Platelet Function in CKD: A Systematic Review and Meta-Analysis

2021 ◽  
pp. ASN.2020101440
Author(s):  
Constance C.F.M.J. Baaten ◽  
Marieke Sternkopf ◽  
Tobias Henning ◽  
Nikolaus Marx ◽  
Joachim Jankowski ◽  
...  
Keyword(s):  
Systematic Review ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Meta Analysis ◽  
Uremic Toxins ◽  
Extensive Literature ◽  
Direct Effects ◽  
Platelet Activity

BackgroundPatients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings.MethodsTo help clarify how CKD affects platelet function, we conducted a systematic review and meta-analysis of platelet activity in CKD, with a focus on nondialysis-induced effects. We also performed an extensive literature search for the effects of individual uremic toxins on platelet function.ResultsWe included 73 studies in the systematic review to assess CKD’s overall effect on platelet function in patients; 11 of them described CKD’s effect on ex vivo platelet aggregation and were included in the meta-analysis. Although findings on platelet abnormalities in CKD are inconsistent, bleeding time was mostly prolonged and platelet adhesion mainly reduced. Also, the meta-analysis revealed maximal platelet aggregation was significantly reduced in patients with CKD upon collagen stimulation. We also found that relatively few uremic toxins have been examined for direct effects on platelets ex vivo; ex vivo analyses had varying methods and results, revealing both platelet-stimulatory and inhibitory effects. However, eight of the 12 uremic toxins tested in animal models mostly induced prothrombotic effects.ConclusionsOverall, most studies report impaired function of platelets from patients with CKD. Still, a substantial number of studies find platelet function to be unchanged or even enhanced. Further investigation of platelet reactivity in CKD, especially during different CKD stages, is warranted.

Novel 12-LOX Inhibitor ML355 Attenuates Platelet Reactivity and Impairs Thrombus Growth, Stability and Vessel Occlusion In Vivo

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3442-3442 ◽  
Author(s):  
Reheman Adili ◽  
Theodore R Holman ◽  
Michael Holinstat
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Vessel Occlusion ◽  
Growth Stability

Abstract Background: Adequate platelet reactivity is required for platelet adhesion and aggregation at the site of vascular injury to maintain hemostasis. However, excessive platelet reactivity can also lead to the formation of occlusive thrombi, the predominate underlying cause of myocardial infarction and stroke. While current anti-platelet treatments limit platelet function, they often result in an increased risk of bleeding. 12-lipoxygenase (12-LOX), an oxygenase highly expressed in the platelet, has been demonstrated by our lab and others to regulate PAR4 and GPVI-mediated platelet reactivity suggesting a role of 12-LOX in regulation of vivo thrombosis. However, the ability to pharmacologically target 12-LOX in vivo has not been established to date. Aims: To determine how 12-LOX regulates thrombus formation in vivo and whether platelet 12-LOX is an effective target for anti-platelet therapeutics, wild-type (WT) or 12-LOX deficient (12-LOX-/-) mice were treated with or without the 12-LOX inhibitor, ML355, and were assessed for inhibitory effects on platelet activation in vitro, ex-vivo and in vivo. Methods: The effect of the novel 12-LOX inhibitor ML355 on human platelet function was assessed in vitro by platelet aggregometry, ex vivo by perfusion chamber. In vivo thrombus formation and vessel occlusion in small and large vessels were studied in 12-LOX-/-, WT mice and mice treated with ML355 using intravital microscopy using the FeCl3 injury models. Results: Using in vitro platelet aggregation assays, ML355 dose dependently inhibited thrombin, PAR1-AP, and PAR4-AP-induced aggregation in washed human platelets. Interestingly, the negative regulatory effects of ML355 inhibition of 12-LOX can be overcome by high concentration of thrombin. Additionally, ML355 was able to attenuate ADP-induced platelet aggregation both in platelet-rich-plasma and whole blood. In ex vivo flow chamber assays, platelet adhesion and thrombus formation on collagen-coated surfaces at high shear was attenuated in both mouse and human whole blood after incubation with ML355. Further, platelet aggregation and thrombus growth in 12-LOX-/- mice was impaired in FeCl3-induced mesenteric or carotid artery thrombosis models. Thrombi in 12-LOX-/- mice were unstable and frequently form emboli, which resulted in impaired vessel occlusion or reopening. Additionally, thrombus formation and vessel occlusion was impaired in ML355 treated WT mice. Conclusions: The highly selective 12-LOX inhibitor ML355 inhibits platelets aggregation induced by various platelet agonists and ML355 inhibition of platelet function is not agonist specific. Platelet function at high shear in ex vivo conditions in both mice and human was attenuated in the presence of ML355. Thrombus growth, stability, and vessel occlusion was impaired in mice deficient for 12-LOX. Finally, the highly selective 12-LOX inhibitor ML355 attenuates thrombus formation and prevents vessel occlusion in vivo. Our data strongly indicates 12- LOX is an important determinant of platelet reactivity and inhibition of platelet 12-LOX may represent a new target for anti-platelet therapeutics. Disclosures No relevant conflicts of interest to declare.

