Lupus anticoagulant
Encyclopedia
Lupus anticoagulant is an immunoglobulin that binds to phospholipid
s and protein
s associated with the cell membrane. It is important to note that this disease name is actually a misnomer. Lupus anticoagulant is actually a prothrombotic agent, that is, presence of Lupus anticoagulant antibodies precipitates the formation of thrombi in vivo. Their name derives from their properties in vitro, since in laboratory tests, presence of these antibodies causes an increase in aPTT
. It is speculated that the presence of the antibodies interferes with phospholipids utilized to induce in vitro coagulation.
In vivo, it is thought to interact with platelet membrane phospholipids, increasing adhesion and aggregation of platelets; thus its in vivo prothrombotic characteristics.
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 diagnosis of an inhibitor such as the lupus anticoagulant is excluded; the diagnosis is a deficient clotting factor that is replenished by the normal plasma.
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.
, 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..
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. See the Cochrane Database of Systematic Reviews http://apps.who.int/rhl/reviews/CD002859.pdf , and consult an obstetrician for specific medical advice.
Thrombosis is treated with anticoagulant
s (LMWHs
and warfarin
).
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
s and protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s associated with the cell membrane. It is important to note that this disease name is actually a misnomer. Lupus anticoagulant is actually a prothrombotic agent, that is, presence of Lupus anticoagulant antibodies precipitates the formation of thrombi in vivo. Their name derives from their properties in vitro, since in laboratory tests, presence of these antibodies causes an increase in aPTT
Partial thromboplastin time
The partial thromboplastin time or activated partial thromboplastin time is a performance indicator measuring the efficacy of both the "intrinsic" and the common coagulation pathways...
. It is speculated that the presence of the antibodies interferes with phospholipids utilized to induce in vitro coagulation.
In vivo, it is thought to interact with platelet membrane phospholipids, increasing adhesion and aggregation of platelets; thus its in vivo prothrombotic characteristics.
Terminology
Both words in the term "lupus anticoagulant" can be misleading:- Most patients with a lupus anticoagulant do not actually have lupus erythematosusLupus erythematosusLupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
, 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 erythematosusLupus erythematosusLupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
are more likely to develop a lupus anticoagulant than the general population.
- The term "anticoagulant" accurately describes its function in vitroIn vitroIn vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
, but in vivoIn vivoIn vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
, it is now known that it functions as a coagulant.
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 coagulationCoagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
in phospholipid-dependent laboratory tests such as the partial thromboplastin time
Partial thromboplastin time
The partial thromboplastin time or activated partial thromboplastin time is a performance indicator measuring the efficacy of both the "intrinsic" and the common coagulation pathways...
.
The initial workup of a prolonged PTT is a mixing test
Mixing test
Mixing studies are tests performed on blood plasma used to distinguish factor deficiencies from factor inhibitors, such as lupus anticoagulant, or specific factor inhibitors, such as antibodies directed against factor VIII...
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 diagnosis of an inhibitor such as the lupus anticoagulant is excluded; the diagnosis is a deficient clotting factor that is replenished by the normal plasma.
If the mixing test indicates an inhibitor, diagnosis of a lupus anticoagulant is then confirmed with phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
-sensitive functional clotting testing, such as the dilute Russell's viper venom time
Dilute Russell's viper venom time
Dilute Russell's viper venom time is a laboratory test often used for detection of lupus anticoagulant .Variations in the test can affect the results.-Mechanism:...
, 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 thrombosisThrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
, 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
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
should be considered candidates for indefinite treatment with anticoagulants. Patients with no history of thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
and a lupus anticoagulant should probably be observed. Current evidence suggests that the risk of recurrent thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
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..
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. See the Cochrane Database of Systematic Reviews http://apps.who.int/rhl/reviews/CD002859.pdf , and consult an obstetrician for specific medical advice.
Thrombosis is treated with anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
s (LMWHs
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
and warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
).