RESUMO
The cumulative incidence of symptomatic venous thromboembolism (VTE) among patients with malignant gliomas (MG) is estimated to be as high as 36% during the course of therapy. Development of VTE is associated with an increased risk of hospitalization, delays in cancer treatment, and an increased risk of complications including intracranial hemorrhage as well as VTE specific symptoms. Despite the high risk of VTE and associated morbidity, there is no standard recommendations regarding long term outpatient VTE prophylaxis in patients with MG due to the lack of clinical trial evidence in this patient population. In this study, we treated ten patients with newly diagnosed MG with apixaban, 2.5 mg twice daily beginning 2-21 days after craniotomy and continuing for up to 6 months. Unacceptable toxicity was defined by ≥ grade 2 CNS or non-CNS hemorrhage, a thromboembolic event (i.e. stroke) or cardiovascular event requiring anticoagulation or anti-platelet therapy. There were no unacceptable toxicities to report and no treatment-related adverse events. None of the patients on the study were diagnosed with a VTE while receiving apixaban. We conclude that apixaban can be given safely to patients with primary MG shortly after craniotomy and should be considered for VTE prevention in these high-risk patients.
Assuntos
Glioma , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Glioma/complicações , Glioma/tratamento farmacológico , Glioma/cirurgia , Humanos , Pirazóis , Piridonas/efeitos adversos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
INTRODUCTION: Drug options for VTE prophylaxis are increasing for ambulatory cancer patients and data regarding anticoagulant-drug interactions and their relationship to VTE and bleeding are needed to improve care. METHODS: Over one year, 108 cancer patients with high VTE risk were prospectively identified. Potential anticoagulant-drug interactions were ascertained by chart review and graded on need for intervention. Providers selected anticoagulant prophylaxis based on potential drug interactions and patient-provider discussion. A cross-sectional analysis was performed thereafter to evaluate VTE and bleeding endpoints within one year of anticoagulant initiation. RESULTS: The average number of potential drug interactions per patient was higher for warfarin than others (3.04 vs. 1.28 (apixaban), 1.02 (rivaroxaban), and 0.98 (LMWH)). The severity of the interactions based on grade was, for apixaban: 1.6% grade X, 50.8% grade D, and 47.5% grade C; for rivaroxaban: 2.1% grade X, 64.9% grade D, 33.0% grade C; for LMWH, 0% grade X, 66.7% grade D, 33.3% grade C; and for warfarin, 0% grade X, 29.4% grade D, 70.6% grade C. At the end of the investigational period, 11 bleeds and 7 VTEs were reported. Drug combinations significantly associated with an increased bleeding risk were crizotinib with apixaban or rivaroxaban and PPIs with warfarin. The use of sulfamethoxazole-trimethoprim with warfarin was associated with an increased VTE risk. CONCLUSIONS: DOACs had fewer DDIs than warfarin, although interaction severity differed between anticoagulants. Some anticoagulant-drug interactions were associated with bleeding or VTE. Although not powered for analysis, DDI severity did not affect bleeding rates and inversely correlated with VTE risk.
Assuntos
Anticoagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Estudos Transversais , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Extended half-life (EHL) factor VIII (FVIII) and IX (FIX) products are intended to decrease the burden of prophylaxis for patients with haemophilia A or B. Whether these newer concentrates have led to meaningful clinical practice change remains vague. AIM: To characterize the longitudinal use of standard (SHL) and EHL factor concentrates at haemophilia treatment centres (HTCs), using the ATHNdataset, a US database of 138 ATHN-affiliated HTCs. METHODS: Factor concentrate use among moderate and severe haemophilia A and B patients without inhibitors was analysed at three time points over 18 months. RESULTS: Use of EHL concentrates rose from 10% of patients to 22% during this study. EHL FVIII prophylaxis is prescribed to the minority of patients, 28%; EHL FIX now predominates for prophylaxis, 52%. Rates of prescribed EHL products varied significantly by age group and HTC region. Median prescribed prophylaxis for SHL compared to EHL products was FVIII 6240 and 5200 and FIX 6968 and FIX 3900 IU/kg/y, respectively. On-demand EHL use has grown but has minimal contribution to overall usage (2%). CONCLUSION: Haemophilia treatment centre region and patient age impact the rate of adoption of EHL products; however, EHL prescribing continues to rise nationally, particularly for EHL FIX. Careful attention to annual cost of prophylaxis is imperative as the decrease in median EHL prophylaxis consumption is not offset by the higher unit cost of these products. It is unclear how further growth in use of EHLs will be impacted by emerging non-factor replacement and gene therapies.
