Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.851
Filtrar
1.
Phytomedicine ; 80: 153363, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33070081

RESUMO

BACKGROUND: The ingestion of flavonoids has been reported to be associated with reduced cardiovascular disease risk. Quercitrin is a common flavonoid in nature, and it exhibits antioxidant properties. Although the process of thrombogenesis is intimately related to cardiovascular disease risk, it is unclear whether quercitrin plays a role in thrombogenesis. PURPOSE: The aim of this study was to examine the antiplatelet effect of quercitrin in platelet activation. METHODS: Platelet aggregation, granule secretion, calcium mobilization, and integrin activation were used to assess the antiplatelet activity of quercitrin. Antithrombotic effect was determined in mouse using ferric chloride (FeCl3)-induced arterial thrombus formation in vivo and thrombus formation on collagen-coated surfaces under arteriolar shear in vitro. Transection tail bleeding time was used to evaluate whether quercitrin inhibited primary hemostasis. RESULTS: Quercitrin significantly impaired collagen-related peptide-induced platelet aggregation, granule secretion, reactive oxygen species generation, and intracellular calcium mobilization. Outside-in signaling of αIIbß3 integrin was significantly inhibited by quercitrin in a concentration-dependent manner. The inhibitory effect of quercitrin resulted from inhibition of the glycoprotein VI-mediated platelet signal transduction during cell activation. Further, the antioxidant effect is derived from decreased phosphorylation of components of the TNF receptor-associated factor 4/p47phox/Hic5 axis signalosome. Oral administration of quercitrin efficiently blocked FeCl3-induced arterial thrombus formation in vivo and thrombus formation on collagen-coated surfaces under arteriolar shear in vitro, without prolonging bleeding time. Studies using a mouse model of ischemia/reperfusion-induced stroke indicated that treatment with quercitrin reduced the infarct volume in stroke. CONCLUSIONS: Our results demonstrated that quercitrin could be an effective therapeutic agent for the treatment of thrombotic diseases.


Assuntos
Fibrinolíticos/farmacologia , Hemostasia/efeitos dos fármacos , Quercetina/análogos & derivados , Trombose/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Animais , Artérias , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Quercetina/efeitos adversos , Quercetina/farmacologia , Traumatismo por Reperfusão/induzido quimicamente , Trombose/induzido quimicamente , Trombose/metabolismo
2.
Int Heart J ; 61(5): 865-871, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921667

RESUMO

Bleeding complication has been considered as a serious problem in current percutaneous coronary interventions (PCI). Fortunately, several groups have already reported the effectiveness of protamine use just after PCI to immediately remove any arterial sheath. However, there is a concern that protamine reversal may increase non-occlusive thrombus and, in turn, lead to mid-term cardiovascular events such as target vessel revascularization (TVR) or stent thrombosis. Thus, the purpose of this study was to evaluate whether protamine use following elective PCI was associated with mid-term clinical outcomes. In total, 472 patients were included in this study; subsequently, they were divided into protamine group (n = 142) and non-protamine group (n = 330). The primary endpoint was the composite of ischemia-driven TVR and stent thrombosis. The median follow-up period was determined to be at 562 days. In total, 32 primary endpoints were observed during the study period, and the incidence of primary endpoints tended to be greater in the protamine group than in the non-protamine group (P = 0.056). However, the lesion length, the degree of calcification, and the prevalence of hemodialysis were significantly determined greater in the protamine group than in the non-protamine group. In the multivariate Cox proportional hazards model, the use of protamine (versus non-protamine: hazard ratio 0.542 and 95% confidence interval 0.217-1.355, P = 0.191) was deemed not to be associated with the primary endpoint after controlling legion length, calcification, and hemodialysis. In conclusion, immediate protamine use following elective PCI did not increase mid-term ischemia-driven TVR or stent thrombosis. However, immediate protamine use after PCI should be discussed further for the safety of the patient.


