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1.
Nat Genet ; 51(11): 1574-1579, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31676865

RESUMO

Venous thromboembolism is a significant cause of mortality1, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought.


Assuntos
Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Doenças Vasculares/genética , Tromboembolia Venosa/genética , Idoso , Animais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/genética , Fatores de Risco , Reino Unido/epidemiologia , Doenças Vasculares/epidemiologia , Doenças Vasculares/patologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/patologia
2.
Lancet Haematol ; 6(10): e500-e509, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31420317

RESUMO

BACKGROUND: Rivaroxaban has been shown to be efficacious for treatment of venous thromboembolism in adults, and has a reduced risk of bleeding compared with standard anticoagulants. We aimed to develop paediatric rivaroxaban regimens for the treatment of venous thromboembolism in children and adolescents. METHODS: In this phase 2 programme, we did three studies to evaluate rivaroxaban treatment in children younger than 6 months, aged 6 months to 5 years, and aged 6-17 years. Our studies used a multicentre, single-arm design at 54 sites in Australia, Europe, Israel, Japan, and north America. We included children with objectively confirmed venous thromboembolism previously treated with low-molecular weight heparin, fondaparinux, or a vitamin K antagonist for at least 2 months or, in children who had catheter-related venous thromboembolism for at least 6 weeks. We administered rivaroxaban orally in a bodyweight-adjusted 20 mg-equivalent dose, based on physiologically-based pharmacokinetic modelling predictions and EINSTEIN-Jr phase 1 data in young adults, in either a once-daily (tablets; for those aged 6-17 years), twice-daily (in suspension; for those aged 6 months to 11 years), or three times-daily (in suspension; for those younger than 6 months) dosing regimen for 30 days (or 7 days for those younger than 6 months). The primary aim was to define rivaroxaban treatment regimens that match the target adult exposure range. The principal safety outcome was major bleeding and clinically relevant non-major bleeding. Analyses were per-protocol. The predefined efficacy outcomes were symptomatic recurrent venous thromboembolism, asymptomatic deterioration on repeat imaging at the end of the study treatment period. These trials are registered at ClinicalTrials.gov, numbers NCT02564718, NCT02309411, and NCT02234843. FINDINGS: Between Feb 11, 2013, and Dec 20, 2017, we enrolled 93 children (ten children younger than 6 months; 15 children aged 6 months to 1 year; 25 children aged 2-5 years; 32 children aged 6-11 years; and 11 children aged 12-17 years) into our study. 89 (96%) children completed study treatment (30 days of treatment, or 7 days in those younger than 6 months), and 93 (100%) children received at least one dose of study treatment and were evaluable for the primary endpoints. None of the children had a major bleed, and four (4%, 95% CI 1·2-10·6) of these children had a clinically relevant non-major bleed (three children aged 12-17 years with menorrhagia and one child aged 6-11 years with gingival bleeding). We found no symptomatic recurrent venous thromboembolism in any patients (0%, 0·0-3·9). 24 (32%) of 75 patients with repeat imaging had their thrombotic burden resolved, 43 (57%) patients improved, and eight (11%) patients were unchanged. No patient deteriorated. We confirmed therapeutic rivaroxaban exposures with once-daily dosing in children with bodyweights of at least 30 kg and with twice-daily dosing in children with bodyweights of at least 20 kg and less than 30 kg. Children with low bodyweights (<20 kg, particularly <12 kg) showed low exposures so, for future studies, rivaroxaban dosages were revised for these weight categories, to match the target adult exposure range. 61 (66%) of 93 children had adverse events during the study. Pyrexia was the most common adverse event (ten [11%] events), and anaemia and neutropenia or febrile neutropenia were the most frequent grade 3 or worse events (four [4%] events each). No children died or were discontinued from rivaroxaban because of adverse events. INTERPRETATION: Treatment with bodyweight-adjusted rivaroxaban appears to be safe in children. The treatment regimens that we confirmed in children with bodyweights of at least 20 kg and the revised treatment regimens that we predicted in those with bodyweights less than 20 kg will be evaluated in the EINSTEIN-Jr phase 3 trial in children with acute venous thromboembolism. FUNDING: Bayer AG, Janssen Research and Development.


