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Direct oral anticoagulants have demonstrated efficacy and safety in the treatment of venous thromboembolic disease. A review is presented of the results of direct oral anticoagulants in the published clinical trials of extended anticoagulant treatment (after the first 3-6 months of treatment) of venous thromboembolic disease., (Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To assess whether there are differences between atrial fibrillation (AF) patients initiating new direct-acting oral anticoagulants (DOAC) therapy and vitamin K antagonist (VKA) therapy in an emergency service., Methods: Descriptive, observational, prospective study. We enrolled patients with AF who were visited in a hospital emergency service over one year., Results: This study included 492 patients with AF, and 189 subjects received anticoagulant therapy, 104 with VKA (55%), and 85 with DOAC (45%). The VKA group: mean age 76.1 years, male 50.9% and female 49.1%, CHA 2 DS 2 -VASc mean 3.2±1.3 points, and a HAS-BLED mean of 1.9±0.8 points. The DOAC group: mean age 73.4 years, male 37.6% and female 63.3%, CHA 2 DS 2 -VASc mean 3.1±1.6 points, and a HAS-BLED mean of 1.7±0.8 points. On analysing the medical history, 17.3% of patients in the VKA group had a previous stroke, and 13.5% significant valve disease, as well as 7.1 and 1.2% of patients, respectively, in the DOAC group. In the analysis of the DOAC types, 24.2% of patients in the dabigatran group had a previous stroke, 22.7% in the rivaroxaban group had ischaemic heart disease., Conclusions: Patients with AF who start on treatment in emergency services with VKA or with DOAC show a similar profile of age, gender, CHA 2 DS 2 -VASc score, and HAS-BLED score. The patients with a history of valvular or ischaemic heart disease received more VKA than DOAC. When the patient has a history of stroke, the DOAC more used is dabigatran, and in patients with ischaemic heart disease it is preferred to give rivaroxaban., (Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

The present article provides an update on anticoagulant treatment in patients with atrial fibrillation in distinct clinical scenarios requiring particular considerations, such as ischaemic heart disease, electrical cardioversion, pulmonary vein ablation, the presence of valvular disease with or without prosthetic valves, and renal insufficiency, as well as old age and frailty. In patients with non-valvular atrial fibrillation, the presence of renal insufficiency increases both thrombotic and haemorrhagic risk. In mild and moderate stages, direct-acting anticoagulants confer a greater benefit than warfarin, although they usually require dose adjustment. In renal failure/dialysis, there is no solid evidence that warfarin is beneficial and the use of direct-acting anticoagulants is not recommended. Because of its pathophysiology, oral anticoagulation could have a beneficial effect in patients with heart disease. However, vitamin K antagonists have not shown a satisfactory risk-benefit ratio. In contrast, direct-acting anticoagulants, at reduced doses, could have a beneficial effect in this scenario in association with antiplatelet agents. The use of direct-acting anticoagulants prior to electrical cardioversion in patients with non-valvular atrial fibrillation seems to be associated with a risk of cardioembolic events that is at least comparable to that of vitamin K antagonists. Their use avoids delay in the application of electrical cardioversion in patients without adequate INR levels. In the context of their use before and after atrial fibrillation ablation, dabiga-tran and rivaroxaban have demonstrated at least non-inferiority with vitamin K antagonists in terms of safety. In patients with any type or grade of valvular disease and atrial fibrillation, the indication of antithrombo-tic treatment must be evaluated in the same way as in patients with atrial fibrillation and no valvular di-sease. Whenever anticoagulation is required, direct-acting anticoagulants are the treatment of choice in nearly all situations, except in patients with mechanical valves or who have significant rheumatic mitral disease, who should be treated with vitamin K antagonists. The choice of appropriate antithrombotic stra-tegy in frail elderly patients is complex and involves multiple factors beyond assessment of embolic and haemorrhagic risk. Comprehensive geriatric assessment is essential for an individualised final decision. Moreover, any such decision should be consensus-based and periodically reviewed. Direct-acting anticoa-gulants could be the most beneficial alternative in most elderly patients with non-valvular atrial fibrillation., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Knowing the real impact of atrial fibrillation in the stroke, the Sociedad Mexicana of Electrofisiología y Estimulación Cardiaca (SOMEEC) had the initiative to develop a multidisciplinary meeting of experts the with the purpose to update the available scientific evidence from clinical practice guidelines, meta-analyses, controlled clinical trials, and complementing with the experience and views of a group of experts. To meet this goal, SOMEEC gathered a group of specialists in the area of cardiology, electrophysiology, neurology and hematology that given their experience in certain areas, they share the scientific evidence with the panel of experts to leave open a discussion about the information presented in this article. This document brings together the best scientific evidence available and aims to be a useful tool in the decision to use of new oral anticoagulants in nonvalvular atrial fibrillation and ischemic heart disease, or relating to the management of patients with stroke or renal failure, and even those that will be submitted to elective surgery and invasive procedures. In the same, they handled comparative schemes of follow-up and treatment which simplifies the decision making by the specialists participants., (Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.)

