Lupus anticoagulant

Last updated
Lupus anticoagulant
Other namesLupus antibody, LA, LAC, lupus inhibitors

Lupus anticoagulant is an immunoglobulin [1] that binds to phospholipids and proteins associated with the cell membrane. Its name is a partial misnomer, as it is actually a prothrombotic antibody in vivo. The name derives from their properties in vitro, as these antibodies increase coagulation times in laboratory tests such as the activated partial thromboplastin time (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. [2]

Contents

The condition was first described by hematologist C. Lockard Conley in 1952. [3] [4]

Terminology

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

Indications for testing

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. [8]

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. [9]

Testing for lupus anticoagulant can also be indicated by a prolonged aPTT test that is unexplained. [8]

Workup

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. [10]

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. [11]

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. [12] 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:

Guidelines for lupus anticoagulant testing have been issued by the ISTH, [16] CLSI, [17] and the British Committee for Standards in Haematology. [18] The result may be reported as a ratio used to identify the cutoff. A ratio of 1.2 is commonly used, such that a value <1.2 indicates the absence of a lupus anticoagulant, while a value >1.2 indicates the presence of a lupus anticoagulant. [19] Direct oral anticoagulants and vitamin K antagonists used to treat thrombosis can interfere with lupus anticoagulant assays and generate either false-positive or false-negative findings. [20]

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. [21]

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. [22] For refractory cases, hydroxychloroquine may be considered. [23]

Thrombosis is treated with anticoagulants (LMWHs and warfarin). [24]

Related Research Articles

<span class="mw-page-title-main">Coagulation</span> Process of formation of blood clots

Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin.

<span class="mw-page-title-main">Antiphospholipid syndrome</span> Immune disorder leading to increased risk of blood clots

Antiphospholipid syndrome, or antiphospholipid antibody syndrome, is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS can lead to blood clots (thrombosis) in both arteries and veins, pregnancy-related complications, and other symptoms like low platelets, kidney disease, heart disease, and rash. Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease.

<span class="mw-page-title-main">Haemophilia C</span> Medical condition

Haemophilia C (also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome) is a mild form of haemophilia affecting both sexes, due to factor XI deficiency. It predominantly occurs in Ashkenazi Jews. It is the fourth most common coagulation disorder after von Willebrand's disease and haemophilia A and B. In the United States, it is thought to affect 1 in 100,000 of the adult population, making it 10% as common as haemophilia A.

Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention of blood clots and, in the treatment of venous thromboembolism, and the treatment of myocardial infarction.

<span class="mw-page-title-main">Prothrombin time</span> Blood test that evaluates clotting

The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the extrinsic pathway and common pathway of coagulation. This blood test is also called protime INR and PT/INR. They are used to determine the clotting tendency of blood, in such things as the measure of warfarin dosage, liver damage, and vitamin K status. PT measures the following coagulation factors: I (fibrinogen), II (prothrombin), V (proaccelerin), VII (proconvertin), and X.

<span class="mw-page-title-main">Partial thromboplastin time</span> Test for coagulation of blood

The partial thromboplastin time (PTT), also known as the activated partial thromboplastin time, is a blood test that characterizes coagulation of the blood. A historical name for this measure is the kaolin-cephalin clotting time (KCCT), reflecting kaolin and cephalin as materials historically used in the test. Apart from detecting abnormalities in blood clotting, partial thromboplastin time is also used to monitor the treatment effect of heparin, a widely prescribed drug that reduces blood's tendency to clot.

Mixing studies are tests performed on blood plasma of patients or test subjects to distinguish factor deficiencies from factor inhibitors, such as lupus anticoagulant, or specific factor inhibitors, such as antibodies directed against factor VIII. Mixing studies are screening tests widely performed in coagulation laboratories. The basic purpose of these tests is to determine the cause of prolongation of Prothrombin Time (PT), Partial Thromboplastin Time, or sometimes of thrombin time (TT). Mixing studies take advantage of the fact that factor levels that are 50 percent of normal should give a normal Prothrombin time (PT) or Partial thromboplastin time (PTT) result.