Assuntos
Estenose Coronária/cirurgia , Antagonistas de Heparina/uso terapêutico , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/epidemiologia , Hemorragia Pós-Operatória/prevenção & controle , Protaminas/uso terapêutico , Trombose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Estudos de Casos e Controles , Estenose Coronária/epidemiologia , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Heparina/efeitos adversos , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/estatística & dados numéricos , Complicações Pós-Operatórias/induzido quimicamente , Hemorragia Pós-Operatória/induzido quimicamente , Modelos de Riscos Proporcionais , Diálise Renal , Estudos Retrospectivos , Stents , Trombose/induzido quimicamente , Calcificação Vascular/epidemiologia
3.
Transplant Proc ; 52(6): 1778-1783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32571699

RESUMO

There is no consensus regarding the use of systemic heparin, and long-term outcomes of living donor hepatectomy (LDH) without systemic heparinization have not yet been determined. This study was performed to determine whether systemic heparinization can be omitted during LDH, with a focus on donor safety and long-term outcomes. We retrospectively analyzed the outcomes of 175 cases of LDH performed in our institution between January 2011 and December 2014: group I (n = 79) received systemic heparinization, whereas group II (n = 96) did not, but liver graft was flushed with a heparinized perfusate. Postoperative bleeding requiring blood transfusion or intervention was more frequent in group I than in group II (P = .028). The decreases in donor hemoglobin and hematocrit levels, and platelet count during the early postoperative period, were greater in group I than in group II. In multivariate analysis, systemic heparin was the only independent risk factor for blood transfusion (odds ratio [OR] = 5.114; 95% confidence interval [CI]: 1.201-21.775; P = .027) and significant postoperative bleeding (OR = 7.731; 95% CI: 1.345-44.429; P = .022) after LDH. Most postoperative complications including graft vascular thrombosis were similar between the 2 groups, as was the survival rate, and neither graft loss due to vascular thrombosis nor non-anastomotic biliary stricture was evident. In conclusion, omission of systemic heparinization during LDH is a feasible and safe option without adverse effects.


Assuntos
Heparina/administração & dosagem , Hepatectomia/métodos , Doadores Vivos , Complicações Pós-Operatórias/induzido quimicamente , Coleta de Tecidos e Órgãos/métodos , Adulto , Transfusão de Sangue/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Heparina/efeitos adversos , Hepatectomia/efeitos adversos , Humanos , Fígado/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Hemorragia Pós-Operatória/induzido quimicamente , Período Pós-Operatório , Estudos Retrospectivos , Trombose/induzido quimicamente , Coleta de Tecidos e Órgãos/efeitos adversos , Transplantes/cirurgia , Resultado do Tratamento
4.
Gan To Kagaku Ryoho ; 47(6): 989-992, 2020 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-32541181

RESUMO

A 61-year-old man underwent CapeOX plus bevacizumab chemotherapyafter right hemicolectomyfor metastatic ascending colon cancer. On the 7th dayafter the first administration, he had sudden abdominal pain and nausea. Contrast-enhanced computed tomographyrevealed aortic thrombosis and a superior mesenteric artery(SMA)embolism that was considered to be associated with bevacizumab. Bevacizumab was discontinued and anticoagulation therapyusing heparin and urokinase was performed. Brain infarction of the left middle cerebral arteryoccurred on the 15th dayafter the first administration and thrombectomywas performed. Anticoagulation therapyusing heparin, bayaspirin, and edoxaban tosilate hydrate was performed. The aortic thrombosis and SMA embolism resolved with treatment, but the patient died following an increase in peritoneal dissemination. It should be noted that unexpectedlysevere aortic thrombosis occurred during the first administration of CapeOX plus bevacizumab for metastatic colon cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo , Trombose , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Capecitabina , Neoplasias do Colo/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos , Oxaliplatina , Trombose/induzido quimicamente
5.
Lancet Haematol ; 7(6): e490-e497, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32470440