Objectives: To determine the prevalence of international normalized ratio (INR) findings outside the normal range in hospital emergency department patients on vitamin K antagonists (VKAs). To identify factors associated with abnormal anticoagulant levels in these patients., Material and Methods: Observational, cross-sectional, multicentric study in 4 hospital emergency departments. We included a convenience sample of patients on VKA treatment for whom INR levels were on record and who had sought emergency care for complications unrelated to anticoagulant treatment., Results: We included 376 patients with a mean (SD) age of 76.8 (10.1) years; 50.3% were women and 86.7% had atrial fibrillation. We found that 60.4% (95% CI, 55.3%-65.2%) had INRs outside the reference range. Multivariate analysis showed that changes in the patients' other long-term medications were independently associated with nontherapeutic INR results (odds ratio, 1.6; 95% CI, 1.02-2.79; P=.035)., Conclusion: Over 60% of patients on VKA treatment who come to hospital emergency departments with complaints unrelated to anticoagulant therapy have INR values outside the normal range. Changes in a patient's usual medications are significantly associated with nontherapeutic INR findings.

This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations., (Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.)

Thromboembolic disease, both arterial and venous, is a major cause of morbidity and mortality in developed countries. The new anticoagulants exert their action by selective, direct and reversible inhibition of a single coagulation factor. Although the results of several phase III trials have demonstrated the safety and efficacy of these drugs, their mechanism of action, as well as the pharmacodynamics and pharmacokinetics of these drugs, need to be understood for their correct use. The present review discusses the features of the new anticoagulants whose clinical development is more advanced, both those designed to block active factor X, such as rivaroxaban or apixaban, and those designed to block thrombin (also active factor II): dabigatran., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Vitamin K antagonists have been shown to be effective in the primary and secondary prevention of systemic and cerebral emboli in patients with cardiac causes of embolism, especially atrial fibrillation. The reduced risk of stroke is greater in secondary prevention, although this reduction is accompanied by an inherent risk of hemorrhagic complications, among which cerebral hemorrhage is especially serious. The therapeutic window of these agents is limited and the best benefit/risk profile is obtained with an INR of between 2 and 3. The anticoagulant effect obtained shows marked variability, requiring frequent clinical and laboratory monitoring of the treatment. The introduction of oral anticoagulants that would aid the administration of these agents with equal or greater efficacy and lower risk is required., (Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

The vitamin K antagonists (VKA) available for stroke prevention in patients with atrial fibrillation have many drawbacks due to their difficult clinical use and high risk of bleeding. Currently, several drugs are being developed as possible substitutes for VKA that have many advantages such as the lack of monitoring requirement and scarce pharmacologic and food interactions. The present article provides an update on the new oral anticoagulants that are in a more advanced stage of clinical research, their pharmacologic properties, advantages and disadvantages and their results in recent clinical trials., (Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

