Genomes and Genes
lupus coagulation inhibitor
Summary: An antiphospholipid antibody found in association with systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC;), ANTIPHOSPHOLIPID SYNDROME; and in a variety of other diseases as well as in healthy individuals. In vitro, the antibody interferes with the conversion of prothrombin to thrombin and prolongs the partial thromboplastin time. In vivo, it exerts a procoagulant effect resulting in thrombosis mainly in the larger veins and arteries. It further causes obstetrical complications, including fetal death and spontaneous abortion, as well as a variety of hematologic and neurologic complications.
- de Laat B, Wu X, van Lummel M, Derksen R, de Groot P, Rand J. Correlation between antiphospholipid antibodies that recognize domain I of beta2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5. Blood. 2007;109:1490-4 pubmed..These results are consistent with a model in which aPL antibodies may promote thrombosis by interfering with the anticoagulant activity of AnxA5. ..
- Van Hylckama Vlieg A, Montes R, Rosendaal F, Hermida J. Autoantibodies against endothelial protein C receptor and the risk of a first deep vein thrombosis. J Thromb Haemost. 2007;5:1449-54 pubmed..This study demonstrates that the presence of anti-EPCR autoantibodies is a moderate risk factor for DVT in the general population. ..
- Galli M, Borrelli G, Jacobsen E, Marfisi R, Finazzi G, Marchioli R, et al. Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood. 2007;110:1178-83 pubmed..They also suggest that the measurement of aPT and aAnAV antibodies is useful in some selected situations and that there is little role for IgM antibody detection. ..
- Galli M, Reber G, de Moerloose P, de Groot P. Invitation to a debate on the serological criteria that define the antiphospholipid syndrome. J Thromb Haemost. 2008;6:399-401 pubmed
- Ruffatti A, Tonello M, Cavazzana A, Bagatella P, Pengo V. Laboratory classification categories and pregnancy outcome in patients with primary antiphospholipid syndrome prescribed antithrombotic therapy. Thromb Res. 2009;123:482-7 pubmed publisher..However, it has been seen that a greater predictability is achieved when category I patients are grouped into triple and double positivity states. ..
- Ruffatti A, Olivieri S, Tonello M, Bortolati M, Bison E, Salvan E, et al. Influence of different IgG anticardiolipin antibody cut-off values on antiphospholipid syndrome classification. J Thromb Haemost. 2008;6:1693-6 pubmed publisher..7%). The 99th percentile cut-off level seems more sensitive than the >40 GPL value for APS classification, as it includes subjects with aCL positivity alone as well as patients with pregnancy morbidity. ..
- Pengo V, Ruffatti A, Legnani C, Gresele P, Barcellona D, Erba N, et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost. 2010;8:237-42 pubmed publisher..Patients with APS and triple positivity for aPL are at high risk of developing future thromboembolic events. Recurrence remains frequent despite the use of oral anticoagulants, which significantly reduces the risk of thromboembolism. ..
- Chauleur C, Galanaud J, Alonso S, Cochery Nouvellon E, Balducchi J, Mares P, et al. Observational study of pregnant women with a previous spontaneous abortion before the 10th gestation week with and without antiphospholipid antibodies. J Thromb Haemost. 2010;8:699-706 pubmed publisher..Although this diagnostic classification of APS appeared to be the most sensitive, the APS-associated serological criteria are still debated...
- Petri M. Update on anti-phospholipid antibodies in SLE: the Hopkins' Lupus Cohort. Lupus. 2010;19:419-23 pubmed publisher..Anti-phospholipid antibodies are not associated with atherosclerosis. ..
- Pierrot Deseilligny Despujol C, Michel M, Khellaf M, Gouault M, Intrator L, Bierling P, et al. Antiphospholipid antibodies in adults with immune thrombocytopenic purpura. Br J Haematol. 2008;142:638-43 pubmed publisher..9; 95% CI: 2.3-43.4) or high IgG-aCL level (HR: 7.5; 95% CI; 1.8-31.5). Although the thrombosis rate was low, the significant associations between thrombosis and LA or high aCL level suggest that aPL should be tested at ITP diagnosis. ..
- Esmon N, Smirnov M, Esmon C. Thrombogenic mechanisms of antiphospholipid antibodies. Thromb Haemost. 1997;78:79-82 pubmed..It is unlikely any single mechanism is responsible for the thrombogenic activity of all APAs associated with thrombosis and this will be a fertile field of investigation for a significant time to come. ..
