Venous thromboembolism: thrombosis, inflammation, and immunothrombosis for clinicians.

Venous thromboembolism (VTE) is a worldwide disease related with mortality, cardiovascular disability, impaired quality of life and, cause major long-term complications. Clinicians related to the acute and long-term patients care must be involved in the molecular mechanisms of thrombosis. The vessel wall and its inner lining of the endothelium are critical to the maintenance of a patent vasculature. After endothelial disruption, collagen (first line of endothelial defense) and intravascular tissue factor (second line of endothelial defense) are exposed to blood flow, starting the formation of a thrombus. Anticoagulant endovascular proteins and endogenous fibrinolysis have an active role in hemostasis. Currently, the process of coagulation is a cell surface-based model that includes three overlapping phases: initiation, amplification, and propagation. From a simple view, inflammation is one of the first responses of the immune system to infection; inflammation is driven by eicosanoids and cytokines, which are released by injured or infected cells. Common cytokines, which regulate inflammatory response, include interleukins (mainly interleukin-6) that are responsible for communication among white blood cells, chemokines that promote chemotaxis, and interferons that have anti-viral effects. Acute infections have been associated with a transient increase in the risk of myocardial infarction, stroke and recently with venous thrombosis, supporting the notion that systemic and respiratory infections increase the risk of thromboembolic events. Recently, immunothrombosis, another thrombosis mechanism that includes innate immune mechanisms, the neutrophil extracellular genetic traps, and the immunothrombosis dysregulation, could explain some cases of "unprovoked" VTE especially in elderly, a high-risk population for thrombosis.

Inferior vena cava filters in pulmonary embolism: A historic controversy.

OBJECTIVE: Rationale for non-routine use of inferior venous cava filters (IVCF) in pulmonary embolism (PE) patients. METHODS: Thrombosis mechanisms involved with IVCF placement and removal, the blood-contacting medical device inducing clotting, and the inorganic polyphosphate in the contact activation pathway were analyzed. In addition, we analyzed clinical evidence from randomized trials, including patients with and without cancer. Furthermore, we estimated the absolute risk reduction (ARR), the relative risk reduction (RRR), and the number needed to treat (NNT) based on the results of each study using a frequency table. Finally, we analyzed the outcome of our PE patients that were submitted to thrombolysis with short and long term follow-up. RESULTS: IVCF induces thrombosis by several mechanisms including placement and removal, rapid protein adsorption, and simultaneous surface-induced activation via the contact activation pathway. Also, inorganic polyphosphate has an important role as a procoagulant, reversing the effect of anticoagulants. Randomized control trials included 904 cancer and non-cancer PE patients. In terms of ARR, RRR, and NNT, there is no evidence for routine use of IVCF. In 290 patients with proved PE, extensive thrombotic burden and right ventricular dysfunction under thrombolysis and oral anticoagulation, we observed a favorable outcome in a short- and long-term follow-up; additionally, IVCF was only used in 5% of these patients. CONCLUSION: Considering the complex mechanisms of thrombosis related with IVCF, the evidence from randomized control trials and ARR, RRR, and NNT obtained from venous thromboembolism patients with and without cancer, non-routine use of IVCF is recommended.

Inferior vena cava filters in pulmonary embolism: A historic controversy / Filtros de vena cava inferior en tromboembolia pulmonar: Una controversia histórica

Abstract: Objective: Rationale for non-routine use of inferior venous cava filters (IVCF) in pulmonary embolism (PE) patients. Methods: Thrombosis mechanisms involved with IVCF placement and removal, the blood-contacting medical device inducing clotting, and the inorganic polyphosphate in the contact activation pathway were analyzed. In addition, we analyzed clinical evidence from randomized trials, including patients with and without cancer. Furthermore, we estimated the absolute risk reduction (ARR), the relative risk reduction (RRR), and the number needed to treat (NNT) based on the results of each study using a frequency table. Finally, we analyzed the outcome of our PE patients that were submitted to thrombolysis with short and long term follow-up. Results: IVCF induces thrombosis by several mechanisms including placement and removal, rapid protein adsorption, and simultaneous surface-induced activation via the contact activation pathway. Also, inorganic polyphosphate has an important role as a procoagulant, reversing the effect of anticoagulants. Randomized control trials included 904 cancer and non-cancer PE patients. In terms of ARR, RRR, and NNT, there is no evidence for routine use of IVCF. In 290 patients with proved PE, extensive thrombotic burden and right ventricular dysfunction under thrombolysis and oral anticoagulation, we observed a favorable outcome in a short- and long-term follow-up; additionally, IVCF was only used in 5% of these patients. Conclusion: Considering the complex mechanisms of thrombosis related with IVCF, the evidence from randomized control trials and ARR, RRR, and NNT obtained from venous thromboembolism patients with and without cancer, non-routine use of IVCF is recommended.

Resumen: Objetivo: Racionalidad para no utilizar en forma rutinaria filtros de vena cava inferior (FVCI) en pacientes con tromboembolia pulmonar (TEP). Métodos: Analizamos mecanismos de trombosis relacionados con la colocación o retiro de estos dispositivos médicos, incluyendo la importancia del polifosfato inorgánico en la vía de activación de contacto. Analizamos evidencia clínica de estudios aleatorizados controlados en pacientes con y sin cáncer. Mediante tablas de frecuencia estimamos de cada estudio reducción del riesgo absoluto (RRA) y relativo (RRR) y el número necesario a tratar (NNT). Finalmente, examinamos la evolución de nuestros pacientes con TEP llevados a trombolisis con seguimientos a corto y largo plazo. Resultados: FVCI inducen trombosis por diferentes mecanismos: colocación y retiro, adsorción rápida de proteínas y activación de superficie inducida en la vía de activación de contacto. El polifosfato inorgánico es un procoagulante importante para la anticoagulación. Estudios aleatorizados controlados incluyeron 904 pacientes con TEP con y sin cáncer. En términos de RRA, RRR y NNT no existe evidencia para el uso rutinario. En 290 pacientes con TEP probada, importante carga de trombo y disfunción del ventrículo derecho llevados a trombolisis y anticoagulación observamos una evolución favorable en seguimientos a corto y largo plazo. En estos pacientes los FVCI se utilizaron solo en el 5%. Conclusión: Considerando los mecanismos complejos de trombosis relacionados con los FVCI, la evidencia obtenida de los estudios aleatorizados y controlados, así como la RRA, RRR y NNT en pacientes con tromboembolismo venoso con y sin cáncer, no recomendamos el uso rutinario de FVCI.