The role of leukocytes in thrombosis

Abstract

In recent years, the traditional view of the hemostatic system as being regulated by a coagulation factor cascade coupled with platelet activation has been increasingly challenged by new evidence that activation of the immune system strongly influences blood coagulation and pathological thrombus formation. Leukocytes can be induced to express tissue factor and release proinflammatory and procoagulant molecules such as granular enzymes, cytokines, and damage-associated molecular patterns. These mediators can influence all aspects of thrombus formation, including platelet activation and adhesion, and activation of the intrinsic and extrinsic coagulation pathways. Leukocyte-released procoagulant mediators increase systemic thrombogenicity, and leukocytes are actively recruited to the site of thrombus formation through interactions with platelets and endothelial cell adhesion molecules. Additionally, phagocytic leukocytes are involved in fibrinolysis and thrombus resolution, and can regulate clearance of platelets and coagulation factors. Dysregulated activation of leukocyte innate immune functions thus plays a role in pathological thrombus formation. Modulation of the interactions between leukocytes or leukocyte-derived procoagulant materials and the traditional hemostatic system is an attractive target for the development of novel antithrombotic strategies.

Anticoagulant Activity of Low-Molecular Weight Compounds from Heterometrus laoticus Scorpion Venom

“…Under certain conditions, leukocytes can express tissue factor and release proinflammatory and procoagulant molecules [32]. These molecules can influence platelet activation and adhesion as well as activation of the intrinsic and extrinsic coagulation pathways.…”

Exposure to hypoglycemia and risk of stroke

“…Other proinflammatory changes include an increase in the plasma concentration of IL‐6, IL‐8, IL‐1β, and other proinflammatory mediators that includes leukocytosis, reactive oxygen species (ROS) generation, lipid peroxidation, and increased levels of tumor necrosis factor‐α (TNF‐α) . It is well established that proinflammatory mediators can increase systemic thrombogenicity by affecting multiple pathways …”

Regulation of immune cell signaling by activated protein C

“…Pathologic leukocyte activation also contributes to increased thrombotic risk [15,17,26]; however, the complex topic of immunothrombosis will not be addressed in this review. As part of the normal host defense response to pathogen-associated or damage-associated molecular patterns (PAMPs and DAMPs, respectively), pattern recognition receptors (PRRs) are activated to elicit rapid responses either against foreign pathogens or to endogenous host-derived signals [3,23,27,28].…”

“…The crosstalk between leukocytes, especially neutrophils, and coagulation serine proteases is a broad area that has been extensively reviewed [15–17]. Here, we focus on the crosstalk between leukocytes and the serine protease activated protein C (APC).…”