Abstract Number: PB0604
Meeting: ISTH 2020 Congress
Background: A patient with Waldenstrom’s Macroglobulinaemia had samples sent to Laboratory-1 who found a raised prothrombin time (PT) ratio (3.7), activated partial thromboplastin time (APTT) ratio (1.3), factor (F)V≤1IU/dL, and FVII 18IU/dL. Samples were referred to Laboratory-2 for confirmation and to Laboratory-3 and Laboratory-4 in an inter-laboratory exchange.
Aims: Establish consensus between laboratories in diagnosis of rare inhibitors.
Methods: Laboratories performed screening, one-stage clotting assays (OSCA) and inhibitor screening by their routine methods.
Laboratory-2 measured FVII≥59IU/dL, FII≥41IU/dL and FX≥23IU/dL (non-parallel curves), and FV≤1.0IU/dL at all dilutions. A Bethesda-principle inhibitor assay was consistent with a FV-inhibitor (18.1BU/mL). Lupus anticoagulant (LA) was detected by dilute Russell’s viper venom time (DRVVT), dilute APTT and Taipan Snake Venom Time (TSVT) confirmed by Ecarin Clotting Time (ECT).
Laboratory-3 measured FV and FVII activity below 1IU/dL, a FV-inhibitor (16.6BU/mL), a FVII-inhibitor (not quantified) and LA detected by DRVVT, dilute APTT and TSVT/ECT.
Laboratory-4 found normal levels of FII, FV, FVII and FX using PT reagent, but reduced FX using an APTT-based OSCA, and a FX-inhibitor (16BU/mL). No LA was detected by DRVVT or Silica Clotting Time.
Further OSCA were performed using a variety of different reagents on new samples (see table 1).
|Lab 1||Lab 2||Lab 3||Lab 4|
|Aug 19||Sept 19||Nov 19||Sept 19||Nov 19||Sept 19||Nov 19|
|Factor II [IU/dL]||40.5Innovin||69.0Innovin 92.3ThromborelS 92.6ActinFS||>10.2Innovin||>36.9Innovin||52Recombiplastin||49Recombiplastin|
|Factor V [IU/dL]||<1Innovin||<1.0Innovin||<1.0Innovin 95.8ThromborelS 162.8ActinFS||<1.0Innovin 70.7Antigen||>28.8Innovin 107.7Antigen||60Recombiplastin||79Recombiplastin|
|Factor VII [IU/dL]||18Innovin||>=59.2Innovin||>=73.1Innovin 77.4ThromborelS||<1.0Innovin||>6.2Innovin||49Recombiplastin||46Recombiplastin|
|Factor X [IU/dL]||>=22.7Innovin||>=39.4Innovin 77.5ThromborelS 81.1ActinFS||>11.7Innovin 58.6Antigen||>19.6Innovin||58Recombiplastin 17Synthasil||58Recombiplastin 14Synthasil|
|Factor VIII [IU/dL]||108.5Chromogenic||116.5ActinFS 60.8ActinFSL 82.9PathromtinSL 89.6Chromogenic||106Synthasil|
|Factor IX [IU/dL]||59.1Actin FS||77.2ActinFS 47.4ActinFSL 61.8PathromtinSL||20Synthasil|
|Factor XI [IU/dL]||61.5ActinFS 37.8ActinFSL 52.3PathromtinSL||25Synthasil|
|Factor XII [U/dL]||55.8ActinFS 49.0ActinFSL 55.8PathromtinSL||55Synthasil|
[Factor Assay Results]
Using LA-sensitive reagents, PT and APTT were prolonged even when mixed with normal plasma, and OSCA showed non-parallel curves, indicating the presence of an inhibitor. Using LA-insensitive PT and APTT reagents showed mildly prolonged clotting times and normal factor assays.
Conclusions: This patient had a strong LA that interfered with all OSCA performed with LA-sensitive reagents, even at high dilutions. These findings highlight: that LA can affect PT and/or APTT; the importance of using LA-insensitive reagents for performing OSCA; the importance of checking parallelism in OSCA, even when factor levels appear to be normal; and that even expert laboratories find such scenarios challenging.
To cite this abstract in AMA style:Platton S, McCormick A, Riddell A, Bromidge E, Fenoo C, Moore GW, Boshier C. Variable Findings in One-Stage Clotting Assays in a Patient with Waldenstrom’s Macroglobulinaemia [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/variable-findings-in-one-stage-clotting-assays-in-a-patient-with-waldenstroms-macroglobulinaemia/. Accessed November 29, 2023.
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