Elevation of Endothelial Microparticles, Platelets, and Leukocyte Activation in Patients With Venous Thromboembolism

Chirinos, Julio A.; Heresi, Gustavo A.; Velasquez, Hermes; Jy, Wenche; Jiménez, Joaquín J.; Ahn, Eugene; Horstman, Lawrence L.; Soriano, Andres O.; Zambrano, Juan P.; Ahn, Yeon S.

doi:10.1016/j.jacc.2004.12.075

Cited by 299 publications

(218 citation statements)

References 25 publications

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“…Large platelets have a higher thrombotic potential than small platelets [11], and express higher levels of platelet activation markers, such as P-selectin [12]. Recently, increased levels of P-selectin have been shown in VTE patients [29], and a higher level of circulating P-selectin was associated with increased risk of recurrent VTE in patients with first unprovoked VTE [30]. Altogether, these studies support the hypothesis that platelet activation may also play a role in the pathogenesis of VTE.…”

Section: Discussionmentioning

confidence: 99%

Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø study

Brækkan¹,

Mathiesen

Njølstad

et al. 2010

Journal of Thrombosis and Haemostasis

282

252

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Summary. Background: Platelet size, measured as mean platelet volume (MPV), is associated with platelet reactivity. MPV is increased in acute myocardial infarction, and has been identified as an independent risk factor for future myocardial infarction and stroke. Objectives: The purpose of the study was to determine the impact of platelet count and MPV on the incidence of venous thromboembolism (VTE) in a prospective, population-based study. Methods: Platelet count, MPV and baseline characteristics were registered in 25 923 subjects aged 25-96 years who participated in the Tromsø Study in 1994-1995. Incident VTE events were registered to the end of followup (1 September 2007). Results: There were 445 validated incident VTE events (1.6 per 1000 person-years), of which 186 (42%) were unprovoked, during a mean of 10.8 years of followup. Subjects with MPV ‡ 9.5 fL had a 1.3-fold [95% confidence interval (CI) 1.0-1.7] higher risk of total VTE and a 1.5-fold (95% CI 1.1-2.3) higher risk of unprovoked VTE than subjects with MPV < 8.5 fL in analyses adjusted for age, sex, smoking, body mass index, and platelet count. Increasing MPV was associated with increased risk of total VTE (P for trend = 0.09) and unprovoked VTE (P for trend = 0.03) in analyses adjusted for age and sex. There was no significant association between increasing platelet count and risk of VTE. Conclusions: An increasing MPV was identified as a predictor for VTE, in particular VTE of unprovoked origin. The present findings support the concept that platelet reactivity is important in the pathogenesis of VTE.

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Section: Discussionmentioning

confidence: 99%

Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø study

Brækkan¹,

Mathiesen

Njølstad

et al. 2010

Journal of Thrombosis and Haemostasis

282

252

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“…While highly elevated MP levels were measured shortly after an acute VTE event in cancer and non-cancer patients [13,14] MP levels were not elevated 3 months after a VTE event in a high-risk population of non-cancer patients with a history of recurrent VTE [15]. Although cancer patients have a 4-to 7-fold increased risk of VTE and VTE is the second leading cause of death in this population, after cancer itself [16][17][18] large prospective clinical studies investigating the predictive role of MPs in cancer-associated VTE are still lacking.…”

