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Introduction Retinal vein occlusion (RVO) is a common cause of unilateral visual loss. Evidence based treatment recommendations for patients with RVO cannot be made because of the lack of adequate clinical trials. To compare the efficacy and safety of aspirin and of a low molecular weight heparin, parnaparin, in the treatment of RVO. Materials and Methods In a multicenter, randomized, double blind, controlled trial eligible patients with a delay between symptoms onset and objective diagnosis of less than 15 days were randomized to aspirin 100 mg/day for 3 months or to a fixed daily dose of parnaparin, 12.800 IU for 7 days followed by 6.400 IU for a total of 3 months. Primary end-point of the study was the incidence of functional worsening of the eye with RVO at 6 months, as assessed by fluorescein angiography, visual acuity, and visual field. Study end-points were adjudicated by an independent committee. Results Sixty-seven patients were enrolled in the study and 58 of them (28 treated with parnaparin, 30 with aspirin) were evaluable for the analysis. Baseline characteristics were well balanced between groups. Functional worsening was adjudicated in 20.7% of patients treated with parnaparin and in 59.4% of patients treated with ASA (p = 0.002). Recurrent RVO was diagnosed in 3 patients, all treated with ASA (p = n.s.). Bleeding rates were similar between the two groups. Conclusions Parnaparin appears to be more effective than aspirin in preventing functional worsening in patients with RVO. The results of this study need to be confirmed in a larger clinical trial. Trial registration number: Clinical trials.gov NCT00732927.

Bleeding is the main complication of oral anticoagulant therapy, and one in five bleeding events occur in patients who are not excessively anticoagulated (1). The most common site of clinically important bleeding is the gastrointestinal tract, especially from peptic ulcers (2). There is unequivocal evidence that Helicobacter pylori is the most important risk factor for peptic ulcer disease, as well as for chronic gastritis (3) and gastric cancer (4). Therefore, we performed a prospective study in anticoagulated patients who had mild or no symptoms of dyspepsia to investigate the prevalence of H. pylori infection, the frequency of H. pylori–associated disease as identified by endoscopy, and the safety of eradication therapy.

The lymph node sentinel method is today used for staging the axillary lymph node stations. Ultrasonography is widely available and inexpensive method to study axillary status.One hundred fourteen patients were studied consecutively using axillary ultrasonography and ultrasound guided fine needle aspiration of the lymph node. We used ATL Ultramark 9 with 5-7.5 MHz multiple frequency linear probe or Aloka SSDD-1400 with 7.5 MHz linear probe.One hundred fourteen patients were examined; six were excluded because of definitive histological diagnosis of non-infiltrating carcinoma. 106 had monofocal carcinomas, 2 had bifocal carcinoma in 104/108 ultrasonography was carried out successfully. The axillary cytological examination was positive in 18 cases (17.3%) who were subjected to axillary examination. 86 patients were subjected to sentinel lymph node biopsy: positive 13 cases (6 micrometastases). 31 cases/104 (29.8%) showed positive axilla. Sensitivity of ultrasonography was 58%, 100%specificity. Predictive positive value 100%, Negative value 84.9% for an accuracy of 87.5%.Ultrasonography is useful in all cases eligible to sentinel lymph node examination; the minimum cost of the procedure and of the human resources is amply rewarded by the direct indication for surgical axillary dissection in case of a positive result (17.3% in our experience).

The treatment of venous thromboembolism (VTE) in cancer patients remains controversial.The Italian Society for Thrombosis and Haemostasis (SISET) commissioned a project to develop clinical practice guidelines for the therapy of VTE in patients with malignancies.Key questions about the treatment of VTE in patients with malignancies were formulated by a multidisciplinary working group consisting of experts in clinical medicine and research. After a systematic review and discussion of the literature, recommendations were formulated and graded according to the supporting evidence. For those questions for which the literature search did not yield any definitive answer (absence of evidence evidence of low quality, and contradictory evidence), a formal consensus method was used to issue clinical recommendations.The results of the available literature on VTE treatment in cancer patients were reviewed and clinical recommendations were drafted.We describe the results of a systematic literature review and an explicit approach to consensus techniques which resulted in recommendations for the key therapeutic issues in cancer patients with VTE.

