Benilde Cosmi

Publications (49)301.05 Total impact

• Article: The influence of VKORC1 3730 G > A polymorphism on warfarin dose: reply.

  Michela Cini, Cristina Legnani, Benilde Cosmi, Giuliana Guazzaloca, Lelia Valdrè, Mirella Frascaro, Gualtiero Palareti
  European Journal of Clinical Pharmacology 10/2012; · 2.85 Impact Factor
• Article: A randomized double-blind study of low-molecular-weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum).

  B Cosmi, M Filippini, D Tonti, G Avruscio, A Ghirarduzzi, E Bucherini, G Camporese, D Imberti, G Palareti
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  ABSTRACT: Optimal doses and duration of low-molecular-weight heparin (LMWH) for the treatment of superficial vein thrombosis (SVT) are still uncertain. To compare the efficacy and safety of different doses and durations of LMWH parnaparin for symptomatic lower limb SVT. Outpatients with at least a 4-cm-long SVT of long or short saphenous veins or their collaterals were randomized to receive parnaparin either 8500 UI once daily ( o.d.) for 10 days followed by placebo for 20 days (group A) or 8500 UI o.d. for 10 days followed by 6400 UI once daily (o.d.) for 20 days (group B) or 4250 UI o.d. for 30 days (group C) in a double-blind fashion in 16 clinics. Primary outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT), symptomatic pulmonary embolism (PE) and relapse and/or symptomatic or asymptomatic SVT recurrence in the first 33 days with 60 days follow-up. Among 664 patients, primary outcome occurred in 33/212 (15.6%), 4/219 (1.8%) and 16/217 (7.3%) subjects in groups A, B and C, respectively (B vs. A: absolute risk reduction [ARR]: 13.7%, 95% confidence intervals [CI]: 8-18.9 P<0.001; B vs. C: ARR: 5.5%; 95% CI: 1.6-9.4 P= 0.011; C vs. A: ARR: 8.2%, 95% CI: 2-14 P=0.012). During days 0-93, the event rate was higher in group A (22.6%) than either in group B (8.7%; P=0.001) or C (14.3%, P=0.034). No major hemorrhages occurred. An intermediate dose of parnaparin for 30 days is superior to either a 30-day prophylactic dose or a 10-day intermediate dose for lower limb SVT treatment.
  Journal of Thrombosis and Haemostasis 04/2012; 10(6):1026-35. · 5.73 Impact Factor
• Article: The negative predictive value of D-dimer on the risk of recurrent venous thromboembolism in patients with multiple previous events: a prospective cohort study (the PROLONG PLUS study).

  Walter Ageno, Benilde Cosmi, Angelo Ghirarduzzi, Rita Santoro, Eugenio Bucherini, Daniela Poli, Domenico Prisco, Adriano Alatri, Vittorio Pengo, Luca Galli, Francesco Dentali, Gualtiero Palareti
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  ABSTRACT: The optimal duration of anticoagulation after recurrent venous thromboembolism(VTE) is poorly established [1,2]. Recent studies suggested that D-dimer may identify patients at low risk of recurrence after a first VTE [3,4]. In a pilot, prospective, cohort study we aimed to assess the negative predictive value of D-dimer in patients with recurrent VTE. Patients with negative D-dimer while on treatment stopped anti coagulation and underwent repeated testing after 7, 15, and 30 days; treatment was resumed if D-dimer turned positive and permanently stopped if it remained negative. The study was interrupted after the enrolment of 75 patients. At that time, treating physicians decided treatment resumption in 12.2% of the patients, but the majority of events were distal or superficial vein thromboses. The rate of objectively documented recurrent proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) was 2.56% (95% CI 0.13, 15.07%) in the 39 patients with persistently negative D-dimer at 30 days, for an annual incidence of VTE of 5.65 events/100 patient/years. These preliminary findings suggest that negative D-dimer may identify patients with history of previous VTE at low risk of recurrences, but this approach should be tested in larger trials in highly selected patients.
  American Journal of Hematology 03/2012; 87(7):713-5. · 4.67 Impact Factor
• Article: A new warfarin dosing algorithm including VKORC1 3730 G > A polymorphism: comparison with results obtained by other published algorithms.