- Day H, Thiagarajan P, Ahn C, Reveille J, Tinker K, Arnett F. Autoantibodies to beta2-glycoprotein I in systemic lupus erythematosus and primary antiphospholipid antibody syndrome: clinical correlations in comparison with other antiphospholipid antibody tests. J Rheumatol. 1998;25:667-74 pubmed..Multivariate analyses suggest that anti-beta2-GPI antibodies may play a more central role in certain clinical manifestations of APS than antibodies detected by the aPL ELISA or LAC. ..
- Galli M, Finazzi G, Barbui T. Antiphospholipid antibodies: predictive value of laboratory tests. Thromb Haemost. 1997;78:75-8 pubmed
- Ahn E, Lander G, Bidot C, Jy W, Ahn Y. Long-term remission from life-threatening hypercoagulable state associated with lupus anticoagulant (LA) following rituximab therapy. Am J Hematol. 2005;78:127-9 pubmed..Rituximab induced a lasting remission in a woman suffering from life-threatening hypercoagulable state associated with LA. Her clinical remission was associated with disappearance of LA. ..
- de Moerloose P, Reber G. Antiphospholipid antibodies: do we still need to perform anticardiolipin ELISA assays?. J Thromb Haemost. 2004;2:1071-3 pubmed
- Pengo V, Biasiolo A, Brocco T, Rampazzo P. Effect of anti-beta2glycoprotein I Lupus Anticoagulants on fibrin polymerization and fibrinolysis. Autoimmunity. 2000;32:39-44 pubmed..These data provide evidence that anti-beta2GPI LA may act as either anticoagulants or procoagulants in different in vitro coagulation tests. ..
- Csepany T, Bereczki D, Kollar J, Sikula J, Kiss E, Csiba L. MRI findings in central nervous system systemic lupus erythematosus are associated with immunoserological parameters and hypertension. J Neurol. 2003;250:1348-54 pubmed
- Simmelink M, Derksen R, Arnout J, de Groot P. A simple method to discriminate between beta2-glycoprotein I- and prothrombin-dependent lupus anticoagulants. J Thromb Haemost. 2003;1:740-7 pubmed
- Nojima J, Kuratsune H, Suehisa E, Futsukaichi Y, Yamanishi H, Machii T, et al. Association between the prevalence of antibodies to beta(2)-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications. Clin Chem. 2001;47:1008-15 pubmed..4-14.8). Patients with SLE frequently have some aPL Abs to beta(2)-GPI, prothrombin, protein C, protein S, and annexin V. Thrombotic complications in SLE may depend on the antigenic specificities of these Abs, alone or in combination. ..
- Somers E, Magder L, Petri M. Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol. 2002;29:2531-6 pubmed..Both the presence of a LAC and of polyclonal aCL are associated with the risk of VT, but LAC is a better predictor of risk than is aCL. ..
- Arnout J. Antiphospholipid syndrome: diagnostic aspects of lupus anticoagulants. Thromb Haemost. 2001;86:83-91 pubmed..These LA positive monoclonal antibodies may be helpful in further improving the laboratory diagnosis of LA. ..
- Bertolaccini M, Gomez S, Pareja J, Theodoridou A, Sanna G, Hughes G, et al. Antiphospholipid antibody tests: spreading the net. Ann Rheum Dis. 2005;64:1639-43 pubmed..1 for aPS-PT). Testing for aPT in patients with SLE with thrombosis, but persistently negative for aCL and LA, may be helpful in some selected cases. Anti-beta(2)GPI are not present in patients who are negative for aCL. ..
- Arnout J, Wittevrongel C, Vanrusselt M, Hoylaerts M, Vermylen J. Beta-2-glycoprotein I dependent lupus anticoagulants form stable bivalent antibody beta-2-glycoprotein I complexes on phospholipid surfaces. Thromb Haemost. 1998;79:79-86 pubmed..In summary, these experiments indicate that the beta2GPI-dependent LA effect depends on the formation of bivalent beta2GPI-antibody complexes on phospholipid surfaces. ..
- Jones D, Gallimore M, Harris S, Winter M. Antibodies to factor XII associated with lupus anticoagulant. Thromb Haemost. 1999;81:387-90 pubmed..These results suggest that FXII antibodies are present in a significant proportion of LA+ patients and may lead to an erroneous diagnosis of FXII deficiency. ..
