Armen Yuri Gasparyan

Mean platelet volume: A link between thrombosis and inflammation?

Platelet activation is a link in the pathophysiology of diseases prone to thrombosis and inflammation. Numerous platelet markers, including mean platelet volume (MPV), have been investigated in connection with both thrombosis and inflammation. This review considers MPV as a prognostic and therapeutic marker as well as the factors influencing its measurement. Established cardiovascular risk factors, such as smoking, hypertension, dyslipidemia, and diabetes, can influence MPV, depending on confounding factors. Low-grade inflammation is one such factor. Evidence, particularly derived from prospective studies and a meta-analysis, suggest a correlation between an increase in MPV and the risk of thrombosis. High MPV associates with a variety of established risk factors, cardio- and cerebrovascular disorders, and low-grade inflammatory conditions prone to arterial and venous thromboses. High-grade inflammatory diseases, such as active rheumatoid arthritis or attacks of familial Mediterranean fever, present with low levels of MPV, which reverse in the course of anti-inflammatory therapy. Lifestyle modification, antihypertensive, lipid lowering and diet therapies can also affect MPV values, but these effects need to be investigated in large prospective studies with thrombotic endpoints.

Writing a narrative biomedical review: Considerations for authors, peer reviewers, and editors

Review articles comprehensively covering a specific topic are crucial for successful research and academic projects. Most editors consider review articles for special and regular issues of journals. Writing a review requires deep knowledge and understanding of a field. The aim of this review is to analyze the main steps in writing a narrative biomedical review and to consider points that may increase the chances of success. We performed a comprehensive search through MEDLINE, EMBASE, Scopus, and Web of Science using the following keywords: review of the literature, narrative review, title, abstract, authorship, ethics, peer review, research methods, medical writing, scientific writing, and writing standards. Opinions expressed in the review are also based on personal experience as authors, peer reviewers, and editors.

Platelet function in rheumatoid arthritis: arthritic and cardiovascular implications

Patients with rheumatoid arthritis (RA) are at high risk of cardiovascular events. Platelet biomarkers are involved in inflammation, atherosclerosis and thrombosis. Cardiovascular and RA-associated factors can alter the structure and function of platelets, starting from megakaryocytopoiesis. Reactive megakaryocytopoiesis increases circulating platelets count and triggers hyperactivity. Hyperactive platelets target synovial membranes with subsequent local rheumatoid inflammation. Hyperactive platelets interact with other cells, and target the vascular wall. Accumulating evidence suggests that disease modifying anti-rheumatic drugs (DMARD) decrease platelet activity.

Association of mean platelet volume with hypertension in rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory disorders associated with enhanced cardiovascular morbidity and mortality. Established high prevalence of classical cardiovascular risk factors may only partly explain cardiovascular phenomenon in this disease. Emerging risk factors, markers of inflammation and prothrombotic state such as platelet size are believed to reflect activity of RA. We aimed to study mean platelet volume (MPV) in a cohort of patients with RA and to clarify possible effects of classical cardiovascular and RA-associated risk factors on MPV. Demographic, clinical and a wide range of laboratory parameters, including MPV and platelet count, were obtained for 400 RA patients. Platelet size and count were also assessed in 360 non-RA controls from the local population. We found significantly increased MPV in RA patients compared with controls (P=0.001). The difference retained significant after adjustment for age and sex. High values of MPV (>or=10.7 femtoliter [fL]) were more frequent in RA patients than in controls (21% vs. 9.2%; P<0.0001). In RA patients, blood pressure greater than 140/90 mmHg was associated with high levels of MPV (Odds Ratio [OR] 2.2, 95% Confidence Interval [CI] 1.3-3.7; P=0.003). It is possible that MPV as a surrogate marker of platelet function reflects enhanced vascular risk. To further explore the role of MPV as a marker for cardiovascular risk in RA, prospective studies are warranted.

Behçet’s Disease as a Model of Venous Thrombosis

Behcet’s disease (BD) is a chronic inflammatory disease of unknown aetiology characterized by recurrent oral, genital aphthous ulcerations, uveitis, skin lesions and other multisystem affections associated with vasculitis. Different types of vessels, predominantly veins, can be affected in BD. The frequency of vascular lesions in BD, such as superficial and deep venous thromboses, arterial aneurysms and occlusions, ranges between 7-29%. In this review, various factors of thrombogenesis in BD, particularly pro- and antithrombotic endothelial and non-endothelial factors, factors of coagulation, platelet activation and rheological changes are presented and discussed from positions of Virchow’s triad of venous thrombosis. Despite advances in understanding of thrombogenesis in BD, still many issues of diagnosis and targeted preventive and therapeutic measures remain unresolved. Further studies are needed to clarify the pathobiology of BD-related thrombosis and to provide the clinicians with recommendations over the utility, safety and effectiveness of the antithrombotic therapy in BD.

