Antonella Mameli

Absence of epicardial coronary stenosis in patients with systemic sclerosis with severe impairment of coronary flow reserve

Systemic sclerosis (SSc) is known to be characterised by a diffuse microvascular pathological process leading to cutaneous and visceral changes and to related clinical manifestations. Both necropsy studies1,2 and in vivo investigations3–5 have shown that in a number of patients with SSc there is evidence of a coronary microvascular disease, while coronary artery disease does not exceed that seen in a control group. In particular, myocardial perfusion defects on thallium-201 scintigraphy usually occur in the absence of angiographic evidence of coronary stenosis.3 Recently, we used a new and non-invasive method of contrast enhanced, transthoracic, second harmonic echo Doppler in patients with SSc to evaluate the coronary flow reserve (CFR), a functional variable measuring the ability of the coronary microvasculature to adapt its lumen to a vasodilating stimulus.6 We detected a significant reduction of the CFR …

Antiphospholipid antibodies in patients with scleroderma: prevalence and clinical significance

Antiphospholipid antibodies (aPL) are detected in a variety of autoimmune disorders, most commonly systemic lupus erythematosus, but also in some infectious diseases, lymphoproliferative disorders, and even in apparently healthy people. Although a wide prevalence of aPL in systemic sclerosis has been reported (between 0 and 41%), most studies have focused on anticardiolipin antibodies (aCL) and very little is known about other aPL in this disease. We determined the prevalence and clinical significance of aCL, antibodies to β2-glycoprotein I (anti-β2GPI), and antibodies to phosphatidylserine-prothrombin complex (aPS-PT) in 25 patients with scleroderma (18 with limited and 7 with diffuse scleroderma, as defined by LeRoy et al 1) (table 1). Twenty four patients were female (median age 50 years (range 28–70), median disease duration 3 years (range 1–20)). …

High frequency of inadequate test requests for antiphospholipid antibodies in daily clinical practice

Abstract Background: We have empirically noted that many physicians routinely request anti-phospholipid antibodies (aPL) without a correct clinical indication. The aim of this study was to evaluate retrospectively whether aPL testing at our Thrombosis Centre was justified. Methods: Medical records from 520 subjects for aPL screening tests for various clinical conditions were reviewed. The aPL screening tests were: lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL) and anti-β2 glycoptotein I (aβ2 GPI). Requests for aPL screening were divided into justified, potentially justified or not adequately justified. Results: aPL testing requests were considered justified in 358 (69%) patients, potentially justified in 66 (12.6%) and not adequately justified in 96 (18.4%). LA was positive in 65 (18%) of justified requests and in only one (1%) of the 96 potentially justified requests. None of the 66 not adequately justified for aPL testing was positive for LA. aβ2 GPI was positive in 63 (17.6%) of the 358 justified, in four (6%) of the 66 potentially justified and in five (5.2%) of the 96 not adequately justified requests; aCL IgG were positive in 59 (16.4%) of the 358 justified and in five (7.5%) and six (6.2%) of the potentially justified and not adequately justified requests, respectively. The presence of the triple aPL positivity was found exclusively in the justified requests. Conclusions: This study suggests that requests for aPL tests should be addressed more adequately. This work could be an example of how to focus attention on requests for laboratory tests especially on the basis of valid clinical criteria before the analyte is measured.

Primary antiphospholipid syndrome with mesenteric venous thrombosis presenting with intestinal infarction: a case description

