From Scott Miller, St. Mary’s of Michigan Medical Center. Is there any consensus on whether anti-phospholipid antibodies (APAs) like lupus anticoagulant (LA) have any effect on prothrombin times and international normalized ratios (PT/INRs)? We have a patient who has been tested positive in the past for LA, and her INRs consistently run a bit higher in the lab (2.2) vs. a point-of-care (POC) device (1.7). Some studies conclude that there is no significant and consistent relationship. Others suggest there is, but that it may depend more on the type of reagent or platform. If the presence of APAs like LA is an issue, are there any guidelines on how a physician is to monitor therapy in a LA positive patient, especially considering the tendency for LA titers to rise and fall over time?
Hi, Scott, and thank you for your question. I’m an old Grand Rapids boy who trained at the original Butterworth Hospital, now Spectrum Health System. Back in my day, Butterworth and St. Mary’s were crosstown rivals! Anyway, yes, some thromboplastin reagents are sensitive to LA, probably those that are synthetic and employ relatively small concentrations of phospholipid. LA sensitivity may vary from lot to lot as well as among reagents from various manufacturers. While your plasma-based assay and POC results may remain consistently 0.5 units apart, they may change with a change in reagent lot or POC cartridge lot. See Balaban M, Stanrić V, Rincić G, et al. Recurrent venous thrombosis despite ‘optimal anticoagulation therapy’ for antiphospholipid syndrome–could new oral anticoagulants solve the problem? Acta Clin Croat 2010;49:469–77.
The Balaban article makes reference to the chromogenic factor X assay (CFX, not the same as the chromogenic anti-Xa) as an appropriate substitute when the PT/INR is unreliable. For more CFX documentation, check McGlasson DL, Romick BG, Rubal BJ. Comparison of a chromogenic factor X assay with INR for monitoring oral anticoagulation therapy. Blood Coag Fibrinolys 2008;19:513–7, and also Rosborough TK, Shepherd MF. Unreliability of international normalized ratio for monitoring warfarin therapy in patients with lupus anticoagulant. Pharmacotherapy. 2004;24:838–42. The only company that provides an FDA-cleared CFX is DiaPharma, Inc. The assay correlates nicely with the standard clot-based factor X assay. Geo.