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1.
J Clin Oncol ; 37(31): 2892-2898, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31545663

RESUMO

PURPOSE: Chemotherapy-induced thrombocytopenia (CIT) leads to delay or reduction in cancer treatment. There is no approved treatment. METHODS: We conducted a phase II randomized trial of romiplostim versus untreated observation in patients with solid tumors with CIT. Before enrollment, patients had platelets less than 100,000/µL for at least 4 weeks, despite delay or dose reduction of chemotherapy. Patients received weekly titrated romiplostim with a target platelet count of 100,000/µL or more, or were monitored with usual care. The primary end point was correction of platelet count within 3 weeks. Twenty-three patients were treated in a randomization phase, and an additional 37 patients were treated in a single-arm, romiplostim phase. Resumption of chemotherapy without recurrent CIT was a secondary end point. RESULTS: The mean platelet count at enrollment was 62,000/µL. In the randomization phase, 14 of 15 romiplostim-treated patients (93%) experienced correction of their platelet count within 3 weeks, compared with one of eight control patients (12.5%; P < .001). Including all romiplostim-treated patients (N = 52), the mean platelet count at 2 weeks of treatment was 141,000/µL. The mean platelet count in the eight observation patients at 3 weeks was 57,000/µL. Forty-four patients who achieved platelet correction with romiplostim resumed chemotherapy with weekly romiplostim. Only three patients (6.8%) experienced recurrent reduction or delay of chemotherapy because of isolated CIT. CONCLUSION: This prospective trial evaluated treatment of CIT with romiplostim. Romiplostim is effective in correcting CIT, and maintenance allows for resumption of chemotherapy without recurrence of CIT in most patients.

2.
Cancer Treat Res ; 179: 1-9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317477

RESUMO

"The frequent concurrence of phlegmasia alba dolens with an appreciable cancerous tumor, led me to the inquiry whether a relationship of cause and effect did not exist between the two, and whether the phlegmasia was not the consequence of the cancerous cachexia." (translated from the original French). This famous quote, delivered in a lecture by Armand Trousseau in 1865, is widely recognized as the initial and insightful understanding of the relationship of thrombosis and cancer.Although the association of thrombosis with cancer has been recognized for over 150 years, only recently has there been meaningful advances in our understanding of the relationship. Contemporary translational research tools have greatly enhanced our understanding the unique aspects of the pathophysiology of the relationship; how cancer cells exploit multiple aspects of the coagulation system for primary and metastatic growth leading, leading to an increased thrombotic risk. Further, there has been a growing appreciation of the complexity of the treatment of cancer-associated thrombosis. The superiority of low molecular weight heparin over warfarin, published in 2003, represented the first important divergence from the approach to management of thrombosis in the non-cancer population. With the introduction of the new generation of anticoagulants, the direct oral anticoagulants, there has been continued evolution of management guidelines.This text presents a much needed and comprehensive update of the field of thrombosis and hemostasis in cancer. We are fortunate to have so many leading authorities contribute their expertise and insight into this work. In the following chapters, the reader will find insight and guidance that will enhance scholarship, as well as patient care.


Assuntos
Hemostasia , Neoplasias/fisiopatologia , Trombose/etiologia , Anticoagulantes/uso terapêutico , Hemostasia/efeitos dos fármacos , Hemostasia/fisiologia , Humanos , Neoplasias/complicações , Trombose/tratamento farmacológico
3.
Cancer Treat Res ; 179: 103-115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317483

RESUMO

The management of cancer-associated thrombosis (CAT) is complex, and treatment strategies have been evolving over the past 15 years. It is well recognized that oral vitamin K antagonists are difficult to use in cancer patients, with higher rates of treatment failure and bleeding complications than in non-cancer patients. Low-molecular-weight-heparin (LMWH) became the widely accepted standard of care for treatment of cancer-associated thrombosis, following the CLOT study comparing dalteparin with warfarin in 2003. LMWH remains widely used for the treatment of CAT. However, in the past two years, several studies have served to validate direct oral anticoagulants as a safe and effective alternative to LMWH. Two randomized clinical trials comparing edoxaban and rivaroxaban with dalteparin, and several retrospective studies have shown the efficacy of edoxaban and rivaroxaban for the treatment of CAT. However, there is an evidence of increased bleeding with the DOACs, particularly gastrointestinal or urinary tract bleeding in patients with lesions within the gastrointestinal or urinary tracts. This chapter discusses the ongoing development of optimal treatment strategies for cancer-associated thrombosis.