RESUMO

Evaluation of tolerability is increasingly relevant for patients with haematological malignancies treated with chronically administered therapies. Adverse events from these agents might affect the ability of patients to tolerate treatment over time. Conventional toxicity tables that include the incidence of high-grade adverse events, defined by the Common Terminology Criteria for Adverse Events, do not provide information on the time profile of these adverse events or reflect the continuous, lower grade symptomatic toxicities that are particularly relevant to treatment tolerability for patients living with indolent disease. Modern approaches to the evaluation and reporting of toxicity that capture the tolerability of treatment to the patient are imperative. In this Viewpoint, we present a focused, pilot, and longitudinal Toxicity over Time analysis of adverse events from lenalidomide and lenalidomide with rituximab in patients with follicular lymphoma treated in the CALGB 50401 (Alliance; NCT00238238) trial to define the trajectory of adverse events and quantify the burden of continuous, low-grade events. Toxicity over Time analyses provided clinically relevant descriptions of neutropenia and fatigue trajectories caused by lenalidomide that were not identified by standard analysis of the maximum grade events defined by the Common Terminology Criteria for Adverse Events. Systematic, rigorous incorporation of patient-reported outcomes in clinical trials will be crucial to our understanding of the tolerability of chronically administered therapies in patients with haematological malignancies.


Assuntos
Inibidores da Angiogênese/toxicidade , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Neoplasias Hematológicas/tratamento farmacológico , Lenalidomida/toxicidade , Linfoma Folicular/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tolerância a Medicamentos/fisiologia , Fadiga/induzido quimicamente , Fadiga/classificação , Fadiga/epidemiologia , Humanos , Infusões Intravenosas , Lenalidomida/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/classificação , Neutropenia/epidemiologia , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Trombose/induzido quimicamente , Trombose/classificação , Trombose/epidemiologia
6.
BMC Cardiovasc Disord ; 20(1): 182, 2020 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306901

RESUMO

BACKGROUND: Combined oral contraceptive pills are associated with an established risk for venous thrombosis; however, their risk for arterial thrombosis remains uncertain, especially with the development of low dose new generations of combined oral contraceptive. Arterial thrombosis is less likely to occur with the use of oral contraceptive pills in the absence of cardiovascular risk factors. CASE PRESENTATION: We report a 35-year old female with no cardiovascular risk factors who presented with thrombotic anterior wall myocardial infarction 6 months after using a third generation low dose combined oral contraceptive pills (Marvelon; ethinylestradiol 30 mcg and desogestrel 150 mcg). CONCLUSION: Third generation low dose combined oral contraceptives may lead to myocardial infarction in young women, even in the absence of other cardiovascular risk factors.


Assuntos
Infarto Miocárdico de Parede Anterior/induzido quimicamente , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Anticoncepcionais Orais Sintéticos/efeitos adversos , Desogestrel/efeitos adversos , Trombose/induzido quimicamente , Adulto , Infarto Miocárdico de Parede Anterior/diagnóstico por imagem , Infarto Miocárdico de Parede Anterior/tratamento farmacológico , Anticoagulantes/uso terapêutico , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Hormonais/administração & dosagem , Anticoncepcionais Orais Sintéticos/administração & dosagem , Desogestrel/administração & dosagem , Enoxaparina/uso terapêutico , Feminino , Humanos , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Resultado do Tratamento
7.
Vasc Med ; 25(3): 246-254, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32303152

RESUMO

Tyrosine kinase inhibitors (TKIs) of the BCR-ABL fusion protein have dramatically changed the mortality of chronic myeloid leukemia (CML) but they carry a risk of serious vascular morbidity. While TKIs do not cure CML, daily oral administration of a TKI can control CML and TKIs are chronic medications. Interestingly, vascular complications can occur at any time a patient is on a TKI. Therefore, it is imperative that all care team members and patients are aware of and watching for possible vascular complications. In the following review, a case of arterial thrombosis secondary to the TKI ponatinib is presented as well as a discussion of thrombotic and vascular adverse events reported with TKIs. TKIs are metabolized through the cytochrome P450 system and important drug interactions to consider are reviewed. Finally, we present a multidisciplinary approach to the management of patients with CML on TKIs.


