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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.

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.

Enoxaparin is the most frequently used low-molecular weight heparin in the world, given in order to prevent venous thromboembolism (VTE) in patients undergoing major orthopaedic surgery (MOS). Fondaparinux is an effective and safe alternative. The aim of our study was to compare the cost-effectiveness of enoxaparin and fondaparinux in the extended thromboprophylaxis of patients undergoing MOS in Italy. A decision-tree model was developed: probabilities of symptomatic events were derived from the published trials; use of resources in Italy was evaluated by means of a questionnaire administered to a panel of experts. Only the direct costs of VTE (acute treatment of events and of complications) were considered. Cost units were derived from the current cost of drugs, and from the Italian National Healthcare tariffs in 2007. Incremental cost-effectiveness ratios were analysed at three time points: 30 days, 1 year and 5 years. The higher cost of fondaparinux was counterbalanced by reduced rates of early DVT, early PE and prophylaxis-related major bleeding. If compared with enoxaparin, after 30 days of extended prophylaxis, fondaparinux is associated with a savings ofeuro48.83 per patient; at the end of the first year, the savings increased toeuro72.13, and after 5 years, the savings areeuro74.36. One-way sensitivity analysis shows that the results are robust to the variation in unit costs for VTE-related care, or in event rates for both treatments. In conclusion, our model shows that, when administered for extended prophylaxis of VTE following MOS, fondaparinux is more effective and cost saving than enoxaparin.

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.

A current goal of the Italian Society for Thrombosis and Haemostasis (SISET) is the production of guidelines for clinical conditions related to haemostasis and thrombosis. In 2006, the Executive Committee of SISET adopted a new program for the production of methodologically and scientifically sound guidelines aimed at both addressing clinical practice and stimulating new research. The first major step for this program was to train methodologists to manage working groups that compose the guidelines, and to create a reference document that describes the development of the program. The aim of the present paper is to report a short version of this methodological document, for those who wish to follow SISET guidelines. We start by giving a brief outline of the SISET mission, then present the SISET guideline development process, which includes: project funding, selection of guidelines topics, multidisciplinary group composition, definition of clinical questions, literature search, evidence appraisal, grading recommendations, guideline implementation, external peer review, and guideline updating.

Many studies showed that the occurrence of cardiovascular and cerebrovascular events exhibits a seasonal variation. As for venous thromboembolism (VTE), not univocal results are available, and studies are mainly retrospective. We aimed to confirm the existence of a seasonal pattern in the occurrence of VTE on a large prospective population. The analysis considered consecutive cases of VTE enrolled into the MASTER Registry in 25 Italian hospitals, between January 2002 and November 2004. The total population consisted of 2119 subjects (1056 men, mean age 59 ± 18 years). The total sample was divided into subgroups by gender, age (2test for goodness of fit and chronobiological analysis. VTE was most frequent in Autumn and less frequent in Spring (32.9% vs 19%, respectively, χ2= 90.62; P < .001). This pattern was shown for most subgroups. Chronobiological analysis identified a significant rhythmic annual pattern, with a main September—October peak for several subgroups (men, age 41—60 and 61—80 years, secondary event, previous VTE, immobilization), and a trend for most of the others. It is possible that subjects at increased risk could perhaps deserve appropriate or potentiated VTE prophylaxis in certain periods of the year.

