Danieli Andrade

14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends.

Antiphospholipid Syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity occurring in patients with persistent antiphospholipid antibodies (aPL). The primary objective of the APS Treatment Trends Task Force, created as part of the 14th International Congress on aPL, was to systematically review the potential future treatment strategies for aPL-positive patients. The task force chose as future clinical research directions: a) determining the necessity for controlled clinical trials in venous thromboembolism with the new oral direct thrombin or anti-factor Xa inhibitors pending the results of the ongoing rivaroxaban in APS (RAPS) trial, and designing controlled clinical trials in other forms of thrombotic APS; b) systematically analyzing the literature as well as aPL/APS registries, and creating specific registries for non-warfarin/heparin anticoagulants; c) increasing recruitment for an ongoing primary thrombosis prevention trial, and designing secondary thrombosis and pregnancy morbidity prevention trials with hydroxychloroquine; d) determining surrogate markers to select patients for statin trials; e) designing controlled studies with rituximab and other anti-B-cell agents; f) designing mechanistic and clinical studies with eculizumab and other complement inhibitors; and g) chemically modifying peptide therapy to improve the half-life and minimize immunogenicity. The report also includes recommendations for clinicians who consider using these agents in difficult-to-manage aPL-positive patients.

Catastrophic antiphospholipid syndrome during pregnancy and puerperium: maternal and fetal characteristics of 15 cases

Background: The catastrophic variant of the antiphospholipid syndrome (APS) is a life-threatening form of presentation of this syndrome that can be triggered by several factors. Aim: To describe the characteristics of patients who developed catastrophic APS triggered during pregnancy and puerperium. Methods: A review of the first 255 cases collected in the website-based “CAPS Registry” was undertaken. Three new and unpublished cases of catastrophic APS developed during pregnancy and puerperium were added. Results: Fifteen cases were identified. The mean (range) age was 27 (17–38) years. Most patients had a previous unsuccessful obstetric history. In 7 of 14 (50%) cases with available medical history, the catastrophic APS appeared during pregnancy, in 6 (43%) during the puerperium and in 1 (7%) after curettage for a fetal death. The main clinical and serological characteristics were similar to those patients with catastrophic APS triggered by other factors, except for a history of a higher prevalence of previous abortions (p<0.01). Several specific features were found, including the HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome in 8 (53%) patients, placental infarctions in 4 (27%) patients, and pelvic vein thrombosis and myometrium thrombotic microangiopathy in 1 (7%) patient each. Mortality rate was high for the mothers (46%), and for the babies (54%). Conclusions: It is important to consider the possibility of the development of catastrophic APS in those patients with signs of HELLP syndrome and multiorgan failure during pregnancy or puerperium, especially in those patients with previous history of abortions and/or thrombosis.

Quantifying subclinical central nervous lesions in primary antiphospholipid syndrome: The role of magnetization transfer imaging

To define the role of magnetization transfer imaging (MTI) in detecting subclinical central nervous system (CNS) lesions in primary antiphospholipid syndrome (PAPS).

Difficult Clinical Situations in the Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. However, there is a range of other manifestations associated with APS, called non-criteria manifestations that add significant morbidity to this syndrome and, some of them, represent difficult clinical situations to deal with. Other issues such as refractory treatment also represent challenging situations poorly addressed in the literature. Therefore, the purpose of this article is to review the management of difficult clinical situations in APS and provide information to help the readers in their decision-making process.

Emerging Therapies in Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is a hypercoagulable state characterized by arterial and venous thromboses and pregnancy morbidity in the presence of antiphospholipid antibodies. Although warfarin remains the main therapeutic choice in APS, there is still concern about its efficacy, safety, and patient compliance. Patients with refractory APS to conventional therapy as well as patients with non-classical manifestations of APS may have alternative treatment approaches. APS pathogenesis has been further elucidated over the past years identifying new molecules as potential new treatment targets. This review summarizes available data from in vitro and animal models and clinical studies on the role of new potential treatment approaches including new oral anticoagulants and immunoregulatory agents: direct thrombin or factor Xa inhibitors, hydroxychloroquine, statins, B cell inhibition, complement inhibition, peptide therapy, nuclear factor κB and p38 mitogen-activated kinase inhibitors, defibrotide, abciximab, mTOR inhibitor, and other potential targets. Large multicenter prospective studies of well-characterized APS patients are needed to assess the efficacy and safety profile of these potential treatment alternatives.

15th International Congress on Antiphospholipid Antibodies Task Force on Antiphospholipid Syndrome Treatment Trends Report

A challenge in antiphospholipid syndrome (APS) is to translate targeted therapies from animal and in vitro models to clinical trials. The 15th International Congress on Antiphospholipid Antibodies (aPL) Task Force on Treatment Trends summarized new developments in APS targeted treatment since the 14th International Congress on aPL (September 2013). The task force also discussed additional treatments and/or pathways that can be considered in the management of aPL-positive patients.