Familial Mediterranean Fever as an Emerging Clinical Model of Atherogenesis Associated with Low-Grade Inflammation

Numerous inflammatory and innate immune pathways are involved in atherogenesis. Elaboration of clinical models of inflammation-induced atherogenesis may further advance our knowledge of multiple inflammatory pathways implicated in atherogenesis and provide a useful tool for cardiovascular prevention. Familial Mediterranean fever (FMF) is a chronic inflammatory disorder with profiles of inflammatory markers close to that seen in the general population. In a few recent studies, it has been shown that endothelial dysfunction, increased atherosclerotic burden and activation of platelets accompany attack-free periods of FMF. Colchicine is proved to be useful in suppression of inflammation in FMF. Preliminary basic and clinical studies suggest that this relatively safe drug may be useful for cardiovascular protection in patients with FMF and in the general population. Multinational prospective studies are warranted to further elaborate clinical model of inflammation-induced atherosclerosis associated with FMF.

Biomedical journal editing: elements of success

The current pace of developments in virtually every aspect of our life and scientific innovations pose ever increasing challenges in ensuring the highest possible quality of publications, satisfying the needs of both publishers and readers. Scholarly journals are essential tools for communication between experts and for advancement of research and practice in various fields of science (1). By communicating original research data, comprehensively covering emerging scientific concepts and directions and analyzing news reports, journals are being increasingly recognized as educational tools. Relevant examples are top general medical journals, such as The Lancet, The New England Journal of Medicine, and The British Medical Journal, reflecting developments in science and educating physicians and eventually changing clinical practice worldwide. Multiple functions assigned to scholarly journals raise the issues of trustworthiness and quality of the publications. The latter is of particular importance in view of recent trends in information flow, digitalization, and acceleration of the publishing process, which may increase the rate of errors and mistakes.

Aspirin and clopidogrel resistance: methodological challenges and opportunities.

Antiplatelet drug resistance is one of the urgent issues in current cardiovascular medicine. Many platelet function tests have been used to define responsiveness of patients with cardiovascular disease to aspirin and clopidogrel. In most studies, cut-off values of platelet function tests for defining responsiveness to antiplatelets were chosen arbitrarily. Different tests provided wide-ranging figures of the prevalence of aspirin and clopidogrel resistance, suggesting poor correlation between currently available platelet function tests. Measurement of platelet size seems to be a promising approach for monitoring antiplatelet drug therapy. This commentary highlights some limitations of studies on aspirin and clopidogrel resistance in patients undergoing coronary interventions.

Behçet’s Disease: an Insight from a Cardiologist’s Point of View

Behcets disease (BD) is an enigmatic inflammatory disorder, with vasculitis (perivasculitis) underlying pathophysiology of its multisystemic affections. Venous pathology and thrombotic complications are hallmarks of BD. However, it has been increasingly recognized that cardiac involvement and arterial complications (aneurysms, pseudoaneurysms, rupture and thrombosis) are important part of the course of BD. Pericarditis, myocardial (diastolic and/or systolic dysfunction), valvular and coronary (thrombosis, aneurysms, rupture) involvement, intracardiac thrombi (predominantly right-sided) are, probably, the most frequent cardiac manifestations. Treatment of cardiovascular involvement in BD is largely empirical and aimed at suppression of vasculitis. The most challenging seems to be the treatment of arterial aneurysms and thromboses due to the associated risk of bleedings. Cardiologists should always bear in mind potential threats of (a)symptomatic cardiovascular involvement in BD.

Platelets in rheumatic diseases: friend or foe?

Platelets are intimately involved in hemostasis, inflammation, innate and adaptive immunity, tissue regeneration and other physiological and pathological processes. Their granular structure is programmed to release a wide range of bioactive substances in response to agonists. Upon activation, platelet membranes display thrombotic and inflammatory agents, which may take an active part in the pathophysiology of autoimmune and autoinflammatory disorders. The aim of this review is to analyze current evidence of platelet (dys)function in inflammatory rheumatic diseases and overview platelettargeting mechanisms of antirheumatic drug therapies. A comprehensive search through Medline/PubMed, SciVerse/Scopus and Web of Science was performed for English-language original research papers, using the keywords related to platelets in autoimmune and autoinflammatory rheumatic disorders. Additionally, the Cochrane Collaboration database was searched for the literature on the effects of antirheumatic drugs on platelet function. A variety of platelet markers have been tested in systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, spondyloarthropathies, vasculitides, and some autoinflammatory disorders. It has been shown that platelets circulate in an activated state in most of these disorders and tend to form complexes with other inflammatory and immune cells. Thrombotic and inflammatory agents, released from platelets, may trigger disease-specific complications (e.g., extraarticular features, fibrosis in systemic sclerosis) and propagate endothelial dysfunction. Whether platelet activation is a primary or secondary feature in rheumatic disorders remains to be elucidated. Some widely used antirheumatic drugs may suppress thrombopoiesis and platelet activity, however the clinical implications of this effect have yet to be examined in specifically designed prospective studies. Large retrospective cohort studies supported the use of low-dose aspirin for suppressing platelet function and preventing cerebrovascular events in giant-cell arteritis. However, emerging data suggest that the release rate of activated platelets applied topically to the inflamed cartilage in arthritis or skin ulcers in scleroderma may suppress the inflammation and facilitate tissue repair. Taken together, current evidence necessitates a balanced approach to platelet-activating and suppressing drug therapies in inflammatory rheumatic diseases.