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Inflammation and Thrombosis – Brothers in Arms Elena M Faioni1

and Marco Cattaneo2

1. Senior Researcher, Internal Medicine, Department of Medicine, Surgery and Dentistry, University of Milan; 2. Professor, Internal Medicine, University of Milan, and Director of Medicine III, San Paolo Hospital, Milan


Several interactions occur between inflammation and thrombosis that become more apparent with ageing. It is a two-way process: inflammation promotes aggregation and coagulation, while activated platelets and coagulation factors or peptides promote inflammation by several mechanisms. Recent evidence points to the role played by platelets and possibly coagulation factors in the regulation of innate immunity. Physiological anticoagulant pathways also have anti-inflammatory properties. This strong interdependence has an evolutionary origin. Current viewpoints are that inflammation, and thus coagulation, have a role in ageing. ‘Inflamm-ageing’ is a neologism that denotes a low-grade inflammation that accompanies healthy ageing, but can evolve towards excessive inflammation and clotting. It can thus be associated with thrombosis and early death. These fascinating pathophysiological discoveries provide novel targets for the development of new, potentially efficacious antithrombotic drugs.

Keywords Inflammation, thrombosis, ageing, immunity, platelets, anticoagulant pathways

Disclosure: The authors have no conflicts of interest to declare. Received: 21 June 2010 Accepted: 27 January 2011 Citation: European Oncology & Haematology, 2011;7(1):81–4 Correspondence: Elena M Faioni, University of Milan, via A Di Rudini, 8, 20142 Milan, Italy. E:

In the field of thrombosis a distinction has traditionally been maintained between venous and arterial thrombosis in terms of both the composition of the thrombus (fibrin- and cell-rich red thrombus in the veins versus platelet-rich white thrombus in the arteries) and risk factors. Venous thrombosis has been associated with hypercoagulability and/or reduced blood flow, whereas arterial thrombosis has been linked to atherosclerosis. However, more recently clinical epidemiology has suggested that risk factors for venous and arterial thrombosis in part overlap.1,2

This rather subversive

observation is apparently without an explanation and seems, at first glance, to contradict everything that has been accepted about thrombosis for decades.

Chronic inflammation is increasingly recognised as a fundamental pathogenetic mechanism in a large number of diseases and conditions associated with an increased prevalence of thrombosis, some of which are listed in Table 1. C-reactive protein, an established and widely used marker of inflammation, is known to be associated with arterial thrombosis3

associated with venous thromboembolism.4

and was recently shown to be independently Inflammation does not

occur alone, or so practitioners like to believe: it is usually associated with infection or some other kind of toxicity, such as persistent hyperglycaemia or immune response, whether physiological or pathological, so it can be difficult to separate the effect of toxicity from that of inflammation.

Recently, experimental evidence has accumulated in terms of the effect of chronic inflammation, whatever its origin, on haemostatic response and endothelial and immune function. The main results of this research point to the conclusion, at least provisionally, that at some point in


chronic disease progression inflammation does occur alone and is sufficient by itself to provoke and maintain a prothrombotic condition. Moreover, inflammation and its regulation is emerging as a fundamental feature of ageing, giving rise to the new term ‘inflamm-ageing.’5

On the whole, the evidence points to the fact that haemostasis and inflammation are tightly linked and that platelets and coagulation factors participate in inflammation and immune responses. The resulting prothrombotic phenotype predisposes to both arterial and venous thrombosis.

Inflammation and Platelets

Platelets play a major role in haemostasis: they bind to the exposed subendothelium, even at high shear, expose procoagulant surfaces and secrete vasoactive proaggregants, procoagulant substances and growth factors. Platelets thus participate in amplification of the coagulant response and the formation of stable clots and vessel wall repair. Recent evidence points to platelets being inflammatory cells.6,7 The activation of platelets may result in the release of multiple and diverse soluble mediators with pleiotropic functions in inflammation. Chemokines are an example of these mediators; they are responsible for the recruitment of immune cells, lipid mediators and cytokines.6,8 On activation, platelets express new surface proteins, some of which are implicated in leukocyte recruitment and chemokine deposition. One example of such surface proteins is P-selectin. This serves as an anchor for inflammatory leukocytes, facilitating the delivery and immobilisation of platelet-derived chemokines on the activated endothelium.9,10

Another important platelet surface receptor is CD40L,

a tumour necrosis factor-alpha (TNF-α)-related transmembrane receptor implicated in inflammation and innate immunity.8 evidence suggests that CD40L is involved in enhancing the signals

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