Primary antiphospholipid syndrome: absence of premature atherosclerosis in patients without traditional coronary artery disease risk factors.

Objective To investigate if patients with Primary Antiphospholipid Syndrome (PAPS) with venous and/or arterial thrombosis without traditional coronary artery disease (CAD) risk factors develop early atherosclerotic vascular damage. Methods 27 female patients with PAPS (Sidney criteria) and 27 age, body mass index (BMI), and sex matched controls were consecutively selected. Exclusion criteria were: black race, age ≥55 years, traditional cardiovascular risk factors, other thrombophilias or connective tissue diseases, corticosteroids use and pregnancy. All subjects underwent Pulse Wave Velocity (PWV) and Echo-Tracking (ET), both in carotidal bed, to analyse vascular functional properties. Results Age (p = 0.92) and BMI (p = 0.91) were comparable in both groups. PAPS patients and controls had similar PWV (9.07 ± 1.08 m/s vs 9.42 ± 1.47 m/s, p = 0.34) as well as echo tracking parameters such as intima-media thickness (683 ± 171 µm vs 636 ± 140 µm, p = 0.52), carotideal diameter (p = 0.26), distensibility (p = 0.92), compliance coefficients (p = 0.36) and elastic modulus (p = 0.78). Patients with exclusively venous thrombosis showed lower PWV than patients with arterial thrombosis (8.55 ± 0.70 m/s vs 9.56 ± 0.94 m/s, p = 0.01), but no difference regarding intima-media thickness (683 ± 171 µm vs 636 ± 140 µm, p = 0.52) was observed. Conclusion Patients with PAPS do not seem to be at higher risk of developing premature atherosclerosis. Patients who suffered exclusively venous thrombosis seem to be at lower risk than those with exclusively arterial events. Other studies need to confirm our findings.

AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION): 5-Year Update

Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) is the first-ever international network created to design and conduct large-scale, multicenter clinical trials and research in persistently antiphospholipid antibody (aPL)-positive patients. Since its inception in 2010, the APS ACTION has made important strides toward our goal of international research collaboration and data sharing. Through the dedication and hard work of 50 APS ACTION members, collaborative international projects are currently underway including a multicenter web-based registry and repository of aPL-positive patients, a randomized controlled clinical trial assessing the efficacy of hydroxychloroquine for primary thrombosis prevention in persistently aPL-positive but thrombosis-free patients, standardization of aPL testing through the use of core laboratories worldwide, identification of the limitations in the existing aPL/APS literature, and conducting observational research studies to further our understanding of the disease. Thus far, APS ACTION has held annual workshops and summits with the aim of facilitating international collaboration and developing initiatives to recruit young scholars to APS research. This paper describes updates related to the organization’s structure, ongoing research efforts, and recent accomplishments and discusses future directions.

Update on antiphospholipid antibody syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations) add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE) but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy.

Pandemic non-adjuvanted influenza A H1N1 vaccine in a cohort of patients with systemic sclerosis

Abstract Objective To assess the possible effect of therapy, disease subtype and severity on H1N1 immunogenicity in patients with SSc. Methods Ninety-two patients and 92 age- and gender-matched healthy controls received adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Blood samples were collected immediately before and 3 weeks after vaccination to evaluate antibody responses to the H1N1 virus. Efficacy was assessed by seroprotection (SP) and seroconversion (SC) rates and the factor increase in geometric mean antibody titre. Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. Results SSc patients were predominantly females (91%) and 61% had limited SSc, 12% had severe skin involvement and 57.6% were on immunosuppressive (IS) therapy. SSc patients and controls presented comparable overall SP (P = 0.20) and SC (P = 0.61) rates. Further evaluation of the possible effect of disease and therapy revealed similar rates of SP and SC in patients with dcSSc vs lcSSc (SP P = 0.62 and SC P = 0.66), severe vs mild/moderate skin involvement (SP P = 1 and SC P = 0.45) and with vs without IS (SP P = 0.26 and SC P = 0.10). The frequency of mild local and minor systemic reactions was similar in patients with dcSSC vs lcSSc (P = 0.70 vs 0.32) and in those with and without severe skin involvement (P = 0.59 vs 0.28). Conclusion The non-adjuvanted influenza H1N1 virus vaccine proved to be safe and effective, independent of SSc clinical subtype, disease severity or therapy. These latter factors do not seem to contribute to mild adverse events observed in SSc. Our data support the annual influenza vaccination recommendation for these patients. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov), NCT01151644