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BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

Did producers benefit from the risk management training program? Overall, responses to program evaluations indicate a positive impact on knowledge levels relating to risk management and the importance of incorporating family aspects into risk management decision making. Moreover, responses to the follow-up questionnaire indicate that respondents had taken steps to adjust their risk management, as it related to training provided in the workshop series. Every respondent indicated specific areas which they had evaluated in the two months since the workshop series to reduce production, marketing, family finance, and business financial risks. More than half the respondents reported evaluating overall risk management and strategic plans and 78 percent reported evaluating their production risk. What sessions or points within each session were most helpful? The specific financial definitions such as the Accrual Adjusted Income statement may have been clarified in the Surviving Ag session; however, producers who participated were already well educated in most of the financial areas discussed. For example: most participants already prepared budgets before training, and the vast majority of participants demonstrated general financial competency. Family Finance session responses showed general movement from “Agree” to “Strongly Agree” for statements regarding general knowledge. Questions regarding a pre-formed process for family finance and financial management showed significant improvement in attitude. These results indicate that a major impact of this session was to evaluate family financial management as an important component of a risk management plan for agricultural families. The Risks in Family Business workshop elicited the most positive responses of the four risk management workshops. This seems to follow findings in Fetsch et al. (2001) that human relationship risks in the management of the farm business were ranked as being a high priority amongst survey respondents. Overall, workshops incorporating family relationships with risk management concepts seemed to show the greatest increase in knowledge. Given the importance of family business and the prevalence of family involvement in farm businesses, it is somewhat surprising that most agricultural risk management education curricula do not seem to integrate traditional risk management concepts with family systems concepts. This paper presents a case for doing just that. We propose a conceptual model to guide curriculum development for extension programs on agricultural risk

BACKGROUND In patients on anticoagulant treatment, the major bleeding (MB) definition released by the International Society of Thrombosis and Haemostasis (ISTH) is widely accepted. However, this definition identifies MBs with highly variable short-term risk of death. OBJECTIVES The study aims were to derive and validate a classification of ISTH-defined MBs for the risk of short-term death. METHODS Consecutive patients admitted for ISTH-defined MB occurring while on treatment with oral anticoagulants were included in the study and divided into a derivation and a validation cohort. Death within 30 days was the primary study outcome. RESULTS Among 1077 patients with MB, 64/517 and 63/560 patients in the derivation and validation cohort died, respectively. In the derivation cohort, Glasgow coma scale (GCS)

I farmaci anticoagulanti orali diretti (direct oral anticoagulants, DOAC) dabigatran, rivaroxaban e apixaban sono farmaci alternativi a warfarin, che hanno cambiato in pochi anni la gestione del paziente con disordini tromboembolici. Tra le caratteristiche innovative vi sono la somministrazione a dose fissa e la non necessita di monitoraggio di routine. Questo non significa che non sia necessaria la loro determinazione in alcuni casi, principalmente in urgenza. In questo lavoro riportiamo il percorso adottato per la determinazione di questi farmaci in urgenza, al fine di ottimizzare e ridurre il tempo di refertazione del valore plasmatico dei DOAC. Il dosaggio di dabigatran e stato effettuato utilizzando il tempo di trombina diluito (dTT) con reattivo BC Thrombin (Siemens, Milano, Italia); quello di rivaroxaban e apixaban con il test dell’anti-FXa, con reagenti Biophen DiXa (Hyphen BioMed, Neuville-sur-Oise, France). Come calibratori e controlli sono stati utilizzati quelli forniti da HyphenBioMed. Tutti i test sono stati eseguiti su strumento BCS XP (Siemens). Dall’aprile 2016 il Laboratorio di Patologia Clinica ha introdotto la determinazione dei DOAC sia in routine sia in regime di urgenza, con particolare attenzione all’ottimizzazione di questo percorso che e stato condiviso sia con i medici del policlinico sia con quelli dell’area vasta Toscana sud-est, essendo il nostro l’unico Laboratorio che esegue questo tipo di dosaggio. In sintesi, il reparto del policlinico e, in maniera ancora piu stringente, l’ospedale dell’area vasta, deve telefonare prima di inviare il campione specificando il tipo di farmaco, se il paziente assume altri anticoagulanti e, quando possibile, il tempo intercorso dall’ultima somministrazione e il prelievo di sangue. Nel periodo in esame sono state eseguite 22 determinazioni di DOAC: 11 per dabigatran, 3 per rivaroxaban e 8 per apixaban. Le richieste piu frequenti si sono avute in urgenza (68%) rispetto alla routine (32%). Il maggiore richiedente e stato il dipartimento di emergenza, seguito dai reparti chirurgici e di medicina. I risultati ottenuti nei singoli pazienti confermano gli ampi range che si possono ottenere per questi farmaci, che risentono sia del momento di esecuzione del prelievo rispetto all’ultima assunzione, sia dell’ampia variabilita inter-individuale. L’ottimizzazione del percorso della determinazione dei DOAC ci ha permesso di poter refertare il valore del farmaco entro 30 minuti dall’arrivo della provetta in Laboratorio. Poter garantire il dosaggio quantitativo dei DOAC in meno di 1 ora in tutto l’arco delle 24 ore si e dimostrato utile nella gestione dei pazienti critici in trattamento con questi farmaci.

Background The recanalization rate in patients with deep venous thrombosis (DVT) of the legs treated with the direct oral anticoagulants (DOAC) is unknown. Methods In an Italian cohort, we investigated the rate of residual vein thrombosis (RVT) after three and/or six months in 352 patients with proximal DVT who had been treated with the DOACs as a stand-alone therapy or lead-in parenteral anticoagulants, and compared it to that recorded in a historical cohort of 1094 patients in which vitamin K antagonists (VKAs) had been employed. In both cohorts, RVT was defined as the ultrasound persistence of thrombotic material resulting in a diameter of at least 4 mm of incompressibility of the proximal veins. Results RVT was detected in 143 patients treated with DOACs (41.2%) after three months and in 58 patients (21.1%) after six months; the corresponding figure in patients treated with conventional anticoagulation was 52.3% and 54.5%, respectively. After adjusting for the baseline characteristics, the odds ratio of RVT in patients treated with the DOACs as compared with those treated with conventional anticoagulation was 0.63 (95% CI, 0.48–0.81) after three months, and 0.17 (95% CI; 0.11–0.26) after six months. Conclusions In patients with proximal DVT treated with the DOACs, the persistence of ultrasound detectable RVT is likely to occur less frequently than in patients treated with conventional anticoagulation. These results may have implications for the prognosis of patients with DVT.

