Cancer-Associated Thrombosis: Prevention and Treatment

Brose, Kelsey; Lee, A.Y.Y.

doi:10.3747/co.2008.177

Cited by 57 publications

(44 citation statements)

References 59 publications

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“…29 The classic mode of action is that heparins are able to bind antithrombin III and thereby accelerate the blockage of thrombin and mainly factor Xa. However, as shown in this work, heparins are also able to directly interact with VWF, thereby blocking DNA binding to VWF, which demonstrates that the prothrombotic effect of extracellular DNA traps 6,13,14 could be diminished by heparin.…”

Section: Discussionmentioning

confidence: 99%

von Willebrand Factor Directly Interacts With DNA From Neutrophil Extracellular Traps

Grässle

Huck

Pappelbaum

et al. 2014

ATVB

142

128

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Objective—Inflammatory conditions provoke essential processes in the human vascular system. It leads to the formation of ultralarge von Willebrand factor (VWF) fibers, which are immobilized on the endothelial cell surface and transform to highly adhesive strings under shear conditions. Furthermore, leukocytes release a meshwork of DNA (neutrophil extracellular traps) during the process of the recently discovered cell death program NETosis. In the present study, we characterized the interaction between VWF and DNA and possible binding sites to underline the role of VWF in thrombosis and inflammation besides its function in platelet adhesion. Approach and Results—Both functionalized surfaces and intact cell layers of human umbilical vein endothelial cells were perfused with isolated, protein-free DNA or leukocytes from whole blood at distinct shear rates. DNA–VWF interaction was monitored using fluorescence microscopy, ELISA-based assays, molecular dynamics simulations, and electrostatic potential calculations. Isolated DNA, as well as DNA released by stimulated leukocytes, was able to bind to shear-activated, but not inactivated, VWF. However, DNA–VWF binding does not alter VWF degradation by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13. Moreover, DNA–VWF interaction can be blocked using unfractionated and low-molecular-weight heparin, and DNA–VWF complexes attenuate platelet binding to VWF. These findings were supported using molecular dynamics simulations and electrostatic calculations of the A1- and A2-domains. Conclusions—Our findings suggest that VWF directly binds and immobilizes extracellular DNA released from leukocytes. Therefore, we hypothesize that VWF might act as a linker for leukocyte adhesion to endothelial cells, supporting leukocyte extravasation and inflammation

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Section: Discussionmentioning

confidence: 99%

von Willebrand Factor Directly Interacts With DNA From Neutrophil Extracellular Traps

Grässle

Huck

Pappelbaum

et al. 2014

ATVB

142

128

View full text Add to dashboard Cite

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“…A incidência de TVP em pacientes com câncer, de acordo com alguns estudos internacionais é de 20% (Heit et al, 2002;Brose & Lee et al, 2008). Em um estudo realizado no Instituto Nacional de Câncer (Inca), observou-se que o evento de TVP ocorreu em 7,3% das pacientes portadoras de câncer ginecológico em estádio IIIB, com redução da sobrevida quando comparadas com as pacientes sem evento tromboembólico (Renni et al, 2011).…”

Section: Discussionunclassified

Análise de custo-efetividade da rivaroxabana versus enoxaparina no tratamento da trombose venosa profunda em pacientes com câncer ginecológico

Leira¹,

Costa²

2018

JBES

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Objetivo: A trombose venosa profunda (TVP) é uma das principais complicações em pacientes com câncer e tem impacto socioeconômico relevante. Novos anticoagulantes orais inibidores diretos do fator X estão sendo introduzidos na prática clínica, prometendo trazer maior facilidade no seu manejo. Porém, os protocolos clínicos ainda não discutem o emprego deles em pacientes com câncer, principalmente pela falta de evidências. Este artigo avalia o custo-efetividade da rivaroxabana (RVXB) versus enoxaparina (ENOXA) no tratamento da TVP em pacientes com câncer ginecológico. Métodos: Foi realizada uma análise de custo-efetividade sob a perspectiva de um hospital federal do SUS. A partir de um modelo de árvore de decisão, foram considerados os desfechos de efetividade e segurança da RVXB e da ENOXA em tratamento ambulatorial, sendo os dados clínicos extraídos de uma coorte retrospectiva e os custos diretos obtidos das plataformas SIGTAP-SUS e do Ministério da Saúde. Resultados: Sessenta e cinco pacientes foram selecionados e tiveram tempo médio de sete meses de tratamento. O custo de tratamento com a RVXB e a ENOXA foi de R$ 1.172,02 e R$ 7.490,49, respectivamente, com custo incremental de R$ 7.789,61 por paciente tratado com ENOXA. A robustez do modelo foi testada por análises de sensibilidade determinísticas e a economia de recursos promovida pela rivaroxabana foi mantida em todas as variações. Conclusão: A RVXB neste contexto é a tecnologia dominante no tratamento ambulatorial de pacientes com câncer ginecológico como importante alternativa farmacoterapêutica.

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“…as well as initiation of LMWH is warranted. In patients with apparently therapeutic LMWH levels, empiric dose escalation also has been a successful management strategy (89). Vena cava filters are also an option for selected patients with recurrent VTE despite adequate anticoagulation.…”

Section: Management Of Cancer Patients With Recurrent Vtementioning

confidence: 99%

An Overview of the NCCN and ASCO Guidelines on Cancer-Associated Venous Thromboembolism

Streiff

2009

Cancer Investigation

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Venous thromboembolism (VTE) is a common complication of cancer and its treatment.The National Comprehensive Cancer Center Network (NCCN) and the American Society of Clinical Oncology (ASCO) have published evidence-based guidelines on the management of VTE in the cancer patient. This paper will review the literature basis and substance of the NCCN and ASCO guidelines. Topics include the prevention, diagnosis, and treatment of deep and superficial vein thrombosis, catheter-associated thrombosis, and pulmonary embolism. Management of recurrent thromboembolism and the use of anticoagulation to improve cancer survival as well as indications for thrombolytic therapy and vena cava filters are also reviewed.

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Cancer-Associated Thrombosis: Prevention and Treatment

Cited by 57 publications

References 59 publications

von Willebrand Factor Directly Interacts With DNA From Neutrophil Extracellular Traps

von Willebrand Factor Directly Interacts With DNA From Neutrophil Extracellular Traps

Análise de custo-efetividade da rivaroxabana versus enoxaparina no tratamento da trombose venosa profunda em pacientes com câncer ginecológico

An Overview of the NCCN and ASCO Guidelines on Cancer-Associated Venous Thromboembolism

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