(Press-News.org) Investigators from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) presented new research findings in antiphospholipid syndrome (APS) at the American College of Rheumatology (ACR) Convergence 2023, the ACR’s annual meeting.
Hospital for Special Surgery (HSS), one of the leading centers in the United States providing care for adults and children with APS, is the lead coordinating center for APS ACTION, an international research network of 34 academic institutions dedicated to advancing the understanding and management of APS. APS ACTION conducts large, multicenter clinical studies and trials in patients with positive antiphospholipid antibodies (aPL).
APS is a systemic autoimmune disorder characterized by the production of aPL, which attack proteins binding the cell walls of blood cells located on the inner layer of veins and arteries. APS increases the risk of dangerous blood clots, strokes, heart attacks and pregnancy complications.
APS ACTION created the APS ACTION Clinical Database and Repository (APS ACTION Registry) to study the natural course of disease in patients with persistently positive aPL, with or without other systemic autoimmune diseases. Investigators worldwide collect blood samples and clinical data annually and follow patients for 10 years. As of November 2023, the registry included samples and data for about 1,200 patients.
“Since the registry began in 2010, APS ACTION investigators have published 28 studies in peer-reviewed journals and delivered 50 podium and poster presentations at international congresses,” said Doruk Erkan, MD, MPH, a physician-scientist at the Barbara Volker Center for Women and Rheumatic Diseases and rheumatologist at HSS. Dr. Erkan is also a founding member of APS ACTION and the current chair of its Executive Committee. “It’s exciting to see six new studies presented at ACR Convergence 2023 that advance our understanding of APS.”
These six studies were based on the analysis of registry clinical data alone, registry clinical data in combination with patient samples and efforts of APS ACTION International Core Laboratories to improve the reliability of aPL tests.
Highlights are as follows:
Three Studies Based on APS ACTION Registry Clinical Data
First and Recurrent Thrombosis Risk after 4,454 Patient-Years of Follow-Up
The study updated the incident first and recurrent thrombosis risk, previously reported in 2021 as 1.02 and 2.09 per 100 patient-years, respectively. Based on 4,454 patient-years of follow-up, the risk of first and recurrent thrombosis events remained relatively low at 1.00 and 2.13 per 100 patient-years in aPL-positive patients with and without a history of thrombosis, respectively. A secondary analysis revealed potential differences in medications and cardiovascular risk factors at enrollment between patients with and without thrombosis at follow-up. The researchers concluded these findings should be interpreted cautiously, given the multifactorial nature of thrombosis and the relatively small number of new events during follow-up. New APS ACTION studies are already in progress to better define independent thrombosis risk and protective factors in this patient population.
HSS authors: Jonathan Thaler, MD (presenting), Doruk Erkan, MD, MPH (senior).
Complete author list: Refer to ACR Convergence 2023 Abstract 1604 (podium presentation).
Clinical Characteristics of Patients Presenting with Transient Ischemic Attack
Transient ischemic attack (TIA) can occur in aPL-positive patients. However, diagnosing TIA is challenging due to the need to rule out other conditions, such as complex migraine with aura or seizure. This study analyzed the clinical characteristics of persistently aPL-positive patients with reported TIA before enrolling in the registry and/or during follow-up. The investigators retrospectively compared patients’ baseline characteristics, including those with and without a history of thrombosis before they joined the registry. Next, the researchers prospectively assessed patients with new onset TIA. The study found that 8% of patients had a history of TIA at registry entry and the recurrence rate during follow-up was 8%. However, the new TIA rate was less than 1%. About two-thirds of TIA patients without a history of thrombosis were treated with anticoagulants, and all patients with new or recurrent TIA during follow-up were on anticoagulation. The researchers concluded the findings highlight the need for controlled studies of TIA in aPL-positive patients using strict TIA definitions.
Presenting author: Zeynep Belce Erton, MD (SUNY Downstate Medical Center).
HSS authors: Jonathan Thaler, MD, Doruk Erkan, MD, MPH (senior author).
Complete author list: Refer to ACR Convergence 2023 Abstract 0097 (poster presentation).
Predictors of Mortality
The study aimed to determine the mortality rate and the causes and predictors of mortality in aPL-positive patients. The researchers analyzed reported causes of death and compared the clinical and laboratory characteristics of patients who died with patients still living. The study found that the mortality rate among 963 patients was 5% after a median follow-up of five years. The five-year survival probability declined with age and was lowest for patients over 60 when they joined the registry. A history of arterial thrombosis, catastrophic APS, cardiovascular disease risk factors and co-existing systematic autoimmune diseases independently predicted future mortality. The investigators emphasized that a better understanding of the predictors of mortality is critical to help tailor treatment plans to improve patient outcomes.