Assuntos
Anticoagulantes/uso terapêutico , Antineoplásicos/efeitos adversos , Estenose das Carótidas/tratamento farmacológico , Imidazóis/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Piridazinas/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Trombose/tratamento farmacológico , Idoso , Estenose das Carótidas/induzido quimicamente , Estenose das Carótidas/diagnóstico por imagem , Interações Medicamentosas , Feminino , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Terapia de Alvo Molecular/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico por imagem , Trombose/induzido quimicamente , Trombose/diagnóstico por imagem , Resultado do Tratamento
8.
Minerva Med ; 111(2): 173-180, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32338843

RESUMO

INTRODUCTION: Clinical data on short mandatory dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy, compared with prolonged DAPT in patients undergoing percutaneous coronary intervention (PCI) are insufficient. We aim to evaluate the effectiveness and safety of P2Y12 inhibitor monotherapy and prolonged DAPT after short mandatory DAPT on cardiovascular events in patients undergoing PCI. EVIDENCE ACQUISITION: A systematic literature search was performed in seven medical databases from building the database until July 2019. Three studies with randomized controlled trial (RCTs), totaling 21,970 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager v. 5.3 software. EVIDENCE SYNTHESIS: Our result of pooled analysis showed that there was noninferior rates of in major adverse cardiac and cerebrovascular events (MACCE), stroke, myocardial infarction and cardiac death between short mandatory DAPT followed by P2Y12 inhibitor monotherapy and prolonged DAPT in patients undergoing PCI. Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5 (OR=0.47, 95% CI: 0.31-0.70, P=0.002), compared with prolonged DAPT in patients undergoing PCI. However, Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy was not associated with BARC type 3-5, compared with prolonged DAPT. CONCLUSIONS: This meta-analysis demonstrated that short mandatory DAPT followed by P2Y12 inhibitor monotherapy compared with prolonged DAPT resulted in noninferior rates of MACCE, all-cause mortality, cardiac death, stroke, myocardial infarction and stent thrombosis. Furthermore, short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5.


Assuntos
Aspirina/efeitos adversos , Cardiopatias/mortalidade , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Acidente Vascular Cerebral/mortalidade , Aspirina/uso terapêutico , Causas de Morte , Cardiopatias/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Trombose/induzido quimicamente , Trombose/mortalidade
10.
Cardiovasc Pathol ; 47: 107210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32142924

RESUMO

Nonbacterial thrombotic endocarditis is a form of a thrombotic angiopathy involving the endothelial lined endocardial surfaces of the heart which includes valves and the chamber walls. Underlying etiologies for nonbacterial thrombotic endocarditis include autoimmune diseases, hypercoagulable states, in the setting of certain malignant neoplasms, and physical injury. The pathogenesis for these processes is that of primary endothelial injury resulting in a thrombotic angiopathy. We present a patient with heart failure being evaluated before hematopoietic stem cell transplantation who had previously been provided with chemotherapy and whose cardiac magnetic resonance imaging reveals findings suggestive of amyloidosis. A subsequent endomyocardial biopsy instead showed nonbacterial thrombotic endocarditis characterized by the endocardium with fibromyxoid thickening and overlying fresh fibrin. This case highlights histopathologic findings of chemotherapy-associated nonbacterial thrombotic endocarditis involving the right ventricle wall of the endocardium, therefore expanding the radiological differential in patients with cardiac magnetic resonance imaging findings suggestive of amyloidosis.


Assuntos
Amiloidose/patologia , Antineoplásicos/efeitos adversos , Endocardite não Infecciosa/induzido quimicamente , Cardiopatias/patologia , Valvas Cardíacas/efeitos dos fármacos , Trombose/induzido quimicamente , Amiloidose/diagnóstico por imagem , Biópsia , Cardiotoxicidade , Diagnóstico Diferencial , Endocardite não Infecciosa/diagnóstico por imagem , Endocardite não Infecciosa/patologia , Cardiopatias/diagnóstico por imagem , Valvas Cardíacas/diagnóstico por imagem , Valvas Cardíacas/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Trombose/diagnóstico por imagem , Trombose/patologia
11.
Cardiovasc Drugs Ther ; 34(1): 15-23, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32062793