Assuntos
Anticoagulantes/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Tromboembolia Venosa/etiologia
4.
Cancer Treat Res ; 179: 139-150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317485

RESUMO

Chemotherapy-induced thrombocytopenia (CIT) is a frequent complication of cancer therapy, leading to increased risk of bleeding, when the thrombocytopenia is severe (<10,000/mcL). However, the major clinical relevance of CIT is the subsequent delay or dose reduction in chemotherapy. CIT, therefore, leads to reduced relative dose intensity (RDI) of cancer therapy. Reduced RDI has been shown in several studies to impact progression-free survival and other cancer outcomes. While there are a number of factors leading to reduced RDI, CIT is a common cause. We review the causes and clinical manifestations of CIT, the current recommendations for management, and the status of research to develop targeted therapies to treat CIT.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Trombocitopenia/terapia , Antineoplásicos/uso terapêutico , Humanos , Neoplasias/complicações , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente , Trombocitopenia/etiologia
5.
Res Pract Thromb Haemost ; 3(3): 349-356, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31294321

RESUMO

Background: Low-molecular-weight heparin has been the preferred treatment of cancer-associated thrombosis (CAT); however, emerging data support the use of direct oral anticoagulants (DOACs). Objectives: The Memorial Sloan Kettering Cancer Center Clinical Pathway has served as the institutional guideline for the use of rivaroxaban to treat CAT since 2014. Key elements are to recommend against use of a DOAC in patients with active gastrointestinal (GI) or genitourinary tract lesions, and a prespecified dose reduction in the elderly (75+ years old). We present our institutional experience for treatment of CAT. Methods: From January 2014 through September 2016, 1072 patients began rivaroxaban treatment for CAT; 91.9% had a solid tumor, 8.1% had hematologic malignancies, and 75% of patients with solid tumors had metastatic disease. All patients with CAT treated with rivaroxaban were included in this analysis, regardless of adherence to the Clinical Pathway. Results: The 6-month cumulative incidence of recurrent venous thromboembolism and major bleeding were 4.2% (95% confidence interval [CI], 2.7%-5.7%) and 2.2% (95% CI, 1.1%-3.2%), respectively. The incidence of clinically relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days was 5.5% (95% CI,  3.7%-7.1%), and 73.3% of major bleeds occurred in the GI tract. The 6-month cumulative mortality rate was 22.2% (95% CI, 19.4%-24.9%). The elderly had similar rates of recurrent thrombosis and bleeding as those aged under 75 years. Conclusion: Our institutional experience suggests that in appropriately selected patients, rivaroxaban may be used for treatment of CAT with promising safety and efficacy.

7.
N Engl J Med ; 380(8): 720-728, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30786186

RESUMO

BACKGROUND: Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain. METHODS: In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep-vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding. RESULTS: Of 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49). CONCLUSIONS: In high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials.gov number, NCT02555878.).


Assuntos
Inibidores do Fator Xa/uso terapêutico , Neoplasias/tratamento farmacológico , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Fatores de Risco , Rivaroxabana/efeitos adversos , Resultado do Tratamento , Tromboembolia Venosa/etiologia
8.
J Natl Compr Canc Netw ; 16(11): 1289-1303, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30442731

RESUMO

Venous thromboembolism (VTE) is common in patients with cancer and increases morbidity and mortality. VTE prevention and treatment are more complex in patients with cancer. The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of VTE in adult patients diagnosed with cancer or in whom cancer is clinically suspected. These NCCN Guidelines Insights explain recent changes in anticoagulants recommended for the treatment of cancer-associated VTE.


Assuntos
Anticoagulantes/administração & dosagem , Hemorragia/prevenção & controle , Oncologia/normas , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Humanos , Oncologia/métodos , Adesão à Medicação , Neoplasias/mortalidade , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Sociedades Médicas/normas , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/mortalidade
9.
J Investig Med ; 66(7): 1055-1063, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29967012