Sir—Antiphospholipid syndrome (APS) is an autoimmune hypercoagulability syndrome in which a wide variety of thromboembolic manifestations may occur. Thrombotic events can involve any arterial or venous vessel, although deep vein thrombosis in the lower limbs is the most frequent manifestation.1 Portal vein thrombosis is infrequent and thrombosis of the portal branches is rare, with only 12 cases reported in literature. We report a 53-year-old woman, who was admitted to the general surgery department complaining of nausea, vomiting and pain in the epigastrium, right hypochondrium and at the base of the homolateral hemithorax. On questioning, past medical history was unremarkable apart from hypertension that was being treated with atenolol 100 mg/day and enalapril 20 mg plus hydrochlorotiazide 12.5 mg/day. On physical examination, her abdomen was tender in the epigastrium and right hypochondrium. Hematochemical tests revealed leukocytosis (WBC 11.500/mm3), while hepatic, renal and coagulation parameters were within normal ranges. Abdominal X-ray was normal, and abdominal colourDoppler sonography and gastroduodenoscopy showed no abnormalities. Seven days after admission, the patient complained of a worsening of abdominal pain. Multiple and small air-fluid levels, particularly in the mid-low right quadrant were revealed by a further abdominal X-ray and portal thrombosis of the spleno-mesenteric axis was shown by colour Doppler sonography. Emergency surgery revealed 30 cm of cyanotic terminal ileum loop at about 60 cm from the ileocaecal valve and a mesenteric venous thrombosis in the corresponding section of the mesentery. Therefore, intestinal resection (about 50 cm), and terminoterminal, entero-enteric anastomosis were performed. Laboratory investigations at the time of the surgery showed erythrocyte sedimentation rate (ESR) 58 mm, international normalized ratio (INR) 1.02 ( 1.2), activated partial thromboplastin time (aPTT) 21 s (18–29 s) and fibrinogen 476 mg/dL (150–450 mg/dL). Rheumatoid factor, antinuclear antibodies, antiextractable nuclear antigens, anti-ds-DNA and anti-neutrophil cytoplasmatic antibodies (ANCA) were all negative. No congenital deficiencies of antithrombin III, protein C and protein S were present. Lupus anticoagulant (LA) was negative. Immunoglobulin M (IgM) anticardiolipin antibodies (aCL) were negative (3.4I U for a normal 5 IU) with positive IgG aCL of 46 IU ( 15). The histology revealed intense oedema of the submucosa and subserous tunica with diffuse haemorrhagic extravasation, diffuse leucocytoclastic vasculitis with scattered signs of recent thrombosis, diffuse dilation of lymphatic vessels and exudation foci. Primary APS (PAPS) was suspected and low molecular weight heparin was started. Two months after the first admission an abdomen echo colour-Doppler sonography showed signs of thrombosis of the mesenteric vein with signs of cavernomatosis, while calibre and flow of the right branch appeared normal. The upper mesenteric vein appeared pervious and normal for calibre and flow, with signs of venous ectasia in the epigastrium from porto-systemic shunts. Positivity for IgG aCL was confirmed with titres present at 40 IU. The diagnosis of PAPS was confirmed and the patient was switched to acenocumarol with a target INR of 2.0–3.0. After three years follow-up the patient was in reasonably good health. aCL were negative for two years and became positive (aCL IgG 40 IU) in the last period, however, in the absence of new symptoms and/or signs of APS. Portal vein thrombosis is rare.2 It occurs in association with several conditions that can act as inducing or precipitating factors. It can present as an acute, subacute or chronic manifestation with symptoms of portal hypertension or nonspecific symptoms (i.e., vomiting, abdominal pain and fever). Venae portae thrombosis as a clinical manifestation of APS has been scarcely reported in the literature3–13 and its exact frequency is not known despite a number of reports of APS involving hepatic circulation (i.e., Budd-Chiari syndrome).14 In our case, the thrombosis of the spleno-mesenteric axis presented as an intestinal infarct with a subacute onset in a patient who was otherwise healthy. Previous case reports3,4,12 show a presentation with signs and symptoms of portal hypertension or hepatic infarct. Four patients were affected by an underlying autoimmune disease: three by systemic lupus erythematosus and one by rheumatoid arthritis.

Fatal Cytopenia Induced by Low-Dose Methotrexate in Elderly With Rheumatoid Arthritis. Identification of Risk Factors

To the Editor: Methotrexate (MTX) is the disease-modifying antirheumatic drug (DMARD) most commonly used in the treatment of a variety of inflammatory rheumatological disorders. In the treatment of rheumatoid arthritis (RA), it is recommended as first-line DMARD by the American College of Rheumatology (ACR), alone or in combination with other DMARDs and biological agents. We report the case of a female patient aged 82, diagnosed with RA 3 years before. She was treated with MTX with oral doses of 7.5 mg/wk, together with weekly folinic acid. The patient came to the emergency room for lethargy. Physical examination disclosed the following: temperature 38.4°C, blood pressure 80/50 mm Hg, and heart rate 132 bpm. The laboratory data showed the following: hemoglobin 7.5 g/dL, white blood cells (WBC) 600/mm3, neutrophils 200/mm3, platelets 4000/mm3, creatinine 3.9 mg/dL, and total bilirubin 6.70 mg/dL. Chest computer tomography (CT) revealed diffuse areas of ground-glass opacities and bilateral pleural effusion. Microbiological studies were negative (cultures of blood, pleural fluid, sputum, and urine). The patient was admitted to the Intensive Care Unit (ICU) for clinical pulmonary sepsis and severe pancytopenia. The problem was interpreted as toxicity secondary to MTX. She was treated with broad-spectrum antibiotics, hydration, granulocyte colony-stimulating factor, and IV methylprednisolone. She received transfusions of packed red blood cells and platelets. The patient died after 2 days. In patients with RA treated with MTX, the prevalence of hematologic toxicity is estimated at 3%. The mortality of severe MTX-induced pancytopenia is unknown. We searched in PubMed to identify articles published during the last 11 years (2005–2016) dealing with MTX associated to severe pancytopenia in patients with rheumatic diseases to assess risk factors of poor prognosis. We have identified a total of 94 patients in whom pancytopenia due to MTX was reported. The mortality was found to be 25%. After having added the patient described here, we looked for a relationship between pancytopenia and mortality and several variables (Table 1) by a multivariate logistic regression, calculating the odds ratio and 95% confidence intervals. Results show that sepsis was significantly associated to mortality, but the interaction with albumin reached a much more significant relationship (Table 1). The other variables showed only a trend probably because of the small sample size. We conclude that if a relationship between mortality and sepsis is to be expected, hypoalbuminemia may be an early and helpful marker in predicting a poor outcome in MTX-induced cytopenia especially when other critical conditions are present.

The venous thromboembolic risk and the clot wave analysis: a useful relationship?

