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1.
Clin Appl Thromb Hemost ; 26: 1076029620954913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33030036

RESUMO

INTRODUCTION: Sulodexide represents a mixture of fast-moving heparin (FMH) and dermatan sulfate (DS) and has been used for the management of venous diseases such as DVT and related disorders. The purpose of this study is to compare sulodexide and its components with unfractionated heparin (UFH) to determine its suitability for the indications in which UFH is used. MATERIALS AND METHOD: Active pharmaceutical ingredients (API) versions of sulodexide, FMH and DS were obtained from Alfasigma. API versions of UFH were obtained from Medefil Inc. Normal human citrated plasma was obtained from blood bank of the Loyola University Medical Center. Each of the individual agents were supplemented in plasma at a graded concentration of 0.0-10 µg/mL. Clotting assays (PiCT, aPTT, PT and TT), anti-Xa and anti-IIa and thrombin generation studies were carried out. Results were compiled as mean ± SD of 3 individual determination. RESULT: In the clot based (PiCT, aPTT and TT), anti-Xa and IIa assays, both the UFH and FMH produced stronger activities in these assays followed by sulodexide. DS did not show any anticoagulant activity. In the thrombin generation assay, FMH and UFH produced comparable inhibition of thrombin generation as measured by various parameters. Sulodexide was slightly weaker in this assay, whereas DS produced relatively weaker effects. CONCLUSION: In comparison to sulodexide, both UFH and FMH exhibit comparable anticoagulant activity despite differences in their molecular weight. These results suggest that sulodexide can be developed as a parenteral anticoagulant for indications in which UFH is used.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Glicosaminoglicanos/farmacologia , Trombina/farmacologia , Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Antitrombinas/farmacologia , Glicosaminoglicanos/administração & dosagem , Heparina/administração & dosagem , Heparina/farmacologia , Humanos , Itália , Sensibilidade e Especificidade , Trombina/administração & dosagem
2.
Clin Trials ; 17(5): 491-500, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32815416

RESUMO

BACKGROUND: Mortality from COVID-19 is high among hospitalized patients and effective therapeutics are lacking. Hypercoagulability, thrombosis and hyperinflammation occur in COVID-19 and may contribute to severe complications. Therapeutic anticoagulation may improve clinical outcomes through anti-thrombotic, anti-inflammatory and anti-viral mechanisms. Our primary objective is to evaluate whether therapeutic-dose anticoagulation with low-molecular-weight heparin or unfractionated heparin prevents mechanical ventilation and/or death in patients hospitalized with COVID-19 compared to usual care. METHODS: An international, open-label, adaptive randomized controlled trial. Using a Bayesian framework, the trial will declare results as soon as pre-specified posterior probabilities for superiority, futility, or harm are reached. The trial uses response-adaptive randomization to maximize the probability that patients will receive the more beneficial treatment approach, as treatment effect information accumulates within the trial. By leveraging a common data safety monitoring board and pooling data with a second similar international Bayesian adaptive trial (REMAP-COVID anticoagulation domain), treatment efficacy and safety will be evaluated as efficiently as possible. The primary outcome is an ordinal endpoint with three possible outcomes based on the worst status of each patient through day 30: no requirement for invasive mechanical ventilation, invasive mechanical ventilation or death. CONCLUSION: Using an adaptive trial design, the Anti-Thrombotic Therapy To Ameliorate Complications of COVID-19 trial will establish whether therapeutic anticoagulation can reduce mortality and/or avoid the need for mechanical ventilation in patients hospitalized with COVID-19. Leveraging existing networks to recruit sites will increase enrollment and mitigate enrollment risk in sites with declining COVID-19 cases.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Heparina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Trombose/prevenção & controle , Adolescente , Adulto , Anticoagulantes/administração & dosagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Trombose/etiologia , Resultado do Tratamento , Adulto Jovem
3.
Trials ; 21(1): 724, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807241