  Michela Cini, Cristina Legnani, Benilde Cosmi, Giuliana Guazzaloca, Lelia Valdrè, Mirella Frascaro, Gualtiero Palareti
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  ABSTRACT: Warfarin dosing is affected by clinical and genetic variants, but the contribution of the genotype associated with warfarin resistance in pharmacogenetic algorithms has not been well assessed yet. We developed a new dosing algorithm including polymorphisms associated both with warfarin sensitivity and resistance in the Italian population, and its performance was compared with those of eight previously published algorithms. Clinical and genetic data (CYP2C9*2, CYP2C9*3, VKORC1 -1639 G > A, and VKORC1 3730 G > A) were used to elaborate the new algorithm. Derivation and validation groups comprised 55 (58.2% men, mean age 69 years) and 40 (57.5% men, mean age 70 years) patients, respectively, who were on stable anticoagulation therapy for at least 3 months with different oral anticoagulation therapy (OAT) indications. Performance of the new algorithm, evaluated with mean absolute error (MAE) defined as the absolute value of the difference between observed daily maintenance dose and predicted daily dose, correlation with the observed dose and R(2) value, was comparable with or slightly lower than that obtained using the other algorithms. The new algorithm could correctly assign 53.3%, 50.0%, and 57.1% of patients to the low (≤25 mg/week), intermediate (26-44 mg/week) and high (≥ 45 mg/week) dosing range, respectively. Our data showed a significant increase in predictive accuracy among patients requiring high warfarin dose compared with the other algorithms (ranging from 0% to 28.6%). The algorithm including VKORC1 3730 G > A, associated with warfarin resistance, allowed a more accurate identification of resistant patients who require higher warfarin dosage.
  European Journal of Clinical Pharmacology 02/2012; 68(8):1167-74. · 2.85 Impact Factor
• Article: Thigh-length versus below-knee compression elastic stockings for prevention of the postthrombotic syndrome in patients with proximal-venous thrombosis: a randomized trial.

  Paolo Prandoni, Franco Noventa, Roberto Quintavalla, Carlo Bova, Benilde Cosmi, Sergio Siragusa, Eugenio Bucherini, Francesco Astorri, Stefano Cuppini, Fabio Dalla Valle, Anthonie W A Lensing, Martin H Prins, Sabina Villalta
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  ABSTRACT: Although below-knee compression elastic stockings (CES) are effective for the prevention of the postthrombotic syndrome (PTS), a substantial number of patients with deep venous thrombosis still develop PTS. In the present open-label, randomized clinical trial, we compared thigh-length with below-knee CES for the prevention of PTS. A total of 267 patients with the first episode of proximal deep venous thrombosis were randomized to wear either thigh-length or below-knee CES for 2 years. After 3, 6, 12, 18, 24, and 36 months, they were assessed for PTS manifestations according to the Villalta scale. PTS developed in 44 (32.6%) of the 135 patients randomized to thigh-length CES and in 47 (35.6%) of the 132 allocated to below-knee CES, for an adjusted hazard ratio of 0.93 (95% confidence interval, 0.62-1.41). Severe PTS developed in 3 patients in each group. CES-related side effects developed in 55 (40.7%) of the 135 patients allocated to thigh-length CES and in 36 (27.3%) of those randomized to the below-knee group (P = .017), and led to premature discontinuation of their use in 29 (21.5%) and 18 (13.6%) patients, respectively. We conclude that thigh-length CES do not offer a better protection against PTS than below-knee CES and are less well tolerated.
  Blood 12/2011; 119(6):1561-5. · 9.90 Impact Factor
• Article: Old and new heparins.

  Benilde Cosmi, Gualtiero Palareti
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  ABSTRACT: Heparin is an effective, relatively safe, inexpensive parenteral antithrombotic agent widely used in the prevention and treatment of thromboembolic disorders, but it has several limitations such as the marked intra- and inter-patient variability in its anticoagulant response, its poor bioavailability at low doses and its relatively narrow risk to benefit ratio. Low molecular weight heparins ( LMWHs), ultra LMWHs and synthetic pentasaccharides have been developed from heparin to overcome its limitations. The characteristics of these compounds are reviewed along with the description of their approved clinical uses.
  Thrombosis Research 12/2011; 129(3):388-91. · 2.44 Impact Factor
• Article: Risk of early recurrent fetal loss and levels of thrombin-activatable fibrinolysis inhibitor.

