Platelet Polymorphisms

Afshar-Kharghan, Vahid; Vijayan, K. Vinod; Bray, Paul F.

doi:10.1016/b978-012369367-9/50776-x

Cited by 10 publications

(18 citation statements)

References 324 publications

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“…Polymorphisms in platelet surface glycoproteins that have received particular attention include the Pl A1/A2 polymorphism, resulting in conformational change at the amino terminus of the β 3 chain of the platelet fibrinogen receptor glycoprotein complex IIb/IIIa, the polymorphisms in platelet collagen receptors (GPIa-IIa and GPVI) and GPIbα ('Variable Number of Tandem Repeats' polymorphism, VNTR, and Kozak polymorphism, located in a non-coding GPIb gene region), as well as the polymorphisms of platelet purinoreceptor P2Y 12 [13,14,[88][89][90]. Of these the Pl A1/A2 polymorphism and GPIa SNPs have been most profoundly studied as the potential candidates offering a plausible explanation for the increased risk of thrombotic events.…”

Section: Glycoprotein Polymorphismsmentioning

confidence: 99%

“…The subunit β 3 (GPIIIa) of this platelet membrane integrin appears to be dimorphic at the position of Leu 33 →Pro, which results from a single nucleotide 1565 C→T substitution in the GPIIIa gene and is commonly known as platelet-specific antigen (Pl A1/A2 ) polymorphism [88,89,92].…”

Section: Glycoprotein Complex Iib-iiiamentioning

confidence: 99%

“…It is more even so since the influence of genetic make-up of natural platelet reactivity seems essential also in the context of effective antiplatelet therapy. Once established as a risk factor, a genetic polymorphism of platelet receptor glycoprotein has the potential to aid selective prophylaxis and therapy of disease [13,85,86,88,89].…”

Section: Glycoprotein Polymorphismsmentioning

confidence: 99%

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Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus

Watała

2005

CPD

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Blood platelets play a crucial role in physiological haemostasis and in pathology of prothrombotic states, including atherosclerosis. In this paper, we review major factors underlying altered platelet reactivity, with special attention paid to abnormalities in platelet function in people with diabetes mellitus (DM). The overall picture of platelet abnormalities in DM, including altered adhesion and aggregation, is hypersensitivity of diabetic platelets to agonists. "Primed" diabetic platelets respond more frequently even to subthreshold stimuli, sooner become exhausted, consumed and finally hyposensitive, thus contributing to accelerated thrombopoiesis and release of 'fresh' hyperreactive platelets. In diabetes disturbed carbohydrate and lipid metabolism may lead to physicochemical changes in cell membrane dynamics, and consequently result in altered exposure of surface membrane receptors. These phenomena, together with increased fibrinogen binding, prostanoid metabolism, phosphoinositide turnover and calcium mobilisation often present in diabetic patients, contribute to enhanced risk of small vessel occlusions and accelerated development of atherothrombotic disease of coronary, cerebral and other vessels in diabetes. As platelet hypersensitivity in DM makes a major contribution to enhanced risk of thromboembolic macroangiopathy, and consequently enhanced morbidity and mortality, it validates use of antiplatelet agents in diabetic individuals. Platelet hyperreactivity may be cured with various antiplatelet drugs to a considerably large extent notwithstanding, evidence gathered from clinical and experimental surveys shows that this approach may not always be equally efficient in people with diabetes. Observations from clinical studies rather support the use of multifactorial strategy under such circumstances, like a combined therapy of aspirin plus either purinoreceptor blocker or GPIIb-IIIa antagonist.

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Section: Glycoprotein Polymorphismsmentioning

confidence: 99%

Section: Glycoprotein Complex Iib-iiiamentioning

confidence: 99%

Section: Glycoprotein Polymorphismsmentioning

confidence: 99%

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Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus

Watała

2005

CPD

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“…51 The Pl A2 polymorphism of GPIIIa has been reported to be associated with ischemic coronary syndromes. 52 Flow cytometry has been used to demonstrate that a) Pl A2 -positive platelets display a lower threshold for activation, and b) platelets heterozygous for Pl A alleles show increased sensitivity to antiplatelet drugs. 53 Circulating leukocyte-platelet aggregates are increased in stable coronary artery disease, 27,53 unstable angina, 38 acute myocardial infarction, 26,[54][55][56] and cardiopulmonary bypass.…”

Section: Acute Coronary Syndromesmentioning

confidence: 99%

Evaluation Of Platelet Function By Flow Cytometry

Michelson¹

2006

Pathophysiol Haemos Thromb

142

120

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“…Family studies have shown that there is a genetic component to coronary disease risk, and estimates of the effects of inheritance on myocardial infarction (MI) have ranged from 20 to 80% [1]. However, attempts to identify polymorphisms that influence coronary disease risk have yielded only weak associations thus far.…”

Section: Genetics and Cardiovascular Diseasementioning

confidence: 99%

Platelet Transcriptome and Cardiovascular Disease

2007

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Platelet hyper-reactivity is likely to play a role in cardiovascular disease, but there are no standardized tests to evaluate platelet responsiveness. A 'platelet chip' (a synthetic oligonucleotide microarray representing all platelet-restricted genes) is under development as a tool for high-throughput characterization of platelet-based bleeding and clotting disorders. In future, platelet gene profiling may be used to improve thrombohemorrhagic risk assessment and to guide antiplatelet therapy for patients at risk of cardiovascular disease.

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Platelet Polymorphisms

Cited by 10 publications

References 324 publications

Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus

Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus

Evaluation Of Platelet Function By Flow Cytometry

Platelet Transcriptome and Cardiovascular Disease

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