Abstract Background: Hospitalized patients with acute medical conditions have higher venous thromboembolism (VTE) risk. A patient with a final Padua Prediction Score (PPS) of ≥4 is considered to be at high risk for VTE. The aim of this study was to investigate on a possible relationship between PPS, the dynamics of the clot formation, i.e. the clot waveform analysis (CWA) of aPTT, fibrinogen and D-Dimer in a large group of medical patients. Methods: CWA in terms of velocity (first derivative), acceleration (second derivative), density (Delta) of aPTT, fibrinogen, D-Dimer and PPS for VTE were determined in 801 medical patients divided in three groups (without antithrombotic prophylaxis and high PPS, without antithrombotic prophylaxis and low PPS, with antithrombotic prophylaxis and high PPS) and a group of healthy subjects. Results: CWA, fibrinogen and D-Dimer values were higher in the medical patients with high PPS with or without antithrombotic prophylaxis when compared with patients without antithrombotic prophylaxis with low PPS and healthy subjects. The second derivative, fibrinogen and D-Dimer were significantly associated with a high PPS score (≥4): odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.03–2.28; OR = 1.91, 95% CI = 1.3–2.79; OR = 3.16, 95% CI = 2.29–4.36, respectively. Interactions between first derivative and D-Dimer (OR = 2.14, 95% CI = 1.23–3.72) and first derivative and fibrinogen (OR = 1.75, 95% CI = 1.02–2.98) were found. Conclusions: CWA could give useful information to recognize a hypercoagulable state in patients admitted to a medical ward with high and low PPS. First and second derivative aPTT, D-Dimer and fibrinogen levels could be added to PPS to better assess the global thromboembolic risk of these patients.

Dabigatran overdose: a case report of acute hepatitis. Extracorporeal treatment

Dabigatran is an oral, direct thrombin inhibitor approved by international regulatory agencies for stroke prevention in patients with paroxysmal or persistent non-rheumatic atrial fibrillation (AF). The benefits of dabigatran are widely described, but its use in the geriatric population is not without risk. Chronic kidney disease is a common comorbidity with AF, and thus frequent checks of renal function in elderly patients are recommended. We report a case of dabigatran intoxication in an elderly man affected by heart failure and worsening renal function, who developed acute hepatitis and coma, which was successfully treated with continuous veno-venous hemodiafiltration. Although extracorporeal therapy has been suggested as a strategy for clearing dabigatran during acute bleeding, this approach may be useful in other dabigatran-related, life-threatening conditions, such as that described in this report.

A retrospective cohort study of patients with pulmonary embolism: the impact of comorbidities on patient's outcome.

Despite considerable advances in diagnosis and treatment, pulmonary embolism (PE) remains is an important clinical entity with a high risk of death. Due to pulmonary bed obstruction, PE can result in acute right ventricular failure, a life-threatening condition. Possible protective effect against mortality from pulmonary embolism may relate to concomitant DVT and hypertension http://ow.ly/4nfs7v

Plasmapheresis for Preventing Complication of Hypertriglyceridemia: A Case Report and Review of Literature.

Severe hypertriglyceridemia is a common indication for the need of plasma exchange in treatment of hypertriglyceridemic-induced pancreatitis when normal therapies fail to garner a response. Application of plasmapheresis to prevent complication of hypertriglyceridemia is limited because of its cost and availability. We present a case of a 44-year-old man with metabolic syndrome and a medical history of secondary polycythemia in obesity hypoventilation syndrome, whose laboratory tests revealed a triglycerides value of 3965 mg/dL. To prevent the complication of pancreatitis due to hypertriglyceridemia, we performed plasma exchange 3 times when conventional treatments did not sufficiently reduce the high level of triglycerides. A review of the current available literature was therefore conducted to provide an overview of the present data on apheretic treatment for patients with severe hypertriglyceridemia. Several case reports and case series have used plasmapheresis in acute treatment of hypertriglyceridemia pancreatitis related. In our case, the choice of plasmapheresis was applied in prevention of possible complications of hypertriglyceridemia.

Thromboembolic disease in patients with rheumatoid arthritis undergoing joint arthroplasty: Update on prophylaxes.

The risk of venous thromboembolism (VTE) in rheumatoid arthritis (RA) and the higher incidence of RA patients undergoing major orthopedic surgery is well recognized. The objective of the present study is to describe the incidence of VTE and discuss the correct prophylaxis in RA patients undergoing knee or hip replacement. A systematic review of studies on thromboprophylaxis in RA patients undergoing major orthopedic surgery was performed. Detailed information was extracted to calculate the rate of VTE in RA orthopedic patients and analyze the thromboprophylaxis performed and bleeding complications. Eight articles were eligible for full review. No difference in the overall rate of VTE was observed between RA patients and controls. No significant differences were found in RA patients in terms of bleeding complications. The data on the optimal prophylaxis to be used in RA patients were insufficient to recommend any of the several options available. In the absence of dedicated guidelines for the care of RA patients undergoing orthopedic surgery, management must be individualized to obtain favorable patient outcome, weighing up all the factors that might put the patient at risk for higher bleeding and thrombotic events.