Neutrophils and Deep Venous Thrombosis

Abstract

A case can be made for the participation of polymorphonu-clears (PMN) in the initiation and propagation of venous thrombosis. In animal models leukocytes adhered to areas of veins that serve as sites for initiation of thrombi in patients. In addition, PMN are found in white layers of thrombin where they may interact with platelets to attract more of each. This would add bulk and promote coagulation so that red layers are formed. Lidocaine and one of its derivatives inhibited leukocyte adhesion to veins in dogs and lidocaine reduced the incidence of deep venous thrombosis (DVT) in patients after hip replacement, suggesting but not proving that inhibition of PMN adhesion might have contributed. A new approach for preventing PMN contribution to DVT is suggested by recent studies wich identified three families of adhesive receptors (integrins, intercellular adhesion molecules and selectins) on endothelium, leukocytes and platelets. Monoclonal antibodies against β₂-integrins on leukocytes reduced leukocyte adhesion, emigration and PMN-dependent tissue injury in infection, inflammation and ischemia-reperfusion injury in animals. Selectins bind to specific carbohydrate ligands containing sialylated Lewis X, suggesting that relatively small analogues might inhibit PMN adhesion. Both platelets and PMN adhere to polymerizing fibrin through undefined mechanisms. Inhibition of this process might inhibit the buildup of white layers of thrombi.

The prognostic value of increased leukocyte and neutrophil counts in the early phase of cerebral venous sinus thrombosis

“…Benzer şekilde koroner arter hastalıklarında, periferik damar hastalıklarında, inmede ve derin ven trombozunda nötrofil sayısındaki artışın trombüs oluşumunda artışla ve iskemik hasarın daha yaygın olmasıyla ilişkili olduğu gösterilmiştir (12)(13)(14)(15). Kardiovasküler hastalıklarda lökositler ve trombositler arasındaki etkileşimin, özellikle trombositlerle nötrofillerin bir arada kümeleşmesinin daha aktive trombositlerin oluşmasına neden olduğu belirtilmektedir.…”

Absence of IFN-γ accelerates thrombus resolution through enhanced MMP-9 and VEGF expression in mice

“…The potential contribution of intrathrombotic leukocytes to the resolution of venous thrombi (12)(13)(14)(15)(16)(17)(18) prompted us to investigate the effects of IFN-γ deficiency on intrathrombotic leukocyte recruitment. Myeloperoxidase (MPO)-positive neutrophils infiltrated thrombi in WT and Ifng -/-mice to similar extents, reaching a maximal level at 1 day after the IVC ligation and decreasing gradually thereafter ( Figure 3, A and C).…”

“…Several lines of evidence indicate the involvement of proinflammatory cytokines and chemokines in the thrombus formation and resolution (7)(8)(9)(10). Indeed, TNF-α and IL-1β can potently activate endothelial cells, increase the expression of adhesion molecules by endothelial cells, and promote thrombosis (11)(12)(13)(14)(15). Moreover, TNF-α and IL-1β can induce the expression of chemokines, which can activate leukocytes to accelerate thrombus resolution and intrathrombotic neovascularization (16)(17)(18).…”

Inferior Vena Cava Ligation Rapidly Induces Tissue Factor Expression and Venous Thrombosis in Rats

“…17 When blood flow is blocked for many hours or days to create a mature thrombus, it is difficult to differentiate the triggers of thrombosis from the effects of prolonged vascular obstruction. Although Stewart proposed a 4-stage model for the initiation and propagation of DVT, 20 the detailed morphological changes that coincide with thrombus formation have not been determined. To address this issue, we examined the IVC of rats after 15 or 60 minutes of ligation.…”