Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Rheumatology Reports
Published in: Current Rheumatology Reports 8/2017

01-08-2017 | Antiphospholipid Syndrome (S Zuily, Section Editor)

How to Identify High-Risk APS Patients: Clinical Utility and Predictive Values of Validated Scores

Authors: Kenji Oku, Olga Amengual, Shinsuke Yasuda, Tatsuya Atsumi

Published in: Current Rheumatology Reports | Issue 8/2017

Login to get access

Abstract

Purpose of Review

Antiphospholipid syndrome (APS) is a clinical disorder characterised by thrombosis and/or pregnancy morbidity in the persistence of antiphospholipid (aPL) antibodies that are pathogenic and have pro-coagulant activities. Thrombosis in APS tends to recur and require prophylaxis; however, the stereotypical treatment for APS patients is inadequate and stratification of the thrombotic risks is important as aPL are prevalently observed in various diseases or elderly population.

Recent Findings

It is previously known that the multiple positive aPL or high titre aPL correlate to thrombotic events. To progress the stratification of thrombotic risks in APS patients and to quantitatively analyse those risks, antiphospholipid score (aPL-S) and the Global Anti-phospholipid Syndrome Score (GAPSS) were defined. These scores were raised from the large patient cohort data and either aPL profile classified in detail (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS) was put into a scoring system. Both the aPL-S and GAPSS have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis. However, there are several areas requiring improvement, or at least that clinicians should be aware of, before these instruments are applied in clinical practice. One such issue is standardisation of the aPL tests, including general testing of phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT).