  Cristina Legnani, Monica Bovara, Lelia Valdrè, Benilde Cosmi, Andrea Caniato, Gualtiero Palareti
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  ABSTRACT: Though thrombin-activatable fibrinolysis inhibitor (TAFI) may contribute to hypercoagulability during pregnancy, limited data are available on the role of TAFI in women with recurrent fetal loss. We performed a case-control study aimed at evaluating any possible association between TAFI levels and early recurrent fetal loss (≥ 3, or 2 with at least one normal fetal karyotype, before the 10th week of gestation). 140 women with early recurrent fetal loss and 140 age-matched healthy controls with at least one normal pregnancy were included. The number of miscarriages was 2.59 and occurred at gestational age 6.89 weeks. TAFI levels were determined by a chromogenic assay measuring total potential activatable TAFI. TAFI levels were significantly lower in early recurrent fetal loss women (12.2 ± 2.3 μg/ml vs 13.2 ± 2.6 μg/ml in healthy controls, p=0.001). ORs of early recurrent fetal loss (crude and adjusted for possible confounding variables) were calculated after stratification of TAFI levels into quartiles. 25/140 (17.8%) early recurrent fetal loss women had TAFI levels above 14.0 μg/ml (4th quartile) vs 44/140 (31.3%) in healthy women (p=0.014). Crude and adjusted ORs of early recurrent fetal loss in women with TAFI levels in the 4th quartile vs those in the reference category (1st quartile=below 11.0 μg/ml) were 0.42 (95%CI: 0.22-0.82) and 0.39 (95%CI: 0.19-0.80), respectively. Our study provides evidence that high TAFI levels are associated with reduced risk of early recurrent fetal loss. Further studies are needed to better understand the actual role of TAFI in recurrent fetal loss.
  Thrombosis Research 10/2011; 130(2):237-41. · 2.44 Impact Factor
• Article: Age and gender specific cut-off values to improve the performance of D: -dimer assays to predict the risk of venous thromboembolism recurrence.

  Cristina Legnani, Michela Cini, Benilde Cosmi, Paolo Carraro, Armando Tripodi, Nicoletta Erba, Gualtiero Palareti
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  ABSTRACT: The Prolong study shows that continuing vitamin K antagonists (VKA) in patients with abnormal D: -dimer (evaluated by a qualitative assay, Clearview Simplify D: -dimer) results in a significant reduction of venous thromboembolism (VTE) recurrence. The present study retrospectively analyzes a subgroup of patients enrolled in the Prolong study with a view to calculate cut-off values for six quantitative D: -dimer methods to predict the risk of VTE recurrence. We measured D: -dimer levels by VIDAS D: -dimer Exclusion (bioMerieux), STA Liatest D: -dimer (DiagnosticaStago), HemosIL D: -dimer and HemosIL D: -dimer HS (Instrumentation Laboratory), Innovance D: -dimer (Siemens) and AutoDimer (Trinity Biotech) in frozen plasma aliquots sampled 30 ± 10 days after VKA cessation in 390 patients enrolled in the Prolong study. During follow-up (562.7 years), 28 patients had recurrent VTE (7.2%, 5.0% person-years). Since D: -dimer levels are positively correlated with age and significantly lower in men, we calculated method-specific cut-off values according to age and gender. The HRs for VTE recurrence calculated using method-specific cut-off values based on age and gender are higher than those using cut-off values indicated by the manufacturers for VTE exclusion in symptomatic outpatients. These data suggest that method-specific cut-off values calculated according to patient age and gender can be more accurate in identifying patients at a higher risk for VTE recurrence. These method-specific cut-off values are being evaluated in the ongoing prospective management multicenter DULCIS study.
  Internal and Emergency Medicine 05/2011; · 2.06 Impact Factor
• Article: Residual emboli on lung perfusion scan or multidetector computed tomography after a first episode of acute pulmonary embolism.

