Antiphospholipid syndrome (APS) is an autoimmune disorder typically characterized by blood clots and pregnancy complications. However, the spectrum of APS-related clinical symptoms is much broader (see below). APS can develop alone or in association with other autoimmune conditions such as lupus. (Learn more about antiphospholipid syndrome terminology.)
Table showing different organ systems and how APS may affect them
Organ System | Selected Antiphospholipid Syndrome-related Clinical Problems |
---|---|
Nervous system | Stroke, transient ischemic attacks1, memory problems |
Kidney | High blood pressure, chronic kidney disease, protein in the urine |
Heart | Myocardial infarctions, vegetations2 on valves, thickened and leaky valves |
Blood | Anemia, low platelet counts |
Skin | Livedo3, skin ulcerations |
Blood vessels | Deep venous thrombosis4 (DVT) |
Lungs | Pulmonary embolism5, pulmonary hypertension6 |
Pregnancy | Miscarriages, premature births, fetal growth restriction |
Classification criteria are intended to be used in a medical research setting. Diagnostic criteria are used in a clinical setting for the purpose of managing diseases in patients. 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. This helps ensure the integrity of the research data during the analysis of the study. Classification criteria do not necessarily encapsulate all of the clinical or laboratory features of that particular disease. Rather, the goal is to capture a uniform group of patients with a similar clinical presentation for medical research purposes only.
The goal of diagnostic criteria is to identify, as accurately as possible, whether patients have that particular disease. While some of the diagnostic criteria may overlap with the classification criteria, many of the uncommon signs and symptoms of a disease are not included in the classification criteria. However, this does not mean they are not a feature of that disease. Diagnostic criteria aim to maximize the number of patients that can be identified as having a particular disease. This is in contrast to classification criteria, which are more stringent in order to identify a more specific cohort of patients.
Yes, the revised Sapporo APS Classification Criteria are used for classifying APS patients. These criteria allow researchers to determine who can be identified as an APS patient if they will participate in laboratory or clinical research.
A simplified version of the APS classification criteria is shown below. Based on these classification criteria, patients who have at least one positive clinical and one positive laboratory criteria are considered to have a diagnosis of APS suitable for research purposes.
There are no diagnostic criteria for APS.
If a patient has signs and symptoms that suggest they have APS, laboratory testing to determine the presence of antiphospholipid antibody (aPL) is ordered to establish the diagnosis. However, aPL test results need to be interpreted cautiously, because not every person who has a positive aPL test result necessarily has APS or clinically relevant aPL positivity.
Our bodies may develop aPL due to conditions other than APS, such as in responses to infections. Patients who have positive initial aPL tests, but test negatively in repeated confirmatory tests after a period of time are said to have "transient aPL positivity." In other words, the aPL positivity is temporary. If their aPL results remain positive, then patients are said to have persistent aPL positivity. Some people may also have aPL levels that are frequently slıghtly elevated (techıcally a posıtıve result) but in such low levels that these results are not considered "clinically meaningful" – meaning they do not indicate that a person has APS.
To be considered clinically meaningful, an aPL test should:
Antiphospholipid syndrome is diagnosed by your physician based on the careful assessment of:
Antiphospholipid syndrome diagnosis can be challenging due to two problems: missed diagnosis and overdiagnosis.
As discussed above, the goal of the APS classification criteria is to identify patients that have a high likelihood of having APS based on common and typical APS-related clinical manifestations. A common misconception is that the classification criteria for APS should also be used as diagnostic criteria. Although APS classification criteria may guide physicians in making a diagnosis, it should not be substituted for a doctor’s clinical judgment, which is based on a complete evaluation of the patient.
Current APS classification criteria were published in 1999 and updated in 2006. Some of the limitations include:
An international effort is underway to develop a more comprehensive classification, with the use of the same methods that were used to develop the most recent classification criteria for other systemic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (lupus).
There are efforts to develop new tests to diagnose APS. Antiphosphatidylserine/prothrombin antibodies or anti-Domain-I antibodies are two tests that may be used more commonly in the future; however, more clinical studies are required to understand their potential diagnostic role.
As discussed above in question 3, the aPL laboratory profile assessment is critical. Depending on the type, subtype, level and persistence of the aPL laboratory tests, patients may or may not have a "clinically significant" aPL profile.
Even if you have a clinically significant aPL profile, it does not mean that you have APS. There are patients without any symptoms that have positive aPL. This condition is commonly referred to as "asymptomatic aPL positivity".
In summary, a full assessment should be performed by your doctor taking into account your medical history along with your aPL test results.
Not necessarily. Lupus anticoagulant is one of the tests to detect aPL. The reason why it is named "lupus anticoagulant" is because the discovery of the test was originally made in lupus patients. However, our understanding of this test has since evolved and now we know that lupus anticoagulant positivity is not exclusive to lupus patients, and does not necessarily indicate that a person has lupus.
Aggarwal R, Ringold S, Khanna D, et al. Distinctions between diagnostic and classification criteria? Arthritis Care Res (Hoboken) 2015;67: 891-897.
Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis Ann Rheum Dis 2019;78: 1151-1159.
Barbhaiya M, Zuily S, Ahmadzadeh Y, et al. Development of New International Classification Criteria for Antiphospholipid Syndrome: Phase II Results [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/development-of-new-international-classification-criteria-for-antiphospholipid-syndrome-phase-ii-results/. Accessed January 24, 2020.
Garcia D, Erkan D, Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med 2018;378: 2010-2021.
Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4: 295-306.
Sciascia S, Amigo MC, Roccatello D, et al. Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances. Nat Rev Rheumatol 2017;13: 548-560.
Singh JA, Solomon DH, Dougados M, et al. Development of classification and response criteria for rheumatic diseases. Arthritis Rheum 2006;55: 348-352.
Zuily S, Barbhaiya M, Costenbader KH, et al. 15th International Congress on Antiphospholipid Antibodies Task Force on Antiphospholipid Syndrome Classification Report. In: Antiphospholipid Syndrome: Current Research Highlights and Clinical Insights. Eds: Erkan and Lockshin. Springer, 2017, pp 279-290.
Posted: 6/2/2020
Mert Sevgi, MD
Academic Visitor, Department of Rheumatology, Hospital for Special Surgery
Yasaman Ahmadzadeh, MD
Visiting Research Fellow, Department of Rheumatology, Hospital for Special Surgery
Stephane Zuily, MD, PhD
Attending Cardiovascular Specialist, Nancy Academic Hospital; Professor of Medicine, School of Medicine of Nancy, Lorraine University, Nancy, France
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