RESUMO

OBJECTIVES: To assess the hypothesis that an adjunctive therapy with methylprednisolone and unfractionated heparin (UFH) or with methylprednisolone and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill ventilated patients with pneumonia from SARS-CoV-2 infection compared to LMWH alone. TRIAL DESIGN: The study is designed as a multi-centre, interventional, parallel group, superiority, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the three treatment groups in a ratio 1:1:1. PARTICIPANTS: Inpatients will be recruited from 8 Italian Academic and non-Academic Intensive Care Units INCLUSION CRITERIA (ALL REQUIRED): 1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 2. Positive pressure ventilation (either non-invasive or invasive) from > 24 hours 3. Invasive mechanical ventilation from < 96 hours 4. PaO2/FiO2 ratio lower than 150 mmHg 5. D-dimer level > 6 times the upper limit of normal reference range 6. C-reactive Protein > 6-fold upper the limit of normal reference range EXCLUSION CRITERIA: 1. Age < 18 years 2. On-going treatment with anticoagulant drugs 3. Platelet count < 100.000/mm3 4. History of heparin-induced thrombocytopenia 5. Allergy to sodium enoxaparin or other LMWH, UFH or methylprednisolone 6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment 7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery 8. Chronic assumption or oral corticosteroids 9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available 10. Clinical decision to withhold life-sustaining treatment or "too sick to benefit" 11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 12. Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: • LMWH group: patients in this group will be administered enoxaparin at standard prophylactic dosage. • LMWH + steroid group: patients in this group will receive enoxaparin at standard prophylactic dosage and methylprednisolone. • UFH + steroid group: patients in this group will receive UFH at therapeutic dosages and methylprednisolone. UFH will be administered intravenously in UFH + steroid group at therapeutic doses. The infusion will be started at an infusion rate of 18 UI/kg/hour and then modified to obtain aPTT Ratio in between the range of 1.5-2.0. aPTT will be periodically checked at intervals no longer than 12 hours. The treatment with UFH will be administered up to ICU discharge. After ICU discharge anticoagulant therapy may be interrupted or switched to prophylaxis with LMWH in the destination ward up to clinical judgement of the attending physician. Enoxaparin will be administered in both LMWH group and LMWH + steroid group at standard prophylactic dose (i.e., 4000 UI once day, increased to 6000 UI once day for patients weighting more than 90 kg). The treatment will be administered subcutaneously once a day up to ICU discharge. After ICU discharge it may be continued or interrupted in the destination ward up to clinical judgement of the attending physician. Methylprednisolone will be administered in both LMWH + steroid group and UHF + steroid group intravenously with an initial bolus of 0,5 mg/kg followed by administration of 0,5 mg/kg 4 times daily for 7 days, 0,5 mg/kg 3 times daily from day 8 to day 10, 0,5 mg/kg 2 times daily at days 11 and 12 and 0,5 mg/kg once daily at days 13 and 14. MAIN OUTCOMES: Primary Efficacy Endpoint: All-cause mortality at day 28 Secondary Efficacy Endpoints: - Ventilation free days (VFDs) at day 28, defined as the total number of days that patient is alive and free of ventilation (either invasive or non-invasive) between randomization and day 28 (censored at hospital discharge). - Need of rescue administration of high-dose steroids or immune-modulatory drugs; - Occurrence of switch from non-invasive to invasive mechanical ventilation during ICU stay; - Delay from start of non-invasive ventilation to switch to invasive ventilation; - All-cause mortality at ICU discharge and hospital discharge; - ICU free days (IFDs) at day 28, defined as the total number of days between ICU discharge and day 28. - Occurrence of new infections from randomization to day 28; including infections by Candida, Aspergillus, Adenovirus, Herpes Virus e Cytomegalovirus - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay. - Objectively confirmed venous thromboembolism, stroke or myocardial infarction; Safety endpoints: - Occurrence of major bleeding, defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); - Occurrence of clinically relevant non-major bleeding, defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm2, intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug. RANDOMIZATION: A block randomisation will be used with variable block sizes (block size 4-6-8), stratified by 3 factors: Centre, BMI (<30/≥30) and Age (<75/≥75). Central randomisation will be performed using a secure, web-based, randomisation system with an allocation ratio of 1:1:1. The allocation sequence will be generated by the study statistician using computer generated random numbers. BLINDING (MASKING): Participants to the study will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size is based on the hypothesis that the combined use of UHF and steroid versus the LMWH group will significantly reduce the risk of death at day 28. The overall sample size in this study is expected to be 210 with a randomization 1:1:1 and seventy patients in each group. Assuming an alpha of 2.5% (two tailed) and mortality rate in LMWH group of 50%, as indicated from initial studies of ICU patients, the study will have an 80% power to detect at least a 25 % absolute reduction in the risk of death between: a) LMHW + steroid group and LMWH group or b) UHF + steroid group and LMWH group. The study has not been sized to assess the difference between LMHW + steroid group and UHF + steroid group, therefore the results obtained from this comparison will need to be interpreted with caution and will need further adequately sized studies confirm the effect. On the basis of a conservative estimation, that 8 participating sites admit an average of 3 eligible patients per month per centre (24 patients/month). Assuming that 80 % of eligible patients are enrolled, recruitment of 210 participants will be completed in approximately 10 months. TRIAL STATUS: Protocol version 1.1 of April 26th, 2020. Recruitment start (expected): September 1st, 2020 Recruitment finish (expected): June 30th, 2021 TRIAL REGISTRATION: EudraCT number 2020-001921-30 , registered on April 15th, 2020 AIFA approval on May 4th, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in 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
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Estado Terminal , Heparina/administração & dosagem , Metilprednisolona/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Adulto , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Metilprednisolona/efeitos adversos , Pandemias , Tempo de Tromboplastina Parcial
4.
Blood Adv ; 4(16): 4028, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32841342