Assuntos
Anticoagulantes/uso terapêutico , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Adolescente , Anemia/etiologia , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Peso Corporal , Criança , Pré-Escolar , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Fator Xa/análise , Feminino , Meia-Vida , Hemorragia/etiologia , Humanos , Lactente , Masculino , Neutropenia/etiologia , Tempo de Protrombina , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacocinética , Resultado do Tratamento , Tromboembolia Venosa/patologia
4.
Lancet Haematol ; 6(10): e530-e539, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31444124

RESUMO

BACKGROUND: Hospital-associated venous thromboembolism is a major patient safety concern. Provision of prophylaxis to patients admitted for elective total knee replacement surgery has been proposed as an effective strategy to reduce the incidence of venous thromboembolism. We aimed to assess the relative efficacy and safety of all available prophylaxis strategies in this setting. METHODS: We did a systematic review and Bayesian network meta-analyses of randomised controlled trials to assess the relative efficacy and safety of venous thromboembolism prophylaxis strategies and to populate an economic model that assessed the cost-effectiveness of these strategies and informed the updated National Institute for Health and Care Excellence (NICE) guideline recommendations for patients undergoing elective total knee replacement surgery. The Cochrane Library (CENTRAL), Embase, and Medline were last searched on June 19, 2017, with key terms relating to the population (venous thromboembolism and total knee replacement) and the interventions compared, including available pharmacological and mechanical interventions. Outcomes of interest were deep vein thrombosis (symptomatic and asymptomatic), pulmonary embolism, and major bleeding. Risk of bias was assessed, and relevant data extracted from the included randomised controlled trials for the network meta-analyses. Relative risks (RR; with 95% credible intervals [95% CrI]) compared to no prophylaxis, median ranks (with 95% CrI), and the probability of being the best intervention were calculated. The study was done in accordance with PRISMA guidelines. FINDINGS: 25 randomised controlled trials were included in the network meta-analyses. 23 trials (19 interventions; n=15 028) were included in the deep vein thrombosis network, 12 in the pulmonary embolism network (13 interventions; n=15 555), and 19 in the major bleeding network (11 interventions; n=19 797). Risk of bias ranged from very low to high. Rivaroxaban ranked first for prevention of deep vein thrombosis (RR 0·12 [95% CrI 0·06-0·22]). Low molecular weight heparin (LMWH; standard prophylactic dose, 28-35 days) ranked first in the pulmonary embolism network (RR 0·02 [95% CrI 0·00-3·86]) and LMWH (low prophylactic dose, 10-14 days) ranked first in the major bleeding network (odds ratio 0·08 [95% CrI 0·00-1·76]), but the results for pulmonary embolism and major bleeding are highly uncertain. INTERPRETATION: Single prophylaxis strategies are more effective in prevention of deep vein thrombosis in the elective total knee replacement population than combination strategies, with rivaroxaban being the most effective. The results of the pulmonary embolism and major bleeding meta-analyses are uncertain and no clear conclusion can be made other than what is biologically plausible (eg, that no prophylaxis and mechanical prophylaxis strategies should have the lowest risk of major bleeding). FUNDING: National Institute for Health and Care Excellence.


Assuntos
Anticoagulantes/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Artroplastia do Joelho , Hemorragia/etiologia , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Razão de Chances , Risco , Tromboembolia Venosa/patologia
6.
J Surg Oncol ; 120(3): 494-500, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31222842