Assuntos
Custos e Análise de Custo , Fator IX/economia , Fator IX/uso terapêutico , Fator VIII/economia , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Criança , Prescrições de Medicamentos/economia , Prescrições de Medicamentos/estatística & dados numéricos , Fator IX/farmacocinética , Fator VIII/farmacocinética , Feminino , Geografia , Meia-Vida , Hemofilia A/metabolismo , Hemofilia B/metabolismo , Humanos , Estudos Longitudinais , Masculino , Estados Unidos , Adulto JovemRESUMO
Acute myelogenous leukemia (AML) is an aggressive hematologic cancer characterized by infiltration of proliferative, clonal, abnormally differentiated cells of myeloid lineage in the bone marrow and blood. Malignant cells in AML often exhibit chromosomal and other genetic or epigenetic abnormalities that are useful in prognostic risk assessment. In this study, the relative expression and novel single-stranded DNA (ssDNA) binding function of purine-rich element binding proteins A and B (Purα and Purß) were systematically evaluated in established leukemia cell lines and in lineage committed myeloid cells isolated from patients diagnosed with a hematologic malignancy. Western blotting revealed that Purα and Purß are markedly elevated in CD33+ /CD66b+ cells from AML patients compared to healthy subjects and to patients with other types of myeloid cell disorders. Results of in silico database analysis of PURA and PURB mRNA expression during hematopoiesis in conjunction with the quantitative immunoassay of the ssDNA-binding activities of Purα and Purß in transformed leukocyte cell lines pointed to Purß as the more distinguishing biomarker of myeloid cell differentiation status. Purß ssDNA-binding activity was significantly increased in myeloid cells from AML patients but not from individuals with other myeloid-related diseases. The highest levels of Purß activity were detected in myeloid cells from primary AML patients and from AML patients displaying other risk factors forecasting a poor prognosis. Collectively, these findings suggest that the enhanced ssDNA-binding activity of Purß in transformed myeloid cells may serve as a unique and measurable phenotypic trait for improving prognostic risk stratification in AML.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , DNA de Cadeia Simples/metabolismo , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ligação Proteica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Published reports indicate low retrieval rates for retrievable inferior vena cava (IVC) filters. We performed a historic-controlled study of a 5-year intervention (March 2007 to February 2012) to improve IVC filter retrieval rates at a university medical center serving a rural area. All adults with a retrievable filter placed were included, except those with a life expectancy <6 months. The intervention included initial verbal counseling and printed educational materials, correspondence after discharge, and a hematology consultation. The control group included patients with retrievable filters placed in the 15 months preceding study initiation. In the control group, 116 filters were placed and 27 (23%) were removed, compared to 378 filters placed and 169 (45%) removed during the intervention. Adjusting for patient characteristics, the odds ratio of retrieval during the intervention was 3.03 (95% CI 1.85-4.27) compared to the control period. An intervention including patient education and hematology follow-up appeared to significantly improve IVC filter retrieval rates.