<span class="mw-page-title-main">Thrombophilia</span> Abnormality of blood coagulation increasing the risk of blood clotting (thrombosis)

Thrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis. Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes. A significant proportion of the population has a detectable thrombophilic abnormality, but most of these develop thrombosis only in the presence of an additional risk factor.

<span class="mw-page-title-main">Dilute Russell's viper venom time</span> Laboratory test

Dilute Russell's viper venom time (dRVVT) is a laboratory test often used for detection of lupus anticoagulant (LA). It is an assessment of the time for blood to clot in the presence of a diluted amount of venom from Russell's viper, a highly venomous snake native to the Indian subcontinent and named after the herpetologist Patrick Russell.

<span class="mw-page-title-main">Activated protein C resistance</span> Medical condition

Activated protein C resistance (APCR) is a hypercoagulability characterized by a lack of a response to activated protein C (APC), which normally helps prevent blood from clotting excessively. This results in an increased risk of venous thrombosis, which resulting in medical conditions such as deep vein thrombosis and pulmonary embolism. The most common cause of hereditary APC resistance is factor V Leiden mutation.

Catastrophic antiphospholipid syndrome (CAPS), also known as Asherson's syndrome, is a rare autoimmune disease in which widespread, intravascular clotting causes multi-organ failure. The syndrome is caused by antiphospholipid antibodies that target a group of proteins in the body that are associated with phospholipids. These antibodies activate endothelial cells, platelets, and immune cells, ultimately causing a large inflammatory immune response and widespread clotting. CAPS was first described by Ronald Asherson in 1992. The syndrome exhibits thrombotic microangiopathy, multiple organ thromboses, and in some cases tissue necrosis and is considered an extreme or catastrophic variant of the antiphospholipid syndrome.

<span class="mw-page-title-main">Thrombin time</span>

The thrombin time (TT), also known as the thrombin clotting time (TCT), is a blood test that measures the time it takes for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added. It is used to diagnose blood coagulation disorders and to assess the effectiveness of fibrinolytic therapy. This test is repeated with pooled plasma from normal patients. The difference in time between the test and the 'normal' indicates an abnormality in the conversion of fibrinogen to fibrin, an insoluble protein.

<span class="mw-page-title-main">Apolipoprotein H</span> Protein-coding gene in humans

β2-glycoprotein 1, also known as beta-2 glycoprotein 1 and Apolipoprotein H (Apo-H), is a 38 kDa multifunctional plasma protein that in humans is encoded by the APOH gene. One of its functions is to bind cardiolipin. When bound, the structure of cardiolipin and β2-GP1 both undergo large changes in structure. Within the structure of Apo-H is a stretch of positively charged amino acids, Lys-Asn-Lys-Glu-Lys-Lys, are involved in phospholipid binding.

<span class="mw-page-title-main">Ecarin clotting time</span>

Ecarin clotting time (ECT) is a laboratory test used to monitor anticoagulation during treatment with hirudin, an anticoagulant medication which was originally isolated from leech saliva. Ecarin, the primary reagent in this assay, is derived from the venom of the saw-scaled viper, Echis carinatus.

Hypercoagulability in pregnancy is the propensity of pregnant women to develop thrombosis. Pregnancy itself is a factor of hypercoagulability, as a physiologically adaptive mechanism to prevent post partum bleeding. However, when combined with an additional underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.

<span class="mw-page-title-main">Anti-cardiolipin antibodies</span> Type of autoantibody

Anti-cardiolipin antibodies (ACA) are antibodies often directed against cardiolipin and found in several diseases, including syphilis, antiphospholipid syndrome, livedoid vasculitis, vertebrobasilar insufficiency, Behçet's syndrome, idiopathic spontaneous abortion, and systemic lupus erythematosus (SLE). They are a form of anti-mitochondrial antibody. In SLE, anti-DNA antibodies and anti-cardiolipin antibodies may be present individually or together; the two types of antibodies act independently. This is in contrast to rheumatoid arthritis with systemic sclerosis (scleroderma) because anti-cardiolipin antibodies are present in both conditions, and therefore may tie the two conditions together.

