Publications by authors named "Guglielmo Mariani"

35 Publications

Deferment of objective assessment of deep vein thrombosis and pulmonary embolism without increased risk of thrombosis: a practical approach based on the pretest clinical model, D-dimer testing, and the use of low-molecular-weight heparins.

Arch Intern Med 2004 Dec 13-27;164(22):2477-82

Thrombosis and Hemostasis Unit, Division of Haematology, University of Palermo, Palermo, Italy.

Background: Treatment of patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) is problematic if diagnostic imaging is not immediately available. Pretest clinical probability (PCP) and D-dimer assessment can be used to identify patients for whom empirical protective anticoagulation is indicated. To evaluate whether PCP and D-dimer assessment, together with the use of low-molecular-weight heparins (LMWHs), allow objective appraisal of DVT and PE to be deferred for up to 72 hours, patients with suspected DVT and PE were prospectively examined.

Methods: Patients identified with a high PCP or a moderate PCP with positive D-dimer test results received a protective full-dose treatment of LMWH; the remaining patients were discharged without anticoagulant administration. However, all patients were scheduled to undergo objective tests for DVT or PE within 72 hours. Standard antithrombotic therapy was administered when deferred diagnostic tests confirmed venous thromboembolism.

Results: In total, 409 consecutive patients with suspected DVT and 124 with suspected PE were included in this study. A total of 23.8% (95% confidence interval [CI], 20.3%-27.3%) of patients had confirmed venous thromboembolism. At the short-term follow-up (72 hours), only a single thromboembolic event (0.2%; upper 95% CI, 0.6%) had occurred, whereas at the 3-month follow-up, 5 events (1.2%; 95% CI, 0.2%-2.1%) had occurred in patients in whom diagnosis of DVT or PE had previously been ruled out. None of the patients had major bleeding events. Ninety percent of patients were treated as outpatients.

Conclusion: Our study demonstrates that this approach allows the safe deferral of diagnostic procedures for DVT and PE for up to 72 hours.
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http://dx.doi.org/10.1001/archinte.164.22.2477DOI Listing
January 2005

Continuous intravenous infusion of dipyridamole as adjunctive therapy in the treatment of thrombotic thrombocytopenic purpura.

Transfus Apher Sci 2003 Oct;29(2):141-5

Cattedra e Divisione di Ematologia con Unità Trapianto, Policlinico Universitario di Palermo, via del Vespro 129, 90127 Palermo, Italy.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon hematologic thrombotic disorder characterized by fever, hemorrhagic and neurologic signs. The advent of plasma exchange has dramatically improved the prognosis of this disease, which was once inevitably fatal. However, mortality rates remain significant. Antiplatelet drugs have been widely used in combination with plasma exchange. In this pilot study we investigated the effects of an adjunctive therapy consisting of the continuous, intravenous infusion of dipyridamole, a modality of administration that has not been previously tested in this setting. Sixteen untreated TTP patients, diagnosed consecutively at our clinic, received daily plasma exchange together with intravenous methylprednisolone (1-2 mg/kg/twice daily) and a continuous i.v. infusion of dipyridamole (100 mg/day). A complete response was defined as an improvement in the platelet count to more than 150 x 10(9)/l for two consecutive days and no neurologic deterioration. The overall response rate was 87.5%. One patient failed to respond to the combination therapy but attained a consistent remission after autologous stem cells transplant. One patient was refractory to the combination therapy and died, after an initial but unsustained response. The results of this pilot study suggest that the continuous infusion of dipyridamole is safe and might provide additional benefit in the treatment of TTP when combined with plasma exchange and steroids. However, a randomized study will be necessary to properly test whether the addition of dipyridamole improves the efficacy of plasma exchange in patient with TTP.
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http://dx.doi.org/10.1016/S1473-0502(03)00118-6DOI Listing
October 2003

Immune tolerance induction in hemophilia A: a review.

Semin Thromb Hemost 2003 Feb;29(1):69-76

Hematology and BMT Unit, University of Palermo Medical School, Palermo, Italy.

