Int J Clin Lab Res 22: 106-110, 1992 9 Springer-Verlag1992
An evaluation of several laboratory tests and test combinations in the detection of lupus anticoagulant Cristina Legnani, Guaitiero Palareti, Ottavio Boggian, Katia Cavallaroni, Gaetana Oca, Giuseppa Lo Manto, Carmela Abate, and Sergio Coeeheri Department of Angiology and Blood Coagulation, University Hospital S. Orsola, Via Massarenti 9, 1-40138, Bologna, Italy
Summary. The laboratory assessment of the lupus anticoagulant, a factor frequently associated with venous and arterial thrombosis, recurrent miscarriages and abortions, is not straightforward, as indicated by the variety of tests proposed and the different results obtained. On account of the marked variability and heterogeneity of lupus anticoagulant among patients, no single test or reagent will identify all patients with lupus anticoagulant, and a panel of several tests has to be used. This is time consuming and increases the workload of the laboratory. The aim of this study was to assess the minimum number of tests necessary for the satisfactory identification of the patient with lupus anticoagulant. Our study confirms that lupus anticoagulant may be present in a significant number of patients with normal routine activated partial thromboplastin time, a test which therefore cannot be used as the sole criterion for identifying patients suspected of having lupus anticoagulant. In contrast all patients who had positive results in at least one test could be detected (100% sensitivity) with two combinations of tests: (1) dilute activated partial thromboplastin time and Kaolin clotting time and (2) dilute activated partial thromboplastin time and tissue thromboplastin inhibition test. Since the latter inhibition test has been reported to give a high number of false-positive or negative results, we suggest the combination of dilute activated partial thromboplastin time and Kaolin clotting time as the standard pair of tests for the screening of suspected lupus anticoagulant patients. Key words: Lupus anticoagulant - Activated partial thromboplastin time - Kaolin clotting time - Dilute Russell's viper venom time - Tissue thromboplastin inhibition test
Introduction The laboratory detection of lupus anticoagulant (LA) is clinically important since it is frequently associated with Offprint requests to: C. Legnani
episodes of venous and arterial thrombosis, recurrent miscarriages and abortions. However, laboratory assessment of LA is not straightforward, as indicated by the variety of tests proposed and the different results obtained. According to the criteria recently revised by the Subcommittee for Standardization of Lupus Anticoagulant of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis [9], the laboratory detection o f LA is based on the initial use of phospholipid- or platelet-depleted coagulation tests such as kaolin clotting time (KCT) [6], dilute Russell's venom viper time (dRVVT) [26], tissue thromboplastin inhibition test (TTIT) [24], dilute activated partial thromboplastin time [2] or "sensitive" aPTT. The prolongation of one of the above-mentioned phospholipid-dependent coagulation times and the failure of the defect to be corrected by mixing the patient's plasma with normal plasma are the minimal criteria for the identification of LA. That the inhibitor is directed against phospholipids rather than a specific coagulation factor should be subsequently demonstrated by the correction of the LA defect by the addition of washed, frozen-thawed platelets [29] or preferably phospholipids [5, 15, 21]. The large number of screening tests proposed for the detection of LA reflects the unsatisfactory state of the laboratory diagnosis of this condition. A recent international survey on LA [8] and the experience in the United Kingdom [19] indicated that in LA diagnosis problems can occur before analysis, in the choice of screening tests and in the confirmation of the antiphosphotipid nature of the inhibitor. It is generally believed that strong LA can be detected by all currently available single tests; weaker anticoagulants, however, may reportedly affect one but not necessarily another screening test. On account of the marked heterogeneity of LA among patients, no single test or reagent will identify all patients with LA, and a panel of several tests has to be used. This is time consuming and increases the workload of the laboratory. The aim of this study was to compare several tests currently used for LA detection in order to establish the
C. Legnani et al.: Detection of lupus anticoagulant m i n i m u m c o m b i n a t i o n o f tests necessary for identifying the m a x i m u m n u m b e r o f p a t i e n t s w i t h L A .
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Table 1. Normal values in tests for lupus anticoagulant (LA) detection a.b CT PP/CT NP
CT mixture/CT NP _