Recommendations for the measurement of thrombin generation: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

Ninivaggi, Marisa; Laat-Kremers, Romy de; Tripodi, Armando; Wahl, Denis; Zuily, Stéphane; Dargaud, Yesim; Cate, Hugo Ten; Ignjatović, Vera; Devreese, Katrien; Laat, Bas de

doi:10.1111/jth.15287

Cited by 36 publications

(43 citation statements)

References 61 publications

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“…Results are expressed as normalized ratio (Table 8). Normalization of TG parameters was performed by an untreated NPP analyzed in every run 38 . The thrombogram showed a significantly higher peak height (PH) and velocity index (VI) and a lower time to peak (TTP).…”

Section: Resultsmentioning

confidence: 99%

“…Normalization of TG parameters was performed by an untreated NPP analyzed in every run. 38 The thrombogram showed a significantly higher peak height (PH) and velocity index (VI) and a lower time to peak (TTP). In addition, a statistically significant but very limited increase in endogen thrombin potential (ETP) was observed, while a significant shortening of the lag time (LT) could not be detected.…”

Section: Effect Of Df On Routine and Specialized Coagulation Assaysmentioning

confidence: 99%

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Direct Oral Anticoagulant removal by a DOAC filter: Impact on lupus anticoagulant testing – Evaluation on spiked and patient samples

Linskens

Kesel

Devreese

2022

Research and Practice in Thrombosis and Haemostasis

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Background DOAC Filter (DF) is a new device to overcome interference in lupus anticoagulant (LAC) testing by direct oral anticoagulants (DOACs). Objectives We evaluated DOAC removal from plasma and elimination of DOAC interference in LAC testing by DF, and impact of DF on LAC assays in a representative patient cohort, including a comparison with DOAC‐Stop (DS). Methods Normal pooled plasma (NPP) was spiked with increasing concentrations of apixaban, rivaroxaban, edoxaban, and dabigatran. DOAC and LAC was measured on untreated, DF‐treated, and DS‐treated spiked samples. Coagulation parameters and thrombin generation were measured on patient samples (n = 20) before and after DF. Patients treated with DOAC, vitamin K antagonist, or heparin and nonanticoagulated patient samples (n = 139) were tested for LAC before and after DF. Results In spiked NPP, levels were below the lower limit of quantification (LLoQ) after DF/DS treatment for all DOAC concentrations. Following DF, levels were below LLoQ for 53 of 56 DOAC‐containing patient samples. Twenty‐eight of 33 LAC‐positive DOAC‐containing samples became negative after filtration, whereas 5 remained LAC‐positive (1/5 from a patient with antiphospholipid syndrome [APS]). Four LAC‐positive DOAC‐containing samples (from patients without APS), became negative after filtration, whereas they remained LAC positive after DS. In the non‐DOAC patient groups following DF, LAC changed from positive to negative in 8 (due to a procoagulant effect) and vice versa in 2 cases. Conclusion DF reduces DOAC interference in LAC testing. As incomplete DOAC removal may occur, DOAC measurements should be performed after filtration. A procoagulant effect after filtration may lead to erroneous LAC results in non–DOAC‐containing samples. Therefore, using DF should be restricted to DOAC‐containing samples.

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Section: Resultsmentioning

confidence: 99%

Section: Effect Of Df On Routine and Specialized Coagulation Assaysmentioning

confidence: 99%

Direct Oral Anticoagulant removal by a DOAC filter: Impact on lupus anticoagulant testing – Evaluation on spiked and patient samples

Linskens

Kesel

Devreese

2022

Research and Practice in Thrombosis and Haemostasis

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“…Recent work by Douxfils et al showed that by implementing a validated and standardised method, using commercially available reference plasma and quality control samples [ 17 ], and normalising APCr [ 40 ], steps could be made towards implementing APCr TG in routine practice as a predictive biomarker [ 10 , 11 , 12 , 13 , 17 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. More recently, ISTH provided further guidance and recommendations for (pre)analytical steps when standardising the TG assay aiming to harmonise differences between methods and laboratories [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

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

Efthymiou

Lane

Isenberg

et al. 2021

JCM

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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.

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“…Attempts have been made to quantify or measure LA by other methods such as thrombin generation assays [ [31] , [32] , [33] ]. It is too premature to use this method in daily practice by lack of standardization [ 34 ]. So far, LA is regarded positive if the three steps within at least one test system have a normalized ratio above the local cutoff value.…”

Section: Lupus Anticoagulantmentioning

confidence: 99%

Role of antiphospholipid antibodies in the diagnosis of antiphospholipid syndrome

Devreese

Zuily

Meroni

2021

Journal of Translational Autoimmunity

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Recommendations for the measurement of thrombin generation: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

Cited by 36 publications

References 61 publications

Direct Oral Anticoagulant removal by a DOAC filter: Impact on lupus anticoagulant testing – Evaluation on spiked and patient samples

Direct Oral Anticoagulant removal by a DOAC filter: Impact on lupus anticoagulant testing – Evaluation on spiked and patient samples

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

Role of antiphospholipid antibodies in the diagnosis of antiphospholipid syndrome

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