Thrombosis Update · Published 2026-03-01 · DOI 10.1016/j.tru.2026.100239
Lupus anticoagulant–associated hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder, and interpretation of coagulation mixing tests can be challenging, particularly in the presence of direct oral anticoagulants (DOACs).We report an adult-onset case of LAHPS associated with Sjögren's syndrome and aimed to clarify discrepant cross-mixing test results using a mathematical modeling approach.Cross-mixing tests were performed twice during the diagnostic workup: first using a single-centrifuged plasma sample obtained 2 days after initiating DOAC therapy, and the second using a double-centrifuged sample collected on day 7. Mixing test patterns were evaluated morphologically and using quantitative indices, including the index of circulating anticoagulant (ICA), mixing test–specific cutoffs, and %C indices. A mathematical model incorporating features of coagulation factor deficiency and lupus anticoagulant–type inhibition was constructed to aid interpretation.The first test showed an almost linear activated partial thromboplastin time–patient plasma ratio curve in immediate and delayed reactions. The second test demonstrated convex upward curves in both reactions, consistent with an inhibitor-type pattern. Quantitative indices supported inhibitor-type reactions in both tests, whereas additional parameters (ICAwi–ICAwo, ICAwi/ICAwo, and WaS–ALD50) indicated a lupus anticoagulant–like profile rather than a coagulation factor–specific inhibitor. The model reproduced these patterns and discrepancies by accounting for DOAC effects and centrifugation differences.We present a simple, robust mathematical framework for interpreting cross-mixing test results. This approach may improve differentiation between factor deficiency and lupus anticoagulant–type inhibition, particularly in complex clinical settings involving DOAC therapy.
Abstract from DOAJ. Public domain (CC0 1.0).
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