In autoimmune disease, anti-apolipoprotein H (AAHA) antibodies, also called anti-β2 glycoprotein I antibodies, comprise a subset of anti-cardiolipin antibodies and lupus anticoagulant. These antibodies are involved in sclerosis and are strongly associated with thrombotic forms of lupus. As a result, AAHA are strongly implicated in autoimmune deep vein thrombosis.

Thrombodynamics test is a method for blood coagulation monitoring and anticoagulant control. This test is based on imitation of coagulation processes occurring in vivo, is sensitive both to pro- and anticoagulant changes in the hemostatic balance. Highly sensitive to thrombosis.

Blood clotting tests are the tests used for diagnostics of the hemostasis system. Coagulometer is the medical laboratory analyzer used for testing of the hemostasis system. Modern coagulometers realize different methods of activation and observation of development of blood clots in blood or in blood plasma.

Kaolin clotting time (KCT) is a sensitive test to detect lupus anticoagulants. There is evidence that suggests it is the most sensitive test for detecting lupus anticoagulants. It can also detect factor VIII inhibitors but is sensitive to unfractionated heparin as well.

References

  1. ↑ Antonia Joussen; T.W. Gardner; B. Kirchhof (2007). "21.3.1 Antiphospholipid Antibodies: Lupus Anticoagulant and Anticardiolipin Antibodies". Retinal Vascular Disease. Springer. pp. 430–. ISBN   978-3-540-29541-9 . Retrieved 29 June 2010.
  2. ↑ Tohidi-Esfahani I, Mittal P, Isenberg D, Cohen H, Efthymiou M (January 2024). "Platelets and Thrombotic Antiphospholipid Syndrome". J Clin Med. 13 (3): 741. doi: 10.3390/jcm13030741 . PMC   10856779 . PMID   38337435.
  3. ↑ Conley, C. Lockard (1952). "A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus". Journal of Clinical Investigation. 31 (6): 621–2. doi:10.1172/JCI102648. PMC   436459 . PMID   14938435.
  4. ↑ "Lock Conley looks back and blushes". Hopkins Medicine. Spring–Summer 2006. Archived from the original on 21 June 2013. Retrieved 5 December 2013.
  5. ↑ "wustl.edu". Archived from the original on 2008-08-21. Retrieved 2009-02-17.
  6. ↑ Molhoek JE, de Groot PG, Urbanus RT (July 2018). "The Lupus Anticoagulant Paradox". Semin Thromb Hemost. 44 (5): 445–452. doi:10.1055/s-0037-1606190. PMID   28898901.
  7. ↑ Hu J, Chen L, Ruan J, Chen X (2024). "The role of the annexin A protein family at the maternal-fetal interface". Front Endocrinol (Lausanne). 15: 1314214. doi: 10.3389/fendo.2024.1314214 . PMC   10940358 . PMID   38495790.
  8. 1 2 "Lupus Anticoagulant Testing". Lab Tests Online. 6 December 2019. Last reviewed on August 22, 2018. This article was last modified on December 6, 2019.
  9. ↑ "Antiphospholipid Syndrome". APS | Action. Archived from the original on 2013-07-25. Retrieved 2013-11-06.
  10. ↑ Htet, S.; Hayes, L.; Leung, T. (2015). "Strong lupus anticoagulant (LA) as a cause for prolonged prothrombin time (PT), activated partial thromboplastin time (APTT) and abnormally low intrinsic factor (IF) levels". Pathology. 47: S90. doi:10.1097/01.PAT.0000461585.89264.ae. ISSN   0031-3025. S2CID   74865864.