RESUMO

The high incidence of thromboembolic disease, and in particular venous thromboembolism (VTE), has emerged as an important consideration in hospitalized and critically ill patients with coronavirus disease 2019 (COVID-19). The coagulopathy of COVID-19 is postulated to result from interactions of the inflammatory and immune systems with the coagulation system, manifesting as a cytokine storm associated with hyperinflammation and coagulation and platelet activation. Unique characteristics of VTE in hospitalized and critically ill patients with COVID-19 include the high incidence of VTE (and especially pulmonary embolism) when compared with historical controls; the finding of in situ pulmonary embolism associated with microthrombi, which suggests a thrombotic microangiopathic process in addition to classic macrovessel disease; and, most important from a clinical perspective, the unusually high rate of VTE that has been reported despite standard thromboprophylaxis. This raises the possibility that intermediate or weight-based heparin dosing may be more effective than fixed dosing for thromboprophylaxis in high-risk subsets of patients hospitalized with COVID-19. There have been several guidance statements focusing on the management of VTE in hospitalized and critically ill patients with COVID-19, including the most recent statement by the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis, which includes comprehensive guidance on the diagnosis, prevention, and treatment of VTE in this patient population. Ongoing randomized trials that address key clinical questions, especially more intense thromboprophylactic strategies and novel antithrombotic approaches, have the potential to reduce the morbidity and mortality from VTE in hospitalized and critically ill patients with COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Tromboembolia Venosa/etiologia , Anticoagulantes/administração & dosagem , Gerenciamento Clínico , Heparina/administração & dosagem , Hospitalização , Humanos , Pandemias , Guias de Prática Clínica como Assunto , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle
5.
Am Heart J ; 227: 19-30, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32663660

RESUMO

BACKGROUND: Current guidelines recommend anticoagulation therapy during primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). However, whether anticoagulation should be continued after pPCI has not been well investigated. METHODS/DESIGN: The RIGHT trial is a prospective, multicenter, randomized, double-blind, placebo-controlled trial in STEMI patients treated with pPCI evaluating the prolongation of anticoagulation after the procedure. Patients are randomized in a 1:1 fashion to receive either prolonged anticoagulant or matching placebo (no anticoagulation) for at least 48 hours after the procedure. When randomized to anticoagulation prolongation, the patient is assigned to intravenous unfractionated heparin (UFH) or subcutaneous enoxaparin or intravenous bivalirudin (same drug and same regimen at each center). The primary efficacy endpoint is the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, stent thrombosis (definite) or urgent revascularization (any vessel) at 30 days. The primary safety endpoint is major bleeding (BARC 3-5) at 30 days. Based on a superiority design and assuming a 35% relative risk reduction (from 7% to 4.5%), 2856 patients will be enrolled, accounting for a 5% drop-out rate (α = 0.05 and power = 80%). CONCLUSION: The RIGHT trial tests the hypothesis that post-procedural anticoagulation is superior to no anticoagulation in reducing ischemic events in STEMI patients undergoing pPCI.


Assuntos
Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Heparina/administração & dosagem , Hirudinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Intervenção Coronária Percutânea , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto/métodos , Período Pós-Operatório , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Fatores de Tempo
6.
BMC Infect Dis ; 20(1): 476, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631238

RESUMO

BACKGROUND: Blood culture-negative endocarditis (BCNE) is diagnosed in 2-7% of patients with infective endocarditis (IE) and recent antibiotic use is a known risk factor. Altered mental status may be a presenting symptom. Besides empiric antibiotics, intravenous anticoagulation using heparin may have a role in the management of such patients. CASE PRESENTATION: A 23-year-old male patient was referred to our center with fever, altered mental status and abnormal gait. Neurologic examination revealed Wernicke's aphasia. Cardiac auscultation revealed systolic murmur at the left sternal border. ECG (electrocardiogram) was unremarkable. Brain MRI showed multiple cerebellar lesions. Transthoracic echocardiography (TTE) demonstrated three large masses on the right ventricle (RV), tricuspid valve (TV), and anterior mitral valve (MV) leaflet. Blood cultures (three sets) were negative. Intravenous heparin therapy was administered. After 48 h, the second TTE demonstrated that one valvular lesion disappeared and the other two lesions showed a significant decrease in size. The patient's neurological symptoms resolved gradually. Further workup for collagen vascular disorders did not show any abnormality. CONCLUSION: BCNE should be considered in patients with fever and neurologic manifestations. TTE should be performed to detect valvular abnormalities. Intravenous heparin could be used in such patients when TTE demonstrate valvular vegetations.