Background Limited data are available on major bleeding (MB) occurring during treatment with vitamin K (VKAs) or direct oral anticoagulants (DOACs) outside clinical trials. Methods Patients hospitalized for MB while on treatment with VKAs or DOACs were included in a multicenter study to compare clinical presentation, management and outcome of bleeding. The primary study outcome was death at 30days. Results Between September 2013 and September 2015, 806 patients were included in the study, 76% on VKAs and 24% on DOACs. MB was an intracranial hemorrhage in 51% and 21% patients on VKAs or DOACs, respectively (Odds Ratio [OR] 3.79; 95% confidence interval [CI] 2.59–5.54) a gastrointestinal bleeding in 46% and 25% patients on DOACs and VKAs, respectively (OR 2.62; 95% CI 1.87–3.68). Death at 30days occurred in 130 patients (16%), 18% and 9% of VKA and DOAC patients (HR 1.95; 95% CI 1.19–3.22, p=0.008). The rate of death at 30days was similar in VKA and DOAC patients with intracranial hemorrhage (26% and 24%; HR 1.05, 95% CI 0.54–2.02) and gastrointestinal bleeding (11% and 7%; HR 1.46, 95% CI 0.57–3.74) and higher in VKA than DOAC patients with other MBs (10% and 3%; HR 3.42, 95% CI 0.78–15.03). Conclusions Admission for ICH is less frequent for DOAC patients compared with VKA patients. Admission for gastrointestinal MB is more frequent for DOAC as compared to VKA patients. Mortality seems lower in patients with MBs while on DOACs than VKAs but this finding varies across different types of MBs.

The association between preceding treatment with antiplatelet agents (APs), vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) and mortality after intracerebral hemorrhage (ICH) remains unclear. The aim of this multicenter, prospective cohort study was to assess the risk for death after ICH in consecutive patients who were on treatment with APs, VKAs, DOACs, or no antithrombotic agent. The primary outcome was in-hospital death by day 30. ICH volume at admission and volume expansion were centrally assessed. Out of 598 study patients, in-hospital death occurred in 21% of patients who were on treatment with APs, 25% with VKAs, 30% with DOACs, and 13% with no antithrombotics. Crude death rate was higher in patients on antithrombotics as compared to patients receiving no antithrombotic agent. At multivariate analysis, age (HR 1.07; 95% CI 1.04-1.10), previous stroke (HR 1.83; 95% CI 1.14-2.93), GCS ≤8 at admission (HR 6.06; 95% CI 3.16-9.74) and GCS 9-12 (HR 3.38; 95% CI 1.81-6.33) were independent predictors of death. Treatment with APs (HR 1.29; 95% CI 0.61-2.76), VKAs (HR 1.42; 95% CI 0.70-2.88) or DOACs (HR 1.28; 95% CI 0.61-2.73) were not predictors of death in the overall study population, in non-trauma associated ICH as well as when GCS was not included in the model. ICH volume and volume expansion were independent predictors of death. In conclusion, preceding treatment with antithrombotic is associated with the severity of ICH. Age, previous stroke and clinical severity at presentation were independent predictors of in-hospital death in patients with ICH.

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Da oltre un anno, anche in Italia sono in uso i nuovi anticoagulanti orali diretti: dabigatran, diretto antagonista della trombina, e rivaroxaban, inibitore diretto del fattore Xa. Il vantaggio di questi nuovi farmaci, a parita di efficacia e sicurezza rispetto agli anticoagulanti antagonisti della vitamina K, e dovuto alla loro somministrazione a dose fissa, al minor numero di interazioni con i farmaci e nessuna con il cibo, ma soprattutto non richiedono monitoraggio di laboratorio, se si esclude la periodica valutazione della funzione renale. Hanno una breve emivita, con inizio e termine d’azione rapidi. D’altro canto, potenziali svantaggi riguardanti l’uso di questi farmaci sono rappresentati dalla mancanza di antidoti in caso di sovradosaggio o emorragie e dalla difficolta di controllare l’aderenza del paziente. Da un punto di vista laboratoristico lo svantaggio e dato dalla difficolta di monitorare il loro effetto con gli attuali test, perche i test standard non risultano adeguati a fornire un’accurata risposta, per la loro scarsa o eccessiva sensibilita. Ogni Laboratorio dovra pertanto organizzarsi per poter determinare, in presenza di eventi emorragici maggiori e/o per eseguire interventi chirurgici in urgenza, il livello di anticoagulazione del sangue del paziente. Il miglior modo per rispondere al quesito clinico sara dare il valore del farmaco presente in quel momento nel plasma del paziente. Lo scopo di questo lavoro e la messa a punto del dosaggio di questi farmaci nel coagulometro disponibile nel nostro Laboratorio, in modo da poter fornire in futuro, anche in regime di urgenza, una risposta veloce al clinico. I metodi per il dosaggio dei nuovi anticoagulanti orali diretti sono stati applicati sullo strumento BCS XP (Siemens Healthcare, Erlangen, Deutschland). Il kit utilizzato per la determinazione quantitativa di dabigatran e il BC Thrombin (Siemens Healthcare), reagente usato per valutare il tempo di trombina nel plasma umano citrato. Il metodo e stato opportunamente modificato in modo da fornire un tempo di trombina definito diluito. Il kit utilizzato per la determinazione quantitativa di rivaroxaban e Berichrom Heparin (Siemens Healthcare) specifico per il dosaggio cromogenico del fattore Xa. E stato possibile costruire le adeguate curve di taratura grazie ai plasma calibratori e verificate con i plasma controllo, entrambi forniti dalla Hyphen BioMed (Neuville-sur-Oise, France). I metodi utilizzati sono attendibili e riproducibili in un range compreso tra 24 e 497 ng/ml. Al di sotto dei 24 ng/ml non sara possibile dare un valore esatto e per valori superiori a 497 ng/ml, se richiesto, sara necessario diluire il campione. I coefficienti di variazione percentuale intra-day e inter-day sono tutti al di sotto del 10% e la curve di taratura presentano un $r^{2} = 0{,}96$ . Il nostro studio dimostra che i metodi scelti e applicati sul coagulometro BCS XP in uso nel nostro Laboratorio sono eseguibili con procedura completamente automatizzata, in regime di urgenza, in un tempo di circa 30 minuti. L’incremento dell’uso di questi farmaci nella pratica clinica aiutera i medici a valutare come la quantita plasmatica del farmaco possa essere collegata con la capacita anticoagulante del paziente.

