Haematologica 2004;89: supplement no. 8 - Supplements ...

18Selected Oral CommunicationsSISET PrizeCOS-14THE G20210A PROTHROMBIN GENE MUTATION: IS THEREROOM FOR SCREENING FAMILIES?Tognin G, Tormene D, Perlati M, Zerbinati P,Fadin M, Gavasso S, Rossetto V, Pagnan A,Prandoni P, Simioni PDept. of Medical and Surgical Sciences, 2 nd Chair ofInternal Medicine, University of Padua MedicalSchool, Padua, ItalyBackground. The G20210A prothrombin variant is acommon polymorphism associated with an increasedrisk of venous thromboembolism (VTE). A clear definitionof the thrombotic risk in heterozygous carriers ofthis defect is necessary to establish prophylacticguidelines. Methods. First-degree relatives of consecutivepatients referred to our Center with a history ofthrombotic disease and identified as heterozygouscarriers of prothrombin G20210A were enrolled in thestudy, provided that they were aged above 15 years.Before DNA testing, a medical history was taken withspecific attention to previous VTE (objectively documented)and concomitant risk factors. Results. A totalnumber of 294 individuals belonging to 88 familieswere studied. One-hundred and fifty-two were carriersand 142 had no mutation. A total of 4338patients–years were obtained in the carriers group ascompared to 4309 in the non-carriers. Out of the 152affected family members, 5 experienced objectivelydocumented VTE (one spontaneous). Three thromboticevents occurred in non-carriers (two spontaneous).The overall annual incidence of VTE was 0.11% in thecarriers of the prothrombin mutation, and 0.07% innon-carriers (RR=1.7; 95% CI, 0.4 to 7). The incidenceof risk period-related thrombotic events was 1.0% inthe carriers group and 0.3% in non-carriers (RR=3.6;95% CI, 0.4 to 32). When we considered the thromboticrisk before and after 45 years of age the relativerisk was 2.0 (95% CI 0.2 to 21.6) and 1.5 (95% CI0.3 to 9.3) respectively. Conclusions. The results of ourretrospective family-study suggest that screening relativesof symptomatic carriers of single G20210A prothrombinmutation has the potential to identifyasymptomatic carriers in whom a mild increased riskfor thrombosis possibly exist. Whether this informationmight offer a real advantage in the prevention ofVTE remains to be proven.SISET PrizeCOS-15MELAGATRAN IS A BETTER PROFIBRINOLYTIC AGENTTHAN HEPARINPiro D, Rossiello MR, Rotunno C, Semeraro N,Colucci MDipartimento di Scienze Biomediche, Sezione diPatologia Generale, Università di Bari, ItalyThrombin generation inhibits fibrinolysis throughdifferent mechanisms, including clot stabilization,alteration of mass-to-length ratio of fibrin fibers, andremoval of plasminogen binding sites from partiallydegraded fibrin (via TAFI). We compared the fibrinolyticactivity of melagatran (active form of the oral,direct thrombin inhibitor, ximelagatran, AstraZeneca)with that of unfractionated heparin in platelet-poor(PPP) and platelet-rich (PRP) plasma clot models. Clotswere formed in the presence of t-PA, tissue factor,phospholipids, Ca ++ and different concentrations ofthe anticoagulants, and fibrinolysis was monitored bythe reduction in turbidity. Fibrinolytic activity of drugswas expressed as clot lysis ratio (lysis time in theabsence of the drug divided by lysis time in its presence).Drug potency, assessed by aPTT prolongation,was expressed as aPTT ratio. In PPP clot model, bothheparin and melagatran caused a concentrationdependentshortening of lysis time. However, whenfibrinolytic activity was expressed in function of aPTTratio, heparin resulted markedly less efficient thanmelagatran. At concentrations giving an aPTT ratio of2, the clot lysis ratios for heparin (0.3 U/mL) and melagatran(0.37 uM) were 1.29±0.13 and 1.75±0.19,respectively (p=0.01). In PRP clot model, heparin wasvirtually ineffective even at concentration as high as0.6 U/mL (aPTT ratio: 3.1±0.43; clot lysis ratio:1.15±0.21), whereas melagatran displayed a fibrinolyticactivity comparable to that observed in PPPclots at all tested concentrations (0.05-0.75 uM). Theeffect of heparin was also abrogated when PPP wassupplemented with platelet membranes but not withplatelet cytosolic fraction or the releasate of activatedplatelets, thus ruling out the involvement ofplatelet factor 4. We conclude that melagatran issuperior to heparin in promoting fibrinolysis, particularlyin platelet-rich clots in which clotting factorsbound to platelet membranes are protected from inhibitionby antithrombin-dependent anticoagulants.haematologica vol. 89(suppl. n. 8):september 2004