Comparison of Acquired Activated Protein C Resistance, Using the CAT and ST-Genesia® Analysers and Three Thrombin Generation Methods, in APS and SLE Patients

Abstract

Background: Acquired activated protein C resistance (APCr) has been identified in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Objective: To assess agreement between the ST-Genesia® and CAT analysers in identifying APCr prevalence in APS/SLE patients, using three thrombin generation (TG) methods. Methods: APCr was assessed with the ST-Genesia using STG-ThromboScreen and with the CAT using recombinant human activated protein C and Protac® in 105 APS, 53 SLE patients and 36 thrombotic controls. Agreement was expressed in % and by Cohen's kappa coefficient. Results: APCr values were consistently lower with the ST-Genesia® compared to the CAT, using either method, in both APS and SLE patients. Agreement between the two analysers in identifying APS and SLE patients with APCr was poor (≤65.9%, ≤0.20) or fair (≤68.5%, ≥0.29), regardless of TG method, respectively; no agreement was observed in thrombotic controls. APCr with both the ST Genesia and the CAT using Protac®, but not the CAT using rhAPC, was significantly greater in triple antiphospholipid antibody (aPL) APS patients compared to double/single aPL patients (p < 0.04) and in thrombotic SLE patients compared to non-thrombotic SLE patients (p < 0.05). Notably, the ST-Genesia®, unlike the CAT, with either method, identified significantly greater APCr in pregnancy morbidity (median, confidence intervals; 36.9%, 21.9–49.0%) compared to thrombotic (45.7%, 39.6–55.5%) APS patients (p = 0.03). Conclusion: Despite the broadly similar methodology used by CAT and ST-Genesia®, agreement in APCr was poor/fair, with results not being interchangeable. This may reflect differences in the TG method, use of different reagents, and analyser data handling.

Application of the thrombin generation assay in patients with antiphospholipid syndrome: A systematic review of the literature

“…-Language other than English. distinguished thrombotic and obstetric APS patients as separate patient groups (36,38), including 118 thrombotic APS patients and 34 obstetric APS patients (36,38). Four studies included thrombotic APS patients (n = 102) only (35,37,43,47).…”

“…Preanalytical and analytical aspects of all included studies are summarised in Table 2. Twelve articles measured TG via the calibrated automated thrombogram (CAT) method, according to the principles described by Hemker et al in 2003. One study compared the CAT assay to the ST Genesia ® (Stago, Asnièressur-Seine, France) methodology, an automated TG analyser based on the same principles as the CAT assay (36). TG methods can be performed using platelet-rich plasma (PRP), platelet-poor plasma (PPP), or whole blood.…”

“…We identified multiple records from the same research groups. We could rule out overlapping populations between studies for some research groups, although for three studies overlap is not unlikely since they use patient populations recruited under the same ethical reference number (35)(36)(37). However, the information provided in these three studies is relevant and unique since they compare the APS patient population against distinct control groups.…”

“…All studies were retrospective and had an observational design, of which four were identified as cross-sectional studies, ten casecontrol studies, and zero cohort studies. Characteristics and main findings of all included studies are summarised in Supplementary Table S4 (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). Only one record described information on the ethnicity of the cases (37).…”

“…Most studies identified thrombotic and obstetric manifestations retrospectively based on medical records. However, only eight studies specified the location or type of thrombotic and obstetric adverse events (35,37,38,43,45,46,36,44). Two studies…”