Non-criteria Antiphospholipid Antibodies: a narrative review

Abstract

SUMMARY The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose accuracy was regarded as satisfactory according to the evidence available at that time. In practice, however, the sensitivity and specificity of these “criteria” of antiphospholipid antibodies are sometimes insufficient for identifying or ruling out antiphospholipid syndrome. It has been studied whether the accuracy of the laboratory diagnosis of the syndrome could be improved by testing for non-criteria antiphospholipid antibodies. In this work, we review evidence on the clinical associations and diagnostic value of the most commonly studied non-criteria antibodies, namely: antiphosphatidylethanolamine, anti-annexin A5, anti-prothrombin, anti-phosphatidylserine/prothrombin complex, IgA anticardiolipin, and IgG anti-domain I of the β2 glycoprotein antibodies.

Are antiphospholipid antibodies just a common epiphenomenon or are they causative of immune-mediated coagulopathy in COVID-19?

“…Overall, the frequency of circulating aPL in COVID-19 patients has been consistently high, with figures around 54%, although the frequency between studies varies widely, ranging from 8 to 96% [5,6]. This heterogenicity may reflect differences between the clinical phenotype of the patients studied (mild versus severe disease and early versus late disease), the type of aPL evaluated ("criteria" versus "non-criteria" antibodies) [7], or the presence of disease complications (i.e., venous and pulmonary thromboembolism or stroke). The role of ethnic, genetic, and geographic background cannot be ruled out.…”

“…A positive test for LA is found in approximately one of every two patients with COVID-19, while the presence of aCL and aβ2GPI antibodies has been observed less frequently (around 10% for each) [8]. Concerning "non-criteria" antibodies, it should be noted that a wide variety of aPLs have been des c r i b e d i n C O V I D -1 9 [ 7 ] . T h e s e i n c l u d e a n t iphosphatidylserine (aPS), anti-prothrombin (aPT), and antiannexin V (aAnnV) antibodies in both IgG and IgM isotypes, as well as aCL and aβ2GPI in IgA isotypes [6,[9][10][11][12][13].…”