RESUMO

BACKGROUND AND OBJECTIVES: Pancreatic cancer is strongly associated with thrombosis. We investigated early postoperative venous thromboembolism (PVTE) mortality among patients with pancreatic surgery and compared outcomes in adenocarcinoma pancreatic cancer (ACPC) to non-adenocarcinoma pancreatic neoplasm (NACPN). METHODS: We analyzed a prospectively collected database of patients who underwent pancreatic cancer or neoplasm-related surgery. As NACPN is underrepresented in other studies, we selected NACPN patients and a random sample of ACPC patients. PVTE was defined as VTE occurring within 3 months of surgical intervention. Statistical analysis was performed using Cox proportional hazards regression. RESULTS: A total of 441 pancreatic surgery patients were included, with 331 ACPC and 110 NACPN. Median follow-up was 449 days during which 90 (20.4%) patients developed VTE. PVTE occurred in 53 (12.0%) patients, including 41 (12.4%) ACPC patients and 12 (10.9%) NACPN patients. Those with PVTE had 60% higher mortality rate. A multivariable analysis found that PVTE is an independent predictor of increased mortality (HR Adj, 1.6; 95% CI, 1.1-2.2; P < .01). The mortality impact was not consistent between ACPC (HR, 3.2; 95% CI, 1.3-7.9) and NACPN groups (HR, 1.3; 95% CI, 0.9-1.8). CONCLUSIONS: Postoperative venous thromboembolism is an independent predictor of increased mortality in pancreatic surgery, specifically in adenocarcinoma pancreatic cancer surgery.


Assuntos
Carcinoma Ductal Pancreático/mortalidade , Neoplasias Pancreáticas/mortalidade , Tromboembolia Venosa/mortalidade , Idoso , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/patologia , Estudos Prospectivos , Estudos Retrospectivos , Tromboembolia Venosa/patologia , Tromboembolia Venosa/fisiopatologia
7.
Lupus ; 28(7): 903-905, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31018760

RESUMO

Protein S deficiency is rare in systemic lupus erythematosus (SLE) and is generally associated with the presence of antiphospholipid (APL) antibodies. Lack of protein S can cause skin necrosis, but when it does it is generally in response to warfarin exposure. In this article, we describe the case of a patient who had not received warfarin and without APL antibodies who developed extensive skin necrosis due to protein S deficiency. It is important to investigate protein S deficiency in patients with lupus and extensive skin ulcers as it is a sign of arterial thrombosis and venous thromboembolism.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Deficiência de Proteína S/diagnóstico , Pele/patologia , Feminino , Humanos , Necrose/patologia , Trombose/patologia , Tromboembolia Venosa/patologia , Adulto Jovem
8.
PLoS One ; 14(4): e0214134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30933993

RESUMO

BACKGROUND: Extended treatment is preconized in a significant proportion of patients with unprovoked venous thromboembolism (VTE). However, limited direct/indirect comparisons are available to appropriately weight the benefit/risk ratio of the diverse treatments available. We aimed to compare the rate of symptomatic recurrent VTE and major bleeding (MB), the net clinical benefit (VTE+MB) and death on vitamin-K antagonist (VKA), direct oral anticoagulants (DOAC) and antiplatelet drugs for extended anticoagulation. METHODS: A systematic literature search through September 2018 identified randomized trials studying these pharmacologic therapies for extended anticoagulation following VTE. Treatment effects were calculated using network meta-analysis with frequentist fixed-effects model. RESULTS: 18 trials (18,221 patients) were included in the analysis. All treatments reduced the risk of recurrence compared to placebo/observation. Nonetheless, VKA (RR 0.22; 95%CI 0.13-0.39) and DOAC (RRs ranging from 0.25-0.32; 95%CI ranging from 0.13-0.52) were more effective than aspirin, whereas low-dose VKA was less effective than standard-dose VKA (RR 2.47; 95%CI 1.34-4.55). The efficacy of DOAC was globally comparable to standard-adjusted dose VKA. Low- (RR 3.13; 95%CI 1.37-7.16) and standard-dose (RR 3.23; 95%CI 1.16-8.99) VKA also increased the risk of MB, which was not the case for any DOAC. Low-dose VKA and low-dose DOAC had similar effects on MB compared to standard-doses. Although there was a trend for reduced MB and enhanced net clinical benefit for DOAC compared to VKA, this was not statistically significant. The specific anticoagulant therapies had no significant effects on deaths. CONCLUSION: Standard-dose VKA and low/standard-dose DOAC share similar effects on VTE recurrence and MB, whereas aspirin and low-dose VKA were associated with lower benefit/risk ratio.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle , Vitamina K/antagonistas & inibidores , Varfarina/uso terapêutico , Administração Oral , Anticoagulantes/uso terapêutico , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/patologia , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Masculino , Meta-Análise em Rede , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Prevenção Secundária , Tromboembolia Venosa/sangue , Tromboembolia Venosa/patologia , Trombose Venosa/sangue , Trombose Venosa/patologia , Varfarina/efeitos adversos
9.
Clin Appl Thromb Hemost ; 25: 1076029619832111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30813755

