**7. Antiphospholipid antibodies in healthy individuals**

Low aCL levels are found in up to 10% of healthy individuals, and the prevalence of a positive aPL test increases with age [10]. High aPL levels and persistent positivity are rare in healthy individuals (less than 1%). There are no recent studies investigating the level of criterion-related or non-criterion-related aPL in the general population. The clinical significance of aPL in healthy individuals remains unclear. It is important to emphasize that not every positive test for aPL is of clinical significance, and patients with aPL are at different risk for adverse events related to aPL. A rare prospective study in which healthy blood donors were tested for aPL twice 1 year apart showed 10% positivity for aCL and 1% positivity LA at the first measurement. Of note, less than 1% of subjects were still positive after 1 year [54]. Therefore, in parallel with other cardiovascular risk factors such as hypertension, elevated cholesterol, diabetes, smoking or obesity, patients with aPL have a higher risk of adverse events. It is known that aPL can occur transiently during infections or other occasions. This is an important reason why aPL should be tested twice within 12 weeks, which is also embodied in the international classification criteria for APS.

Recently, an administrative database study of aPL in the general population was published that characterized patterns of aPL testing in a sample from the United States using laboratory data from 2010 to 2015. They identified 33,456 individuals with at least one aPL test. Of these, only 6391 (19%) had all three tests (LA, aCL, aGP1) performed. Confirmatory aPL tests were performed at least 12 weeks later in 77, 45, and 41% of initially positive LA, aCL, and aGP1, respectively. Of those retested, only 255 (10.6%) had a confirmatory positive aPL test. The most important finding is the low rate of a confirmatory positive aPL test ≥12 weeks after the first test, indicating that aPL testing is often be incomplete. Further investigation in the form of large-scale population studies as well as longitudinal studies is needed to better understand the clinical relevance of aPL in healthy individuals from different backgrounds.
