Valentina Vedovetto

The impact of residual thrombosis on the long-term outcome of patients with deep venous thrombosis treated with conventional anticoagulation.

The impact of residual vein thrombosis (RVT) on the long-term outcome of patients with deep vein thrombosis (DVT) is unknown. We assessed the incidence of recurrent venous thromboembolism (VTE), postthrombotic syndrome (PTS), arterial thrombotic events, and cancer in patients with DVT with and without RVT. For this purpose, we evaluated up to 3 years 869 consecutive patients with acute proximal DVT who had conventional anticoagulation. RVT, defined as ultrasound incompressibility of at least 4 mm in the common femoral and/or the popliteal vein after 3 months, was detected in 429 (49.4%) patients, and was more likely in males (adjusted odds ratio [OR], 1.82; 95% confidence interval [CI], 1.37-2.04), in patients with previous VTE (OR, 1.64; 95% CI, 1.06-2.54), and in those with extensive thrombosis (OR, 3.58; 95% CI, 2.19-5.86). During the 3-year follow-up, recurrent VTE developed in 84 (19.6%) patients with RVT and 43 (9.8%) patients without RVT (adjusted hazard ratio [HR], 2.03; 95% CI, 1.40-2.94); PTS in 225 (52.4%) and 118 (26.8%), respectively (HR, 2.34; 95% CI, 1.87-2.93); arterial thrombosis in 29 (6.7%) and 14 (3.2%), respectively (HR, 2.05; 95% CI, 1.08-3.88); and cancer in 21 (4.9%) and 8 (1.8%), respectively (HR, 3.09; 95% CI, 1.31-7.28). In conclusion, in patients treated with vitamin K antagonists for prevention of recurrent VTE, RVT doubles the risk of recurrent VTE, PTS, arterial thrombosis, and cancer. Males, patients with previous VTE, and those with extensive thrombosis are independent risk factors of RVT development. Studies addressing the impact of the novel direct anticoagulants on the development of RVT as well as the long-term complications of DVT are needed.

Residual vein thrombosis and trans-popliteal reflux in patients with and without the post-thrombotic syndrome

Residual vein thrombosis and trans-popliteal reflux in patients with and without the post-thrombotic syndrome -

Unexpectedly High Recanalization Rate in Patients with Pulmonary Embolism Treated with Anticoagulants Alone

The rate of residual thrombosis, defined as the long-term persistence of thrombotic material in the pulmonary artery tree after pulmonary embolism (PE), is uncertain. Although a systematic review reported low recanalization rates (43% at 6 mo) (1), most studies used perfusion or ventilation–perfusion lung scanning or older generation computed tomography (CT) scanners. In a prospective study we determined the rate of residual thrombosis in a cohort of consecutive patients with acute PE as detected by 64-row multidetector CT (MDCT), treated with anticoagulants alone and reassessed 6 months later with the same high-technology procedure.

The risk of recurrent thromboembolic disorders in patients with unprovoked venous thromboembolism: New scenarios and opportunities

The risk of recurrent thromboembolic disorders in the 10-year period following an episode of unprovoked venous thromboembolism (VTE) ranges between 30 and 50%, the rate being higher in patients with primary deep venous thrombosis (DVT) than in those with primary pulmonary embolism (PE). The clinical presentation with primary PE increases by more than three times the risk of a new PE episode over that with isolated DVT. Baseline parameters that increase this risk are the proximal location of DVT, obesity, old age and male sex, whereas the role of thrombophilia is controversial. An increasing role is played by post-baseline parameters such as the ultrasound assessment of residual vein thrombosis and the determination of D-dimer. While the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, new scenarios are being offered by the identification of risk stratification models and by strategies that have the potential to help identify patients in whom anticoagulation can be safely discontinued, such as those that incorporate the assessment of D-dimer and residual vein thrombosis. New opportunities are being offered by low-dose aspirin, which has recently been reported to decrease by more than 30% the risk of recurrent events without increasing the bleeding risk; and especially by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving at least the same effectiveness, do not require laboratory monitoring, and can be used immediately after the thrombotic episode.