RESUMO

Our aim was to measure the venous blood flow velocity (VBFV) in case of hemiparetic patients, after passive and active thromboembolic methods, as well as the consensual effect in the hemiparetic limb following the active venous exercises in the healthy limb. We examined 215 patients, with the median age of 58.0 (55.0-63.0) years. The VBFV was measured with a HADECO BIDOP ES-100 V II type Doppler ultrasound device, using an 8 MHz head, on the femoral vein at the level of the hip joint. For statistical analysis, SPSS version 22 was used. After passive movement, on the hemiparetic side, compared to the value in resting state, the VBFV significantly (12.6; 11.6-13.5 cm/s; P < .001) increased. Following active venous exercises performed on the healthy side, the VBFV significantly (18.0; 15.6-19.6 cm/s; P < .001) increased compared to the value in resting state. Following the active venous exercises performed on the healthy side, the VBFV measured on the hemiparetic side (consensual effect) was significantly (15.1 [14.1-16.5] cm/s; P < .001) higher than the value on the hemiparetic side in resting state. Active and passive mechanical thromboprophylaxis methods can be effective. Movements of the healthy limb significantly increase the VBFV in the inactive limb, and patients can perform it themselves several times a day.


Assuntos
Velocidade do Fluxo Sanguíneo/genética , Paresia/sangue , Tromboembolia Venosa/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paresia/patologia , Estudos Prospectivos , Tromboembolia Venosa/patologia
10.
Blood ; 133(21): 2269-2278, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-30926593

RESUMO

Anticoagulant therapy is the most effective strategy to prevent arterial and venous thromboembolism, but treating older individuals is challenging, because increasing age, comorbidities, and polypharmacy increase the risk of both thrombosis and bleeding. Warfarin and non-vitamin K antagonist oral anticoagulants are underused and often underdosed in the prevention of stroke in older patients with atrial fibrillation because of concerns about the risk of bleeding. Poor adherence to anticoagulant therapy is also an issue for older patients with atrial fibrillation and those at risk of recurrent pulmonary embolism. In this review, we present 5 clinical cases to illustrate common challenges with anticoagulant use in older patients and discuss our approach to institute safe and effective antithrombotic therapy.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Varfarina/uso terapêutico , Administração Oral , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/patologia , Feminino , Humanos , Masculino , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Tromboembolia Venosa/complicações , Tromboembolia Venosa/patologia , Varfarina/efeitos adversos
11.
Clin Appl Thromb Hemost ; 25: 1076029619833480, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30841720

RESUMO

Unfractionated heparin dosing is unpredictable and subject to numerous pharmacokinetic changes including distribution and metabolic changes associated with obesity and age. Weight-based dosing is commonly used to better predict the dose for a patient when targeting a therapeutic range. A dosing equation that adjusts weight-based doses for age and body mass index may improve therapeutic dose prediction. We conducted a 2-phase observational study with a derivation and validation period to develop an equation to adjust weight-based unfractionated heparin for age and body mass index to target a therapeutic activated partial thromboplastin time of 60 to 80 seconds. The first phase retrospectively identified patients who acheived therapeutic anticoagulation and utilized linear regression to determine a predictive equation for weight-based dosing that adjusts for age and body mass index. The second phase prospectively identified patients in an observational manner and compared the dose of unfractionated heparin on which they became therapeutic against both the weight-based dose and the predicted dose adjusted for age and body mass index. The correlation between predictive age and body mass index adjusted dose and actual therapeutic dose was 0.703 compared to the correlation between the empiric weight-based dose and actual therapeutic dose which was 0.532 ( P = .05). Age and body mass index adjusted weight-based dosing significantly improved therapeutic dose prediction for unfractionated heparin. Further study in a prospective, randomized trial is warranted for validation of this approach in a real world setting.