BACKGROUND The optimal duration of oral anticoagulant therapy in patients with deep venous thrombosis (DVT) of the lower extremities remains uncertain. OBJECTIVE To assess whether tailoring the duration of anticoagulation on the basis of the persistence of residual thrombi on ultrasonography reduces the rate of recurrent venous thromboembolism (VTE) compared with the administration of conventional fixed-duration treatment in adults with proximal DVT. DESIGN Parallel, randomized trial from 1999 to 2006. Trained physicians who assessed outcomes were blinded to patient assignment status, but patients and providers were not. SETTING 9 university or hospital centers in Italy. PATIENTS 538 consecutive outpatients with a first episode of acute proximal DVT at completion of an uneventful 3-month period of anticoagulation. INTERVENTION Patients were randomly assigned (stratified by center and secondary vs. unprovoked DVT by using a computer-generated list that was accessible only to a trial nurse) to fixed-duration anticoagulation (no further anticoagulation for secondary thrombosis and an extra 3 months for unprovoked thrombosis) or flexible-duration, ultrasonography-guided anticoagulation (no further anticoagulation in patients with recanalized veins and continued anticoagulation in all other patients for up to 9 months for secondary DVT and up to 21 months for unprovoked thrombosis). For the primary outcome assessment, 530 patients completed the trial. MEASUREMENTS The rate of confirmed recurrent VTE during 33 months of follow-up. RESULTS Overall, 46 (17.2%) of 268 patients allocated to fixed-duration anticoagulation and 32 (11.9%) of 270 patients allocated to flexible-duration anticoagulation developed recurrent VTE (adjusted hazard ratio [HR], 0.64 [95% CI, 0.39 to 0.99]). For patients with unprovoked DVT, the adjusted HR was 0.61 (CI, 0.36 to 1.02) and 0.81 (CI, 0.32 to 2.06) for those with secondary DVT. Major bleeding occurred in 2 (0.7%) patients in the fixed-duration group and 4 (1.5%) patients in the flexible-duration group (P = 0.67). LIMITATIONS The trial lacked a double-blind design. The sample size was not powered to detect differences in bleeding between groups and to detect effectiveness of the intervention in the subgroups of patients with unprovoked and secondary DVT. Patients with previous thromboembolism, permanent risk factors for thrombosis, and thrombophilic abnormalities other than factor V Leiden and prothrombin mutation were excluded. CONCLUSION Tailoring the duration of anticoagulation on the basis of ultrasonography findings reduces the rate of recurrent VTE in adults with proximal DVT. PRIMARY FUNDING SOURCE None.

Summary. Background: In patients with venous thromboembolism (VTE), 15–20% will have prevalent cancer when VTE is diagnosed but little is known about such patients’ long-term risk, time course and predictors of new cancer. Patients and methods: We studied an inception cohort of patients with a first VTE who were not diagnosed with cancer within 3 months after VTE and who had follow-up for up to 120 months. We determined the annual risk for a new cancer [number of events and 95% confidence interval (CI)] per 100 person-years in all patients and in those with unprovoked VTE and identified predictors for new cancer. Results: We studied 1852 patients with VTE who received anticoagulant therapy for 12 months (mean) and were followed for 4.2 years (mean). During follow-up, there were 105 (5.7%) patients diagnosed with new cancer during the period after the initial 3 months from diagnosis, for an annual risk of 1.32 (CI, 1.09–1.60) per 100 person-years. The risk for new cancer appeared uniform over time. The annual risk for new cancer was more than 2-fold higher in patients presenting with unprovoked compared with those with provoked VTE [1.76 (CI, 1.39–2.20) vs. 0.83 (CI, 0.58–1.16) per 100 person-years; P

