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Baseline Platelet Activation and Reactivity in Patients with Critical Limb Ischemia.

Wisman PP, Teraa M, de Borst GJ, Verhaar MC, Roest M, Moll FL - PLoS ONE (2015)

Bottom Line: Patients with critical limb ischemia (CLI) have a high risk to develop cardiovascular events (CVE).Maximal reactivity to stimulation of the collagen and thrombin activation pathway was decreased in CLI patients compared to healthy controls.In line, attenuated platelet reactivity to stimulation of multiple activation pathways was associated with several traditional risk factors for cardiovascular disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, 3584CX, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, 3584CX, The Netherlands.

ABSTRACT

Background: Patients with critical limb ischemia (CLI) have a high risk to develop cardiovascular events (CVE). We hypothesized that in CLI patients platelets would display increased baseline activation and reactivity.

Objectives: We investigated baseline platelet activation and platelet reactivity in patients with CLI.

Patients/methods: In this study baseline platelet activation and platelet reactivity in response to stimulation of all major platelet activation pathways were determined in 20 CLI patients (11 using aspirin and 9 using vitamin K-antagonists) included in the Juventas-trial (clinicaltrials.gov NCT00371371) and in 17 healthy controls. Platelet activation was quantified with flow cytometric measurement of platelet P-selectin expression and fibrinogen binding.

Results: CLI patients not using aspirin showed higher baseline platelet activation compared to healthy controls. Maximal reactivity to stimulation of the collagen and thrombin activation pathway was decreased in CLI patients compared to healthy controls. In line, attenuated platelet reactivity to stimulation of multiple activation pathways was associated with several traditional risk factors for cardiovascular disease.

Conclusions: Baseline platelet activation was increased in CLI patients, whereas the reactivity of circulating platelets to several stimulatory agents is decreased. Reactivity of platelets was inversely correlated with cardiovascular risk factors.

No MeSH data available.


Related in: MedlinePlus

Platelet reactivity of CLI A- patients versus healthy controls.MFI for fibrinogen binding or P-selectin expression per agonist, stratified for CLI A- patients versus healthy controls. CLI A- CLI patients not treated with aspirin, MFI median fluorescence intensity, CVX Convulxin, ADP Adenosine Diphosphate, TRAP Thrombin receptor agonist SFLLRN, Tx Thromboxane receptor agonist, Curve dose-response curves of each group differ significantly (p<0.05), Max maximal platelet reactivity of each group differ significantly (p<0.05), EC50 half maximal effective concentration of each group differ significantly (p<0.05).
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pone.0131356.g002: Platelet reactivity of CLI A- patients versus healthy controls.MFI for fibrinogen binding or P-selectin expression per agonist, stratified for CLI A- patients versus healthy controls. CLI A- CLI patients not treated with aspirin, MFI median fluorescence intensity, CVX Convulxin, ADP Adenosine Diphosphate, TRAP Thrombin receptor agonist SFLLRN, Tx Thromboxane receptor agonist, Curve dose-response curves of each group differ significantly (p<0.05), Max maximal platelet reactivity of each group differ significantly (p<0.05), EC50 half maximal effective concentration of each group differ significantly (p<0.05).

Mentions: Platelet reactivity was determined with P-selectin expression or the fibrinogen binding capacity after stimulation to four major platelet agonists. Overall, in-vitro platelet reactivity in CLI A- patients was not elevated for any of the agonists, when compared to healthy controls. Instead, CLI A- patients’ maximal platelet αIIBβ3 activation and P-selectin expression was decreased for CVX (p = 0.001) and TRAP (p = 0,004) activation (Fig 2 and Fig B,C in S1 file). CLI A- patients had a lower EC50 platelet P-selectin expression for CVX activation than healthy donors (2.28±0.24 vs 3.25±0.21; p = 0.005).


Baseline Platelet Activation and Reactivity in Patients with Critical Limb Ischemia.

Wisman PP, Teraa M, de Borst GJ, Verhaar MC, Roest M, Moll FL - PLoS ONE (2015)

Platelet reactivity of CLI A- patients versus healthy controls.MFI for fibrinogen binding or P-selectin expression per agonist, stratified for CLI A- patients versus healthy controls. CLI A- CLI patients not treated with aspirin, MFI median fluorescence intensity, CVX Convulxin, ADP Adenosine Diphosphate, TRAP Thrombin receptor agonist SFLLRN, Tx Thromboxane receptor agonist, Curve dose-response curves of each group differ significantly (p<0.05), Max maximal platelet reactivity of each group differ significantly (p<0.05), EC50 half maximal effective concentration of each group differ significantly (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492682&req=5

pone.0131356.g002: Platelet reactivity of CLI A- patients versus healthy controls.MFI for fibrinogen binding or P-selectin expression per agonist, stratified for CLI A- patients versus healthy controls. CLI A- CLI patients not treated with aspirin, MFI median fluorescence intensity, CVX Convulxin, ADP Adenosine Diphosphate, TRAP Thrombin receptor agonist SFLLRN, Tx Thromboxane receptor agonist, Curve dose-response curves of each group differ significantly (p<0.05), Max maximal platelet reactivity of each group differ significantly (p<0.05), EC50 half maximal effective concentration of each group differ significantly (p<0.05).
Mentions: Platelet reactivity was determined with P-selectin expression or the fibrinogen binding capacity after stimulation to four major platelet agonists. Overall, in-vitro platelet reactivity in CLI A- patients was not elevated for any of the agonists, when compared to healthy controls. Instead, CLI A- patients’ maximal platelet αIIBβ3 activation and P-selectin expression was decreased for CVX (p = 0.001) and TRAP (p = 0,004) activation (Fig 2 and Fig B,C in S1 file). CLI A- patients had a lower EC50 platelet P-selectin expression for CVX activation than healthy donors (2.28±0.24 vs 3.25±0.21; p = 0.005).

Bottom Line: Patients with critical limb ischemia (CLI) have a high risk to develop cardiovascular events (CVE).Maximal reactivity to stimulation of the collagen and thrombin activation pathway was decreased in CLI patients compared to healthy controls.In line, attenuated platelet reactivity to stimulation of multiple activation pathways was associated with several traditional risk factors for cardiovascular disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, 3584CX, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, 3584CX, The Netherlands.

ABSTRACT

Background: Patients with critical limb ischemia (CLI) have a high risk to develop cardiovascular events (CVE). We hypothesized that in CLI patients platelets would display increased baseline activation and reactivity.

Objectives: We investigated baseline platelet activation and platelet reactivity in patients with CLI.

Patients/methods: In this study baseline platelet activation and platelet reactivity in response to stimulation of all major platelet activation pathways were determined in 20 CLI patients (11 using aspirin and 9 using vitamin K-antagonists) included in the Juventas-trial (clinicaltrials.gov NCT00371371) and in 17 healthy controls. Platelet activation was quantified with flow cytometric measurement of platelet P-selectin expression and fibrinogen binding.

Results: CLI patients not using aspirin showed higher baseline platelet activation compared to healthy controls. Maximal reactivity to stimulation of the collagen and thrombin activation pathway was decreased in CLI patients compared to healthy controls. In line, attenuated platelet reactivity to stimulation of multiple activation pathways was associated with several traditional risk factors for cardiovascular disease.

Conclusions: Baseline platelet activation was increased in CLI patients, whereas the reactivity of circulating platelets to several stimulatory agents is decreased. Reactivity of platelets was inversely correlated with cardiovascular risk factors.

No MeSH data available.


Related in: MedlinePlus