Antiphosphatidylserine, IgA, IgG, IgM

CPT: 86148(x3)
Updated on 07/31/2022
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3 - 5 days

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3 - 5 days



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Procedures for Hemostasis and Thrombosis: A Clinical Test Compendium


Specimen Requirements


Specimen

Serum


Volume

1 mL


Minimum Volume

0.5 mL


Container

Red-top tube or gel-barrier tube


Collection

Separate serum from cells by centrifugation after clot formation.


Storage Instructions

Room temperature

Refrigerate

Room temperature


Stability Requirements

Temperature

Period

Room temperature

14 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3

Temperature

Period

Room temperature

14 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3


Causes for Rejection

Gross hemolysis; bacterial contamination; lipemia


Test Details


Use

As an aid in the diagnosis of certain autoimmune thrombotic disorders, such as antiphospholipid syndrome (aPS). Antibodies to PS/PT correlate with the presence of lupus anticoagulants (LA) and this test may be useful in cases with difficult LA test interpretation. This assay may also assist in the determination of risk for thrombosis as well as obstetric complications in patients with antiphospholipid antibodies.

An adjunct to β2-glycoprotein and anticardiolipins in diagnosing aPS (antiphospholipid syndrome) for assessing thrombotic risk and other obstetric complications such as miscarriage or fetal growth restriction

As an aid in the diagnosis of certain autoimmune thrombotic disorders, such as antiphospholipid syndrome (aPS). Antibodies to PS/PT correlate with the presence of lupus anticoagulants (LA) and this test may be useful in cases with difficult LA test interpretation. This assay may also assist in the determination of risk for thrombosis as well as obstetric complications in patients with antiphospholipid antibodies.


Limitations

• The pathogenic mechanism of aPS-PT antibody morbidity is substantially undefined, although under investigation.1 To date, aPS/PT antibodies are not included among the formal laboratory classification criteria for APS but are suggested as supplemental assays.

• The clinical significance of PS/PT IgG or IgM antibodies in diseases other than SLE or APS is currently under investigation.

• When negative PS/PT IgG or IgM titers are found in the presence of clinical indications, a lupus anticoagulant, anticardiolipin, anti-β2 or other additional testing is indicated.

• Diagnosis cannot be made on the basis of PS/PT IgG or IgM results alone. These results must be interpreted in conjunction with physical findings.

• Treatment must not be initiated on the basis of a positive PS/PT IgG or IgM titer alone. Supportive clinical indications must also be present.

• It is to be expected that some samples can be anticardiolipin positive and/or anti-β2 GPI positive yet PS/PT IgG or IgM negative. The anti-β2 GPI test is a specific marker of thrombotic risk.

• Patients with APS can be PS/PT positive yet lupus anticoagulant, anticardiolipin or anti-β2 negative.

• The pathogenic mechanism of aPS-PT antibody morbidity is substantially undefined, although under investigation.1 To date, aPS/PT antibodies are not included among the formal laboratory classification criteria for APS but are suggested as supplemental assays.

• The clinical significance of PS/PT IgG or IgM antibodies in diseases other than SLE or APS is currently under investigation.

• When negative PS/PT IgG or IgM titers are found in the presence of clinical indications, a lupus anticoagulant, anticardiolipin, anti-β2 or other additional testing is indicated.

• Diagnosis cannot be made on the basis of PS/PT IgG or IgM results alone. These results must be interpreted in conjunction with physical findings.

• Treatment must not be initiated on the basis of a positive PS/PT IgG or IgM titer alone. Supportive clinical indications must also be present.

• It is to be expected that some samples can be anticardiolipin positive and/or anti-β2 GPI positive yet PS/PT IgG or IgM negative. The anti-β2 GPI test is a specific marker of thrombotic risk.

• Patients with APS can be PS/PT positive yet lupus anticoagulant, anticardiolipin or anti-β2 negative.


Methodology

Enzyme-linked immunosorbent assay (ELISA)


Reference Interval

• IgG = 0–30 Units

• IgM = 0–30 Units

• IgA = 0–19 APS Units

• IgG = 0–30 Units

• IgM = 0–30 Units

• IgA = 0–19 APS Units


Additional Information

The antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia characterized by recurrent arterial and/or venous thrombosis, pregnancy-related complications (including miscarriages, fetal deaths, premature births, and preeclampsia), and the persistent presence of antiphospholipid antibodies (aPL).2 The original APS classification criteria required positivity for any one of 1) anticardiolipin (aCL) IgG or IgM antibodies or 2) lupus anticoagulant (LA) as diagnostic laboratory criteria.3 In 2006, the sensitivity of the classification criteria was improved by the including positivity for 3) β2-glycoprotein 1 (β2GPI) IgG or IgM antibodies as additional laboratory criteria for APS and the specificity of diagnosis was improved by extending the requirement of persistent presence of aPL to 12 weeks.4 At least one clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive test result for LA, aCL IgG/IgM or β2GPI IgG/IgM) criterion have to be met for a patient to be classified as having APS.

