RESUMO
A broad range of studies suggest a two-way relationship between cancer and venous thromboembolism (VTE). Patients with cancer have consistently been shown to be at elevated risk for VTE; this risk is partly driven by an intrinsic hypercoagulable state elicited by the tumour itself. Conversely, thromboembolic events in patients without obvious risk factors are often the first clinical manifestation of an undiagnosed malignancy. The relationship between VTE and cancer is further supported by a number of trials and meta-analyses which, when taken together, strongly suggest that antithrombotic therapy can extend survival in patients with cancer by a mechanism that extends beyond its effect in preventing VTE. Moreover, accumulating evidence from in vitro and in vivo studies has shown that tumour growth, invasion, and metastasis are governed, in part, by elements of the coagulation system. On 22 May 2009, a group of health-care providers based in the United Kingdom met in London, England, to examine recent advances in cancer-associated thrombosis and its implications for UK clinical practice. As part of the discussion, attendees evaluated evidence for and against an effect of antithrombotic therapy on survival in cancer. This paper includes a summary of the data presented at the meeting and explores potential mechanisms by which antithrombotic agents might exert antitumour effects. The summary is followed by a consensus statement developed by the group.
Assuntos
Fibrinolíticos/uso terapêutico , Neoplasias/complicações , Neoplasias/mortalidade , Tromboembolia Venosa/tratamento farmacológico , Heparina de Baixo Peso Molecular/uso terapêutico , HumanosRESUMO
BACKGROUND: The safety and efficacy of edoxaban and dalteparin is unclear for several cancer groups. METHODS: We evaluated the occurrence of the primary outcome in large cancer groups. The primary outcome was the composite of recurrent VTE or major bleeding over 12â¯months. RESULTS: In patients with gastrointestinal cancer, the primary outcome occurred in 19.4% patients given edoxaban and in 15.0% given dalteparin (risk difference [RD], 4.4%; 95%-CI, -4.1% to 12.8%). The corresponding rates for edoxaban and dalteparin were 10.4% and 10.7% for lung cancer (RD, -0.3%; 95%-CI, -10.0% to 9.5%), 13.6% and 12.5% for urogenital cancer (RD, 1.1; 95%-CI, -10.1-12.4), 3.1% and 11.7% for breast cancer (RD, -8.6; 95%-CI, -19.3-2.2), 8.9% and 10.9% for hematological malignancies (RD, -2.0; 95%-CI, -13.1-9.1), and 10.4% and 17.4% for gynecological cancer (RD, -7.0; 95%-CI, -19.8-5.7). In the subgroup of gastrointestinal cancer, edoxaban was associated with a 3.5% lower absolute risk of recurrent VTE and a 7.9% higher risk of major bleeding. CONCLUSION: Edoxaban has a similar risk-benefit ratio to dalteparin in most cancer groups. In those with gastrointestinal cancer, the lower risk of recurrent VTE and the advantages of oral therapy need to be balanced against the increased risk of major bleeding.
Assuntos
Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Humanos , Recidiva Local de Neoplasia , Piridinas , Tiazóis/efeitos adversos , Tromboembolia Venosa/tratamento farmacológicoRESUMO
AIM: Development of antithrombotic compounds has traditionally been performed in patients undergoing total hip and knee replacement surgery. A high number of asymptomatic deep-vein thromboses are radiologically detectable, and bleeding and other adverse events (AE) are easy to observe. However, standardization of study procedures and endpoints in early proof-of-concept studies and late pure clinical endpoint studies has been lacking. This has made comparison between studies difficult, economic analyses speculative and potential benefits of applying the drug regimen in non-selected patients uncertain. In this paper, the International Surgical Thrombosis Forum proposes a strategy for the clinical investigation of new pharmacological agents for the prophylaxis of postoperative thrombotic events. METHODS: First, dose titration safety studies of short duration, in highly selected patients using objective venographic endpoints are recommended. Bleeding should be divided into the quantified volume of surgical bleeding and other adjudicated clinical bleeding events. The number of AE should be described for each dose step and classified according to International Coding of Diagnoses (ICD). Second, a dose confirmatory study of moderate exposure period and sufficient follow-up time is recommended. The exclusion criteria should be restricted to contraindications of the compared drugs and technical procedure. RESULTS: The efficacy, bleeding and AE should be similar to those used in dose-titration studies. In addition, the failure rate of the drug to exert its effect and the net clinical benefit should be calculated. CONCLUSION: Finally, trials with simple clinical endpoints and long follow-up should be conducted to evaluate the potential benefits of the drug-regimen in non-selected populations.
