Aleksandra Antovic

Bakgrund: Antiphospholipid syndrome (APS) is a rare autoimmune disorder affecting women in reproductive age with high morbidity and mortality due to direct association with severe clinical manifestations as stroke, myocardial infarction and pulmonary embolism. Women with APS suffer severe, even lifethreatening pregnancy complications during late preganancy, like preeclampsia. Målsättning: This project is composed of 4 subprojects. The aims are described for each subproject: 1. To investigate risk factors for recurrent thrombosis and to evaluate the risk scoring system adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) in relation to recurrent thrombosis in the cohort of APS patients followed at the Karolinska University Hospital (KUH). 2. To study the prevalence and occurrence of other autoimmune diseases in the same cohort of patients with APS compared to general population during five years follow-up. 3. To study the occurrence of venous thromboembolism in patients with systemic lupus erythemathosus (SLE) compared to general population. and particularly in relation to the concomitant presence of APS and SLE-related nephritis. 4. To identify important serologic biomarkers for improved and earlier diagnosis of APS and for measuring APS disease activity. Arbetsplan: For assessing aims 1 and 2 we have retrospectively included 250 patients with APS followed at the Department of Hematology, KUH between 2014 and 2020. Considering the rarity of APS, this is one of the largest single-center APS cohorts in the world. For study 3 adults with incident SLE are identified from the Swedish National Patient Register (n=4342) and general population comparators from the Total Population Register were matched on age, sex and county (TPR n=43395). KUH SLE cohort (n=846) with matched TPR comparators (n=8058) is also assessed for incident VTE where the start of follow-up was the inclusion date. For analysis of novel antibodies in order to improve eraly APS diagnosis, we will use blood samples from 100 patients sampled at KUH. Betydelse: Our findings will be used to build strategies for early diagnosis, effective prophylaxis, personalized treatment and follow-up of APS patients in order to decrease mortality and improve quality of life for these patients.

Bakgrund: Venous thromboembolism (VTE) is a common thrombotic vascular condition, comprising deep venous thrombosis-DVT and pulmonary embolism-PE. PE has a mortality rate of >15% in the first 3 months after diagnosis. Many studies show that patients with rheumatic diseases have an increased risk for cardiovascular disease. Despite the suggestive mechanistic links between systemic autoimmune diseases and VTE, these highly inflammatory conditions are under-recognized as risk factors for hypercoagulability, and the underlying mechanisms explaining the increased risk for VTEs have not been clarified. Målsättning: To identify, understand and eventually treat the underlying causes for VTE in consecutive cohorts of patients with ANCA-associated vasculitis (AAV), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), systemic sclerosis (SSc), rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In addition, we include the studies on hemostatic disturbances in pregnanat women with SLE. Arbetsplan: The cross-link between the coagulation, fibrinolysis and inflammation will be studied by investigating endothelial activation, the levels and activity of extracellular vesicles, thrombin generation, fibrin formation, fibrinolyisis and fibrin clot structure in relation to complement activation and inflammatory markers. In this way we would be able to link different steps of hemostatic process with inflammatory response and clinical characteristics of patients with AAV, SLE, APS, SSc, RA and PsA. Performing all analysis simultaneously in a single plasma sample comprises the investigation of virtually all components of hemostais without the need to analyse the whole blood. Betydelse: Identifying clinical- and laboratory characteristics of patients at VTE-risk among patients with AAV, SLE, APS, SSc, RA and PsA has important consequences in terms of management and treatment

one might speculate that an addition of anticoagulant treatment to the aggressive anti-inflammatory treatment during flares could remodel vascular involvement especially in early stages of these diseases. The knowledge and clinical experience from this project should lead to favorable prognosis for individual patients.