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1.
BMJ Case Rep ; 14(5)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039554

RESUMO

COVID-19 is an infectious disease caused by the novel coronavirus. It presents as an acute respiratory illness, however, it also affects multiple other organ systems. One such unique manifestation is systemic coagulopathy involving arterial and venous systems. We present a 29-year-old woman with Hodgkin's lymphoma, who was diagnosed with COVID-19 infection prior to initiating chemotherapy. Two months after resolution of symptoms and testing negative for COVID-19, she presented with multiple acute thromboembolic complications of the infection, including bilateral jugular venous thrombosis, right atrial clot and arterial emboli in the brain resulting in cerebrovascular injury. These were thought to be delayed manifestations of the systemic coagulopathy secondary to infection. Also, some of these thromboembolic phenomena occurred while the patient was on anticoagulation, which emphasises the extensive hyperinflammatory state caused by the virus. This case highlights the importance of thromboprophylaxis especially in high-risk patients with this infection.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Tromboembolia Venosa , Adulto , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Feminino , Humanos , SARS-CoV-2
2.
Am J Case Rep ; 22: e930667, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33967265

RESUMO

BACKGROUND Coronavirus Disease 2019 (COVID-19) has been associated with a hypercoagulability state. Clinical presentation can range from asymptomatic to severe illness and mortality. Thrombotic complications in COVID-19 have been associated with mortality. The incidence of systemic hypercoagulation in COVID-19 is associated with the process of severe inflammation. The majority of severely ill patients have developed coagulopathy, and this condition is associated with poor outcomes. CASE REPORT A 72-year-old man presented with respiratory symptoms and was diagnosed with a COVID-19 infection. He presented with tachypnea, tachycardia, increased blood pressure, and 74% peripheral oxygen saturation under 15 L/min oxygen per non-rebreather mask. Initial laboratory test results showed severe hypoxemia as per blood gas analysis (pH 7.42, pCO2 23 mmHg, pO2 43 mmHg, HCO3 15 mmol/L, base deficit -9 mmol/L), with increased procalcitonin, high-sensitivity C-reactive protein, D-dimer, fibrinogen, creatine kinase myocardial band, and Troponin I. He subsequently developed thrombosis of the pulmonary arteries and multiple branches of the pulmonary vein despite therapeutic anticoagulation. We initiated heparin therapy (average dose 25 191 units per day, mean activated partial thromboplastin time, 64.35 seconds). Radiological investigations revealed multiple thromboses on pulmonary arteries and pulmonary veins, as well as multiple locations of brain infarction. Rescue thrombolytic therapy was given, but unfortunately, the patient died due to multiple end-organ failures. CONCLUSIONS Controlling coagulopathy, and thrombolytic therapy type and timing, are critical issues, and new strategies must be sought to lower its morbidity and mortality rates further.


Assuntos
Transtornos da Coagulação Sanguínea , Idoso , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Humanos , Masculino , Terapia Trombolítica
3.
BMJ Case Rep ; 14(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795273

RESUMO

Acute intoxication with a vitamin K antagonist may cause serious coagulopathy. We report the accidental ingestion of a high dose of acenocoumarol in a young child. Two intravenous administrations of 5 mg of vitamin K, in combination with fast and repeated administration of activated charcoal and sodium sulfate, were sufficient to prevent coagulopathy and related symptoms, despite a confirmed elevated blood acenocoumarol concentration (260 µg/L).


Assuntos
Acenocumarol , Transtornos da Coagulação Sanguínea , Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/induzido quimicamente , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Criança , Ingestão de Alimentos , Humanos , Vitamina K
4.
Res Vet Sci ; 136: 472-477, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33838456