In this article, a comparative analysis of the data stemming from the studies conducted in the field of immune tolerance treatment (ITT) of hemophilia A was attempted. Comparisons are difficult because previous studies differ in many respects, including the dosage of factor (F) VIII, the number of FVIII administrations per day, the association with immunosuppressive drugs (prednisone, cyclophosphamide), and, most importantly, the definition of success in terms of the reacquisition of tolerance. However, a number of variables consistently influenced outcome: the inhibitor titer, either the maximum one or the one assayed before immune tolerance (IT) start and age. As to the FVIII dose, results are contrasting, even though the overall impression is that high dosages are associated with higher success rates. Treatment duration analyses appear to be fairly consistent in all the studies, with 1 year as the crucial time period useful in predicting outcome. Preliminary data suggest that concentrates containing von Willebrand factor may increase the success rate and allow patients refractory to IT procedures carried out with ultrapure or recombinant concentrates to become tolerant in the end. These data need to be formally confirmed in trials that compare the different brands. In the studies published so far, a common language and widely accepted definitions of the variables have emerged, which are important in setting up the controlled trials and improving the comparison among published data.
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http://dx.doi.org/10.1055/s-2003-37941DOI Listing
February 2003

Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up.

Blood 2002 Nov;100(9):3141-6

Hematology, Università Campus-Bio-Medico, 83 Via Emilio Longoni, 00155 Rome, Italy.

Shortly before the all-trans retinoic acid (ATRA) era, the GIMEMA cooperative group initiated a randomized study comparing idarubicin (IDA) alone with IDA plus arabinosylcytosine (Ara-C) as induction treatment in patients with newly diagnosed hypergranular acute promyelocytic leukemia (APL). Of the 257 patients evaluable for induction treatment, 131 were randomized to receive IDA alone (arm A) and 126 to receive IDA + Ara-C (arm B). Treatment in arm A consisted of 10 mg/m(2) IDA daily for 6 consecutive days, whereas in arm B it consisted of 12 mg/m(2) IDA daily for 4 days combined with 200 mg/m(2) Ara-C daily in continuous infusion for 7 days. Once in complete remission (CR), patients received 3 consolidation courses of standard chemotherapy, and those still in CR at the end of the consolidation were randomized to receive or not receive 1 mg/kg 6-mercaptopurine daily and intramuscular injections of 0.25 mg/kg methotrexate weekly for 2 years. Overall, 100 (76.3%) patients in arm A and 84 (66.6%) patients in arm B achieved CR (P = NS). Event-free survival (EFS) rates were 35% and 23% for patients in arm A and arm B, respectively (P =.0352). Multivariate analysis revealed that EFS was favorably influenced by induction treatment with IDA alone (P =.0352) and unfavorably influenced by white blood cell (WBC) counts greater than 3000/microL (P =.0001) and increasing age (P =.0251). These results indicate that anthracycline monochemotherapy with IDA favorably influences the EFS of patients with newly diagnosed hypergranular APL.
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http://dx.doi.org/10.1182/blood-2002-02-0352DOI Listing
November 2002

Residual factor VII activity and different hemorrhagic phenotypes in CRM(+) factor VII deficiencies (Gly331Ser and Gly283Ser).

Blood 2002 Feb;99(4):1495-7

Dipartimento di Biochimica e Biologia Molecolare-CIBF, University of Ferrara, Italy.

Two cross-reacting material-positive (CRM(+)) factor VII (FVII) mutations, associated with similar reductions in coagulant activity (2.5%) but with mild to asymptomatic (Gly331Ser, c184 [in chymotrypsin numbering]) or severe (Gly283Ser, c140) hemorrhagic phenotypes, were investigated. The affected glycines belong to structurally conserved regions in the c184 through c193 and c140s activation domain loops, respectively. The natural mutants 331Ser-FVII and 283Ser-FVII were expressed, and in addition 331Ala-FVII and 283Ala-FVII were expressed because 3 functional serine-proteases bear alanine at these positions. The 331Ser-FVII, present in several asymptomatic subjects, showed detectable factor Xa generation activity in patient plasma (0.7% +/- 0.2%) and in reconstituted system with the recombinant molecules (2.7% +/- 1.1%). The reduced activity of recombinant 283Ala-FVII (7.2% +/- 2.2%) indicates that the full function of FVII requires glycine at this position, and the undetectable activity of 283Ser-FVII suggests that the oxydrile group of Ser283 participates in causing severe CRM(+) deficiency. Furthermore, in a plasma system with limiting thromboplastin concentration, 283Ser-FVII inhibited wild-type FVIIa activity in a dose-dependent manner.
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http://dx.doi.org/10.1182/blood.v99.4.1495DOI Listing
February 2002