Thrombocytopenia and coagulation disorders due to COVID 19 infection with concomitant cardiovascular diseases requiring anti-platelet and anticoagulant therapy, which strategy?

Coagulation disorders of the intrinsic and extrinsic pathways are monitored by measuring such clotting times as partial thromboplastin time (PTT), prothrombin time (PT), and thrombin time (TT). These laboratory tests reflect the congenital and acquired deficiencies of clotting factors and are used for controlling anticoagulant therapy. We have previously reported that meglumine (cation) in radiologic contrast media (CM) inhibits factor VIII, IX, and thrombin (Fed. Proc. 36 (3), 317, 1977) and consequently prolonges clotting times. The effects of ionic and nonionic CM on pathological plasma were investigated by employing routine clotting assays. Patient plasmas showing PT values >15 secs., were mixed with Renografin-60 (Squibb and Sons, Princeton, New Jersey), P-297, iothalamic acid, and ioxigalic acid (Laboratoire Guerbet, Paris, France) and PTs were then determined. Renografin-60 (30 mg/ml), iothalamic acid (10 mg/ml) and ioxigalic acid (10 mg/ml) produced an increase in the PT values by 60-80% base levels, whereas no such effect was seen with P-297. In normal plasma (NHP), the PT values were elevated only by 5-10%. In another study, patient plasmas showing PTT > 40 secs., were supplemented with CM and the mixtures were assayed for PTT. Except with P-297 there was a 50-60% increase in PTT due to the interactions of ionic CM. Our studies show that during anticoagulant therapy, if clotting assays are performed immediately after radiologic diagnostic procedures, utilizing intravascular contrast agents, erroneous conclusions can be drawn. Our studies have also shown that certain ionic CM can produce transient effects on coagulation parameters and therefore, due consideration be given to the presence of these agents in patients suffering from platelet function defects and other coagulation disorders.

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LONG TERM ANTICOAGULANT THERAPY FOR CARDIOVASCULAR DISEASES

The American Journal of the Medical Sciences ◽

10.1097/00000441-194902000-00003 ◽

1949 ◽

Vol 217 (2) ◽

pp. 136-142 ◽

Cited By ~ 31

Author(s):

William T. Foley ◽

Irving S. Wright

Keyword(s):

Cardiovascular Diseases ◽

Anticoagulant Therapy

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Therapeutic Enzymes Used for the Treatment of Cardiovascular Diseases and Coagulation Disorders

Research Advancements in Pharmaceutical, Nutritional, and Industrial Enzymology - Advances in Medical Technologies and Clinical Practice ◽

10.4018/978-1-5225-5237-6.ch002 ◽

2018 ◽

pp. 23-45

Author(s):

Abderrezak Khelfi

Keyword(s):

Cardiovascular Diseases ◽

Blood Clot ◽

Hereditary Diseases ◽

Coagulation Disorders ◽

Recombinant Enzymes ◽

Enzyme Preparations ◽

Enzyme Replacement ◽

Key Factor ◽

Foreign Proteins ◽

Therapeutic Enzymes

The successful introduction of enzyme replacement therapy opened the way for the use of enzymes, first as crude preparations and later as highly purified enzymes for use in cardiovascular diseases, clotting disorders, etc. Elimination of blood clot is the key factor in thrombolytic therapy and fibrinolytic enzyme therapy can be practiced to remove the clot. Based on the mechanism of action, they are of two types of enzymes: plasminogen activators and plasmin-like enzymes. Plasma products are usually employed as a source of several enzymes used for the treatment of coagulation disorders. While these products have traditionally been purified from blood donations and obtained as foreign proteins obtained from heterogeneous sources, most are now produced by biotechnology. The therapeutic enzymes reviewed in this chapter are used for the treatment of cardiovascular diseases and hereditary diseases leading to coagulation disorders. Enzyme preparations obtained by direct fractionation from a naturally producing source and recombinant enzymes are considered in this chapter.

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The current profile of the patient with atrial fibrillation

International Archives of Medicine ◽

10.3823/2572 ◽

2018 ◽

Vol 11 ◽

Author(s):

Iuliana Ardeleanu ◽

Liviu Macovei ◽

Larisa Anghel ◽

Ana Tanasa ◽

Mircea Balasanian ◽

...

Keyword(s):

Atrial Fibrillation ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Diseases ◽

Sinus Rhythm ◽

Anticoagulant Therapy ◽

Current Profile ◽

Cardiovascular Pathology ◽

Ischemic Coronary Artery Disease ◽

Artery Disease

Abstract: Atrial fibrillation (AF) is the most common supraventricular arrhythmia, characterized by an irregular and extremely rapid atrial electrical activation that causes loss of atrial mechanical function and important hemodynamic consequences. AF classification is important in both the therapeutic approach and the prognosis. Several classifications based on the ECG patch, epicardial or endocavitary records have been performed over time, but no classification can take into account all the characteristics of AF and especially associated diseases, which may be both the cause and consequence of arrhythmia. Aim: The aim of the study is to establish the current profile of the patient with atrial fibrillation in the new era of oral anticoagulant therapy and sinus rhythm restoration. Material and methods: The trial was conducted on patients with atrial fibrillation hospitalized between 01.10.2014-31.03.2015 at Institute of Cardiovascular Diseases ”Prof. Dr. G. Georgescu”, Iasi. Patients included in the study were analyzed according to age and sex, criteria for the clinical and paraclinic definition for atrial fibrillation. Results: Atrial fibrillation is an extremely common cardiovascular pathology and is present in about one-third of patients admitted to our clinic. Cardiovascular diseases such as hypertension, ischemic coronary artery disease, and valvulopathy are common in patients with AF. Patients with AF are usually elderly patients with many associated diseases in whom sinus rhythm restoration treatment and anticoagulant therapy are difficult to establish. AF is one of the most common arrhythmias that complicates the evolution of acute myocardial infarction, association between dual antiplatelet therapy and anticoagulation treatment, increasing the risk of bleeding complications. Conclusions: Atrial fibrillation is an extremely common cardiovascular pathology and is present in about one-third of patients admitted to our hospital. The data obtained revealed that this arrhythmia occurs in a small number of cases as the only pathology of the patient, usually associated with numerous comorbidities. Cardiovascular diseases such as hypertension, ischemic coronary artery disease, valvulopathy are common in our practice. Patient with AF is a patient who requires long-term anticoagulant therapy and in whom sinus rhythm recovery therapy is dependent on the precocity of presentation to the physician, as well as on the therapeutic resources of current medicine.

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Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

Clinical Science ◽

10.1042/cs20191213 ◽

2020 ◽

Vol 134 (17) ◽

pp. 2243-2262

Author(s):

Danlin Liu ◽

Gavin Richardson ◽

Fehmi M. Benli ◽

Catherine Park ◽

João V. de Souza ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Cardiovascular System ◽

Nlrp3 Inflammasome ◽

Molecular Mechanisms ◽

Molecular Targets ◽

Therapeutic Interventions ◽

Low Grade ◽

Cardiovascular Research ◽

Inflammatory Processes ◽

Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

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