RESUMO

Primary hyperfibrinolysis is not well characterised in canine cancer. This prospective case-control pilot study aimed to evaluate tissue plasminogen activator-modified thromboelastography (tPA-TEG) for diagnosis of primary hyperfibrinolysis in dogs with cancer and establish the in vitro therapeutic concentration of tranexamic acid (TXA). Nine dogs with sarcomas and normocoagulable thromboelastograms and 11 healthy dogs were included. For each a whole blood tPA-TEG, and four tPA-TEGs with added TXA in different concentrations were analysed. Lysis percentage at 30/60 min following maximal amplitude (LY30/60), clot lysis index (CL30/60), maximum rate of lysis (MRL), and total lysis (L) were investigated as diagnostic parameters of primary hyperfibrinolysis. In vitro TXA concentrations needed to inhibit 50% (IC50) and 90% (IC90) of the fibrinolytic potential were compared between groups. Significant primary hyperfibrinolysis (LY30 (P = 0.0001), LY60 (P = 0.003), CL30 (P = 0.01), and L (P = 0.02)) was observed in dogs with sarcomas. IC50 and IC90 of in vitro TXA for normalizing LY30 were 13.34 (SE 1.52) and 31.10 (SE 3.01) mg/L for dogs with sarcomas and 4.41 (SE 5.84) and 20.00 (SE 6.18) mg/L for healthy dogs. IC50 and IC90 for normalizing LY60 were 22.18 (SE 1.27) and 58.94 (SE 5.47) mg/L for dogs with sarcomas and 11.25 (SE 2.82) and 56.20 (SE 11.61) mg/L for healthy dogs. The IC50 for LY60 was significantly increased for dogs with sarcomas (P = 0.0003). Primary hyperfibrinolysis was documented by tPA-TEG in dogs with sarcomas. In vitro IC50 and IC90 for TXA were established. Clinical studies are required to establish therapeutic dosages in vivo.


Assuntos
Antifibrinolíticos/uso terapêutico , Transtornos da Coagulação Sanguínea/veterinária , Doenças do Cão/tratamento farmacológico , Fibrinólise/efeitos dos fármacos , Sarcoma/veterinária , Ácido Tranexâmico/uso terapêutico , Animais , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Testes de Coagulação Sanguínea/veterinária , Estudos de Casos e Controles , Cães , Feminino , Masculino , Projetos Piloto , Estudos Prospectivos , Sarcoma/complicações , Tromboelastografia/veterinária , Ativador de Plasminogênio Tecidual
5.
Ned Tijdschr Geneeskd ; 1652021 03 25.
Artigo em Holandês | MEDLINE | ID: mdl-33793123

RESUMO

Tranexamic acid is a cheap and easy to use drug for the treatment and prevention of bleeding. In the past, its use was mainly empiric and primarily in patients with coagulation disorders. More recently, large scale randomized controlled trials have shown that tranexamic acid reduces mortality in women with postpartum hemorrhage and in victims of trauma. In a number of surgical settings, including cardiothoracic and orthopedic, tranexamic acid reduces bleeding complications. In these studies, there was no signal of increased risk of thrombosis. Tranexamic acid is also effective in reducing heavy menstrual bleeding, the prevention of bleeding after dental interventions and a number of other high-prevalence conditions. There are no data that support an increased risk of thrombosis when patients without haemostatic disorders use tranexamic acid for a longer period, but addition studies would be helpful. Finally, the topical administration of the drug for mucocutaneous nuisance bleeds deserves more attention.


Assuntos
Antifibrinolíticos/uso terapêutico , Hemorragia/tratamento farmacológico , Técnicas Hemostáticas/tendências , Ácido Tranexâmico/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Feminino , Humanos , Masculino , Gravidez
6.
Sci Rep ; 11(1): 6515, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753759

RESUMO

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Cardiopatias/diagnóstico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Proteína C-Reativa/análise , /mortalidade , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Cardiopatias/etiologia , Hemodinâmica , Heparina de Baixo Peso Molecular/uso terapêutico , Mortalidade Hospitalar , Humanos , Inflamação , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Risco , Troponina T/sangue
7.
Trials ; 22(1): 202, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691765

