[MANAGEMENT OF VENOUS THROMBOEMBOLISM: WHICH DRUG, WHAT DOSE AND FOR HOW LONG].

INTRODUCTION: Venous thromboembolism is a major cause of morbidity and mortality. The main initial therapy for thromboembolism is anticoagulation for a period of three months (active treatment period). The aim of treatment beyond three months is prevention of recurrence. The duration of anticoagulation is being determined by the degree of provocation leading to the thromboembolic event, but other factors like the patient's gender, oral contraceptive use, cancer etc. may influence the period of anticoagulation. The direct oral anticoagulants (DOACs) are as effective as warfarin with less major bleeding events. Despite their growing use, it is important to remember that there is still a lack of evidence about their safety and efficacy in many clinical situations. Preliminary evidence for their efficacy in venous thromboembolic diseases (VTE) in cancer patients has been published. In this article we will address these and other issues arising in treating VTE by discussing common clinical scenarios.

Cardiac Manifestations of Antiphospholipid Syndrome With Focus on Its Primary Form.

Antiphospholipid syndrome (APS) is a multisystem autoimmune disease most commonly associated with recurrent arterial and venous thromboembolism and recurrent fetal loss. Other possible antiphospholipid antibody (aPL)-related clinical manifestations include cardiac involvement. The heart can be involved through immune mediated and /or thrombotic mechanisms. Mortality due to cardiovascular problems is elevated in APS. However, the cardiovascular risk in patients with primary APS (PAPS) compared with lupus-related APS is yet to be established. Cardiac symptoms of APS include valve abnormalities (thickening and vegetations), coronary artery disease (CAD), myocardial dysfunction, pulmonary hypertension, and intracardiac thrombi. Heart valve lesions are the most common cardiac manifestation, observed in approximately one third of PAPS patients and usually do not cause hemodynamic significance. Deposits of immunoglobulins including anticardiolipin (aCL), and of complement components, are commonly observed in affected heart valves from these patients. This suggests that an inflammatory process is initiated by aPL deposition, eventually resulting in the formation of valvular lesion. aPL may have a direct role in the atherosclerotic process via induction of endothelial activation. Multiple traditional and autoimmune-inflammatory risk factors are involved in triggering an expedited atherosclerotic arterial disease evident in APS. It is imperative to increase the efforts in early diagnosis, control of risk factors and close follow-up, in the attempt to minimize cardiovascular risk in APS. Clinicians should bear in mind that a multidisciplinary therapeutic approach is of paramount importance in these patients. This article reviews the cardiac detriments of APS, including treatment recommendations for each cardiac complication.

The complexity of an overlap type resistant cryoglobulinemia: a case report and review of the literature.

Type I cryoglobulinemia is associated with B cell proliferative diseases, whereas essential mixed cryoglobulinemia is classically associated with infections, malignancy, and autoimmune diseases, but may be idiopathic. Prognosis in patients with grave manifestations and renal involvement is often poor. We report a case of a 40-year-old woman, 2 weeks post-partum for pre-eclampsia who was hospitalized with nephritic syndrome and acute renal failure. The patient harbored type I and type II cryoglobulinemia. Renal and cutaneous biopsies confirmed the diagnosis; however, an underlying etiology was not established. A bone marrow biopsy suggested monoclonal gammopathy of undetermined source (MGUS). Despite therapy with intravenous cyclophosphamide, rituximab, plasmapheresis, dialysis, and bortezomib, the patient succumbed after 8 months of hospitalization. We suggest that an overlap entity of types I and II cryoglobulinemia with severe multi-organ involvement not only is rare but also may be resistant to conventional therapy and fatal.

Laryngeal Side Effects of Tyrosine Kinase Inhibitors.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) are common targeted drugs, used in the treatment of hematological and solid malignancies. These drugs present a multitude of potential adverse effects. Laryngeal manifestations, including laryngeal edema, secondary to TKIs treatment have not been well studied, despite their potential lethality. METHODS: This cross-sectional study included adult patients (>18 years) treated with TKIs who were followed in a secondary medical center and underwent a voluntary otolaryngological examination, which included laryngeal fiber-optic laryngoscopy (FOL). FOL was independently performed by two senior otolaryngologists, and results were recorded and evaluated by two grading systems, to assess the degree of laryngeal edema. In addition, medical files were reviewed, and data collected included past medical history, signs and symptoms, physical examination, laboratory results, treatment type, and duration. RESULTS: Sixteen patients, aged 68.2 ± 13.6 years, were examined during October 2014 to December 2014. Of them, three (19%) were males. Eleven (68%) patients presented with varying degrees of laryngeal edema. A significant correlation was found between gastroesophageal reflux symptoms and laryngeal edema (P = 0.02). TKI treatment was stopped in one patient, because of symptomatic laryngeal edema, which completely resolved within 2 weeks. CONCLUSIONS: Laryngeal edema was common in our study group. This edema was most often not life threatening. Yet, because of the potential severity of this side effect, we propose a routine FOL examination of patients before commencing TKI treatment and a reevaluation performed during treatment.

