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1.
Biomed Pharmacother ; 139: 111569, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243622

RESUMO

BACKGROUND: Alveolar hypercoagulation and fibrinolysis inhibition were associated with the refractory hypoxemia and the high mortality in patient with acute respiratory distress syndrome (ARDS), and NF-κB pathway was confirmed to contribute to the process. Triptolide (TP) significantly inhibited NF-κB pathway and thus depressed accessive inflammatory response in ARDS. We speculate that TP could improve alveolar hypercoagulation and fibrinolytic inhibition in LPS-induced ARDS via NF-κB inactivation. PURPOSE: The aim of this experiment was to explore the efficacy and potential mechanism of TP on alveolar hypercoagulation and fibrinolysis inhibition in LPS-induced ARDS in mice. METHODS: 50 µl of LPS (5 mg/ml) was inhalationally given to C57BL/6 mice to set up ARDS model. Male mice were randomly accepted with LPS, LPS + TP (1 µg/kg, 10 µg/kg, 50 µg/kg respectively), or with NEMO Binding domain peptide (NBD), an inhibitor of NF-κB. TP (1 µg/kg, 10 µg/kg, 50 µg/kg) were intraperitoneally injected or 10 µg/50 µl of NBD solution were inhaled 30 min before LPS inhalation. A same volume of normal saline (NS) substituted for TP in mice in control. The endpoint of experiment was at 8 hours after LPS stimulation. Pulmonary tissues were taken for hematoxylin-eosin (HE) staining, wet / dry ratio and for lung injury scores (LIS). Tissue factor (TF) and plasminogen activator inhibitor (PAI)-1 in lung tissue were detected by Western-blotting and by quantitative Real-time PCR(qPCR) respectively. Concentrations of TF, PAI-1, thrombin-antithrombin complex (TAT), procollagen peptide type Ⅲ (PⅢP) and activated protein C (APC) in bronchoalveolar lavage fluid (BALF) were measured by ELISA. NF-κB activation and p65-DNA binding activity in pulmonary tissue were simultaneously determined. RESULTS: LPS stimulation resulted in pulmonary edema, neutrophils infiltration, obvious alveolar collapse, interstitial congestion, with high LIS, which were all dose-dependently ameliorated by Triptolide. LPS also dramatically promoted the expressions of TF and PAI-1 either in mRNA or in protein in lung tissue, and significantly stimulated the secretions of TF, PAI-1, TAT, PⅢP but inhibited APC production in BALF, which were all reversed by triptolide treatment in dose-dependent manner. TP dose-dependently inhibited the activation of NF-κB pathway induced by LPS, indicated by the changes of phosphorylations of p65 (p-p65), p-IKKα/ß and p-IκBα, and weakened p65-DNA binding activity. TP and NBD had same efficacies either on alveolar hypercoagulation and fibrinolysis inhibition or on NF-κB signalling pathway in ARDS mice. CONCLUSIONS: TP dose-dependently improves alveolar hypercoagulation and fibrinolysis inhibition in ARDS mice through inhibiting NF-κB signaling pathway. Our data demonstrate that TP is expected to be an effective selection in ARDS.


Assuntos
Diterpenos/farmacologia , Fibrinólise/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , NF-kappa B/metabolismo , Fenantrenos/farmacologia , Trombofilia/induzido quimicamente , Trombofilia/tratamento farmacológico , Animais , Modelos Animais de Doenças , Compostos de Epóxi/farmacologia , Pulmão/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Síndrome do Desconforto Respiratório , Transdução de Sinais/efeitos dos fármacos , Trombofilia/metabolismo , Tromboplastina/metabolismo
2.
Int J Lab Hematol ; 43 Suppl 1: 36-42, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34288440

RESUMO

The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID-19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID-19 patients. Elevated D-dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID-19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID-19 patients but have currently no place in diagnosis or management in COVID-19 patients. For monitoring the heparin anticoagulant therapy, the anti-Xa assay is suggested, because the severe acute-phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.


