Are Microparticles the Missing Link between Thrombosis and Autoimmune Diseases? Involvement in Selected Rheumatologic Diseases

Abstract

Microparticles (MPs) are membrane-bound vesicles with important physiologic effects. MPs exchange information intercellularly, with each kind of MP carrying antigens and receptors of the cells from which they originated. They are biologic effectors in inflammation, angiogenesis, vascular injury, and thrombosis. Thrombosis is generally caused by abnormalities in blood flow, blood composition, and/or properties of the vessel wall. Thrombosis is a well-described feature of cardiovascular disease and cerebrovascular disease. Accumulating evidence suggests that increased risk of thrombosis is also characteristic of autoimmune disorders and immune-mediated diseases affecting all age groups, although the older adults are most vulnerable. Current research has also implicated MPs as a source of autoantigenic nuclear material that can form immune complexes, activate the innate immune system, and may lead to autoimmunity. This review focuses on the contribution of MPs to both the pathogenesis of autoimmune diseases and, as the immune and coagulation systems are tightly linked, their role in hypercoagulability in the setting of autoimmunity in an aging population.

From blood coagulation to innate and adaptive immunity: the role of platelets in the physiology and pathology of autoimmune disorders

“…The enzymes and growth factors delivered by platelets facilitate tissue degeneration and neovasculogenesis. Mechanisms and pathways described for platelets in the context of AD overlap with those characteristic of thrombosis and atherosclerosis, which explains the increased cardiovascular risk of AD patients [ 5 , 8 , 88 , 153 ].…”

“…The platelet cell membrane bears a nett negative charge, and this accelerates the activation of factor X and prothrombin, by providing sites for the assembly of enzyme substrate complexes. Changes in the platelet cell membrane lead also to the generation of platelet-derived microparticles and a body of evidence points towards their role as initiators of thrombosis via the tissue factor pathway [ 8 ]. In mouse models, platelets were shown to become hyperactive after induction by microparticles derived from damaged endothelial cells [ 9 ].…”

“…They have been shown to increase the expression of adhesion molecules on endothelial and immune cells, enhance cytokine release, and consequently induce angiogenesis [ 50 ]. Moreover, PMPs are highly procoagulant and play important role in haemostasis and thrombosis [ 8 , 51 ]. PMPs provide a surface for complement deposition and participate in complement activation [ 52 , 53 ].…”

“…SLE patients have an increased risk of developing cardiovascular disease, stroke, and venous thrombosis, which cannot be explained by classic cardiac risk factors [ 134 ]. Platelet activation seems to be a potential link between atherosclerotic lesions and systemic inflammation [ 20 ], and many patients have been diagnosed with comorbidity of SLE and APS [ 8 ].…”

Age-Related Changes in Thrombosis and Hemostasis

“…9 The remaining part of this issue is devoted to situations seen in the clinical practice in the aging population, starting with a review by Cunningham et al of the role of thrombogenic microparticles in autoimmune diseases, including rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus affecting older individuals. 10 Next is the discussion by McMahon and Kwaan on the increased hazards in the older patients with immune thrombocytopenic purpura. Older adults are also more often taking multiple drugs and are at higher risk for drug-induced thrombocytopenia.…”