RESUMO

PURPOSE: Drugs inhibiting the platelet P2Y12 receptor, such as clopidogrel and prasugrel, are potent antithrombotic agents and are widely used in cardiovascular disease. However, the adverse effects of these drugs have limited their clinical use. For example, clopidogrel resistance occurs in approximately one third of patients, while prasugrel increases the risk of major bleeding. Therefore, new generations of such drugs are of clinical interest. METHODS: In this study, the pharmacodynamics of a new P2Y12 antagonist, CN-218, was compared with that of clopidogrel and prasugrel in rats and mice. The differences between CN-218 and clopidogrel include deuteration of the 7-position methyl carboxylate and the introduction of cinnamate in the 2-position of thiophene. RESULTS: CN-218 had an antiaggregatory efficacy that was at least five times more potent than that of clopidogrel but not as potent as that of prasugrel. It had a significant impact on activated partial thromboplastin time (APTT), whereby the APTT of CN-218-treated rats was approximately 9 s longer than that of the vehicle- or clopidogrel-treated group, while it had no impact on prothrombin time (PT) in rats. CN-218 had a similar potent antithrombotic effect to that of prasugrel and clopidogrel and also reduced the risk of bleeding compared to prasugrel. CONCLUSION: CN-218 may be a promising antithrombotic agent, with potent antiplatelet and significant anticoagulant activity, as well as a lower risk of bleeding compared to clopidogrel and prasugrel.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Fibrinolíticos/farmacologia , Piperidinas/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Tiofenos/farmacologia , Trombose/prevenção & controle , Animais , Plaquetas/metabolismo , Carragenina , Clopidogrel/farmacologia , AMP Cíclico/sangue , Modelos Animais de Doenças , Fibrinolíticos/toxicidade , Hemorragia/induzido quimicamente , Masculino , Camundongos , Piperidinas/toxicidade , Inibidores da Agregação de Plaquetas/toxicidade , Cloridrato de Prasugrel/farmacologia , Antagonistas do Receptor Purinérgico P2Y/toxicidade , Ratos Wistar , Receptores Purinérgicos P2Y12/sangue , Tiofenos/toxicidade , Trombose/sangue , Trombose/induzido quimicamente
12.
Arterioscler Thromb Vasc Biol ; 40(2): 335-349, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31941383

RESUMO

OBJECTIVE: Cardiovascular disease is a major public health problem. Among cardiovascular disease's risk factors, tobacco smoking is considered the single most preventable cause of death, with thrombosis being the main mechanism of cardiovascular disease mortality in smokers. While tobacco smoking has been on the decline, the use of waterpipes/hookah has been rising, mainly due to the perception that they are less harmful than regular cigarettes. Strikingly, there are few studies on the negative effects of waterpipes on the cardiovascular system, and none regarding their direct contribution to thrombus formation. Approach and Results: We used a waterpipe whole-body exposure protocol that mimics real-life human exposure scenarios and investigated its effects, relative to clean air, on platelet function, hemostasis, and thrombogenesis. We found that waterpipe smoke (WPS)-exposed mice exhibited both shortened thrombus occlusion and bleeding times. Further, our results show that platelets from WPS-exposed mice are hyperactive, with enhanced agonist-induced aggregation, dense and α-granule secretion, αIIbß3 integrin activation, phosphatidylserine expression, and platelet spreading, when compared with clean air-exposed platelets. Finally, at the molecular level, it was found that Akt (protein kinase B) and ERK (extracellular signal-regulated kinases) phosphorylation are enhanced in the WPS and in nicotine-treated platelets. CONCLUSIONS: Our findings demonstrate that WPS exposure directly modulates hemostasis and increases the risk of thrombosis and that this is mediated, in part, via a state of platelet hyperactivity. The negative health impact of WPS/hookah, therefore, should not be underestimated. Moreover, this study should also help in raising public awareness of the toxic effects of waterpipe/hookah.


Assuntos
Plaquetas/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Ativação Plaquetária/fisiologia , Cachimbos de Água , Fumar/efeitos adversos , Trombose/metabolismo , Animais , Plaquetas/metabolismo , Artérias Carótidas/patologia , Cotinina/toxicidade , Modelos Animais de Doenças , Citometria de Fluxo , Seguimentos , Immunoblotting , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nicotina/toxicidade , Contagem de Plaquetas , Fumaça/efeitos adversos , Trombose/induzido quimicamente , Fatores de Tempo
13.
J Oncol Pharm Pract ; 26(1): 74-92, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30917738

RESUMO

The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.