Assuntos
Testes de Coagulação Sanguínea , COVID-19/sangue , SARS-CoV-2 , Trombofilia/etiologia , Anticorpos Antifosfolipídeos/sangue , Biomarcadores/sangue , Fatores de Coagulação Sanguínea/análise , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Fator Xa/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Fibrinólise , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Tempo de Protrombina , Tromboelastografia , Trombina/biossíntese , Trombofilia/sangue , Trombofilia/tratamento farmacológico
3.
Hum Reprod ; 36(8): 2083-2090, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34195794

RESUMO

STUDY QUESTION: What evaluation and care is offered to women after unexplained recurrent pregnancy loss (RPL) or intra-uterine foetal death (IUFD) and what are the reproductive outcomes? SUMMARY ANSWER: Women are assessed for thrombophilia and often treated with low-molecular weight heparin (LMWH) and/or low-dose aspirin (ASA). WHAT IS KNOWN ALREADY: Randomized controlled trials (RCTs) on possible efficacy of heparins and/or aspirin have been inconclusive due to limited power to detect a difference and patient heterogeneity. STUDY DESIGN, SIZE, DURATION: Prospective multicentre cohort study performed in 12 hospitals in three countries between 2012 and 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: All consecutive pregnant women with recurrent PL (≥3 losses or 2 losses in the presence of at least one euploid foetal karyotype) or at least one IUFD. Eligible women may have undergone thrombophilia testing before conception, at the discretion of local providers. The possible assignment of women to treatments (such as LMWH) was not decided a priori but was determined based on the responsible provider's current practice. Aims of the study were: (i) to evaluate factors associated with pregnancy outcome; (ii) to compare clinical management strategies in women with and without a subsequent successful pregnancy; and (iii) to evaluate characteristics of women who may benefit from antithrombotic therapy. A propensity score matching method was used to balance the differences in baseline characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: A matched sample of 265 pregnant women was analysed, with all undergoing thrombophilia screening; 103 out of 119 (86.6%) with and 98/146 (67.1%) without thrombophilia were prescribed with LMWH and/or ASA. Overall, live-births were recorded in 204 cases (77%), PL or IUFD in 61 (23%) pregnancies. Logistic regression showed a significant interaction between thrombophilia and treatment with LMWH (P = 0.03). Findings from sensitivity analysis showed odds ratio (OR) for pregnancy loss in women with inherited or acquired thrombophilia in absence of any treatment was 2.9 (95% CI, 1.4-6.1); the administration of LMWH (with or without ASA) was associated with higher odds of live-birth (OR, 10.6; 95% CI, 5.0-22.3). Furthermore, in women without thrombophilia, the odds of live-birth was significantly and independently associated with LMWH prophylaxis (alone or in association with ASA) (OR, 3.6; 95% CI, 1.7-7.9). LIMITATIONS, REASONS FOR CAUTION: While the propensity score matching allows us to balance the differences in baseline characteristics, it does not eliminate all confounding. WIDER IMPLICATIONS OF THE FINDINGS: Antithrombotic prophylaxis during pregnancy may be effective in women with otherwise unexplained PL or IUFD, and even more useful in those with thrombophilia. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Italian Ministry of Health (Ricerca Corrente 2018-2020). Dr G.P. has received research grant support from Bristol Myers Squibb/Pfizer Alliance, Janssen, Boston Scientific Corporation, Bayer, and Portola and consultant fees from Amgen and Agile Therapeutics. Dr E.G. has received consultant fees from Italfarmaco and Sanofi. All other authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: NCT02385461.


Assuntos
Aborto Habitual , Trombofilia , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Nascido Vivo , Gravidez , Sistema de Registros , Trombofilia/complicações , Trombofilia/tratamento farmacológico
5.
Nutrients ; 13(5)2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-34063322

RESUMO

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.


Assuntos
Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Vitis/química , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anticoagulantes/farmacologia , Anti-Hipertensivos/farmacologia , Catequina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Humanos , Hipertensão/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proantocianidinas/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Sirtuínas/metabolismo , Trombofilia/tratamento farmacológico , Vasodilatadores/farmacologia
6.
Inflammopharmacology ; 29(4): 1017-1031, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34185200

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-COV-2) is the culprit of the Coronavirus Disease (COVID-19), which has infected approximately 173 million people and killed more than 3.73 million. At risk groups including diabetic and obese patients are more vulnerable to COVID-19-related complications and poor outcomes. Substantial evidence points to hypovitaminosis D as a risk factor for severe disease, the need for ICU, and mortality. 1,25(OH)D, a key regulator of calcium homeostasis, is believed to have various immune-regulatory roles including; promoting anti-inflammatory cytokines, down regulating pro-inflammatory cytokines, dampening entry and replication of SARS-COV-2, and the production of antimicrobial peptides. In addition, there are strong connections which suggest that dysregulated 1,25(OH)D levels play a mechanistic and pathophysiologic role in several disease processes that are shared with COVID-19 including: diabetes, obesity, acute respiratory distress syndrome (ARDS), cytokine storm, and even hypercoagulable states. With evidence continuing to grow for the case that low vitamin D status is a risk factor for COVID-19 disease and poor outcomes, there is a need now to address the public health efforts set in place to minimize infection, such as lock down orders, which may have inadvertently increased hypovitaminosis D in the general population and those already at risk (elderly, obese, and disabled). Moreover, there is a need to address the implications of this evidence and how we may apply the use of cheaply available supplementation, which has yet to overcome the near global concern of hypovitaminosis D. In our review, we exhaustively scope these shared pathophysiologic connections between COVID-19 and hypovitaminosis D.


