PB0119 - The Benefit of Lab Modified Tests in Detection of Antithrombin Deficiency in era of In Vitro Medical Devices Regulation (IVDR)

Background: Antithrombin (AT) is a serine protease inhibitor, deficiency of which precipitates a hypercoagulable state, increasing thrombotic risk (5-50 fold), prevalence between 1-5% in VTE population. AT activity (ATa) is measured by chromogenic Xa or IIa assays. Literature indicates reduced incubation times, increases assay sensitivity, particularly for type II defects. Locally AT antigen (ATag) assay performed on all ATa < 0.91 IU/mL (reference interval (RI) 0.85 -1.31 IU/mL), and ratio ATa/ATag calculated (RI 0.89-1.12). Type I AT deficiency: reduced ATa and ATag with ratio within RI. Type II defects: abnormal ratio, even if ATa and/or ATag within RI.

Aims: IVDR potentially limits the use lab modified tests. This study evaluates the advantage of modified incubation times of an ATa to improve sensitivity to AT deficiency.

Methods: Residual citrated (0.109M) plasma samples stored at -80 degrees used. Antithrombin (n=129) assessed using Berichrom Antithrombin (IIa based, Siemens, UK) with manufacturer's recommended ~180 sec (AT180) and modified ~30 sec incubation (AT30) on ACL TOP 700 (Werfen UK).

Results: AT30and AT180 correlated well (n=129): AT30 mean (median) 0.94 (0.99) IU/mL vs AT180 mean (median) 0.97 (1.01) IU/mL, R2 = 0.8093 (figure1). Within this 22 AT deficient samples (type 1 congenital/acquired) were all classified correctly with both assays: AT180 mean (median) 0.67 (0.66) IU/mL vs AT30 mean (median) 0.65 (0.64) IU/mL. A further group (n=19), suggestive of Type II AT deficiency: AT180 mean (median) 0.96 (0.98) IU/mL vs AT30 mean (median) 0.73 (0.78) IU/mL. 15/19 AT180 and 3/19 AT30 were within RI (Table 1). The AT30 within RI all had ATa ( < 0.91 IU/mL) triggering ATag thus identify query Type II defects.

Conclusion(s): The use of modified AT incubation time assay improves AT assay sensitivity. Clinically important defects can be missed utilising manufacture recommended protocols. IVDR must allow flexibility like this in laboratory assays to ensure best outcome for patients.