- Jones D, Mackie I, Gallimore M, Winter M. Antibodies to factor XII and recurrent fetal loss in patients with the anti-phospholipid syndrome. Br J Haematol. 2001;113:550-2 pubmed..4, p = 0.025). ..
- Diz Kucukkaya R, Hacihanefioglu A, Yenerel M, Turgut M, Keskin H, Nalcaci M, et al. Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study. Blood. 2001;98:1760-4 pubmed..In patients with ITP, the persistent presence of APAs is an important risk factor for the development of APS. ..
- Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003;101:1827-32 pubmed..However, to take full advantage of the conclusions provided by the available evidence, there is an urgent need to harmonize investigational methods. ..
- de Laat B, Derksen R, Urbanus R, de Groot P. IgG antibodies that recognize epitope Gly40-Arg43 in domain I of beta 2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis. Blood. 2005;105:1540-5 pubmed..In conclusion, antibodies directed at domain I (epitope comprising Gly40 and Arg43) have lupus anticoagulant activity and strongly associate with thrombosis. ..
- Nash M, Camilleri R, Kunka S, Mackie I, Machin S, Cohen H. The anticardiolipin assay is required for sensitive screening for antiphospholipid antibodies. J Thromb Haemost. 2004;2:1077-81 pubmed..5 GPLU (normal < 5 GPLU). These data indicate that omission of aCL testing from the clinical investigation of APS could lead to a failure to diagnose the syndrome in a proportion of patients. ..
- Willems G, Janssen M, Comfurius P, Galli M, Zwaal R, Bevers E. Kinetics of prothrombin-mediated binding of lupus anticoagulant antibodies to phosphatidylserine-containing phospholipid membranes: an ellipsometric study. Biochemistry. 2002;41:14357-63 pubmed..The kinetics of adsorption and desorption indicate that divalent binding of LA IgG to prothrombin at the lipid membrane occurs. ..
- Sanna G, Bertolaccini M, Cuadrado M, Laing H, Khamashta M, Mathieu A, et al. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol. 2003;30:985-92 pubmed..Neuropsychometric testing was applied by a neuropsychologist. Univariate and multivariate statistical analyses were applied to evaluate the association bewteen NP manifestations, magnetic resonance imaging (MRI) abnormalities, and aPL...
- Jayakody Arachchillage D, Greaves M. The chequered history of the antiphospholipid syndrome. Br J Haematol. 2014;165:609-17 pubmed publisher..However many gaps in our knowledge remain. ..
- Devreese K. Antiphospholipid antibodies: evaluation of the thrombotic risk. Thromb Res. 2012;130 Suppl 1:S37-40 pubmed publisher..Multiple positivity of tests seems clinically more relevant. The strengths and weaknesses of the current laboratory criteria for APS are discussed in view of their role in risk stratification of patients with thrombotic events. ..
- Dembitzer F, Ledford Kraemer M, Meijer P, Peerschke E. Lupus anticoagulant testing: performance and practices by north american clinical laboratories. Am J Clin Pathol. 2010;134:764-73 pubmed publisher..These data provide new insights into LAC testing in North America and identify opportunities for standardization. ..
- Belvis R, Santamaria A, Marti Fabregas J, Cocho D, Borrell M, Fontcuberta J, et al. Diagnostic yield of prothrombotic state studies in cryptogenic stroke. Acta Neurol Scand. 2006;114:250-3 pubmed..One of every six patients with initial CS present a PS. Age or sex and conventional cardiovascular risk factors were not related to PS study findings, supporting the relevance of such studies in all patients with an initial CS. ..
- Pengo V, Biasiolo A, Gresele P, Marongiu F, Erba N, Veschi F, et al. Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples. J Thromb Haemost. 2007;5:925-30 pubmed..A false-positive LAC diagnosis is not uncommon across specialized centers. Patients' characteristics and a complete antiphospholipid antibody profile may help to identify these individuals. ..
- Bellver J, Soares S, Alvarez C, Muñoz E, Ramirez A, Rubio C, et al. The role of thrombophilia and thyroid autoimmunity in unexplained infertility, implantation failure and recurrent spontaneous abortion. Hum Reprod. 2008;23:278-84 pubmed..TSH and free thyroxine levels all remained within a normal range. When embryo aneuploidy is ruled out, thrombophilia could constitute an etiologic factor in IF. Furthermore, thyroid autoimmunity is strongly related to UI and IF. ..
- Koch M, Beckmann R. Transitory lupus anticoagulant antibodies leading to a quickly resolvable left ventricular thrombus in a young female patient on peritoneal dialysis. Clin Nephrol. 2009;71:575-8 pubmed..We assume that the patient may have had infection- or cortisone-triggered transitory LA antibodies causing the serious heart thrombus with hypokinesia in the apex cordis. ..
- Naito S, Ieko M, Yoshida M, Tarumi T, Nakabayashi T, Nishio H, et al. [Study on usefulness of different APTT test kit in variable coagulopathy]. Rinsho Byori. 2008;56:195-202 pubmed..Further, kits that employ synthetic phospholipids are useful for detecting abnormal coagulopathy in patients with intrinsic coagulation factor deficiencies and patients taken heparin, as well as for detection of LA. ..
- McDonald E, Butler A. Immune thrombocytopaenia in adults: a single-centre retrospective review of patients presenting over 7 years. N Z Med J. 2010;123:18-25 pubmed..Asymptomatic patients have a low risk of serious or life-threatening bleeding and do not require admission to hospital. Most patients will eventually achieve a platelet count >30x10(9)/L off treatment. ..
- Cuffaro S, Del Ross T, Tonello M, Bontadi A, Olivieri S, Salvan E, et al. [Confirmation of antiphospholipid antibody positivity: a year's results in a cohort of 113 patients]. Reumatismo. 2010;62:51-9 pubmed..Our data emphasize aPL positivity confirmation selectivity, and medium-high antibody levels and category I antibodies (multiple positivity) had the best confirmation rates. ..
- Adelowo O, Adetoro O. Recurrent pregnancy loss and antiphospholipid syndrome: an overlooked association. Afr J Med Med Sci. 2010;39:227-31 pubmed..A high index of suspicion is needed for this otherwise treatable condition. Management is ideally best done by an obstetrician and a rheumatologist. ..
- Schleinitz N, Camoin L, Bernit E, Reviron D, Veit V, Harle J. Monoclonal antibody immunospecific platelet assay in patients with lupus anticoagulant and prolonged bleeding time: Comment on the article by Urbanus et al. Arthritis Rheum. 2005;52:1949; author reply 1949-50 pubmed
- Dacosta V, Chin L, Wynter S, Harriott J, Christie L, Frederick Johnston S, et al. Anticardiolipin antibodies and lupus anticoagulants among women undergoing in vitro fertilization in Jamaica. West Indian Med J. 2012;61:789-94 pubmed..Screening women undergoing IVF for these antibodies is not justified. ..
- Cojocaru I, Cojocaru M, Tanasescu R, Burcin C, Mitu A, Iliescu I, et al. Detecting anti-prothrombin antibodies in young women with acute ischemic stroke. Rom J Intern Med. 2008;46:337-41 pubmed..03287 [95% CI 0.001794-0.6022], p < 0.001). aCL, LA and anti-beta2-GPI were not found both in nonischemic neurological disorders patients and in healthy controls. ..
- Bu C, Li Z, Zhang C, Gao L, Cai G. IgG antibodies to plasminogen and their relationship to IgG anti-beta(2)-glycoprotein 1 antibodies and thrombosis. Clin Rheumatol. 2008;27:171-8 pubmed..In conclusion, the prevalence of IgG anti-PLG was high in patients with PAPS and SLE and might relate with thrombosis. Cross-reactivity of IgG anti-beta(2)GP1 antibodies with PLG may occur in the sera of patients. ..
- Kitagawa Y. [Antiphospholipid syndrome and stroke]. Rinsho Shinkeigaku. 2005;45:852-5 pubmed..In SLE patients with stroke, multi-antiphospholipid-protein antibodies was inclined to be present. LA is closely related to ant-PS-PT and aPI and aPS are associated with anti-nuclear antibody and precipitation of atherosclerosis. ..
- Avcin T, Benseler S, Tyrrell P, Cucnik S, Silverman E. A followup study of antiphospholipid antibodies and associated neuropsychiatric manifestations in 137 children with systemic lupus erythematosus. Arthritis Rheum. 2008;59:206-13 pubmed publisher..Our data suggest an association between LAC and cerebrovascular disease at the time of SLE diagnosis and chorea over the disease course, but not between aPL and other neuropsychiatric manifestations. ..