Leukocyte adhesion and thrombosis.
OBJECTIVE
The consequences of arterial thrombosis such as myocardial infarction, stroke and peripheral vascular occlusion are the leading causes of morbidity and mortality. A high leukocyte count and an elevation in inflammatory markers are identified as significant risk factors for thrombosis. Leukocytes form the front line in defense against infection and are the first cells arriving at the site of inflammation. This review summarizes the cellular and molecular mechanisms by which adherent leukocytes can induce a prothrombotic state.


RESULTS
Circulating tissue factor has been recognized as a potential prothrombotic factor initiating thrombosis after vascular injury. The tissue factor is present on microvesicles originated from activated leukocytes. Leukocytes generate tissue factor containing microvesicles following stimulation with cytokines and following platelet adhesion via P-selectin. Additionally, activated leukocytes release several mediators, such as cathepsin G and elastase, which can activate both the coagulation cascade and platelets. Furthermore, new roles for leukocytes have been identified in vascular injury in sickle cell anemia, in vascular occlusion following the rupture of atherosclerotic plaque, and in thrombotic complications of myeloproliferative diseases.


CONCLUSIONS
Leukocyte adhesion to endothelium and platelets plays an important role in the activation of the coagulation cascade. An excessive activation of leukocytes during the inflammatory process may induce a systemic procoagulant state. Elucidation of critical steps in activation of coagulation by leukocytes may offer a new therapeutic target for antithrombotic therapy based on blocking leukocyte adhesion.
Afshar-Kharghan
Vahid
V
Department of Pathology and Medicine (Thrombosis Research), Baylor College of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas 77030, USA.
Thiagarajan
Perumal
P
D000818:Animals; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D010974:Platelet Aggregation; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
D001779:Blood Coagulation Factors