Among antiphospholipid antibodies, Lupus Anticoagulant (LAC) is recognized as the strongest risk factor for thromboembolic events or pregnancy morbidity.1 The presence of LAC in a subject with previously documented thromboembolism or a significant history of pregnancy loss defines the Antiphospholipid Syndrome (APS). Some patients, however, are diagnosed with LAC without ever having experienced previous vascular thrombosis or pregnancy morbidity. The antiphospholipid antibody profiles of LAC positive patients with or without associated clinical features of APS have been evaluated by us in a multicenter study. Centers affiliated with Italian Federation of Thrombosis Centers (FCSA) were invited to identify consecutive LAC positive patients diagnosed over a 1-year period. Three hundred twenty-one recruited patients were contacted and after giving informed consent they underwent testing for LAC after at least 12 weeks from the first one using routine laboratory procedures. LAC was not confirmed by Thrombosis Centers in 19 patients (6 were …

Summary. Objective: To determine whether the diagnosis of lupus anticoagulant (LAC) in a large cohort of positive patients was confirmed at a reference laboratory. Methods: Over a 1-year period, each participating center collected samples from LAC-positive patients. Plasma was filtered and kept deep-frozen until it was sent on dry ice to the reference laboratory by express courier. Centers returned detailed laboratory information and clinical data from each patient. The reference laboratory screened plasma samples by diluted Russell viper venom time (dRVVT) and kaolin clotting time (KCT). When these were prolonged, 1:1 mixing studies were carried out, and confirmatory tests were performed as appropriate. Positive samples were further tested by thrombin time (TT). The presence of heparin was checked by measuring antifactor Xa activity when TT was prolonged. Negative samples were tested by activated partial thromboplastin time using hexagonal phospholipids. Results: Plasma samples from 302 patients from 29 anticoagulation clinics were analyzed. LAC was excluded in 71 samples (24%), because dRVVT and KCT screening test results were normal (34) or reversed to normal by mixing studies (35). The remaining two samples were considered negative because they contained heparin. LAC-negative patients showed different characteristics from those in whom diagnosis was confirmed. They were significantly older (49.7 vs. 45.0 years, P

BACKGROUND The long-term risk for fatal pulmonary embolism (PE) after treatment of venous thromboembolism (VTE) may be an important factor in the decision to discontinue this treatment. OBJECTIVE To provide reliable and precise estimates of the annual risk for fatal PE and the case-fatality rate of disease recurrence and to assess these outcomes according to the initial presentation of VTE (deep venous thrombosis [DVT], PE, or both) and its etiology (secondary or idiopathic) in patients who have discontinued anticoagulant therapy. DESIGN Prospective cohort study. SETTING Academic medical centers. PATIENTS Inception cohort of patients with a first episode of symptomatic VTE who discontinued anticoagulant therapy. MEASUREMENTS Incidence rates of any fatal PE (which included sudden death from possible fatal PE) and definite or probable PE per 100 person-years of follow-up and case-fatality rate of recurrent VTE. RESULTS Of 2052 patients studied, 1450 had DVT, 310 had PE, and 292 had DVT and PE. The mean duration of previous anticoagulant therapy was 6 months (range, 3 to 39 months), and the mean duration of follow-up after discontinuation of treatment was 54 months (range, 1 to 120 months). The annual risk for any fatal PE and definite or probable fatal PE after discontinuation of anticoagulation was 0.49 events (95% CI, 0.36 to 0.64 events) per 100 person-years and 0.19 events (CI, 0.12 to 0.30 events) per 100 person-years, respectively. The case-fatality rate of recurrent disease was 9.0% (CI, 6.8% to 11.8%) for any fatal PE and 3.8% (CI, 2.4% to 5.9%) for definite or probable fatal PE. LIMITATION The findings are less pertinent to patients with active cancer, permanent immobility, or high-risk thrombophilia. CONCLUSION The risk for fatal PE is 0.19 to 0.49 events per 100 person-years for patients who have finished a course of anticoagulant therapy for a first episode of symptomatic VTE. The case-fatality rate for death from recurrent PE is 4% to 9%. This information helps to inform patient prognosis and may assist clinicians in deciding whether to discontinue anticoagulant therapy for VTE.

