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Neutrophils and deep venous thrombosis
1Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa 19140.
Abstract:
A case can be made for the participation of polymorphonuclears (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 which identified three families of adhesive receptors (integrins, intercellular adhesion molecules and selectins) on endothelium, leukocytes and platelets. Monoclonal antibodies against beta 2-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.
Insights
Polymorphonuclears (PMN) play a role in venous thrombosis. Inhibiting PMN adhesion may prevent deep venous thrombosis (DVT), offering a new therapeutic strategy.
Area of Science:
- Vascular biology
- Hematology
- Immunology
Background:
- Polymorphonuclears (PMN) are implicated in the initiation and progression of venous thrombosis.
- Leukocyte adhesion to veins is observed in animal models at sites of thrombus formation.
- PMN interaction with platelets in thrombi may promote coagulation and thrombus development.
Purpose of the Study:
- To explore the role of PMN in venous thrombosis.
- To investigate potential therapeutic strategies targeting PMN adhesion in deep venous thrombosis (DVT).
Main Methods:
- Review of animal models demonstrating leukocyte adhesion to veins.
- Analysis of clinical data on lidocaine's effect on DVT incidence post-hip replacement.
- Examination of studies on adhesive receptors (integrins, ICAMs, selectins) and monoclonal antibody interventions.
- Consideration of PMN and platelet adhesion to fibrin.
Main Results:
- Lidocaine and derivatives inhibited leukocyte adhesion in canine models.
- Lidocaine reduced DVT incidence in patients after hip replacement.
- Monoclonal antibodies against beta 2-integrins decreased leukocyte adhesion and injury in animal models.
- Selectin ligands suggest potential for small molecule inhibitors of PMN adhesion.
Conclusions:
- PMN adhesion is a key factor in venous thrombosis.
- Targeting PMN adhesion mechanisms, particularly involving integrins and selectins, presents a promising avenue for DVT prevention.
- Further research into PMN-fibrin interactions could yield novel therapeutic targets.