POS0172 THROMBIN GENERATION ASSAY AND LUPUS ANTICOAGULANT IDENTIFY DIFFERENT POPULATIONS OF PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES
Authors: M. Radin, A. Barinotti, I. Cecchi, S. G. Foddai, E. Rubini, D. Roccatello, E. Menegatti, S. Sciascia
Journal: Annals of the Rheumatic Diseases (2021)

Background: Risk stratification in patients with antiphospholipid antibodies (aPL) remains a clinical challenge [1]. Objectives: 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. Methods: 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. Results: 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&lt;0.05), the number of venous events (9vs.3,p&lt;0.05), the recurrence of thrombosis (19%vs.0%,p&lt;0.05). Group 2 and Group 4 showed differences in the occurrence of venous thromboses (50vs.20,p&lt;0.05), and in the occurrence of DVT (8vs.2,p&lt;0.05). Group 3 and Group 4, had higher number of thrombotic events (36vs15, p&lt;0.05), the occurrence and the number of venous events (46%-15vs20%-3,p&lt;0.05), the occurrence of TIA and DVT (4-11vs0-2,p&lt;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&lt;0.05). Conclusion: 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. References: [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 manifestations Thrombosis (Y/N), n (%) 14 (87,5%) 16 (80%) 21 (87,5%) 13 (86,6%) N of thrombotic events 21 23 36 15 Arterial thrombosis (Y/N), n (%) 10 (62,5%) 9 (45%) 14 (58,3%) 11 (73,3%) Arterial events, n 13 10 21 12 Venous thrombosis (Y/N), n (%) 6 (37,5%) 10 (50%) 11 (45,8%) 3 (20%) Venous events, n 9 13 15 3 Pregnancy 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%) 0 Livedo reticularis, n (%) 1 (6,2%) 1 (5%) 4 (16,6%) 0 Thrombocytopenia, n (%) 4 (25%) 4 (20%) 6 (25%) 2 (13,3%) Valvular, n (%) 1 (6,2%) 0 2 (8,3%) 0 Peripheral artery disease, n (%) 0 3 (15%) 4 (16,6%) 0 Diffuse alveolar hemorrhage, n (%) 0 0 1 (4,1%) 0 Figure 1. Graphical representation of the differences between TGA and LA profiles between groups. Disclosure of Interests: None declared