Hipercoagulabilidade e câncer de pulmão

Abstract

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.

Does the Evaluation of Coagulation Factors Contribute to Etiological Diagnosis of Pleural Effusions?

“…High levels of fibrin degradation products and fragment 1+2 (markedly higher than in serum levels) reveal greater activity of the coagulation system in the pleural space, suggesting participation of this system in invasive cancer 4,11,12. These findings, which denote a predominance of procoagulant activity, were not demonstrated in the present study.…”

“…The coagulation system prevents hemorrhage and initiates tissue repair and remodeling, in addition to orchestrating cellular proliferation, cellular migration and synthesis of inflammatory mediators. The coagulation system, when chronically activated and in the presence of an inflammatory state, can generate adverse effects such as chronic release of procoagulant factors (e.g., tissue factor), cellular activation (adhesion molecules), protein modulation (transformation of fibrinogen into fibrin), and even histological changes promoted by cytokines 4. All these changes in exudative effusions contribute to tissue remodeling and lead to pleural thickening, trapped lung and functional impairment 4.…”

“…The coagulation system, when chronically activated and in the presence of an inflammatory state, can generate adverse effects such as chronic release of procoagulant factors (e.g., tissue factor), cellular activation (adhesion molecules), protein modulation (transformation of fibrinogen into fibrin), and even histological changes promoted by cytokines 4. All these changes in exudative effusions contribute to tissue remodeling and lead to pleural thickening, trapped lung and functional impairment 4. It is worth noting that chronic transudates, which have no inflammatory response, are rarely associated with pleural thickening 1.…”

Lung Cancer and Pulmonary Embolism: What Is the Relationship? A Review

“…And the correlation between risk of PE and cisplatin-based chemotherapy has been observed (HR, 1.51; 95% CI: 1.12-2.36) 31 . Lung cancer chemotherapy agents such as cisplatin, carboplatin, gemcitabine and paclitaxel increase procoagulant activity on endothelial cells by TF decryption through a disulfide bond formation in a PDI-dependent (protein disulfide isomerase) mechanism 72 , and could have a thrombogenic effect due to direct endothelial lesion 73 .…”

Technology Advancements in Blood Coagulation Measurements for Point-of-Care Diagnostic Testing

“…affect the coagulation stages and create serious complications, as well. For example, the tumor cells can cause thromboembolic complications due to activation of blood coagulation by producing procoagulants such as tissue factor (the primary activator of blood coagulation), releasing soluble factors such as thrombin that induce platelet activation, aggregation, expressing proteins regulating the fibrinolytic system and causing impairment in plasma fibrinolytic activity (Marinho and Takagaki, 2008). Therefore, accurate measurement and understanding of hemostasis including blood coagulation and fibrinolysis is highly demanded to study defects from sensing parameters in different disease models.…”