RESUMO

Regulatory brain cytoplasmic 200 RNA (BC200 RNA) is highly expressed in human mammary carcinoma cells. Here, we ask whether BC200 RNA becomes detectable in peripheral blood of patients with invasive breast cancer. Using quantitative reverse-transcription PCR (qRT-PCR) methodology, we observed that BC200 RNA blood levels were significantly elevated, in comparison with healthy subjects, in patients with invasive breast cancer prior to tumorectomy (p=0.001) and in patients with metastatic breast cancer (p=0.003). In patients with invasive breast cancer who had recently undergone tumorectomy, BC200 RNA blood levels were not distinguishable from levels in healthy subjects. However, normality analysis revealed a heterogeneous distribution of patients in this group, including a subgroup of individuals with high residual BC200 RNA blood levels. In blood from patients with invasive breast cancer, BC200 RNA was specifically detected in the mononuclear leukocyte fraction. The qRT-PCR approach is sensitive enough to detect as few as three BC200 RNA-expressing tumor cells. Our work establishes the potential of BC200 RNA detection in blood to serve as a molecular indicator of invasive breast malignancy.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/genética , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Invasividade Neoplásica , Curva ROC , Sensibilidade e Especificidade
10.
J Natl Compr Canc Netw ; 16(5S): 670-673, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29784753

RESUMO

For patients with cancer who experience venous thromboembolism (VTE), low-molecular-weight heparin (LMWH) remains the standard of care in the NCCN Guidelines for VTE, but under certain conditions direct oral anticoagulants (DOACs) are acceptable alternatives. A growing body of literature suggests that DOACs may more effective than LMWHs in preventing recurrences, but they do carry some increased risk of bleeding. Most of this risk is seen in patients with gastrointestinal or urinary pathology or implanted devices. DOACs are also acceptable when the pain, cost, and inconvenience of LMWHs are expected to be obstacles to compliance. Through careful patient selection, most patients can be treated successfully with a DOAC, although for most patients with gastrointestinal or urinary pathology, LMWH remains the safer choice.


Assuntos
Anticoagulantes/administração & dosagem , Hemorragia/prevenção & controle , Neoplasias/complicações , Prevenção Secundária/métodos , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/normas , Ensaios Clínicos como Assunto , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Injeções Subcutâneas/efeitos adversos , Oncologia/normas , Guias de Prática Clínica como Assunto , Recidiva , Sociedades Médicas/normas , Resultado do Tratamento , Estados Unidos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/patologia
11.
Thromb Res ; 164 Suppl 1: S98-S102, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29703492

RESUMO

Acute promyelocytic leukemia (APL) is associated with a profound coagulopathy. Based on retrospective assessments, several potential risk factors for hemorrhagic morbidity and mortality have emerged. Several studies have shown elevated white blood cell (WBC) count at presentation to be a robust predictor of bleeding events. Other clinical and laboratory parameters have been evaluated with variable association with hemorrhagic morbidity or mortality. These include ECOG performance status, age, morphological subtype, platelet count, peripheral blood blast count, ethnicity, body mass index, prothrombin time, activated partial thromboplastin time, lactate dehydrogenase, d-dimers, creatinine and fibrinogen levels. Unfortunately, most of those assessments were based on a small patient sample and the results have been at times contradictory in terms of which parameters are independent predictors. More recently, two large retrospective studies have reported on the issue. They included data from several international trials of chemotherapy for APL, one on adults and the other focused on the pediatric population. Importantly, both analyses found that WBC count at presentation is the main predictor of early hemorrhagic death and early thrombo-hemorrhagic death, respectively. Much remains to be done if the rate of induction mortality in APL is going to be reduced significantly. One approach would be to incorporate the known risk factors for early hemorrhagic death into a risk stratification system and devise personalized transfusion interventions to meet an individual patient's risk, which could be evaluated in future randomized trials.


Assuntos
Hemorragia/etiologia , Leucemia Promielocítica Aguda/complicações , Feminino , Hemorragia/patologia , Humanos , Masculino , Fatores de Risco
12.
J Thromb Thrombolysis ; 44(4): 489-493, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28993967