Presenting author: Yasaman Ahmadzadeh, MD (Roger Williams Medical Center).
HSS author: Doruk Erkan, MD, MPH (senior author).
Complete author list: Refer to ACR Convergence 2023 Abstract 0098 (poster presentation).
Two Studies Based on APS ACTION Registry Clinical Data and Patient Samples
Complement Activation as a Marker of Thrombosis Risk
Recent studies suggest additional markers of thrombosis risk are present in patients with severe APS, such as catastrophic APS (CAPS), a life-threatening condition that involves the formation of multiple blood clots in a very short period. The study evaluated plasma levels of three complement activation markers—C5b-9, C4d and Bb fragment—using ELISA and the modified HAM assay that measures complement-dependent cell killing. The investigators compared results for patients who experienced thrombosis with those who did not over a median prospective follow-up time of 4.6 years. In general, the investigators found that elevated C4d levels and a positive modified HAM result were associated with a higher risk of new thrombosis. They concluded these complement markers might be useful tools for stratifying patients by risk.
Presenting author: Cecile Yelnik, PhD (Lille University).
HSS authors: Jane Salmon, MD, Doruk Erkan, MD, MPH (senior author).
Complete author list: Refer to ACR Convergence 2023 Abstract 1605 (podium presentation).
Plasma Proteomic Profiling of Different APS Phenotypes
APS is a heterogeneous autoimmune disease with complications arising from interaction between the innate immune system and coagulation. Patients may present with different phenotypes, such as thrombotic, obstetric or catastrophic/microvascular APS, while others may be aPL-positive without the presence of disease. To better understand the mechanisms driving immunothrombotic events, the investigators performed multiplex proteomic profiling of about 7,000 unique proteins found in plasma samples of 40 patients and compared results with 10 healthy controls. The plasma proteome of APS subtypes revealed alteration in several pathways, particularly receptor signaling, signal transduction, regulation of cellular differentiation, neutrophil, complement, coagulation and cytokine activation notable in all individuals with aPL-positivity. Several pathways, notably associated with immunothrombosis, revealed an escalating activation from the non-thrombotic aPL-positivity to the most thrombotic phenotype (catastrophic/microvascular APS).
Presenting author: Alexander Pine, MD, PhD (Yale University School of Medicine).
HSS authors: Doruk Erkan, MD, MPH.
Complete author list: Refer to ACR Convergence 2023 Abstract 1608 (podium presentation).
APS ACTION Core Laboratories Study to Improve aPL Test Reliability
An Assessment of Lupus Anticoagulant Tests Using Different Snake Venom Clotting Times
The lupus anticoagulant (LA) test is essential for diagnosing and managing patients with APS. However, variability in test results is challenging, especially in anticoagulated samples. The two commonly used tests as part of LA are the activated partial thromboplastin time and dilute Russell’s viper venom time (DRVVT). Based on a standardized protocol, four APS ACTION Core Laboratories assessed the performance of the LA test using the prothrombin-activating Taipan snake venom time (TVST) test and the Ecarin clotting time (ECT) confirmatory test, which are insensitive to vitamin K antagonists. The investigators compared the agreement in LA status between the DRVVT and the TVST/ECT. Preliminary study results suggested that the TVST/ECT could serve as an adjunct to DRVVT, providing high specificity without requiring mixing studies.
Presenting author: Maria Efthymiou, Phd, BSc, MSc (University College London).
HSS authors: Doruk Erkan, MD, MPH.
Complete author list: Refer to ACR Convergence 2023 Abstract 0096 (poster presentation).
About HSS
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 14th consecutive year), No. 2 in rheumatology by U.S. News & World Report (2023-2024), and the best pediatric orthopedic hospital in NY, NJ and CT by U.S. News & World Report “Best Children’s Hospitals” list (2023-2024). In a survey of medical professionals in more than 20 countries by Newsweek, HSS is ranked world #1 in orthopedics for a fourth consecutive year (2023). Founded in 1863, the Hospital has the lowest readmission rates in the nation for orthopedics, and among the lowest infection and complication rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center five consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. In addition, more than 200 HSS clinical investigators are working to improve patient outcomes through better ways to prevent, diagnose, and treat orthopedic, rheumatic and musculoskeletal diseases. The HSS Innovation Institute works to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 165 countries. The institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally. www.hss.edu.
END
New antiphospholipid syndrome research findings presented at ACR Convergence 2023
2023-11-14
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