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Direct oral anticoagulants have emerged as the drugs that have changed the management of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagulants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.

Treating an anticoagulated patient with vitamin K antagonists (VKA) remains a challenge, especially in areas where dicoumarins are still the first drug of choice due to the cost of other oral anticoagulants. Anticoagulation clinics have proven to be the most efficient and safe way to avoid thrombotic and hemorrhagic complications and to keep patients in optimal treatment range. However, they require adequate infrastructure and trained personnel to work properly. In this Argentine consensus we propose a series of guidelines for the effective management of the anticoagulation clinics. The goal is to achieve the excellence in both the clinical healthcare and the hemostasis laboratory for the anticoagulated patient. The criteria developed in the document were agreed upon by a large group of expert specialists in hematology and biochemistry from all over the country. The criteria presented here must always be considered when indicating VKA although they had to be adapted to the unequal reality of each center. Taking these premises into consideration will allow us to optimize the management of the anticoagulated patient with VKA and thus minimize thrombotic and hemorrhagic intercurrences, in order to honor our promise not to harm the patient.

Venous thromboembolic disease (VTE) in hospitalized adults has high morbidity and mortality, is the origin of chronic complications and increased cost for the health system. Since the publication of recommendations for thromboprophylaxis in hospitalized patients in 2013, new alternatives and strategies have emerged, which motivated us to update our recommendations. Although there are different consensus and clinical practice guidelines, adherence to them is suboptimal. The different therapeutic alternatives for hospitalized adult patients (non-surgical, surgical non-orthopedic, with and without cancer, orthopedic an d pregnant) have been updated, paying particular attention to the drugs available in Argentina.

Although the incidence is uncertain, some case reports suggest that COVID 19 infection is associated with an increased risk of venous thromboembolism. We suggest starting prophylactic anticoagulant therapy for all patients hospitalized with a symptomatic infection with COVID-19, unless contraindicated, with enoxaparin 40 mg SC daily if creatinine clearance is greater than 30 ml/min.

Salicylic acid (SA) or 2-hydroxybenoic acid is a phenolic plant hormone that plays an essential role in plant defense against biotrophic and semi-biotrophic pathogens. In Arabidopsis, SA is synthesized from chorismate in the chloroplast through the ICS1 (isochorismate synthase I) pathway during pathogen infection. The transcription co-activator NPR1 (Non-Expresser of Pathogenesis-Related Gene 1), as the master regulator of SA signaling, interacts with transcription factors to induce the expression of anti-microbial PR (Pathogenesis-Related) genes. To establish successful infections, plant bacterial, oomycete, fungal, and viral pathogens have evolved at least three major strategies to disrupt SA-mediated defense. The first strategy is to reduce SA accumulation directly by converting SA into its inactive derivatives. The second strategy is to interrupt SA biosynthesis by targeting the ICS1 pathway. In the third major strategy, plant pathogens deploy different mechanisms to interfere with SA downstream signaling. The wide array of strategies deployed by plant pathogens highlights the crucial role of disruption of SA-mediated plant defense in plant pathogenesis. A deeper understanding of this topic will greatly expand our knowledge of how plant pathogens cause diseases and consequently pave the way for the development of more effective ways to control these diseases., (Copyright © 2018 The Author. Published by Elsevier Inc. All rights reserved.)

Hemophilia A and B are rare, X-linked bleeding disorders resulting from a partial or total deficiency of functionally active coagulation factor VIII or factor IX, respectively. Endogenous factor levels have traditionally been used to characterize the severity of the disorder, with severe hemophilia considered as circulating levels of factor less than 1% of normal. Identifying patients with severe hemophilia is essential to effective treatment, since these patients are at highest risk of spontaneous life or limb-threatening bleeding and disability resulting from repeated joint bleeding and are most likely to benefit from prophylaxis. However, there is variability in bleeding tendency, even among patients with severe hemophilia. This article will review potential modifiers of hemophilia-associated bleeding other than endogenous factor activity, which may influence bleeding tendencies and complications in hemophilic patients considered to have severe hemophilia. These potential modifiers include physiologic factors, such as elements of the hemostatic system; pathophysiologic factors, such as hemophilic arthropathy, associated inflammation, and angiogenesis; and others, such as seasonal variation, body weight, and physical activity.

Bleeding is the main complication of oral anticoagulants, anti-vitamin K or new drugs such as anti-factor Xa or anti-thrombin agents. Risk factors associated with bleeding during warfarin therapy are discussed. For the new drugs no published data is available yet. Comparative frequencies of major bleeding during anticoagulation in atrial fibrillation and venous thromboembolism are shown. Beyond the intrinsic properties of the classic and new agents, patients characteristics and co-morbidities and an appropriate management of the antithrombotic therapy will be the factors associated with bleeding incidence in real life.

