Evidence of platelet activation in multiple sclerosis

Sheremata, William A.; Jy, Wenche; Horstman, Lawrence L.; Ahn, Yeon S.; Alexander, J. Steven; Minagar, Alireza

doi:10.1186/1742-2094-5-27

Cited by 162 publications

(136 citation statements)

References 38 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…There is evidence that homocysteine plasma levels, a risk factor for CVD, may be higher in patients with MS [42][43][44] . Thrombogenic factors [26,42,45] and endothelial function [47] may also be altered in patients with MS. As mentioned, MS patients may have a healthier lifestyle after MS diagnosis, and cardiovascular risk factors may be identified and treated during frequent health care contacts, which may explain the attenuated cardiovascular risk during follow-up.…”

Section: Discussionmentioning

confidence: 99%

Risk of Arterial Cardiovascular Diseases in Patients with Multiple Sclerosis: A Population-Based Cohort Study

et al. 2010

View full text Add to dashboard Cite

Background: Patients with multiple sclerosis (MS) may have a higher risk of cardiovascular diseases (CVD) than the general population, but data are limited. Methods: We conducted a population-based cohort study involving Danish citizens diagnosed with MS (n = 13,963) from 1977 to 2006 and an age- and sex-matched population cohort (n = 66,407) using data on MS, arterial CVD and comorbidity from the Danish National Registry of Patients. We calculated the risk of arterial CVD for all subjects and computed adjusted incidence rate ratios (IRRs). Results: During the first year of follow-up, the risk of myocardial infarction (MI) was 0.2% among patients with MS (adjusted IRR = 1.84; 95% confidence interval, CI: 1.28–2.65, compared with population cohort members), whereas the 1-year risk of overall stroke was 0.3% (adjusted IRR = 1.96; 95% CI: 1.42–2.71). IRRs were 1.92 (95% CI: 1.27–2.90) for heart failure and 0.77 (95% CI: 0.42–1.39) for atrial fibrillation/flutter. During the subsequent 2–30 years of follow-up, IRRs remained elevated for overall stroke (1.23; 95% CI: 1.10–1.38) and heart failure (1.53; 95% CI: 1.37–1.71) but decreased for acute MI (1.10; 95% CI: 0.97–1.24). Conclusion: In this Danish cohort, the risk of CVD among MS patients was low, but greater than that in the general population, particularly in the short term.

show abstract

Section: Discussionmentioning

confidence: 99%

Risk of Arterial Cardiovascular Diseases in Patients with Multiple Sclerosis: A Population-Based Cohort Study

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Moreover, some evidence exists that the coagulation pathway is activated in MS [15,16] and homocysteine plasma levels, a risk factor for VTE, might be higher in untreated MS patients than in healthy controls [15,17] . There is also some evidence that platelets may be activated in treatment-naïve MS patients [18] . Other factors involved may include differing use of pro-or anti-thrombotic medications (e.g.…”

Section: Discussionmentioning

confidence: 99%

Multiple Sclerosis and Risk of Venous Thromboembolism: A Population-Based Cohort Study

et al. 2012

View full text Add to dashboard Cite

Background: Multiple sclerosis (MS) patients may be at increased risk of venous thromboembolism (VTE), but evidence is limited. Objectives: To examine long-term risk of VTE among MS patients. Patients and Methods: We conducted a population-based cohort study among 17,418 Danish MS patients and 87,090 comparison cohort members from the general population. Data on MS, VTE and comorbidities were obtained from the Danish National Registry of Patients including all admissions to Danish hospitals since 1977. We computed cumulative risks for VTE and adjusted incidence rate ratios (IRRs). Results: A total of 34 (0.2%) MS patients and 36 (0.04%) comparison cohort members had a deep venous thrombosis (DVT) within 1 year following the date of initial MS diagnosis/index date [adjusted IRR = 3.02 (95% CI: 2.14–4.27)]. During this period, 16 (0.09%) MS patients and 26 (0.03%) comparison cohort members had a documented pulmonary embolism (PE) [adjusted IRR = 2.85 (95% CI: 1.72–4.70)]. During the subsequent up to 29 years, 315 (1.9% of MS patients alive at year 1) MS patients had a record of a DVT [adjusted IRR = 2.28 (95% CI: 2.01–2.59)] and 129 (0.8%) had PE [IRR = 1.58 (95% CI: 1.31–1.92]. Conclusion: MS is a risk factor for VTE, but the absolute risk is low.

