Update on Tumor Cell Procoagulant Factors

Gale, Andrew J.; Gordon, Stuart G.

doi:10.1159/000046586

Cited by 98 publications

(55 citation statements)

References 52 publications

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“…The development of thrombi within vessels results from the disruption of the equilibrium between the prothrombotic and the antithrombotic factors that control clotting homeostasis; this imbalance may occur due to ongoing stimulus to thrombogenesis or a defect in the natural anti-coagulant or the fibrinolytic system. In cancer patients, several studies have reported high plasma concentrations of procoagulant proteins and decreased concentrations of functionally attenuated anti-coagulant factors [23][24][25]. Low fibrinolytic function has been also reported to be an important cause of vascular thrombosis in cancer patients [17].…”

Section: Discussionmentioning

confidence: 99%

Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients

et al. 2004

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Impairment of fibrinolytic function plays an important role in the mechanism of thrombotic disorders in cancer patients. This study assessed the circulating level of thrombin-activatable fibrinolysis inhibitor in patients with lung cancer and its expression by several lung cancer cell lines. The plasma concentrations of thrombin-activatable fibrinolysis inhibitor were significantly increased in lung cancer patients compared to healthy subjects. The concentration of thrombin-activatable fibrinolysis inhibitor was particularly higher in patients with small cell carcinoma compared to those with adenocarcinoma or squamous cell carcinoma, and in cancer patients that responded to chemotherapy compared to nonresponders. In vitro studies showed more expression of thrombin-activatable fibrinolysis inhibitor in small cell carcinoma than in adenocarcinoma cell lines and more expression in lung cancer cell lines sensitive to anti-cancer agents than in resistant cell lines. This study suggests that thrombin-activatable fibrinolysis inhibitor, in part secreted from lung cancer cells, may play a role in the pathogenesis of thrombotic disorders in lung cancer patients.

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Section: Discussionmentioning

confidence: 99%

Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients

et al. 2004

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“…(6)(7)(8) Tissue factor, the main activator of the coagulation cascade, forms a complex with factor VII in order to activate factors X and XI. The final pathway of this process is the transformation of prothrombin into thrombin.…”

Section: Procoagulant Factorsmentioning

confidence: 99%

Hipercoagulabilidade e câncer de pulmão

Marinho

Takagaki

2008

J. bras. pneumol.

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The relationship between cancer and coagulopathy was suggested by Trousseau nearly 150 years ago. Later, it became more evident that oncologic patients are at a higher risk of experiencing thromboembolic events. This can be due to activation of the coagulation system either by neoplastic cells or by prescribed therapies (chemotherapy or surgical procedures). In fact, these events can constitute the first manifestation of cancer, and their recurrence, despite efficient anticoagulation, has been described. The coagulation system is normally activated in order to provide healing. In the presence of neoplasms, this complex system is activated as a response to multiple stimuli and seems to contribute to cancer progression. Activation of the coagulation system has a greater effect on metastatic foci than on the primary tumor. However, most cancer victims die from complications caused by metastasis, which underscores the importance of this theme. In this area, various mechanisms have been described, creating promising perspectives for future treatments. The current success in using low-molecular-weight heparins against small cell lung cancer is encouraging. Although the knowledge of those mechanisms is relatively incipient, many basic research and clinical studies are underway.Keywords: Lung neoplasms; Thrombophilia. ResumoA relação entre câncer e alteração na coagulação já havia sido sugerida há quase 150 anos por Trousseau e, subseqüentemente, ficou claro o maior risco que os pacientes oncológicos têm de desenvolverem fenômenos tromboembólicos. Isto pode ser conseqüência da ativação do sistema de coagulação pelas células neoplásicas ou pelas terapias empregadas (quimioterapias e cirurgias). Tais fenômenos podem, ainda, ser a primeira manifestação do câncer e a sua recorrência, mesmo com anticoagulação adequada, foi descrita. O sistema de coagulação é ativado, normalmente, com finalidade reparativa. Na presença de neoplasias, este complexo sistema está atuante frente a variados estímulos e parece contribuir para a progressão tumoral. Este efeito é mais importante para os focos metastáticos que para o próprio tumor primário. Contudo, a maior parte das vítimas de neoplasias morre das complicações das metástases, revelando a importância deste tema. Nesta área, vários mecanismos já são conhecidos e geram interessantes perspectivas para tratamentos futuros. Atualmente, o sucesso obtido com as heparinas de baixo peso molecular no carcinoma de pequenas células de pulmão é animador. Embora o conhecimento sobre esses mecanismos sejam relativamente recentes, os campos de pesquisa e tratamento estão amplamente abertos.

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“…A classic review of 182 cases of this "paraneoplastic" phenomenon emphasized the formation of venous and arterial platelet-rich microthrombi with secondary microangiopathic hemolytic anemia and a frequent association with mucin-rich adenocarcinomas (3). The term Trousseau syndrome is sometimes used more broadly to refer to any form of excessive coagulation associated with cancer (2,(4)(5)(6)(7)(8)(9)(10). The underlying pathophysiology is thought to be chronic subclinical disseminated intravascular coagulation caused by activated procoagulants.…”

Section: Introductionmentioning

confidence: 99%

Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas

Wahrenbrock¹,

Borsig²,

Le³

et al. 2003

J. Clin. Invest.

249

136

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Trousseau described spontaneous, recurrent superficial migratory thrombophlebitis associated with occult cancers, and this was later correlated with disseminated microangiopathy (platelet-rich clots in small blood vessels). Trousseau syndrome often occurs with mucinous adenocarcinomas, which secrete abnormally glycosylated mucins and mucin fragments into the bloodstream. Since carcinoma mucins can have binding sites for selectins, we hypothesized that selectin-mucin interactions might trigger this syndrome. When highly purified, tissue-factor free carcinoma mucin preparations were intravenously injected into mice, platelet-rich microthrombi were rapidly generated. This pathology was markedly diminished in P-or L-selectin-deficient mice. Heparin (an antithrombin-potentiating agent that can also block P-and L-selectin recognition of ligands) ameliorated this platelet aggregation, but had no additional effect in P-or L-selectin-deficient mice. Inhibition of endogenous thrombin by recombinant hirudin also did not block platelet aggregation. Mucins generated platelet aggregation in vitro in hirudinized whole blood, but not in platelet-rich leukocyte-free plasma nor in whole blood from L-selectin-deficient mice. Thus, Trousseau syndrome is likely triggered by interactions of circulating carcinoma mucins with leukocyte L-selectin and platelet P-selectin without requiring accompanying thrombin generation. These data may also explain why heparin ameliorates Trousseau syndrome, while vitamin K antagonists that merely depress thrombin production do not.

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Update on Tumor Cell Procoagulant Factors

Cited by 98 publications

References 52 publications

Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients

Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients

Hipercoagulabilidade e câncer de pulmão

Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas

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