Oral anticoagulant therapy with coumarins is widelyused for the prevention and treatment of venous andarterial thrombosis. The most common complication ofvitamin K antagonist therapy is bleeding, with majorbleeding events occurring in 1–3% of patients annually.Although a number of potential predictors for bleedinghave been described, little research is available to pro-vide evidence-based guidelines for the prevention ofbleeding. To address this knowledge gap, we assembleda panel of international experts and posed a series offocused clinical questions. The experts were asked toperform a systematic literature review and summarize theresults of that review within the context of their clinicalquestion. In many cases, data were lacking and theexperts were asked to supplement their answer with clin-ical expertise. To minimize bias the reviews were vettedby three internationally recognized scholarly bodies. Ourgoal in this project is to provide ‘‘best evidence’’ forclinicians faced with the problem of minimizing the riskof bleeding in patients on vitamin K antagonist therapy.The number of patients receiving vitamin K antagonisttherapy increases annually and probably exceeds three mil-lion in the United States. Despite monitoring and carefuldose adjustment, the time spent in the therapeutic Interna-tional Normalized Ratio (INR) range varies from below 47%to a maximum of 81% of the time [1]. Major bleedingevents occur in up to 3% of ‘‘standard risk’’ patients treatedwith an oral vitamin K antagonist in one year. Despite thehigh frequency of use of vitamin K antagonists, very littleresearch has been performed examining techniques toreduce the risk of bleeding. In particular, the role of clinicalbleeding prediction rules is uncertain and further study ofthe role of drug and food interactions, the impact of patienteducation, the risk to benefit ratio of combining differentantithrombotic drugs, the role of pharmacogenomic testing,and on the optimal management of patients presentingwith elevated INR values is required. However, despitethese needs clinicians are still required to initiate andmonitor vitamin K antagonists while mitigating the risks ofbleeding and thrombosis. This article provides recommen-dations designed to assist clinicians in estimating andmanaging bleeding risk in patients receiving oral vitamin Kantagonists.Clinical questions were formulated by three of theauthors (WA, MC, DG) and authors were selected basedon their published experience. In each case, a North Ameri-can and Italian expert were asked to co-author theresponse to the question. The authors were asked to per-form a comprehensive literature review and make specificrecommendations on the basis of this review in concertwith their clinical experience. Given the anticipated lack ofevidence, the recommendations are largely opinion-based.To increase the rigor of the recommendations, each sectionwas carefully reviewed by members of the Italian Societyfor Studies on Haemostasis and Thrombosis, the Federa-tion of Centers for the Diagnosis of Thrombosis and Sur-veillance of Antithrombotic Therapies, and the Anticoagula-tion Forum.To provide readers with information on the strength of therecommendations, we have asked the authors to use theAmerican College of Chest Physicians GRADE system toevaluate the quality of the recommendations [2]. In thissystem, grades of 1A, 1B, 1C, 2A, 2B, and 2C are possible.A 1A recommendation is a strong recommendation basedon evidence from randomized trials or exceptional qualityobservational data which is thought to apply to mostpatients, in most circumstances. A 2C recommendation is avery weak recommendation, based on poor quality evi-dence, and for which there is doubt as to which patientsthe recommendation applies. Our goal with this project is toboth provide guidance to clinicians and to stimulate addi-tional research designed to improve the quality of evidenceon which treatments for vitamin K antagonist associatedbleeding are based.Clinical Scenario 1A 79-year-old woman with atrial fibrillation and well-con-trolled hypertension is assessed for anticoagulant therapy.She has no history of diabetes, congestive heart failure,stroke, or transient ischemic attack (TIA). Two years agoshe had an upper gastrointestinal bleed treated with a pro

Approximately 50-75% of patients with venous thromboembolism have a readily identifiable risk factor, either transient or permanent, whereas the remaining episodes are classified as unprovoked. The incidence of first-time venous thromboembolism rises exponentially with age. Whether the prevalence and the relative weight of major risk factors differ between elderly and younger patients is unclear. We performed a multicenter, prospective, observational study on consecutive patients with objectively confirmed acute venous thromboembolism admitted to 25 Italian hospitals. Baseline characteristics and information on temporary and permanent risk factors at the time of the index event were secured by an electronic data network. We enrolled 2119 patients (49.8% men), of whom 440 (20%) were more than 75 years of age and 1679 (79.2%) 75 years of age or less. Elderly patients were more likely to have pulmonary embolism at presentation (33.6 and 25.6%, respectively, P0.001). After binary logistic regression analysis, we found that the risk of venous thromboembolism in the elderly, compared with the younger age group, was significantly associated with immobilization (odds ratio: 2.46, 95% confidence interval: 1.85-3.27) and with severe medical disorders (odds ratio: 1.99, 95% confidence interval: 1.41-2.80), whereas male sex (odds ratio: 0.53, 95% confidence interval: 0.42-0.66), surgery (odds ratio: 0.61, 95% confidence interval: 0.43-0.85), and trauma (odds ratio: 0.49, 95% confidence interval: 0.31-0.77) were less common risk factors in the elderly than in younger patients. Use of thromboprophylaxis prior to the index event was not different between the two age groups. Severe medical disorders and immobilization are strongly associated with the occurrence of venous thromboembolism in the elderly. Our findings stress the need for adequate thromboprophylaxis in this setting.