Assuntos
COVID-19/metabolismo , Síndrome da Liberação de Citocina/metabolismo , Trombofilia/metabolismo , Deficiência de Vitamina D/metabolismo , Vitamina D/administração & dosagem , Vitamina D/metabolismo , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/fisiopatologia , Humanos , Obesidade/epidemiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Fatores de Risco , Trombofilia/tratamento farmacológico , Trombofilia/fisiopatologia , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/fisiopatologia
7.
Clin Appl Thromb Hemost ; 27: 10760296211021495, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34142564

RESUMO

The treatment process of patients using warfarin is expected to be hindered during the COVID-19 pandemic. Therefore we investigated whether the time in therapeutic range (TTR) and bleeding complications were affected during the COVID-19 pandemic. 355 patients using warfarin were included between March 2019 to March 2021. Demographic parameters, INR (international normalized ratio), and bleeding rates were recorded retrospectively. The TTR value was calculated using Rosendaal's method. The mean age of the patients was 61 ± 12 years and 55% of them were female. The mean TTR value during the COVID-19 pandemic was lower than the pre-COVID-19 period (56 ± 21 vs 68 ± 21, P < 0.001). Among the patients, 41% had a lack of outpatient INR control. During the COVID-19 pandemic, 71 (20%) patients using VKA suffered bleeding. Among patients with bleeding, approximately 60% did not seek medical help and 6% of patients performed self-reduction of the VKA dose. During the COVID-19 pandemic, TTR values have decreased with the lack of monitoring. Furthermore, the majority of patients did not seek medical help even in case of bleeding.


Assuntos
Anticoagulantes/farmacologia , Tempo de Sangramento , Coagulação Sanguínea/efeitos dos fármacos , COVID-19/sangue , Hemorragia/induzido quimicamente , Coeficiente Internacional Normatizado , Pandemias , SARS-CoV-2 , Trombofilia/sangue , Varfarina/farmacologia , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , COVID-19/complicações , Relação Dose-Resposta a Droga , Feminino , Próteses Valvulares Cardíacas/efeitos adversos , Hemorragia/psicologia , Humanos , Hipertensão/complicações , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Embolia Pulmonar/tratamento farmacológico , Estudos Retrospectivos , Automedicação , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Varfarina/administração & dosagem , Varfarina/efeitos adversos , Varfarina/uso terapêutico
9.
Arch Cardiovasc Dis ; 114(5): 381-393, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33846096

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated with coagulation disorders, in particular high concentrations of D-dimer, and increased frequency of venous thromboembolism. AIM: To explore the association between D-dimer at admission and in-hospital mortality in patients hospitalised for COVID-19, with or without symptomatic venous thromboembolism. METHODS: From 26 February to 20 April 2020, D-dimer concentration at admission and outcomes (in-hospital mortality and venous thromboembolism) of patients hospitalised for COVID-19 in medical wards were retrospectively analysed in a multicenter study in 24 French hospitals. RESULTS: Among 2878 patients enrolled in the study, 1154 (40.1%) patients had D-dimer measurement at admission. Receiver operating characteristic curve analysis identified a D-dimer concentration>1128ng/mL as the best cut-off value for in-hospital mortality (area under the curve 64.9%, 95% confidence interval [CI] 60-69), with a sensitivity of 71.1% (95% CI 62-78) and a specificity of 55.6% (95% CI 52-58), which did not differ in the subgroup of patients with venous thromboembolism during hospitalisation. Among 545 (47.2%) patients with D-dimer concentration>1128ng/mL at admission, 86 (15.8%) deaths occurred during hospitalisation. After adjustment, in Cox proportional hazards and logistic regression models, D-dimer concentration>1128ng/mL at admission was also associated with a worse prognosis, with an odds ratio of 3.07 (95% CI 2.05-4.69; P<0.001) and an adjusted hazard ratio of 2.11 (95% CI 1.31-3.4; P<0.01). CONCLUSIONS: D-dimer concentration>1128ng/mL is a relevant predictive factor for in-hospital mortality in patients hospitalised for COVID-19 in a medical ward, regardless of the occurrence of venous thromboembolism during hospitalisation.