Summary

Additionally, clinicians may need to be aware of the patient’s medical history, particularly with respect to the incidence of SLE, which influences the cutoff value for identifying high-risk patients.
Literature
1.
Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306.CrossRefPubMed
2.
Bohgaki M, Atsumi T, Yamashita Y, Yasuda S, Sakai Y, Furusaki A, et al. The p38 mitogen-activated protein kinase (MAPK) pathway mediates induction of the tissue factor gene in monocytes stimulated with human monoclonal anti-beta2 glycoprotein I antibodies. Int Immunol. 2004;16(11):1633–41.CrossRefPubMed
3.
Oku K, Amengual O, Zigon P, Horita T, Yasuda S, Atsumi T. Essential role of the p38 mitogen-activated protein kinase pathway in tissue factor gene expression mediated by the phosphatidylserine-dependent antiprothrombin antibody. Rheumatology (Oxford). 2013;52(10):1775–84.CrossRef
4.
Long AA, Ginsberg JS, Brill-Edwards P, Johnston M, Turner C, Denburg JA, et al. The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study. Thromb Haemost. 1991;66(5):520–4.PubMed
5.
Mok CC, Tang SS, To CH, Petri M. Incidence and risk factors of thromboembolism in systemic lupus erythematosus: a comparison of three ethnic groups. Arthritis Rheum. 2005;52(9):2774–82.CrossRefPubMed
6.
Vianna JL, Khamashta MA, Ordi-Ros J, Font J, Cervera R, Lopez-Soto A, et al. Comparison of the primary and secondary antiphospholipid syndrome: a European Multicenter Study of 114 patients. Am J Med. 1994;96(1):3–9.CrossRefPubMed
7.
Derksen RH, de Groot PG, Kater L, Nieuwenhuis HK. Patients with antiphospholipid antibodies and venous thrombosis should receive long term anticoagulant treatment. Ann Rheum Dis. 1993;52(9):689–92.CrossRefPubMedPubMedCentral
8.
Ambrozic A, Avicin T, Ichikawa K, Kveder T, Matsuura E, Hojnik M, et al. Anti-beta(2)-glycoprotein I antibodies in children with atopic dermatitis. Int Immunol. 2002;14(7):823–30.CrossRefPubMed
9.
Giron-Gonzalez JA, Garcia del Rio E, Rodriguez C, Rodriguez-Martorell J, Serrano A. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol. 2004;31(8):1560–7.PubMed
10.
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(5):925–30.CrossRefPubMed
11.
Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. 2006;295(9):1050–7.CrossRefPubMed
12.
Tektonidou MG, Laskari K, Panagiotakos DB, Moutsopoulos HM. Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies. Arthritis Rheum. 2009;61(1):29–36.CrossRefPubMed
13.
Ruiz-Irastorza G, Egurbide MV, Ugalde J, Aguirre C. High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. Arch Intern Med. 2004;164(1):77–82.CrossRefPubMed
14.
Zuily S, Rat AC, Regnault V, Kaminsky P, Mismetti P, Ninet J, et al. Impairment of quality of life in patients with antiphospholipid syndrome. Lupus. 2015;24(11):1161–8.CrossRefPubMed
15.
Fleck RA, Rapaport SI, Rao LV. Anti-prothrombin antibodies and the lupus anticoagulant. Blood. 1988;72(2):512–9.PubMed
16.
Bevers EM, Galli M, Barbui T, Comfurius P, Zwaal RF. Lupus anticoagulant IgG’s (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost. 1991;66(6):629–32.PubMed
17.
Oosting JD, Derksen RH, Bobbink IW, Hackeng TM, Bouma BN, de Groot PG. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism? Blood. 1993;81(10):2618–25.PubMed
18.
Atsumi T, Ieko M, Bertolaccini ML, Ichikawa K, Tsutsumi A, Matsuura E, et al. Association of autoantibodies against the phosphatidylserine-prothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant. Arthritis Rheum. 2000;43(9):1982–93.CrossRefPubMed
19.
Matsuda J, Saitoh N, Gotoh M, Kawasugi K, Gohchi K, Tsukamoto M. Phosphatidyl serine-dependent antiprothrombin antibody is exclusive to patients with lupus anticoagulant. Br J Rheumatol. 1996;35(6):589–91.CrossRefPubMed
20.
Galli M, Beretta G, Daldossi M, Bevers EM, Barbui T. Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies. Thromb Haemost. 1997;77(3):486–91.PubMed
21.
Oku K, Atsumi T, Amengual O, Koike T. Antiprothrombin antibody testing: detection and clinical utility. Semin Thromb Hemost. 2008;34(4):335–9.CrossRefPubMed
22.
de Laat B, Pengo V, Pabinger I, Musial J, Voskuyl AE, Bultink IE, et al. The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study. J Thromb Haemost. 2009;7(11):1767–73.CrossRefPubMed
23.
Finazzi G, Brancaccio V, Moia M, Ciaverella N, Mazzucconi MG, Schinco PC, et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry. Am J Med. 1996;100(5):530–6.CrossRefPubMed
24.