scholarly journals PLGA-PEG Nanoparticles Show Minimal Risks of Interference with Platelet Function of Human Platelet-Rich Plasma

2020 ◽  
Vol 21 (24) ◽  
pp. 9716
Author(s):  
Rana Bakhaidar ◽  
Sarah O’Neill ◽  
Zebunnissa Ramtoola
Keyword(s):  
Drug Delivery ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Platelet Activity ◽  
Blood Constituents ◽  
Activation Profile ◽  
The Impact

The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0–2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.

Effects of Ticlopidine of Platelet Function in Men with Stable Angina Pectoris

1985 ◽  
Vol 54 (04) ◽  
pp. 808-812 ◽  
Author(s):  
Ulf Berglund ◽  
Henning von Schenck ◽  
Lars Wallentin
Keyword(s):  
Platelet Aggregation ◽  
Angina Pectoris ◽  
Platelet Function ◽  
Plasma Levels ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Controlled Study ◽  
Double Blind ◽  
Platelet Factor

SummaryThe effects of ticlopidine (T) (500 mg daily) on platelet function were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. The in vitro platelet reactivity to aggregating agents, the platelet sensitivity to prostacyclin and the plasma levels of platelet specific proteins and fibrinogen were determined before and after 4 and 8 weeks of treatment. T exerted a potent inhibitory effect on ADP- and collagen-induced platelet aggregation. The effect of T was proportional to the pretreatment reactivity to ADP and collagen. The inhibitory effect of T on the epinephrine response was less pronounced. The plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen were not influenced by T. The platelet inhibition of prostacyclin was potentiated by T, and it was demonstrated that T and prostacyclin had synergistic inhibitory effects on platelet aggregation.

Assessment of Antithrombotic Properties of Sodium Ibuprofen

1982 ◽  
Vol 48 (01) ◽  
pp. 087-090 ◽  
Author(s):  
Carlos O Esquivel ◽  
David Bergqvist ◽  
Claes-Göran Björck ◽  
Stan N Carson ◽  
Bodil Nilsson
Keyword(s):  
Drug Administration ◽  
Platelet Function ◽  
Ex Vivo ◽  
Inhibitory Effect ◽  
Formation Time ◽  
Platelet Activity ◽  
Laser Injury ◽  
Sodium Ibuprofen ◽  
Plug Formation

SummaryThe effect of sodium ibuprofen on platelet activity in vivo and the lysability of ex vivo thrombi was investigated. The formation of a hemostatic platelet plug in the rabbit mesentery and platelet embolism as a response to a laser-induced injury in the ear chamber of rabbits were used as models for determining platelet activity. Ibuprofen at a dose of 25 mg/kg i.v. was found to increase the primary (PHT) and the total hemostatic plug formation time (THT). The same dose decreased the number of cumulative emboli over a 10 min period after a laser injury to arterioles. A dose of 10 mg/kg i.v. did not affect the formation of the hemostatic platelet plug. In dogs, doses of 10, 25 und 50 mg/kg did not enhance the release of 125I-FDP from the thrombi after incubation in plasmin, but the largest dose which is approximately five times the recommended dose in humans, did significantly decrease the thrombus weight 90 and 180 min after the drug administration. In conclusion, sodium ibuprofen was shown to have an inhibitory effect on platelet function in vivo and in large doses was also found to diminish the thrombus weight.

scholarly journals Clinical Anatomy of the Posterior Meniscofemoral Ligament of Wrisberg: An Original MRI Study, Meta-analysis, and Systematic Review

2021 ◽  
Vol 9 (2) ◽  
pp. 232596712097319
Author(s):  
Przemysław A. Pękala ◽  
Dominik P. Łazarz ◽  
Mateusz A. Rosa ◽  
Jakub R. Pękala ◽  
Adam Baginski ◽  
...  
Keyword(s):  
Systematic Review ◽  
Quality Assessment ◽  
Meta Analysis ◽  
Lateral Meniscus ◽  
Lower Limbs ◽  
Clinical Anatomy ◽  
Extensive Literature ◽  
Anatomic Structure ◽  
Meniscofemoral Ligament ◽  
The Mean

