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Monitoring Therapy with Vitamin K Antagonists in Patients with Lupus Anticoagulant: Effect on Different Tests for INR Determination

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Abstract

Background: Lupus anticoagulant (antiphospholipid antibodies) is associated with venous and arterial thrombosis in patients with and without autoimmune disorders. Vitamin K antagonists are the treatment of choice in patients with thrombosis, of which the dose is titrated by INR monitoring. Several recent reports suggest that the presence of the lupus anticoagulant disturbs the INR test and may lead to unreliable results with a large variation in INR values, dependent on the reagents used.

Methods: We studied 11 lupus anticoagulant positive patients and 11 lupus anticoagulant negative patients, all using vitamin K antagonists. The INR value was determined using seven different tests and the variation in INR values was compared between the two groups. The amidolytic Factor X levels were used as an phospholipid independent measure for intensity of warfarin therapy. Factor VII and X activity were measured to assess the stability of warfarin therapy.

Results: The variation of the results with different INR tests within one patient was minimal and comparable in the two groups for INR's in the therapeutic range. The coefficient of variation for the cases and control group was 10.43 and 9.35, respectively. Variation in both groups increased at supratherapeutic levels of anticoagulation and when the anticoagulation was unstable (measured with Factor X/Factor VII ratio). The relationship between INR values and Factor X analysis revealed no influence of the lupus anticoagulant.

Conclusions: In this study, lupus anticoagulant antibodies do not disturb INR laboratory tests. Differences in INR measurements are seen in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved.

Abbreviated Abstract. This study investigates the influence of lupus anticoagulant on INR determination tests in patients treated with warfarin. Eleven cases and eleven lupus anticoagulant negative control patients, also on warfarin therapy, were included. Seven INR results per patient were obtained using different laboratory tests. A factor X assay was performed to obtain an independent measure for the intensity of warfarin therapy.

The variation of INR results between the cases and controls revealed no difference in these groups. In addition, the relationship between INR values and Factor X analysis indicated no influence of the lupus anticoagulant. What was observed was an increased difference in INR values in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved

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Authors and Affiliations

  1. Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

    Nick R. Bijsterveld, Saskia Middeldorp & Harry R. Büller

  2. Department of Clinical Chemistry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

    Fenny Berends

Authors
  1. Nick R. Bijsterveld
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  2. Saskia Middeldorp
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  3. Fenny Berends
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  4. Harry R. Büller
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Bijsterveld, N.R., Middeldorp, S., Berends, F. et al. Monitoring Therapy with Vitamin K Antagonists in Patients with Lupus Anticoagulant: Effect on Different Tests for INR Determination. J Thromb Thrombolysis 9, 263–269 (2000). https://doi.org/10.1023/A:1018722829498

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