RESUMO

Venous thromboembolism (VTE) is a common complication in cancer patients and anticoagulation (AC) remains the standard of care for treatment. Inferior vena cava (IVC) filters may also used to reduce the risk of pulmonary embolism, either alone or in addition to AC. Although widely used, data are limited on the safety and efficacy of IVC filters in cancer patients. We performed a retrospective review of outcomes after IVC filter insertion in a database of 1270 consecutive patients with cancer-associated pulmonary embolism (PE) at our institution between 2008 and 2009. Outcomes measured included rate of all recurrent VTE, recurrent PE, and overall survival within 12 months. 317 (25%) of the 1270 patients with PE had IVC filters placed within 30 days of the index PE event or prior to the index PE in the setting of prior DVT. Patients with IVC filters had markedly lower overall survival (7.3 months) than the non-IVC filter patients (13.2 months). Filter patients also had a lower rate of AC use at time of initial PE. There was a trend towards higher recurrent VTE in patients with IVC filters (11.9%) compared to non-filter patients (7.7%), but this was not significant (p = 0.086). The risk of recurrent PE was similar between the IVC filter cohort (3.5%) and non-filter group (3.5%, p = 0.99). Cancer patients receiving IVC filters had a similar risk of recurrent PE, but a trend towards more overall recurrent VTE. The filter patients had poorer overall survival, which may reflect a poorer cancer prognosis, and had greater contraindication to AC; therefore these patients likely had a higher inherent risk for recurrent VTE. A prospective study would be helpful for further clarification on the partial reduction in the recurrent PE risk by IVC filter placement in cancer patients.


Assuntos
Neoplasias/complicações , Embolia Pulmonar/etiologia , Filtros de Veia Cava/efeitos adversos , Tromboembolia Venosa/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
13.
Thromb Haemost ; 117(11): 2135-2145, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28933799

RESUMO

Venous thromboembolism (VTE) is a frequent complication of cancer associated with morbidity, mortality, increased hospitalizations and higher health care costs. Cancer patients at increased risk for VTE can be identified using a validated risk assessment score, and the incidence of VTE can be reduced in high-risk settings using anticoagulation. Rivaroxaban is a potent, oral, direct, factor Xa inhibitor approved for the prevention and treatment of thromboembolic events, including VTE. CASSINI is a double-blind, randomized, parallel-group, multicentre study comparing rivaroxaban with placebo in adult ambulatory patients with various cancers who are initiating systemic cancer therapy and are at high risk of VTE (Khorana score ≥ 2). Patients with primary brain tumours or those at risk for bleeding are excluded. Approximately 700 patients will be randomized 1:1 to rivaroxaban 10 mg daily or placebo for up to 6 months if there is no evidence of VTE from compression ultrasonography (CU) during screening or from routine care imaging within 30 days prior to randomization. Mandatory CU will also be performed at weeks 8 and 16 (±7 days), and at study end (±3 days). The primary efficacy hypothesis is that anticoagulation with rivaroxaban reduces the composite of objectively confirmed symptomatic or asymptomatic, lower-extremity, proximal deep-vein thrombosis (DVT); symptomatic, upper-extremity DVT; symptomatic or incidental pulmonary embolism; and VTE-related death compared with placebo. The primary safety objective is to assess major bleeding events (Clinical trial information: NCT02555878).


Assuntos
Assistência Ambulatorial , Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/administração & dosagem , Neoplasias/tratamento farmacológico , Embolia Pulmonar/prevenção & controle , Rivaroxabana/administração & dosagem , Tromboembolia Venosa/prevenção & controle , Trombose Venosa/prevenção & controle , Protocolos Clínicos , Método Duplo-Cego , Europa (Continente) , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Neoplasias/sangue , Neoplasias/complicações , Neoplasias/diagnóstico , América do Norte , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiologia , Projetos de Pesquisa , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia
14.
Am J Cardiol ; 120(2): 213-217, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28549819

RESUMO

Rivaroxaban is broadly used for the primary prevention of stroke and systemic embolism in the general population with nonvalvular atrial fibrillation (AF). However, there is little published evidence on the safety and efficacy of rivaroxaban for AF in patients with active cancer. The aim of this study was to assess the safety and efficacy of rivaroxaban in patients with active cancer and AF. The use of rivaroxaban in patients with cancer at the Memorial Sloan Kettering Cancer Center is monitored in the setting of a Quality Assessment Initiative. Patients with active cancer and AF, treated with rivaroxaban from January 1, 2014, to March 31, 2016, are included in this analysis. Clinical end points were defined a priori and assessed through text searches of medical records. A total of 163 evaluable patients were identified. After adjusting for competing risks, the estimated 1-year cumulative incidence of ischemic stroke was 1.4% (95% CI 0% to 3.4%) and major bleeding was 1.2% (95% CI 0% to 2.9%). The risk of clinically relevant nonmajor bleeding leading to discontinuation of anticoagulation at 1 year was 14.0% (95% CI 4.2% to 22.7%). The cumulative incidence of mortality was 22.6% (95% CI 12.2% to 31.7%) at 1 year, reflecting an active cancer population. One patient died after developing an acute ischemic cerebrovascular insult. In conclusion, the safety and efficacy of rivaroxaban treatment for nonvalvular AF in patients with active cancer is comparable to the results of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) study in the general population.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Neoplasias/complicações , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Relação Dose-Resposta a Droga , Método Duplo-Cego , Inibidores do Fator Xa/administração & dosagem , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida/tendências , Resultado do Tratamento
15.
J Thromb Thrombolysis ; 43(4): 514-518, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28205078

