Lupus anticoagulant

Lupus antibody, LA, LAC, lupus inhibitors

Most patients with a lupus anticoagulant do not actually have , and only a small proportion will proceed to develop this disease (which causes joint pains, skin problems and kidney failure, amongst other complications). People with lupus erythematosus are more likely to develop a lupus anticoagulant than the general population.

lupus erythematosus

The term "anticoagulant" accurately describes its function . However in vivo, it functions as a procoagulant.[4]

in vitro

Both words in the term "lupus anticoagulant" can be misleading:

Indications for testing[edit]

The main indication for testing for lupus anticoagulant is a suspected antiphospholipid syndrome, whose main manifestations are blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia.[5]


In a suspected antiphospholipid syndrome, lupus anticoagulant is generally tested in conjunction with anti-apolipoprotein antibodies and anti-cardiolipin antibodies, and diagnostic criteria require one clinical event (i.e. thrombosis or pregnancy complication) and two positive blood test results spaced at least three months apart that detect at least one of the three types of antibodies.[6]


Testing for lupus anticoagulant can also be indicated by a prolonged aPTT test that is unexplained.[5]

-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.

Phospholipid

Lupus-sensitive aPTT, of which many variants exist, but have the common feature of having a greater of becoming prolonged in the presence of lupus anticoagulant compared to a regular aPTT.[9]

sensitivity

Hexagonal (II) phase phospholipid neutralization, wherein such phospholipids specifically neutralize lupus anticoagulant, so a normalization of aPTT after adding it specifically indicates the presence lupus anticoagulants.

[10]

An aPTT is generally included in a differential diagnosis in vague symptoms, and is a non-specific test of coagulation. In contrast, the prothrombin time (PT), another non-specific coagulation test, is normally unaffected by lupus anticoagulant. Nevertheless, falsely increased PT has been reported, likely by lupus anticoagulant interfering with the phospholipid component of the PT reagent, particularly when using recombinant tissue factor and purified phospholipids. [7]


A mixing test is generally in the initial workup of a prolonged aPTT. In a mixing test, patient plasma is mixed with normal pooled plasma and the clotting is reassessed. 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 generally 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 less likely, instead indicating a deficient quantity of clotting factor (that is replenished by the normal plasma). In case of a corrected mixing test, a lower dose of normal pooled plasma is often used, such as a 4:1 mix (4 times as much patient plasma than normal pooled plasma), as some studies suggest that this method is more sensitive for the detection of a weak lupus anticoagulant that is not enough prevalent or potent to affect a 1:1 mix.


However, only about 60 per cent of patients with lupus anticoagulants have a both a prolonged APTT and APTT mix, making it unsuitable as the only test in case of a high suspicion of the antiphospholipid syndrome.[8] Thus, one or more of the following tests are generally performed to detect lupus anticoagulant if a high suspicion remains, and/or specify lupus anticoagulant as the cause of an abnormal mixing test:

Treatment[edit]

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.[11]


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.[12]


Thrombosis is treated with anticoagulants (LMWHs and warfarin).[13]