Assuntos
Artroplastia de Substituição , Avaliação de Medicamentos/métodos , Fibrinolíticos/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Trombose Venosa/prevenção & controle , Protocolos Clínicos , Relação Dose-Resposta a Droga , Humanos , Tromboembolia/prevenção & controleRESUMO
BACKGROUND: Venography is currently used to assess the incidence of deep vein thrombosis (DVT) in dose-finding and confirmatory trials of new antithrombotic agents. Centrally adjudicated, complete compression ultrasound (CCUS) could be a non-invasive alternative to venography. OBJECTIVES: A substudy of two, similarly designed, phase IIb trials of a novel, oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to validate CCUS against venography. PATIENTS/METHODS: Patients received study drugs until mandatory, bilateral venography was performed 7 +/- 2 days after surgery. CCUS was performed within 24 h after venography by sonographers blinded to the venography result. Sonographers were trained and certified for the standardized examination and documentation procedure. Venograms and sonograms were adjudicated centrally at different sites by two independent readers; discrepancies between readers were resolved by consensus. RESULTS: A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials (n = 1435): 19% of venograms and 20% of sonograms were not evaluable. The observed frequency of any DVT was 18.9% with venography and 11.5% with CCUS. Sensitivity of CCUS compared with venography was 31.1% for any DVT (95% confidence interval 23.4, 38.9), 21.0% (2.7, 39.4) for proximal DVT, and 30.8% (23.1, 38.6) for distal DVT. The figures for specificity were 93.0% (91.0, 95.1), 98.7% (98.0, 99.5), and 93.3% (91.5, 95.3), respectively. CONCLUSIONS: Based on these results, centrally adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs.
Assuntos
Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Anticoagulantes/efeitos adversos , Enoxaparina/administração & dosagem , Prótese de Quadril/efeitos adversos , Humanos , Prótese do Joelho/efeitos adversos , Morfolinas/administração & dosagem , Flebografia/estatística & dados numéricos , Complicações Pós-Operatórias/prevenção & controle , Rivaroxabana , Sensibilidade e Especificidade , Tiofenos/administração & dosagem , Ultrassonografia/métodos , Ultrassonografia/estatística & dados numéricos , Trombose Venosa/prevenção & controleRESUMO
INTRODUCTION: Venous Thromboembolism is an important healthcare problem the world over, resulting in significant morbidity, mortality and resource expenditure. The rationale for use of thromboprophylaxis is based on solid principles and scientific evidence. Indian perspective on this topic is lacking due to the non-availability of published Indian data. This document reviews the available International and Indian data and discusses the relevance of recommendations for prevention and management of Venous Thromboembolism (VTE) in the Indian context. MATERIALS AND METHODS: Meetings of various specialists from different Indian hospitals in the field of Gastrointestinal Surgery, General and Vascular Surgery, Hematology, Intensive Care, Obstetrics and Gynecology, Oncology and Orthopedics were held in the months of August 2005 to January 2006. The guidelines published by American College of Chest Physicians (ACCP), the International Union of Angiology (IUA), and the Royal College of Obstetricians and Gynecologists (RCOG), were discussed during these meetings. The relevance of these guidelines and the practical implications of following these in a developing country like India were also discussed. Any published data from India was collected from data base searches and the results, along with personal experiences of the participating specialists were discussed. The experiences and impressions of the experts during these meetings have been included in this document. Data from recent sources (International Union of Angiology and the National Comprehensive Cancer Network (NCCN) Practice guidelines in Oncology on Venous thromboembolic disease) was subsequently also included in this document. RESULTS: The suggestions formulated in this document are practical, and would intend to serve as a useful practical reference. CONCLUSIONS: A number of unanswered questions remain in the field of thromboprophylaxis, and carefully designed research protocols may help answer some of these. Implementation of the suggestions outlined in the document remains to be studied in the Indian context.