Assuntos
Antineoplásicos/administração & dosagem , Asparaginase/administração & dosagem , Institutos de Câncer/normas , Gerenciamento Clínico , Monitoramento de Medicamentos/normas , Polietilenoglicóis/administração & dosagem , Guias de Prática Clínica como Assunto/normas , Adulto , Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Pré-Escolar , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Humanos , Polietilenoglicóis/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Trombose/induzido quimicamente , Trombose/epidemiologia , Trombose/prevenção & controle , Resultado do Tratamento
14.
Hematology Am Soc Hematol Educ Program ; 2019(1): 198-203, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808835

RESUMO

Bleeding is the main complication of oral anticoagulant (OAC) therapy, with major bleeds occurring in about 2% to 4% of OAC-treated patients per year. Although direct oral anticoagulants (DOACs) reduce the risk of major, fatal, and intracranial hemorrhage, major DOAC-related bleeding is associated with substantial morbidity and mortality, with case-fatality rates of 8% to 15% reported. Specific reversal agents for dabigatran (idarucizumab) and factor Xa inhibitors (andexanet) correct laboratory indices of anticoagulant effect. Clinical studies suggest that the majority of patients receiving these agents for DOAC-associated major bleeds experience clinical hemostasis. However, uncertainty remains regarding the incremental benefit of these agents and prothrombin complex concentrates over supportive measures alone, based on cohort studies that lacked control groups. Similar methodologic limitations preclude firm conclusions regarding the harms associated with use of these agents. Importantly, patients with DOAC-related major bleeding have substantial short-term risks of thrombosis and mortality, emphasizing the need for individualized patient assessment and protocolized bleed management strategies that include assessment of candidacy for safe resumption of OACs. With expanding indications and increasing prevalence of DOAC-eligible patients, bleeding complications and their management represent an ever-greater major health problem.


Assuntos
Anticoagulantes/efeitos adversos , Administração Oral , Idoso de 80 Anos ou mais , Hemorragia/induzido quimicamente , Humanos , Masculino , Fatores de Risco , Trombose/induzido quimicamente
15.
Hematology Am Soc Hematol Educ Program ; 2019(1): 204-208, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808849

RESUMO

A 77-year-old man with atrial fibrillation and a CHA2DS2Vasc score of 6 for hypertension, age, diabetes, and previous stroke is brought to the emergency department with decreased level of consciousness. He is anticoagulated with rivaroxaban (a direct oral factor Xa inhibitor [FXaI]) and received his last dose about 4 hours before presentation. Urgent computed tomography of the head shows intracerebral hemorrhage. Because of his previous stroke, the patient's family is concerned about treating the bleed with pharmacological agents that may increase the risk of stroke. What are the risks of thrombosis and mortality related to the use of prothrombin complex concentrates (PCCs) and andexanet alfa for patients with direct oral FXaI-associated major bleeding?


Assuntos
Fatores de Coagulação Sanguínea/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Proteínas Recombinantes/efeitos adversos , Trombose/induzido quimicamente , Trombose/mortalidade , Idoso , Ensaios Clínicos como Assunto , Humanos , Masculino
16.
Medicine (Baltimore) ; 98(50): e18249, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852092

RESUMO

RATIONALE: Cancer and chemotherapy individually confer hypercoagulability and increased risks of thrombosis. Most thromboembolic complication after breast cancer chemotherapy was venous thrombosis after multiagent chemotherapy. Arterial thrombosis is extremely rare in early breast cancer patients receiving adjuvant chemotherapy. PRESENTING CONCERNS: A 55-year-old woman with right breast cancer presented to the emergency department with sudden pain, numbness, and swelling in her left hand. She underwent breast conserving surgery and sentinel lymph node biopsy 2 months before the visit. She received the second cycle of adjuvant Adriamycin-cyclophosphamide chemotherapy 5 days before. INTERVENTIONS: Computed tomography angiography revealed acute arterial thrombosis in the left brachial, radial, and ulnar arteries. Unfractionated heparin was initiated immediately, followed by brachial and radial-ulnar thrombectomy, restoring perfusion to the extremity. The postoperative course was uncomplicated; she was discharged on warfarin at a daily dose of 4 mg. OUTCOMES: Chemotherapy was discontinued. Anticoagulation with warfarin was continued. She subsequently received adjuvant endocrine therapy with an aromatase inhibitor and adjuvant radiotherapy. MAIN LESSONS: Despite the low risks of arterial thrombosis in breast cancer, it is a devastating complication with significant morbidity and mortality. Thromboprophylaxis should be considered in those at risk. Immediate anticoagulant therapy and surgical intervention should be considered in affected cases.


