Serotonin Antagonism Improves Platelet Inhibition in Clopidogrel Low-Responders after Coronary Stent Placement: An In Vitro Pilot Study

BACKGROUND:Platelet volume indices (PVI) such as mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR) are the indicators of increased platelet activity and can be considered as potential biomarkers for diabetic complications.PURPOSE:To study PVI in Type 2 diabetics with and without complications in comparison to nondiabetic patients.MATERIALS AND METHODS:A case–control study was conducted on 300 Type 2 diabetics and 200 nondiabetics. Detailed clinical history regarding duration, hypertension, and complications was taken. PVI was obtained using automated cell counter. Fasting blood glucose, hemoglobin A1c, lipid profile, creatinine were also obtained. Diabetics were further categorized into patients with complications and without complications. Statistical analysis was performed by Statistical Package for the Social Sciences Version 17 (Chicago, IL) Student's t-test and ANOVA test.RESULTS:Platelet count was significantly decreased in diabetics (P = 0.005). MPV was significantly increased in diabetic patients with complications as compared to diabetics without complications and nondiabetic group (P < 0.0001). PDW showed statistically significant difference between diabetics with and without complications and nondiabetics (P < 0.0001). However, no statistically significant difference was observed in platelet-large cell ratio (P-LCR) among all the three study groups. We found statistically significant correlation of MPV with diabetic retinopathy (P = 0.000), nephropathy (P = 0.005), and diabetic foot (P = 0.048). PDW was significantly increased in diabetic retinopathy (P = 0.035) and nephropathy (P = 0.007). P-LCR had no statistically significant correlation with diabetic complications.CONCLUSION:MPV and PDW are predictive biomarkers of diabetic vascular complications. They are more significant in microvascular complications than macrovascular complications.

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“…Thus, it shows that there are many other factors which may account for the thrombotic potential of diabetics with time. [ 25 ]…”

Section: Discussionmentioning

confidence: 99%

Platelet volume indices as predictive biomarkers for diabetic complications in Type 2 diabetic patients

et al. 2017

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“…Thus, it shows that there are many other factors which may account for the thrombotic potential of diabetics with time. [23] Insulin resistance plays a pivotal role in the development of diabetic dyslipidemia by influencing several factors. In insulin resistance and Type 2 diabetes, increased efflux of free fatty acids from adipose tissue and impaired insulin mediated skeletal muscle uptake of free fatty acids increase fatty acid influx into the liver.…”

Section: Discussionmentioning

confidence: 99%

An Evaluation study of Platelet Volume Indices (PVI) in Type-2 Diabetes Mellitus and its Micro and Macro Vascular Complications

Desai¹,

Lakum

2018

APALM

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Background:The study was performed to analyse PVI such as mean platelet volume (MPV), platelet distribution width (PDW) and plateletlarge cell ratio (P-LCR) that are useful for identifying large and haemostatically active platelets, which are risk factors for developing diabetes and its complication.Methods: Case-control study was conducted on 1026 Type 2 diabetics and 616 nondiabetics. Detailed clinical history regarding duration, hypertension and complications was taken. PVI was obtained using three part automated cell counter. Fasting blood glucose, hemoglobin A1C, lipid profile, creatinine were also obtained. Diabetics were further categorized into patients with complications and without complications.Result: MPV, PDW, P-LCR and platelet count were significantly increased in diabetic patients with complications as compared to diabetics without complications and nondiabetic group (P < 0.0001, < 0.0001, 0.0044, 0.023 respectively). We found statistically significant correlation between MPV and diabetic retinopathy (P < 0.0001), nephropathy (P = 0.04), neuropathy (P < 0.0001), coronary artery disease (P < 0.0001), diabetic foot (P = 0.005). PDW was statistically significantly increased in diabetic retinopathy (P < 0.0001), neuropathy (P < 0.0001), coronary artery disease (P < 0.0001), diabetic foot (P = 0.005). P-LCR was statistically significantly increased in diabetic retinopathy (P < 0.0001), neuropathy (P = 0.003), coronary artery disease (P < 0.0001), diabetic foot (P = 0.034). Conclusion:MPV, PDW and P-LCR are predictive biomarkers of diabetic vascular complications. They are more significant in microvascular complications than macrovascular complications.

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“…These results may suggest an alternative potential pathway to target in patients with depression, who have enhanced platelet reactivity to 5-HT, and in patients who are low-responders to Clopidogrel. Clopidogrel low-responders have been shown to have improved platelet inhibition with serotonin receptor antagonism 10 . This has led to the theory of triple therapy of a serotonin antagonist in addition to the aspirin and clopidogrel regimen, especially in those patients with hypo-responsiveness to clopidogrel.…”

Section: Discussionmentioning

confidence: 99%

Platelet Response to Serotonin in Patients With Stable Coronary Heart Disease

Kim¹,

McClure²,

Neighoff³

et al. 2014

The American Journal of Cardiology

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Patients with heart disease and depression have an increased mortality rate. Both behavioral and biologic factors have been proposed as potential etiologic mechanisms. Given that the pathophysiology of depression is thought to involve disruption in brain serotonergic signaling, we investigated platelet response to serotonin stimulation in patients with stable coronary artery disease (CAD). We enrolled 92 patients with stable CAD. Platelet response to increasing concentrations of serotonin (5HT), epinephrine-augmented 5HT, and ADP was measured by optical aggregation and flow cytometry. As concentrations of 5HT and ADP increased, so did the activation and aggregation of the platelets. However, upon addition of the highest concentration of 5HT (30 uM), a significant decrease in platelet activation (p = 0.005) was detected by flow cytometry. This contrasts the increase in platelet activation seen with the addition of the highest concentration of ADP. In conclusion, we found increased platelet activation and aggregation with increased concentrations of ADP; however, when platelets are stimulated with a high concentration of 5HT (30 uM), there is decreased platelet activation. The data demonstrate unique patterns of platelet activation by 5HT in patients with stable CAD. The cause of this phenomenon is unclear. Our study sheds light on the in-vitro response of platelet function to serotonin in patients with stable CAD which may further the mechanistic understanding of heart disease and depression.

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Serotonin Antagonism Improves Platelet Inhibition in Clopidogrel Low-Responders after Coronary Stent Placement: An In Vitro Pilot Study

Cited by 13 publications

References 46 publications

Platelet volume indices as predictive biomarkers for diabetic complications in Type 2 diabetic patients

Platelet volume indices as predictive biomarkers for diabetic complications in Type 2 diabetic patients

An Evaluation study of Platelet Volume Indices (PVI) in Type-2 Diabetes Mellitus and its Micro and Macro Vascular Complications

Platelet Response to Serotonin in Patients With Stable Coronary Heart Disease

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