From the Guidelines
Heparin, specifically unfractionated heparin, can interfere with antiphospholipid antibody testing, potentially leading to inaccurate results. This is crucial to consider in the context of diagnosing antiphospholipid syndrome (APS), where accurate detection of antiphospholipid antibodies is key 1. The interference by heparin occurs due to its effects on the coagulation cascade, which is central to the methods used for detecting these antibodies.
Key Considerations for Testing
- The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee (ISTH-SSC) provides guidance on the laboratory detection and interpretation of antiphospholipid antibodies 1.
- For accurate testing, it is recommended to collect blood samples before initiating heparin therapy or after discontinuing it, considering the half-life and effects of heparin on coagulation tests.
- If testing must be conducted while a patient is on heparin, this should be clearly indicated on the laboratory requisition, and the results should be interpreted with caution, considering potential interferences 1.
Recommendations for Antiphospholipid Antibody Testing
- Concurrent testing for lupus anticoagulant (LA), anticardiolipin (aCL) IgG and IgM, and anti-beta2 glycoprotein I (aβ2GPI) IgG and IgM is recommended 1.
- Measurement of LA in citrated plasma according to ISTH-SSC recommendations, using a 3-step methodology (screening, mixing, and confirmation) with parallel testing in activated partial thromboplastin time (APTT) and dilute Russell’s viper venom time (dRVVT) as first-choice clotting tests, is advised 1.
- The use of alternative approaches like solid-phase assays for specific antiphospholipid antibodies may be considered, especially in patients requiring continued anticoagulation during testing 1.
Interpretation of Results
- Results should be interpreted according to local cutoff values and in a clinical context, considering anticoagulation therapy and potential interferences 1.
- A final conclusion as positive or negative for LA, along with warnings for potential interferences, should be reported 1.
- The level of aCL and aβ2GPI should be reported, with each level higher than the cutoff value for positivity considered positive 1.
From the Research
Interference of Heparin with Antiphospholipid Antibody Testing
- Heparin, specifically unfractionated heparin, can interfere with antiphospholipid antibody testing, leading to false-negative or false-positive results 2, 3, 4.
- The interference occurs because heparin affects clotting assays, which are used to detect the presence of lupus anticoagulants, a type of antiphospholipid antibody 2.
- Strategies to mitigate this interference include avoiding testing while patients are on anticoagulants, temporarily switching to an anticoagulant with less assay interference, testing for antiphospholipid antibodies at nadir levels of anticoagulants, and using anticoagulant neutralizers 2, 3, 4.
- It is essential to consider the potential interference of heparin when interpreting antiphospholipid antibody test results, especially in patients with thrombotic antiphospholipid syndrome 3, 4.
- False-positive tests for heparin-induced thrombocytopenia can also occur in patients with antiphospholipid syndrome, which can further complicate the interpretation of test results 5.
- In some cases, heparin therapy has been associated with catastrophic thromboses and severe thrombocytopenia in patients with anti-phospholipid syndrome, highlighting the need for careful consideration of anticoagulant therapy in these patients 6.