Ruffatti A, Del Ross T, Ciprian M, Nuzzo M, Rampudda M, Bertero MT, et al. Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study. Ann Rheum Dis. 2009;68(3):397–9.CrossRefPubMed
25.
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(5):1827–32.CrossRefPubMed
26.
de Groot PG, Lutters B, Derksen RH, Lisman T, Meijers JC, Rosendaal FR. Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. J Thromb Haemost. 2005;3(9):1993–7.CrossRefPubMed
27.
De Laat B, Derksen RH, Reber G, Musial J, Swadzba J, Bozic B, et al. An international multicentre-laboratory evaluation of a new assay to detect specifically lupus anticoagulants dependent on the presence of anti-beta2-glycoprotein autoantibodies. J Thromb Haemost. 2011;9(1):149–53.CrossRefPubMed
28.
De Craemer AS, Musial J, Devreese KM. Role of anti-domain 1-beta2 glycoprotein I antibodies in the diagnosis and risk stratification of antiphospholipid syndrome. J Thromb Haemost. 2016;14(9):1779–87.CrossRefPubMed
29.
Sciascia S, Bertolaccini ML. Antibodies to phosphatidylserine/prothrombin complex and the antiphospholipid syndrome. Lupus. 2014;23(12):1309–12.CrossRefPubMed
30.
Heikal NM, Jaskowski TD, Malmberg E, Lakos G, Branch DW, Tebo AE. Laboratory evaluation of anti-phospholipid syndrome: a preliminary prospective study of phosphatidylserine/prothrombin antibodies in an at-risk patient cohort. Clin Exp Immunol. 2015;180(2):218–26.CrossRefPubMedPubMedCentral
31.
Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Noventa F, Iliceto S. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost. 2005;93(6):1147–52.PubMed
32.
Pengo V, Ruffatti A, Legnani C, Testa S, Fierro T, Marongiu F, et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood. 2011;118(17):4714–8.CrossRefPubMed
33.
Mustonen P, Lehtonen KV, Javela K, Puurunen M. Persistent antiphospholipid antibody (aPL) in asymptomatic carriers as a risk factor for future thrombotic events: a nationwide prospective study. Lupus. 2014;23(14):1468–76.CrossRefPubMed
34.
Becarevic M, Stojanovic L, Ignjatovic S, Dopsaj V. The IgM isotype of anti-annexin A5 antibodies and multiple positivity of conventional antiphospholipid antibodies: increasing the number of clinical manifestations of primary antiphospholipid syndrome. Clin Rheumatol. 2016;35(5):1361–5.CrossRefPubMed
35.
Sciascia S, Murru V, Sanna G, Roccatello D, Khamashta MA, Bertolaccini ML. Clinical accuracy for diagnosis of antiphospholipid syndrome in systemic lupus erythematosus: evaluation of 23 possible combinations of antiphospholipid antibody specificities. J Thromb Haemost. 2012;10(12):2512–8.CrossRefPubMed
36.
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(3):482–7.CrossRefPubMed
37.
Ruffatti A, Salvan E, Del Ross T, Gerosa M, Andreoli L, Maina A, et al. Treatment strategies and pregnancy outcomes in antiphospholipid syndrome patients with thrombosis and triple antiphospholipid positivity. A European multicentre retrospective study. Thromb Haemost. 2014;112(4):727–35.CrossRefPubMed
38.
Saraiva Sda S, Custodio IF, Mazetto Bde M, Collela MP, de Paula EV, Appenzeller S, et al. Recurrent thrombosis in antiphospholipid syndrome may be associated with cardiovascular risk factors and inflammatory response. Thromb Res. 2015;136(6):1174–8.CrossRefPubMed
39.
Gustafsson JT, Gunnarsson I, Kallberg H, Pettersson S, Zickert A, Vikerfors A, et al. Cigarette smoking, antiphospholipid antibodies and vascular events in systemic lupus erythematosus. Ann Rheum Dis. 2015;74(8):1537–43.CrossRefPubMed
40.
Otomo K, Atsumi T, Amengual O, Fujieda Y, Kato M, Oku K, et al. Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum. 2012;64(2):504–12.CrossRefPubMed
41.
Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost. 1995;74(4):1185–90.PubMed
42.
Amengual O, Atsumi T, Khamashta MA, Koike T, Hughes GR. Specificity of ELISA for antibody to beta 2-glycoprotein I in patients with antiphospholipid syndrome. Br J Rheumatol. 1996;35(12):1239–43.CrossRefPubMed
43.
Harris EN, Gharavi AE, Patel SP, Hughes GR. Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986. Clin Exp Immunol. 1987;68(1):215–22.PubMedPubMedCentral
44.
Sciascia S, Bertolaccini ML, Roccatello D, Khamashta MA. Independent validation of the antiphospholipid score for the diagnosis of antiphospholipid syndrome. Ann Rheum Dis. 2013;72(1):142–3.CrossRefPubMed
45.
Sciascia S, Cuadrado MJ, Sanna G, Murru V, Roccatello D, Khamashta MA, et al. Thrombotic risk assessment in systemic lupus erythematosus: validation of the global antiphospholipid syndrome score in a prospective cohort. Arthritis Care Res (Hoboken). 2014;66(12):1915–20.CrossRef
