P-selectin and Platelet-Derived Microparticles Associated with Monocyte Activation Markers in Patients with Pulmonary Embolism
ABSTRACT Platelet activation markers (platelet-derived microparticles and P-selectin on activated platelets), chemokines (monocyte chemotactic peptide and regulated on activation normally T-cell expressed and secreted), and soluble markers (sP-selectin, sE-selectin, sVCAM-1, and sCD14) were measured and compared in patients with pulmonary embolism (PE). These substances are thought to participate in the pathogenesis of PE. Levels of all of the platelet activation markers, chemokines, and soluble markers were higher in the patients with PE than in normal controls. Levels of platelet activation markers were also significantly increased postoperatively after total knee arthroplasty. Anti-platelet therapy significantly inhibited the elevation of platelet activation markers after total knee arthroplasty. These findings suggest that antiplatelet therapy may be useful for PE-related interaction of platelets, leukocytes, and endothelial cells.
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- "Two previous clinical studies have reported elevated levels of CPMPs — mainly PMPs and EMPs — by flow cytometry, in patients hospitalized for deep-vein thrombosis. However , they had different phenotypic representations, and the authors did not take into account potential confounders, such as cardiovascular risk factors  . Experimental studies in vivo are supportive of the involvement of human cell-derived microparticles in venous thrombogenesis in a tissue factor-dependent manner, and have described a correlation of leukocyte-and PMPs with thrombus weight and tissue factor activity  . "
ABSTRACT: Flow cytometry has shown levels of platelet-derived microparticles (PMPs) and endothelial-derived microparticles (EMPs) to be elevated in deep-vein thrombosis. Cardiovascular risk factors can also contribute to hypercoagulability due to circulating procoagulant microparticles (CPMPs). To investigate in a case-control study the respective contribution of pulmonary embolism and cardiovascular risk factors to the level of hypercoagulability due to CPMPs. CPMP, PMP and EMP levels were measured in 45 consecutive patients (age 67.9 +/- 11.6 years; 66.7% men) admitted to an intensive care unit for acute pulmonary embolism (APE), 45 healthy control subjects with no history of venous thromboembolism or vascular risk factors (Controls(noCVRFs)), and 45 patients with cardiovascular risk factors (Controls(CVRFs)). APE was diagnosed by spiral computed tomography or scintigraphy. CPMP levels were assessed using a prothrombinase assay on platelet-depleted plasma (results expressed as nmol/L equivalent). CPMP levels were higher in APE patients than in Controls(noCVRFs) (medians 4.7 vs 3.2 nmol/L, interquartile ranges [IQRs] 2.9-11.1 vs 2.3-4.6 nmol/L; p=0.02). Similar results were reported for PMPs (medians 2.2 vs 1.9 nmol/L, IQRs 1.7-5.8 vs 1.4-2.4 nmol/L; p=0.02), whereas EMP levels were not significantly different. However, CPMP procoagulant activity was not significantly different in APE patients and Controls(CVRFs). CPMPs and PMPs were significantly elevated in APE patients vs Controls(noCVRFs), but this correlation was not significant when APE patients were compared with Controls(CVRFs). Our observations highlight the importance of adjusting for the presence of cardiovascular risk factors in conditions in which microparticle levels are raised.Archives of cardiovascular diseases 06/2010; 103(6-7):394-403. DOI:10.1016/j.acvd.2010.06.005 · 1.66 Impact Factor
- "Predictive role of circulating levels of sP-selectin in assessing cardiovascular risks. Coronary artery disease References Stable coronary arterial disease Atalar et al (2000) Acute coronary syndrome Matsumoto et al (2004) Coronary artery bypass grafting Li et al (2003) Acute myocardial infarction Sakurai et al (1997); Shimomura et al (1998) Peripheral arterial disease Signorelli et al (2003) Ischaemic stroke Cherian et al (2003) Pulmonary embolism Inami et al (2003) Thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome Katayama et al (1993) Kawasaki disease Furui et al (2002) (which must be newly synthesized) on the surface of endothelial cells following vascular injury and/or inflammation, supports leucocyte tethering and rolling, a step required for the firm adhesion/activation and transmigration of leucocytes (Mayadas et al, 1993; Frenette et al, 1996), a critical phenomenon of the early phase of the atherosclerotic process. One should mention that other molecules responsible for leucocyte rolling and adhesion have been also shown to impact atherosclerosis, notably the intercellular adhesion molecule 1/lymphocyte functions associated antigen 1 system (Russell et al, 1995; Sigal et al, 2000). "