  Benilde Cosmi, Mathilde Nijkeuter, Massimo Valentino, Menno V Huisman, Libero Barozzi, Gualtiero Palareti
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  ABSTRACT: The rate of resolution of a first episode of pulmonary embolism (PE) is uncertain. A baseline test indicating any residual PE is pivotal in aiding a more accurate diagnosis of recurrent PE. This study aimed to assess the rate and risk factors of residual PE with either multidetector computed tomography imaging (MDCT) or lung perfusion scan (LPS) using a cross-sectional study in which consecutive patients were enrolled with a first objectively documented episode of symptomatic PE, and who were considered for possible treatment withdrawal after at least 3 months of anticoagulation. A first cohort of patients (n = 80) underwent MDCT, while the subsequent cohort (n = 93) underwent LPS. The two cohorts had similar characteristics, and 98.3% of patients had non high-risk index PE. MDCT detected residual PE in 15% of subjects (12/80, 95% CI 8-25%) after a mean of 9 months of anticoagulation. No clinical characteristics were significantly associated with residual PE at MDCT. LPS detected residual PE in 28% (26/93, 95% CI 19-38%) of patients after a period of a mean of 9 months of anticoagulation with a significant association with increasing age and known pulmonary disease. Resolution of PE was high after a first episode of non high-risk PE treated with heparin followed by at least 3 months of anticoagulation. Age and coexistent pulmonary disease influence the presence of residual PE detected by LPS, but not by MDCT. Further studies are warranted in which the presence of residual embolism is detected by repetition of the same test that had been initially carried out.
  Internal and Emergency Medicine 04/2011; 6(6):521-8. · 2.06 Impact Factor
• Source

  Available from: Alfonso Iorio

  Article: Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis.

  James Douketis, Alberto Tosetto, Maura Marcucci, Trevor Baglin, Benilde Cosmi, Mary Cushman, Paul Kyrle, Daniela Poli, R Campbell Tait, Alfonso Iorio
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  ABSTRACT: To determine the effect of sex on the risk of recurrent venous thromboembolism in all patients and in patients with venous thromboembolism that was unprovoked or provoked (by non-hormonal factors). Data source Comprehensive search of electronic databases (Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials) until July 2010, supplemented by review of conference abstracts and contact with content experts. Seven prospective studies investigating an association between D-dimer, measured after anticoagulation was stopped, and disease recurrence in patients with venous thromboembolism. Patient level databases were obtained, transferred to a central database, checked, and completed with further information provided by authors. 2554 patients with a first venous thromboembolism had follow-up for a mean of 27.1 (SD 19.6) months. The one year incidence of recurrent venous thromboembolism was 5.3% (95% confidence interval 4.1% to 6.7%) in women and 9.5% (7.9% to 11.4%) in men, and the three year incidence of recurrence was 9.1% (7.3% to 11.3%) in women and 19.7% (16.5% to 23.4%) in men. Among patients with unprovoked venous thromboembolism, men had a higher risk of recurrence than did women (hazard ratio 2.2, 95% confidence interval 1.7 to 2.8). After adjustment for women with hormone associated initial venous thromboembolism, the risk of recurrence remained higher in men (hazard ratio 1.8, 1.4 to 2.5). In patients with provoked venous thromboembolism, occurring after exposure to a major risk factor, recurrence of disease did not differ between men and women (hazard ratio 1.2, 0.6 to 2.4). In women with hormone associated venous thromboembolism and no other risk factors, recurrence was lower than that in women with unprovoked venous thromboembolism and no previous hormone use (hazard ratio 0.5, 0.3 to 0.8). In patients with a first unprovoked venous thromboembolism, men have a 2.2-fold higher risk of recurrent venous thromboembolism than do women, which remained 1.8-fold higher in men after adjustment for previous hormone associated venous thromboembolism in women. In patients with a first provoked venous thromboembolism, risk of recurrence does not differ between men and women with or without hormone associated venous thromboembolism. Indefinite anticoagulation may be given greater consideration in men than in women after a first venous thromboembolism.
  BMJ (Clinical research ed.). 01/2011; 342:d813.
• Source

  Available from: Michelangelo Sartori

  Article: Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study.