Background: Prognostic stratification is of utmost importance for management of acute Pulmonary Embolism (PE) in clinical practice. Many prognostic models have been proposed, but which is the best prognosticator in real life remains unclear. The aim of our study was to compare and combine the predictive values of the hemodynamics/biomarkers based prognostic model proposed by European Society of Cardiology (ESC) in 2008 and simplified PESI score (sPESI). Methods: Data records of 452 patients discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. The ESC model and sPESI were retrospectively calculated and compared by using Areas under Receiver Operating Characteristics (ROC) Curves (AUCs) and finally the combination of the two models was tested in hemodinamically stable patients. All cause and PE-related in-hospital mortality and fatal or major bleedings were the analyzed endpoints Results: All cause in-hospital mortality was 25% (16.6% PE related) in high risk, 8.7% (4.7%) in intermediate risk and 3.8% (1.2%) in low risk patients according to ESC model. All cause in-hospital mortality was 10.95% (5.75% PE related) in patients with sPESI score ≥1 and 0% (0%) in sPESI score 0. Predictive performance of sPESI was not significantly different compared with 2008 ESC model both for all cause (AUC sPESI 0.711, 95% CI: 0.661-0.758 versus ESC 0.619, 95% CI: 0.567-0.670, difference between AUCs 0.0916, p=0.084) and for PE-related mortality (AUC sPESI 0.764, 95% CI: 0.717-0.808 versus ESC 0.650, 95% CI: 0.598-0.700, difference between AUCs 0.114, p=0.11). Fatal or major bleedings occurred in 4.30% of high risk, 1.60% of intermediate risk and 2.50% of low risk patients according to 2008 ESC model, whereas these occurred in 1.80% of high risk and 1.45% of low risk patients according to sPESI, respectively. Predictive performance for fatal or major bleeding between two models was not significantly different (AUC sPESI 0.658, 95% CI: 0.606-0.707 versus ESC 0.512, 95% CI: 0.459-0.565, difference between AUCs 0.145, p=0.34). In hemodynamically stable patients, the combined endpoint in-hospital PE-related mortality and/or fatal or major bleeding (adverse events) occurred in 0% of patients with low risk ESC model and sPESI score 0, whilst it occurred in 5.5% of patients with low-risk ESC model but sPESI ≥1. In intermediate risk patients according to ESC model, adverse events occurred in 3.6% of patients with sPESI score 0 and 6.65% of patients with sPESI score ≥1. Conclusions: In real world, predictive performance of sPESI and the hemodynamic/biomarkers-based ESC model as prognosticator of in-hospital mortality and bleedings is similar. Combination of sPESI 0 with low risk ESC model may identify patients with very low risk of adverse events and candidate for early hospital discharge or home treatment.

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2–54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23–4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension.

Historically, standard treatment of haemodynamically stable pulmonary embolism (PE) in the acute phase consists in parenteral anticoagulants overlapped with oral anticoagulants vitamin K antagonists (VKAs) for at least 5-7 days followed by VKAs alone when their therapeutic range is reached and prolonged for at least three-six months (long term phase). However standard treatment has many pharmacological and practical limitations. For overcoming these limitations, new anticoagulant drugs with better pharmacological profile and easier to use, have been manufactured and tested in pre-clinical and clinical trials with the aim to reach at least non inferiority compared to standard treatment. In the setting of PE, new oral anticoagulants (NOACs), direct inhibitors of thrombin (dabigatran) or activated factor X (apixaban, edoxaban, rivaroxaban) have been tested in the acute and long-term phases of treatment in phase III randomized clinical trials (RCTs). Rivaroxaban (EINSTEIN-PE study) and apixaban (AMPLIFY study) have been tested directly from diagnosis, dabigatran (RE-COVER I and II studies) and edoxaban (HOKUSAI study) starting after 7-10 days of standard treatment. Overall, these trials have demonstrated that NOACs are effective and safe at least as standard treatment, promising a revolutionary approach to PE treatment in acute/sub-acute PE based on single drug approach or rapid switch from parenteral to oral anticoagulation. In this paper the Authors focus on phase III RCTs on NOACs in the acute and long-term phases of PE treatment, highlighting the first two weeks of treatment.

Introduction: Critical limb ischemia (CLI) is a clinical entity that is not well known to patients or the mass media, and it often receives inadequate attention by medical specialists as well. In most cases, patients with CLI already have advanced disease when they are first seen by physicians, and they frequently arrive on internal medicine wards without having received appropriate treatment. The numerous comorbidities that characterize these cases really require multidisciplinary management. Materials and methods: We sent multiple-choice questionnaires to 26 internal medicine units in hospitals located in the Tuscany region of Italy to learn more about the true incidence and impact of CLI. Results: As expected, in most wards, there is no specific, structured clinical protocols for effective management of CLI patients.Discussion: We analyze the current situation and propose a multidisciplinary network for structured, integrated management of CLI. The network would operate throughout the region and be composed of internist-angiologists and vascular surgeons with greater awareness of CLI and experience in its management. This initiative, if effectively implemented, will help increase awareness of this condition and the fact that CLI patients are suffering from what is unacceptably an ‘‘orphan’’ illness.