The antibodies associated with APS are known to react with phospholipids and/or with their binding proteins, either independently or in phospholipid–protein complexes. Early assays for antibodies to the lipid anticardiolipin were quite non-specific and were eventually replaced with assays employing complexes of cardiolipin with the protein β2GPI.2,5 Assays for antibodies to β2GPI have been shown to be more specific for APS albeit with somewhat lower sensitivity. Antibodies to prothrombin (aPT), have also been shown to occur in patients with APS.6-12 A large amount of data obtained mainly from retrospective studies provides contrasting evidence concerning the clinical significance of aPT antibodies.13-16 It has been shown that aPT associated with LA activity or APS clinical manifestations can be detected only using assays employing purified PT antigen immobilized on irradiated plates or as a complex with the lipid phosphatidylserine (aPS/PT).10,11,14,17,18

A systematic review and meta-analysis of 10 studies performed before 2014 found that aPS/PT antibody positivity is a strong risk factor for thrombosis and venous events independent from sites and type of thrombosis.6 A more recent meta-analysis, published in 2020,19 reviewing 15 studies published since the 2014 analysis20-34 further confirmed the association between aPS/PT antibodies and thrombosis. Pooled analysis revealed a significant association between aPS/PT-IgG/IgM21-23,31,32,34 and thrombotic events with mean Odds Ratio (mOR = 6.8) relative to controls. Pooled analysis further found an association between thrombotic events and aPS/PT-IgG6,20,22-29,31-34 positivity (mOR = 6.7) and aPS/PT-IgM20-23,25,28-32,34 positivity (mOR = 4.35). A subset of studies,21,24,26,27,31-33 including 1,388 patients, evaluated the association between aPS/PT antibodies and pregnancy morbidity (PM) as defined by the 2006 criteria for the definition of APS.4 Pooled analysis of the results from these studies found a statistically significant association between any PM and aPS/PT IgG/IgM positivity (mOR = 10.6) and, specifically, aPS/PT IgG positivity (mOR = 6.7).19

While the tests currently included in the classification criteria for APS are able to detect the great majority of the cases, some patients present clinical manifestations highly suggestive of APS while being persistently negative for the aPL tests included in the guidelines.1,35-39 These patients have been termed to have seronegative APS (SNAPS).36,37,40 Testing for aPS/PT antibodies has been proposed as an additional tool to be considered when investigating a patient suspected of having APS, particularly in the absence of guideline aPL positivity9,26,28,32,36,37,40-48 or as a part of risk assessment strategies.49 A number of studies have found that approximately 50 percent of patients with SNAPS were positive for IgG and/or IgM aPS/PT.33,35,37,39,50,51

The addition of aPS/PT to current criteria aPL assays has been reported to contribute to the identification of patients with a history of thrombosis and/or pregnancy-related morbidity that would go undiagnosed using current criteria aPL assays.21,23,32,36,37,42,45,52-56 In a number of studies, aPS/PT positivity was reported to be an independent risk factor for LA activity and to occur in LA-negative SLE or APS patients with thrombosis and pregnancy loss.23,54,56 Other investigators comparing different aPL combinations in patients with systemic lupus erythematosus observed that aPS/PT antibodies were significantly associated with both LA and pregnancy-related morbidity, while the combination of LA, anti-β2GPI and aPS/PT had superior diagnostic accuracy for thrombosis and pregnancy loss in APS.57,58 These studies suggest that aPS/PT and LA are, at least in part, independent risk factors for clinical manifestations of APS. A recent study demonstrated that determination of aPS/PT antibodies in concert with β2GPI antibodies in patients positive for LA might be useful for identifying patients at different risk of thromboembolic events.59 In addition, patients with triple positivity for LA, β2GPI and aPS/PT have been shown to be at a higher risk of developing thromboembolic events, risk even higher than that seen for the “classical” aCL, β2GPI and LA triple positivity.52,58 aPS/PT have been shown to be associated with recurrent early or late abortions and with premature delivery irrespective of other aPL.51 aPS/PT positivity also has been found to be predicative of non-criteria clinical symptoms4 including thrombocytopenia or hemolytic anemia.34

