Reference Intervals of the Dilute Tissue Thromboplastin Inhibition and Dilute Russell's Viper Venom Tests Revisited

Abstract

Reference intervals for two well-recognized tests for the lupus anticoagulant were determined using 98 healthy subjects. The purpose of the study was to compare the reference intervals for the dilute tissue thromboplastin inhibition test on this group of healthy subjects calculated by parametric and nonparametric statistical methods, and to compare these results with results obtained on subsets of 20 and 40 randomly selected individuals from the group of 98. The same procedures were followed for the dilute Russell's viper venom test. Results were recorded in seconds of clotting times and in ratios (subject/mean of that set or subset). Statistical analysis revealed Gaussian distribution of the results in the large group as well as in each subset for both tests. The results showed more variation between sets of the dilute tissue thromboplastin inhibition test than of the dilute Russell's viper venom test. Nonparametrically calculated reference intervals were wider than those determined by the parametric method, especially if confidence intervals are provided for both reference limits in a group of 94 controls or in a subset of 40 subjects. The nonparametric technique uses all data for the calculation of reference interval of such sample sizes no matter how widely spread the results are. There was no significant difference between the reference intervals of subsets and the whole group (p > 0.05) calculated by both statistical techniques. Very few outliers were observed among these subjects in both tests.

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

“…Reference intervals were calculated as the mean ± 2 standard deviations. 7,8,22,[24][25][26][27] Shapiro-Wilk test was performed to confirm the Gaussian distribution of the reference intervals.…”

Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants

“…[13][14][15] In common with many other analytes, RIs for LA assays have historically been derived from the RI mean AE 2 standard deviations (SD). This is not inappropriate since data from normal donor populations for clotting tests are commonly Gaussian or near Gaussian, or can be made so by data transformation, 14,16 although this requires confirmation with each assessment to enable data to be suitable for parametric statistics. 17 The upper limit operates as the cutoff (97.5th percentile) for determining positivity and initiating confirmatory tests, while the RI mean clotting time can be employed to generate normalized ratios.…”

The association of serum antiphospholipid antibodies and dilute Russell's viper venom times

“…It has been pointed out previously that the inaccuracy of the reference interval estimation is underappreciated10 and that the factor most uncertain in the literature recommendations for APLA testing is the number of healthy subjects required for determination of the reference interval, generally varying from 401 11 to optimally 120 or more 12. Even then, the results will be imprecise,13 as demonstrated by the distribution of our reference population.…”

“…However, if we excluded the upper five values in the controls and assumed a Gaussian distribution, the upper limit of the reference range would decrease to 1.22. There are two reports that found that dRVVT distributes normally,12 14 but they were either based on a very small reference group14 or excluded patients with an abnormal activated partial thromboplastin time (aPTT) result 12. Occasional elevated functional APLA test results in apparently otherwise normal donors is a well recognised phenomenon and it is unclear when to exclude outliers from the control group.…”