The optimal management of major bleeding associated with vitamin K antagonists remains unclear.The aim of the study was to assess the determinants of outcome of vitamin K antagonists-associated major bleeding and the outcome of bleeding in relation with the therapeutic management.Patients hospitalized for major bleeding while on vitamin K antagonists were included in a prospective, cohort study. Major bleeding was defined according to the criteria of the International Society of Thrombosis Haemostasis. The primary study outcome was death at 30days from major bleeding.544 patients were included in this study, of which 282 with intracranial hemorrhage. Prothrombin complex concentrates were used in 51% and in 23% of patients with intracranial hemorrhage or non-intracranial major bleeding, respectively (p0.001); fresh frozen plasma was used in 7% and in 17% of patients with intracranial hemorrhage or non-intracranial major bleeding (p0.001). Death at 30days occurred in 100 patients (18%), 72 patients with intracranial hemorrhage and 28 patients with non-intracranial major bleeding. Age over 85years, low Glasgow Coma Scale score and shock were independent predictors of death at 30days. Invasive procedures were associated with decreased risk of death.Among the patients hospitalized for major bleeding while on vitamin K antagonists, the risk for death is substantial. The risk for death is associated with the clinical severity of major bleeding as assessed by the GCS score and by the presence of shock more than with the initial localization of major bleeding (ICH vs other sites).

Summary Introduction Critical limb ischemia (CLI) is a clinical entity that is not well known to patients or the mass media, and it often receives inadequate attention by medical specialists as well. In most cases, patients with CLI already have advanced disease when they are first seen by physicians, and they frequently arrive on internal medicine wards without having received appropriate treatment. The numerous comorbidities that characterize these cases really require multidisciplinary management. Materials and methods We sent multiple-choice questionnaires to 26 internal medicine units in hospitals located in the Tuscany region of Italy to learn more about the true incidence and impact of CLI. Results As expected, in most wards, there is no specific, structured clinical protocols for effective management of CLI patients. Discussion We analyze the current situation and propose a multidisciplinary network for structured, integrated management of CLI. The network would operate throughout the region and be composed of internist-angiologists and vascular surgeons with greater awareness of CLI and experience in its management. This initiative, if effectively implemented, will help increase awareness of this condition and the fact that CLI patients are suffering from what is unacceptably an “orphan” illness.

Background Telemedicine could be useful in countries like Italy to meet the needs of elderly patients and in particular in those in precarious general conditions, for whom travelling even short distances can pose considerable practical and economical difficulties. Objective The aim of this study was to determine the efficacy of store-and-forward teledermatology vs face-to-face consultations in elderly patients. Methods A total of 130 geriatric patients with skin diseases requiring dermatological examination were enrolled. The patients examined, consisting of 60 men (46.15%) and 70 women (53.85%), were aged between 66 and 97 years (mean age 80.58 years). Three dermatologists of the department, with equal experience took turns in face-to-face examination and teledermatology (store-and-forward). To compare face-to-face dermatological examinations with the asynchronous store-and-forward approach of teledermatology, we considered diagnostic agreement (ICD-9 code), therapeutic agreement and concordance of diagnostic confidence. Results One hundred and fourteen of 130 patients were diagnosed with the same ICD-9 code, making a total observed agreement of 87.7% with a Cohen's κ estimated of 0.863. Agreement between therapies was 69.6% (Cohen's κ = 0.640). As it concerns diagnostic confidence, dermatologists appeared generally slightly less certain of their diagnosis by telemedicine. Conclusions Store-and-forward teledermatology can improve diagnostic and therapeutic care for skin disease in elderly who lack easy and/or direct access to dermatologists.

One of the main innovation emerged in recent years in the field of venous thromboembolism (VTE) has been represented by the clinical development and marketing of new oral anticoagulant agents used for prophylaxis and acute treatment. These drugs are represented by direct thrombin inhibitors (anti-factor IIa) and the direct inhibitors of activated factor X (anti-Xa). The main achievement of these new agents is represented by their ease of use without laboratory monitoring or dose adjustment. Dabigatran (anti-factor IIa), rivaroxaban, and apixaban (anti-Xa) are in advanced phase of clinical development with concluded phase III trials. Up to now the results of efficacy and safety of phase III clinical trials are available, while phase IV studies are currently ongoing. Overall, the phase III clinical trials showed the non inferiority of new oral anticoagulants in VTE prophylaxis of patients undergone to major orthopedic surgery, such as hip and knee arthroplasty, compared to conventional prophylaxis represented by subcutaneous low molecular weight heparin with similar safety. Moreover dabigatran has shown to be not inferior when compared to warfarin for the prevention of six months VTE recurrences, with a significative lower incidence of bleedings. Awaiting the results of many other ongoing phase III trials, since now it is possible to think that, in the next future, new oral anticoagulants will be widely diffused in clinical practice for their ease of use and feasibility. In this review the Authors analyse the available results of phase III clinical trials for dabigatran, rivaroxaban and apixaban, focusing on the antithrombotic endpoints for prevention and treatment of VTE and the bleeding risk. Moreover synthesis of ongoing trials will be displayed.