RESUMO

OBJECTIVES: To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days. TRIAL DESIGN: Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial PARTICIPANTS: The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have already have any component of the primary composite outcome. Participants are recruited from hospital sites in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and the United States of America. The inclusion criteria are: 1) Laboratory confirmed COVID-19 (diagnosis of SARS-CoV-2 via reverse transcriptase polymerase chain reaction as per the World Health Organization protocol or by nucleic acid based isothermal amplification) prior to hospital admission OR within first 5 days (i.e. 120 hours) after hospital admission; 2) Admitted to hospital for COVID-19; 3) One D-dimer value above the upper limit of normal (ULN) (within 5 days (i.e. 120 hours) of hospital admission) AND EITHER: a. D-Dimer ≥2 times ULN OR b. D-Dimer above ULN and Oxygen saturation ≤ 93% on room air; 4) > 18 years of age; 5) Informed consent from the patient (or legally authorized substitute decision maker). The exclusion criteria are: 1) pregnancy; 2) hemoglobin <80 g/L in the last 72 hours; 3) platelet count <50 x 109/L in the last 72 hours; 4) known fibrinogen <1.5 g/L (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 5) known INR >1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 6) patient already prescribed intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high risk patients into consideration); 7) patient already prescribed therapeutic anticoagulation at the time of screening [low or high dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran, apixaban, rivaroxaban, edoxaban)]; 8) patient prescribed dual antiplatelet therapy, when one of the agents cannot be stopped safely; 9) known bleeding within the last 30 days requiring emergency room presentation or hospitalization; 10) known history of a bleeding disorder of an inherited or active acquired bleeding disorder; 11) known history of heparin-induced thrombocytopenia; 12) known allergy to UFH or LMWH; 13) admitted to the intensive care unit at the time of screening; 14) treated with non-invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening; 15) Imminent death according to the judgement of the most responsible physician; 16) enrollment in another clinical trial of antithrombotic therapy involving hospitalized patients. INTERVENTION AND COMPARATOR: Intervention: Therapeutic dose of LMWH (dalteparin, enoxaparin, tinzaparin) or high dose nomogram of UFH. The choice of LMWH versus UFH will be at the clinician's discretion and dependent on local institutional supply. Comparator: Standard care [thromboprophylactic doses of LMWH (dalteparin, enoxaparin, tinzaparin, fondaparinux)] or UFH. Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is generally considered standard care. MAIN OUTCOMES: The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Secondary outcomes include (evaluated up to day 28): 1. All-cause death 2. Composite of ICU admission or all-cause death 3. Composite of mechanical ventilation or all-cause death 4. Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation; 5. Red blood cell transfusion (>1 unit); 6. Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate; 7. Renal replacement therapy; 8. Hospital-free days alive; 9. ICU-free days alive; 10. Ventilator-free days alive; 11. Organ support-free days alive; 12. Venous thromboembolism (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 13. Arterial thromboembolism (defined as suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 14. Heparin induced thrombocytopenia; 15. Trajectories of COVID-19 disease-related coagulation and inflammatory biomarkers. RANDOMISATION: Randomisation will be stratified by site and age (>65 versus ≤65 years) using a 1:1 computer-generated random allocation sequence with variable block sizes. Randomization will occur within the first 5 days (i.e. 120 hours) of participant hospital admission. However, it is recommended that randomization occurs as early as possible after hospital admission. Central randomization using an interactive web response system will ensure allocation concealment. BLINDING (MASKING): No blinding involved. This is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 462 patients (231 per group) are needed to detect a 15% risk difference, from 50% in the control group to 35% in the experimental group, with power of 90% at a two-sided alpha of 0.05. TRIAL STATUS: Protocol Version Number 1.4. Recruitment began on May 11th, 2020. Recruitment is expected to be completed March 2022. Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04362085 Date of Trial Registration: April 24, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , /tratamento farmacológico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , /complicações , Ensaios Clínicos Fase III como Assunto , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Hospitalização , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Ventilação não Invasiva/estatística & dados numéricos , Ensaios Clínicos Pragmáticos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/estatística & dados numéricos
8.
Pediatr Blood Cancer ; 68(7): e28975, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33661561

