Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The only major and potentially fatal risk for patients with atrial fibrillation is the development of systemic thromboembolism. Stroke occurs five times more frequently in patients with atrial fibrillation than in comparable patients in sinus rhythm. The yearly incidence of stroke in atrial fibrillation largely depends on the underlying heart disease: from 0.5% in "lone" atrial fibrillation up to 20% in rheumatic heart valve disease. Oral anticoagulation with vitamin K antagonists dramatically reduces the stroke risk by two-thirds, but is a laborious and patient-unfriendly therapy. Oral direct thrombin blockers and oral factor Xa antagonists, both without therapy monitoring, may replace warfarin for this indication, but there are safety and efficacy issues to be resolved. Oral antiplatelet agents are effective, but clearly less than warfarin. Angiotensin receptor blockers are currently under investigation. Routine electrocardioversion for atrial fibrillation does not reduce the stroke risk, but promising techniques include electroablation of the left atrium and occlusion of the left atrial appendage.
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PMID:Stroke prevention in atrial fibrillation. 1651 85

Nearly every second patient, who needs an oral anticoagulation with vitamin K antagonists, is feasible to perform INR-self-management after participation in a structured teaching program. Patient self-testing or measuring the INR value by relatives or nurses would increase this method of control by the aid of telemedicine systems. An accurately, weekly measurement leads to an optimal therapeutic control of anticoagulation intensity, which results in an impressive risk reduction up to 50%. This depends not on the underlying heart disease and had been demonstrated in patients older than 60 years. Due to the small INR variability and therefore a higher percentage in target range, a lower anticoagulation intensity in patients with mechanical heart valve prosthesis should be justifiable. For the next decade, INR self-management/self-testing should be the method of choice, even direct thrombin inhibitors or factor Xa antagonists would be available. An advantage of INR self-management is the control of drug adherence, which could be an unresolved problem for new anticoagulants.
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PMID:[Update of INR-selfmonitoring]. 1883 50

Atrial fibrillation (AF) requires anticoagulation for prevention of arterial embolism, especially in the presence of defined risk factors summarized in the CHADS (2) score (congestive heart disease, hypertension, age >75 years, diabetes, history of ischemic stroke or transient cerebral ischemia). Vitamin K antagonists as drugs of choice have several limitations. International normalized ratio (INR) adjustment to 2.0 to 3.0 may be difficult to maintain, and doses vary widely between patients. Inherited variations of the vitamin K epoxide reductase C1 enzyme and of the cytochrome P450 2C9 system influence the dosage as well as exogenous factors such as food and drug intake or intercurrent diseases. Increasing age and risk of falling are the main factors behind the underuse of anticoagulation in AF. Anticoagulants with a lack of all or most of these characteristics and without need of regular monitoring for dose adjustment may improve the adherence to the indication for anticoagulation. Indirect systemic and oral direct factor Xa and oral direct thrombin inhibitors are currently being developed for the prevention of embolism in patients with AF.
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PMID:New anticoagulants in atrial fibrillation. 1978 62

Anticoagulation for thromboembolic disease and bleeding, the main complication of anticoagulation therapy, are uncommon but are potentially life- or limb-threatening conditions that may present in the pediatric emergency department. Thromboembolic disease in children usually occurs as a complication of vascular access, primarily in children with congenital heart disease or cancer. However, complications of anticoagulation therapy used in the treatment of venous thromboembolism, pulmonary embolism, and blocked central venous catheter; arterial thromboembolism, including arterial ischemic stroke, Kawasaki disease, and after cardiac surgery, may warrant a visit to n the pediatric emergency department. Anticoagulation therapy may take the form of unfractionated heparin, low-molecular weight heparin, vitamin K antagonists, acetylsalicylic acid, or thrombolytic therapy. Monitoring anticoagulation therapy in children is very important and follows adult guidelines. Anticoagulant dosing may be adjusted based on activated partial thromboplastin time, anti-factor Xa level, and international normalized ratio.
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PMID:Anticoagulation therapy: indications, monitoring, and complications. 2120 60

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel envelope virus that causes coronavirus disease 2019 (COVID-19). Hallmarks of COVID-19 are a puzzling form of thrombophilia that has elevated D-dimer but only modest effects on other parameters of coagulopathy. This is combined with severe inflammation, often leading to acute respiratory distress and possible lethality. Coagulopathy and inflammation are interconnected by the transmembrane receptor, tissue factor (TF), which initiates blood clotting as a cofactor for factor VIIa (FVIIa)-mediated factor Xa (FXa) generation. TF also functions from within the nascent TF/FVIIa/FXa complex to trigger profound changes via protease-activated receptors (PARs) in many cell types, including SARS-CoV-2-trophic cells. Therefore, aberrant expression of TF may be the underlying basis of COVID-19 symptoms. Evidence suggests a correlation between infection with many virus types and development of clotting-related symptoms, ranging from heart disease to bleeding, depending on the virus. Since numerous cell types express TF and can act as sites for virus replication, a model envelope virus, herpes simplex virus type 1 (HSV1), has been used to investigate the uptake of TF into the envelope. Indeed, HSV1 and other viruses harbor surface TF antigen, which retains clotting and PAR signaling function. Strikingly, envelope TF is essential for HSV1 infection in mice, and the FXa-directed oral anticoagulant apixaban had remarkable antiviral efficacy. SARS-CoV-2 replicates in TF-bearing epithelial and endothelial cells and may stimulate and integrate host cell TF, like HSV1 and other known coagulopathic viruses. Combined with this possibility, the features of COVID-19 suggest that it is a TFopathy, and the TF/FVIIa/FXa complex is a feasible therapeutic target.
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PMID:Antiviral anticoagulation. 3268 86