Article: P-selectin in haemostasis[Show abstract] [Hide abstract]
ABSTRACT: During the past decade, interrelationships between inflammation and thrombosis have been the subject of extensive works, and it is now commonly recognized that inflammation (notably leucocyte recruitment) directly affects thrombosis, and that thrombosis also constitutes a pro-inflammatory event. This tight link is partly attributable to P-selectin, which is functional not only when expressed on the surface of activated platelets and endothelial cells, but also when shed, generating its soluble form, termed sP-selectin. In this review, we will provide an overview of the relative roles of the different compartments of P-selectin (platelet, endothelial cell, plasma) in haemostasis and vascular pathologies, and the potential therapeutic benefits achievable in targeting this molecule.British Journal of Haematology 09/2004; 126(3):298-306. DOI:10.1111/j.1365-2141.2004.05032.x · 4.96 Impact Factor
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ABSTRACT: Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a common disease, with serious short- and long-term complications and a potential fatal outcome. Despite the knowledge of several inherited and acquired risk factors for VTE, still 30-50 % of the VTE events occur in the absence of obvious predisposing factors. Traditionally, arterial and venous thrombosis has been considered as separate disease entities with different pathology, epidemiology and treatments. However, recently this concept has been challenged, and a potential link between arterial cardiovascular disease and VTE has been suggested. The aim of this thesis was to investigate the impact of traditional cardiovascular risk factors on the risk of VTE in a prospective population-based study. Subjects were recruited from the fourth survey of the Tromsø study, conducted in 1994-95. A total of 27 158 men and women, aged 25-97 years, participated. Incident VTE events were registered from the date of inclusion through the end of follow-up, September 1, 2007. In summary, age, male gender, obesity, mean platelet volume and family history of myocardial infarction were identified as risk factors for venous thrombosis, which makes these factors, shared risk factors for both arterial and venous thrombosis. Other traditional cardiovascular risk factors such as serum lipid levels, blood pressure, smoking and diabetes were not associated with risk of VTE. Subjects with the metabolic syndrome had higher risk of VTE, but this relationship was essentially dependent on the presence of abdominal obesity. Taken together, these findings imply that traditional atherosclerotic risk factors are not shared by arterial and venous thrombosis, and suggest that common determinants for arterial and venous thrombosis are probably related to mechanisms of thrombus formation. The papers of the thesis are not available in Munin, due to publisher's restrictions: 1. Brækkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J, Hansen JB: 'Family history of myocardial infarction is an independent risk factor for venous thromboembolism – The Tromsø Study', Journal of Thrombosis and Haemostasis, 2008, Nov; 6(11): 1851–1857 (Wiley-Blackwell). Available at http://dx.doi.org/10.1111/j.1538-7836.2008.03102.x 2. Borch KH, Brækkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J, Hansen JB: 'Abdominal obesity is essential for the risk of venous thromboembolism in the metabolic syndrome - the Tromsø study', Journal of Thrombosis and Haemostasis, 2009 May; 7(5): 739-45. Available at http://dx.doi.org/10.1111/j.1538-7836.2008.03234.x 3. Brækkan SK, Borch KH, Mathiesen EB, Njølstad I, Wilsgaard T, Hansen JB: 'HDL-cholesterol and future risk of venous thromboembolism – The Tromsø Study', Journal of Thrombosis and Haemostasis, 2009 Aug; 7(8): 1428-30. Available at http://dx.doi.org/10.1111/j.1538-7836.2009.03481.x 4. Brækkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J, Hansen JB: 'Mean platelet volume is an independent risk factor for venous thromboembolism – The Tromsø Study', Journal of Thrombosis and Haemostasis, 2010 Jan; 8(1): 157-162. Available at http://dx.doi.org/10.1111/j.1538-7836.2009.03498.x