Thromboembolic disease is the main preventable cause of in-hospital death. Approximately 10% of nosocomial deaths are attributable to pulmonary embolism and in most cases, the diagnosis is not suspected before the autopsy. There are cost effective measures to decrease the incidence of thromboembolic disease. Pharmacological prophylaxis decreases the incidence of deep venous thrombosis by 65% and the incidence of pulmonary embolism by 35 to 55%. Despite this data and the presence of clinical guidelines, prophylaxis of thromboembolic disease is used only in 40% of medical patients and in 65% of surgical patients with recommended indications. We review the evidence that supports the use of thromboprophylaxis and the different strategies that may increase the compliance of physicians with its use. A protocol implemented in our institution is also proposed.

Dabigatran is the first available oral direct thrombin inhibitor anticoagulant. Absorption of the prodrug, dabigatran etexilate and its conversion to dabigatran is rapid (peak plasma concentrations are reached 4-6 hours following surgery, and a further 2 hours later). Its oral bioavailability is low, but shows reduced interindividual variability. Dabigatran specifically and reversibly inhibits thrombin, the key enzyme in the coagulation cascade. Studies both in healthy volunteers and in patients undergoing major orthopaedic surgery show a predictable pk/pd profile that allows for fixed-dose regimens. The anticoagulant effect correlates adequately with the plasma concentrations of the drug, demonstrating effective anticoagulation combined with a low risk of bleeding. Dabigatran is mainly eliminated by renal excretion (a fact which affects the dosage in elderly and in moderate-severe renal failure patients), and no hepatic metabolism by cytochrome P450 isoenzymes has been observed, showing a good interaction profile. Rivaroxaban will probably be the first available oral factor Xa (FXa) direct inhibitor anticoagulant drug. It produces a reversible and predictable inhibition of FXa activity with potential to inhibit clot-bound FXa. Its pharmacokinetic characteristics include rapid absorption, high oral availability, high plasma protein binding and a half-life of aprox. 8 hours. Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. Although the drug has demonstrated moderate potential to interact with strong CYP3A4 inhibitors, it does not inhibit or induce any major CYP450 enzyme.

The search for the ideal anticoagulant has been one of the most active research fields in medicine in the past few years. Anti-vitamin K replacement, particularly in the long term treatment of venous thromboembolism is a difficult objective to achieve due to the wide experience gathered in normal practice and low costs. But to improve the weak points of these drugs is an attractive challenge and would have a great health and social impact. It can be seen that the low molecular weight heparins, or even pentasaccharide, drugs that are already available on the market, although the have very predictable pharmacokinetics, their parenteral use, or their long half life, they are far from being ideal anticoagulants. Ximelagatran, a promising drug, a direct inhibitor of thrombin seemed to be a step forward, but the appearance of undesirable side effects led to its withdrawal. However, this line of investigation has remained open, as such that we now have data from clinical trials that back it up: the direct inhibition of thrombin and activated factor X. These two different mechanisms of action are showing promising results, in that the direct inhibitors of thrombin (dabigatran, hirudins...) are showing not to be inferior in efficacy and safety to enoxaparin in the primary prophylaxis of venous thromboembolism. Similarly, the activated factor X inhibitors (Rivaroxaban, Apixaban ) are also showing the same and in some cases, superior in its prevention. This review looks at the mechanisms of action of both pharmacological groups, their effects on haemostasis, and how they are reflected in coagulation times, their pharmacokinetics and pharmacodynamics. These new anticoagulants are nearer to the ideal anticoagulant and may, in the near future, change the panorama of anticoagulation, not only at health level, but also by achieving improved levels in the quality of life of the patients.

