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Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers’ pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss (p = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.

International audience; Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

Background:The role of complement in the antiphospholipid (aPL) related pathology has been widely studied in animal models. Antiphospholipid antibodies can induce fetal loss in experimental animals but mice deficient in specific complement components (C4, C3, C5) appear somehow protected. In addition, in pregnant mice injected with aPL, antibody deposition has been found at decidual level causing focal necrosis, apoptosis and neutrophil infiltrates and supporting aPL pathogenetic potential. On the other hand, human studies did find hypocomplementemia associated to pregnancy complications in patients with obstetric antiphospholipid syndrome (APS). These results, however, are not unanimously confirmed and, in addition, some studies only show increased levels of complement activation products (i.e. Bb) and not decreased levels of C3 and/or C4. A recently study focusing on complement level in early pregnancy and before pregnancy showed a significant correlation with pregnancy complications and loss in a large cohort of primary APS.Objectives:To investigate if the simple detection of low C3 and/or C4 could be considered a risk factor for adverse pregnancy outcome in APS and aPL carriers pregnancies.Methods:We performed a multicentric study including patients from 10 Italian and 1 Russian Centers. Data on pregnancies in women with primary APS (n=434) and asymptomatic carriers with persistently positive aPL but not fulfilling clinical criteria for APS (n=218) were retrospectively collected. Serum C3 and C4 levels were evaluated by nephelometry; hypocomplementemia was defined by local laboratory reference values. Statistical analysis was performed using GraphPad.Results:Preconceptional complement levels and gestational outcome were available for 107 (25%) pregnancies in APS out of 434 and for 196 (90%) pregnancies in aPL carriers women out of 218. In pregnancies with low preconceptional C3 and/or C4, a significantly higher prevalence of pregnancy losses was observed (p=0.019). A subgroup analysis focusing on triple aPL positive patients was also performed. Preconceptional low C3 and/or C4 levels were found to be associated with an increased rate of pregnancy loss (p = 0.027) in this subgroup also. Otherwise, adverse pregnancy outcomes in single or double aPL positive women were not related to preconception complement levels (p = 0.44) (Table 1). Of note, all the pregnancy losses in the triple positive group occurred in patients treated with low dose aspirin and low molecular weight heparin from the time of positive pregnancy test.Conclusion:Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of adverse outcome. This has been seen only in in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss. test positivity.References:[1]De Carolis S, et al. Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome. Lupus (2012) 21:776–8.[2]Kim MY, et al. Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis (2018) 77:549–55.[3]Fredi M, et al. Risk Factors for Adverse Maternal and Fetal Outcomes in Women With Confirmed aPL Positivity: Results From a Multicenter Study of 283 Pregnancies. Front Immunol. 2018 May 7;9:864.Triple aPL positivitySingle or double aPL positivityGestational outcomeLow C3/C4 (n=49)Normal C3/C4(n=17)pLow C3/C4 (n=57)Normal C3/C4(n=165)pTerm live birth (>37w)15 (31%)6 (35%)ns34 (60%)110 (67%)nsPreterm live birth (≤37w)22 (45%)11 (65%)ns15 (26%)38 (23%)nsPregnancy losses (abortion and miscarriages)12 (24%)0 (0%)0.0278 (14%) 17 (10%)nsDisclosure of Interests:None declared

Background:Although guidelines do not recommend antiphospholipid antibodies testing after 60 yo, recent data reported late onset antiphospholipid syndrome (APS).Objectives:To comparatively analyse the clinical, laboratory features and outcomes in 695 cases with primary APS between patients older and younger than 70 yo.Methods:we have performed an international study within the framework of the International Registry of primary APS patients treated with Hydroxychloroquine, HIBISCUS (an ongoing retrospective and prospective register launched in 2016). 28 centres from 17 countries participate. Data about late onset APS were analysed in 695 patients and were obtained from a standardized form registered in the database containing 66 items with respect to demographics, clinical and biological features.Results:Arterial events and especially stroke represented the main initial and recurrent clinical manifestation in 40 primary APS patients older than 70 yo. There were not statistically significant differences with respect to cardiovascular risk factors between the two groups of patients. A significant male predominance, a familial APS history, a higher prevalence of triple positivity, lower complement levels, and anticardiolipin antibodies (aCL) IgA isotype were found in older patients. Low anticoagulation regimens were safe and efficient, with a low relapse rate in older patients.Conclusion:we suggest that the detection of aPL antibodies should be included into the initial screening panel tests in elderly with thrombotic events, especially arterial, in particular those with recurrent stroke and familial APS.Our study further suggests that lower intensity anticoagulation regimens could be a therapeutic option in older APS patients, as no differences in outcomes and relapse rate were found between patients with high and low intensity anticoagulation regimens.References:[1]Grimaud F et al. Rheumatology. 2019;58:1006-10.[2]Goldman-Mazur S et al. Thromb Res. 2019;176:67-73.[3]Hirmerova J et al. 2017;36:167-73.Disclosure of Interests:Cristina Belizna: None declared, Omar Latino: None declared, Ljudmila Stojanovich: None declared, Patrick Saulnier: None declared, Katrien Devreese: None declared, Sebastien Udry: None declared, Natasa Stanisavljevic: None declared, Aleksandra Djokovic Speakers bureau: KRKA, Astra Zeneca, Actavis, Jaume Alijotas-Reig: None declared, Enrique Esteve-Valverde: None declared, Raquel Ferrer-Oliveras: None declared, Angela Tincani: None declared, Laura Andreoli: None declared, Francesca Regola: None declared, Maarten Limper: None declared, Alexander Makatsariya: None declared, Jamilya Khizroeva: None declared, Viktoria Bitsadze: None declared, Cecilia Chighizola: None declared, Francesca Pregnolato: None declared, Maria Orietta Borghi: None declared, Pier Luigi Meroni: None declared