Assuntos
Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacologia , Índice de Massa Corporal , Peso Corporal , Feminino , Heparina/administração & dosagem , Heparina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboembolia Venosa/patologia
12.
J Thromb Thrombolysis ; 47(4): 495-504, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30859370

RESUMO

In patients with active cancer and acute venous thromboembolism (VTE), the low-molecular-weight-heparin (LMWH) dalteparin is more effective than vitamin K antagonist (VKA) in reducing the risk of recurrent venous thromboembolism (rVTE) without increasing the risk of bleeding. However, the relative benefit of LMWH versus VKA in patients with active cancer at high or low risk of rVTE and bleeding is unclear. This post hoc analysis used data from the CLOT study to explore the efficacy and safety of LMWH versus VKA in preventing recurrent thrombosis in high- and low-risk patients with active cancer. High-risk patients were defined by metastatic disease and/or antineoplastic treatment at baseline; low-risk patients presented with neither. Among high-risk patients, rVTE occurred in 25/318 (8%) (LMWH) versus 53/314 (17%) (VKA) (hazard ratio, 0.44; p = 0.001). No significant difference was detected in the rate of major or any bleeding. The 6-month mortality rate was 40% (LMWH) versus 41% (VKA). In low-risk patients, 2/20 (10%) (LMWH) had rVTE versus 0/24 (0%) (VKA) (hazard ratio, not estimable; p = 0.998). No significant difference was detected in the rate of major or any bleeding. The 6-month mortality rate was 20% (LMWH) versus 29% (VKA). In patients with cancer-associated thrombosis at high risk of rVTE and bleeding, the LMWH dalteparin was more effective than VKA in reducing the risk of rVTE without increasing the risk of bleeding. No difference in rate of rVTE or bleeding was observed between LMWH and VKA among low-risk patients.


Assuntos
Cumarínicos/administração & dosagem , Dalteparina/administração & dosagem , Neoplasias/tratamento farmacológico , Trombose/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Idoso , Cumarínicos/efeitos adversos , Dalteparina/efeitos adversos , Intervalo Livre de Doença , Feminino , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Taxa de Sobrevida , Trombose/mortalidade , Trombose/patologia , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/patologia
13.
J Thromb Thrombolysis ; 47(4): 572-577, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30756343

RESUMO

It is unknown whether the risk factor profile for mesenteric venous thrombosis (MVT) is different from systemic venous thromboembolism (VTE). The aim of the present population-based study was to compare acquired and inherited risk factors in MVT versus VTE. Identification of all MVT patients at Skåne University Hospital between 2000 and 2015 was performed in patient records and AuriculA (Swedish anticoagulation registry). VTE patients were retrieved from the Malmö Thrombophilia Study (MATS), including 1465 consecutive unselected VTE patients between 1998 and 2008. Patients with MVT (n = 120) were younger (p < 0.001), had higher glomerular filtration rate (p < 0.001), lower smoking rate (p < 0.001), and had less often undergone recent surgery (p = 0.025). The prevalence of solid cancer (19.2% in MVT versus 12.1% in VTE; p = 0.026) and intra-abdominal cancer (16.7% versus 2.3%; p < 0.001) were higher in MVT. The prevalence of factor V Leiden mutation without presence of cancer was lower in MVT compared to VTE (26.6% versus 38.9%; p = 0.031). Thirty-day mortality was higher in the MVT group (9.2% versus 0.6%; p < 0.001), but did not differ at long-term follow-up according to Kaplan-Meier analysis (p = 0.73). Patients with MVT have a higher prevalence of cancer and lower prevalence of factor V Leiden mutation than those with systemic VTE. Intra-abdominal cancer should be excluded in MVT patients, and the high prevalence of factor V Leiden mutation in patients without cancer in both groups suggests that screening for thrombophilia in patients without cancer should be considered in this population for both groups.