  Gualtiero Palareti, Benilde Cosmi, Gianfranco Lessiani, Giuseppina Rodorigo, Giuliana Guazzaloca, Carlotta Brusi, Lelia Valdré, Eleonora Conti, Michelangelo Sartori, Cristina Legnani
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  ABSTRACT: The natural history of calf deep-vein thrombosis (DVT) is still uncertain and it is debated whether it warrants to be diagnosed and treated. We aimed to investigate the complication rate of untreated isolated calf DVT (ICDVT). Symptomatic outpatients were prospectively managed with serial compression ultrasonography (SCUS). Those without proximal DVT and with likely pre-test clinical probability (PCP) or altered D-dimer received immediate subsequent complete examination of calf deep veins (CCUS) by a different operator. The result of CCUS was kept blind both to the managing doctor and the patient and disclosed after three months. Primary outcome was the rate of venous thromboembolism at three months. We examined 431 subjects (196 males; median age 68.0 years) in whom five outcomes were recorded (1.2%; 95% confidence intervals [CI]: 0.4-2.7). If CCUS results had been available, outcomes would have been recorded in 3/424 patients (0.7%; 95% CI: 0.2-2.1) with two events in subjects negative at both serial and complete CUS. ICDVT was diagnosed in 65 subjects (15.3%; 95% CI: 12-19); of whom 59 remained uneventful (one was lost to follow-up). A significant higher rate of outcomes was recorded in subjects with than without ICDVT (5/64; 7.8%; 95% CI: 3-17 vs. 3/351; 0.8%; 95% CI: 0-2; p=0.003). However, after excluding two events picked at serial CUS in subjects with ICDVT, the difference became barely significant (3/64; 4.7%; 95% CI: 1-13; p=0.049). Thrombotic evolution of untreated ICDVT in high-risk subjects may be relevant. Larger studies are needed to address this issue.
  Thrombosis and Haemostasis 11/2010; 104(5):1063-70. · 5.04 Impact Factor
• Article: Abnormal Protac-induced coagulation inhibition chromogenic assay results are associated with an increased risk of recurrent venous thromboembolism.

  Armando Tripodi, Cristina Legnani, Laura Lemma, Benilde Cosmi, Gualtiero Palareti, Veena Chantarangkul, Pier Mannuccio Mannucci
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  ABSTRACT: Evaluation of the risk of recurrent venous thromboembolism (VTE) is required to determine the optimal duration of secondary prophylaxis. Application of global assays reflecting the pro- versus anti-coagulant balance in vivo would be desirable. We aimed at investigating the relationship between recurrent VTE and the Protac-induced coagulation inhibition (PICI) assay, which is based on tissue factor-induced thrombin generation measured by a chromogenic substrate. One-hundred-ninety patients were followed-up after a first episode of unprovoked, objectively documented VTE for 2.7 years after stopping treatment with vitamin K antagonists (VKA). PICI was measured 1 month after stopping treatment as the percentage of the OD values recorded without or with Protac. The lower the PICI%, the greater the pro- versus anti-coagulant imbalance. The study outcome was objectively-documented symptomatic recurrent VTE. Patients with PICI% <or= 74% had crude hazard-ratios (HR) (95% CI) for recurrent VTE of 2.86 (1.01-8.12) as compared to those with PICI% > 87%. After adjustment for age, gender, type of index event, VKA duration and normal/abnormal D-Dimer, HR (95% CI) were substantially unchanged [2.91 (1.01-8.38)]. The corresponding values after further adjustment for the above variables plus the absence/presence of the most frequent thrombophilic alterations were 3.38 (1.16-9.84). These HR values compare favorably with those obtained in a previous study investigating the thrombin generation test performed in the presence of thrombomodulin. In conclusion, the measurement of PICI helps to identify patients at higher risk of VTE recurrence. Advantages of PICI over thrombin generation tests are easy performance in general clinical laboratories, easy standardization and no special equipment.
  Journal of Thrombosis and Thrombolysis 08/2010; 30(2):215-9. · 1.48 Impact Factor
• Chapter: Anticoagulation

  Gualtiero Palareti, Benilde Cosmi
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  ABSTRACT: Administration of vitamin K antagonists has been the mainstay of anticoagulation for more than 50 years and an increasing number of subjects receive this treatment all over the world. This chapter is dedicated to helping doctors deal with the most important practical aspects in managing the treated patients.
  05/2010: pages 164 - 176; , ISBN: 9781444306286
• Article: Anticoagulation

  Gualtiero Palareti, Benilde Cosmi
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  ABSTRACT: Administration of vitamin K antagonists has been the mainstay of anticoagulation for more than 50 years and an increasing number of subjects receive this treatment all over the world. This chapter is dedicated to helping doctors deal with the most important practical aspects in managing the treated patients.
  05/2010;
• Article: Update on the predictive value of D-dimer in patients with idiopathic venous thromboembolism.