Aspirin and recurrent venous thromboembolism in patients with symptomatic atherosclerosis: retrospective cohort study

thesis by platelets: historical and new perspectives. J Thromb Haemost 2009; 7: 241–6. 11 Massberg S, Konrad I, Schurzinger K, Lorenz M, Schneider S, Zohlnhoefer D, Hoppe K, Schiemann M, Kennerknecht E, Sauer S, Schulz C, Kerstan S, Rudelius M, Seidl S, Sorge F, Langer H, Peluso M, Goyal P, Vestweber D, Emambokus NR, et al. Platelets secrete stromal cell-derived factor 1{alpha} and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo. J ExpMed 2006; 203: 1221– 33. 12 Stellos K, Langer H, Daub K, Schoenberger T, Gauss A, Geisler T, Bigalke B, Mueller I, Schumm M, Schaefer I, Seizer P, Kraemer BF, Siegel-Axel D, May AE, Lindemann S, Gawaz M. Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes differentiation of human CD34+ cells to endothelial progenitor cells. Circulation 2008; 117: 206–15.

Residual vein thrombosis and serial D-dimer for the long-term management of patients with deep venous thrombosis

BACKGROUND The optimal long-term strategy for preventing recurrent venous thromboembolism (VTE) in patients with deep-vein thrombosis (DVT) is uncertain. METHODS In 620 consecutive outpatients with a first proximal DVT who had completed at least three months of anticoagulation (unprovoked in 483, associated with minor risk factors in 137), the ultrasound presence of residual vein thrombosis (RVT) was assessed and defined as an incompressibility of at least 4mm. In 517 patients without RVT and with negative D-dimer, anticoagulation was stopped and D-dimer was repeated after one and three months. Anticoagulation was resumed in 63 of the 72 patients in whom D-dimer reverted to positivity. RESULTS During a mean follow-up of three years, recurrent VTE developed in 40 (7.7%) of the 517 patients, leading to an annual rate of 3.6% (95% CI, 2.6 to 4.9): 4.1% (95% CI, 2.9 to 5.7) in individuals with unprovoked DVT, and 2.2% (95% CI, 1.1 to 4.5) in those with DVT associated with minor risk factors. Of the 233 males with unprovoked DVT, 17 (7.3%) developed events in the first year of follow-up. Major bleeding complications occurred in 8 patients while on anticoagulation, leading to an annual rate of 1.2% (95% CI, 0.6 to 2.4). CONCLUSIONS Discontinuing anticoagulation in patients with a first episode of proximal DVT based on the assessment of RVT and serial D-dimer leads to an overall annual rate of recurrent VTE lower than 5.0%, which is the rate deemed as acceptable by the Subcommittee on Control of Anticoagulation of the ISTH. However, in males with unprovoked DVT there is room for further improving the long-term strategy of VTE prevention. (ClinicalTrials.gov number, NCT01285661).

Further evidence in support of the association between venous thrombosis and atherosclerosis: a case-control study.

INTRODUCTION Whether there is an association between venous thromboembolism (VTE) and atherosclerosis is still controversial. AIMS In a case-control study conducted on subjects older than 50, we assessed the prevalence of symptomatic or subclinical atherosclerosis in a group of unselected patients with unprovoked VTE, and compared it with that of patients with secondary VTE and of matched control individuals free from VTE disorders. METHODS Cases and controls were enquired about the presence of previous symptomatic manifestations of atherosclerosis. Those with a negative history underwent the ultrasound assessment of carotid arteries following a standardized procedure. An intima-media thickness higher than 0.9 mm or the detection of at least one carotid plaque was regarded as a subclinical manifestation of atherosclerosis. After adjusting for age, gender and risk factors for atherosclerosis, we calculated the odds ratio (OR) for symptomatic or subclinical atherosclerosis in patients with unprovoked VTE as compared to those with secondary VTE and controls. RESULTS We recruited 100 patients with unprovoked VTE, 100 with secondary VTE and 100 control individuals. In patients with unprovoked VTE, the adjusted OR for symptomatic or subclinical atherosclerosis was 5.1 (95% CI, 2.0 to 13.1) in comparison to patients with secondary VTE, and 14.5 (95% CI, 5.8 to 36.3) in comparison to controls. The prevalence of atherosclerosis was higher in patients with secondary VTE than in controls (OR, 3.1; 95% CI, 1.6 to 6.1). CONCLUSION The results of this study confirm the presence of a strong association between venous thrombosis and atherosclerosis.

