Inflammation and Acute Venous Thrombosis

Abstract

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE occurs worldwide, and in all age groups and socioeconomic populations in North America and western Europe.1,2 In a recent study by Heit et al., the estimated total annual cases of VTE occurring in the US exceeded 900,000, of which more than 250,000 were fatal. 3 Despite progress in medicine and biology, no changes in the incidence of VTE were noted during the 25-year cohort study. InflammationInflammation is a complex, highly regulated biological process that can be triggered by several stimuli, such as pathogens, noxious mechanical and chemical agents, and autoimmune responses. 10 In the clinical setting, inflammation is described as redness and swelling with heat and pain. Biologically, these signs and symptoms are explained by an increasing microvascular caliber, enhanced vascular permeability, leukocyte recruitment, and the release of inflammatory mediators. 10Inflammation in physiologic states is a controlled response that protects against further injury and clears damaged tissue. In disease states such as sepsis, however, uncontrolled inflammation can lead to a marked breakdown of the extracellular matrix as well as organ destruction. 10Inflammation can also be acute or chronic-two well-characterized states in which neutrophils and monocytes, respectively, play an important role. Similarly, DVT is a process with acute and chronic phases. In this setting, the main cells observed during acute DVT are the neutrophils.Monocytes are observed during the chronic phase. This parallel between inflammation and DVT is highly suggestive of a relationship. Inflammation and Vein Thrombosis Endothelial CellsECs play a pivotal role in venous thrombosis in healthy individuals. While arterial thrombosis requires EC disruption with collagen exposure (as Inflammation and Acute Venous ThrombosisJose Antonio Diaz, MD published material that assesses the relationship between inflammation and acute vein thrombosis. The article will focus on the role of endothelial cells, leukocytes, platelets, and microparticles in acute vein thrombosis and discuss the role of thrombin, P-selectin, platelet-activating factor, endothelin-1, and nitric oxide from the perspective of inflammation.

Galectin‐3 and venous thromboembolism incidence: the Atherosclerosis Risk in Communities (ARIC) Study

“…In mouse models, elevated galectin-3 is correlated with thrombus size, and in human patients it correlated with acute VT. 9 The partial attenuation of the association between galectin-3 and VTE by other inflammatory and cardiac biomarkers suggests that galectin-3 level may also reflect the role of inflammation in VTE pathogenesis. 6,8 This attenuation may be the result of the other biomarkers being mediators of the galectin-3 association with VTE or reflect similar pathways between these biomarkers in VTE pathogenesis. Galectin-3 has been reported to interact with gal3bp at the thrombus-vein wall interface, and may contribute to thrombosis through proinflammatory, interleukin-6-dependent mechanisms.…”

“…Venous thromboembolism (VTE), presenting as deep venous thrombosis (DVT) and/or pulmonary embolism (PE), is a major public health problem with a multifactorial etiology . Risk of VTE is increased in patients with inflammatory diseases or with elevated levels of inflammation markers, such as C‐reactive protein and interleukin‐6 . Among inflammatory pathways, galectin‐3–binding protein (gal3bp) and its receptor/ligand, galectin‐3, are secreted proteins that can interact with each other to promote cell‐to‐cell adhesion and initiate pathologic, proinflammatory signaling cascades .…”

“…1,2 Risk of VTE is increased in patients with inflammatory diseases or with elevated levels of inflammation markers, such as C-reactive protein and interleukin-6. [5][6][7][8] Among inflammatory pathways, galectin-3-binding protein (gal3bp) and its receptor/ligand, galectin-3, are secreted proteins that can interact with each other to promote cell-to-cell adhesion and initiate pathologic, proinflammatory signaling cascades. 9 Gal3bp and galectin-3 play important roles in a number of pathological conditions, such as cancer, diabetes, atherosclerosis, and heart failure, and some evidence suggests a role in VTE.…”

The role of galectin-3 and galectin-3–binding protein in venous thrombosis

“…11,12 Cell-to-cell adhesion plays a major role in thrombogenesis, both at the thrombus-vein wall interface and within the thrombus itself. 29,30 The adhesive properties of gal3 multimers may contribute to gal3's apparent prothrombotic function. We suspect that the increase in gal3 protein observed during VT in PLTs may be caused by in situ translation of preexisting gal3 mRNA, because PLTs, although lacking in nuclei, have been shown to possess translational machinery.…”

Association of Peripheral Arterial Occlusive Disease and Deep Venous Thrombosis with Risk of Consequent Sepsis Event: A Retrospective Population-Based Cohort Study

“…Several studies examined the endothelial damage and dysfunction in DVT. A literature review indicated that, in patients in the acute phase of VTE, endothelial cells produced IL-6, platelet-activating factor, and other substances that affect the inflammatory response and involve the formation of thrombi [ 26 ]. Persistently increased levels of inflammatory factors, such as tumor necrosis factor alpha (TNF-α), IL-6, and CXCL-8, accompanied by certain markers of endothelial damage, such as tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), and vWF, were detected in patients with a history of idiopathic DVT.…”