Assuntos
Remoção de Dispositivo/métodos , Equipe de Assistência ao Paciente , Avaliação de Processos em Cuidados de Saúde , Implantação de Prótese/instrumentação , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Filtros de Veia Cava , Centros Médicos Acadêmicos , Adulto , Idoso , Remoção de Dispositivo/normas , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hematologia , Estudo Historicamente Controlado , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Equipe de Assistência ao Paciente/normas , Educação de Pacientes como Assunto , Avaliação de Processos em Cuidados de Saúde/normas , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Melhoria de Qualidade/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Encaminhamento e Consulta , Estudos Retrospectivos , Serviços de Saúde Rural , Fatores de Tempo , Resultado do Tratamento , VermontRESUMO
Platelets and their granular contents influence both angiogenesis and breast cancer progression. This study was performed to assess the effect of breast cancer and its treatment on platelet biology and the response to inhibition of the platelet P2Y12 receptor. Receptor-specific platelet activation and inhibition was studied for three platelet-associated proteins important in cancer angiogenesis and progression, vascular endothelial growth factor (VEGF), thrombospondin1 (TSP1), and transforming growth factor beta 1 (TGF-ß1). Twenty-four women with active breast cancer and 10 healthy controls not receiving antiplatelet therapy participated in the study. Ex vivo activation of platelets in whole blood was accomplished using PAR1AP, PAR4AP, convulxin, and ADP. Platelet inhibition was accomplished using the P2Y12 receptor antagonist cangrelor (the in vitro equivalent of clopidogrel). VEGF, TSP1, and TGF-ß1 were measured using standard ELISA. Platelet activation by ADP, PAR1, PAR4, and collagen receptors increased VEGF, TSP1, and TGF-ß1 secretion in patients with breast cancer. Agonist-induced release of VEGF was greater in cancer patients as compared to healthy controls (p = 0.02 for ADP, p < 0.001 for PAR1AP, PAR4AP, and convulxin) despite a decrease in the efficiency of VEGF secretion in patients with breast cancer. These differences were not observed for TSP1 and TGF-ß1 secretion. P2Y12 receptor inhibition decreased VEGF, TSP1, and TGF-ß1 secretion. In patients with cancer, cangrelor inhibited TSP1 release to a greater extent than VEGF and TGF-ß1 release. In patients with breast cancer, the magnitude of platelet inhibition achieved by cangrelor was greater than that achieved with healthy controls for all agonists and platelet proteins studied. While platelets are known to influence progression of breast cancer, our results show that breast cancer and its treatment influence the platelet phenotype by increasing the secretion of pro-angiogenic proteins following platelet activation, modulating the efficiency of platelet protein release as well as increasing the response to antiplatelet therapy.
Assuntos
Plaquetas/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/terapia , Fenótipo , Biomarcadores , Plaquetas/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y12/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
While platelets are well known to play a central role in hemostasis and thrombosis, there is emerging experimental evidence to suggest that they also mediate tumor cell growth, dissemination, and angiogenesis. An increase in platelet number (thrombocytosis) and activity is seen in patients with a wide spectrum of malignancies, and the former is correlated with a decrease in overall survival and poorer prognosis. Preclinical data suggest that circulating tumor cell partnerships with platelets in the blood facilitate tumor metastases through direct interactions and secreted bioactive proteins. Platelets form aggregates with tumor cells, thereby protecting them from host immune surveillance through physical shielding and induction of "platelet mimicry." There is also laboratory evidence to suggest that activated platelets interact with cancer cells within the tumor microenvironment through paracrine signaling and direct contact, thereby promoting tumor cell growth and survival. For example, platelets release mediators of both tumor angiogenesis and osteoclast resorption. The interplay between platelets and tumor cells is complex and bidirectional with involvement of multiple other components within the tumor microenvironment, including immune cells, endothelial cells, and the extracellular matrix. We review the role of platelets in tumor progression, emphasizing the opportunity these interactions afford to target platelets and platelet function to improve patient outcomes in the cancer prevention and treatment setting.
Assuntos
Plaquetas/fisiologia , Neoplasias/metabolismo , Humanos , Metástase Neoplásica/patologia , Osteoclastos , Comunicação Parácrina/fisiologiaRESUMO
Treatment options for established post-thrombotic syndrome (PTS) are limited. Complex lymphedema therapy (CLT), a non-invasive treatment that improves lymphatic flow, may have the potential to improve PTS. We conducted a single-center, investigator-blind, randomized controlled trial of 31 patients with a clinically established diagnosis of PTS and compared the efficacy of graduated compression stockings alone (30-40 mmHg) with CLT, a treatment that includes compression stockings, exercise, patient education, skin care and lymphatic drainage. Primary outcomes were the 1- and 3-month changes in PTS severity by the Villalta score and disease-specific quality of life using the VEINES-QOL (Venous Insufficiency Epidemiological and Economic Study Quality of Life) questionnaire. Analysis was by intent-to-treat. We found from a baseline average score of 9.9 points, CLT reduced mean PTS severity scores by -2.4 points (p=0.02) at the 1-month and -2.3 points (p=0.05) at the 3-month follow-up. Score reductions with stockings only were similar at -2.1 (p=0.03) and -3.3 points (p=0.03) at 1 and 3 months. The differences in score between treatments were not significant. Neither treatment significantly changed the VEINES-QOL score except in patients with severe disease. Patients with moderate to severe PTS derived the greatest benefit from either therapy and the two therapies differentially impacted PTS signs and symptoms. We found a short course of lymphedema therapy and compression stockings offer similar benefit in patients with PTS; however, larger studies are needed to further explore the potential use of CLT in PTS, particularly in patients with more severe disease. ClinicalTrials.gov Identifier: NCT00633971.
