POS0172\u2005THROMBIN GENERATION ASSAY AND LUPUS ANTICOAGULANT IDENTIFY DIFFERENT POPULATIONS OF PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES

Abstract

Risk stratification in patients with antiphospholipid antibodies (aPL) remains a clinical challenge [1].We aimed to evaluate the role of Thrombin Generation Assay (TGA) in distinguishing various populations of aPL positive patients (with and without lupus anticoagulant - LA) and its association with β2GPI-dependent and anti-phosphatidyl-serine/prothrombin(aPS/PT) antibodies.One-hundred-and-eight patients were tested with TGA and divided as follows: 21 patients with aPS/PT IgG/IgM (Group 1), 29 with aβ2GPI IgG/IgM (Group 2), 31 with aPS/PT and aβ2GPI IgG/IgM (Group 3), 27 with aPS/PT and/or aβ2GPI IgM low-titers (Group 4). Table 1 resumes the clinical characteristics of the APS patients (excluding aPL asymptomatic). Thirty-one healthy donors (HDs) and 24 controls treated with VKA were also included.The most deranged TGA and LA profile was observed in patients with both aPS/PT and aβ2GPI when compared to those with an isolated positivity for aPS/PT or aβ2GPI and patients with aPS/PT and/or aβ2GPI IgM at low titres (Figure 1). Similarly, patients with aPS/PT and/or aβ2GPI at medium/high titres presented with the higher rate of clinical manifestations.When comparing the TGA curves of APS patients, asymptomatic aPL positive (aPL+) subjects, HDs and controls treated with VKA, we observed that aPL+ patients (particularly those with a confirmed diagnosis of APS) showed a characteristic profile.Differences among groups were confirmed also when comparing APS clinical manifestations. When comparing Group 1 and Group 4 we found significant differences with respect to the number of thrombotic events (21vs.15,p<0.05), the number of venous events (9vs.3,p<0.05), the recurrence of thrombosis (19%vs.0%,p<0.05). Group 2 and Group 4 showed differences in the occurrence of venous thromboses (50vs.20,p<0.05), and in the occurrence of DVT (8vs.2,p<0.05). Group 3 and Group 4, had higher number of thrombotic events (36vs15, p<0.05), the occurrence and the number of venous events (46%-15vs20%-3,p<0.05), the occurrence of TIA and DVT (4-11vs0-2,p<0.05).When analysing the cumulative frequency of extra-criteria APS manifestations, Group 1,2 and 3 were comparable, while comparing Group 3 and those positive for aβ2GPI and/or aPS/PT IgM at low titres (Group 4) we found a statistically significant difference (71%vs13%,p<0.05).TGA seems a valuable approach to stratify aPL+ patients according to their risk profile. The differences among groups and different populations of autoantibodies specificities obtained from this test can be considered a translational validation of the increased thrombotic risk of patients with triple or tetra aPL positivity.[1]Miyakis S et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost. 2006;4(2):295–306.Table 1.“Classical” and “Extra-criteria” APS clinical manifestations of each group (considering solely patients with a confirmed diagnosis of APS).Group 1: isolated aPS/PT+ IgG/IgM (16)Group 2: isolated aβ2GPI+ IgG/IgM(20)Group 3: aPS/PT+ and aβ2GPI+ IgG/IgM (24)Group 4: aPS/PT+ and/or aβ2GPI+ IgM low titres (15)APS clinical manifestationsThrombosis (Y/N), n (%)14 (87,5%)16 (80%)21 (87,5%)13 (86,6%)N of thrombotic events21233615Arterial thrombosis (Y/N), n (%)10 (62,5%)9 (45%)14 (58,3%)11 (73,3%)Arterial events, n13102112Venous thrombosis (Y/N), n (%)6 (37,5%)10 (50%)11 (45,8%)3 (20%)Venous events, n913153Pregnancy morbidity, n (%)3 (18,8%)4 (20%)3 (12,5%)2 (13,3%)Recurrent thrombosis (Y/N), n (%)3 (18,8%)3 (15%)7 (29,1%)0Livedo reticularis, n (%)1 (6,2%)1 (5%)4 (16,6%)0Thrombocytopenia, n (%)4 (25%)4 (20%)6 (25%)2 (13,3%)Valvular, n (%)1 (6,2%)02 (8,3%)0Peripheral artery disease, n (%)03 (15%)4 (16,6%)0Diffuse alveolar hemorrhage, n (%)001 (4,1%)0Figure 1.Graphical representation of the differences between TGA and LA profiles between groups.None declared