RESUMO

The development of thrombocytopenia in the setting of therapeutic anticoagulation for venous thromboembolic disease (VTE) is common in cancer patients, but guidelines for management are based on limited past data and have not been validated. In 2011, Memorial Sloan Kettering Cancer Center (MSKCC) implemented the following guidelines in this setting: administer full dose enoxaparin for a platelet count > 50,000/mcL, half-dose enoxaparin for a platelet count of 25,000-50,000/mcL, and hold anticoagulation for a platelet count < 25,000/mcL. We now report validation of safety and efficacy of these guidelines. As a Quality Assessment Initiative, we evaluated our guidelines for adult cancer patients at MSKCC who were on therapeutic-dose enoxaparin for VTE during the years 2011 through 2013 and experienced at least one 7-day period of thrombocytopenia (platelet count ≤ 50,000/mcL). We assessed adherence to the enoxaparin dose modification guidelines, major bleeding, clinically relevant non-major bleeding, recurrent VTE, and mortality during the thrombocytopenic episodes. We identified 99 patients with 140 episodes of thrombocytopenia of 7 or more days. The median duration of these thrombocytopenic episodes was 12 days. The enoxaparin dose was modified in 133 of the 140 episodes (95%), reflecting satisfactory adherence to our institutional guidelines. There were no recurrent VTE events or major bleeding episodes when the anticoagulant dose was reduced or held. In this cohort, there was only one major bleeding episode, a trauma-associated retroperitoneal hemorrhage that occurred on the third day of a thrombocytopenic episode, prior to enoxaparin dose modification. There were 13 clinically relevant non-major bleeding episodes. Lastly, 10 patients died of cancer-related causes during an episode of thrombocytopenia. This Quality Assessment Initiative supports the safety and efficacy of our guidelines for therapeutic enoxaparin dose modification.


Assuntos
Enoxaparina/administração & dosagem , Neoplasias/complicações , Garantia da Qualidade dos Cuidados de Saúde , Trombocitopenia/etiologia , Adulto , Anticoagulantes/administração & dosagem , Feminino , Fidelidade a Diretrizes , Hemorragia/induzido quimicamente , Humanos , Masculino , Contagem de Plaquetas , Guias de Prática Clínica como Assunto/normas , Recidiva
16.
J Thromb Thrombolysis ; 43(2): 166-171, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27696084

RESUMO

Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. Rivaroxaban was approved in 2012 for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but no prior studies have been reported specifically evaluating the efficacy and safety of rivaroxaban for cancer-associated thrombosis (CAT). Under a Quality Assessment Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT and now report a validation analysis of our first 200 patients. A 200 patient cohort with CAT (PE or symptomatic, proximal DVT), whose full course of anticoagulation was with rivaroxaban, were accrued. In competing risk analysis, primary endpoints at 6 months included new or recurrent PE or symptomatic proximal lower extremity DVT, major bleeding, clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. In competing risk analysis, the 6 months cumulative incidence of new or recurrent VTE was 4.4 % (95 % CI = 1.4-7.4 %), major bleeding was 2.2 % (95 % CI = 0-4.2 %) and all-cause mortality 17.6 % (95 % CI = 11.7-23.0 %). In this cohort of 200 patients with active cancer and CAT the rates of new or recurrent VTE and major bleeding were comparable to the cancer subgroup analysis from the EINSTEIN studies. The results of our Clinical Pathway provide guidance on Rivaroxaban use for treatment of CAT, and suggest that safety and efficacy is preserved, compared with past-published experience with LMWH.


