An international team of more than 80 collaborators led by Hospital for Special Surgery (HSS) investigators is developing new classification criteria for clinical research of antiphospholipid syndrome (APS), a life-threatening autoimmune clotting disorder.
In their paper, published online ahead of print on November 30, 2020, in Arthritis Care & Research, the investigators reported on the first two of four phases of criteria development. Phase I and II involved generating 261 candidate criteria for defining APS and reducing the list to 27 finalist criteria, grouped into six specific categories: laboratory tests, macrovascular, microvascular, obstetric, cardiac and hematologic. The ultimate goal is to develop a threshold-based scoring system that will allow researchers worldwide to determine which patients most likely have APS and should be included in research studies.
APS is an autoimmune disorder in which the immune system produces antibodies against specific normal proteins in the blood, causing clots in blood vessels, low platelet counts, heart valve abnormalities and pregnancy complications. It is the leading cause of stroke in young people, causing one in three strokes in people under the age of 50, one in five recurrent miscarriages and up to 20 percent of all deep vein thromboses. The disease is often found in patients with other autoimmune conditions, especially lupus.
The current APS Sapporo Classification System was published in 1999, validated in 2000, and revised in 2006. "The previous classification system was based on the available evidence at the time," says lead author Medha Barbhaiya, MD, MPH, rheumatologist at the Barbara Volcker Center for Women and Rheumatic Diseases at HSS and assistant professor of medicine and population health sciences at Weill Cornell Medicine. "In the last decade, researchers have identified additional features of APS that deserve inclusion. We also now have more rigorous methods for developing and validating disease classification criteria."
The international initiative is jointly funded by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), in recognition of the need for improving the method of classifying patients for APS research to be used worldwide. Doruk Erkan, MD, MPH, rheumatologist at the Barbara Volcker Center for Women and Rheumatic Diseases at HSS and associate professor of medicine at Weill Cornell Medicine, is the senior author and co-principal investigator together with Stephane Zuily, MD, MPH, PhD, a vascular medicine specialist and professor of medicine at the Université de Lorraine, Nancy, France.
Emphasizing the difference between classification versus diagnosis criteria for APS, Dr. Erkan says, "Classification criteria are intended to be used in a research setting whereas diagnostic criteria are used in a clinical setting for the purpose of managing diseases; the two sets of criteria may have overlapping elements, but they have separate goals. The goal of classification criteria is to ensure that patients with common characteristics, thought to be specific for a certain disease, are included in appropriate research studies. In contrast, the goal of diagnostic criteria is to identify, as accurately as possible, whether patients have that particular disease."
The next phase of the new APS classification criteria methodology involves defining, refining, and weighting the candidate criteria and assigning a threshold score for identifying APS using real-world cases and a computer-based decision tool. Following the final validation phase of the project, researchers plan to report their results in 2021. Dr. Barbhaiya is also supported by a separate but related grant, the 2018 Rheumatology Research Foundation Investigator Award, to investigate risk factors for APS using the data collected during new classification criteria development.
"We are excited to be developing validated classification criteria for APS as previously done for other rheumatologic diseases, such as lupus and rheumatoid arthritis," says Dr. Erkan, who is also co-chair of the AntiPhospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION). "A threshold score for identifying patients with the disease will go a long way to advancing APS research, with the ultimate goal of high-quality research to improve APS prevention and treatment options for patients."
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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 11th consecutive year), No. 4 in rheumatology by U.S. News & World Report (2020-2021), and named a leader in pediatric orthopedics by U.S. News & World Report "Best Children's Hospitals" list (2020-2021). Founded in 1863, the Hospital has the lowest complication and readmission rates in the nation for orthopedics, and among the lowest infection rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. 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. The HSS Global Innovation Institute was formed in 2016 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 130 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. http://www.hss.edu.
Journal
Arthritis Care & Research