Background and Purpose—Several studies have shown, in different populations, that modest elevation of plasma C-reactive protein (CRP) in the range seen in apparently healthy individuals is a strong predictor of future vascular events. Elevated plasma CRP concentrations are also associated with an increased risk of cerebrovascular events and an increased risk of fatal and nonfatal cardiovascular events in ischemic stroke patients. These epidemiological and clinical observations suggest that determination of plasma CRP concentrations could be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease and be of prognostic value. The aim of this review is to summarize the evidence for CRP as an independent predictor of cerebrovascular events in at-risk individuals and ischemic stroke patients and to consider its usefulness in evaluating prognosis after stroke.Summary of Review—CRP fulfils most of the requirements of a new risk and prognostic predictor, but several issues await further confirmation and clarification before this marker can be included in the routine evaluation of stroke patients and subjects at risk for cerebrovascular disease. Potentially important associations have been established between elevated plasma CRP concentrations and increased efficacy of established therapies, particularly lipid-lowering therapy with statins.Conclusion—At present, there is not sufficient evidence to recommend measurement of CRP in the routine evaluation of cerebrovascular disease risk in primary prevention, because there is insufficient evidence as to whether early detection, or intervention based on detection, improves health outcomes, although shared risk of cardiovascular disease indicates this may be of value. In secondary prevention of stroke, elevated CRP adds to existing prognostic markers, but it remains to be established whether specific therapeutic options can be derived from this.

Background and aims: Diagnosis of pulmonary embolism (PE) in the elderly remains difficult and is often late, although its incidence increases steadily with age. Since few studies have reported the clinical picture of this disease in very old patients, the aim of our study was to focus on clinical, instrumental and laboratory aspects in patients 75 years of age and over with suspected PE. Methods: Symptoms, signs, risk factors for venous thromboembolic diseases, 12-lead electrocardiograms, B-mode echocardiograms, chest X-rays, leg compression venous ultrasonography, latex-assay quantitative D-dimer, and arterial blood gas analyses were collected for 96 elderly patients of 75 years and over (mean age 81.22±4.81) with suspected PE, admitted to our acute geriatric ward from 1997 to 2000. Patients were divided into two groups: 59 patients with PE (PE+) confirmed by pulmonary angiography, scintigraphic lung scan or necropsy, and 37 patients with normal lung scan or without PE at necropsy (PE−). Results: Dyspnea and chest pain were the most common symptoms in both groups, but significantly more frequent in the PE+ group. Tachycardia, fever, cyanosis, and tachypnea were the most common objective signs in both groups; tachycardia and tachypnea were not significantly different between the two groups. Bed rest, venous insufficiency and leg deep vein thrombosis were the most common venous risk factors in PE+ and significantly different with respect to PE−. Sinus tachycardia, ST-T abnormalities and right bundle branch block were the most common electrocardiographic aspects in PE+; echocardiograms showed significantly more frequent acute involvement of right heart in PE+, whereas chest X-rays were rarely compatible with PE and did not reveal differences between the two groups. D-Dimer was significantly higher in PE+ but was below 500 ng/mL only in 25% of cases in PE−. More severe hypoxemia, oxy-hemoglobin hyposaturation and increased alveolar-arterial oxygen gradients were found at arterial blood gas analysis in PE+. Conclusions: Although many analyzed clinical, instrumental and laboratory aspects were significantly more frequent in the PE+ group, they were all non-specific and not conclusive for diagnosis of PE. Our retrospective study focus may add information about the picture and diagnostic difficulties of PE in very old patients.

Recent literature and our previous proteomic findings prompted us to study the coagulation system in idiopathic pulmonary fibrosis (IPF), the pathogenesis of which remains unclear. The aim of this study was to compare coagulation factors in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia (NSIP) patients and healthy controls. Thirty-three IPF patients (23 acute exacerbation and 10 stable IPF patients), 7 NSIP patients, and 44 controls were enrolled. Concentrations of D-dimer, homocysteine, functional protein C, protein C antigen, free and total protein S antigen and activity, fibrinogen and factor VIIIc were analyzed in serum of patients and controls. The lupus anticoagulant (LAC) test was also performed. Factor VIIIc levels were significantly higher in acute exacerbation IPF patients than controls (p = 0.0001) and in stable IPF patients than controls (p = 0.002). Factor VIIIc levels were higher and PT levels were lower in acute exacerbation IPF patients who died after exacerbation than in patients who survived (p = 0.04 and p = 0.003, respectively). D-dimer, fibrinogen, and homocysteine levels were also significantly higher in IPF patients than controls (p < 0.01). Protein C activity was increased in acute exacerbation IPF patients than controls (p = 0.005). The LAC test was positive in seven IPF patients and negative in controls. Procoagulant status was demonstrated in IPF patients (mainly in acute exacerbation/IPF) than controls and NSIP patients, probably due to endothelial activation and microvascular injury. These preliminary results are of interest because of their potential implications in the pathogenesis and treatment of this disease.

Although new oral anticoagulants (NOAs) have been marketed in many countries, concern exists about the management of bleedings related to these drugs due to the lack of specific antidotes. The aim of our study was to report on real life management of NOAs-related life-threatening or major bleedings. We report data from consecutive cases of NOAs related major bleedings admitted to 4 hospitals since NOAs became marketed in Italy. We treated 8 patients, 4 males, with mean age 84 ± 7 years, 7 of whom were on dabigatran and one on rivaroxaban. The indication for NOA was atrial fibrillation. All bleedings were spontaneous and involving the gastro-intestinal tract. At the time of bleeding all patients had a drop in hemoglobin levels over 20 g/L. Creatinine clearance was ≤30 mL/min in 4 patients. All patients received general supportive measures, 4 of 8 patients were transfused with packed red cells and one patient received platelet transfusion. Three patients were treated with tranexamic acid and one patient on dabigatran received 4-factor prothrombin complex concentrate (PCC) with bleeding cessation, although coagulation parameters were not corrected. The median time for normalization of coagulation parameters was 3 days (range 1–6 days). All patients were discharged alive and NOAs were discontinued. In NOAs related major gastro-intestinal bleeding general supportive measures seem to be effective for the majority of patients. Despite promoting bleeding cessation, 4-factor PCC does not reverse abnormal coagulation parameters.