Sepsis is a leading cause of morbidity and mortality worldwide, and the magnitude of the problem seems higher in developing countries. In the last two decades the accepted standard treatment has resulted in only a slight decrease in mortality, and that decrease has been overshadowed by an almost 300% increase in incidence. Recently has been documented the close relationship between infection, inflammation and coagulation in sepsis has been documented; and although clinically overt disseminated intravascular coagulation may occur in only 30% to 50% of septic patients, the activation of the coagulation cascade is an early and common response to the infectious challenge. Moreover most of the molecules involved in the pro-coagulant state that characterizes sepsis are also powerful generators or amplifiers of the inflammatory response. These findings have fostered a comprehensive body of research regarding biological products with anticoagulant activity, as additional therapies for patients with the most severe states of the sepsis syndrome. This review explains the biological and molecular aspects that support the potential use of anticoagulant treatments in sepsis. Furthermore, we analyze the evidence provided by experimental and pre-clinical studies, which suggest the usefulness of heparin as an effective complementary treatment throughout the clinical stages of the disease.

Thrombocytopenia is a potential complication of heparin therapy. There are two forms of heparin-induced thrombocytopenia (HIT). Type-I HIT is characterized by a mild decrease in platelet count that occurs within the first 2-4 days after heparin initiation. The platelet count often returns to normal without stop heparin treatment. The mechanism of thrombocytopenia appears to be due to a direct effect of heparin on platelet activation. The second form (type-II) is an immune-mediated disorder characterized by severe thrombocytopenia, which may include both arterial and venous thrombosis. We present a case of type-II HIT occurred in a hemodialysis patient resulting in acute pulmonary embolism and peripheral venous thrombosis, and review the literature.

Objective: To analyze the different presentations of ischemic cerebrovascular disease and develop algorithms for treatment in those different possible settings., Development: We present an analysis of the publications in which the clinical, diagnostic and therapeutic features of aorto-emboli and cardio-emboli (patent foramen ovale, septal aneurysm, bacterial endocaritis, etc.) have been defined. We suggest an algorithm with general parameters for the use of anticoagulants in cerebrovascular disease. Subsequently we specifically consider the decision as to the moment to start anticoagulation, selection of the type of anticoagulant, dosage, route of administration and duration of the treatment. Because of the implications for treatment, we assess the therapeutic options when haemorrhagic infarcts occur., Conclusions: Based on studies in the literature showing benefit in individualized cerebrovascular disorders, and the anecdotic experiences of Drs. Miller Fisher, Caplan, Pessin and the writer, over the past 40 years using anticoagulants in the different clinical settings described, some parameters for treatment are proposed. We emphasize that whilst patients with different types of cerebrovascular disease are all grouped together under the unifying term 'stroke', the various treatments evaluated will probably be shown to be inefficient or deleterious. The line of treatment suggested in this review is based on the definition of the different cerebrovascular scenarios according to their aetiology and mechanisms, so as to obtain the most suitable treatment in each case.

Vitamin K is a cofactor for the synthesis of blood coagulation Factors II, VII, IX and X, and inhibitors such as Protein C and S and bone matrix protein. Its active form is a coenzyme in the glutamic acid carboxylation. Vitamin K-dependent factors form enzymatic complexes with calcium and membrane phospholipids. The insufficiency of gamma glutamic carboxylation impairs the hemostatic function. Hereditary deficiencies, antibiotics and oral anticoagulants, decrease the capacity of complex formation giving way to hemorrhage or thrombosis, or bone mass disturbances which are easily treated with administration of Vitamin K. The main causes of Vitamin K deficiency are lack of hepatic storage in newborns, liver insufficiency, malabsorption, dietetic deficiency, therapy with the antibiotics and coumarin administration. For the study of Vitamin K there are methods to measure the Vit K dependent proteins and as well methods to measure specifically the quinonas.

Low molecular weight heparins are a group of drugs that have only recently been introduced in clinical practice. The are widely used for prophylaxis in thromboembolic disease and are being employed increasingly to treat established venous thrombosis. One way in which these drugs are often used is for prophylaxis in the perioperative period for patients at high risk of developing venous thromboembolism, and the anesthesiologist must therefore be familiar with the main aspects of this application. We review pharmacological characteristics of these drugs as well as the literature on low molecular weight heparins, stressing points of main interest to the anesthesiologist and intensive care recovery unit specialist, namely adverse effects (mainly bleeding) and the implications that use of low molecular weight heparin will have on choice of anesthetic (in particular the dilemma of whether to use local/regional anesthesia).