Background: The posterior meniscofemoral ligament (pMFL) of Wrisberg attaches to the posterior horn of the lateral meniscus and the lateral intercondylar aspect of the medial femoral condyle and passes posteriorly to the posterior cruciate ligament (PCL). The pMFL plays a role in recovery after PCL injuries and offers stability to the lateral meniscus, promoting normal knee function. Purpose/Hypothesis: The aim of the magnetic resonance imaging (MRI) arm of this study was to evaluate the prevalence of the pMFL in Polish patients. The purpose of the systematic review and meta-analysis was to evaluate the clinical relevance of the pMFL in knee surgery. It was hypothesized that extensive variability exists in reports on the prevalence, function, and clinical significance of the pMFL. Study Design: Cross-sectional study and systematic review; Level of evidence, 3. Methods: A retrospective MRI investigation was conducted on 100 randomly selected lower limbs of Polish patients (56 male, 44 female) performed in 2019 to determine the prevalence of the pMFL. Additionally, an extensive literature search of major online databases was performed to evaluate all reported data on the pMFL. Assessments of article eligibility and data extraction were completed independently by 2 reviewers, and all disagreements were resolved via a consensus. A quality assessment of the included articles was performed using the Anatomical Quality Assessment tool. Results: In the MRI arm of this study, the pMFL was observed in 73 of the 100 limbs. In the meta-analysis, 47 studies were included, totaling 4940 lower limbs. The pooled prevalence of the pMFL was found to be 70.4% (95% CI, 63.4%-76.9%); the mean length was 27.7 mm (95% CI, 24.8-30.5 mm) and the mean widths were 4.5, 6.1, and 4.1 mm for the meniscal and femoral attachments and midportion, respectively. The mean pMFL thickness was 2.3 mm (95% CI, 1.8-2.7 mm). Conclusion: Despite the variability in the literature, the pMFL was found to be a prevalent and large anatomic structure in the knee joint. The shared features of this ligament with the PCL necessitate the consideration of its value in planning and performing arthroscopic procedures of the knee.

Abstract 2214: The Aptamer ARC1779 Is A Potent And Specific Inhibitor Of von Willebrand Factor (vWF) Mediated Ex Vivo Platelet Function In ST-elevation (STEMI) and non-ST elevation (NSTEMI) Acute Myocardial Infarction (AMI)

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Bernd Jilma ◽  
Florian B Mayr ◽  
Alexander O Spiel ◽  
Patricia G Merlino ◽  
Harold N Marsh ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
Citrate Anticoagulation ◽  
St Elevation ◽  
A1 Domain ◽  
The Impact ◽  
Novel Therapeutic

Background: ARC1779 is an aptamer which blocks the A1 domain binding of the vWF A1 domain to platelet GPIb receptors that is now in development for the treatment of AMI. vWF is increased in the elderly and in the setting of AMI, as reflected in higher vWF levels in circulation and in increased shear-dependent platelet function as measured by the platelet function analyzer (PFA-100) and cone and plate analyzer (IMPACT). Conventional therapy of AMI partially reduces platelet activation and aggregation, but does not address excessive vWF activity or platelet adhesion. Methods: We studied the ex vivo dose response curves for ARC1779 on PFA-100 and IMPACT platelet function tests, agonist-induced platelet aggregation, and vWF activity (free A1 domain sites) of patients with AMI on standard treatment including aspirin and clopidogrel (n=40), young (n=20) and elderly controls (n=20). Results: ARC1779 fully blocked collagen ADP induced platelet plug formation as measured by PFA-100 with an IC100 of ~ 1–2 mcg/mL with citrate anticoagulation, and 3–5 mcg/mL with hirudin anticoagulation. ARC1779 fully blocked shear-dependent platelet adhesion measured by the IMPACT analyzer with an IC100 of ~ 1 mcg/mL with citrate anticoagulation. In contrast to GPIIb/IIIa antagonists, ARC1779 did not inhibit platelet aggregation by ADP, collagen or arachidonic acid at concentrations (10mcg/mL) that fully inhibited vWF dependent platelet function. ARC1779 fully blocked vWF activity ex vivo with an IC90 of ~ 1 mcg/mL in young controls and 6 – 8 mcg/mL in STEMI and NSTEMI patients. Conclusions: ARC1779 potently and specifically inhibits vWF activity and vWF dependent platelet function, even in the setting of AMI where vWF activity is increased. ARC1779 represents a novel therapeutic principle (vWF antagonism) and a novel therapeutic class (aptamers). Potent and specific inhibition of VWF makes ARC1779 a promising development candidate for patients with AMI. Results