RESUMO

We report the clinical and laboratory coagulation characteristics of 27 pediatric and young adult patients (2 months to 21 years) treated for symptomatic COVID-19 at a children's hospital in the Bronx, New York, between March 1 and May 31, 2020. D-Dimer was > 0.5 µg/mL (upper limit of normal) in 25 (93%) patients at admission; 11 (41%) developed peak D-dimer > 5 µg/mL during admission. Seven (26%) patients developed venous thromboembolism: three with deep vein thrombosis and four with pulmonary embolism. Requirement of increased ventilatory support was a risk factor for thrombosis (P = 0.006). Three of eight (38%) patients on prophylactic anticoagulation developed thrombosis; however, no patients developed VTE on low-molecular-weight heparin prophylaxis titrated to anti-Xa level. Manifestation of COVID-19 disease was severe or critical in 16 (59%) patients. Four (15%) patients died of COVID-19 complications: all had comorbidities. Elevated D-dimer and increased VTE rate were observed in this young cohort, particularly in those with severe respiratory complications, suggesting thrombotic coagulopathy. More data are needed to guide thromboprophylaxis in this age group.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/epidemiologia , Hospitalização/estatística & dados numéricos , Tromboembolia Venosa/epidemiologia , Adolescente , Adulto , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/virologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , New York/epidemiologia , Fatores de Risco , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/virologia , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-33572570

RESUMO

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease. Bilateral pneumonia, acute respiratory failure, systemic inflammation, endothelial dysfunction and coagulation activation are key features of severe COVID-19. Fibrinogen and D-dimer levels are typically increased. The risk for venous thromboembolism is markedly increased, especially in patients in the intensive care unit despite prophylactic dose anticoagulation. Pulmonary microvascular thrombosis has also been described and the risk for arterial thrombotic diseases also appears to be increased while bleeding is less common than thrombosis, but it can occur. Evaluation for venous thromboembolism may be challenging because symptoms of pulmonary embolism overlap with COVID-19, and imaging studies may not be feasible in all cases. The threshold for evaluation or diagnosis of thromboembolism should be low given the high frequency of these events. Management and treatment are new challenges due to the paucity of high-quality evidence regarding efficacy and safety of different approaches to prevent or treat thromboembolic complications of the disease. All inpatients should receive thromboprophylaxis unless contraindicated. Some institutional protocols provide more aggressive anticoagulation with intermediate or even therapeutic dose anticoagulation for COVID-19 patients admitted to ICU. Therapeutic dose anticoagulation is always appropriate to treat deep venous thrombosis or pulmonary embolism, unless contraindicated. This article reviews evaluation and management of coagulation abnormalities in individuals with COVID-19.


Assuntos
Transtornos da Coagulação Sanguínea , Gestão de Riscos , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Humanos , Tromboembolia Venosa/complicações , Tromboembolia Venosa/tratamento farmacológico
10.
Heart Lung ; 50(2): 357-360, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33524866

RESUMO

COVID-19-associated coagulopathy (CAC) is a feature of COVID-19 that can lead to various thrombotic complications and death. In this review, we briefly highlight possible etiologies, including direct cytotoxicity caused by the SARS-CoV-2 virus, and the activation of proinflammatory molecules such as cytokines, underlying coagulopathy. Endothelial dysfunction has been highlighted as pivotal, irrespective of the mechanism involved in CAC. Specific features of CAC distinguishing it from disseminated intravascular coagulopathy and sepsis or ARDS-associated coagulopathy have been discussed. We have also highlighted some hematological parameters, such as elevated d-dimers and partial prothrombin and prothrombin times prolongation, which can guide the use of anticoagulation in critically ill patients. We conclude by highlighting the importance of prophylactic anticoagulation in all COVID-19 hospitalized patients and reiterate the need for institution-specific guidelines for anticoagulation COVID-19 patients since individual institutions have different patient populations.


Assuntos
Transtornos da Coagulação Sanguínea , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos
11.
Ann Intern Med ; 174(5): 622-632, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33493012

RESUMO

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.