Several epidemiological studies have shown a high prevalence of venous thromboembolism (VTE) complications in patients with acute heart failure; in addition, the level of risk associated with this disease is notable, ranging from 15 to 30%. Three large clinical trials have clearly demonstrated the efficacy and safety of pharmacological prophylaxis in internal medicine patients hospitalized for an acute medical disease; on the contrary, until now there are no studies which have evaluated antithrombotic prophylaxis in a selected population of patients with heart failure only. Moreover, discrepancies existing among recommendations reported in different guidelines may produce uncertainties in the management of VTE prevention in patients with heart failure and may contribute to an underuse of thromboprophylaxis in the daily clinical practice. The aim of this review is to analyze the existing evidence about VTE risk in patients with heart failure as well as the efficacy and safety of antithrombotic prevention, and to underline which are the most important unmet clinical issues for the optimal management of thromboprophylaxis in this particular clinical setting.

The close correlation between venous thromboembolism (VTE) and cancer has been known for some time, and numerous reports in the literature have highlighted the epidemiological significance. Moreover, VTE has a substantial impact on morbidity and mortality in oncological patients. The prevention and treatment of VTE are important aspects of the clinical management of patients with cancer. The presence of a tumour is often associated with thrombotic complications that are more difficult to diagnose, and sometimes make the treatment of VTE less effective and more likely to cause haemorrhages.

Purpose of review To examine the current literature regarding retrievable inferior vena cava filters and to discuss the appropriate indications for their clinical use. Recent findings Permanent filters have been shown to be effective, but have a number of long-term complications such as filter thrombosis or migration. Indications for their placement should be accurately evaluated, especially in patients with a long life expectancy, or in whom the period of contraindication to anticoagulation is short. On the other hand, temporary filters are difficult to manage and their maximum implantation time is often insufficient to solve the clinical problem leading to their placement. Four different retrievable filters recently received approval for temporary insertion. Recent data suggest that the use of these filters may be related to a low rate of pulmonary embolism and insertion complications. Nevertheless, no randomized clinical trials have been performed, and the only available data refer to retrospective or prospective studies. Summary Retrievable filters are a new generation of filter that offers the attractive possibility of being left in place permanently or being removed after quite a long period when they become unnecessary.

Purpose of review To summarize currently available literature regarding indications for inferior vena cava filters, potential problems associated with the different filters available, and the efficacy and safety of retrievable inferior vena cava filters. Recent findings The placement of permanent filters may present a number of long-term complications such as filter occlusion and an increased risk of recurrent deep vein thrombosis. Furthermore, patients who require inferior vena cava interruption often have short-term contraindications to anticoagulant therapy, and thus only require filters for temporary indications. Four different retrievable filters have recently received approval for temporary insertion, and preliminary data suggest that the use of these filters is associated with a low rate of pulmonary embolism and complications related to filter insertion. Retrieval was uneventful in almost all patients. No randomized clinical trials have yet been performed, and available information is based on the results of either retrospective or prospective cohort studies. Summary Retrievable filters are a very attractive alternative to either permanent or temporary filters when inferior vena cava interruption becomes necessary, thanks to the advantages of very easy management and the possibility of their being left in place for a long time and removed when they become unnecessary.

Venous thromboembolism (VTE) is a common disorder that can affect apparently healthy as well as hospitalized patients. The actual incidence and prevalence of this disease are difficult to estimate because of its often silent nature. The clinical relevance of VTE is highlighted by the important rates of recurrence and mortality. The individual risk of VTE varies as a result of a complex interaction between congenital and transient or permanent acquired risk factors. Risk factors can be either intrinsic (e.g., age, obesity, history of VTE, or thrombophilia) or disease related (e.g., surgical procedures and medical disorders such as cancer, heart failure, or acute respiratory failure). The presence or absence of specific risk factors may play an important role in decisions about the type (and duration) of thromboprophylaxis/anticoagulation to be used.