Assuntos
Artéria Braquial , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Artéria Radial , Trombose/induzido quimicamente , Artéria Ulnar , Doença Aguda , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante/efeitos adversos , Angiografia por Tomografia Computadorizada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Trombectomia/métodos , Trombose/diagnóstico , Trombose/cirurgia , Ultrassonografia Doppler
17.
Blood Coagul Fibrinolysis ; 30(8): 385-392, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31738288

RESUMO

: The novel agent pd-FVIIa/FX is a 1 : 10 protein weight mixture of activated factor VII (FVIIa) and factor X (FX) derived from donated blood plasma. A phase III clinical trial of pd-FVIIa/FX revealed high efficacy for bleeding episodes in haemophilia patients with inhibitors. However, up to now, only one case of this new agent being used for surgery had been reported. The objective of this study is to evaluate the perioperative haemostatic efficacy and safety of pd-FVIIa/FX in haemophilia patients with inhibitors. We retrospectively reviewed 25 operation charts from 14 haemophilia patients with high-responding inhibitors using pd-FVIIa/FX during the perioperative period. Efficacy was evaluated by attending physicians and results divided into four groups (excellent, good, fair, and poor). The operation chart was provided by nine Japanese medical institutes with expertise in haemophilia management. Out of the total of 25 surgical procedures, 44% (11/25) were classified as major surgery and the remainders were minor surgeries. In all of the surgeries but one, rFVIIa and/or APCC were administered in combination or sequential method. In all cases except one, the haemostatic efficiency rate was judged as excellent or good by treating physicians for an overall efficacy rate of 96%. No thrombotic adverse effects were reported. This study's results suggest that both combination and sequential therapy of pd-FVIIa/FX and other bypassing agents are well tolerated and effective for the control of perioperative bleeding in haemophilia patients with high-responding inhibitors.


Assuntos
Fator VIIa/uso terapêutico , Fator X/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Hemostáticos/normas , Assistência Perioperatória/métodos , Adulto , Combinação de Medicamentos , Quimioterapia Combinada/efeitos adversos , Fator VIIa/efeitos adversos , Fator X/efeitos adversos , Hemofilia A/imunologia , Hemofilia B/imunologia , Hemorragia/prevenção & controle , Hemostáticos/efeitos adversos , Hemostáticos/uso terapêutico , Humanos , Masculino , Assistência Perioperatória/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/normas , Trombose/induzido quimicamente , Resultado do Tratamento , Adulto Jovem
18.
Blood ; 134(26): 2346-2353, 2019 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-31697819

RESUMO

Genetic predispositions to venous thromboembolism (VTE) are relatively frequent in the general population and comprise a heterogeneous group of disorders. Whereas the most frequent congenital risk factors for thrombosis only moderately increase the risk, a deficiency in antithrombin (AT), one of the most important natural inhibitors of blood coagulation, carries a higher risk. Congenital AT deficiency is an infrequently encountered genetic risk factor for VTE, and different subtypes vary with regard to their thrombotic risk. Patients with congenital AT deficiency, especially those with quantitative deficiency (type 1), may develop thrombosis early in life and often have a conspicuous family history of first- and second-degree relatives with VTE. Women are particularly affected because of the risk potentiation by combined estrogen/progestogen oral contraceptive use or pregnancy. The lack of controlled trials or even observational studies of large cohorts does not allow therapeutic decisions to be based on scientific evidence. In this review, we will discuss cases with thrombotic manifestations and the tailored management of patients with this congenital thrombosis risk factor.


