia
11.
PLoS One ; 17(1): e0262600, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35030224

RESUMO

In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.


Assuntos
Coagulação Sanguínea , COVID-19/sangue , Tromboelastografia , Trombofilia/sangue , Adulto , Idoso , Algoritmos , COVID-19/complicações , COVID-19/diagnóstico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Trombofilia/diagnóstico , Trombofilia/etiologia , Adulto Jovem
12.
Microvasc Res ; 140: 104310, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979154

RESUMO

Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.


Assuntos
COVID-19/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Endotélio Vascular/patologia , Microcirculação , Pandemias , SARS-CoV-2 , Trombofilia/etiologia , Albuminúria/etiologia , COVID-19/complicações , Permeabilidade Capilar , Atenção à Saúde , Angiopatias Diabéticas/complicações , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/complicações , Neuropatias Diabéticas/fisiopatologia , Retinopatia Diabética/complicações , Retinopatia Diabética/fisiopatologia , Endotélio Vascular/lesões , Humanos , Obesidade/complicações , Obesidade/fisiopatologia , Circulação Pulmonar , Edema Pulmonar/etiologia , Edema Pulmonar/fisiopatologia , Índice de Gravidade de Doença , Trombofilia/fisiopatologia , Resultado do Tratamento
13.
J Mol Cell Cardiol ; 164: 69-82, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34838588

RESUMO

The global propagation of SARS-CoV-2 leads to an unprecedented public health emergency. Despite that the lungs are the primary organ targeted by COVID-19, systemic endothelial inflammation and dysfunction is observed particularly in patients with severe COVID-19, manifested by elevated endothelial injury markers, endotheliitis, and coagulopathy. Here, we review the clinical characteristics of COVID-19 associated endothelial dysfunction; and the likely pathological mechanisms underlying the disease including direct cell entry or indirect immune overreactions after SARS-CoV-2 infection. In addition, we discuss potential biomarkers that might indicate the disease severity, particularly related to the abnormal development of thrombosis that is a fatal vascular complication of severe COVID-19. Furthermore, we summarize clinical trials targeting the direct and indirect pathological pathways after SARS-CoV-2 infection to prevent or inhibit the virus induced endothelial disorders.


Assuntos
COVID-19/patologia , Endotélio Vascular/patologia , SARS-CoV-2 , Adolescente , Adulto , Idoso , Enzima de Conversão de Angiotensina 2/fisiologia , Animais , COVID-19/sangue , COVID-19/complicações , COVID-19/fisiopatologia , COVID-19/terapia , Ensaios Clínicos como Assunto , Células Endoteliais/patologia , Células Endoteliais/virologia , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Proteína HMGB1/fisiologia , Humanos , Macaca mulatta , Camundongos , Neuropilina-1/fisiologia , Estresse Oxidativo , Espécies Reativas de Oxigênio , Receptores Virais/fisiologia , Receptores Depuradores Classe B/fisiologia , Índice de Gravidade de Doença , Transdução de Sinais , Síndrome de Resposta Inflamatória Sistêmica/patologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Trombofilia/etiologia , Trombofilia/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Vasculite/etiologia , Vasculite/imunologia , Vasculite/fisiopatologia , Adulto Jovem
14.
Br J Haematol ; 196(4): 902-922, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34888860

RESUMO

In 145 previously healthy non-critically ill young adults, coronavirus disease 2019 (COVID-19)-related symptoms, risk factors for thrombosis, coagulation and inflammatory parameters were compared, with 29 patients reporting unusual thrombotic events (UTEs) and 116 not having thrombotic events. The inflammatory indices, coagulation and prothrombotic platelet phenotype (PTPP) were significantly higher in patients with UTEs versus those without. Patients with UTEs were categorised according to detection of thrombophilic genes (TGs), coagulation and inflammatory markers to the non-TG and TG subcohort. A total of 38 UTEs were identified, which included splanchnic vein thrombosis (SVT; 11), stroke (six), cerebral vein thrombosis (five), thrombotic microangiopathy (four), limb ischaemia and inferior vena cava thrombosis (three each), ST-segment elevation myocardial infarction (two), superior vena cava thrombosis (two), upper limb deep venous thrombosis and retinal vein thrombosis, one each. We found a 55% prevalence of TGs mainly heterozygous coagulation factor II, thrombin (FII)-G20210A, Janus kinase 2 (JAK2)-V617F, protein-S, and antithrombin III deficiency with a high (76·9%) prevalence of venous UTEs, multiple vessels thrombosis, and recurrence rate among the TG versus non-TG subcohort. The presence of JAK2-V617F, and FII-G20210A mutations was linked with SVT. Thrombosis in the non-TG subcohort was associated with more haemorrhagic problems, thrombosis progression and a significantly higher level of inflammatory markers, PTPP, mean platelet volume, von Willebrand factor, and factor VIII, which remained high for up to 6 months, as well as elevated D-dimer. Acquired and inherited thrombophilia with endotheliopathy appeared to be a relevant mechanism to explain the occurrence of UTEs that are not correlated to COVID-19 severity.


Assuntos
COVID-19/complicações , Trombofilia/diagnóstico , Trombose/diagnóstico , Plaquetas/patologia , COVID-19/diagnóstico , Fator VIII/análise , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Trombofilia/etiologia , Trombose/etiologia , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Adulto Jovem , Fator de von Willebrand/análise
16.
J Thromb Thrombolysis ; 53(3): 646-662, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34581945

RESUMO

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 µg/mL (IQR 0.6, 1.4) (p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p = 0.02), PT clot acceleration (min 2) 3.6%/s2 (IQR 3.2, 4.5) (p = 0.02) and PT clot deceleration (max2) 2.9%/s2 (IQR 2.5, 3.5) (p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.