Assuntos
Fator V/genética , Veias Mesentéricas , Mutação de Sentido Incorreto , Neoplasias , Trombofilia , Trombose , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/genética , Neoplasias/patologia , Prevalência , Fatores de Risco , Trombofilia/epidemiologia , Trombofilia/genética , Trombofilia/patologia , Trombose/epidemiologia , Trombose/genética , Trombose/patologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/genética , Tromboembolia Venosa/patologia
14.
Circulation ; 139(10): e56-e528, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30700139
15.
Clin Appl Thromb Hemost ; 25: 1076029618821184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30808213

RESUMO

A variety of viral infections are associated with hypercoagulable states and may be linked to the development of deep venous thrombosis and pulmonary embolism. The Zika and Chikungunya viral infections spread through the South and Central American continents, moving to North America in 2016, with severe cases of polyarthralgia, fever, and Guillain-Barré syndrome leading eventually to death. A decreased trend for both infections was reported in the first quarter of 2017. In this article, we report the possible association of venous thromboembolic events associated with Zika infection. After 2 cases of deep venous thrombosis in patients with acute Zika infections, D-dimer levels were measured in 172 consecutive patients who presented to the emergency department of a university hospital in an endemic region of Brazil with either Zika or Chikungunya infections confirmed by polymerase chain reaction tests. D-dimer levels were increased in 19.4% of 31 patients with Zika and in 63.8% of 141 patients with Chikungunya infections. The mechanisms behind this association are yet to be elucidated as well as the potential for venous thromboembolism prevention strategies for in-hospital patients affected by Zika and Chikungunya infections.


Assuntos
Vírus Chikungunya/patogenicidade , Tromboembolia Venosa/etiologia , Infecção por Zika virus/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tromboembolia Venosa/patologia
16.
Clin Appl Thromb Hemost ; 25: 1076029618823288, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30808214

RESUMO

Tumor thrombus is a unique characteristic of renal cell carcinoma (RCC). However, only a few studies have reported its clinical influence on the occurrence of venous thromboembolism (VTE). This study aimed to clarify the influence of tumor thrombus and other risk factors for VTE and to elucidate the impact of tumor thrombus on survival outcomes. We retrospectively reviewed data from patients with RCC who underwent radical or partial nephrectomy from September 1999 to August 2015 at Seoul National University Hospital. A total of 2762 patients were enrolled. The 1- and 5-year cumulative incidences of VTE were 0.5% ± 0.1% and 1.5% ± 0.3%, respectively. During a median follow-up of 39.0 months (95% confidence interval [CI], 37.1-41.0 months), deep vein thrombosis occurred in 13 patients and pulmonary embolism in 15 patients. Patients with tumor thrombus (diagnosed by surgical pathology findings) had a significantly higher incidence of VTE than those without thrombus (odds radio 8.160, 95% CI, 1.480-45.004). Older age (≥60 years) and higher preoperative C-reactive protein (>0.5 mg/dL) were also significant risk factors for VTE. Additionally, tumor thrombus was independently associated with worse progression-free survival (PFS) but not with overall survival (OS) in multivariable analysis (hazard ratio [HR] 1.916, 95% CI, 1.295-2.834 for PFS; HR 1.164, 95% CI, 0.755-1.793 for OS). In conclusion, the incidence of VTE was relatively low in patients who underwent surgery for RCC. Nevertheless, patients with tumor thrombus had an increased risk of VTE and should be closely monitored for VTE.


Assuntos
Carcinoma de Células Renais/cirurgia , Tromboembolia Venosa/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/patologia , Adulto Jovem
17.
Clin Appl Thromb Hemost ; 25: 1076029618823287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30808218