scholarly journals ROLE OF NITRIC OXIDE (NO) IN CAPSAICIN MEDIATED ANTI-PLATELET ACTIVITY IN IN VITRO, IN VIVO, EX-VIVO MODEL OF PLATELET AGGREGATION ASSAY AND ARTERIAL THROMBOSIS IN RAT: POTENTIAL THERAPEUTIC TARGET?

2018 ◽  
Vol 10 (4) ◽  
pp. 44
Author(s):  
Mihir K Patel ◽  
Kiranj K. Chaudagar ◽  
Anita A. Mehta
Keyword(s):  
Platelet Aggregation ◽  
Arterial Thrombosis ◽  
Ex Vivo ◽  
Platelet Activity ◽  
Aggregation Assay ◽  
Thrombosis Model ◽  
Platelet Aggregation Assay

Objective: Although recent advances in the treatment of congestive heart disease, mortality among patients’ remains a questionable remark. Therefore, we evaluated the role of capsaicin on in vitro and ex vivo platelet aggregation induced by Adenosine Di-Phosphate (ADP) as well as in in vivo thrombosis models and role of NO, KATP was also identified in the capsaicin-induced anti-platelet animal model as well as in vivo model of arterial thrombosis.Methods: According to body weight wistar rats were divided into five groups. Group I and Group II was treated with saline and capsaicin (3 mg/kg, i. v), while animals from Group III were treated with N(ω)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg, i. v) 30 min before administration of capsaicin (3 mg/kg, i. v). Group IV animals were treated with glibenclamide (10 mg/kg,i. v) 30 min before administration of capsaicin (3 mg/kg, i. v). Group V was considered as a positive control and administered clopidogrel (30 mg/kg, p. o). Animals were subjected for in vitro, ex-vivo platelet aggregation assay. ADP (30µM) was utilized as an aggregating agent in these experiments. After these assays; animals of each group were subjected for subaqueous tail bleeding time in a rat model and FeCl3-induced arterial thrombosis model in rats.Results: In ADP-induced in vitro platelet aggregation, a significant reduction in % platelet aggregation was observed at 50µM (64.35±4.641) and 100µM (52.72±4.192) concentration of capsaicin as compared to vehicle control (85.82±3.716). Capsaicin (3 mg/kg, i. v) also showed a significant reduction (49.53±4.075) in ex-vivo ADP-induced platelet aggregation as compared to vehicle control (89.38±2.057). In FeCl3 induced arterial thrombosis model, Capsaicin (3 mg/kg, i. v) exhibited an increase in time to occlusion in this rodent model and presence of the L-NAME and glibenclamide had inhibited the activity of capsaicin.Conclusion: In our study, capsaicin (50 µM, 100µM) exhibited potent anti-platelet activity in ADP-induced platelet aggregation, similarly capsaicin exhibited significant anti-platelet action in the ex-vivo study. Moreover, the presence of L-NAME and glibenclamide inhibited the anti-thrombotic and anti-platelet action of capsaicin. Therefore, it was concluded that NO and KATP may be involved in the anti-thrombotic action of capsaicin.

Comparison of the effect of coagulation and platelet function impairments on various mouse bleeding models

2014 ◽  
Vol 112 (08) ◽  
pp. 412-418 ◽  
Author(s):  
Nima Vaezzadeh ◽  
Ran Ni ◽  
Paul Y. Kim ◽  
Jeffrey I. Weitz ◽  
Peter L. Gross
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Saphenous Vein ◽  
Ex Vivo ◽  
Arterial Injury ◽  
Inhibitory Antibody ◽  
Study Objective ◽  
Tail Tip

SummaryHaemostatic impairments are studied in vivo using one of several murine bleeding models. However it is not known whether these models are equally appropriate for assessing coagulation or platelet function defects. It was our study objective to assess the performance of arterial, venous and combined arterial and venous murine bleeding models towards impaired coagulation or platelet function. Unfractionated heparin (UFH) or αIIbβ3 inhibitory antibody (Leo.H4) were administered to mice, and their effects on bleeding in saphenous vein, artery, and tail tip transection models were quantified and correlated with their effects on plasma clotting and ADP-induced platelet aggregation, respectively. All models exhibited similar sensitivity with UFH (EC50 dose = 0.19, 0.13 and 0.07 U/g, respectively) (95% CI = 0.14 – 0.27, 0.08 – 0.20, and 0.03 – 0.16 U/g, respectively). Maximal inhibition of ex vivo plasma clotting could be achieved with UFH doses as low as 0.03 U/g. In contrast, the saphenous vein bleeding model was less sensitive to αIIbβ3 inhibition (EC50 = 6.9 µg/ml) than tail transection or saphenous artery bleeding models (EC50 = 0.12 and 0.37 µg/ml, respectively) (95% CI = 2.4 – 20, 0.05 – 0.33, and 0.06 – 2.2 µg/ml, respectively). The EC50 of Leo.H4 for ADP-induced platelet aggregation in vitro (8.0 µg/ml) was at least 20-fold higher than that of the tail and arterial, but not the venous bleeding model. In conclusion, venous, arterial and tail bleeding models are similarly affected by impaired coagulation, while platelet function defects have a greater influence in models incorporating arterial injury.

scholarly journals COVID-19 induces a hyperactive phenotype in circulating platelets

2020 ◽  
Author(s):  
Shane P Comer ◽  
Sarah Cullivan ◽  
Paulina B Szklanna ◽  
Luisa Weiss ◽  
Steven Cullen ◽  
...  
Keyword(s):  
Intensive Care ◽  
Platelet Function ◽  
Clinical Laboratory ◽  
Platelet Reactivity ◽  
Severe Disease ◽  
Blood Parameters ◽  
Full Blood Count ◽  
Specific Marker ◽  
Platelet Activity ◽  
Thrombotic Risk

Background Coronavirus disease 2019 (COVID-19), caused by novel coronavirus SARS-CoV-2, has to date affected over 13.3 million globally. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Objectives Here, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and non-severe COVID-19. Methods An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with non-severe disease (not requiring intensive care), general medical in-patients without COVID-19 and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. Results We show that routine clinical blood parameters including increased MPV and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit admission. Strikingly, agonist-induced ADP release was dramatically higher in COVID-19 patients compared with non-COVID-19 hospitalized patients and circulating levels of PF4, sP-selectin and TPO were also significantly elevated in COVID-19. Conclusion Distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and non-severe COVID-19. Moreover, we have determined that COVID-19 patients possess hyperactive circulating platelets. These data suggest that abnormal platelet reactivity may contribute to hypercoagulability in COVID-19. Further investigation of platelet function in COVID-19 may provide additional insights into the aetiology of thrombotic risk in this disease and may contribute to the optimisation of thrombosis prevention and treatment strategies.

scholarly journals Clopidogrel Resistance: Current Issues

2016 ◽  
Vol 6 (1) ◽  
pp. 38-46
Author(s):  
NS Neki
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Clinical Problem ◽  
Coronary Intervention ◽  
Platelet Activity ◽  
Clopidogrel Resistance ◽  
Underlying Mechanisms

Antiplatelet agents are mainly used in the prevention and management of atherothrombotic complications. Dual antiplatelet therapy, combining aspirin and clopidogrel, is the standard care for patients having acute coronary syndromes or undergoing percutaneous coronary intervention according to the current ACC/AHA and ESC guidelines. But in spite of administration of dual antiplatelet therapy, some patients develop recurrent cardiovascular ischemic events especially stent thrombosis which is a serious clinical problem. Antiplatelet response to clopidogrel varies widely among patients based on ex vivo platelet function measurements. Clopidogrel is an effective inhibitor of platelet activation and aggregation due to its selective and irreversible blockade of the P2Y12 receptor. Patients who display little attenuation of platelet reactivity with clopidogrel therapy are labeled as low or nonresponders or clopidogrel resistant. The mechanism of clopidogrel resistance remains incompletely defined but there are certain clinical, cellular and genetic factors including polymorphisms responsible for therapeutic failure. Currently there is no standardized or widely accepted definition of clopidogrel resistance. The future may soon be realised in the routine measurement of platelet activity in the same way that blood pressure, cholesterol and blood sugar are followed to help guide the therapy, thus improving the care for millions of people. This review focuses on the methods used to identify patients with clopidogrel resistance, the underlying mechanisms, metabolism, clinical significance and current therapeutic strategies to overcome clopidogrel resistance.J Enam Med Col 2016; 6(1): 38-46

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