The effect of unfractionated heparin, enoxaparin and danaparoid on lupus anticoagulant testing. Can activated carbon eliminate false positive results?
Open accessAbstract
BACKGROUND: Heparins and heparinoids interfere with functional clotting assays used for lupus anticoagulant (LAC) detection. However, current guidelines for LAC testing do not provide clear guidance on this matter. OBJECTIVES: We aimed to assess to effect of unfractionated heparin (UFH), enoxaparin, and danaparoid on LAC assays over broad anti-Xa activity ranges and to evaluate whether activated carbon (AC) is able to neutralize these effects. METHODS: UFH (0.1-3.0 IU/mL), enoxaparin (0.2-2.9 IU/mL), and danaparoid (0.6-2.2 IU/mL) were spiked to normal pooled plasma. AC was added at multiple activity levels. Anti-Xa assays and LAC tests were performed on all samples using Stago analyzers and reagents. RESULTS: Abnormal activated partial thromboplastin time (APTT) screening and mixing tests were obtained at the lowest levels for all compounds. Abnormal APTT confirmation tests were seen from 2.5 and 1.9 anti-Xa IU/mL for enoxaparin and danaparoid, respectively. Abnormal dilute Russell's viper venom test (dRVVT) screening tests were obtained from 1.6, 1.4, and 1.1 anti-Xa IU/mL for UFH, enoxaparin, and danaparoid, respectively. Mixing tests were abnormal from 2.5 and 1.3 anti-Xa IU/mL for enoxaparin and danaparoid, respectively. Abnormal dRVVT confirmation results were seen for danaparoid only from 1.9 anti-Xa IU/mL. AC was unable to neutralize anti-Xa activity in plasma and overcome the effect of the tested anticoagulants on LAC assays but may cause prolongation of APTT clotting times. CONCLUSIONS: UFH, enoxaparin, and danaparoid clearly affected LA tests; however, false-positive LAC conclusions were obtained at supratherapeutic enoxaparin and danaparoid levels only. AC may prolong APTT screen clotting times, requiring 3-step testing to avoid potential misdiagnosis of LAC.
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Pretreatment with adsorbents may alter clotting times, producing false-positive or false-negative LA results or incomplete removal of direct oral anticoagulants.
“Several studies indicated that pretreatment with adsorbents may affect clotting times resulting in false-positive or false-negative LA results, or incomplete removal of DOACs.33,[41][42][43]”
From Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis (2020) · cites this paper as [33]
The Results and Discussion report that activated-carbon pretreatment prolonged APTT screening clotting times, and the Conclusions warn that three-step testing is needed to avoid potential misdiagnosis. But the study found that pretreatment did not alter its final LA interpretations; it does not report false-negative LA results or incomplete DOAC removal. Its false-positive LA findings concerned high levels of enoxaparin and danaparoid, not adsorbent pretreatment. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEnoxaparin caused false-positive APTT-based LA detection only at supra-therapeutic anti-Xa activity levels.
“In contrast, enoxaparin caused false-positive aPTT-based LA detection only at supra-therapeutic anti-Xa activity levels.”
Unfractionated heparin and enoxaparin affect dRVVT at supra-therapeutic anti-Xa levels but did not cause false-positive LA in the three-step procedure.
“a recent study 33 showed unfractionated heparin (UFH) and enoxaparin affect the dRVVT at supra-therapeutic anti-Xa levels but did not lead to false-positive LA in the three step procedure.”
False positives have been described for aPTT and dRVVT even when utilizing heparin neutralizers.
“False positives have been described for aPTT and dRVVT even when utilizing neutralizers [68,69,70].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [70]
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- Authors
- De Kesel, P. M. M., & Devreese, K. M. J.
- Affiliations
- Ghent University Hospital (BE)
- Corresponding author
- Devreese, Katrien M.J.
- Venue
- Research and Practice in Thrombosis and Haemostasis
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 4
- Issue
- 1
- Pages
- 161-168
- ISSN
- 2475-0379 (ISSN-L)
- PMC
- PMC6971310
- OpenAlex
- W2995572514
- Cited by
- 47
- References
- 26
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 8 · 2023: 9 · 2022: 8 · 2021: 7 · 2020: 9
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Research and Practice in Thrombosis and Haemostasis (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- lupus anticoagulant, unfractionated heparin, enoxaparin, danaparoid, heparinoids, activated carbon, false positives, anti-Xa activity, activated partial thromboplastin time, mixing test, anticoagulant interference
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