Assuntos
Linfedema/terapia , Síndrome Pós-Trombótica/terapia , Meias de Compressão , Adulto , Idoso , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Insuficiência Venosa/terapiaRESUMO
BACKGROUND: Regulatory organizations recommend assessing hospital-acquired (HA) venous thromboembolism (VTE) risk for medical inpatients. OBJECTIVES: To develop and validate a risk assessment model (RAM) for HA-VTE in medical inpatients using objective and assessable risk factors knowable at admission. METHODS: The development cohort included people admitted to medical services at the University of Vermont Medical Center (Burlington, Vermont) between 2010 and 2019, and the validation cohorts included people admitted to Hennepin County Medical Center (Minneapolis, Minnesota), University of Michigan Medical Center (Ann Arbor, Michigan), and Harris Health Systems (Houston, Texas). Individuals with VTE at admission, aged <18 years, and admitted for <1 midnight were excluded. We used a Bayesian penalized regression technique to select candidate HA-VTE risk factors for final inclusion in the RAM. RESULTS: The development cohort included 60 633 admissions and 227 HA-VTE, and the validation cohorts included 111 269 admissions and 651 HA-VTE. Seven HA-VTE risk factors with t statistics ≥1.5 were included in the RAM: history of VTE, low hemoglobin level, elevated creatinine level, active cancer, hyponatremia, increased red cell distribution width, and malnutrition. The areas under the receiver operating characteristic curve and calibration slope were 0.72 and 1.10, respectively. The areas under the receiver operating characteristic curve and calibration slope were 0.70 and 0.93 at Hennepin County Medical Center, 0.70 and 0.87 at the University of Michigan Medical Center, and 0.71 and 1.00 at Harris Health Systems, respectively. The RAM performed well stratified by age, sex, and race. CONCLUSION: We developed and validated a RAM for HA-VTE in medical inpatients. By quantifying risk, clinicians can determine the potential benefits of measures to reduce HA-VTE.
Assuntos
Trombose , Tromboembolia Venosa , Trombose Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/complicações , Pacientes Internados , Teorema de Bayes , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologia , Trombose Venosa/complicações , Trombose/etiologia , Medição de Risco/métodos , Fatores de Risco , Hospitais , Estudos RetrospectivosRESUMO
The progression of breast cancer from early-stage to metastatic disease results from a series of events during which malignant cells invade and travel within the bloodstream to distant sites, leading to a clonogenic accumulation of tumor cells in non-breast tissue. While mechanistically complex, an emerging literature supports hemostatic elements as an important patient factor that facilitates the metastatic potential of breast cancer. Hemostatic elements involved include platelets, coagulation, and fibrinolysis. Key steps in breast tumor progression, including cellular transformation, proliferation, tumor cell survival, and angiogenesis, can be mediated by components of the hemostatic system. Thus, the hemostatic system provides potential targets for novel therapeutic approaches to breast cancer therapy with drugs in current use and in development. The present article provides a comprehensive overview of the evidence and mechanisms supporting the roles played by platelets, coagulation activation, and the fibrinolytic system in breast cancer progression.
