Coagulation mixing studies: utility, algorithmic strategies and limitations for lupus anticoagulant testing or follow up of abnormal coagulation tests
Open accessAbstract
Coagulation testing underpins the investigation of hemostasis and/or monitoring of anticoagulation therapy for prevention and/or treatment of thrombosis related pathology. Assessment of coagulation results requires comparison against a normal reference range or interval (NRR/NRI). Results flagged as "abnormal" (ie, above the NRR/NRI for patients not on anticoagulant therapy), typically require further evaluation. eg, follow up or reflexive testing is used to identify the reason for prolongation, especially when supported by clinical context (eg, bleeding). Mixing tests may have utility to help identify the pathway of follow-up testing (ie, towards investigation of factor deficiencies, or else inhibitors), and are also useful for investigation of lupus anticoagulants (LA). In general, mixing tests that "correct" tend to suggest the presence of factor deficiencies, where as those that do not correct suggest the presence of "inhibitors". Various approaches can be used to identify correction/non-correction, and all have strengths and limitations. Furthermore, eventual identification of causal factor deficiencies or even "inhibitors" may (eg, factor VIII or IX deficiencies or inhibitors) or may not (eg, factor XII deficiency) be clinically important. Ultimately, mixing studies performed in view of appropriate clinical scenarios (eg, bleeding patient) and for LA investigations in symptomatic patients will have best utility.
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The mixing test is useful to investigate the cause of unexpectedly prolonged activated partial thromboplastin time (APTT).
“The mixing test is useful to investigate the cause of unexpectedly prolonged activated partial thromboplastin time (APTT).”
Correction generally indicates coagulation factor deficiency, whereas non-correction suggests the presence of an inhibitor.
“Correction generally indicates coagulation factor deficiency, whereas non-correction suggests the presence of an inhibitor (eg, lupus anticoagulant [LA] or a specific coagulation factor inhibitor) [3].”
Numerical indexes are reportedly useful in observed correction.
“Because the correction/non-correction interpretation is subjective, numerical indexes are reportedly useful in observed correction [[1], [2], [3], [4], [5]].”
No indexes permit 100% accurate discrimination.
“because no indexes permit 100% accurate discrimination [3].”
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Percentages, sums and reported differences re-computed from the paper’s own numbers.
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Cites
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Flagged first, then by citations
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Cited by
Sorted by citations
Mixing studies for lupus anticoagulant: mostly yes, sometimes no
Favaloro, E. (2020) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2019-1240 · Cited by 20 · see citing works
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- Authors
- Favaloro, E. J.
- Affiliations
- Westmead Hospital (AU)
- Corresponding author
- Favaloro, Emmanuel J.
- Venue
- American Journal of Hematology
- Publisher
- Wiley
- Published
- 2019-11-20
- Volume
- 95
- Issue
- 1
- Pages
- 117-128
- ISSN
- 0361-8609 (ISSN-L)
- 1096-8652
- OpenAlex
- W2987416135
- Cited by
- 53
- References
- 38
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 9 · 2023: 11 · 2022: 9 · 2021: 4 · 2020: 1 · 2019: 1
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Hematology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
- Keywords
- lupus anticoagulant, anticoagulants, factor deficiency, hemophilia A, hemophilia B, factor XII deficiency, hemorrhage, anticoagulation monitoring, thrombosis
- MeSH terms
- Algorithms, Blood Coagulation Disorders, Blood Coagulation Tests, Hemostasis, Humans, Lupus Coagulation Inhibitor
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