Assuntos
Tromboembolia , Trombose Venosa , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Humanos , Incidência , Índia/epidemiologia , Tromboembolia/diagnóstico , Tromboembolia/tratamento farmacológico , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controle , Trombofilia/etiologia , Trombose Venosa/diagnóstico , Trombose Venosa/tratamento farmacológico , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controleRESUMO
BACKGROUND: Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants. OBJECTIVES: To assess the efficacy and safety of a novel, oral, direct factor Xa (FXa) inhibitor--BAY 59-7939--relative to enoxaparin in patients undergoing elective total hip replacement. METHODS: In this double-blind, double-dummy, dose-ranging study, patients were randomized to oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6-8 h after surgery, or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery. Treatment was continued until mandatory bilateral venography was performed 5-9 days after surgery. RESULTS: Of 706 patients treated, 548 were eligible for the primary efficacy analysis. The primary efficacy endpoint was the incidence of any deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality; rates were 15%, 14%, 12%, 18%, and 7% for BAY 59-7939 2.5, 5, 10, 20, and 30 mg b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy analysis did not demonstrate any significant trend in dose-response relationship for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding; there was a significant increase in the frequency of events with increasing doses of BAY 59-7939 (P = 0.045), but no significant differences between individual BAY 59-7939 doses and enoxaparin. CONCLUSIONS: When efficacy and safety were considered together, the oral, direct FXa inhibitor BAY 59-7939, at 2.5-10 mg b.i.d., compared favorably with enoxaparin for the prevention of venous thromboembolism in patients undergoing elective total hip replacement.
Assuntos
Anticoagulantes/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Inibidores do Fator Xa , Trombose Venosa/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Artroplastia de Quadril/métodos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Enoxaparina/administração & dosagem , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Morfolinas/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/prevenção & controle , Rivaroxabana , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Tromboembolia/tratamento farmacológico , Tromboembolia/prevenção & controle , Trombose Venosa/tratamento farmacológico , Trombose Venosa/mortalidadeRESUMO
Overexpression of tissue factor (TF) is characteristically observed in advanced pancreatic cancer and has been associated with invasion and metastasis. Functional responses of TF activation are here investigated using as a model system the human pancreatic cancer cell lines SW979 (which overexpresses TF) and MIAPaCa2 (which does not express detectable levels). After stimulation of these cell lines with factor VIIa (FVIIa), the only known TF ligand, expression of urokinase receptor (uPAR) gene was up-regulated in SW979 cells in a dose-dependent manner but not in MIAPaCa2 cells. Interestingly, urokinase (uPA) and its specific inhibitor PAI-1 were not up-regulated. Exposure to functionally inactivated FVIIa did not show any effect on uPAR expression on SW979 cells despite binding to TF with higher efficiency. The neutralizing anti-TF antibody 5G9 blocked the FVIIa-induced up-regulation of uPAR completely, whereas hirudin failed to block this up-regulation. Treatment of SW979 cells with Factor Xa did not up-regulate the expression of uPAR gene, whereas treatment with FVII induced the same level of enhanced uPAR gene expression as that with FVIIa. In the matrigel invasion assay, enhanced invasion of SW979 cell line induced by FVIIa was completely inhibited by anti-TF antibody and alpha2-antiplasmin. Moreover, the endogenous levels of uPAR gene expression were significantly correlated with the level of TF gene expression in 19 human cancer cell lines (P < 0.05). These data suggest that up-regulation of uPAR expression by tumor cells leading to tumor invasion is induced through the TF-FVIIa pathway rather than TF-initiated thrombin generation. This is the first report that TF may be one of the key receptors that can up-regulate expression of the plasminogen activator receptor in human cancer cells to enhance tumor invasion and metastasis.
