Antiphospholipid Syndrome (APS) is a systemic autoimmune disorder associated with abnormal blood clotting. In patients with APS, the immune system creates autoantibodies known as antiphospholipid antibodies (aPL) that increase risk of blood clots by targeting the blood vessels and clotting proteins.
Antiphospholipid antibodies occur in otherwise healthy individuals or in patients with autoimmune disorders such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Individuals with positive aPL may or may not develop clinical problems, so positive aPL test alone without any clinical problems is not enough to confirm the APS diagnosis.
Based on the International APS Classification Criteria a clinical event (blood clot or pregnancy complications) and one of the following blood tests are required for the APS diagnosis (patients should undergo at least two blood tests, which should be spaced three months apart to show persistent levels of aPL).
Commonly used tests include:
Positive LA as well as higher levels (> 40 units) of aCL and aB2GPI correspond to an increased risk of an aPL-related events whereas lower levels (especially <20 units) are clinically less significant. Patients who are positive for all three of the aPL blood tests seem to have a higher likelihood of an aPL-related event than those with only one or two positive tests.
- Lupus anticoagulant (LA) test
- Anticardiolipin antibody (aCL) test
- Anti-Beta-2 glycoprotein-I (aB2GPI) test.
Major clinical problems associated with APS include blood clots in the veins or arteries, and pregnancy losses. Deep vein thrombosis is the most common type of blood clot to form in the veins, and a stroke is the most common type of blood clot to occur in the arteries. Some of the other clinical problems related to aPL include livedo reticularis (lacey purple pattern on skin), heart valve disease, low platelet count, anemia, and kidney disease.
Antiphospholipid Syndrome is considered to be a leading cause of pregnancy complications such as fetal loss, strokes, and other blood clots, especially among young people. However, well-designed population-based studies aimed at assessing the true frequency of positive antiphospholipid antibodies (aPL) are lacking.
One of the first needs of APS ACTION was to review the literature to estimate the aPL frequency in patients with pregnancy complications, stroke, myocardial infarction, and deep venous thrombosis. Based on the analysis of 120 full-text papers*, we calculated the median frequency for positive aPL tests (LA test, aCL, and aβ2GPI) for each outcome.
The overall aPL frequency was estimated as:
In the process of reviewing the papers, we also recognized several limitations that would make it difficult to determine precise estimates of aPL frequency. Major limitations of the literature were:
- 9% for patients with pregnancy loss
- 10% for patients with deep vein thrombosis
- 11% for patients with myocardial infarction
- 14% for patients with stroke
- 17% for patients with stroke under age 50*
All these limitations suggest that our aPL frequency estimates should be taken with caution and need to be confirmed with appropriately designed population studies. However, this was the first approach to derive “real” numbers on aPL frequency from the existing literature. This exercise, designed and completed by APS ACTION Young Scholars, was also valuable in highlighting the current limitations of APS research, which should be hopefully taken into consideration in designing future studies.
- Most of the papers were quite old (published before the year 2000) and therefore they did not take into consideration a complete aPL profile (all the 3 criteria tests – LA, aCL, aβ2GPI - were included in only 11% of the papers).
- 36% of papers used a low-titer aCL cut-off instead of the recommended medium-high titer threshold; aβ2GPI cut-off was quite heterogeneous (reflecting the lack of international reference units); aPL confirmation (6-12 weeks apart) was performed in only one-fifth of papers.
- Study design was quite heterogeneous and nearly half of the papers were retrospective studies.
*For more information please refer to: Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, de Jesus GR, Erkan D; on behalf of APS ACTION. The estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis. Arthritis Care Res (Hoboken) 2013;65(11):1869-1873. PubMed PMID: 23861221.
* Unpublished Data
The Antiphospholipid Syndrome (APS) Clinical Research Task Force (CRTF) was one of six task forces developed by the organization committee of the 13th International Congress on Antiphospholipid Antibodies (aPL), which was held in Galveston, Texas in April 2010.
The task force recommended that there is an urgent need for a true international collaborative approach to design and conduct well-designed prospective large-scale multi-center clinical trials of patients with persistent and clinically significant aPL profiles1.
Thus, an international collaborative working meeting took place in Miami (Nov 2-4, 2010) that resulted in the formation of a clinical trial research alliance entitled: AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking ("APS ACTION").2
1Erkan D, Derksen R, Levy R, Machin S, Ortel T, Pierangeli S, Roubey R, Lockshin MD. Antiphospholipid
Syndrome Clinical Research Task Force Report. Lupus 2011;20:219-224
2Erkan et al. Antiphospholipid Syndrome Clinical Research Task Force Report. Lupus 2011;20:219-224