Assuntos
COVID-19/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombofilia/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Área Sob a Curva , COVID-19/complicações , COVID-19/mortalidade , Teste de Ácido Nucleico para COVID-19 , Criança , Pré-Escolar , Registros Eletrônicos de Saúde , França/epidemiologia , Mortalidade Hospitalar , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Quartos de Pacientes , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Tromboembolia Venosa/epidemiologia , Adulto Jovem
10.
Thromb Res ; 202: 134-138, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33836493

RESUMO

Exogenous hormone therapies, such as combined oral contraceptives (COC) and hormone replacement therapy (HRT), cause blood hypercoagulability and are a risk factor for venous thromboembolism (VTE). There is controversy on how strong this "provoking" risk factor is, and how other risk factors may synergise VTE risk. We aim to review the latest literature on the risk of initial and recurrent VTE with COC and HRT use to provide guidance for decision-making about duration of anticoagulation, and guide future research efforts.


Assuntos
Trombofilia , Tromboembolia Venosa , Anticoncepcionais Orais Combinados/efeitos adversos , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Fatores de Risco , Trombofilia/tratamento farmacológico , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/tratamento farmacológico
11.
Blood Coagul Fibrinolysis ; 32(3): 167-171, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33827111

RESUMO

Coronavirus disease 2019 infection produce a prothrombotic state. This is initiated through multiple pathways and is finally aggravated by cross talks with cytokine storm and neutrophil, platelet, complement activation. All these combine towards the second week of illness to produce thrombosis in the lung capillaries surrounding the alveolus producing characteristic pulmonary dysfunction (PaO2/FiO2 > 300, normal or minimally increased lung compliance and very high d-dimer levels) and a high rate of peripheral venous thrombosis. International and many national guidelines have approached this state in different ways but all emphasized the need for management and prevention of widespread thrombosis. It is felt more aggressive and graded thrombosis prevention and management should be initiated early in the treatment. d-Dimer, neutrophil count, SaO2, fibrinogen levels should be used to control the hypercoagulability. Drugs like statins which have anti-inflammatory action as well as ability to reduce fibrinogen and other clotting factors should be used in the beginning along with antiplatelet drugs and progressively complement activation and neutrophil extracellular traps inhibitors, oral mucopolysaccharides, full-scale anticoagulation along with judicial use of fibrinolysis supporting drugs should be added. In the present review, we have evaluated the various studies and argued the rationality that the anticoagulation in this condition should be initiated early during the infection and should be increased in a graded manner depending on clinical and laboratory progression of the condition until a strong specific antiviral drug for coronavirus disease 2019 infection is available.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Trombofilia/tratamento farmacológico , Trombose/tratamento farmacológico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Plaquetas/efeitos dos fármacos , Armadilhas Extracelulares/efeitos dos fármacos , Fibrinolíticos/uso terapêutico , Glicosaminoglicanos/farmacologia , Glicosaminoglicanos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/tratamento farmacológico , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/virologia , Inibidores da Agregação Plaquetária/uso terapêutico
12.
Int J Mol Sci ; 22(8)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923802

RESUMO

Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder.


Assuntos
Anastrozol/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Coagulação Sanguínea , Neoplasias da Mama/tratamento farmacológico , Transição Epitelial-Mesenquimal , Inibidores da Agregação Plaquetária/efeitos adversos , Trombofilia/prevenção & controle , Adulto , Anastrozol/administração & dosagem , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Neoplasias da Mama/complicações , Células Cultivadas , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Iminas/administração & dosagem , Iminas/efeitos adversos , Iminas/uso terapêutico , Células MCF-7 , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/uso terapêutico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Trombina/metabolismo , Trombofilia/tratamento farmacológico , Trombofilia/etiologia
15.
Ann Hematol ; 100(7): 1647-1665, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33712866

RESUMO

Secondary thrombocytosis is a frequent secondary finding in childhood infection and inflammation. Primary hereditary thrombocytosis may be caused by germline mutations within the genes encoding key regulators of thrombopoiesis, i.e., thrombopoietin (THPO) and its receptor c-MPL (MPL) or the receptor's effector kinase Januskinase2 (JAK2). Furthermore, somatic mutations in JAK2, MPL, and in the gene-encoding calreticulin (CALR) have been described to act as driver mutations within the so-called Philadelphia-negative myeloproliferative neoplasms (MPNs), namely essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). Increasing knowledge on the molecular mechanisms and on the clinical complications of these diseases is reflected by the WHO diagnostic criteria and European LeukemiaNet (ELN) recommendations on the management of adult MPN. However, data on childhood thrombocytosis are rare, and no consensus guidelines for pediatric thrombocytosis exist. Current literature has highlighted differences in the epidemiology and molecular pathogenesis of childhood thrombocytosis as compared to adults. Furthermore, age-dependent complications and pharmacological specificities suggest that recommendations tailored to the pediatric population are necessary in clinical practice. Here we summarize literature on classification, diagnostics, and clinical management of childhood thrombocytosis.