Background. Arterial blood gas analysis (BGA) remains a first-step diagnostic approach in patients with suspected pulmonary embolism (PE). The aim of this study was to evaluate BGA parameters in elderly patients with suspected pulmonary embolism for diagnosis and 14-day prognosis. Methods. We performed a retrospective cohort observational study of 6 years (1994‐1999) in a 60-bed acute geriatric ward of University Hospital in Siena, Italy. Room air arterial oxygen partial pressure (pO 2 ), arterial carbon dioxide partial pressure (pCO 2 ), pH, arterial oxyhemoglobin saturation (SO 2 ), and alveolar-arterial oxygen gradient [D(A-a)O 2 ] were performed on hospital admission of 75 patients with confirmed PE (CPE) and were compared with data from 43 patients with unconfirmed PE (UCPE). The same parameters of 54 CPE surviving patients were compared with 21 CPE nonsurviving patients. Results. Significantly lower pO 2 and SO 2, and higher DA-aO 2 were found in CPE patients. Respiratory alkalosis was found in one third of the patients in both groups (no significant difference). In the CPE group, there was a significantly lower SO 2 in nonsurviving patients, without significant differences for the other parameters. Metabolic acidosis was significantly more frequent in nonsurviving patients. Conclusion. More severe hypoxemia, oxyhemoglobin hyposaturation, and higher D(A-a)O 2 are associated with the diagnosis of PE in elderly patients. Respiratory alkalosis is less frequent than in younger patients, and metabolic disorders are negative prognostic indicators.

Felodipine is a second-generation dihydropyridine calcium antagonist used to treat mild to moderate arterial hypertension. The authors used venous occlusion plethysmography to study the effect of this drug on lower limb arterial inflow and venous outflow in 10 at rest patients with mild essential hypertension. They also sought correlations between changes in district blood flow and blood pressure. Plethysmography was carried out at 8 AM and 4, 8, and 24 hours later at baseline (after washout), on the first day of treatment with a single daily administration of 10 mg felodipine ER, and after 7 and 30 days of treatment. The drug was given after the 8 AM evaluation. The authors determined rest flow, maximal venous incremental volume (MVIV) at 40 mmHg and 60 mmHg, and gradient of venous volume between 60 and 40 mmHg divided by the pressure difference (DV/DP) as index of venous distensibility. On the days of plethysmographic evaluation, arterial blood pressure and heart rate were measured continuously over 24 hours by the ABPM (Ambulatory Blood Pressure Monitoring). The results were analyzed by ANOVA. Rest flow, MVIV, and DV/DP were stable at the baseline evaluation. On days 1, 7, and 30 of treatment the rest flow after 4 and 8 hours was significantly greater than at 8 AM but had always returned to normal after 24 hours. No other plethysmographic parame ters changed significantly; in particular venous outflow remained unchanged. Mean arterial, systolic, and diastolic blood pressure were significantly reduced, compared with baseline, following treatment on the first day and after 7 and 30 days' treatment. There was no effect on heart rate. The authors conclude that felodipine is useful for the treatment of mild essential hypertension, since it reduces arterial resistance without altering venous capacitance or distensibility.

IntroductionThe prophylaxis of thromboembolic events represents a key point in the modern management of patients with non valvular atrial fibrillation (AF), both paroxysmal and persistent/permanent. Up to now, vitamin K antagonist (VKA) drugs are the first choice in thromboembolic prophylaxis. Their treatment limitations have lead to development and clinical experimental use of new molecules aimed to overcome their limits. The new oral anticoagulants, such as dabigatran, a direct inhibitor of thrombin or rivaroxaban and apixaban, direct inhibitors of activated factor X, have been compared to warfarin in randomized clinical phase three trials (RCTs) for thromboembolic prevention in patients with non valvular AF with the aim to demonstrate their non inferiority when compared to warfarin. The results of these trials have been recently published. In this article the authors review the results of efficacy and safety of these three more recently published large RCTs.Conclusions All RCTs, RE-LY for dabigatran, ROCKET-AF for rivaroxaban and ARISTOTLE for apixaban met the study end-points and demonstrated a good safety profile of each new oral anticoagulant, so promising a new era for thromboembolic prevention therapy in AF.

Venous thromboembolism (VTE) represents one of the leading causes of mortality and morbidity in ill medical patients. Avoiding VTE is therefore of utmost importance in clinical practice. VTE prophylaxis can be assured by pharmacological strategies, such as heparinoids, unfractioned heparin, low molecular weight heparins, fondaparinux or oral anticoagulants and, when these are contraindicated, by mechanical measures, such as graduated compression stockings (GCS) and/ or intermittent pneumatic compression (ICP). However, due to the lack of solid literature evidence, VTE mechanical prophylaxis is not standardized in hospitalized ill medical patients. Much recently, findings from randomized clinical trials on VTE prophylaxis in ill medical patients, such as CLOTS I in patients with stroke and LIFENOX in patients with other kind of medical diseases, seem to increase doubts and reduce certainness in this context and recommendations from guidelines don’t help in reducing confusion. Therefore the aim of this review is to focus on mechanical prophylaxis of VTE in hospitalized ill medical patients.http://dx.doi.org/10.7175/rhc.v3i3.202

Intracerebral haemorrhage (ICH) represents the most feared complication of therapy with vitamin K antagonists (VKA), so-called oral anticoagulant therapy (OAT). This is a real emergency in clinical practice, being burdened by high mortality, morbidity and residual functional disability. In recent years, there have been widespread indications for the correct management of VKA associated ICH. The urgent OAT reversal represents the cornerstone of VKA associated ICH therapy. The knowledge of these guidelines is of fundamental importance in clinical practice. The urgent OAT reversal could stop the hematoma enlargement which is considered one of the main risk factor of poor outcome in this clinical setting. The aim of urgent OAT reversal is bringing the INR (International Normalized Ratio) to values ≤ 1.4. It is possible by using prothrombin complex concentrate (PCC), fresh frozen plasma (FFP), recombinant activated factor VII (raFVII) together with vitamin K1 intravenous infusion. In this article the Authors review the practical management of urgent OAT reversal in patients suffering for VKA related ICH.

