Laboratory control of oral anticoagulant treatment by the INR system in patients with the antiphospholipid syndrome and lupus anticoagulant. Results of a collaborative study involving nine commercial thromboplastins

Abstract

Summary. Because of the variable responsiveness of thromboplastins to lupus anticoagulants (LA), concerns have been raised about the validity of the prothrombin time±International Normalized Ratio (PT±INR) in monitoring oral anticoagulant treatment in patients with the antiphospholipid syndrome (APS) and LA. To date, few studies have been performed, numbers of patients investigated are relatively small and results are conflicting. We report on a multicentre study organized to investigate further this clinically relevant issue. Each of nine thrombosis centres was asked to collect plasma samples from patients with APS who were on oral anticoagulants (cases) and patients without APS who were on oral anticoagulants (controls). Nine thromboplastins (three human recombinant, one from human placenta and five from rabbit brain) were calibrated at the co-ordinating centre according to World Health Organization guidelines. Measurements of the INR and factor X amidolytic activity for all frozen plasmas were performed centrally. The numbers of patients investigated were 58 cases and 57 controls. Between-reagent variability of the INR was higher in cases [coefficient of variation (CV) 12´4%] than in controls (CV 6´7%), but this was because of one of the thromboplastins only (Thromborel R, human recombinant), which measured considerably higher INR values than the others in cases but not in controls. In conclusion, our data indicate that LA interference on the PT±INR measured with the majority of commercial thromboplastins is not enough to cause concern if insensitive thromboplastins, properly calibrated to assign them an instrument-specific International Sensitivity Index are used. New thromboplastins, especially those made of relipidated tissue factor, should be checked for their responsiveness to LA before they are used to monitor oral anticoagulant treatment in patients with APS.

Thrombosis and the Antiphospholipid Syndrome

“…43 This is not observed with all thromboplastin reagents, but appears to occur more frequently with recombinant thromboplastins with a low international sensitivity index. 44,45 For patients who appear to have a lupus anticoagulant that affects the prothrombin time, an alternative test, such as the chromogenic factor X assay, would be a more accurate way to monitor oral anticoagulant therapy.…”

Antiphospholipid Syndrome: Changing Knowledge During the Time – The ”Four P” Pattern

“…The potential advantages of these drugs in antiphospholipid antibodies positive patients have to be mentioned. The first of all is well known complicated laboratory monitoring in vitamin K dependent oral anticoagulant in the cases of lupus anticoagulants presence (Tripody A, et al;2001). The second reasons which could favourite the new antithrombotic drugs is the fact that warfarin failures more frequently in secondary prevention in venous thromboembolisms in antiphospholipid antibodies than in other indications (Ames PRJ, et al;2005, Wittkowsky AK, et al;2006, Kearon C, et al;.…”

Trombo biventricular e fibrose endomiocárdica na síndrome antifosfolípide

“…The cardiac alterations are frequently observed, especially valvular heart disease (thickening and vegetations) and coronary artery disease (CAD) [2][3][4] ; the presence of thrombi has been also reported 5 . However, myocardial involvement is rarely described in this pathology 6 .…”

“…It constitutes the main acquired cause of hypercoagulability, occurring in 2% of the general population and has high morbidity and mortality 2 .…”