[Laboratory evaluation of lupus anticoagulant in Israel].

Lupus anticoagulants (LAC) are antibodies which are detected by a prolongation of phospholipid-dependent coagulation assays, and are associated with thrombotic events and pregnancy complications in patients with the antiphospholipid syndrome. The antiphospholipid syndrome is defined by arterial or venous thrombosis and/or pregnancy morbidity and by laboratory diagnosis of antiphospholipid antibodies. The laboratory diagnosis is based on LAC and/or anticardiolipin and/or anti-beta2-glycoprotein I antibodies present in plasma, on two or more occasions at least 12 weeks apart. ALthough the presence of LAC correlates best with thrombosis, the Laboratory testing of LAC is not well standardized. In this article, the Laboratory evaluation of LAC will be explained, including the different tests that are recommended by the Israeli Sub-committee of Thrombosis and Hemostasis Laboratories, the possibility to evaluate LAC in patients treated with antithrombotic therapy, and how to report and interpret the results.

Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome.

Low-risk myelodysplastic syndrome (MDS) is characterized by cytopenia, mainly anemia, because of ineffective hematopoiesis. Some of the patients with ineffective erythropoiesis, with or without ring sideroblasts in their bone marrow, develop severe anemia requiring frequent blood transfusions and consequently develop iron overload. Excess free iron in cells catalyses the generation of reactive oxygen species (ROS) that cause cell and tissue damage. Using flow cytometry techniques, we compared the oxidative status of red blood cells (RBC), platelets and neutrophils in 14 MDS patients with those of normal donors. The results show that ROS were higher while reduced glutathione (GSH) was lower in their RBC and platelets compared with normal cells. In neutrophils, no difference was found in ROS, while the GSH levels were lower. A correlation (r = 0.6) was found between serum ferritin levels of the patients and the ROS in their RBC and platelets. The oxidative stress was ameliorated by a short incubation with the iron-chelators, the deferrioxamine and deferiprone or with antioxidants such as N-acetylcysteine, suggesting that MDS patients might benefit from treatment with iron-chelators and antioxidants.

No evidence for myocardial iron overload in multitransfused patients with myelodysplastic syndrome using cardiac magnetic resonance T2 technique.

The method of cardiovascular T2 magnetic resonance imaging (MRI) allows in vivo estimation of iron in the heart and liver and was used to measure the degree of iron overload in 10 transfused MDS patients (average 90 blood units) and in 3 patients with congenital hemolytic anemia. In all MDS patients iron overload was found in the liver but not in the heart. Patients with congenital anemias had iron in both organs despite iron chelation. It is possible that in MDS more time and more transfusions are required to induce iron accumulation in the myocardium. Therefore, cardiac MRI may serve as a diagnostic tool to assess if and when iron chelation is indicated.

[Anthrax--an overview at 2002].

BACKGROUND: Bacillus anthracis, the causative agent of anthrax, is well known in human history as a major cause of disease in domestic and wild animals and as a rare condition in humans. For the last seventy years, anthrax was developed and occasionally stored as an agent of biological weapon arsenal in numerous countries. The incubation period in humans is 1-6 days and the disease may be present as three distinct clinical syndromes: cutaneous, inhalational, and gastrointestinal disease. The major concern in regard of biological warfare is the inhalational form of anthrax, which starts as a febrile flu-like disease. The development of malaise, fatigue, cough and mild chest discomfort is followed by severe respiratory distress with dyspnea, diaphoresis, stridor, and cyanosis. Shock and death occur within 24-36 hours after onset of severe symptoms. Physical findings are non-specific, but a widened mediastinum is usually seen on chest x-ray. A positive blood culture, immunohistochemical methods and the use of the polymerase chain reaction method confirm the diagnosis. Although effectiveness may be limited after severe symptoms are present, a high dose of antibiotic treatment should be administered and aggressive supportive therapy may be necessary. In the situation of an anthrax attack, as was recently seen in the United States, penicillin is no longer recommended as an acceptable first line therapy. In this case, ciprofloxacin or doxycycline is the recommended drug of choice since penicillin-resistant strains may be used, as well as the possibility of the emergence of an inducible beta-lactamase positive bacterium. Since a high infecting dose may exacerbate the clinical course of the disease, a combination antibiotic regimen should be considered. The disease is not contagious and standard precautions are sufficient. Pre-exposure prophylaxis is based on a vaccine administration, while post-exposure prophylaxis is feasible by the initial use of oral ciprofloxacin or doxycycline. In this article we reviewed the literature with emphasis on the recent medical reports from the United States analyzing the eleven cases of inhalational anthrax as well as the new guidelines for diagnosis and treatment that resulted from the bioterrorism attack in October 2001. Although physical findings were non-specific, abnormal findings on chest x-rays were present in all the eleven cases. A positive blood culture, immunohistochemical methods and the use of the polymerase chain reaction method were highly valuable in revealing and confirming the diagnosis of anthrax. In the case of an attack with anthrax spores, the likelihood of exposure to a large infective dose of high quality spores, may require a prolonged period of treatment as well as prolonged post-exposure therapy.