Oral anticoagulant-associated intracerebral hemorrhage is increasing in incidence and is the most feared complication of therapy with vitamin K1 antagonists. Anticoagulant-associated intracerebral hemorrhage has a high risk of ongoing bleeding, death, or disability. The most important aspect of clinical management of anticoagulant-associated intracerebral hemorrhage is represented by urgent reversal of coagulopathy, decreasing as quickly as possible the international normalized ratio to values ≤1·4, preferably ≤1·2, together with life support and surgical therapy, when indicated. Protocols for anticoagulant-associated intracerebral hemorrhage emphasize the immediate discontinuation of anticoagulant medication and the immediate intravenous administration of vitamin K1 (mean dose: 10–20 mg), and the use of prothrombin complex concentrates (variable doses calculated estimate circulating functional prothrombin complex) or fresh-frozen plasma (15–30 ml/kg) or recombinant activated factor VII (15–120 μg/kg). Because of cost and availability, there is limited randomized evidence comparing different reversal strategies that support a specific treatment regimen. In this paper, we emphasize the growing importance of anticoagulant-associated intracerebral hemorrhage and describe options for acute coagulopathy reversal in this setting. Additionally, emphasis is placed on understanding current consensus-based guidelines for coagulopathy reversal and the challenges of determining best evidence for these treatments. On the basis of the available knowledge, inappropriate adherence to current consensus-based guidelines for coagulopathy reversal may expose the physician to medico-legal implications.

been shown to be a useful aid in the diagnosis of PE. DD, a degradation product of cross-linked fibrin, has high sensitivity (89‐98.8%) and high

Risk evaluation and prognostic stratification based upon clinical and radiological findings and new cardiac biomarkers, such as natriuretic peptides (NP) and troponins, represent key points in modern management of acute pulmonary embolism (PE). Literature evidence shows that normotensive PE with right heart dysfunction (RHD), defined as submassive PE, has poorer prognosis when compared to normotensive PE without RHD, defined as non-massive PE; thus whether submassive PE should be managed more aggressively and with closer monitoring represents the crucial question about acute PE treatment. Although the answer is yet unclear, the most recent guidelines address to thrombolysis as treatment choice in selected high risk patients with submassive PE. Guidelines also clarify the indications for unfractioned and low molecular weight heparins and fondaparinux. Therefore, in the present article, the authors focus on modern risk-based therapeutic guidelines of acute PE. Keywords Pulmonary embolism; Treatment; Prognosis; Biomarkers; Chocardiography; Hemodynamic; Guidelines

Pulmonary embolism (PE) represents a common disease in emergency medicine and guidelines for diagnosis and treatment have had wide diffusion. However, PE morbidity and mortality remain high, especially when associated to hemodynamic instability or right ventricular dysfunction. Prognostic stratification to identify high risk patients needing to receive more aggressive pharmacological and closer monitoring is of utmost importance. Modern guidelines for management of acute PE are based on risk stratification using either clinical, radiological, or laboratory findings. This article reviews the modern treatment of acute PE, which is customized upon patient prognosis. Accordingly the current risk stratification tools described in the literature such as clinical scores, echocardiography, helical computer tomography, and biomarkers will be reviewed.

International audience; OBJECTIVE: Diagnosis of pulmonary embolism (PE) remains difficult and is often missed in the elderly due to nonspecific and atypical presentation. Diagnostic algorithms able to rule out PE and validated in young adult patients may have reduced applicability in elderly patients, which increases the number of diagnostic tools use and costs. The aim of the present study was to analyze the reported clinical presentation of PE in patients aged 65 and more. MATERIALS AND METHODS: Prospective and retrospective English language studies dealing with the clinical, instrumental and laboratory aspects of PE in patients more than 65 and published after January 1987 and indexed in MEDLINE using keywords as pulmonary embolism, elderly, old, venous thromboembolism (VTE) in the title, abstract or text, were reviewed. RESULTS: Dyspnea (range 59%-91.5%), tachypnea (46%-74%), tachycardia (29%-76%), and chest pain (26%-57%) represented the most common clinical symptoms and signs. Bed rest was the most frequent risk factor for VTE (15%-67%); deep vein thrombosis was detected in 15%-50% of cases. Sinus tachycardia, right bundle branch block, and ST-T abnormalities were the most frequent ECG findings. Abnormalities of chest X-ray varied (less than 50% in one-half of the studies and more than 70% in the other one-half). Arterial blood gas analysis revealed severe hypoxemia and mild hypocapnia as the main findings. D-Dimer was higher than cut-off in 100% of patients in 75% of studies. Clinical usefulness of D-Dimer measurement decreases with age, although the strategies based on D-Dimer seem to be cost-effective at least until 80 years. CONCLUSION: Despite limitations due to pooling data of heterogeneous studies, our review could contribute to the knowledge of the presentation of PE in the elderly with its diagnostic difficulties. A diagnostic strategy based on reviewed data is proposed.

In a double-blind study, a single dose of 1600 mg cyclandelate or placebo was administered to 10 patients with cerebrovascular and/or peripheral vascular disease, and fibrinolytic activity was evaluated before and 1, 2, 4 and 6 h after treatment. Cyclandelate induced a reduction in euglobulin lysis time, an increase in tissue plasminogen activator concentration and a reduction in plasminogen activator inhibitor, α2-antiplasmin and immunological fibrinogen concentrations, but no changes in antithrombin III and plasminogen concentrations were observed. After placebo administration no significant changes were observed. After treating two patients with 800 mg cyclandelate twice daily for 14 days, 1600 mg cyclandelate stimulated fibrinolysis for 8 h. It is concluded that the fibrinolytic activity of cyclandelate has implications for the treatment of cardiovascular complications of atherosclerosis.