Assuntos
Trombocitose , Adolescente , Adulto , Idade de Início , Algoritmos , Anticoagulantes/uso terapêutico , Calreticulina/genética , Criança , Gerenciamento Clínico , Feminino , Mutação em Linhagem Germinativa , Humanos , Hidroxiureia/uso terapêutico , Interferon-alfa/uso terapêutico , Janus Quinase 2/genética , Masculino , Doenças Mieloproliferativas-Mielodisplásicas/complicações , Contagem de Plaquetas , Quinazolinas/uso terapêutico , Receptores de Trombopoetina/genética , Índice de Gravidade de Doença , Trombocitemia Essencial/classificação , Trombocitemia Essencial/genética , Trombocitose/classificação , Trombocitose/diagnóstico , Trombocitose/etiologia , Trombocitose/terapia , Trombofilia/tratamento farmacológico , Trombofilia/etiologia
16.
Blood Transfus ; 19(3): 244-252, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33539283

RESUMO

BACKGROUND: Even though it rarely influences venous thromboembolism (VTE) treatment and the fact that it is generally discouraged, thrombophilia testing is still largely prescribed. We assessed: 1) whether/how frequently Italian thrombosis centres requested thrombophilia testing; 2) what results were obtained; and 3) if the results affected treatment and clinical results. MATERIALS AND METHODS: We examined data from 4,826 VTE patients enrolled by 19 clinical centres participating in the START 2-Register. RESULTS: 57.2% of patients were tested. Numbers varied widely among centres (2.9-99.7%). Thrombophilic alterations were recorded in 18.2% of patients and the percentage of positive results was inversely correlated with that of patients tested. Significantly less patients with deep vein thrombosis (DVT) were tested, whereas more were tested when the event was idiopathic, presenting as isolated pulmonary embolism (PE), or in unusual sites. Patients with thrombophilic alterations were younger, more frequently treated with direct oral anticoagulants (DOACs), with lower mortality and less frequently discontinued anticoagulation. DOACs were more frequently prescribed in patients with heterozygous Factor V (FV) Leiden or prothrombin mutations, whereas vitamin K antagonists were preferred in patients with inhibitor deficiencies, combined alterations or antiphospholipid syndrome (APLS). There was no difference in duration of treatment among those with or without alterations, though more APLS patients received an extended treatment course. Bleeding and thrombotic complications occurred with a similar and fairly low incidence in patients with or without thrombophilic alterations. DISCUSSION: Although general testing for thrombophilia in VTE patients is currently discouraged, more than half of the VTE patients included in the START2-Register were tested. However, there were marked differences in practice between Italian thrombosis centres. About 60% of all patients with alterations were treated with DOACs, confirming that DOACs can be a useful option for treatment of thrombophilic VTE patients, with the exclusion of those with APLS.


Assuntos
Trombofilia/diagnóstico , Tromboembolia Venosa/diagnóstico , Inibidores do Fator Xa/uso terapêutico , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Estudos Prospectivos , Trombofilia/tratamento farmacológico , Trombofilia/epidemiologia , Trombose/diagnóstico , Trombose/tratamento farmacológico , Trombose/epidemiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia
17.
Br J Haematol ; 193(1): 43-51, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538335
18.
Semin Respir Crit Care Med ; 42(2): 316-326, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548929

RESUMO

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/tratamento farmacológico , Trombofilia/tratamento farmacológico , Trombose/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Assistência Ambulatorial , Anticorpos Antifosfolipídeos/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , COVID-19/sangue , COVID-19/complicações , COVID-19/imunologia , COVID-19/terapia , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Duração da Terapia , Glucocorticoides/uso terapêutico , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , SARS-CoV-2 , Terapia Trombolítica , Trombofilia/sangue , Trombofilia/etiologia , Trombose/tratamento farmacológico , Trombose/imunologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/imunologia
20.
Am J Hematol ; 96(6): E182-E184, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33617676
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