Assuntos
Coagulação Sanguínea , Plaquetas/fisiologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Progressão da Doença , Feminino , Fibrinólise , Hemostasia , Humanos , Neovascularização Patológica , Ativação PlaquetáriaRESUMO
BACKGROUND: Clinically relevant bleeding risk in discharged medical patients is underestimated and leads to rehospitalization, morbidity, and mortality. Studies assessing this risk are lacking. OBJECTIVE: The aim of this study was to develop and validate a computable phenotype for clinically relevant bleeding using electronic health record (EHR) data and quantify the relative and absolute risks of this bleeding after medical hospitalization. METHODS: We conducted an observational cohort study of people receiving their primary care at sites affiliated with an academic medical center in northwest Vermont, United States. We developed a computable phenotype using EHR data (diagnosis codes, procedure codes, laboratory, and transfusion data) and validated it by manual chart review. Cox proportional hazard models with hospitalization modeled as a time-varying covariate were used to estimate clinically relevant bleeding risk. RESULTS: The computable phenotype had a positive predictive value of 80% and a negative predictive value of 99%. The bleeding rate in individuals with no medical hospitalizations in the past 3 months was 2.9 per 1000 person-years versus 98.9 per 1000 person-years in those who were discharged in the past 3 months. This translates into a hazard ratio (95% CI) of clinically relevant bleeding of 22.9 (18.9, 27.7), 13.0 (10.0, 16.9), and 6.8 (4.7, 9.8) over the first, second, and third months after discharge, respectively. CONCLUSION: We developed and validated a computable phenotype for clinically relevant bleeding and determined its relative and absolute risk in the 3 months after medical hospitalization discharge. The high rates of bleeding observed underscore the clinical importance of capturing and further studying bleeding after medical discharge.
Assuntos
Pacientes Internados , Trombose , Humanos , Estados Unidos , Risco , Estudos de Coortes , Hemorragia , HospitalizaçãoRESUMO
Background: Accurate and efficient methods to identify venous thromboembolism (VTE) events in hospitalized people are needed to support large-scale studies. Validated computable phenotypes using a specific combination of discrete, searchable elements in electronic health records to identify VTE and distinguish between hospital-acquired (HA)-VTE and present-on-admission (POA)-VTE would greatly facilitate the study of VTE, obviating the need for chart review. Objectives: To develop and validate computable phenotypes for POA- and HA-VTE in adults hospitalized for medical reasons. Methods: The population included admissions to medical services from 2010 to 2019 at an academic medical center. POA-VTE was defined as VTE diagnosed within 24 hours of admission, and HA-VTE as VTE identified more than 24 hours after admission. Using discharge diagnosis codes, present-on-admission flags, imaging procedures, and medication administration records, we iteratively developed computable phenotypes for POA-VTE and HA-VTE. We assessed the performance of the phenotypes using manual chart review and survey methodology. Results: Among 62,468 admissions, 2693 had any VTE diagnosis code. Using survey methodology, 230 records were reviewed to validate the computable phenotypes. Based on the computable phenotypes, the incidence of POA-VTE was 29.4 per 1000 admissions and that of HA-VTE was 3.6 per 1000 admissions. The POA-VTE computable phenotype had positive predictive value and sensitivity of 88.8% (95% CI, 79.8%-94.0%) and 99.1% (95% CI, 94.0%- 99.8%), respectively. Corresponding values for the HA-VTE computable phenotype were 84.2% (95% CI, 60.8%-94.8%) and 72.3% (95% CI, 40.9%-90.8%). Conclusion: We developed computable phenotypes for HA-VTE and POA-VTE with adequate positive predictive value and sensitivity. This phenotype can be used in electronic health record data-based research.
RESUMO
BACKGROUND: The relationship between metastatic colorectal cancer (mCRC) and venous thromboembolism (VTE) is poorly defined in the modern era. Our objective was to examine impact of putative risk factors including newer treatments and anti-angiogenic therapy on VTE incidence and survival in a modern older mCRC cohort. METHODS: This is a SEER-Medicare cohort analysis of mCRC patients diagnosed in 2004-2009. Risk factor analysis was conducted using Cox models adjusted for sex, diagnosis age, race, primary tumor location, comorbidity, and prior VTE history, with cancer treatments as time-varying covariates. Main outcomes were VTE incidence and overall survival. RESULTS: Ten thousand nine hundred and seventy six mCRC cases with mean age 77.9 years (range 65-107), 49.7% women, 83.5% white. There were 1306 VTE cases corresponding to 13.7% incidence at 1 year and 20.3% at 3 years. Independent VTE predictors included female sex (HR 1.27; 95% CI 1.14-1.42), African American race (HR 1.49; 1.27-1.73), prior VTE history (HR 16.3; 12.1-22.1), and right sided cancers (HR 1.16; 1.04-1.29). After adjustment, any therapy and bevacizumab (HR 0.68, 0.58-0.78) in particular were protective. Overall survival was 40.1% (39.4-41.3) at 1 year but improved significantly with any treatment. VTE following diagnosis of mCRC was associated with inferior OS (HR 1.09; 1.02-1.15). CONCLUSIONS: In this large contemporary mCRC cohort, effective systemic therapy including anti-angiogenic treatment was associated with lower VTE risk. Overall survival was poor, and modestly worse if a patient had a VTE at any time during treatment.
