Neutrophils: back in the thrombosis spotlight

DF Noubouossie, BN Reeves… - Blood, The Journal of …, 2019 - ashpublications.org
Blood, The Journal of the American Society of Hematology, 2019ashpublications.org
Reactive and clonal neutrophil expansion has been associated with thrombosis, suggesting
that neutrophils play a role in this process. However, although there is no doubt that
activated monocytes trigger coagulation in a tissue factor-dependent manner, it remains
uncertain whether stimulated neutrophils can also directly activate coagulation. After more
than a decade of debate, it is now largely accepted that normal human neutrophils do not
synthetize tissue factor, the initiator of the extrinsic pathway of coagulation. However …
Abstract
Reactive and clonal neutrophil expansion has been associated with thrombosis, suggesting that neutrophils play a role in this process. However, although there is no doubt that activated monocytes trigger coagulation in a tissue factor-dependent manner, it remains uncertain whether stimulated neutrophils can also directly activate coagulation. After more than a decade of debate, it is now largely accepted that normal human neutrophils do not synthetize tissue factor, the initiator of the extrinsic pathway of coagulation. However, neutrophils may passively acquire tissue factor from monocytes. Recently, the contact system, which initiates coagulation via the intrinsic pathway, has been implicated in the pathogenesis of thrombosis. After the recent description of neutrophil extracellular trap (NET) release by activated neutrophils, some animal models of thrombosis have demonstrated that coagulation may be enhanced by direct NET-dependent activation of the contact system. However, there is currently no consensus on how to assess or quantify NETosis in vivo, and other experimental animal models have failed to demonstrate a role for neutrophils in thrombogenesis. Nevertheless, it is likely that NETs can serve to localize other circulating coagulation components and can also promote vessel occlusion independent of fibrin formation. This article provides a critical appraisal of the possible roles of neutrophils in thrombosis and highlights some existing knowledge gaps regarding the procoagulant activities of neutrophil-derived extracellular chromatin and its molecular components. A better understanding of these mechanisms could guide future approaches to prevent and/or treat thrombosis.
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