Lupus anticoagulant
Lupus anticoagulant is an immunoglobulin[1] that binds to phospholipids and proteins associated with the cell membrane. Lupus anticoagulant is a misnomer, as it is actually a prothrombotic antibody. Lupus anticoagulant in living systems cause an increase in inappropriate blood clotting. The name derives from their properties in vitro, as these antibodies increase laboratory coagulation tests such as the aPTT. Investigators speculate that the antibodies interfere with phospholipids used to induce in vitro coagulation. In vivo, the antibodies are thought to interact with platelet membrane phospholipids, increasing adhesion and aggregation of platelets, which accounts for the in vivo prothrombotic characteristics.
| Lupus anticoagulant | |
|---|---|
| Other names | Lupus antibody, LA, LAC, lupus inhibitors |
The condition was first described by hematologist C. Lockard Conley.[2][3]
Terminology
Both words in the term "lupus anticoagulant" can be misleading:
- Most patients with a lupus anticoagulant do not actually have lupus erythematosus, and only a small proportion will proceed to develop this disease (which causes joint pains, skin problems and renal failure, amongst other complications). Patients with lupus erythematosus are more likely to develop a lupus anticoagulant than the general population.
- The term "anticoagulant" accurately describes its function in vitro. However in vivo, it functions as a procoagulant.[4]
Workup
The presence of prolonged clotting times on a routine plasma test often triggers functional testing of the blood clotting function, as well as serological testing to identify common autoantibodies such as antiphospholipid antibodies. These antibodies tend to delay in-vitro coagulation in phospholipid-dependent laboratory tests such as the partial thromboplastin time.
The initial workup of a prolonged PTT is a mixing test whereby the patient's plasma is mixed with normal pooled plasma and the clotting is re-assessed. If a clotting inhibitor such as a lupus anticoagulant is present, the inhibitor will interact with the normal pooled plasma and the clotting time will remain abnormal. However, if the clotting time of the mixed plasma corrects towards normal, the presence of an inhibitor such as the lupus anticoagulant is excluded, and instead a deficient quantity of clotting factor (that is replenished by the normal plasma) is likely.
If the mixing test indicates an inhibitor, diagnosis of a lupus anticoagulant is then confirmed with prolonged phospholipid-sensitive functional clotting testing, such as the dilute Russell's viper venom time, or the Kaolin clotting time. As a further confirmation, a second test with the addition of excess phospholipid will correct the prolongation (conceptually known as "phospholipid neutralization"), confirming the diagnosis of a lupus anticoagulant.
Treatment
Treatment for a lupus anticoagulant is usually undertaken in the context of documented thrombosis, such as extremity phlebitis or dural sinus vein thrombosis. Patients with a well-documented (i.e., present at least twice) lupus anticoagulant and a history of thrombosis should be considered candidates for indefinite treatment with anticoagulants. Patients with no history of thrombosis and a lupus anticoagulant should probably be observed. Current evidence suggests that the risk of recurrent thrombosis in patients with an antiphospholipid antibody is enhanced whether that antibody is measured on serological testing or functional testing. The Sapporo criteria specify that both serological and functional tests must be positive to diagnose the antiphospholipid antibody syndrome.[5]
Miscarriages may be more prevalent in patients with a lupus anticoagulant. Some of these miscarriages may potentially be prevented with the administration of aspirin and unfractionated heparin. The Cochrane Database of Systematic Reviews provide a deeper understanding on the subject.[6]
Thrombosis is treated with anticoagulants (LMWHs and warfarin).[7] However, directly acting oral anticoagulants should not be administerd, because they may even induce an antiphospholipid antibody syndrome in patients suffering from lupus anticoagulant.
References
- Antonia Joussen; T.W. Gardner; B. Kirchhof (23 October 2007). Retinal Vascular Disease. Springer. pp. 430–. ISBN 978-3-540-29541-9. Retrieved 29 June 2010.
- Conley, C. Lockard (1952). "A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus". Journal of Clinical Investigation. 31: 621–622. doi:10.1172/JCI102648. PMC 436459.
- "Lock Conley looks back and blushes". Hopkins Medicine. Spring–Summer 2006. Retrieved 5 December 2013.
- "wustl.edu". Retrieved 2009-02-17.
- Viard JP, Amoura Z, Bach JF (1991). "[Anti-beta 2 glycoprotein I antibodies in systemic lupus erythematosus: a marker of thrombosis associated with a circulating anticoagulant]". Comptes Rendus de l'Académie des Sciences, Série III (in French). 313 (13): 607–12. PMID 1782567.
- Empson, M; Lassere, M; Craig, J; Scott, J (Apr 18, 2005). "Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant" (PDF). The Cochrane Database of Systematic Reviews (2): CD002859. doi:10.1002/14651858.CD002859.pub2. PMID 15846641.
- Dolitzky M, Inbal A, Segal Y, Weiss A, Brenner B, Carp H (2006). "A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages". Fertil Steril. 86 (2): 362–6. doi:10.1016/j.fertnstert.2005.12.068. PMID 16769056.