Percutaneous endoscopic gastrostomy (PEG) is a practical and safe option to place an alimentary gastrostomy. We observed that a relevant rate of complications are related to management of PEG.We registered the patients treated in our Unit from September 1994 to December 2005. We placed 293 PEG (243 pts). Preferably using a tube 16 Fr, in 7 cases 18 Fr, in 21 cases 20 Fr and only in 3 cases 9 Fr. The median age was 69.8 years; ratio female:male 3:1. In 67 cases the treatment was carried out in not hospitalized patients.The incidence of late and early complications is statistically higher in hospitalized patients than at home.We think that a correct management of PEG (nurses correct information) and the experience of endoscopist and a dietician can significantly reduce the rate of complications.

Background: Intracranial haemorrhage (ICH) is the type of stroke associated with the highest death rate, and about 30% of ICH occurs in patients on antithrombotic treatment. This study relates clinical presentations and outcome of ICH patients on oral anticoagulant (OA) or antiplatelet (AP) therapy admitted to 33 Italian emergency departments (ED). Methods: Consecutive patients were enrolled after cranial computed tomography (CT). Primary outcome was the Modified Rankin Scale (MRS) score at 3 months of follow-up. Common descriptive statistics were computed after stratification for traumatic or spontaneous ICH and identification of the anatomical location of bleeding. Multivariate logistic regression was used to assess predictors of death. Results: We recruited 434 patients on AP therapy and 232 on OA. There were 432 spontaneous and 234 traumatic ICH patients. The proportions of AP and OA patients undergoing neurosurgery were 21.8and 19.4%, respectively, while Conclusion: This study confirms the high prevalence of death or disability in OA and AP patients with ICH. As far as the determinants of mortality and disability are concerned, the results of this study might be useful in the clinical management and allocation of resources in the ED setting. The observed low use of procoagulant therapy highlights the need for ED educational programmes to heighten the awareness of available and effective haemostatic treatments.

1928–30. Summary. Background: Recently, we reported an association between asymptomatic carotid atherosclerosis and venous thromboembolism (VTE) of unknown origin. We hypothesized that patients with VTE of unknown origin would be at a higher risk of developing symptomatic atherosclerosis than patients with VTE induced by known risk factors. Methods: To examine this hypothesis, we studied 1919 consecutive patients followed prospectively after their first VTE episode. The primary outcome was non-fatal and fatal symptomatic atherosclerotic disease in patients with VTE of unknown origin as compared to those with secondary VTE. An independent committee assessed all study outcomes, and adjusted hazard ratios (HR) were calculated using the Cox’s proportional hazards model. Results: After a median follow-up of 48 and 51 months, respectively, at least one symptomatic atherosclerotic complication was detected in 160 of the 1063 patients (15.1%) with VTE of unknown origin, and in 73 of the 856 (8.5%) with secondary VTE. After adjusting for age and other risk factors of atherosclerosis, the HR for symptomatic atherosclerotic complications in patients with VTE of unknown origin compared to those with secondary VTE was 1.6 (95% confidence intervals; CI: 1.2–2.0). When the analysis was restricted to patients without previous symptomatic atherosclerosis, the HR became 1.7 (95% CI: 1.1–2.4). Conclusions: Patients with VTE of unknown origin have a 60% higher risk of developing symptomatic atherosclerotic disease than do patients with secondary venous thrombosis.

Although spiral computed tomography (CT) is being used increasingly as the first-line imaging procedure in the diagnostic workup of patients with clinically suspected pulmonary embolism (PE), the diagnostic value of negative findings, at least when using the four-detector row scanners, is still controversial. A total of 702 consecutive patients with clinical symptoms suggestive of PE underwent four-slice CT. Patients with negative findings received the determination of D-dimer. Those with positive D-dimer underwent further diagnostic workup to confirm or rule out the diagnosis of PE. Those with negative D-dimer were followed-up to 6 months to detect the development of symptomatic venous thromboembolism (VTE). The CT test was interpreted as negative in 536 patients (76.3%). These patients had the D-dimer determination, which was positive in 279 and negative in the remaining 257 patients. Of the former, PE subsequently was documented in 55 patients (19.7%). Of the latter, symptomatic VTE in the follow-up period developed in three patients (1.17%; 95% confidence interval, 0.24 to 3.38%). In conclusion, when using the four-detector row, the negative predictive value of CT findings in patients with clinically suspected PE and positive D-dimer is low. In contrast, it is safe to withhold anticoagulation from patients with negative findings and negative D-dimer.