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Neoplasias do Colo , Neoplasias Retais , Tromboembolia Venosa , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Medicare , Fatores de Risco , Estados Unidos/epidemiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Thirty to seventy percent of all venous thromboembolism (VTE) events are associated with hospitalization. The absolute and relative risks during and after hospitalization are poorly characterized. OBJECTIVES: Quantify the absolute rate and relative risk of VTE during and up to 3 months after medical and surgical hospitalizations. PATIENTS/METHODS: We conducted an observational cohort study between 2010 and 2016 of patients cared for by the University of Vermont (UVM) Health Network's primary care population. Cox proportional hazard models with hospitalization modeled as a time-varying covariate were used to estimate VTE risk. RESULTS: Over 4.3 years of follow-up, 55 220 hospitalizations (156 per 1000 person-years) and 713 first venous thromboembolism events (2.0 per 1000 person-years) occurred. Among individuals not recently hospitalized, the rate of venous thromboembolism was 1.4 per 1000 person-years and 71.8 per 1000 person-years during hospitalization. During the first, second, and third months after discharge, the rates of venous thromboembolism were 35.1, 11.3, and 5.2 per 1000 person-years, respectively. Relative to those not recently hospitalized, the age- and sex-adjusted HRs of venous thromboembolism were 38.0 (95% CI 28.0, 51.5) during hospitalization, and 18.4 (95% CI 15.0, 22.6), 6.3 (95% CI 4.3, 9.0), and 3.0 (95% CI 1.7, 5.4) during the first, second, and third months after discharge, respectively. Stratified by medical versus surgical services the rates were similar. CONCLUSION: Hospitalization and up to 3 months after discharge were strongly associated with increased venous thromboembolism risk. These data quantify this risk for use in future studies.
Assuntos
Tromboembolia Venosa , Trombose Venosa , Estudos de Coortes , Hemostasia , Hospitalização , Humanos , Incidência , Pacientes Internados , Fatores de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Trombose Venosa/epidemiologiaRESUMO
BACKGROUND: Diabetes is associated with an increased risk of several malignancies. Both diabetic patients and patients with cancer have an increase in platelet reactivity and platelet activation has recently emerged as a potential mediator of cancer progression. Drug therapies, such as aspirin, that reduce platelet reactivity reduce both cardiovascular and cancer risk. METHODS: We performed a cross-sectional analysis to assess the association between history of cancer and current anti-platelet drug use in a primary care population of adults with diabetes enrolled in the Vermont Diabetes Information System. RESULTS: Self-reported characteristics, medical history, and a complete medication list were recorded on 1007 diabetic adults. Fifty percent of diabetic patients used an anti-platelet drug. In unadjusted analysis, no association was seen between anti-platelet drug use and cancer history (OR = 0.93; P = .70). Platelet inhibitor use was associated with a decreased patient-reported history of malignancy in a multivariate logistic regression adjusted for age, sex, body mass index, comorbidity, and number of medications (OR = 0.66; CI 0.44-0.99; P = .045). Similar odds of association were seen in both males and females, and for aspirin and non-aspirin platelet inhibitor therapy. CONCLUSIONS: Our data suggest an association between anti-platelet drug use and reduced cancer prevalence in patients with diabetes. Given the potentially large implications of our observations in the diabetic population, further studies are required to determine if this association is causal.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Sistemas de Apoio a Decisões Clínicas , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , New York/epidemiologia , Razão de Chances , Medição de Risco , Fatores de Risco , Fatores de Tempo , Vermont/epidemiologia , Adulto JovemRESUMO