Assuntos
Anticoagulantes/uso terapêutico , Afasia de Wernicke/tratamento farmacológico , Hemocultura , Ecocardiografia , Endocardite Bacteriana/diagnóstico por imagem , Heparina/uso terapêutico , Administração Intravenosa , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Anticoagulantes/administração & dosagem , Afasia de Wernicke/microbiologia , Endocardite Bacteriana/sangue , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Heparina/administração & dosagem , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/patologia , Adulto Jovem
7.
Crit Care ; 24(1): 454, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698853

RESUMO

Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes.The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low- and middle-income countries.These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Heparina/administração & dosagem , Nebulizadores e Vaporizadores , Pneumonia Viral/tratamento farmacológico , Humanos , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
BMJ Case Rep ; 13(6)2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: covidwho-599774

RESUMO

COVID-19 became a global pandemic in early 2020. While well known for its pulmonary manifestations, the virus also has a number of cardiac manifestations as well. Takotsubo syndrome has scarcely been reported in patients with COVID-19, but it is possible that the cytokine storm associated with the infection can trigger Takotsubo syndrome in patients with underlying risk factors for Takotsubo (emotional distress, physical distress, history of psychiatric disorders).


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus , Heparina/administração & dosagem , Metilprednisolona/administração & dosagem , Pandemias , Pneumonia Viral , Esquizofrenia/complicações , Cardiomiopatia de Takotsubo , Anticoagulantes/administração & dosagem , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Angiografia Coronária/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Eletrocardiografia/métodos , Humanos , Fatores Imunológicos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Respiração Artificial/métodos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Cardiomiopatia de Takotsubo/sangue , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/etiologia , Resultado do Tratamento
10.
BMJ Case Rep ; 13(6)2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32540884

RESUMO

COVID-19 became a global pandemic in early 2020. While well known for its pulmonary manifestations, the virus also has a number of cardiac manifestations as well. Takotsubo syndrome has scarcely been reported in patients with COVID-19, but it is possible that the cytokine storm associated with the infection can trigger Takotsubo syndrome in patients with underlying risk factors for Takotsubo (emotional distress, physical distress, history of psychiatric disorders).


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus , Heparina/administração & dosagem , Metilprednisolona/administração & dosagem , Pandemias , Pneumonia Viral , Esquizofrenia/complicações , Cardiomiopatia de Takotsubo , Anticoagulantes/administração & dosagem , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Angiografia Coronária/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Eletrocardiografia/métodos , Humanos , Fatores Imunológicos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Respiração Artificial/métodos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Cardiomiopatia de Takotsubo/sangue , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/etiologia , Resultado do Tratamento
11.
Cochrane Database Syst Rev ; 6: CD005982, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32557627

RESUMO

BACKGROUND: The prevalence of children diagnosed with thrombotic events has been increasing in the last decades. The most common thrombosis risk factor in neonates, infants and children is the placement of a central venous catheter (CVC). It is unknown if anticoagulation prophylaxis with low molecular weight heparin (LMWH) decreases CVC-related thrombosis in children. This is an update of the Cochrane Review published in 2014. OBJECTIVES: To determine the effect of LMWH prophylaxis on the incidence of CVC-related thrombosis and major and minor bleeding complications in children. Further objectives were to determine the effect of LMWH on occlusion of CVCs, number of days of CVC patency, episodes of catheter-related bloodstream infection (CRBSI), other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis) and mortality during therapy. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 7 May 2019. We undertook reference checking of identified trials to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-randomised trials comparing LMWH to no prophylaxis (placebo or no treatment), or low-dose unfractionated heparin (UFH) either as continuous infusion or flushes (low-dose UFH aims to ensure the patency of the central line but has no systemic anticoagulation activity), given to prevent CVC-related thrombotic events in children. We selected studies conducted in children aged 0 to 18 years. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible studies, which were assessed for study methodology including bias, and extracted unadjusted data where available. In the data analysis step, all outcomes were analysed as binary or dichotomous outcomes. The effects of interventions were summarised with risk ratios (RR) and their respective 95% confidence intervals (CI). We assessed the certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: One additional study was included for this update bringing the total to two included studies (with 1135 participants). Both studies were open-label RCTs comparing LMWH with low-dose UFH to prevent CVC-related thrombosis in children. We identified no studies comparing LMWH with placebo or no treatment. Meta-analysis found insufficient evidence of an effect of LMWH prophylaxis in reducing the incidence of CVC-related thrombosis in children with CVC, compared to low-dose UFH (RR 0.68, 95% CI 0.27 to 1.75; 2 studies; 787 participants; low-certainty evidence). One study (158 participants) reported symptomatic and asymptomatic CVC-related thrombosis separately and detected no evidence of a difference between LMWH and low-dose UFH (RR 1.03, 95% CI 0.21 to 4.93; low-certainty evidence; RR 1.17, 95% CI 0.45 to 3.08; low-certainty evidence; for symptomatic and asymptomatic participants respectively). There was insufficient evidence to determine whether LMWH impacts the risk of major bleeding (RR 0.27, 95% CI 0.05 to 1.67; 2 studies; 813 participants; low-certainty evidence); or minor bleeding. One study reported minor bleeding in 53.3% of participants in the LMWH arm and in 44.7% of participants in the low-dose UFH arm (RR 1.20, 95% CI 0.91 to 1.58; 1 study; 158 participants; very low-certainty evidence), and the other study reported no minor bleeding in either group (RR: not estimable). Mortality during the study period was reported in one study, where two deaths occurred during the study period. Both were unrelated to thrombotic events and occurred in the low-dose UFH arm. The second study did not report mortality during therapy per arm but showed similar 5-year overall survival (low-certainty evidence). No additional adverse effects were reported. Other pre-specified outcomes (including CVC occlusion, patency and CRBSI) were not reported. AUTHORS' CONCLUSIONS: Pooling data from two RCTs did not provide evidence to support the use of prophylactic LWMH for preventing CVC-related thrombosis in children (low-certainty evidence). Evidence was also insufficient to confirm or exclude a difference in the incidence of major and minor bleeding complications in the LMWH prophylaxis group compared to low-dose UFH (low and very low certainty respectively). No evidence of a clear difference in overall mortality was seen. Studies did not report on the outcomes catheter occlusion, days of catheter patency, episodes of CRBSI and other side effects of LMWH (allergic reactions, abnormal coagulation profile, heparin-induced thrombocytopaenia and osteoporosis). The certainty of the evidence was downgraded due to risk of bias of the included studies, imprecision and inconsistency, preventing conclusions in regards to the efficacy of LMWH prophylaxis to prevent CVC-related thrombosis in children.


