Lupus anticoagulant

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Lupus anticoagulant
ICD-9 289.81
DiseasesDB 775
MeSH D016682

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Lupus anticoagulant (also known as lupus antibody, LA, or lupus inhibitors) is a medical phenomenon where autoantibodies bind to phospholipids and proteins associated with the cell membrane. Since interactions between the cell membrane and clotting factors are necessary for proper functioning of the coagulation cascade, the lupus anticoagulant can interfere with blood clotting as well as in-vitro tests of clotting function. Paradoxically, lupus anticoagulants are also risk factors for thrombosis.

The name "lupus anticoagulant" is a misnomer. 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.

Conceptually, lupus anticoagulants overlap with the antiphospholipid antibody syndrome. Lupus anticoagulants can be understood as the tendency of antiphospholipid antibodies to prolong the clotting times, especially in phospholipid rich clotting testing such as the dilute Russell's viper venom time.

Often, the lupus anticoagulant is diagnosed on asymptomatic patients by a routine blood testing prior to surgery. Patients with a lupus anticoagulant are prone to thrombosis, excess bleeding, and habitual abortion (repeated miscarriages).

Workup

The presence of prolonged clotting times on a routine blood 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 blood is mixed with normal blood and the clotting is re-assessed. If a clotting inhibitor such as a lupus anticoagulant is present, the inhibitor will interact with the normal blood and the clotting time will remain abnormal. However, if the clotting time of the mixed blood corrects towards normal, the diagnosis of an inhibitor such as the lupus anticoagulant is excluded; the diagnosis is a deficient clotting factor that is replenished by the normal blood.

If the mixing test indicates an inhibitor, diagnosis of a lupus anticoagulant is then confirmed with phospholipid-sensitive functional clotting testing, such as the dilute Russell's viper venom time, or the Kaolin clotting time. Excess phospholipid will eventually correct the prolongation of these prolonged clotting tests (conceptually known as "phospholipid neutralization" in the clinical coagulation laboratory), 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 . [1].

Miscarriages may be more prevalent in patients with a lupus anticoagulant. These can be prevented with the administration of low molecular weight heparins (LMWHs), and thrombosis is treated with anticoagulants (LMWHs and warfarin).[2]

Monitoring the INR in a Patient with Lupus Anticoagulant

Some lupus anticoagulants interfere with the INR determination. They may lead to an elevated INR even if a patient is not on warfarin (=coumadin®)[3]

References

  1. 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]". C. R. Acad. Sci. III, Sci. Vie (in French). 313 (13): 607–12. PMID 1782567. 
  2. 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. PMID 16769056. 
  3. Ann Intern Med 1997;127:177-185: "Monitoring Warfarin Therapy in Patients with Lupus Anticoagulants"

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