Several methods have been developed for measurement of plasma total homocysteine (tHcy), a proven graded risk factor for cardiovascular diseases. The aim of the study was to compare 3 commonly used clinical methods (enzyme immunoassay, Axis Biochemicals, Oslo, Norway; and fluorescence polarization immunoassay [FPIA], Axis, on the Abbott IMx System, Abbott Laboratories, Abbott Park, IL; and BioRad high-performance liquid chromatography [HPLC], Laboratories, Munich, Germany) for tHcy determination in samples from cardiovascular patients also undergoing methionine load measurement. Only HPLC reached the required coefficient of variation (6%) for desirable performance for tHcy concentrations ranging between 0.68 and 5.41 mg/L (5 and 40 micromol/L). A higher variability was observed for postmethionine load vs fasting samples, which reached statistical significance for FPIA (P = .0013). The closest agreement between methods was observed between HPLC and FPIA for fasting tHcy concentrations (-0.23 mg/L [-1.69 micromol/L], -30% to 8%).Both immunoassays could be suitable alternatives for laboratories with high workloads when HPLC is not available. Differences among tHcy values must be taken into account when these methods will be used interchangeably for diagnosis and monitoring of treatment.

Anticoagulant (AC) and antiplatelet (AP) drugs are effectively used in the prevention of thromboembolic events, with the trade-off of bleeding side effects, particularly intracranial. The aim of this study was to determine the incidence of intracranial bleeding in the population of Reggio Emilia and to investigate the potential effect of AC and AP drugs.We reviewed all the patients admitted for cerebral hemorrhages to our hospital between April 1998 and September 2000. Data were collected with a standardized form. All the patients were followed-up to estimate long-term mortality. Chi(2) and t-tests were used as appropriate. Logistic regression analysis was performed to test predictors of mortality. Pharmaceutical department data were employed to estimate the total number of patients receiving AC and AP drugs.We found 241 cases (107/134 female/male, mean age 61 years, 133/107 spontaneous/traumatic events, 0.32/1,000/year overall). Twenty-nine and 47 of these patients were being given AC or AP drugs, respectively (4.9/1,000/year and 3.7/1,000/year). The relative risk of intracranial bleeding was 11.5 in AP and 15.3 in AC treated patients. Two patients (one underwent neurosurgery and one thrombolytic treatment) were excluded from mortality and risk factors analysis. Six patients were lost from follow-up and excluded from mortality analysis. Overall mortality was 100/233 (42.9%); mortality in traumatic events was 25/103 (24.2%) versus 75/130 (57.7%) in spontaneous events. Mortality was 19/29 (65.5%), 26/47 (55.3%) and 55/157 (35%) in AC recipients, AP recipients, and untreated patients, respectively. This increased risk was mainly confined to traumatic events (p = 0.06), without difference between AC and AP recipients. At the time of the event, the mean duration of oral AC treatment was 26.3 months (range 1-120). Mean INR was = 3.1 (range 1.6-8.8). Mortality was significantly predicted by the Glasgow Coma Scale Score (GCS) at admission (p0.0001), by the type of bleeding (spontaneous versus traumatic) (p = 0.0026), and by age (p0.0001).Careful selection of patients and prevention of traumatic events are the main candidate mechanisms to reduce intracranial bleeding in patients being treated with AC and AP drugs.