Assuntos
Anticoagulantes/uso terapêutico , Cateterismo Venoso Central/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Trombose/prevenção & controle , Adolescente , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Obstrução do Cateter/estatística & dados numéricos , Criança , Pré-Escolar , Hemorragia/induzido quimicamente , Heparina/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Lactente , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose/etiologia
12.
Paediatr Drugs ; 22(4): 385-397, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32519267

RESUMO

Venous thromboembolism (VTE) is an important but historically under-recognized problem in pediatrics, with an incidence concentrated in hospitalized children. A number of specific VTE diseases with discrete triggers have been described, but the most common pediatric trigger is the presence of central venous access devices. VTE diseases, though heterogenous in etiology, are linked by the common therapeutic strategies shared by their management. Historically, the most commonly used drug therapies have been unfractionated heparin, low-molecular-weight heparins, and vitamin K antagonists, based on extrapolation from adult data rather than any specific pediatric trials. Although these widely used drugs appear safe and effective in expert hands, the historical lack of pediatric data is problematic in view of the recognized significant differences between children and adults with regards to hemostatic physiology, VTE etiology, and drug pharmacokinetics. The increasing adult usage of novel VTE pharmacotherapies such as direct oral anticoagulants (DOACs) has led to considerable interest in exploring the pediatric applications of these newer drugs. This review summarizes the advantages and disadvantages of existing VTE pharmacotherapies and outlines emerging novel pediatric VTE therapies, particularly DOACs, within the context of the current pediatric trial landscape.


Assuntos
Anticoagulantes/administração & dosagem , Tromboembolia Venosa/tratamento farmacológico , Adulto , Criança , Heparina/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Tromboembolia Venosa/epidemiologia
13.
Rev Lat Am Enfermagem ; 28: e3304, 2020.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-32578754

RESUMO

OBJECTIVE: to analyze the evidence available in the literature about the lowest necessary dose of heparin to maintain the patency of the totally implanted central venous catheter in adult cancer patients. METHOD: an integrative literature review, carried out in the following databases: Literatura Latino-Americana e do Caribe em Ciências de Saúde, Sciverse Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, including thirteen studies. RESULTS: the evidence showed that the dose of heparin (300 IU/ml) is the most used in maintaining the patency of the totally implanted central venous catheter. CONCLUSION: according to the selected studies, the lowest dose of heparin found in maintaining the patency of the totally implanted central venous catheter in cancer patients was 10 UN/ml with a volume of 5 ml of the heparin solution.