Assuntos
Fator VIIa/fisiologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Receptores de Superfície Celular/genética , Tromboplastina/metabolismo , Neoplasias da Mama , Movimento Celular , Fator VIIa/farmacologia , Fator Xa/farmacologia , Fator Xa/fisiologia , Feminino , Citometria de Fluxo , Humanos , Neoplasias Pancreáticas/metabolismo , Receptores de Superfície Celular/biossíntese , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Tromboplastina/genética , Transcrição Gênica , Células Tumorais Cultivadas , Regulação para Cima , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
PURPOSE: An increased incidence of thromboembolic events was observed during treatment with cisplatin-gemcitabine plus SU5416 (CG+SU5416), a tyrosine kinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor-1 and -2. Nine thromboembolic events occurred in eight of 19 patients. We performed an analysis of parameters of the coagulation cascade and vessel wall activation. MATERIALS AND METHODS: Markers for thrombin generation and endothelial cell activation were measured in three patients treated with CG+SU5416, two of whom developed a thromboembolic event. The results were compared with measurements in six patients treated with CG alone, and in 17 patients treated with SU5416 alone. RESULTS: During cycles 1 and 2 of treatment with CG+SU5416, a significant cycle-dependent activation of both the coagulation cascade and endothelial cells occurred, whereas platelet counts decreased. Change in platelet number had a significant negative predictive effect on soluble (s)-E-selectin levels. Significant activation of the coagulation cascade only was observed in the patients treated with CG alone, whereas in patients treated with SU5416 alone, significant endothelial cell activation was observed. CONCLUSION: We hypothesize that endothelial cells deprived of VEGF after exposure to SU5416 became activated and more susceptible to damage during treatment with CG+SU5416, which was aggravated by a transient decrease in platelets, which are, among other things, carriers of VEGF. These results suggests that VEGF, in addition to being a permeability, proliferation, and migration factor, also is a maintenance and protection factor for endothelial cells, and that platelets may have a role in maintaining vascular integrity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Plaquetas/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Endotélio Vascular/efeitos dos fármacos , Tromboembolia/induzido quimicamente , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Selectina E/sangue , Fatores de Crescimento Endotelial/sangue , Endotélio Vascular/metabolismo , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Linfocinas/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Análise de Regressão , Tromboembolia/fisiopatologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , GencitabinaRESUMO
OBJECTIVE: The angiogenesis inhibitor SU5416 is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor-1 and -2. VEGF may be involved in hemostasis by altering the hemostatic properties of endothelial cells. We analyzed the effects of SU5416 on the coagulation cascade and the vessel wall in patients with advanced cancer. METHODS AND RESULTS: Markers for thrombin generation, activation of the protein C pathway, fibrinolysis, and endothelial cell activation were measured in patients with renal cell carcinoma, soft tissue sarcoma, or melanoma on days 0, 14, and 28 of treatment with SU5416. Three of 17 sampled patients developed a thromboembolic event in the fifth week of treatment. Markers for thrombin generation and fibrinolysis did not show significant changes. We observed a significant increase in endogenous thrombin potential and of parameters reflecting endothelial cell activation (von Willebrand antigen, soluble tissue factor, and soluble E-selectin) in all patients (P< or =0.001). In patients experiencing a thromboembolic event, endogenous thrombin potential, soluble tissue factor, and soluble E-selectin increased to a significantly greater extent (P=0.029, P=0.021, and P=0.007, respectively). CONCLUSIONS: VEGF is not only a permeability, proliferation, and migration factor, but it is also a maintenance and protection factor for endothelial cells.
Assuntos
Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Carcinoma de Células Renais/tratamento farmacológico , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Esquema de Medicação , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Fibrinólise/efeitos dos fármacos , Fibrinólise/fisiologia , Hemostasia/efeitos dos fármacos , Hemostasia/fisiologia , Humanos , Indóis/administração & dosagem , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Melanoma/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Proteína C/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/fisiologia , Pirróis/administração & dosagem , Pirróis/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/fisiologia , Receptores de Fatores de Crescimento/antagonistas & inibidores , Receptores de Fatores de Crescimento/fisiologia , Receptores de Fatores de Crescimento do Endotélio Vascular , Sarcoma/tratamento farmacológico , Trombina/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio VascularRESUMO
Angiogenesis and activated blood coagulation are involved in tumor growth and metastasis. Although some have suggested that activation of coagulation in tumors is not linked to activation of platelets, no data exist to either support or refute this concept. However, platelet turnover in cancer patients is often increased, and platelets are carriers of angiogenic growth factors. We hypothesized that platelets are involved in tumor-associated angiogenesis. To obtain evidence supporting this hypothesis, we have studied whether the angiogenic and coagulation pathways and platelets are concomitantly activated in cancer patients with soft tissue sarcomas (STSs) using a novel method to detect activated platelets in tumor specimens. Twelve patients with STS were selected on the basis of having intratumoral accumulation of fluid, which was aspirated. These accumulations demonstrated very high concentrations of vascular endothelial growth factor and coagulation factors (including thrombin-antithrombin-complex). Tumor specimens showed dense vascularization with intense vascular endothelial growth factor expression and the presence of activated platelets. Taken together, these results support the concept that angiogenesis, blood coagulation, and platelets are concomitantly activated in STS and support the hypothesis that platelets contribute to tumor-induced angiogenesis.