This multicenter, open-label study evaluated the efficacy and safety of decitabine in patients from Argentina and South Korea with myelodysplastic syndromes or chronic myelomonocytic leukemia. Of 106 patients who received decitabine 20 mg/m(2) intravenously over 1 h once daily for 5 days in 4-week cycles, 99 patients were evaluable after receiving at least two cycles. The overall improvement rate was 35% (19% complete response +4% marrow complete response +4% partial response +8% hematologic improvement). Overall survival at 2 years was 71%. Treatment-related adverse events included febrile neutropenia, thrombocytopenia and bleeding, asthenia, fatigue, and eosinophilia. After complete response (CR), three patients received an allogeneic stem cell transplant. Four patients who relapsed after CR responded to decitabine retreatment. Acute myelogenous leukemia developed during follow-up in 21% of patients. Decitabine in a 5-day outpatient administration schedule was effective and well tolerated in typical clinical practice settings in South America and Asia.

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, neurological symptoms, and renal involvement. The relationship of TTP to systemic lupus erythematosus (SLE) has been recognized in the medical literature since 1939. The differential diagnosis is difficult because both diseases have similar clinical features. The mainstay for recognizing TTP in the context of active SLE is the presence of helmet red cells, marked reticulocytosis, and negative direct Coomb's test. We report three female patients with simultaneous presentation of TTP and SLE. We suggest combined treatment with immunosuppressive therapy and plasma exchange using fresh frozen plasma.

Prevention of venous thromboembolism (VTE) can be achieved through mechanic or pharmacological means. For the latter, unfractionated low dose heparin, low molecular weight heparins and oral anticoagulants are successfully and widely employed. Results of controlled and uncontrolled studies favour the use of prophylactic heparin in different clinical and surgical conditions such as myocardial infarction, stroke, orthopedic or prolonged surgery and surgical interventions in patients older than forty. Useful parameters to evaluate the results of VTE prophylaxis are discussed as well as timing, duration, effectiveness, side effects and costs of therapy. Although the benefits of VTE prophylaxis in high risk patients are clear, it is not routinely employed in Argentina.

Purpose: To evaluate bone marrow granulomatous lesions in order to establish their etiology., Material and Methods: 2,250 bone marrow biopsies were studied during the period of March 1983-March 1991. Granulomas and/or granulomatous lesions were found in 24 of them (1.06%). A correlation between histological characteristics, special stains: PAS, Ziehl Neelsen and Grocott and cultures were done. Immunohistochemistry was done to evaluate B or T cell-lineage in 4 patients., Results: The 24 patients were biopsied because of the clinical diagnosis of haematological and non-haematological neoplasias, infections, AIDS, sarcoidosis and fever of unknown origin. Bone marrow cellularity ranged from 20% to 75% (M: 49.8%). Myeloid cells were increased in 54% of the cases. The number of granulomas ranged from 1 to 19 (M: 3.9). The epithelioid cells were the predominant component in 66% of the cases. Of the 7 patients with non-Hodgkin's lymphoma, 4 had lymphomatous involvement with granulomatous pattern. These cases showed predominance of lymphoid cells and vessels in addition to epithelioid cells., Conclusion: We consider that in order to establish a relationship between infection and granuloma, the identification of a microorganism through a culture is a more reliable test. We couldn't find any morphological characteristic which allowed an etiologic diagnosis of bone marrow granulomas. In case of lesions with a great lymphocytic and vascular proliferation plus the presence of epithelioid cells and fibrosis, NHL with bone marrow involvement with a granulomatous pattern should be strongly considered.

The ninth most common allegation against hospitals in 1989 was infection/contamination exposure, with the average claim costing nearly $34,000. Most malpractice claims are associated with inpatient surgery, according to 1990 statistics, and the average cost of a claim for infection and contamination related to surgery was over $64,000 in 1990. Physicians currently pay as much as $50,000 annually for malpractice insurance, and hospitals in some major metropolitan areas pay $8,000 per bed for insurance. An estimated 5% of hospitalized patients acquire nosocomial infections at an annual cost of approximately $10 billion. Prolonged hospitalization, usually for parenteral antibiotic treatment, accounts for more than three-fourths of this cost. To reduce the costs of malpractice, nosocomial infections can be prevented through infection-control programs, or damages can be reduced by treating infections with more efficacious and safer drugs that decrease the pain and suffering associated with the infection.