What is the interpretation of Anticardiolipin (Antibody) antibody levels?

From the Guidelines

Anticardiolipin antibody levels should be interpreted as negative, low-positive, medium-positive, or high-positive, with results below 20 GPL or MPL units generally considered negative, and thresholds for moderate and high titers defined as 40 and 80 Units, respectively, according to the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria 1.

Interpretation of Anticardiolipin Antibody Levels

The interpretation of anticardiolipin antibody levels is crucial for the diagnosis and management of antiphospholipid syndrome (APS).

• A positive result, particularly if medium or high, suggests an increased risk of thrombosis and may indicate APS, especially if other criteria are met.
• Low-positive results may be seen in healthy individuals or could be due to transient infections.
• Persistently positive results (confirmed on two occasions at least 12 weeks apart) are more clinically significant, as emphasized by the ISTH-SSC subcommittee on lupus anticoagulant/antiphospholipid antibodies 1.

Clinical Context and Further Testing

Interpretation should always be done in the context of clinical symptoms and other laboratory findings.

• In patients with positive results, especially those with a history of thrombosis or pregnancy complications, further testing for lupus anticoagulant and anti-β2 glycoprotein I antibodies is often warranted.
• Management may include anticoagulation therapy, particularly for those with high-positive results or a history of thrombotic events.

Importance of Antibody Panel

Remember that anticardiolipin antibodies are just one part of the antiphospholipid antibody panel, and their presence alone doesn't necessarily indicate disease.

• The antibodies work by interfering with phospholipid-binding proteins, which can lead to a hypercoagulable state and increased risk of blood clots.
• The role of IgM and IgA isotypes, as well as other aPL such as antiphosphatidylserine (aPS)/prothrombin (PT) antibodies, is still a matter of debate and requires further study 1.

From the Research

Interpretation of Anticardiolipin Antibody Levels

The interpretation of anticardiolipin antibody levels is crucial in the diagnosis of antiphospholipid syndrome (APS) and other related disorders.

• Anticardiolipin antibodies (aCL) are measured using various analytical platforms, including enzyme-linked immunosorbent assay (ELISA), chemiluminescent immunoassay (CLIA), and multiplex flow immunoassay (MFI) 2, 3.
• The results of these tests are often reported as positive or negative, but the clinical significance of these results can vary depending on the level of antibodies present 4.
• Studies have shown that high levels of aCL are associated with an increased risk of thrombosis and pregnancy loss, while lower levels may not be associated with these risks 4.
• The use of likelihood ratios (LRs) and interval-specific LRs (IS-LR) can help to identify the power of a test to discriminate between a diseased and nondiseased patient, and may be useful for the semiquantitative interpretation of aCL results 2.

Thresholds for Anticardiolipin Antibody Positivity

• The traditional 40/80-unit thresholds used for aCL and anti-β2-glycoprotein I (aβ2GPI) antibodies may not be suitable for all analytical platforms 3.
• Alternative thresholds have been proposed, including those based on receiver operating characteristic curve analysis and regression analysis on diluted standard material 3.
• These alternative thresholds may improve the agreement between different analytical platforms and provide a more accurate interpretation of aCL results 3.
• The use of semiquantitative thresholds can help to harmonize the interpretation of aCL results across different platforms and improve the diagnosis of APS 2, 3.

Clinical Significance of Anticardiolipin Antibody Levels

• High levels of aCL are associated with an increased risk of thrombosis and pregnancy loss, and are often seen in patients with APS 5, 4.
• Lower levels of aCL may not be associated with these risks, and may be seen in healthy individuals or those with other conditions 4.
• The clinical significance of aCL levels should be interpreted in the context of the patient's clinical presentation and other laboratory results 6, 4.
• Repeat testing may be necessary to confirm the presence of aCL and to rule out other conditions 6.