Paired APTTs of low and high lupus anticoagulant sensitivity permit distinction from other abnormalities and achieve good lupus anticoagulant detection rates in conjunction with dRVVT

Abstract

Introduction A prolonged activated partial thromboplastin time (APTT) may be indicative of a specific or multiple factor deficiency, therapeutic anticoagulation, presence of a nonspecific factor inhibitor, or lupus anticoagulant (LA). Recently, pairing of the LA‐sensitive APTT and standard APTT reagents, Cephen LS and Cephen, respectively, has been shown to be effective in LA detection. The present study aimed to evaluate the usefulness of this reagent pair for discriminating between causes of APTT elevation and the detection of LA in conjunction with dilute Russell's viper venom time (dRVVT). Methods Plasma samples from 50 normal and 105 non‐anticoagulated LA‐positive patients in routine dRVVT and/or dilute APTT (dAPTT) via the percent correction formula were employed. Cephen LS/Cephen and dRVVT reagents LA1/LA2 were used to screen/confirm, respectively. Thirty‐four symptomatic LA‐negative, 25 warfarinised non‐antiphospholipid syndrome, 6 coagulation inhibitors, 17 samples with hereditary elevated APTT, and 24 FVIII/IX/XI/XII and 17 FII/V/X artificial single deficiency plasmas were used. Results Thirty‐three samples out of 105 (31%) were LA‐positive in Cephen LS/Cephen. The total percent positivity in Cephen LS/Cephen and LA1/LA2 pairs was 89.1% against samples with the routine dRVVT/dAPTT double positive. The percent corrections of Cephen LS/Cephen in the routine dAPTT/dRVVT positive group were significantly higher than those in all other groups. Conclusions The percent correction of the APTT reagent pair showed higher values in LA‐positive samples. The combination will be useful with respect to differentiating LA from other abnormal samples and is effective in LA detection when paired with dRVVT.

Applying index of circulating anticoagulant to mixing tests with lupus anticoagulant screen and confirm reagents can distinguish with high specificity between lupus anticoagulants and direct factor Xa inhibitors

“…Recently, Hillarp et al described that phospholipid concentration differences between screen and confirm reagents contribute to discrepancies between them in presence of DOACs, and that between‐manufacturer phospholipid compositional differences account for some reagents being more affected than others, or not being affected at all 12 . On the other hand, Cephen LS and Cephen were similarly albeit not identically affected by each of the DiXaIs despite differences in phospholipid concentration, 18 further suggesting that composition is a key factor in relative DOAC‐responsiveness. APTT normalized ratios were reduced in a dose dependent manner, leading to a risk of false‐negatives at higher DiXaI concentrations, more so with edoxaban than rivaroxaban or apixaban.…”

“…The cut‐off values of the screen ratio and confirm ratio for the Cephen LS / Cephen APTT pair and LA1 screening reagent / LA2 confirmation reagent dRVVT pair were previously established locally as 1.09 / 1.14 and 1.12 / 1.08 by calculating the upper limits of the distribution of 50 normal samples, respectively 4,18,22‐24 . The cut‐off values of the normalized ratios were already locally established at 1.20 for each reagent pair, based on the guidelines 25 .…”

Acquired hemophilia�A presenting as progressive intra‑abdominal hemorrhage, muscle hemorrhage and hemothorax postpartum: A case report and literature review

“…In addition, LA presents with a persistent prolonged aPTT, as does AHA, and may lead to the false appearance of reduced coagulation factors in vitro due to its inhibitory effect on phospholipids (10). In LA, prolonged aPTT cannot be corrected by using normal plasma; however, it can be shortened and corrected by the supplementation of exogenous phospholipids (11). This can be proven more definitively through a variety of phospholipid-dependency experiments and by performing the Dilute Russell's viper venom time test.…”

“…This can be proven more definitively through a variety of phospholipid-dependency experiments and by performing the Dilute Russell's viper venom time test. FVIII autoantibodies and LA may coexist in the same patient (11,12). For complicated cases, ELISA may be used to identify FVIII inhibitors in LA (12).…”

The Russell viper venom time (RVVT) test for investigation of lupus anticoagulant (LA)

“…It is perhaps also historically notable that Thomas Exner was the lead author for the first ISTH SSC LA guideline . Others contributing to the related guidance documents have also continued to publish their recent experience of the RVVT/LA dyad . Some highlights around the history of RVV, RVVT, and dRVVT (representing the “dilute” RVVT) is depicted in Figure .…”