What are the pharmacotherapy options for treating venous thromboembolism in cancer patients

Introduction: Venous thromboembolism (VTE) is a frequent complication in patients with malignancies. The treatment of VTE disorders in cancer patients remains a difficult clinical task. Areas covered: Current evidence on the most appropriate initial and long-term treatment of cancer patients with VTE was addressed, as was the management of recurrent VTE despite anticoagulation, the management of incidentally detected isolated pulmonary embolism (PE), the potential role of the novel direct oral anticoagulants and the impact of low-molecular-weight heparin (LMWH) on cancer evolution. Expert opinion: LMWHs are the cornerstone of VTE treatment in cancer patients. The intensity and duration of treatment are dependent on several factors that need to be individually evaluated. The novel oral anticoagulants should be investigated more carefully before being routinely implemented in the treatment of cancer-associated VTE. Incidentally detected isolated sub-segmental PE is unlikely to require systematic full-dose anticoagulation. Evidence favoring an impact of LMWH on survival in cancer patients is weak.

Physicians’ compliance with the Padua Prediction Score for preventing venous thromboembolism among hospitalized medical patients

Hospitalization for acute medical illnesses confers an 8-fold increased risk of venous thromboembolic (VTE) disorders that persists for up to 3 months and is even higher after discharge than during in-hospital stay [1]. However, in spite of strong evidence in favor of thromboprophylaxis [2–4], several observation studies from various countries found that less than 50% of admitted medical patients at risk receive prophylaxis against VTE [5–8]. We have recently identified and validated a suitable and effective risk assessment model, the Padua Prediction Score (PPS), for optimal stratification of the thrombotic risk in hospitalized medical patients [9]. Its implementation in the Departments of Internal Medicine has recently been suggested by the latest ACCP consensus guidelines [10]. For the purpose of that investigation, attending physicians were not informed about the thrombotic risk of their patients and, as a result, less than 40% managed their patients correctly [9]. In an attempt to assess whether awareness of the thrombotic risk – as assessed with the PPS – has the potential to increase the rate of appropriate thromboprophylaxis in high-risk medical patients, we performed a second prospective investigation within the same framework as the first. On this occasion, we alerted the attending physicians to the thrombotic risk of their patients by tracing a well visible red line on the clinical chart of those who were at high risk. In addition, for further confirmation that the adoption of the PPS has the potential to improve patients’ outcome, we registered the thrombotic and hemorrhagic events occurring up to 90 days after recruitment in the high-risk patients. Any decisions concerning use and timing of prophylaxis were left to the discretion of the attending physicians. The investigation was approved by the Ethical Board of the University Hospital of Padua. Out of 1600 consecutive patients admitted to the Second Division of Internal Medicine of the University Hospital of Padua (Italy) between January 2010 and December 2011, 797 were excluded due to indications for anticoagulant treatment (740), contraindications for pharmacological prophylaxis (40), failure to give informed consent (10) or difficulties in obtaining follow-up information (8). Accordingly, 803 patients were recruited, of whom 296 (39.6%) were at high risk and 507 at low risk of VTE based on the PPS. Table 1 shows the main clinical features of the high-risk patients. Consistent with the previous investigation [8], prescriptions were regarded as adequate if enoxaparin 4000 U, dalteparin 5000 U or fondaparinux 2.5 mg were administered once a day within 48 h of hospital admission and for at least 80% of the hospital stay. Of the 296 high-risk patients, 262 (88.5%) received adequate pharmacological prophylaxis during hospitalization, this proportion being more than twice as high as that (186/469, 39.6%; P < 0.00001) recorded in the previous study [8]. The remaining 34 (11.5%) were either not treated or received inadequate prophylaxis. The median duration of prophylaxis during hospital stay was 12 days (interquartile range, 3–15). Thromboprophylaxis was continued after discharge in 50 patients (19.1%) for variable periods (ranging from 1 to 5 weeks). Thromboprophylaxis was also administered in 15 (2.9%) low-risk patients. Patients developing a clinical suspicion of DVT and/or PE were diagnosed by means of pre-test clinical probability and D-dimer [11,12]. Those with low pre-test probability and negative D-dimer were regarded as free from complications. For all other combinations, objective tests were performed in order to confirm or exclude the clinical suspicion (compression ultrasonography of the whole deep vein system in the case of suspected DVT; spiral CT or V/Q scanning of the lungs in the case of suspected PE) with the use of widely accepted diagnostic criteria. In the event of death, the diagnosis of PE was accepted if it was Correspondence: Paolo Prandoni, Department of Cardiothoracic and Vascular Sciences, Clinica Medica 2, University of Padua, Via Giustiniani 2, 35128 – Padua, Italy. Tel.: +39 49 8212656; fax: +39 49 8218731. E-mail: paoloprandoni@tin.it