Assuntos
COVID-19 , Hemostáticos , Trombofilia , Trombose , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , COVID-19/complicações , Fator VIII , Fibrinogênio/análise , Humanos , Estudos Prospectivos , Tromboelastografia , Trombofilia/diagnóstico , Trombofilia/etiologia , Trombose/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Fator de von Willebrand
18.
J Clin Gastroenterol ; 56(3): e222-e226, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34231498

RESUMO

GOAL: The aim was to assess whether thrombophilia significantly contributes to the risk of venous thromboembolic events (VTEs) in patients with inflammatory bowel disease (IBD). BACKGROUND: Patients with IBD have a high risk of VTE. The underlying mechanism has been only partially defined. METHODS: A case-control study in adults with IBD and an episode of VTE (IBD-VTE) were matched and compared with non-IBD patients with a VTE (non-IBD-VTE). The study population was comprised of patients seen in 2 tertiary medical centers in Israel between 2000 and 2013. Characteristics of IBD and risk factors for VTE were retrieved from medical charts, and a comprehensive thrombophilia panel was completed in all patients. RESULTS: Forty-four IBD-VTE cases (27 Crohn's disease) were matched with 127 non-IBD-VTE controls. The majority of VTE had a clear etiology and were considered provoked events. Provoked and unprovoked VTE rates were not different between the 2 groups. Likewise, thrombophilia rates were similar among patients with IBD-VTE and controls (40.9% vs. 53.5%, respectively, P=0.14). However, among patients with unprovoked VTE, thrombophilia rates were significantly lower in the IBD-VTE group compared with controls (42.1% vs. 70.7%, respectively, P=0.03). Among patients with IBD-VTE, an unprovoked event, and negative thrombophilia, 77% had active inflammation at the time of VTE. CONCLUSION: Thrombophilia rates are similar among patients with IBD-VTE and controls but are less common among patients with unprovoked IBD-VTE. This finding suggests that either inflammation or other novel pathways drive VTE in patients with IBD.


Assuntos
Doenças Inflamatórias Intestinais , Trombofilia , Tromboembolia Venosa , Trombose Venosa , Adulto , Estudos de Casos e Controles , Humanos , Doenças Inflamatórias Intestinais/complicações , Fatores de Risco , Trombofilia/complicações , Trombofilia/etiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
19.
J Endocrinol Invest ; 45(1): 9-16, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34115342

RESUMO

OBJECTIVE: Patients with Cushing's syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. DESIGN AND METHODS: Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6 months and (iii) 5 years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. RESULTS: Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5 years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). CONCLUSIONS: Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients.


Assuntos
Testes de Coagulação Sanguínea/métodos , Síndrome de Cushing , Hidrocortisona/sangue , Trombina/análise , Trombofilia , Tromboembolia Venosa , Adrenalectomia/métodos , Adulto , Coagulação Sanguínea , Síndrome de Cushing/sangue , Síndrome de Cushing/complicações , Síndrome de Cushing/cirurgia , Feminino , Humanos , Hipofisectomia/métodos , Masculino , Período Pós-Operatório , Indução de Remissão , Medição de Risco/métodos , Trombofilia/sangue , Trombofilia/etiologia , Tempo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
20.
Surgery ; 171(4): 1092-1099, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35090739

RESUMO

OBJECTIVES: We evaluated rotational thromboelastometry tracings in 44 critically ill coronavirus disease 2019 patients, to determine whether there is a viscoelastic fingerprint and to test the hypothesis that the diagnosis and prediction of venous thromboembolism would be enhanced by the addition of rotational thromboelastometry testing. RESULTS: Rotational thromboelastometry values reflected an increase in clot strength for the EXTEM, INTEM, and FIBTEM assays beyond the reference range. No hyperfibrinolysis was noted. Fibrinolysis shutdown was present but did not correlate with thrombosis; 32% (14/44) of patients experienced a thrombotic episode. For every 1 mm increase of FIBTEM maximum clot formation, the odds of developing thrombosis increased 20% (95% confidence interval, 0-40%, P = .043), whereas for every 1,000 ng/mL increase in D-dimer, the odds of thrombosis increased by 70% (95% confidence interval, 20%-150%, P = .004), after adjustment for age and sex (AUC 0.96, 95% confidence interval, 0.90-1.00). There was a slight but significant improvement in model performance after adding FIBTEM maximum clot formation and EXTEM clot formation time to D-dimer in a multivariable model (P = .04). CONCLUSIONS: D-dimer concentrations were more predictive of thrombosis in our patient population than any other parameter. Rotational thromboelastometry confirmed the hypercoagulable state of coronavirus disease 2019 intensive care unit patients. FIBTEM maximum clot formation and EXTEM clot formation time increased the predictability for thrombosis compared with only using D-dimer. Rotational thromboelastometry analysis is most useful in augmenting the information provided by the D-dimer concentration for venous thromboembolism risk assessment when the D-dimer concentration is between 1,625 and 6,900 ng/dL, but the enhancement is modest. Fibrinolysis shutdown did not correlate with thrombosis.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Trombofilia , Trombose , COVID-19/complicações , COVID-19/diagnóstico , Humanos , Tromboelastografia , Trombofilia/diagnóstico , Trombofilia/etiologia , Trombose/diagnóstico , Trombose/etiologia
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