Venous thromboembolic disease (VTE) is a major cause of morbidity and mortality. Unfractioned heparin, low-molecular weight heparins and vitamin K antagonists, currently used in the prophylaxis and treatment of VTE, are effective and relatively safe. Otherwise, they have some important limitations (narrow therapeutic window, highly variable dose-response relationship; limitation by the need of parenteral administration for heparins and the risk of heparin-induced thrombocytopenia) which provide opportunities for new antithrombotic drugs. These drugs include: inhibitors of factors IXa and factor VIIa/tissue factor complex, agents that enhance the protein C anticoagulant pathway, direct and antithrombin-dependent Xa inhibitors, direct and indirect thrombin inhibitors. Fondaparinux and idraparinux, two new indirect parenteral factor Xa inhibitors, have been studied in well conducted trials, showing interesting results both in the prevention and in the treatment of VTE. Ximelagatran, the first orally available thrombin inhibitor, represents a promising new anticoagulant drug for the prophylaxis of VTE after major orthopedic surgery and for the treatment of deep vein thrombosis.

Purpose The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. Patients and Methods In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. Results Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period. Conclusion In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.

Aims: To evaluate the incidence of cardiovascular events in the tong-term clinical course of patients with a first episode of symptomatic, objectively confirmed pulmonary embolism. Methods and results: Three hundred and sixty patients with a first episode of pulmonary embolism were included in a prospective study: 209 with idiopathic pulmonary embolism and 151 with pulmonary embolism associated with transient risk factors. The study outcomes were cardiovascular events (recurrent venous thrombo-embolism, acute myocardial infarction, stroke, sudden otherwise unexplained death), cardiovascular death, and death due to any cause. The median follow-up was 38 months. Sixty-four patients had at least one cardiovascular event (5.5% patient-year). Recurrent venous thromboembolism occurred in 45 patients (3.9% patient-year), acute myocardial infarction in 12 patients (1.0% patient-year), stroke in six patients (0.5% patient-year), and sudden otherwise unexplained death in four patients (0.3% patient-year). A cardiovascular event occurred in 47 patients with idiopathic pulmonary embolism (7.5% patient-year) and in 17 patients with pulmonary embolism associated with transient risk factors (3.1% patient-year) (RR 2.0; 95% CI 1.20-3.34; P = 0.006). Twenty patients with idiopathic pulmonary embolism (3.2% patient-year) and two patients with pulmonary embolism associated with transient risk factors (0.4% patient-year) presented an arterial cardiovascular event (RR 7.2; 95% CI 1.71-30.45; P = 0.001). Thirty-three patients died (9.2%). Cardiovascular mortality and cancer mortality accounted for 42.4 and 21.2% of overall mortality, respectively. Idiopathic pulmonary embolism was an independent predictor of cardiovascular events after adjusting for age. Conclusions: Cardiovascular events are more common in patients with idiopathic pulmonary embolism than in patients with pulmonary embolism associated with transient risk factors. Cardiovascular events are the major cause of death in patients with idiopathic pulmonary embolism.

Background Venous thromboembolism (VTE) is a quite common complication in acute leukemia, although its real incidence is unknown. The best treatment of this complication is still a matter of debate due to the very high risk of hemorrhage in this group of patients. Patients and methods From December 2000 to December 2002 four Caucasian patients with acute leukemia developed VTE complications. The patients were three men and one woman, mean age 55.7 years (range, 27-77). Two patients with acute lymphoid leukemia (L1 and L2 according to the FAB classification) developed deep venous thrombosis during the administration of chemotherapy; one patient with acute myeloid leukemia (AML, M2 according to the FAB classification) had pulmonary thromboembolism at diagnosis, while another AML patient (M4 according to FAB) showed deep venous thrombosis as the first symptom of leukemia. The clinical diagnosis of symptomatic VTE was confirmed by objective imaging procedures including lower limb venous color Doppler imaging in all cases and a ventilation-perfusion lung scan in one case. All patients were treated with enoxaparin 100 IU/kg subcutaneously twice daily for one month, followed by 150 IU/kg once daily for at least five months. When the platelet count was below 20,000 × 109/L, the dose was reduced by 50%. Results During antithrombotic treatment neither VTE recurrences nor hemorrhagic complications or heparin-induced thrombocytopenia occurred. The platelet count at the beginning of enoxaparin treatment was very low (mean, 55,750 × 109/L; range, 12,000-121,000 × 109/L) and treatment did not affect platelet recovery. Conclusions Enoxaparin proved to be efficacious and safe in the management of deep venous thrombosis with or without pulmonary embolism in patients affected by acute leukemia. Enoxaparin cured acute venous thrombosis, prevented recurrences and did not cause any hemorrhagic complications despite prolonged severe thrombocytopenia.

