POS0724 GENDER DIFFERENCES IN THROMBOTIC PRIMARY ANTIPHOSPHOLIPID SYNDROME IN A LARGE COHORT OF PATIENTS FROM FOUR EUROPEAN CENTERS
Authors: L. Moschetti, L. Dal Pozzolo, V. Le Guern, N. Morel, C. M. Yelnik, M. Lambert, E. Hachulla, Y. Benhamou, F. Franceschini, L. Andreoli, N. Costedoat-Chalumeau, A. Tincani
Journal: Annals of the Rheumatic Diseases (2021)

Background: Autoimmune diseases occur more frequently in females and their course and severity can be affected by gender. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder in which antiphospholipid antibodies (aPL) exert a pathogenic role resulting in vascular thrombosis and/or pregnancy morbidities. Data about gender differences in thrombotic APS (t-APS) are still scarce 1,2 . Objectives: To evaluate the differences in frequency, disease expression and severity between females and males affected by primary t-APS. Methods: Retrospective study enrolling subjects with a formal diagnosis of primary APS (Miyakis 2006) with vascular thrombosis at onset. Women who presented with obstetric events as first aPL-related manifestation were excluded. All the patients were followed from 1967 to 2019 in four European centers: three French centers and one Italian center. Results: The study included 433 patients (68% females, 32% males). Median age at t-APS onset [31 (24-46) vs 41 (29-53) years, p&lt;0.001 ] and at diagnosis [34 (27-50) vs 46 (34-57) years, p&lt;0.001 ] was significantly lower in females. The most common presenting manifestations were venous thrombosis (60%) followed by arterial events (37%) and catastrophic APS (3%). Venous events were more frequent in women as compared to men (64% vs 51% p:0.012 OR:1.7 [1.1-2.5]). Sites of venous thrombosis included: limbs (35%), pulmonary (17%), cerebral (3%), portal and inferior cava (2%) and retinal (1%) veins, without gender differences. The arterial events were more frequent among men (43% vs 34% p:0.053 ). Strokes (27%) and myocardial infarctions (4%) were the most frequent manifestations, followed by thrombosis of limbs (2%), retina (2%) and abdominal organs (1%). Noteworthy, only men presented with visceral ischemia. During the follow-up, new thrombosis occurred in 41% of patients (179/433). 33% out of them had at least two episodes and these occurred especially among males (22% vs 10% p:0.001 OR:2.5 [1.3-4.8]). New events were mostly of the same type, but ⅓ of patients presented a switch from venous to arterial side and viceversa, with no gender differences. Complete aPL profile was available in 357 subjects: 33% had single aPL positivity, 24% double positivity and 43% triple positivity, with no differences between women and men. About 80% of the patients had a concomitant risk factor (RF) for thrombosis. Established cardiovascular RFs were more represented among men as shown in table 1. In women, estrogenic exposure was the main RFs, present in almost 40% of them. Table 1. MALES n= 137 FEMALES n= 296 P OR [IC 95%] Traditional cardiovascular RFs, n (% ) Smoke 66 (48) 81 (27) &lt;0.001 2.5 [1.6-3.8] Arterial hypertension 59 (43) 75 (25) &lt;0.001 2.2 [1.5-3.4] Dyslipidemia 52 (38) 72 (24) 0.004 1.9 [1.2-2.9] Diabetes 16 (12) 15 (5) 0.014 2.5 [1.8-5.1] Obesity 13 (10) 38 (13) ns Other thrombophilic factors, n (% ) Estrogenic stimuli* 0 116 (39) - Trauma / surgery / immobilization 21 (15) 32 (11) ns Congenital thrombophilia 9/94 (10) 33/204 (16) ns Data were compared using contingency tables, p value was calculated with Chi-Squared or Fisher exact test. *= hormonal therapy, pregnancy, post-partum Conclusion: This gender-oriented analysis of patients with primary t-APS showed that women had the first vascular event at a younger age and mostly on the venous side, while men presented mainly with arterial events, later in life and suffered from more recurrent events. No differences were observed in the distribution of the aPL profile. The different frequency of arterial and venous events in the two groups could be attributed mainly to the presence of additional RFs rather than to biological gender-specific issues. However, it should be underlined that some RFs, such as the use of estrogens or classic cardiovascular RFs, are exclusive or more represented in one gender rather than the other, making it difficult to assess the link of causality between gender and manifestations of t-APS. References: [1]JF de Carvalho. Rheumatol Int. 2011. [2]LJ Jara. Lupus. 2005. Disclosure of Interests: None declared