Assuntos
Neoplasias/complicações , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/uso terapêutico , Estudos de Coortes , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Recidiva , Rivaroxabana/normas , Resultado do Tratamento , Tromboembolia Venosa/etiologia
18.
Curr Opin Hematol ; 23(2): 121-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26760586

RESUMO

PURPOSE OF REVIEW: Acute promyelocytic leukemia (APL) is associated with a complex coagulopathy. In spite of substantial recent improvements in treatment regimens, hemorrhagic death remains the main cause of induction failure. In this review, we delineate recent understanding of the pathophysiology and management of the hemorrhagic diathesis of APL. RECENT FINDINGS: Laboratory and clinical data suggest that the malignant leukocytes mediate the hemorrhagic diathesis associated with APL through multiple mechanisms which lead to a combination of consumptive coagulopathy and primary hyperfibrinolysis. Exposure of tissue factor and Annexin II by the leukemic blasts is the main determinants of these processes. Promyelocyte-derived microparticles have recently been implicated in the coagulopathy as well. Total white cell count and platelet count have emerged as good general predictors of hemorrhagic death, along with the different routine hemostatic parameters. Prompt treatment with all-trans retinoic acid, with or without arsenic trioxide, is the most important step in preventing bleeding complications. Repletion of coagulation factors and platelets with blood products remains the mainstay of supportive treatment, whereas the role of recombinant soluble thrombomodulin is currently being investigated. SUMMARY: The coagulopathy of APL is multifactorial, with both disseminated intravascular coagulation and primary hyperfibrinolysis mediated largely by the malignant leukocytes.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Coagulação Sanguínea , Leucemia Promielocítica Aguda/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/mortalidade , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/mortalidade , Prognóstico , Indução de Remissão , Trombomodulina/uso terapêutico , Resultado do Tratamento , Tretinoína/administração & dosagem
19.
J Am Coll Surg ; 222(2): 129-37, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26711793

RESUMO

BACKGROUND: We prospectively evaluated the safety and efficacy of adding preoperative chemoprophylaxis to our institution's operative venous thromboembolism (VTE) prophylaxis policy as part of a physician-led quality improvement initiative. STUDY DESIGN: Patients undergoing major cancer surgery between August 2013 and January 2014 were screened according to service-specific eligibility criteria and targeted to receive preoperative VTE chemoprophylaxis. Bleeding, transfusion, and VTE rates were compared with rates of historical controls who had not received preoperative chemoprophylaxis. RESULTS: The 2,058 eligible patients who underwent operation between August 2013 and January 2014 (post-intervention) were compared with a cohort of 4,960 patients operated on between January 2012 and June 2013, who did not receive preoperative VTE chemoprophylaxis (pre-intervention). In total, 71% of patients in the post-intervention group were screened for eligibility; 82% received preoperative anticoagulation. When compared with the pre-intervention group, the post-intervention group had significantly lower transfusion rates (pre- vs post-intervention, 17% vs 14%; difference 3.5%, 95% CI 1.7% to 5%, p = 0.0003) without significant difference in major bleeding (difference 0.3%, 95% CI -0.1% to 0.7%, p = 0.2). Rates of deep venous thrombosis (1.3% vs 0.2%; difference 1.1%, 95% CI 0.7% to 1.4%, p < 0.0001) and pulmonary embolus (1.0% vs 0.4%; difference 0.6%, 95% CI 0.2% to 1%, p = 0.017) were significantly lower in the post-intervention group. CONCLUSIONS: In patients undergoing major cancer surgery, institution of a single dose of preoperative chemoprophylaxis, as part of a physician-led quality improvement initiative, did not increase bleeding or blood transfusions and was associated with a significant decrease in VTE rates.


Assuntos
Quimioprevenção , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Neoplasias/cirurgia , Complicações Pós-Operatórias , Tromboembolia Venosa/prevenção & controle , Idoso , Feminino , Estudo Historicamente Controlado , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Melhoria de Qualidade
20.
J Natl Compr Canc Netw ; 13(9): 1079-95, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26358792

RESUMO

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.


Assuntos
Anticoagulantes/administração & dosagem , Neoplasias/complicações , Obesidade/complicações , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Adulto , Índice de Massa Corporal , Peso Corporal , Dalteparina/administração & dosagem , Enoxaparina/administração & dosagem , Fondaparinux , Heparina/administração & dosagem , Humanos , Polissacarídeos/administração & dosagem , Guias de Prática Clínica como Assunto , Insuficiência Renal Crônica/complicações , Tromboembolia Venosa/etiologia
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