The optimal duration of oral anticoagulant treatment after a first episode of pulmonary embolism remains uncertain.To evaluate the long-term clinical benefit of extending a 3-month course of oral anticoagulant therapy to 6 months (pulmonary embolism associated with temporary risk factors) or to 1 year (idiopathic pulmonary embolism) in patients with a first episode of pulmonary embolism.Multicenter randomized study with independent, blinded assessment of the outcome events.19 Italian hospitals.326 patients who had had 3 months of oral anticoagulant therapy without experiencing recurrence or bleeding.The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism.Among 165 patients assigned to extended anticoagulant therapy, 15 patients (9.1%) had a recurrence of venous thromboembolism (3.1% per patient-year; average follow-up, 34.9 months), as compared with 18 of 161 patients (11.2%) assigned to discontinue treatment (4.1% per patient-year; average follow-up, 32.7 months); the rate ratio was 0.81 (95% CI, 0.42 to 1.56). All but one of the recurrences occurred after anticoagulant treatment was discontinued. Nineteen recurrences (57.6%) were episodes of pulmonary embolism, two of which were fatal. Three major bleeding episodes were observed during extended anticoagulation (1.8%). Among patients with idiopathic venous thromboembolism, 11 of 90 patients assigned to extended anticoagulation and 11 of 91 patients assigned to discontinue treatment experienced a recurrence (relative risk, 0.99 [CI, 0.45 to 2.16]).Patients with pulmonary embolism have a substantial risk for recurrence after discontinuation of oral anticoagulation, regardless of treatment duration. Physicians should try to identify patients who are at high risk for recurrent venous thromboembolism and are therefore potential candidates for indefinite oral anticoagulant therapy.

SIMI 2008 The use of central venous catheters (CVC) is becoming increasingly frequent in medical and surgical patients, particularly for measurement of hemodynamic variables, administration of drugs, hemoderivatives, total parenteral nutrition and hemodialysis [1]. Unfortunately, the advantages secured by the extensive use of CVCs are associated with an increased risk of upper limb deep vein thrombosis (DVT) [2]. Several genetic and acquired risk factors may increase the risk of development of upper limb DVT in patients with CVC, such as malignancy, infections, thrombophilia, surgery, plaster cast and oral contraceptive use. Moreover, the risk of thrombosis is also dependent on specific characteristics of the catheters (e.g., diameter, material, type and side of insertion, misplacement of the tip). The clinical signs of CVC-related thrombosis include upper extremity DVT, pulmonary embolism (PE), malfunctioning of the CVC, and infection [3]; however, it should be noted that very fre

Anticoagulant prophylaxis for preventing VTE is a worldwide established procedure in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures, but few data exist in other fields of orthopaedics and traumatology. Thus no guidelines or recommendations are available in the literature except for a limited number of weak statements about knee arthroscopy and lower limb fractures. In any case, none of them is a multidisciplinary effort as the one here presented. The Italian Society for Studies on Haemostasis and Thrombosis (SISET), the Italian Society of Orthopaedics and Traumatology (SIOT), the association of Orthopaedic Traumatology of Italian Hospitals (OTODI) together with the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) and the Italian Society of General Medicine (SIMG) have set down easy and quick suggestions for VTE prophylaxis in a number of surgical conditions for which only scarce evidence is available. This inter-society consensus statement aims at simplifying the approach to VTE prophylaxis in the single patient with the goal to foster its clinical application. This statement is therefore addressed to the Italian scientific community and institutions with the aim of attaining good clinical practice in the profession. The present statement will be published in the “Journal of Orthopaedics and Traumatology”,” Lo Scalpello” and in the websites of the Societies participating this consensus (OTODI, SIAARTI, SIMG, SIOT, SISET). It will be submitted to Minerva Anestesiologica.

