Platelet hyper-reactivity in active inflammatory arthritis is unique to the adenosine diphosphate pathway: a novel finding and potential therapeutic target

Mullan, Paul A. Mac; Peace, Aaron; Madigan, Anne; Tedesco, Anthony; Kenny, Dermot; McCarthy, Géraldine

doi:10.1093/rheumatology/kep377

Cited by 37 publications

(29 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the in vitro exploration of these anti-platelet drugs, 96-well plate aggregometry has been used to describe ex vivo reactivity of platelets from patients with various diseases. Of note, enhanced platelet reactivity, particularly in response to ADP, has been described in patients with active inflammatory arthritis (27), HIV (28) and metastatic cancer (29). …”

Section: -Well Plate Aggregationmentioning

confidence: 99%

96-well plate-based aggregometry

2018

View full text Add to dashboard Cite

While there are many bench and bedside tests to assess platelet reactivity, ex vivo light transmission aggregometry (LTA) remains the gold standard. LTA, however, is expensive, time-consuming and requires dedicated equipment and staff, making it impractical in many situations. In addition, there is significant variability between data generated at different testing sites meaning that tests often need to be repeated if a patient is transferred to the care of a different hospital. As such, there is clearly an unmet need for standardization of platelet testing.Using the principles of LTA, aggregometry can be conducted in 96-well plates with readings being made in a standard plate reader. This approach allows for the assessment of multiple concentrations of agonists, since the volume of platelets required for each test is significantly lower than for LTA. Furthermore, the lyophilization of a set panel of agonists to a 96-well plate to produce a stable assay substrate allows the production of portable, standardized plates that can be used to generate reproducible tests at multiple sites.In this review, we will discuss the methods and uses of 96-well plate aggregometry for both research and the clinic.

show abstract

Section: -Well Plate Aggregationmentioning

confidence: 99%

96-well plate-based aggregometry

2018

View full text Add to dashboard Cite

show abstract

“…This reactivity pathway was also suggested to be a target in the treatment of these diseases. 33 Moreover, significantly decreased levels of MPV were reported after anti-TNF-a therapy in patients with AS. 20 Recently, MPV that was investigated in inflammatory bowel disease, 18 chronic obstructive pulmonary disease, 15 RA and AS [19][20][21] and PLR which was evaluated in some cancers like gastric, 14 colon, 22 and non-small cell lung cancers 23 have become to be prominent markers to indicate inflammatory status and prognosis of several diseases, but there is no cut-off level reported before for PLR and MPV as well as NLR.…”

Section: Discussionmentioning

confidence: 99%

May Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios Indicate Disease Activity in Ankylosing Spondylitis?

et al. 2015

View full text Add to dashboard Cite

Objectives:This study aims to evaluate the associations between neutrophil-lymphocyte ratio (NLR), mean platelet volume, and plateletlymphocyte ratio (PLR) with disease activity in ankylosing spondylitis. Patients and methods:The study included 103 patients (63 males, 40 females; mean age 40.7±12.0 years; range 20 to 70 years) with ankylosing spondylitis and 70 healthy controls (43 males, 27 females; mean age 42.7±15.3 years; range 18 to 66 years). All participants' age, sex, erythrocyte sedimentation rate, C-reactive protein and mean platelet volume levels, total white blood cell, neutrophil, lymphocyte, and platelet counts were recorded while patients' Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index and Bath Ankylosing Spondylitis Metrology Index scores, medication types, duration of disease and medication use were recorded. Patients were divided into three groups: healthy controls (group 1), patients having BASDAI scores <4 with mild disease activity (group 2, n=73), and patients having BASDAI scores ≥4 with moderate-severe disease activity (group 3, n=30). NLR and PLR values were calculated. Results: Counts of neutrophil, NLR, C-reactive protein levels and PLR were significantly higher in group 3 compared to groups 1 and 2 (p<0.05). BASDAI scores were correlated weakly with neutrophil counts, NLR and PLR, and correlated moderately with C-reactive protein and erythrocyte sedimentation rate (p<0.05). Conclusion: Our study results indicate that, in ankylosing spondylitis, mean platelet volume is not associated with disease activity, whereas NLR and PLR may reflect disease activity.

show abstract

“…Thus, antagonists for these receptors may be potential targets for pathophysiological diseases linked to inflammation and articular cartilage resorption. Patients with RA have increased risk of cardiovascular disorders, and it was shown that there was an enhanced response of platelets to ADP in patients with RA [394].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Purinergic signalling in the musculoskeletal system

Burnstock

Arnett

Orriss

2013

Purinergic Signalling

109

114

View full text Add to dashboard Cite

It is now widely recognised that extracellular nucleotides, signalling via purinergic receptors, participate in numerous biological processes in most tissues. It has become evident that extracellular nucleotides have significant regulatory effects in the musculoskeletal system. In early development, ATP released from motor nerves along with acetylcholine acts as a cotransmitter in neuromuscular transmission; in mature animals, ATP functions as a neuromodulator. Purinergic receptors expressed by skeletal muscle and satellite cells play important pathophysiological roles in their development or repair. In many cell types, expression of purinergic receptors is often dependent on differentiation. For example, sequential expression of P2X5, P2Y 1 and P2X2 receptors occurs during muscle regeneration in the mdx model of muscular dystrophy. In bone and cartilage cells, the functional effects of purinergic signalling appear to be largely negative. ATP stimulates the formation and activation of osteoclasts, the bone-destroying cells. Another role appears to be as a potent local inhibitor of mineralisation. In osteoblasts, the bone-forming cells, ATP acts via P2 receptors to limit bone mineralisation by inhibiting alkaline phosphatase expression and activity. Extracellular ATP additionally exerts significant effects on mineralisation via its hydrolysis product, pyrophosphate. Evidence now suggests that purinergic signalling is potentially important in several bone and joint disorders including osteoporosis, rheumatoid arthritis and cancers. Strategies for future musculoskeletal therapies might involve modulation of purinergic receptor function or of the ecto-nucleotidases responsible for ATP breakdown or ATP transport inhibitors.

show abstract

Platelet hyper-reactivity in active inflammatory arthritis is unique to the adenosine diphosphate pathway: a novel finding and potential therapeutic target

Abstract: Patients with active IA demonstrate enhanced platelet reactivity, unique to the ADP pathway. This potential pro-thrombotic bias may contribute to their increased cardiovascular risk.

Cited by 37 publications

References 18 publications

96-well plate-based aggregometry

96-well plate-based aggregometry

May Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios Indicate Disease Activity in Ankylosing Spondylitis?

Purinergic signalling in the musculoskeletal system

Contact Info

Product

Resources

About