Vascular endothelial growth factor (VEGF) and endostatin are key protein modulators of angiogenesis found within platelets. The platelet activation pathways that control angiogenic protein release are incompletely elucidated. The differential release of pro-angiogenic and anti-angiogenic proteins from the platelet has been demonstrated for proteinase activated receptors (PARs). Given the ability of tumors to secrete ADP and the availability of ADP receptor antagonists clinically, we determined the influence of adenosine diphosphate (ADP) and the ADP receptors, P2Y(1) and P2Y(12), on platelet release of the angiogenic stimulator protein, VEGF, and the angiogenic inhibitor protein, endostatin. Minimally altered whole blood (WB) and platelet rich plasma (PRP) from healthy volunteers was stimulated with ADP alone (12.5 uM), in combination with a P2Y(1) antagonist (MRS2179) or a P2Y(12) antagonist (cangrelor). VEGF and endostatin protein concentrations were assessed by an ELISA assay. We report that maximally stimulating concentrations of ADP significantly increased VEGF release from platelets in both PRP and WB by 36+/-12% 36+/-12% 54+/-18% 36 +/- 12% (p < 0.05) respectively as compared to control. Both P2Y(1) and P2Y(12) receptor antagonism inhibited this release. Conversely, endostatin levels did not change following ADP stimulation in PRP, while a 4.7% (p = 0.03) increase was observed in WB. As compared to thrombin receptor activation, ADP activation was a weaker stimulus for VEGF release. We found that activation of platelets by ADP results in an increase in soluble VEGF concentrations with minimal effects on endostatin concentrations, suggesting ADP release in the tumor microenvironment may be, on balance, proangiogenic. P2Y receptor antagonism abrogates ADP mediated proangiogenic protein release and thus may represent a potential pharmacologic strategy for regulating platelet mediated angiogenesis.
Assuntos
Plaquetas/metabolismo , Endostatinas/metabolismo , Ativação Plaquetária/fisiologia , Receptores Purinérgicos P2/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Difosfato de Adenosina/metabolismo , Difosfato de Adenosina/farmacologia , Plaquetas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Patológica/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2 , Receptor PAR-1/agonistas , Receptores Purinérgicos P2Y1 , Receptores Purinérgicos P2Y12RESUMO
PURPOSE: Guidelines recommend venous thromboembolism (VTE) risk assessment in outpatients with cancer and pharmacologic thromboprophylaxis in selected patients at high risk for VTE. Although validated risk stratification tools are available, < 10% of oncologists use a risk assessment tool, and rates of VTE prophylaxis in high-risk patients are low in practice. We hypothesized that implementation of a systems-based program that uses the electronic health record (EHR) and offers personalized VTE prophylaxis recommendations would increase VTE risk assessment rates in patients initiating outpatient chemotherapy. PATIENTS AND METHODS: Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTEPACC) was a multidisciplinary program implemented by nurses, oncologists, pharmacists, hematologists, advanced practice providers, and quality partners. We prospectively identified high-risk patients using the Khorana and Protecht scores (≥ 3 points) via an EHR-based risk assessment tool. Patients with a predicted high risk of VTE during treatment were offered a hematology consultation to consider VTE prophylaxis. Results of the consultation were communicated to the treating oncologist, and clinical outcomes were tracked. RESULTS: A total of 918 outpatients with cancer initiating cancer-directed therapy were evaluated. VTE monthly education rates increased from < 5% before VTEPACC to 81.6% (standard deviation [SD], 11.9; range, 63.6%-97.7%) during the implementation phase and 94.7% (SD, 4.9; range, 82.1%-100%) for the full 2-year postimplementation phase. In the postimplementation phase, 213 patients (23.2%) were identified as being at high risk for developing a VTE. Referrals to hematology were offered to 151 patients (71%), with 141 patients (93%) being assessed and 93.8% receiving VTE prophylaxis. CONCLUSION: VTEPACC is a successful model for guideline implementation to provide VTE risk assessment and prophylaxis to prevent cancer-associated thrombosis in outpatients. Methods applied can readily translate into practice and overcome the current implementation gaps between guidelines and clinical practice.