  11. ↑ Moore GW (March 2014). "Recent guidelines and recommendations for laboratory detection of lupus anticoagulants". Semin Thromb Hemost. 40 (2): 163–71. doi: 10.1055/s-0033-1364185 . PMID   24500573.
  12. ↑ McMahon, Maureen; Kalunian, Kenneth (2005). "17. SLE-Associated Tests". In Lotze, Michael (ed.). Measuring Immunity: Basic biology and clinical assessment. Elsevier. pp. 210–220. doi:10.1016/B978-012455900-4/50279-8. ISBN   978-0-12-455900-4. OCLC   64401294.
  13. ↑ Efthymiou M, Bertolaccini ML, Cohen H (February 2024). "Viewpoint: Lupus anticoagulant detection and interpretation in antiphospholipid syndrome". Rheumatology (Oxford). 63 (SI): SI54–SI63. doi:10.1093/rheumatology/kead623. PMID   38320587.
  14. ↑ Denis-Magdelaine, A.; Flahault, A.; Verdy, E. (1995). "Sensitivity of Sixteen APTT Reagents for the Presence of Lupus Anticoagulants". Pathophysiology of Haemostasis and Thrombosis. 25 (3): 98–105. doi:10.1159/000217148. ISSN   1424-8832. PMID   7607585.
  15. ↑ Triplett DA, Barna LK, Unger GA (1993). "A hexagonal (II) phase phospholipid neutralization assay for lupus anticoagulant identification". Thromb Haemost. 70 (5): 787–93. doi:10.1055/s-0038-1649671. PMID   8128436. S2CID   35046350.
  16. ↑ Devreese KM, de Groot PG, de Laat B, Erkan D, Favaloro EJ, Mackie I, Martinuzzo M, Ortel TL, Pengo V, Rand JH, Tripodi A, Wahl D, Cohen H (November 2020). "Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: Update of the guidelines for lupus anticoagulant detection and interpretation". J Thromb Haemost. 18 (11): 2828–39. doi:10.1111/jth.15047. PMID   33462974.
  17. ↑ CLSI (2014). "Laboratory testing for the lupus anticoagulant: Approved Guideline" (PDF). Clinical and Laboratory Standards Institute. ISBN   1-56238-960-2. CLSI Document H60-A.
  18. ↑ Keeling D, Mackie I, Moore GW, Greer IA, Greaves M (April 2012). "Guidelines on the investigation and management of antiphospholipid syndrome". Br J Haematol. 157 (1): 47–58. doi:10.1111/j.1365-2141.2012.09037.x. PMID   22313321.
  19. ↑ Favaloro EJ (January 2020). "Coagulation mixing studies: Utility, algorithmic strategies and limitations for lupus anticoagulant testing or follow up of abnormal coagulation tests". Am J Hematol. 95 (1): 117–128. doi:10.1002/ajh.25669. PMID   31674066.
  20. ↑ Favaloro EJ, Pasalic L, Selby R (March 2024). "Testing for the lupus anticoagulant: the good, the bad, and the ugly". Res Pract Thromb Haemost. 8 (3): 102385. doi:10.1016/j.rpth.2024.102385. PMC   11017341 . PMID   38623474.
  21. ↑ 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.
  22. ↑ Hamulyák EN, Scheres LJ, Marijnen MC, Goddijn M, Middeldorp S (May 2020). "Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss". Cochrane Database Syst Rev. 2020 (5): CD012852. doi:10.1002/14651858.CD012852.pub2. PMC   7195627 . PMID   32358837.
  23. ↑ Fierro JJ, Velásquez-Berrío M, Ospina A, Henning S, de Leeuw K, Cadavid J ÁP (February 2024). "The effects of hydroxychloroquine and its promising use in refractory obstetric antiphospholipid syndrome". Rheumatol Int. 44 (2): 223–234. doi:10.1007/s00296-023-05457-5. PMC   10796698 . PMID   37741812.
  24. ↑ 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.