  Benilde Cosmi, Gualtiero Palareti
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  ABSTRACT: The optimal duration of oral anticoagulation after a first unprovoked venous thromboembolism (VTE) is uncertain. The aim of this review is to evaluate the predictive role of D-dimer testing for recurrence after idiopathic VTE with the update of the most recent publications. In the PROLONG study patients with normal D-dimer at one month after anticoagulation withdrawal did not resume anticoagulation and had 4.4% patient-years of recurrences. Patients with abnormal D-dimer were randomized to resume or not anticoagulation and had 2% and 10.2% recurrences, respectively. These results were confirmed also after extending the follow-up to a mean of 2.55 years and indicate that patients with abnormal D-dimer after anticoagulation withdrawal are at higher risk for recurrence versus those with normal D-dimer and benefit from prolongation of anticoagulation. However, in patients with a normal D-dimer, the duration of treatment remains uncertain as the recurrence rate of approximately 5% patient-years may also warrant anticoagulation. The prospective observational PROLONG II aimed at assessing D-dimer time course and its relation with late recurrences in patients with normal D-dimer at 1 month. Patients repeated D-dimer testing every two months for one year. The few patients in whom D-dimer became abnormal at the 3(rd) month and remained abnormal afterwards had a higher risk of recurrence (27% patient-years) than patients with persistently normal D-dimer (2.9% patient-years) (adjusted HR: 7.9; 95% CI:2.1-30; p = 0.002). These results indicate that repeated D-dimer testing after anticoagulation suspension may help tailor the individual duration of treatment after a first unprovoked VTE.
  Thrombosis Research 04/2010; 125 Suppl 2:S62-5. · 2.44 Impact Factor
• Article: Emerging drugs for venous thromboembolism.

  Gualtiero Palareti, Benilde Cosmi
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  ABSTRACT: Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, is a frequent and serious condition. Anticoagulant (AC) drugs are necessary and effective for primary prevention, treatment of acute phase and prevention of recurrences. The currently available ACs have several drawbacks which have prompted the search for new drugs. We analysed the advantages and disadvantages of the emerging ACs in comparison to currently available ACs by reviewing the available results of drugs that have Phase III clinical trials for prevention and treatment of VTE, published between 2003 and September 2009. The reader will get information on efficacy and safety of new ACs in comparison to the standard treatment for prevention of VTE after elective major orthopaedic surgery and on the prospects of their use for treatment of VTE. These new ACs will be an important step forward for an easier, effective and safe prophylactic and therapeutic treatment of VTE. Some grey areas in their use require, however, a careful consideration and an accurate post-marketing investigation.
  Expert Opinion on Emerging Drugs 03/2010; 15(1):107-17. · 3.21 Impact Factor
• Article: Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study.

  Benilde Cosmi, Cristina Legnani, Alberto Tosetto, Vittorio Pengo, Angelo Ghirarduzzi, Sophie Testa, Domenico Prisco, Daniela Poli, Armando Tripodi, Francesco Marongiu, Gualtiero Palareti
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  ABSTRACT: The PROLONG randomized trial showed that a normal D-dimer (D-d) 1 month after anticoagulation suspension for unprovoked venous thromboembolism (VTE) was associated with a low risk of late recurrences (4.4% patient years). However, it is unknown whether D-d changes subsequently. The aim of this prospective multicenter study was to assess D-d time course and its relation with late recurrences in patients with normal D-d 1 month after anticoagulation suspension for a first episode of unprovoked VTE. D-d was measured with a qualitative method (Clearview Simplify D-dimer; Inverness Medical Professional Diagnostics). Patients with a normal D-d 1 month after stopping anticoagulation repeated D-d testing every 2 months for 1 year. D-d was normal in 68% (243/355) of patients 1 month after anticoagulation suspension. Patients in whom D-d became abnormal at the third month and remained abnormal afterward had a higher risk of recurrence (7/31; 27% patient years; 95% confidence interval [CI]: 12-48) than patients in whom D-d remained normal at the third month and afterward (4/149; 2.9% patient years; 95% CI: 1-7; adjusted hazard ratio: 7.9; 95% CI: 2.1-30; P = .002). Repeated D-d testing after anticoagulation suspension for a first episode of unprovoked VTE could help tailor the duration of treatment. This trial is registered at http://clinicaltrials.gov as NCT00266045.
  Blood 11/2009; 115(3):481-8. · 9.90 Impact Factor
• Source