Assuntos
Anticoagulantes/administração & dosagem , Obstrução do Cateter , Cateterismo Venoso Central , Heparina/administração & dosagem , Neoplasias/tratamento farmacológico , Medicina Baseada em Evidências , Humanos
14.
Int J Cardiol ; 313: 129-131, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: covidwho-259358

RESUMO

There is some evidence that Covid 19 pneumonia is associated with prothrombotic status and increased risk of venous thromboembolic events (deep venous thrombosis and pulmonary embolism). Over a two-week period we admitted in our Unit 25 patients with Covid-19 pneumonia, of these pulmonary embolism was diagnosed using computed tomography angiography in 7. We report on clinical and biochemical features of these patients. They were all males, with a mean age of 70.3 years (range 58-84); traditional risk factors for venous thromboembolism were identified in the majority of patients with pulmonary embolism, however not differently from those without pulmonary embolism. Clinical presentation of pulmonary embolism patients was usually characterized by persistence or worsening of respiratory symptoms, with increasing oxygen requirement. D-dimer levels were several fold higher than the upper threshold of normal; in patients in whom PE was recognized during hospital stay, a rapid and relevant increase of D-dimer levels was observed. Computed tomographic findings ranged from massive acute pulmonary embolism to a segmental or sub-segmental pattern; furthermore, thrombosis of sub-segmental pulmonary arteries within lung infiltrates were occasionally seen, suggesting local mechanisms. Six out of 7 patients were treated with unfractionated or low molecular weight heparin with clinical benefit within few days; one patient needed systemic thrombolysis (death from hemorrhagic complication).


Assuntos
Infecções por Coronavirus , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Heparina/administração & dosagem , Pandemias , Pneumonia Viral , Embolia Pulmonar , Tromboembolia Venosa , Idoso , Anticoagulantes/administração & dosagem , Betacoronavirus/isolamento & purificação , Comorbidade , Angiografia por Tomografia Computadorizada/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Oxigênio/sangue , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/terapia , Fatores Sexuais , Tromboembolia Venosa/complicações , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/terapia
15.
Khirurgiia (Mosk) ; (4): 88-94, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32352676

RESUMO

OBJECTIVE: Is to evaluate the advantage of Contractubex gel with regards to influence on vascularisation, pigmentation, thickness, surface size, configuration, and elisticity of postsurgical scars of children (after cheilorinoplasty) in comparison to absence of systematized topical treatment. MATERIAL AND METHODS: Into the prospective, non-interventional, observational, multi-centered, in parallel groups, open, controlled study were included 60 patients aged 2,5 months and older with postsurgical scars after first cheilorinoplasty after 7-14 day after operation. Patients were randomized into 2 groups of 30 patients in each. I group - patients get applications of Contractubex gel 3 times a day (in the morning, in the afternoon, in the evening) in accordance with patient information leaflet. II group - control group with no regular therapy of of postsurgical scars (without treatment or without application of oils and gels with anticsarring action). The period of medicine usage - 9 months and more for each patient, the each patient observation duration is 18 months. RESULTS: After analysis of the primary as well as secondary efficacy criteria (total grade based on POSAS scale, reported by investigator/parent) after 3, 6, 12, 18 months of observation in both groups a positive statistically significant dynamics was registered. At the same time in the Contractubex group results were statistically significantly better than in the control group. Positive dynamics was achieved quickier in the main group than in the contol group and was to observe already after 3 months of therapy, during the whole treatment and observation phase, and after 18 months of therapy. Additionally conducted photodocumentation of postsurgical scar development dynamics in terms of the study confirms positive effect of surgery and absence of visual data regarding keloids or hyperthrophic scars formation in patients in both groups. Adverse events, i. a. pain, itch, burning, long-run hyperemia were not registered during the whole period os study. CONCLUSION: The conducted study has shown high efficacy and safety of Contractubex usage for the treatment of postsurgical scars of children with with congenital cleft lip and palate (from 2,5 months old). The statistically significant advantage of the therapy with Contractubex was demonstrated in comparison with the control group (with no regular topical treatment). The obtained results allow to recommend Contractubex gel as an effective and safe medicine for the treatment of scarring after surgeries for kids directly after sutures removal.


Assuntos
Alantoína/administração & dosagem , Cicatriz/tratamento farmacológico , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Fármacos Dermatológicos/administração & dosagem , Heparina/administração & dosagem , Extratos Vegetais/administração & dosagem , Cicatriz/etiologia , Fenda Labial/complicações , Fissura Palatina/complicações , Combinação de Medicamentos , Géis/administração & dosagem , Humanos , Lactente , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Prospectivos , Resultado do Tratamento
16.
Int J Cardiol ; 313: 129-131, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32471650

RESUMO

There is some evidence that Covid 19 pneumonia is associated with prothrombotic status and increased risk of venous thromboembolic events (deep venous thrombosis and pulmonary embolism). Over a two-week period we admitted in our Unit 25 patients with Covid-19 pneumonia, of these pulmonary embolism was diagnosed using computed tomography angiography in 7. We report on clinical and biochemical features of these patients. They were all males, with a mean age of 70.3 years (range 58-84); traditional risk factors for venous thromboembolism were identified in the majority of patients with pulmonary embolism, however not differently from those without pulmonary embolism. Clinical presentation of pulmonary embolism patients was usually characterized by persistence or worsening of respiratory symptoms, with increasing oxygen requirement. D-dimer levels were several fold higher than the upper threshold of normal; in patients in whom PE was recognized during hospital stay, a rapid and relevant increase of D-dimer levels was observed. Computed tomographic findings ranged from massive acute pulmonary embolism to a segmental or sub-segmental pattern; furthermore, thrombosis of sub-segmental pulmonary arteries within lung infiltrates were occasionally seen, suggesting local mechanisms. Six out of 7 patients were treated with unfractionated or low molecular weight heparin with clinical benefit within few days; one patient needed systemic thrombolysis (death from hemorrhagic complication).