Assuntos
Plaquetas/patologia , Fatores de Crescimento Endotelial/análise , Linfocinas/análise , Neovascularização Patológica , Ativação Plaquetária , Sarcoma/patologia , Sarcoma/fisiopatologia , Antitrombina III/análise , Histiocitoma Fibroso Benigno/irrigação sanguínea , Histiocitoma Fibroso Benigno/patologia , Humanos , Leiomiossarcoma/irrigação sanguínea , Leiomiossarcoma/patologia , Peptídeo Hidrolases/análise , Sarcoma/irrigação sanguínea , Trombomodulina/análise , Tromboplastina/análise , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
BACKGROUND: Treatment of venous thromboembolism (VTE) in patients with cancer has a high rate of recurrence and bleeding complications. Guidelines recommend low-molecular-weight heparin (LMWH) for at least 3-6 months and possibly indefinitely for patients with active malignancy. There are, however, few data supporting treatment with LMWH beyond 6 months. The primary aim of the DALTECAN study (NCT00942968) was to determine the safety of dalteparin between 6 and 12 months in cancer-associated VTE. METHODS: Patients with active cancer and newly diagnosed VTE were enrolled in a prospective, multicenter study and received subcutaneous dalteparin for 12 months. The rates of bleeding and recurrent VTE were evaluated at months 1, 2-6 and 7-12. FINDINGS: Of 334 patients enrolled, 185 and 109 completed 6 and 12 months of therapy; 49.1% had deep vein thrombosis (DVT); 38.9% had pulmonary embolism (PE); and 12.0% had both on presentation. The overall frequency of major bleeding was 10.2% (34/334). Major bleeding occurred in 3.6% (12/334) in the first month, and 1.1% (14/1237) and 0.7% (8/1086) per patient-month during months 2-6 and 7-12, respectively. Recurrent VTE occurred in 11.1% (37/334); the incidence rate was 5.7% (19/334) for month 1, 3.4% (10/296) during months 2-6, and 4.1% (8/194) during months 7-12. One hundred and sixteen patients died, four due to recurrent VTE and two due to bleeding. CONCLUSION: Major bleeding was less frequent during dalteparin therapy beyond 6 months. The risk of developing major bleeding complications or VTE recurrence was greatest in the first month of therapy and lower over the subsequent 11 months.
Assuntos
Anticoagulantes/administração & dosagem , Dalteparina/administração & dosagem , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Idoso , Anticoagulantes/efeitos adversos , Canadá , Dalteparina/efeitos adversos , Esquema de Medicação , Europa (Continente) , Feminino , Hemorragia/induzido quimicamente , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/mortalidade , Estudos Prospectivos , Recidiva , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/metabolismoRESUMO
Venous thromboembolism (VTE) commonly occurs in patients with malignant disease. At the 1997 ISTH meeting, cancer and thrombosis was discussed in a state-of-the-art symposium. Since then, there have been many new developments on this topic. Tumors, through expression of tissue factor can activate coagulation. Furthermore, local peritumor activation of coagulation may have important effects on the biology of cancer. A randomized trial has been conducted which evaluated extensive screening to detect underlying malignancy vs. no screening in patients presenting with idiopathic VTE. No statistically significant difference was detected in cancer-related mortality between the two groups. A trial has evaluated extended prophylaxis in patients undergoing surgery for abdominal malignancy. There was a statistically significant reduction in venographically detected deep vein thrombosis in favor of 4 weeks of treatment. In contrast, there is clearly a need for more information on the use of thromboprophylaxis in medical cancer patients. Low molecular weight heparin (LMWH) has replaced unfractionated heparin as the first line treatment in the majority of patients with acute VTE. Many cancer patients with acute VTE can be treated safely at home with subcutaneous LMWH without admission to hospital. The results of a recent trial demonstrated that long-term low molecular weight heparin administered over a 6-month period substantially reduced the rate of recurrent VTE compared with oral anticoagulant therapy with no increase in bleeding. Finally, the first trial specifically designed to evaluate the anticancer effect of long-term LMWH in cancer patients has been conducted and will no doubt stimulate future research.