The aim of this work was to compare the benefits and problems of low molecular weight heparin use in chronic hemodialysis, compared to conventional heparin. We studied 35 patients that received low molecular weight heparin (Enoxaparine, molecular weight 4000) during 115 consecutive hemodialysis procedures and conventional heparin during the subsequent 35 procedures. We assess the heparin dose, partial thromboplastin time before dialysis and at 3 and 120 min during the procedure, arterio-venous fistula compression time, clot formation in the circuit and residual volume of filters. Median total dose of conventional heparin was 6289 U (range 3000-10000) compared to 5555 U (range 2000-8000) of low molecular weight heparin. When the dose was calculated per kg of body weight, it was lower for low molecular weight heparin than for conventional heparin (87.8 U (range 33-100) vs 100 U (range 50-176)). Partial thromboplastin time achieved was lower with low molecular weight heparin, compared with conventional heparin, at 3 (64.26 vs 125.2 sec) and 120 min (39.1 vs 84.45 sec). Clot formation, arteriovenous fistula compression time and residual volume of filters were similar for both types of heparin. It is concluded that a single dose of low molecular weight heparin simplifies anticoagulation during hemodialysis, modifies less the partial thromboplastin time and does not alter filter re-utilization.

Oral anticoagulants are employed very frequently in the prophylaxis and treatment of several diseases. For their optimal effectiveness, many vigilance schedules have been proposed but none has proved to be 100% effective. The international normalization ratio (INR) can be a safer way to monitor oral anticoagulation, and our objective was to determine its clinical usefulness. A prothrombin time test (PT) was carried out by means of either a chromogenic or a coagulometric method, and an INR was obtained using the ratio of the PT patient/PT control elevated to an exponential given by the international sensitivity index (ISI) of our thromboplastin. Our objective was to maintain our patients in a therapeutical INR range between two and three. We present our experience with 77 patients and 810 results during an 18 months period. We observed 26 cases of hemorrhage and three of thrombosis. In all these cases, the INR was out of the desired therapeutical range. No deaths occurred in our patients. Our analysis showed a significative disagreement between the INR and the prothrombin time ratio (PTR) but a better correlation with hemorrhage and thrombosis was seen with the INR than with the PTR. Our experience supports the use of INR in the clinical vigilance of oral anticoagulation as a useful method.

There are many patients on oral anticoagulant therapy monitored with prothrombin time (Quick Test). Differences in sensitivity of the various types of tissue thromboplastins are the cause of the different results and common therapeutic ranges, calibrated reference thromboplastins with a defined International Sensibility Index (ISI) have become available. The ISI is used to estimate the International Normalized Rate (INR) which is used as a universal scale for the expression of the prothrombin time results in the control of oral anticoagulant therapy.

A controlled double-blind study of the effects of oxovinca in the syndrome of diffuse deterioration of vascular origin has been carried out. The measurement and follow-up the degree of deterioration has been done by application of a new scale. The subjects of the study were divided into an experimental sample (formed by 33 patients) and a placebo sample (formed by 6 patients), all with the syndrome of diffuse deterioration of vascular origin, and a control sample formed by 10 normal individuals of comparable age. After three consecutive courses of the drug given within a two-month period to the experimental and placebo groups, and comparing the results with those of the control sample, the statistical analysis of the data demonstrates that, given the temporal limitations of the trial, a partial reversibility of the signs and symptoms of the syndrome of diffuse deterioration is possible and correlates with the therapeutic action of oxovinca.

Anticoagulants are drugs capable to retard or even cancell the process of blood coagulation. They are many factors who influences the intensity and duration of oral anticoagulant acitivity, such as drugs, body constitution, physical agents, diseases, etc. The oral anticoagulants interacts with other drugs at differents levels: at the gut, at the plasma, modiffing the protein binding or the metabolism of such drugs, at the enzimatic induction or inhibition, or at unknown places with many other drugs. These paper deals with the description of such interactions.