Assuntos
Infecções por Coronavirus , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Heparina/administração & dosagem , Pandemias , Pneumonia Viral , Embolia Pulmonar , Tromboembolia Venosa , Idoso , Anticoagulantes/administração & dosagem , Betacoronavirus/isolamento & purificação , Comorbidade , Angiografia por Tomografia Computadorizada/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Oxigênio/sangue , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/terapia , Fatores Sexuais , Tromboembolia Venosa/complicações , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/terapia
17.
BMC Infect Dis ; 20(1): 335, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398134

RESUMO

BACKGROUND: Dengue fever is a hemorrhagic fever caused by flaviviruses. Hemorrhagic manifestations are well known to be associated with dengue fever, though the thrombotic events are only seldom reported. Underlying pathophysiology of thrombotic events is multifactorial and the management is challenging due to associated thrombocytopenia and bleeding tendency. We report a case of dengue shock syndrome with severe thrombocytopenia complicated by ilio-femoral deep vein thrombosis. CASE PRESENTATION: A 16 year old boy presented with dengue fever. He had dengue shock syndrome after entering the critical phase on the fifth day of the illness. With the recovery from the critical phase he developed deep vein thrombosis involving right external iliac, common femoral and superficial femoral veins. There were no provocative factors other than dengue fever itself. His platelet count was 12,000/µl at the time of diagnosis with deep vein thrombosis. Anticoagulation was started with intravenous unfractionated heparin 500 IU/hour while closely being observed for bleeding complications. 1000 IU/hour dose was commenced with the recovery of the platelet count above 50,000/µl. Thrombophilia screening was negative and he was discharged on warfarin. Venous duplex done after 6 weeks showed normal lower limb venous flow and warfarin was omitted after three months. CONCLUSIONS: With dengue fever, complications like deep vein thrombosis can be easily missed given its rarity and that the major concern is on hemorrhagic complications. Management is challenging due to associated thrombocytopenia and hemorrhagic complications.


Assuntos
Vírus da Dengue/imunologia , Veia Femoral/patologia , Extremidade Inferior/irrigação sanguínea , Dengue Grave/complicações , Trombocitopenia/complicações , Trombose Venosa/etiologia , Administração Intravenosa , Adolescente , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Antígenos Virais/análise , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Masculino , Resultado do Tratamento , Trombose Venosa/tratamento farmacológico , Varfarina/uso terapêutico
18.
Cochrane Database Syst Rev ; 4: CD010996, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32352563

RESUMO

BACKGROUND: Guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) around the world vary greatly. Most institutions recommend the use of heparin to prevent occlusion; there is debate, however, regarding the need for heparin and evidence to suggest normal saline (0.9% sodium chloride) may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased cost. This is an update of the review published in 2015. OBJECTIVES: To assess the clinical effects (benefits and harms) of intermittent flushing of normal saline versus heparin to prevent occlusion in long-term central venous catheters in infants and children. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases; World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 9 April 2019. We also undertook reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared the efficacy of intermittent flushing with normal saline versus heparin to prevent occlusion of long-term CVCs in infants and children aged up to 18 years of age. We excluded temporary CVCs and peripherally inserted central catheters (PICC). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial inclusion criteria, trial quality and extracted data. We assessed study quality with the Cochrane 'Risk of bias' tool. For dichotomous outcomes, we calculated the rate ratio (RR) and corresponding 95% confidence interval (CI). We pooled data using a random-effects model; and we used GRADE to assess the overall certainty of the evidence supporting the outcomes assessed in this review. MAIN RESULTS: We identified one new study for this update, bringing the total number of included studies to four (255 participants). The four trials directly compared the use of normal saline and heparin; the studies all used different protocols for the intervention and control arms, however, and all used different concentrations of heparin. Different frequencies of flushes were also reported between studies. In addition, not all studies reported on all outcomes. The certainty of the evidence ranged from moderate to very low because there was no blinding; heterogeneity and inconsistency between studies was high; and the CIs were wide. CVC occlusion was assessed in all four trials. We were able to pool the results of two trials for the outcomes of CVC occlusion and CVC-associated blood stream infection. The estimated RR for CVC occlusion per 1000 catheter days between the normal saline and heparin groups was 0.75 (95% CI 0.10 to 5.51; 2 studies, 229 participants; very low certainty evidence). The estimated RR for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37; 2 studies, 231 participants; low-certainty evidence). The duration of catheter placement was reported to be similar for the two study arms in one study (203 participants; moderate-certainty evidence), and not reported in the remaining studies. AUTHORS' CONCLUSIONS: The review found that there was not enough evidence to determine the effects of intermittent flushing with normal saline versus heparin to prevent occlusion in long-term central venous catheters in infants and children. It remains unclear whether heparin is necessary to prevent occlusion, CVC-associated blood stream infection or effects duration of catheter placement. Lack of agreement between institutions around the world regarding the appropriate care and maintenance of these devices remains.