Assuntos
Anticoagulantes/administração & dosagem , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/virologia , COVID-19/complicações , Idoso , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/mortalidade , COVID-19/mortalidade , Estado Terminal , Feminino , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Hemorragia/virologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Taxa de Sobrevida , Estados Unidos/epidemiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/virologia
12.
Cardiol Rev ; 29(1): 43-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32947478

RESUMO

The novel coronavirus (severe acute respiratory syndrome CoV-2 [SARS-CoV-2]), also known as COVID-19, is a single-stranded enveloped RNA virus that created a Public Health Emergency of International Concern in January 2020, with a global case burden of over 15 million in just 7 months. Infected patients develop a wide range of clinical manifestations-typically presenting with fever, cough, myalgia, and fatigue. Severely ill patients may fall victim to acute respiratory distress syndrome, acute heart injuries, neurological manifestations, or complications due to secondary infections. These critically ill patients are also found to have disrupted coagulation function, predisposing them to consumptive coagulopathies, and both venous and thromboembolic complications. Common laboratory findings include thrombocytopenia, elevated D-dimer, fibrin degradation products, and fibrinogen, all of which have been associated with greater disease severity. Many cases of pulmonary embolism have been noted, along with deep vein thrombosis, ischemic stroke, myocardial infarction, and systemic arterial embolism. The pathogenesis of coronavirus has not been completely elucidated, but the virus is known to cause excessive inflammation, endothelial injury, hypoxia, and disseminated intravascular coagulation, all of which contribute to thrombosis formation. These patients are also faced with prolonged immobilization while staying in the hospital or intensive care unit. It is important to have a high degree of suspicion for thrombotic complications as patients may rapidly deteriorate in severe cases. Evidence suggests that prophylaxis with anticoagulation may lead to a lower risk of mortality, although it does not eliminate the possibility. The risks and benefits of anticoagulation treatment should be considered in each case. Patients should be regularly evaluated for bleeding risks and thrombotic complications.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Embolia/sangue , Trombose/sangue , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/metabolismo , /tratamento farmacológico , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/metabolismo , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/metabolismo , Coagulação Intravascular Disseminada/prevenção & controle , Embolia/etiologia , Embolia/metabolismo , Embolia/prevenção & controle , Endotélio Vascular/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Hipóxia/sangue , Hipóxia/etiologia , Hipóxia/metabolismo , Imobilização , Inflamação/sangue , Inflamação/etiologia , Inflamação/metabolismo , /etiologia , /prevenção & controle , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/prevenção & controle , Guias de Prática Clínica como Assunto , Embolia Pulmonar/sangue , Embolia Pulmonar/etiologia , Embolia Pulmonar/metabolismo , Embolia Pulmonar/prevenção & controle , Índice de Gravidade de Doença , Trombocitopenia/sangue , Trombocitopenia/etiologia , Trombose/etiologia , Trombose/metabolismo , Trombose/prevenção & controle , Trombose Venosa/sangue , Trombose Venosa/etiologia , Trombose Venosa/metabolismo
13.
Eur Rev Med Pharmacol Sci ; 24(23): 12466-12479, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33336766

RESUMO

OBJECTIVE: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated. PATIENTS AND METHODS: Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg·kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days. RESULTS: At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5); TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1.09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mg·dl-1 (303.5 to 605)], and D-dimer levels [1752.5 ng·ml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p  = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02). CONCLUSIONS: SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelastographic abnormalities persist despite full-dose anticoagulation.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/sangue , /sangue , Tromboelastografia , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/sangue , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Testes de Coagulação Sanguínea , Enoxaparina/uso terapêutico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Heparina/uso terapêutico , Humanos , Coeficiente Internacional Normatizado , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Estudos Prospectivos , Resultado do Tratamento
14.
BMJ Case Rep ; 13(12)2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33318272