46.
Chen J, Sun S, Yan Q, Bao C, Fu Q. Elevated partial antiphospholipid score is a strong risk factor for thrombosis in patients with systemic lupus erythematosus: a validation study. Clin Rheumatol. 2016;35(2):333–40.CrossRefPubMed
47.
Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. GAPSS: the Global Anti-phospholipid Syndrome Score. Rheumatology (Oxford). 2013;52(8):1397–403.CrossRef
48.
Zuily S, de Laat B, Mohamed S, Kelchtermans H, Shums Z, Albesa R, et al. Validity of the global anti-phospholipid syndrome score to predict thrombosis: a prospective multicentre cohort study. Rheumatology (Oxford). 2015;54(11):2071–5.CrossRef
49.
Oku K, Amengual O, Bohgaki T, Horita T, Yasuda S, Atsumi T. An independent validation of the Global Anti-phospholipid Syndrome Score in a Japanese cohort of patients with autoimmune diseases. Lupus. 2015;24(7):774–5.CrossRefPubMed
50.
Amengual O, Forastiero R, Sugiura-Ogasawara M, Otomo K, Oku K, Favas C, et al. Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study. Lupus. 2016;
51.
Oku K, Amengual O, Atsumi T. Antiphospholipid scoring: significance in diagnosis and prognosis. Lupus. 2014;23(12):1269–72.CrossRefPubMed
52.
Devreese KM. Standardization of antiphospholipid antibody assays. Where do we stand? Lupus. 2012;21(7):718–21.CrossRefPubMed
53.
Willis R, Lakos G, Harris EN. Standardization of antiphospholipid antibody testing—historical perspectives and ongoing initiatives. Semin Thromb Hemost. 2014;40(2):172–7.CrossRefPubMed
54.
Devreese KM. Antiphospholipid antibody testing and standardization. Int J Lab Hematol. 2014;36(3):352–63.CrossRefPubMed
55.
Chantarangkul V, Biguzzi E, Asti D, Palmucci C, Tripodi A. Laboratory diagnostic outcome applying detection criteria recommended by the Scientific and Standardization Committee of the ISTH on Lupus Anticoagulant. Thromb Haemost. 2013;110(1):46–52.CrossRefPubMed
56.
Pengo V, Denas G, Banzato A, Bison E, Bracco A, Visentin MS, et al. Interpretation of laboratory data and need for reference laboratories. Lupus. 2012;21(7):732–3.CrossRefPubMed
57.
Urbanus RT, de Groot PG. Antiphospholipid antibodies—we are not quite there yet. Blood Rev. 2011;25(2):97–106.CrossRefPubMed
58.
Reber G, Tincani A, Sanmarco M, de Moerloose P, Boffa MC. European forum on antiphospholipid antibodies standardization G. variability of anti-beta2 glycoprotein I antibodies measurement by commercial assays. Thromb Haemost. 2005;94(3):665–72.PubMed
59.
DE Moerloose P, Reber G, Musial J, Arnout J. Analytical and clinical performance of a new, automated assay panel for the diagnosis of antiphospholipid syndrome. J Thromb Haemost. 2010;8(7):1540–6.CrossRef
60.
Oku K, Amengual O, Kato M, Bohgaki T, Horita T, Yasuda S, et al. Significance of fully automated tests for the diagnosis of antiphospholipid syndrome. Thromb Res. 2016;146:1–6.CrossRefPubMed
61.
Oku K, Hisada R, Oomura K, Nakagawa I, Watanabe T, Bohgaki T, et al. Markers of thrombotic events in autoimmune diseases:comparison of antiphospholipid score (aPL-S) and Global Anti-phospholipid Syndrome Score (GAPSS). Arthritis Rheumatol. 2014;66(10(Supplement)):S1251.
Metadata
Title
How to Identify High-Risk APS Patients: Clinical Utility and Predictive Values of Validated Scores
Authors
Kenji Oku
Olga Amengual
Shinsuke Yasuda
Tatsuya Atsumi
Publication date
01-08-2017
Publisher
Springer US
Published in
Current Rheumatology Reports / Issue 8/2017
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-017-0674-4

Other articles of this Issue 8/2017

Current Rheumatology Reports 8/2017 Go to the issue

Osteoarthritis (M Goldring, Section Editor)

Recent Advances in Tissue Engineering Strategies for the Treatment of Joint Damage

Biosimilars (E Mysler, Section Editor)

Update on Biosimilars in Asia

Letters to the Editor

Direct Oral Anticoagulants Use in Antiphospholipid Syndrome: Are These Drugs an Effective and Safe Alternative to Warfarin? A Systematic Review of the Literature: Comment

Orphan Diseases (B Manger, Section Editor)

Schnitzler Syndrome: a Review

Systemic Lupus Erythematosus (G Tsokos, Section Editor)

New Insights on Platelets and Platelet-Derived Microparticles in Systemic Lupus Erythematosus

Osteoarthritis (M Goldring, Section Editor)

Contribution of Circulatory Disturbances in Subchondral Bone to the Pathophysiology of Osteoarthritis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits