Aspirin resistance and diabetes mellitus

Ajjan, Ramzi; Storey, Robert F.; Grant, Peter J.

doi:10.1007/s00125-007-0898-3

Cited by 69 publications

(53 citation statements)

References 44 publications

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“…The other reason of reduced efficiency in aspirin treatment was reported in the patients with diabetes mellitus [29]. High blood glucose causes in glycation of platelet proteins, resulting them less accessible to acetylation, potentially predisposing to treatment failure [30]. But in the present study, no differences were existed in HbA1c % levels and the history of diabetes between two groups.…”

Section: Discussioncontrasting

confidence: 53%

Assessment of platelet aspirin responsiveness in Turkish Population with PFA-100, serum thromboxane B2, soluble CD40 ligand and soluble P-Selectin

Saka¹,

Genç²,

Eroğlu³

et al. 2013

Turk J Bioch

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Section: Discussioncontrasting

confidence: 53%

Assessment of platelet aspirin responsiveness in Turkish Population with PFA-100, serum thromboxane B2, soluble CD40 ligand and soluble P-Selectin

Saka¹,

Genç²,

Eroğlu³

et al. 2013

Turk J Bioch

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“…104 One possible mechanism is related to an interaction between glycation and acetylation. 105 We have shown in 18 T1DM subjects that addition of aspirin to plasma samples ex vivo resulted in either no effect or a paradoxical increase in clot lysis time in the presence of poor glycaemic control, and this was reversed once glycaemic control improved. 106 Further clinical studies are needed to clarify this potential interaction, which will have important clinical implications.…”

Section: Anti-platelet Agentsmentioning

confidence: 94%

Review article: Coagulation and fibrinolysis in diabetes

Alzahrani

Ajjan

2010

Diabetes and Vascular Disease Research

209

188

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Atherothrombotic complications are the main cause of mortality in subjects with diabetes. Premature atherosclerosis, increased platelet reactivity and activation of coagulation factors with associated hypofibrinolysis all contribute to increased cardiovascular risk in this population. Blood clot formation represents the last step in the atherothrombotic process, and the structure of the fibrin network has a role in determining predisposition to cardiovascular disease. In this review, we discuss alterations in coagulation factor plasma levels and/or activity in diabetes and clarify their role in predisposition to cardiovascular events. The effect of diabetes on fibrin network structure/fibrinolysis is reviewed and potential mechanisms that modify clot properties are discussed. Finally, modulation of clotting potential by the various therapeutic agents used in diabetes is examined. Understanding the mechanisms by which diabetes influences the coagulation pathway will help to develop more effective treatment strategies to reduce thrombotic events in subjects with this condition. KeywordsAtherothrombosis, clot structure, coagulation factors, coronary artery disease, diabetes, fibrinogen Clot formation and lysisFibrin clot formation, leading to vessel occlusion, represents the final step in the atherothrombotic process and involves multiple interactions between coagulation factors and platelets.6 Rupture or fissuring in atherosclerotic plaques exposes a prothrombotic core that comes into contact with platelets and coagulation factors. Initially, platelets adhere to the site of the break and become partially activated. Factor VII (FVII) binds to exposed tissue factor (TF) and forms a complex, which subsequently activates FIX and FX, resulting in FV activation. Activated FX and FV cleave prothrombin to generate limited amounts of thrombin, enough to maintain platelet activation but insufficient to sustain thrombus formation. Platelet stimulation by thrombin and exposed collagen results in full activation and degranulation, followed by FV release and activation by both FXa and thrombin. Thrombin also activates FVIII and this can form an active complex with FIXa, further enhancing the coagulation process. Subsequently, enough Diabetes and thrombosis riskCardiovascular disease (CVD) remains the main cause of morbidity and mortality in individuals with diabetes. Up to 80% of diabetes subjects die as a result of cardiovascular complications, and the risk of atherothrombotic events in this population is similar to non-diabetic individuals with a history of ischaemic heart disease (IHD).1 Moreover, the prognosis in these individuals following an event remains poor, despite major advances in treatment.2 Increased atherothrombosis risk is even evident in the pre-diabetes stage, as subjects with insulin resistance and normoglycaemia are at risk of cardiovascular events secondary to clustering of risk factors. 3The underlying mechanisms for increased thrombosis risk in diabetes are complex and involve multiple pathways. S...