Evidence of a dark halo on ultrasonography has been considered a specific sign of giant-cell arteritis and may replace temporal artery biopsy for the diagnosis of giant-cell arteritis in patients with typical clinical manifestations.To assess the usefulness of temporal artery duplex ultrasonography and to compare this mode of ultrasonography with physical examination of temporal arteries for the diagnosis of giant-cell arteritis in patients with suspected giant-cell arteritis or polymyalgia rheumatica.Diagnostic test study.Several divisions of Reggio Emilia Hospital, Reggio Emilia, Italy.86 consecutive patients with a suspected diagnosis of giant-cell arteritis or polymyalgia rheumatica identified over a 22-month period.The temporal arteries were examined in all 86 patients. Duplex ultrasonography of the temporal arteries was then performed by two ultrasonographers who were unaware of the clinical diagnosis. Before corticosteroid therapy was started, temporal artery biopsies were performed in all patients at the site targeted by the ultrasonographer.A hypoechoic halo around the lumen of the temporal arteries had a sensitivity of only 40% (95% CI, 16% to 68%) and a specificity of 79% (CI, 68% to 88%) for the diagnosis of biopsy-proven giant-cell arteritis. The negative likelihood ratio was 0.8 (CI, 0.5 to 1.2), and the positive likelihood ratio was 1.9 (CI, 0.9 to 4.1). When the thickness of the halo was at least 1 mm, specificity increased to 93% (CI, 84% to 98%) and the positive likelihood ratio increased to 5.7 (CI, 2.0 to 16.2); however, sensitivity remained low at 40% (CI, 16% to 68%). On physical examination, temporal artery abnormalities had a higher sensitivity of 67% (CI, 38% to 88%), a higher specificity of 99% (CI, 92% to 100%), and a higher positive likelihood ratio of 47.3 (CI, 6.5 to 342.4) than did ultrasonographic findings. None of the patients with giant-cell arteritis had a normal temporal artery inspection and a hypoechoic halo on ultrasonography.Evidence on ultrasonography of a halo around temporal arteries, either any halo or a halo 1 mm or greater in thickness, only modestly increased the probability of biopsy-proven giant-cell arteritis but did not improve the diagnostic accuracy of a careful physical examination.

Antiphospholipid antibodies are a heterogeneous family of immunoglobulins that includes lupus anticoagulant and anticardiolipin antibodies. They are strongly associated with a clinical syndrome characterized by venous and arterial thrombosis and spontaneous fetal losses. This syndrome may be primary or else secondary to autoimmune or neoplastic diseases. The cardiovascular system is frequently involved with mitral or aortic insufficiency, juvenile myocardial infarction, and primitive pulmonary hypertension. However, the occurrence of intracardiac thrombi is rare. We describe a case of an intracardiac right atrial thrombus in a 19-year-old asymptomatic woman who was admitted in December 1998 to the Thrombosis Center owing to the finding, during routine work-up, of a prolonged activated partial thromboplastin time (71 s) and thrombocytopenia (71 x 1000/mm3), a positive antinuclear antibody test (1/320), positivity for lupus anticoagulant, and increased IgG (92 GPL-U/ml) and IgM (27 MPL-U/ml) anticardiolipin antibodies. Six months later, the patient presented with headache, edema and cyanosis of the face and jugular swelling. Transthoracic and transesophageal echocardiography revealed a right atrial mass which was clearly distinguishable from the tricuspid valve and extended to the superior vena cava. The patient was successfully submitted to surgical excision of the thrombus. Histology revealed that the mass was adherent to an abnormal septum consisting of mesenchymal tissue. Although the American Rheumatology Association criteria for the diagnosis of systemic lupus erythematosus were not fulfilled, the positivity of antinuclear antibody test is in favor of a lupus-like syndrome. The decision to opt for surgical excision of the thrombus was determined by the unclear nature of the atrial mass. It may be necessary that such patients be submitted to anticoagulant therapy for the rest of their lives or temporarily (6-12 months). This underscores the importance of the anatomical abnormality as a promoting factor. Transthoracic echocardiography (as well as transesophageal echocardiography in selected cases) must be considered as an essential component of the initial diagnostic work-up in patients presenting with antiphospholipid antibodies.