RESUMO

The objectives of this study were to examine venous thromboembolism (VTE) prophylaxis patterns and risk for VTE events during hospitalization and in the outpatient continuum of care among patients hospitalized for acute illnesses in the United States with stratification by different age groups and renal disease status. Acutely ill hospitalized patients were identified from the MarketScan databases (January 1, 2012-June 30, 2015) and grouped by age (<65, 65-74, ≥75 years old) and whether or not they had a baseline diagnosis of renal disease, separately. Of acutely ill hospitalized patients, 60.1% (n = 10 748) were <65 years old, 15.7% (n = 2803) were 65 to 74 years old, and 24.3% (n = 4344) were ≥75 years old; 32.9% (n = 5892) had baseline renal disease. Among the study cohorts, the majority of patients received no VTE prophylaxis regardless of age or baseline renal status (52.1%-63.6%). Rates of VTE during hospitalization and in the 6 months postdischarge were 4.7%, 4.6%, and 4.5% for patients <65, 65 to 74, and ≥75 years old, respectively, and 6.3% and 3.8% for patients with and without baseline renal disease. The risk for VTE was elevated for 30 to 40 days after index admission regardless of age and renal disease status.


Assuntos
Nefropatias/terapia , Tromboembolia Venosa/prevenção & controle , Doença Aguda , Fatores Etários , Idoso , Feminino , Humanos , Nefropatias/patologia , Masculino , Fatores de Risco , Tromboembolia Venosa/patologia
18.
Support Care Cancer ; 27(10): 3833-3840, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30734088

RESUMO

PURPOSE: Anticoagulant therapy for at least 3-6 months is currently recommended for treatment of venous thromboembolism (VTE) in patients with cancer, but the optimal duration of treatment is unknown. This study examines the association between the duration of anticoagulation treatment and VTE recurrence in cancer patients. METHODS: The Humana claims database was used to identify newly diagnosed cancer patients who had their first VTE diagnosis between January 1, 2013, and May 31, 2015, and initiated injectable or oral anticoagulant therapy. Follow-up was calculated from the index treatment initiation to the end of eligibility or end of data (June 2015). VTE recurrence was defined as a hospitalization with a primary diagnosis of VTE. Cox proportional hazards models were used to evaluate the risk of VTE recurrence by duration of therapy in patients who discontinued therapy. RESULTS: The study included 1158 patients. Compared to patients treated for 0 to 3 months, VTE recurrences were significantly lower among patients treated for 3 to 6, or over 6 months. After adjustment for baseline characteristics, patients treated for 3 to 6 months (HR [95%CI], 0.53; 0.37-0.76) and more than 6 months (HR [95%CI], 0.48; 0.34-0.68) were still significantly less likely to have VTE recurrences compared to patients treated for 0 to 3 months (both p < 0.01). Findings were similar using a VTE event definition that included outpatient visits. CONCLUSIONS: Among newly diagnosed cancer patients with VTE, anticoagulant therapy lasting more than 3 months was associated with a lower risk of VTE recurrence.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Adulto , Idoso , Bases de Dados Factuais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Modelos de Riscos Proporcionais , Recidiva , Fatores de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/patologia
19.
J Korean Med Sci ; 34(6): e52, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30787683

RESUMO

Cancer-associated venous thromboembolism (CAT) is a common complication associated with high morbidity and mortality. In accordance with major clinical trials comparing low-molecular-weight heparin (LMWH) with a vitamin K antagonist (VKA), LMWH is currently the standard treatment for CAT, owing to its efficacy for thrombosis recurrence and improved safety profile compared to VKA. Over the past few years, direct oral anticoagulants (DOACs) have emerged as potential alternative therapies to LMWH due to their convenient route of administration and predictable pharmacokinetics, but evidence for their use in CAT is inconclusive, as only a small fraction of the study populations in these trials had CAT. Recently, two large head-to-head trials comparing DOACs to LMWH in CAT patients reported comparable efficacies of DOACs with increased bleeding risk. Occasionally, CAT treatment can be challenging due to the heterogeneity of underlying malignancies and comorbidities. Renal insufficiency and gastrointestinal defects are the main obstacles in anticoagulant selection. Careful choice of treatment candidates and proper anticoagulant strategies are critical for the treatment of CAT; hence, more studies are required to address these challenges.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias/patologia , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Ensaios Clínicos como Assunto , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias/complicações , Insuficiência Renal/complicações , Insuficiência Renal/patologia , Fatores de Risco , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/patologia , Vitamina K/antagonistas & inibidores
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