Section: Introductionmentioning

confidence: 99%

Circulating procoagulant microparticles in cancer patients

Thaler

Weinstabl

et al. 2010

Ann Hematol

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Accumulating evidence indicates that microparticles (MPs) are important mediators of the interaction between cancer and the hemostatic system. We conducted a large prospective cohort study to determine whether the number of circulating procoagulant MPs is elevated in cancer patients and whether the elevated MP levels are predictive of occurrence of venous thrombembolism (VTE). We analyzed plasma samples of 728 cancer patients from the ongoing prospective observational Vienna Cancer and Thrombosis Study (CATS). Study endpoint was the occurrence of symptomatic VTE. Sixty-five age-and sex-matched healthy controls were recruited for defining the cut-off point for elevated MPs (4.62 nanomolar phosphatidylserine nM PS ), which was set at the 95th percentile of MP levels in healthy controls. The measurement of MPs was performed after capture onto immobilized annexin-V, and determination of their procoagulant activity was quantified with a prothrombinase assay. During a median observation period of 710 days 53 patients developed VTE. MP levels (nM PS) were significantly higher in cancer patients than in healthy controls (median 25th-75th percentile : 3.95 1.74-7.96 vs. 1.19 0.81-1.67 , p<0.001). Multivariate analysis including age, sex, surgery, chemo-and radiotherapy showed no statistically significant association of the hazard ratio of elevated MPs with VTE (0.95 [95% CI: 0.55-1.64], p=0.856). In conclusion, MP levels were elevated in cancer patients compared to healthy individuals in this study. However, elevated MP levels were not predictive of VTE.

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“…EMPs, quantified in plasma as particles that are CD31 1 (the constitutive endothelial marker PECAM), but CD42b 2 (the constitutive platelet-specific glycoprotein Ib), are present in low levels in plasma of healthy individuals and reflecting normal endothelial turnover (19,21,22). EMP levels are increased in a variety of vascular-related disorders (21,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Using CD62 (E-selectin, an adhesion molecule expressed on activated endothelium), activation-induced EMPs have a high CD42b 2 CD62 1 / CD42b 2 CD31 1 ratio, and apoptosis-induced EMPs have a low ratio (19)(20)(21)34).…”

mentioning

confidence: 99%

Circulating Endothelial Microparticles as a Measure of Early Lung Destruction in Cigarette Smokers

Gordon

Gudi

Krause

et al. 2011

Am J Respir Crit Care Med

205

173

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Rationale: There is increasing evidence that emphysema is associated with primary loss of pulmonary capillary endothelium. Plasma levels of endothelial microparticles (EMPs), small vesicles released from activated or apoptotic endothelial cells, are elevated in vascularrelated disorders. Objectives: To evaluate whether plasma EMP levels are elevated in smokers with early lung destruction as assessed by normal spirometry but reduced diffusing capacity of the lung for carbon monoxide (DL CO ). Methods: Lung health was assessed by pulmonary function tests (PFTs: spirometry, total lung capacity, DL CO ) and chest X-ray; smoking status was assessed by urine nicotine and cotinine. EMP levels (CD42b 2 CD31 1 microparticles) were quantified as activated or apoptotic. The initial cohort (n 5 92) included healthy nonsmokers (normal PFTs), healthy smokers (normal PFTs), and smokers with early evidence of lung destruction (normal spirometry, low DL CO ). Two prospective cohorts were then tested: a group similar to the initial cohort and an HIV1 1 cohort. Measurements and Main Results: Healthy smokers had mildly increased levels of EMPs. Strikingly, 95% of smokers with normal spirometry, low DL CO had increased EMPs, with reduced CD62 1 / CD31 1 ratios (P , 10 24 ) and elevated CD42b 2 CD31 1 annexin V 1 EMPs (P , 10 24 ), suggesting derivation from endothelial apoptosis. Most elevated EMPs were angiotensin-converting enzyme positive, suggesting derivation from pulmonary capillaries. Both prospective cohorts confirmed the initial cohort data. Conclusions: Plasma EMPs with apoptotic characteristics are elevated in smokers with normal spirometry but reduced DL CO , consistent with the concept that emphysema is associated, in part, with capillary endothelium apoptosis, suggesting that the early development of emphysema might be monitored with plasma EMP levels.

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Elevation of Endothelial Microparticles, Platelets, and Leukocyte Activation in Patients With Venous Thromboembolism

Cited by 299 publications

References 25 publications

Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø study

Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø study

Circulating procoagulant microparticles in cancer patients

Circulating Endothelial Microparticles as a Measure of Early Lung Destruction in Cigarette Smokers

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