Assuntos
Neoplasias/terapia , Tromboembolia/terapia , Trombose/terapia , Anticoagulantes/uso terapêutico , Cateterismo Venoso Central , Ensaios Clínicos como Assunto , Humanos , Neoplasias/complicações , Distribuição Aleatória , Recidiva , Tromboembolia/complicações , Trombose/etiologiaRESUMO
Although several authoritative, evidence-based, guidelines for the prevention of venous thromboembolism (VTE) have been published, the use of VTE prophylaxis in routine clinical practice varies markedly. Even in orthopedic surgery, the indication for which prophylaxis is used most often, a significant proportion of surgeons do not use routine prophylaxis. When prophylaxis is used, guideline recommendations are often not followed. A number of factors may contribute to the under-use of guidelines. Physician-related factors include: a lack of awareness of, or familiarity with, the guidelines; a perception that VTE is not a significant problem or that VTE prophylaxis is ineffective; and concern about potential bleeding risks. The guidelines may also be perceived to be too complicated or difficult to apply in a routine manner. In addition, a lack of facilities or resources may also present a barrier to implementation of the guidelines. A number of strategies are being investigated in an attempt to improve compliance with guidelines for VTE prophylaxis. For example, the Investigators Against Thromboembolism (INATE) initiative has developed a simplified pocket guideline on VTE prophylaxis in orthopedic and trauma surgery in order to raise awareness of the current guideline recommendations.
Assuntos
Pré-Medicação , Tromboembolia/prevenção & controle , Trombose Venosa/prevenção & controle , Comportamento Cooperativo , Humanos , Guias de Prática Clínica como Assunto , Tromboembolia/tratamento farmacológico , Trombose Venosa/tratamento farmacológicoRESUMO
BACKGROUND: The history of venous thromboembolism (VTE), and the rationale for thromboprophylaxis in surgical patients are well understood. The situation is less clear for acutely ill medical patients. OBJECTIVES: To compare the clinical presentation of VTE and clinical outcomes of immobile acutely ill medical patients with surgical patients. PATIENTS: RIETE (Registro Informatizado de la Enfermedad TromboEmbolica) is a Spanish registry of consecutively enrolled patients with objectively confirmed, symptomatic acute VTE. In this analysis, clinical characteristics of patients, details of anticoagulant therapy, and outcomes of all enrolled acutely ill medical patients with immobility >/= 4 days, and surgical patients are included. RESULTS: Of 6160 patients enrolled up to December 2003, 756 (12%) were acutely ill medical patients with immobility >/= 4 days, and 884 (14%) were surgical patients who developed VTE within 2 months of surgical intervention. Only 28% of acutely ill medical patients had received thromboprophylaxis, compared with 67% of surgical patients. During the 3-month follow-up period, both fatal pulmonary embolism (PE) and fatal bleeding occurred more frequently in acutely ill medical patients. Immobility in acutely ill medical patients, cancer, and PE were associated with a significantly higher risk of fatal PE or bleeding. CONCLUSIONS: In patients treated for VTE, the incidences of fatal PE, fatal bleeding, and major bleeding were significantly higher in acutely ill medical patients compared with surgical patients. Given the low percentage of acutely ill medical patients who had received thromboprophylaxis, increasing its use appropriately may reduce the incidence of VTE and associated complications.