Abstract 190 Type and duration of anticoagulation is still matter of debate in cancer patients with acute Deep Vein Thrombosis (DVT) of the lower limbs. Residual Vein Thrombosis (RVT) has been proven to be effective for assessing the optimal duration of oral anticoagulants in non cancer patients (Siragusa S et al Blood 2008:112:511-5). In the present study we evaluate the role of a RVT-based management of anticoagulation with Low-Molecular Weight Heparin in cancer patients with acute DVT. Materials and Methods. Patients with active cancer and a first episode of DVT were treated with LMWH for 6 months (the first month at full dosage followed by dose reduction of 25% in the next 5 months). At the end of treatment, they were managed according to RVT findings: those with RVT were randomized to continue anticoagulants for 6 additional months (Group A1) or to stop it (Group A2), while patients without RVT stopped LMWH (Group B). Outcomes were recurrent venous thromboembolism and/or major bleeding; patients were followed up for one year after LMWH discontinuation. Results. Over a period of 36 months, 409 patients were evaluated; 62 were excluded (refusal, need for continuing anticoagulation, etc). In total, 347 were included in the study (Table 1). RVT was detected in 242 (69.7%) patients; recurrent events occurred in 21.9% of those randomized to discontinue and 14.2% of those who continued LMWH. In patients without RVT (105, 30.3%), recurrent events occurred in 3 cases (2.8%) (Table 2 and Figure 1). The adjusted Hazard Ratio (HR) for age and sex between RVT groups (Group A2 vs A1) was 1.58 (95% confidence interval [CI], 0.85–2.93; P=.145). The adjusted HR between group A1 versus RVT-negative group (B) was 4.54 (CI 2.3–6.66; P =.028). Five major bleeding events occurred in Group A1 and two events both in Group A2 and B (Table 2). Overall, 89 (25.6%) patients died due to cancer progression after a median follow-up of 10.2 months after heparin withdrawn. Conclusions. The Cancer DACUS is the first ever study evaluating an individual marker for assessing duration of anticoagulation in active cancer population. Final results of the study show that absence of RVT identifies a group of patients at low risk for recurrent thrombosis who can safely stop LMWH after 6 months. Disclosures: No relevant conflicts of interest to declare.

Abstract 1113 Background: Prothrombin complex concentrates (PCCs) are currently recommended by several international guidelines as the treatment of choice in warfarin-related coagulopathy. However, while the efficacy of PCCs is well established, their safety in terms of risk of thromboembolic complications, some of which may be severe or even life-threatening, is still not clear. Thus, we performed a systematic review of the literature with the aim of evaluating the rate of thromboembolic complications in patients on Vitamin K antagonists (VKAs) treated with PCCs for a bleeding event or before an urgent invasive procedure. Methods: MEDLINE and EMBASE databases were searched up to June 2010. Two reviewers performed study selection independently. Studies providing data on incidence thromboembolic complications in patients on VKAs were potentially eligible for the study. Two reviewers independently extracted data on study and population characteristics, type, dose of PCC treatment. Weighted mean proportion of the rate of thromboembolic complications and the mortality rate were calculated. Results: 28 studies for a total of 1104 patients were included in our systematic review. Seven studies used 3-factor PCCs, 21 studies used 4-factor PCCs. Concomitant vitamin K was administered in 21 studies, while fresh frozen plasma in 6. Seventeen patients had a thromboembolic complication after PCCs administration (weighted mean 1.9%; 95% CI 1.1–2.9 %). Of the thromboembolic events, 4 were fatal (23%). The incidence of thromboembolic events was 1.9%; (95% CI 1.0–3.1 %) in patients treated for bleeding and 0.8% (95% CI 0.1–2.0 %) in patients treated before urgent surgery or invasive procedures. For 5 of the reported events we were unable to define the subgroup. The incidence of thromboembolic events was 2.3% (95% CI 1.2–3.8) in patients treated with 4-factor PCCs, and 0.7% (95% CI 0.0–2.4) in patients treated with 3-factor PCCs. One hundred and seven patients died for a mean mortality rate of 11.1% (95% CI 6.4–17.0 %). Only 7 studies for a total 257 patients provided data on the incidence of viral transmission after PCCs administration. In this subgroup of patients there were 4 episode of positivity for parvovirus B19 for a mean incidence of 1.9% (95% CI 0.3–4.9%). Conclusions: The results of our systematic review of the literature show that the treatment with PCCs in patients on VKAs therapy is associated with a low risk of thromboembolic complications providing important information on the safety of this approach. Moreover, also the risk of viral transmission, although evaluated in few studies only, appears to be negligible. The findings of a low thromboembolic risk have been further confirmed by the results of the subgroup analyses separately evaluating treatment with 3 or 4-factors PCCs and different indications for PCCs therapy. Disclosures: Crowther: Pfizer: Consultancy; Leo Pharma: Research Funding; Boehringer Ingelheim: Research Funding.