High rate of inter-observer agreement between professional-rated scores of the Villalta scale for the assessment of the post-thrombotic syndrome.

The post thrombotic syndrome (PTS) develops in up to 50% of patients with proximal deep vein thrombosis (DVT) of the lower extremities due to venous hypertension [1–3]. It usually appears within two years since the DVT and in approximately 3–10% of cases is reported as moderate or severe with an important impact in daily-life activities [4]. The Villalta scale is recognized by the International Society on Thrombosis and Haemostasis as the gold standard for the assessment of PTS [5]. This scale is based on the evaluation of seven signs and five symptoms with a severity grade scale for each one (0–3) with the exception of leg ulcers that have a dichotomous value (yes/no). PTS is confirmed when the overall score is N4 and is classified according to the value obtained as mild (5–9), moderate (10–14) and severe (≥15 or presence of leg ulcers) [6]. While the correct assessment of PTS has a great value for the identification of those patients who require proper follow-up and therapeutic management, available studies have reported so far only a moderate agreement between patient-rated and professional-rated assessment of the scale, and few data are available on the inter-observer variability between professionals [7–8]. We sought to evaluate the inter-observer agreement of the Villalta scale between professionals assessing PTS. A cross-sectional study was conducted in two Third-level Centres for Thrombotic Disorders in Italy (Padua and Treviso) between January 2014 and April 2016. Consecutive outpatients referring for their regular follow-up visit after a first-ever episode of acute proximal DVT between three months and two years since the eventwere considered for enrolment. Patientswith a proximal bilateral thrombosis were excluded, aswere thosewith a history of previous DVT (within the previous three years) in the same leg. Two trained clinicians assessed the presence and severity of PTS independently from each other with the use of the Villalta scale. Results obtained were compared, and inter-observer agreement was calculated using the Kappa Cohen test. Out of 150 eligible subjects, 36were excluded due to a previous DVT and 7 for bilateral thrombosis. Of the remaining patients, 11 did not give their informed consent. Table 1 shows the main demographic and clinical characteristics of the 96 patients who were recruited. The inter-observer agreement for the presence of PTS was high (Kappa 0.84, 95% CI 0.69–0.95). Indeed, the two assessors agreed on the presence of PTS in 31 subjects (32.3%) and on its absence in 58 (60.4%), whereas their interpretation was discordant in only 7 (7.3%). Details of PTS assessment are shown in Table 2,which reports K scores for each sign and symptom. Mean PTS score values obtained by the two operators were comparable (3.79 ± 3.5 versus 3.97 ± 3.83; p = 0.74). The inter-observer