RESUMO

Viscoelastic monitoring (VEM) tools, such as rotational thrombelastometry, have been used extensively to measure coagulopathy in adults but have received less attention in paediatric care. The presented case involves a 5-year-old boy who was brought to the emergency department after a motor vehicle collision with a Glasgow Coma Scale score of 6T and extensive injuries, including a subdural hematoma. VEM was used to monitor the patient's coagulopathy and to inform treatment measures by allowing real-time visualisation of the patient's coagulation status. VEM was additionally used to direct blood product replacement in preparation for neurosurgical intervention, and 4-factor prothrombin complex concentrate (PCC) was used to help reverse the coagulopathy. The patient underwent successful hemicraniectomy after improvement of his coagulopathy. In paediatrics, VEM and PCC are increasingly being used for post-trauma coagulopathy, and this case highlights their potential promise and the need for further research.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Fatores de Coagulação Sanguínea/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , Hematoma Subdural/complicações , Monitorização Fisiológica/métodos , Acidentes de Trânsito , Transtornos da Coagulação Sanguínea/etiologia , Edema Encefálico/complicações , Edema Encefálico/diagnóstico , Edema Encefálico/cirurgia , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/cirurgia , Pré-Escolar , Craniotomia , Hematoma Subdural/diagnóstico , Hematoma Subdural/cirurgia , Humanos , Masculino
15.
Aging (Albany NY) ; 13(2): 1591-1607, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33318314

RESUMO

Coagulation dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19) has not been well described, and the efficacy of anticoagulant therapy is unclear. In this study, we retrospectively reviewed 75 fatal COVID-19 cases who were admitted to the intensive care unit at Jinyintan Hospital (Wuhan, China). The median age of the cases was 67 (62-74) years, and 47 (62.7%) were male. Fifty patients (66.7%) were diagnosed with disseminated intra-vascular coagulation. Approximately 90% of patients had elevated D-dimer and fibrinogen degradation products, which decreased continuously after anticoagulant treatment and was accompanied by elevated albumin (all P<0.05). The median survival time of patients treated with anticoagulant was 9.0 (6.0-14.0) days compared with 7.0 (3.0-10.0) days in patients without anticoagulant therapy (P=0.008). After anticoagulation treatment, C-reactive protein levels decreased (P=0.004), as did high-sensitivity troponin (P=0.018), lactate dehydrogenase (P<0.001), and hydroxybutyrate dehydrogenase (P<0.001). In conclusion, coagulation disorders were widespread among fatal COVID-19 cases. Anticoagulant treatment partially improved hypercoagulability, prolonged median survival time, and may have postponed inflammatory processes and cardiac injury.


Assuntos
Transtornos da Coagulação Sanguínea/virologia , /complicações , Idoso , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , China , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
BMJ Case Rep ; 13(12)2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33372022

RESUMO

We present a previously healthy man in his 30s who presented with typical viral prodrome symptoms and worsening abdominal pain. He was found to have portal vein thrombosis, with extensive hypercoagulability workup performed. It was determined that the aetiology of thrombus was secondary to acute cytomegalovirus infection. The patient was started on anticoagulation therapy, with later clot resolution demonstrated on abdominal Doppler ultrasound and abdominal CT scan. Given the atypical presentation of this common virus, we performed a literature review of cytomegalovirus-associated portal vein thrombosis in healthy individuals; we found that most patients present with non-specific symptoms of fever and abdominal pain in the setting of a viral prodrome. This case and literature review suggest physicians must consider cytomegalovirus-associated portal vein thrombosis as a potential diagnosis when patients present with abdominal pain and viral symptoms. The literature highlights the need for a consensus on anticoagulation and antiviral therapy.


Assuntos
Infecções por Citomegalovirus/complicações , Veia Porta , Trombose Venosa/virologia , Dor Abdominal/etiologia , Adulto , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/virologia , Angiografia por Tomografia Computadorizada , Infecções por Citomegalovirus/imunologia , Humanos , Imunocompetência , Masculino , Veia Porta/diagnóstico por imagem , Ultrassonografia Doppler , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico
17.
Clin Appl Thromb Hemost ; 26: 1076029620945398, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32883088