OC-01 Prognostic relevance of asymptomatic venous thromboembolism in patients with cancer F. Dentali *, W. Ageno, M. Giorgi Pierfranceschi, D. Imberti, A. Malato, C. Nitti, A. Salvi, S. Siragusa, A. Squizzato, A. Venco, J. Vitale, G. Agnelli. Department of Clinical Medicine, Insubria University, Varese, Emergency Department, Thrombosis Center, Hospital of Piacenza, Department of Hematology, University of Palermo, Clinical Medicine, Hospital of Ancona, Department of Vascular and Internal Medicine, University of Perugia, Italy

BackgroundThe management of acute aortic aneurysm rupture or dissection (AARD) requires specific medical expertise, diagnostic techniques, and therapeutic options, not always available in all hospitals through the entire week. The aim of our study was to evaluate whether an association exists between weekday (WD) or weekend (WE) admission and mortality for patients with ARRD.MethodsBased on the database of routinely collected hospital admissions of the region of Emilia Romagna (RER) of Italy, we examined the discharge sheets of all patients with AARD (January 1999 to December 2009). The risk of in-hospital death was calculated for admissions on the WE compared with the admissions during a WD.ResultsThe analysis considered 4559 events in 4461 patients. AARD admissions were most frequent on Monday (14.7%) and Friday (14.8%) and less frequent on Saturday (12.6%). The percentage of events admitted on Sunday/holiday was 15.0%, whereas the distribution of death rate with respect to day of admission was significantly different (χ2 = 23.472; P < .001) with the highest frequency peak on Sunday/holiday (17.4%) and the lowest on Tuesday (12.9%). WE admissions were associated with significantly higher in-hospital mortality (43.4%) than WD admissions (36.9%, P < .001). Multivariate regression analysis showed that WE admission was an independent risk factor for increased in-hospital mortality odds ratio 1.318; 95% confidence interval, 1.144-1.517; P < .001).ConclusionsOur findings show that hospitalization for AARD on WE is associated with a significantly higher mortality rate than hospitalization on WD. Further studies are needed to investigate whether ensuring optimal diagnostic and therapeutic approaches during the entire week might improve the overall survival of patients with ARRD.

Anticoagulant prophylaxis for preventing venous thromboembolism (VTE) is a worldwide established procedure in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures (FNF). Different guidelines are available in the literature, with quite different recommendations. None of them is a multidisciplinary effort as the one presented. The Italian Society for Studies on Haemostasis and Thrombosis (SISET), the Italian Society of Orthopaedics and Traumatology (SIOT), the association of Orthopaedists and Traumatologists of Italian Hospitals (OTODI), together with the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI) have set down easy and quick suggestions for VTE prophylaxis in hip and knee surgery as well as in FNF treatment. This inter-society consensus statement aims at simplifying the grading system reported in the literature, and its goal is to benefit its clinical application. Special focus is given to fragile patients, those with high bleeding risk, and those receiving chronic antiplatelet (APT) and vitamin K antagonists treatment. A special chapter is dedicated to regional anaesthesia and VTE prophylaxis.