Lupus anticoagulant

Lupus Anticoagulant and thrombosis, monitoring of anticoagulation

Thrombotic complications are limb threatening and life threatening.  There are multiple risk factors for thrombosis in the arteries and veins. Lupus anticoagulant is one of the risk factors for the development of thrombosis. Dr. Lockard Conley, haematologist discovered the Lupus Anticoagulant in 1947. The two words in this term are misnomers. This acts as an anticoagulant in the invitro and as procoagulant in vivo. It was first discovered in Systemic Lupus Erythematosus patient, but not seen in all patients with Lupus. Lupus anticoagulant (LA) is see in 2-4% of the general population. Presence of LA increases the risk of thrombosis 3.6 folds.  LA is positive in 10-30% of the SLE patients. Lupus Anticoagulants are autoantibodies targeting phospholipids and proteins associated with phospholipids on the outer cell membranes. Patients with some infections or those taking certain medications can develop Lupus anticoagulants. Nearly, 20% of the deep vein thrombosis patients with or without pulmonary embolism are associated with antiphospholipid antibodies. The tests are done in 2 stages. At first PTT-LA, DRVVT are done. Then Anticardiolipin antibodies, Beta-2 glycoprotein1 antibody, anti-prothrombin antibodies are tested to confirm the antiphospholipid syndrome (APS) in patients.

It is important to give special attention to the monitoring of warfarin therapy in APS patients. We are concerned about the reliability of INR determinations in this group of patients with DVT/ PE. It was observed that in 6.5% to 10% of patients with Lupus Anticoagulant, antiphospholipid antibodies (aPLs) may prolong the prothrombin time assay leading to an unreliable INR.^1,2,3  It is helpful to validate the INR in individual patients using a coagulation assay that is not affected by aPLs, suc as Factor II activity assay.⁴ After an APS patient is on warfarin with a stable INR of 2.0 to 3.0, an INR and factor II activity assay should be checked simultaneously. If the INR is in range and the factor II level is therapeutic (approximately 15% to 25%), the level of anticoagulation in adequate and the INR is reliable. If the INR is in range but the factor II level is >30%, the level of anticoagulation is inadequate. For such a patient, an individualized INR target range corresponding to a therapeutic factor II level should be established, or the factor II level itself could be followed.⁴

1.      Moll S, Ortel TL. Monitoring warfarin therapy in patients with lupus anticoagulants. Ann Intern Med. 1997; 127: 177–185.

2.      Sanfelippo MJ, Sennet J, McMahon EJ. Falsely elevated INRs in warfarin-treated patients with the lupus anticoagulant. WMJ. 2000; 99: 62–64.

3.      Rosborough TK, Shepherd MF. Unreliability of international normalized ratio for monitoring warfarin therapy in patients with lupus anticoagulant. Pharmacotherapy. 2004; 24: 838–842.

4.      Kasthuri RS, Roubey RA. Warfarin and the antiphospholipid syndrome: does one size fit all? Arthritis Rheum. 2007; 57: 1346–1347.