show abstract

“…The chronic inflammatory environment in RRMS (Lund et al, 2004) probably underlies this inappropriate neutrophil priming, which may result in enhanced neutrophil activation during infection. The higher levels of NETs in serum might also be linked to the chronic inflammatory environment in MS, but may have been caused by other triggers such as infections, that have been associated with relapses in these patients (Granieri et al, 2001) or higher frequency of activated platelets (Sheremata et al, 2008) or endothelial cells (Minagar et al, 2001) both elevated in MS. Due to the central role of T cells in RRMS and the ability of NETs to modulate T cell immunity, an abnormally gender-specific high level of NETs in this disease as consequence of neutrophil priming may play an important role in certain aspects of the pathogenesis and also explain some gender-specific differences.…”

Section: -Introductionmentioning

confidence: 99%

Gender differences in circulating levels of neutrophil extracellular traps in serum of multiple sclerosis patients

Tillack

Naegele

Haueis

et al. 2013

Journal of Neuroimmunology

View full text Add to dashboard Cite

Neutrophil extracellular traps (NETs) trap and kill pathogens very efficiently but also activate dendritic cells and prime T cells. Previously, we demonstrated that neutrophils are primed and circulating NETs are elevated in relapsing remitting multiple sclerosis (RRMS), a T cell-mediated autoimmune disease. Here, we demonstrate gender specific differences in circulating NETs but not in neutrophil priming in RRMS patients. Although the results from our systematic and in depth characterization of these patients argue against a major role of circulating NETs in this disease, they suggest that NETs may underlie gender-specific differences in MS pathogenesis. Abstract (100 words)Neutrophil extracellular traps (NETs) trap and kill pathogens very efficiently but also activate dendritic cells and prime T cells. Previously, we demonstrated that neutrophils are primed and circulating NETs are elevated in relapsing remitting multiple sclerosis (RRMS), a T cell-mediated autoimmune disease. Here, we demonstrate gender specific differences in circulating NETs but not in neutrophil priming in RRMS patients. Although the results from our systematic and in depth characterization of these patients argue against a major role of circulating NETs in this disease, they suggest that NETs may underlie gender-specific differences in MS pathogenesis.Key words: Neutrophil, neutrophil extracellular traps (NETs), multiple sclerosis, genderCirculating NETs in MS patients 3 1-IntroductionThe main function of the innate immune system during infection is to eliminate the pathogen, and neutrophils are key players in innate immune responses.Women of reproductive age are more resistant to sepsis and subsequent morbidity and mortality than men (Schroder et al., 1998), and the incidence of sepsis in postmenopausal women increases to levels almost equal to those seen in age-matched men (Martin et al., 2003). Women also have a higher systemic neutrophil count compared with men (Bain and England, 1975a), and neutrophil counts correlate with estradiol levels during menstruation (Bain and England, 1975b) and pregnancy (Efrati et al., 1964) suggesting that sex hormones influence neutrophilia and overall resistance to sepsis most likely by delaying apoptosis in neutrophils (Molloy et al., 2003). In order to eliminate pathogens during infections, neutrophils are armed with a variety of weapons including engulfment and intracellular degradation of microbes (Hampton et al., 1998;Segal, 2005), release of oxygen species and granule proteins (Lehrer and Ganz, 1999) and release of extracellular chromatin fibers bound to granular, nuclear and cytoplasmic proteins called neutrophil extracellular traps (NETs) (Brinkmann et al., 2004). NETs not only trap and kill pathogens very efficiently but also minimize collateral tissue damage by containing proteases to the DNA fibers and act as physical barriers preventing microbial spread. Despite the well documented importance of NETs as an effective antimicrobial first line defense mechanism, there is increasing ...

show abstract

Evidence of platelet activation in multiple sclerosis

Cited by 162 publications

References 38 publications

Risk of Arterial Cardiovascular Diseases in Patients with Multiple Sclerosis: A Population-Based Cohort Study

Risk of Arterial Cardiovascular Diseases in Patients with Multiple Sclerosis: A Population-Based Cohort Study

Multiple Sclerosis and Risk of Venous Thromboembolism: A Population-Based Cohort Study

Gender differences in circulating levels of neutrophil extracellular traps in serum of multiple sclerosis patients

Contact Info

Product

Resources

About