Assuntos
Doença Aguda , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Tromboembolia/etiologia , Trombose Venosa/etiologia , Anticoagulantes/uso terapêutico , Causas de Morte , Hemorragia/etiologia , Humanos , Imobilização , Neoplasias/complicações , Embolia Pulmonar/etiologia , Sistema de Registros , Fatores de Risco , Tromboembolia/tratamento farmacológico , Resultado do Tratamento , Trombose Venosa/tratamento farmacológicoRESUMO
We have observed a striking neutralisation of the anticoagulant activity of unfractionated heparin in the presence of a pancreatic carcinoma cell line (MIA PaCa-2) due to binding of around 9 microg of heparin per 10(7) cells (apparent Kd, 30 nM). The loss of anticoagulant activity was less marked in the presence of low molecular weight forms of heparin. Binding to the cell blocked acceleration of the thrombin:antithrombin interaction by heparin. Neutralisation of heparin activity was also shown to occur in the presence of a number of other tumour cell lines. FACS analysis demonstrated that live cells did not bind heparin and high affinity binding only occurred to dead MIA PaCa-2 cells. Heparin binding proteins accumulating in cell medium were identified as histone and ribosomal proteins that will become exposed during necrosis. The release of these proteins from cells within the necrotic core of a tumour or from cells killed during chemotherapy may abrogate the heparan sulphate/antithrombin system and possibly contribute to the idiopathic thromboembolism often associated with cancer (Trousseau's syndrome). The findings also suggest a reason for the reported advantage of LMWH over UFH in treating venous thromboembolism in cancer patients and in improving patient survival.
Assuntos
Heparina/farmacocinética , Neoplasias/patologia , Adsorção , Antitrombina III/efeitos dos fármacos , Citometria de Fluxo , Heparina/metabolismo , Heparina de Baixo Peso Molecular/metabolismo , Heparina de Baixo Peso Molecular/farmacocinética , Histonas/metabolismo , Humanos , Necrose , Neoplasias/complicações , Neoplasias/metabolismo , Peptídeo Hidrolases/sangue , Peptídeo Hidrolases/efeitos dos fármacos , Ligação Proteica , Proteínas Ribossômicas/metabolismo , Tromboembolia/etiologia , Células Tumorais CultivadasRESUMO
A patient with the rare presentation of posterior mediastinal echinococcosis is reported. Magnetic resonance imaging (MR) demonstrated the extension of a primary retroperitoneal cyst into the posterior mediastinum which was subsequently confirmed surgically to be of echinococcal origin. Such a case of phrenomediastinal echinococcosis has been described only once before in literature.
Assuntos
Equinococose , Doenças do Mediastino , Adulto , Diafragma/diagnóstico por imagem , Diafragma/patologia , Equinococose/diagnóstico , Equinococose/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Doenças do Mediastino/diagnóstico , Doenças do Mediastino/diagnóstico por imagem , Radiografia , Espaço Retroperitoneal/diagnóstico por imagem , Espaço Retroperitoneal/patologiaRESUMO
A case of papillary cystic neoplasm of the pancreas diagnosed by fine needle aspiration cytology is presented surgical removal of the pancreatic tumour and histological study confirmed the cytologic diagnosis. A brief review of the literature and emphasis on cytological and histological features are discussed.
Assuntos
Cistadenoma Papilar/patologia , Neoplasias Pancreáticas/patologia , Biópsia por Agulha , Cistadenoma Papilar/diagnóstico por imagem , Cistadenoma Papilar/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Fatores de Tempo , UltrassonografiaRESUMO
There is currently limited information available on the benefits and risks of extended thromboprophylaxis after hip fracture surgery. SAVE-HIP3 was a randomised, double-blind study conducted to evaluate the efficacy and safety of extended thromboprophylaxis with the ultra-low molecular-weight heparin semuloparin compared with placebo in patients undergoing hip fracture surgery. After a seven- to ten-day open-label run-in phase with semuloparin (20 mg once daily subcutaneously, initiated post-operatively), patients were randomised to once-daily semuloparin (20 mg subcutaneously) or placebo for 19 to 23 additional days. The primary efficacy endpoint was a composite of any venous thromboembolism (VTE; any deep-vein thrombosis and non-fatal pulmonary embolism) or all-cause death until day 24 of the double-blind period. Safety parameters included major and clinically relevant non-major bleeding, laboratory data, and treatment-emergent adverse events (TEAEs). Extended thromboprophylaxis with semuloparin demonstrated a relative risk reduction of 79% in the rate of any VTE or all-cause death compared with placebo (3.9% vs 18.6%, respectively; odds ratio 0.18 (95% confidence interval 0.07 to 0.45), p < 0.001). Two patients in the semuloparin group and none in the placebo group experienced clinically relevant bleeding. TEAE rates were similar in both groups. In conclusion, the SAVE-HIP3 study results demonstrate that patients undergoing hip fracture surgery benefit from extended thromboprophylaxis.