Background and aim: Prognostic stratification of acute pulmonary embolism (PE) represents the cornerstone of modern management of this potentially life-threatening disease. In the latest years, a lot of clinical prognostic models have been validated. However, these are yet underused in clinical practice, especially in real world populations. The aim of our study was to test the prognostic ability of the Simplified Pulmonary Embolism Severity Index (sPESI) score in a real world population. Methods: Data records of 452 patients that were discharged for acute PE from 28 Internal Medicine wards of Tuscany (Italy) were retrospectively analysed. sPESI was calculated in the identical manner as the original study. Prognostic ability of sPESI score for predicting in-hospital all-cause and PE-related mortality was tested by using Areas under Receiver Operating Characteristics (ROC) curve (AUC). Results: 15.2% of patients were classified as sPESI score 0, whereas 84.8% were classified as sPESI ≥ 1. All causes of in-hospital mortality were 10.95% (5.75% PE-related) in patients with sPESI score ≥ 1 and 0% (0% PE-related) in sPESI score 0. AUC for all causes of mortality was 0.694 (95% CI: 0.650-0.736), whereas it was 0.702 (95% CI: 0.657-0.743) for PE-related mortality. Conclusion: In a real world population, sPESI is a good prognosticator for all causes of in-hospital and PE-related mortality and its use should be encouraged.

We have read with much interest the article of Punukollu et al. [1] recently published in your Journal and focused on differences in clinical presentation and treatment of pulmonary embolism (PE) in elderly compared with younger patients. This article arises important reflections on clinical picture and diagnostic approach to PE in the elderly that it should be important to highlight. Diagnosis of PE in fact is difficult in the elderly because of the nonspecificity of the clinical picture and the instrumental and laboratory tests, making this disease one of the main misdiagnoses in geriatric patients [2]. It is actually accepted in literature and widespread in guidelines [3–5] or recommendations [6] that suspicion of PE is based on history, analysis of risk factors for venous thromboembolic diseases, symptoms and signs together with first level instrumental examinations such as 12-leads electrocardiography (ECG), chest X-ray and blood arterial gas analysis (BGA). Once that clinical suspicion exists a clinical pre-test probability should be performed based on one of the available and validated test [7–10]. Low, moderate or high pre-test probability of PE should be integrated with immunoturbidimetric, simpli-RED or ELISA D-Dimer assay [11]. PE could reasonably be excluded when low pre-test probability and negative DDimer (

Acquired hemophilia is a rare coagulopathy in adults, associated with bleeding complications. Although the etiology of this disorder remains obscure, an autoimmune mechanism produces the development of autoantibodies against factor VIII. About half of cases are associated with other conditions, mainly post-partum, underlying cancer, autoimmune disease. An 81-year-old male was admitted to the hospital with extensive hematomas (neck, chest, arms and lower limbs). There was no family or personal history of congenital bleeding diathesis. He had chronic bronchitis and cerebrovascular disease; no drugs had been used during the month prior to noted symptoms. Laboratory parameters revealed: hemoglobin 10.9 g%, normal platelet count and white blood cells, prolonged activated partial thromboplastin time (98 s), with normal prothrombin time and fibrinogen concentration. An activated partial thromboplastin time mixing study did not show any correction, suggesting a coagulation inhibitor. Lupus anticoagulant and anticardiolipin antibodies were negative. Biochemical, immunological tests and tumor markers were normal. Thoracic and abdominal computed tomographic scan did not reveal pathological images or hematomas. Analysis of clotting factors revealed decreased factor VIII (2%) and elevated factor VIII inhibitor (55 Bethesda units). Idiopathic acquired hemophilia diagnosis was made. Red blood cell transfusion and human factor VIII (2000 U/day for 7 days) infusion were initiated, intravenously with methylprednisolone. A progressive improvement in clinical conditions and laboratory parameters was observed. After 18 days the patient was discharged and treated with prednisone. At follow-up control the clinical conditions and laboratory parameters were normal.

Masotti L, Ceccarelli E, Forconi S,Cappelli R (Cecina Hospital, Physical Medicine andRehabilitation, Livorno; and University of Siena,Siena, Italy). Prognostic role of C-reactive protein invery old patients with acute ischaemic stroke.J Intern Med 2005; 258: 145–152.Background and scope. Recent literature hasdemonstrated that inflammation contributes to allphases of atherosclerosis and brain damage causedby stroke. In acute phase of cerebrovascular diseasesbiochemical markers of inflammation, such as C-reactive protein (CRP), could represent an indicatorof severity of stroke, but few studies have verifiedthis hypothesis, especially in very old patients. Theaim of this study was to evaluate the role of CRP onshort- and long-term prognosis in 75-year old andover elderly patients with acute ischaemic stroke.Materials and methods. We retrospectively eval-uated CRP values (nephelometric method), per-formed within 12 h from hospital admission, in196 elderly patients (124 females and 72 males withmean age ± SD 83.32 ± 10.46 years), dischargedwith diagnosis of acute ischaemic stroke, 68 of themwith atherothrombotic large vessel stroke, 38 withlacunar stroke and 90 with cardioembolic stroke.We studied the relationship between CRP valuesand short-term prognosis [30-day mortality,length of hospitalization (LOS) and physicaldisability measured by modified Rankin scale andlong-term prognosis (12-month mortality andre-hospitalization)].Results. Mean values of CRP were significantlyhigher in patients with cardioembolic strokecompared with atherothrombotic large vessel andlacunar stroke, in patients who died in the first30 days from the acute event compared withsurvivors. LOS and physical disability score rosewith increasing values of CRP for all subtypesof stroke. Higher CRP values were associatedwith the 12-month re-hospitalization for cerebro-vascular events, whereas it did not influence the12-month cumulative re-hospitalization and12-month mortality.Conclusions. Elevation of CRP values at hospitaladmission could represent a negative prognosticindex in elderly patients with ischaemic stroke, inparticular, for short-term prognosis.Keywords: C-reactiveprotein,elderly,inflammation,prognosis, stroke.