In addition to diagnosis, use of biomarkers to help predict risk of thrombosis has been addressed by the development of the anti-PhosphoLipid-Score (aPL-S) and the Global APS Score (GAPSS), Both these scoring systems include levels of aPS/PT antibodies (and not PS or PT) as components of the scoring system.19,48,49,60,61


Footnotes

1. Cifù A, Domenis R, Pistis C, Curcio F, Fabris M. Anti-β2-glycoprotein I and anti-phosphatidylserine/prothrombin antibodies exert similar pro-thrombotic effects in peripheral blood monocytes and endothelial cells. Auto Immun Highlights. 2019 Apr 6;10(1):3.32257059
2. Garcia D, Erkan D. Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med. 2018 May;378(21):2010-2021.29791828
3. Hughes GR. The anticardiolipin syndrome. Clin Exp Rheumatol. Oct-Dec 1985;3(4):285-286.4085158
4. Miyakis S Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306.16420554
5. Peterson LK, Willis R, Harris EN, Branch WD, Tebo AE. Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives. Adv Clin Chem. 2016;73:1-28.26975968
6. Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review. Thromb Haemost. 2014 Feb;111(2):354-364.24172938
7. Bertolaccini ML. Antibodies to prothrombin. Lupus. 2012 Jun;21(7):729-731.22635215
8. Matsuda J, Sanaka T, Nishizawa A, Gotah M, Gohchi K. Two antiprothrombin antibodies against prothrombin and prothrombin-phosphatidyl serine show partial but not total identity. Blood Coagul Fibrinolysis. 2002 Dec;13(8):697-702.12441908
9. Bardin N, Alessi MC, Dignat-George F, et al. Does the anti-prothrombin antibodies measurement provide additional information in patients with thrombosis? Immunobiology. 2007;212(7):557-565.17678713
10. Bertolaccini ML, Atsumi T, Koike T, Hughes GRV, Khamashta MA. Antiprothrombin antibodies detected in two different assay systems. Prevalence and clinical significance in systemic lupus erythematosus. Thromb Haemost. 2005 Feb;93(2):289-297.15711745
11. Bertolaccini ML, Gomez S, Pareja JF, et al. Antiphospholipid antibody tests: spreading the net. Ann Rheum Dis. 2005;64(11):1639-1643.15817655
12. Žigon P, Čučnik S, Ambrožič A, Šemrl SS, Kveder T, Božič B. Antibodies to phosphatidylserine/prothrombin complex as an additional diagnostic marker of APS? Lupus. 2012 Jun;21(7):790-792.22635235
13. Vaarala O, Puurunen M, Mänttäri M, Manninen V, Aho K, Palosuo T. Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men. Thromb Haemost. 1996 Mar;75(3):456-459.8701407
14. Atsumi T, Ieko M, Bertolaccini ML, 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 Sep;43(9):1982-1993.11014348
15. Forastiero R, Martinuzzo M, Pombo G, et al. A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis. J Thromb Haemost. 2005 Jun;3(6):1231-1238.15946213
16. Bizzaro N, Ghirardello A, Zampieri S, et al. Anti-prothrombin antibodies predict thrombosis in patients with systemic lupus erythematosus: a 15-year longitudinal study. J Thromb Haemost. 2007;5(6):1158-1164.17388963
17. 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 Jun;35(6):589-591.8670583
18. 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 May;180(2):218-226.25522978
19. Radin M, Foddai SG, Cecchi I, et al. Antiphosphatidylserine/Prothrombin Antibodies: An Update on Their Association with Clinical Manifestations of Antiphospholipid Syndrome. Thromb Haemost. 2020 Apr;120(4):592-598.32185783
20. Mullen MT, Messé SR, Kasner SE, et al. Anti-Phosphatidylserine-Prothrombin Antibodies are Associated with Outcome in a TIA Cohort. Front Neurol. 2012 Sep 28;3:137.23060855
21. Sciascia S, Sanna G, Murru V, Khamashta MA, Bertolaccini ML. Validation of a commercially available kit to detect anti-phosphatidylserine/prothrombin antibodies in a cohort of systemic lupus erythematosus patients. Thromb Res. 2014 Mar;133(3):451-454.24342537
22. Kim H, Kim JE, Hwang SM, Lee HR, Han KS, Kim HK. Synergistic thrombotic risk of antibodies against phosphatidylserine and prothrombin and β-2-glycoprotein I. Clin Appl Thromb Hemost. 2014 May;20(4):442-447.23892687