RESUMO

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in ECMO devices, all in the face of prophylactic and sometimes even therapeutic anti-coagulation, are frequent features of COVID-19 coagulopathy. The trials available to guide clinicians are methodologically limited. There are several unresolved controversies including 1) Should all hospitalized patients with COVID-19 receive prophylactic anti-coagulation? 2) Which patients should have their dosage escalated to intermediate dose? 3) Which patients should be considered for full-dose anti-coagulation even without a measurable thromboembolic event and how should that anti-coagulation be monitored? 4) Should patients receive post-discharge anti-coagulation? 5) What thrombotic issues are related to the various medications being used to treat this coagulopathy? 6) Is anti-phospholipid anti-body part of this syndrome? 7) How do the different treatments for this disease impact the coagulation issues? The aims of this article are to explore these questions and interpret the available data based on the current evidence.


Assuntos
Anticoagulantes/administração & dosagem , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/epidemiologia , Infecções por Coronavirus/epidemiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/uso terapêutico , Pneumonia Viral/epidemiologia , Tromboembolia Venosa/prevenção & controle , Transtornos da Coagulação Sanguínea/diagnóstico , Estudos de Casos e Controles , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Dexametasona/administração & dosagem , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia , Análise de Sobrevida , Resultado do Tratamento , Tromboembolia Venosa/etiologia
19.
J Thromb Haemost ; 18(9): 2138-2144, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32881336

RESUMO

Hypercoagulability is an increasingly recognized complication of SARS-CoV-2 infection. As such, anticoagulation has become part and parcel of comprehensive COVID-19 management. However, several uncertainties exist in this area, including the appropriate type and dose of heparin. In addition, special patient populations, including those with high body mass index and renal impairment, require special consideration. Although the current evidence is still insufficient, we provide a pragmatic approach to anticoagulation in COVID-19, but stress the need for further trials in this area.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/mortalidade , Transtornos da Coagulação Sanguínea/virologia , Tomada de Decisão Clínica , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Seleção de Pacientes , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Fatores de Risco , Resultado do Tratamento
20.
Inflamm Res ; 69(12): 1181-1189, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32918567

RESUMO

BACKGROUND: COVID-19-associated coagulopathy (CAC) characterized by the elevated D-dimer without remarkable changes of other global coagulation markers is associated with various thrombotic complications and disease severity. The purpose of this review is to elucidate the pathophysiology of this unique coagulopathy. METHODS: The authors performed online search of published medical literature through PubMed using the MeSH (Medical Subject Headings) term "COVID-19," "SARS-CoV-2," "coronavirus," "coagulopathy," and "thrombus." Then, selected 51 articles that closely relevant to coagulopathy in COVID-19. RESULTS: The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the pneumocytes, immune cells, and vascular endothelial cells. The alveolar damage and the pulmonary microvascular thrombosis are the major causes of acute lung injury in COVID-19. The endotheliopathy that occurs is due to direct SARS-CoV-2 infection and activation of other pathways that include the immune system and thromboinflammatory responses leading to what is termed CAC. As a result, both microvascular and macrovascular thrombotic events occur in arterial, capillary, venule, and large vein vascular beds to produce multiorgan dysfunction and thrombotic complications. In addition to the endothelial damage, SARS-CoV-2 also can cause vasculitis and presents as a systemic inflammatory vascular disease. Clinical management of COVID-19 includes anticoagulation but novel therapies for endotheliopathy, hypercoagulability, and vasculitis are needed. CONCLUSION: The endotheliopathy due to direct endothelial infection with SARS-COV-2 and the indirect damage caused by inflammation play the predominant role in the development of CAC. The intensive control of thromboinflammation is necessary to improve the outcome of this highly detrimental contagious disease.


Assuntos
Betacoronavirus , Transtornos da Coagulação Sanguínea/virologia , Infecções por Coronavirus/complicações , Endotélio Vascular/fisiopatologia , Pneumonia Viral/complicações , Vasculite/virologia , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Células Endoteliais , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Pulmão/irrigação sanguínea , Microvasos , Pandemias , Pneumonia Viral/fisiopatologia , PubMed , Embolia Pulmonar , Trombose/virologia
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