Assuntos
Anticoagulantes/uso terapêutico , Deficiência de Antitrombina III/complicações , Antitrombinas/uso terapêutico , Anticoncepcionais Orais Hormonais/efeitos adversos , Trombose/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Adolescente , Adulto , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Gravidez , Prognóstico , Fatores de Risco , Trombose/induzido quimicamente , Tromboembolia Venosa/induzido quimicamente , Adulto Jovem
19.
Vascul Pharmacol ; 122-123: 106598, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31655164

RESUMO

An increase in aldosterone levels positively correlates with an increased risk of acute cardiovascular thrombotic events. The aim of the study was to determine the mechanism of action of prothrombotic aldosterone focusing on the rapid effects of the hormone on platelets, coagulation, and fibrinolysis. A wide panel of advanced ex vivo and in vitro techniques was used for the evaluation of coagulation and fibrinolysis in aldosterone-treated rats. Additionally, two experimental mice models of thrombosis, which allowed for the intravital observation of the first stage of thrombus formation in real time, were used. Acute administration of aldosterone in rats increased the density of fibrin net and platelet aggregates in clots as well as reduced fibrinolysis. These effects were observed within 10 min and were partially suppressed by eplerenone. Moreover, acute administration of aldosterone in mice enhanced platelet accumulation at the site of endothelial injury induced by laser and increased the area of irreversibly activated platelets in FeCl3-induced thrombus. These results demonstrate that aldosterone acutely affects platelets, coagulation, and fibrinolysis, leading to an enhanced thrombosis. The aldosterone effects were mediated partially via a mineralocorticoid receptor. The mechanism seems to involve non-genomic signaling since the effects were observed within a few minutes of aldosterone administration.


Assuntos
Aldosterona/toxicidade , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Fibrinólise/efeitos dos fármacos , Trombose/induzido quimicamente , Animais , Plaquetas/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Agregação Plaquetária/efeitos dos fármacos , Ratos Wistar , Trombose/sangue , Fatores de Tempo
20.
Lupus ; 28(12): 1460-1467, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31594451

RESUMO

Whether the presence or absence of antiphospholipid antibodies (aPL) in patients with lupus nephritis (LN) is associated with differences in clinical outcomes remains unclear. We reviewed LN patients at a single centre during 2000-2017, and compared the clinical features and long-term outcomes between patients who were seropositive or seronegative for aPL. aPL was detected in 53/149 (35.6%) patients with biopsy-proven LN, and anticardiolipin IgM, anticardiolipin IgG, anti-ß2 glycoprotein I and lupus anticoagulant was detected in 18.8%, 18.1%, 10.7% and 8.1%, respectively. Follow-up was 155.8 ± 61.0 months, and was similar between aPL-seropositive and -seronegative patients. aPL seropositivity persisted in 94.3% of patients during remission. aPL-seropositive patients showed inferior patient survival (91% and 85% at 10 and 15 years, respectively, compared to 99% and 95% in aPL-seronegative patients; p = 0.043). Nine (6.0%) patients died during follow-up, including six aPL-seropositive (four thrombotic events and two bleeding complications related to anticoagulation) and three aPL-seronegative patients. aPL seropositivity was associated with more rapid decline in estimated glomerular filtration rate (-1.44 mL/min/year compared to -0.38 mL/min/year in aPL-seronegative patients; p = 0.027) and inferior long-term renal survival (82% and 74% at 10 and 15 years, respectively, compared to 91% and 87% in aPL-seronegative patients; p = 0.034). aPL-seropositive patients also had a higher incidence of thrombotic events and miscarriage (32.1% and 13.2%, respectively, compared to 16.7% and 2.1% in the aPL-seronegative group; p = 0.030 and 0.006). We concluded that aPL seropositivity was associated with inferior long-term patient and renal survival and more frequent thrombotic events and miscarriage in LN patients.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Nefrite Lúpica/sangue , Nefrite Lúpica/patologia , Aborto Espontâneo/etiologia , Adulto , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Feminino , Taxa de Filtração Glomerular , Hemorragia/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Rim/fisiopatologia , Inibidor de Coagulação do Lúpus/sangue , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Trombose/induzido quimicamente , beta 2-Glicoproteína I/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA