To Mix with Pooled Normal Plasma or Not to Mix: A Comparative Study of 2 Approaches for Assessing Lupus Anticoagulant Inhibitory Activity in the Dilute Russell Viper Venom Method

Lupus anticoagulant mixing tests for multiple reagents are more sensitive if interpreted with a mixing test‐specific cut‐off than index of circulating anticoagulant

“…The mixing of weak LA samples may introduce loss of detectable LA activity and the false‐negativity give rise to inaccurate interpretation if the mixing test result is employed as a decision point for subsequent confirmatory test performance 14, 31, 32, 33. For samples from patients with no other causes of clotting time prolongation and LA assay confirmatory test results within reference intervals, the increasingly popular paradigm of integrated testing is sufficient to detect the presence of LA without performing the mixing test at all 6, 7, 8, 9, 26, 27, 28, 31, 33, 34. However, in situations where alternative or co‐existing coagulation abnormalities are present, mixing tests can improve specificity of LA testing 34, 35, 36, 37.…”

Laboratory investigation of lupus anticoagulants: mixing studies are sometimes required

“…By means of electronic noses (eNoses), the sampling of exhaled breath and its VOCs has become readily available, owing to their ability to discriminate biomarker profiles or ÔbreathprintsÕ with composite nanosensor arrays (breathomics). Currently available eNoses include handheld devices using on-board pattern recognition software that is suitable for diagnostic classification without identification of the individual molecular components [3,4]. This provides the potential option of Ôon the spotÕ diagnosis of diseases, as has been investigated in lung cancer [5], chronic obstructive pulmonary disease and asthma [4,6].…”

“…The basis of these tests is the relative shortening (or ÔcorrectionÕ) of the clotting prolongation evident in a low phospholipid containing reagent after retesting of the sample with a high phospholipid containing reagent. This approach saves on the need to perform mixing studies with normal pooled plasma, technically simplifies LA testing, obliterates the need to prepare or purchase large quantities of such plasma, and is supported by workers who cite evidence of false negative LA findings when mixing Ôweak but clinically significantÕ LA samples [4,5]. However, a failure to correct the clotting time with a non-mixed confirmatory test can represent either a factor deficiency/inhibitor, or (as per the current case) a strong LA that is not neutralized by the level of available phospholipids, and we therefore highlight the value of mixing tests (and sample dilutions) in select cases.…”

Decreased mean platelet volume in Gilbert's syndrome

“…They therefore advocated a place for lupus anticoagulant investigations that did not incorporate a mixing step. The authors also cited previous work that supported performance of nonmixing tests because mixing might lead to loss of 'weak' lupus anticoagulant activity [6][7][8]. Although these particular studies did not advocate complete removal of mixing tests, rather highlighting a limitation of mixing, and suggesting that some lupus anticoagulants can be found without them, we have continued to note a general move away from mixing studies in normal laboratory practice, for example including participants of our external quality assessment (EQA) programme [9].…”

“…Although Hong et al [5] considered the possibility of false-negative lupus anticoagulant by performance of mixing studies and dilution of a weak lupus anticoagulant, as previously reported [6][7][8], they failed to consider the alternate, namely the possibility of false-negative lupus anticoagulant by nonperformance of mixing studies and due to the presence of a strong lupus anticoagulant. In the lupus anticoagulant guidelines clarification response [11] to our original correspondence report [12] of the case of a strong lupus anticoagulant sample being falsely 'lupus anticoagulant negative' by virtue of a normal dRVVT screen/confirm ratio, the suggestion was raised that our observations could be explained by the lack of some cofactor when using the native patient plasma.…”