Assuntos
Neoplasias , Trombose , Tromboembolia Venosa , Anticoagulantes , Humanos , Neoplasias/complicações , Fatores de Risco , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
For unclear reasons, anemia is more common in American blacks than whites. The authors evaluated anemia prevalence (using World Health Organization criteria) among 19,836 blacks and whites recruited in 2003-2007 for the REasons for Geographic And Racial Differences in Stroke Renal Ancillary study and characterized anemia by 3 anemia-associated conditions (chronic kidney disease, inflammation, and microcytosis). They used multivariable models to assess potential causes of race differences in anemia. Anemia was 3.3-fold more common in blacks than whites, with little attenuation after adjusting for demographic variables, socioeconomic factors, and comorbid conditions. Increasing age, residence in the US southeast, lower income, vascular disease, diabetes, hypertension, and never smoking were associated with anemia. Age, diabetes, and vascular disease were stronger correlates of anemia among whites than blacks (P < 0.05). Among those with anemia, chronic kidney disease was less common among blacks than whites (22% vs. 34%), whereas inflammation (18% vs. 14%) and microcytosis (22% vs. 11%) were more common. In this large, geographically diverse cohort, anemia was 3-fold more common in blacks than whites with different characteristics and correlates. Race differences in anemia prevalence were not explained by the factors studied. Future research into the causes and consequences of anemia in different racial groups is needed.
Assuntos
Anemia/etnologia , População Negra/estatística & dados numéricos , População Branca/estatística & dados numéricos , Idoso , Doença Crônica , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/epidemiologia , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Doenças Vasculares/epidemiologiaRESUMO
PURPOSE: Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance. We explored the effects of tamoxifen and aromatase inhibitors on concentrations of VEGF and endostatin in plasma, serum, and platelet releasate (induced by platelet activation). EXPERIMENTAL DESIGN: VEGF and endostatin concentrations were measured with a quantitative immunoassay before and after 1 to 5 weeks of treatment in 30 women with breast cancer treated with either tamoxifen (n = 14) or aromatase inhibitors (n = 16). Platelet activation was induced by a thrombin receptor agonist. RESULTS: Tamoxifen therapy resulted in an increase in platelet releasate concentrations of VEGF (P = 0.01) but no change in plasma VEGF. In contrast, aromatase inhibitor therapy did not affect serum, plasma, or platelet releasate VEGF. In univariate analysis, aspirin use attenuated the tamoxifen-associated increase in VEGF in the platelet releasate and decreased serum levels of VEGF (P = 0.03). Aromatase inhibitor therapy resulted in a decrease in serum endostatin concentrations (P = 0.04), whereas plasma concentrations of endostatin tended to be higher during treatment with aromatase inhibitors (P = 0.06). Tamoxifen therapy resulted in no change in serum or plasma endostatin concentrations. Platelet releasate concentrations of endostatin did not change with either treatment. Interindividual variability was noted among both aromatase inhibitor--and tamoxifen-treated patients. CONCLUSIONS: Tamoxifen and aromatase inhibitor therapy affect VEGF and endostatin levels and likely contribute to the angiogenic balance in breast cancer patients. Aspirin decreased the proangiogenic effects of tamoxifen, suggesting that antiplatelet and/or antiangiogenic therapy might improve the effectiveness of tamoxifen in women with breast cancer.
Assuntos
Antineoplásicos/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/sangue , Endostatinas/efeitos dos fármacos , Tamoxifeno/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Adulto , Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Neoplasias da Mama/tratamento farmacológico , Endostatinas/sangue , Feminino , Humanos , Imunoensaio , Pessoa de Meia-Idade , Neovascularização Patológica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêuticoRESUMO
BACKGROUND: Thrombocytopenia is common in critically ill patients who receive continuous renal replacement therapy. Often, these patients receive heparin therapy and the diagnosis of heparin induced thrombocytopenia (HIT) is considered as a potential etiology. No data regarding the clinical diagnosis of HIT is available for patients receiving continuous renal replacement therapy. PATIENTS AND METHODS: We performed a retrospective study of 29 consecutive patients who received CRRT in a medical-surgical intensive care unit (ICU) and determined trends in platelet counts following CRRT and the frequency of meeting platelet based clinical criteria for consideration of a HIT diagnosis. RESULTS: For patient exposures to CRRT concurrent with heparin, 54% met at least one clinical threshold for consideration of the diagnosis of HIT. In 31% of exposures, both a platelet count <100,000/mm3 and a >50% decrease from baseline were seen. In contrast, the majority (73-85%) of patients receiving CRRT had a low pre-test probability of HIT using the "4T's" scoring system. Mean platelet counts while on CRRT concurrent with heparin were significantly lower than when patients received heparin alone (P < 0.02). CONCLUSIONS: The clinical diagnosis of HIT in ICU patients initiating CRRT is challenging given the decrease in platelet counts seen following CRRT initiation in the majority of patients. A prospective study in this population is needed to optimize patient outcomes.