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“…The present study also found that fasting serum glucose level was a risk factor for aspirin resistance. Hyperglycemia may interfere with the acetylation process of platelets by aspirin, which may contribute to aspirin resistance in the presence of diabetes [13]. These studies suggest that glycemic control in CVD patients complicated by diabetes may improve the antithrombotic effects of aspirin.…”

Section: Discussionmentioning

confidence: 99%

“…Possible mechanisms of aspirin resistance include poor compliance or an inadequate dose, increased platelet activity, upregulation of a nonplatelet source of thromboxane production, decreased bioavailability, drug interactions, smoking, hyperlipidemia, hyperglycemia, and genetic variability [11,12,13,14,15]. Despite ongoing research, there is currently no clear consensus on the definition and treatment of aspirin resistance.…”

Section: Introductionmentioning

confidence: 99%

Frequency, Risk Factors, Prognosis, and Genetic Polymorphism of the Cyclooxygenase-1 Gene for Aspirin Resistance in Elderly Chinese Patients with Cardiovascular Disease

Fan¹,

Cao

Li³

et al. 2012

Gerontology

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Background: Cardiovascular disease (CVD) is an important cause of mortality in elderly patients worldwide. Aspirin resistance has been well reported in CVD. Objective: The frequency, risk factors, prognosis, and genetic polymorphism of the cyclooxygenase-1 (COX-1) gene for aspirin resistance have not been reported in elderly patients with CVD. We therefore undertook this study to evaluate these associations among elderly Chinese patients with CVD. Methods: Four hundred thirty-one elderly Chinese patients with CVD receiving daily aspirin therapy (≥75 mg) over 1 month were enrolled. Platelet aggregation was measured by light transmission aggregometry (LTA) and thromboelastography platelet mapping assay (TEG) using arachidonic acid (AA) as a stimulus. The median follow-up was 1.8 years. Results: After the median follow-up, aspirin-resistant patients were at an increased risk of the composite endpoint compared to nonresistant patients by LTA_AA + TEG_AA (23.7 vs. 9.2%, p = 0.025). Additionally, Cox proportional hazards regression modeling demonstrated that aspirin resistance and cerebrovascular disease were associated with major adverse long-term outcomes (HR for aspirin resistance = 2.31, 95% CI 1.11-4.81, p = 0.026). The variant G-allele of COX-1 rs1330344 (-1676 A/G) significantly increased the risk of aspirin resistance defined by LTA_AA + TEG_AA (OR = 1.82, 95% CI 1.13- 2.92, p = 0.01). Conclusions: Aspirin resistance, evaluated by LTA_AA + TEG_AA, is associated with an increased risk of adverse clinical events in elderly Chinese patients with CVD. The variant G-allele of COX-1 rs1330344 is significantly associated with aspirin resistance defined by LTA_AA + TEG_AA.

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Aspirin resistance and diabetes mellitus

Cited by 69 publications

References 44 publications

Assessment of platelet aspirin responsiveness in Turkish Population with PFA-100, serum thromboxane B2, soluble CD40 ligand and soluble P-Selectin

Assessment of platelet aspirin responsiveness in Turkish Population with PFA-100, serum thromboxane B2, soluble CD40 ligand and soluble P-Selectin

Review article: Coagulation and fibrinolysis in diabetes

Frequency, Risk Factors, Prognosis, and Genetic Polymorphism of the Cyclooxygenase-1 Gene for Aspirin Resistance in Elderly Chinese Patients with Cardiovascular Disease

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