Lupus Anticoagulants Can Invalidate INRs
ABSTRACT & COMMENTARY
Source: Moll S, Ortel TC. Monitoring warfarin therapy in patients with lupus anticoagulants. Ann Intern Med 1997; 127:177-185.
Moll and ortel sought to determine the validity of the international normalized ratio (INR) as a monitor for warfarin therapy in patients with lupus anticoagulants (LAC). They determined prothrombin times (PT) using nine thromboplastins in controls (n = 25) and in patients with LAC (n = 34). INRs were calculated for patients receiving warfarin.
Twenty-two patients with LAC who were not receiving warfarin often had PTs that were elevated and varied significantly with different thromboplastins. All had a prolonged PT with at least two thromboplastins (range, 2-9 thromboplastins).
Half of the LAC patients had a PT greater than one second above the upper limit of normal. Five normal control subjects all had normal PTs, and the mean PT ratio for each thromboplastin was close to 1.0. The difference between the two groups was highly significant (P < 0.001).
For LAC patients receiving warfarin, INRs obtained by using different thromboplastins varied greatly and often overestimated the extent of anticoagulation. In 16 patients with LAC on stable warfarin therapy, the difference between the highest and lowest INR for any single patient plasma sample ranged from 0.4 to 6.5. In controls, the range was 0.5-1.2 (P < 0.001).
In patients with LAC, the INR did not standardize PT ratio for the variability in the responsiveness of thromboplastins. Therefore, the INR did not reflect the true level of anticoagulation in some patients with LAC.
COMMENTARY
Clinicians have been puzzled by the wide variation in INR results in their systemic lupus erythematosus patients who reliably take a stable amount of warfarin. This study explains why INR cannot be relied upon to monitor anticoagulation therapy in many patients with LAC. In some patients whose normal baseline PT indicates that the thromboplastin used in the assay is relatively insensitive to LAC, INR may be reliable. It must be remembered that a normal PT does not guarantee that INRs will be accurate during warfarin anticoagulation and also that hospital laboratories may change thromboplastin from time to time.
For patients with a prolonged baseline PT, management of anticoagulation requires alternate approaches in both laboratory testingfor example, use of the prothrombin-proconvertin time test or chromogenic factor X essay, tests that are not widely available, and in therapyperhaps substituting low molecular weight heparin for warfarin. Further studies of the problem are needed to provide practical clinical solutions. jjc
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