Assuntos
Obstrução do Cateter , Cateteres Venosos Centrais , Fibrinolíticos/administração & dosagem , Heparina/administração & dosagem , Cloreto de Sódio/administração & dosagem , Adolescente , Obstrução do Cateter/estatística & dados numéricos , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/estatística & dados numéricos , Criança , Pré-Escolar , Humanos , Lactente , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Khirurgiia (Mosk) ; (3): 29-34, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32271734

RESUMO

OBJECTIVE: Experimental assessment of the effect of modified and unmodified surgical suture material on abdominal adhesive process. MATERIAL AND METHODS: The study was performed on male rats of the Wistar subpopulation. There were 5 animals in each group. In all animals, midline abdominal incision was followed by suturing the parietal peritoneum with modified and unmodified suture material. All animals were euthanized with carbon dioxide vapors in 14 days after surgery. Macro- and microscopic assessment of severity of abdominal adhesive process was carried out. Two types of preparation of excised complexes 'peritoneum-suture material-adhesion' were applied for histological examination: paraffin sections and embedding in epoxy resin. Specimens were stained by Van Gieson and with methylene blue solution. Histological specimens were examined using Axio Imager A1 light microscope (Zeiss, Germany). RESULTS: Polypropylene filaments result extensive adhesions occupying about 75% of the area. Adhesions have a dense structure with signs of vascularization. Modification of suture material with solution of polyhydroxybutyrate/hydroxyvalerate and heparin reduce severity of adhesions. The use of modified suture material was followed by adhesions with more loose structure, no signs of vascularization. Adhesions occupied less than 25% of the area. Histological examination of excised complexes 'peritoneum-suture material-adhesion' revealed accumulation of inflammatory cells around the unmodified suture material, while there were no signs of tissue inflammatory process around the modified sutures. CONCLUSION: Application of polyhydroxybutyrate/hydroxyvalerate and heparin on the surface of surgical sutures is an effective method for prevention of abdominal adhesions.


Assuntos
Materiais Biocompatíveis/efeitos adversos , Heparina/administração & dosagem , Poliésteres/administração & dosagem , Polipropilenos/efeitos adversos , Suturas/efeitos adversos , Aderências Teciduais/prevenção & controle , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/efeitos adversos , Modelos Animais de Doenças , Heparina/efeitos adversos , Masculino , Neovascularização Patológica/etiologia , Neovascularização Patológica/prevenção & controle , Peritônio/irrigação sanguínea , Peritônio/patologia , Peritônio/cirurgia , Poliésteres/efeitos adversos , Polipropilenos/administração & dosagem , Ratos , Ratos Wistar , Aderências Teciduais/etiologia , Aderências Teciduais/patologia
20.
Intern Emerg Med ; 15(5): 751-753, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32297089

RESUMO

The development of COVID-19 syndrome in anticoagulated patients, and especially their admission to intensive-care units with acute severe respiratory syndrome (SARS-CoV-2), expose them to specific problems related to their therapy, in addition to those associated with the acute viral infection. Patients on VKA hospitalized with SARS-CoV-2 show high instability of PT INR due to the variability of vitamin K metabolism, diet, fasting, co-medications, liver impairment, and heart failure. Patients on DOAC are exposed to under/over treatment caused by significant pharmacological interferences. In consideration of the pharmacological characteristics of oral anticoagulant drugs, the multiple pharmacological interactions due to the treatment of acute disease and the possible necessity of mechanical ventilation with hospitalization in intensive-care units, we suggest replacing oral anticoagulant therapies (VKA and DOAC) with parenteral heparin to avoid the risk of over/under treatment.


Assuntos
Anticoagulantes/administração & dosagem , Infecções por Coronavirus/complicações , Heparina/administração & dosagem , Pneumonia Viral/complicações , Administração Oral , Anticoagulantes/efeitos adversos , Betacoronavirus , Cuidados Críticos , Interações Medicamentosas , Heparina/efeitos adversos , Hospitalização , Humanos , Infusões Parenterais , Pandemias
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