  Available from: Marco Cattaneo

  Article: Assessment of the risk of bleeding in patients undergoing surgery or invasive procedures: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET).

  Benilde Cosmi, Adriano Alatri, Marco Cattaneo, Paolo Gresele, Marco Marietta, Francesco Rodeghiero, Armando Tripodi, Luca Ansaloni, Maurizio Fusari, Stefania Taddei
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  ABSTRACT: SYNOPSIS OF RECOMMENDATIONS: The Italian Society for Thrombosis and Haemostasis (SISET: Società Italiana per lo Studio dell' Emostasi e della Trombosi) promoted the development of a series of guidelines which would adopt evidence-based medicine methodology on clinically relevant problems in the field of haemostasis and thrombosis. The objective of the present guidelines is to provide recommendations for the pre-operative and pre-procedural assessment of the bleeding risk with the aim of reducing the incidence of preventable bleeding complications and limiting laboratory tests to the those necessary. The predictive value of haemostatic tests for bleeding complications after surgery or invasive procedures has been evaluated in prospective or retrospective cohort studies only. All retrieved studies were of low methodological quality with a high potential for bias because none conducted a blinded outcome assessment. In addition, different criteria for the severity of bleeding events and different reference values of the laboratory tests were adopted. The low methodological quality limits the validity of the results of these studies. Some of the clinical queries proposed by the working group were not addressed by the studies available in the literature. The areas with evidence, although of low quality, are the following: general surgery in adults (for history, PT, APTT, platelet count and bleeding time), neurosurgery in adults (for history, PT, APTT, platelet count), adenotonsillectomy in children (for history, PT, APTT, platelet count and bleeding time), invasive procedures in adults (for PT, APTT, platelet count), dental extractions (for the bleeding time only), cataract extraction (for platelet count). No studies are available in children for major surgery other than adenotonsillectomy, neurosurgery and invasive procedures.
  Thrombosis Research 10/2009; 124(5):e6-e12. · 2.44 Impact Factor
• Article: Bleeding with anticoagulation therapy - who is at risk, and how best to identify such patients.

  Gualtiero Palareti, Benilde Cosmi
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  ABSTRACT: Anticoagulation with vitamin K antagonists (VKAs) has been shown to be effective in the prevention and treatment of thrombotic complications in various clinical settings, including atrial fibrillation (AF), venous thromboembolism (VTE), acute coronary syndromes and after invasive cardiac procedures. Bleeding is the most important complication of VKAs and a major concern for both physicians and patients. The occurrence of bleeding during treatment is not only important for the treated subjects, but also for a correct and complete use of this therapy in all the subjects who have a clear clinical indication for anticoagulation. This review analyses the treatment- and person-associated risk factors for bleeding during VKAs and their combination in clinical prediction rules that have been proposed in the attempt to identify those patients at higher risk for bleeding. The clinical prediction rules may help physicians stratify patients into categories of risk and thus to evaluate their individual risk/benefit ratio of starting or prolonging an anticoagulant treatment.
  Thrombosis and Haemostasis 09/2009; 102(2):268-78. · 5.04 Impact Factor
• Article: Objectives and methodology: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET).

  Alfonso Iorio, Walter Ageno, Benilde Cosmi, Davide Imberti, Federico Lussana, Sergio Siragusa, Daniela Tormene, Alberto Tosetto, Marco Cattaneo
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  ABSTRACT: 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.
  Thrombosis Research 07/2009; 124(5):e1-5. · 2.44 Impact Factor