23. Hoxha A, Ruffatti A, Mattia E, et al. Relationship between antiphosphatidylserine/prothrombin and conventional antiphospholipid antibodies in primary antiphospholipid syndrome. Clin Chem Lab Med. 2015 Jul;53(8):1265-1270.25562605
24. Žigon P, Pirkmajer KP, Tomšič M, et al. Anti-Phosphatidylserine/Prothrombin Antibodies Are Associated with Adverse Pregnancy Outcomes. J Immunol Res. 2015;2015:975704.26078985
25. Zuily S, de Laat B, Mohamed S, et al. Validity of the global anti-phospholipid syndrome score to predict thrombosis: a prospective multicentre cohort study. Rheumatology (Oxford). 2015 Nov;54(11):2071-2075.26163690
26. Amengual O, Forastiero R, Sugiura-Ogasawara M, et al. Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study. Lupus. 2017 Mar;26(3):266-276.27510605
27. Marchetti T, de Moerloose P, Gris JC. Antiphospholipid antibodies and the risk of severe and non-severe pre-eclampsia: the NOHA case-control study. J Thromb Haemost. 2016 Apr;14(4):675-684.26782635
28. Hoxha A, Mattia E, Tonello M, Grava C, Pengo V, Ruffatti A. Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome. Clin Chem Lab Med. 2017 May 1;55(6):890-898.27816952
29. Lee JS, Gu J, Park HS, Yoo HJ, Kim HK. Coexistence of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies suggests strong thrombotic risk. Clin Chem Lab Med. 2017 May 1;55(6):882-889.28002027
30. Zhang S, Wu Z, Zhang W, et al. Antibodies to phosphatidylserine/prothrombin (aPS/PT) enhanced the diagnostic performance in Chinese patients with antiphospholipid syndrome. Clin Chem Lab Med. 2018 May 24;56(6):939-946.29561729
31. Zhu L, Li C, Liu N, et al. Diagnostic value of antibodies to phosphatidylserine/prothrombin complex for antiphospholipid syndrome in Chinese patients. Clin Rheumatol. 2017 Feb;36(2):401-406.28050648
32. Shi H, Zheng H, Yin YF, et al. Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential diagnostic markers and risk predictors of venous thrombosis and obstetric complications in antiphospholipid syndrome. Clin Chem Lab Med. 2018 Mar 28;56(4):614-624.29166262
33. Ganapati A, Goel R, Kabeerdoss J, Gowri M, Mathew J, Danda D. Study of clinical utility of antibodies to phosphatidylserine/prothrombin complex in Asian-Indian patients with suspected APS. Clin Rheumatol. 2019 Feb;38(2):545-553.30255283
34. Núñez-Álvarez CA, Hernández-Molina G, Bermúdez-Bermejo P, et al. Prevalence and associations of anti-phosphatidylserine/prothrombin antibodies with clinical phenotypes in patients with primary antiphospholipid syndrome: aPS/PT antibodies in primary antiphospholipid syndrome. Thromb Res. 2019 Feb;174:141-147.30612005
35. Sciascia S, Radin M, Ramirez C, et al. Evaluation of novel assays for the detection of autoantibodies in antiphospholipid syndrome. Autoimmun Rev. 2020 Oct;19(10):102641.32801044
36. Pignatelli P, Ettorre E, Menichelli D, Pani A, Violi F, Pastori D. Seronegative antiphospholipid syndrome: refining the value of "non-criteria" antibodies for diagnosis and clinical management. Haematologica. 2020 Mar;105(3):562-572.32001534
37. Liu T, Gu J, Wan L, et al. "Non-criteria" antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort. Arthritis Res Ther. 2020 Feb 21;22(1):33.32085759
38. Hughes GRV, Khamashta MA. 'Seronegative antiphospholipid syndrome': an update. Lupus. 2019 Mar;28(3):273-274.30691344
39. Zohoury N, Bertolaccini ML, Rodriguez-Garcia JL, et al. Closing the Serological Gap in the Antiphospholipid Syndrome: The Value of "Non-criteria" Antiphospholipid Antibodies. J Rheumatol. 2017 Nov;44(11):1597-1602.28864642
40. Nayfe R, Uthman I, Aoun J, Aldin ES, Merashli M, Khamashta MA. Seronegative antiphospholipid syndrome. Rheumatology (Oxford). 2013 Aug;52(8):1358-1367.23502076
41. Bertolaccini ML, Amengual O, Atsumi T, et al. 'Non-criteria' aPL tests: report of a task force and preconference workshop at the 13th International Congress on Antiphospholipid Antibodies, Galveston, TX, USA, April 2010. Lupus. 2011 Feb;20(2):191-205.21303836
42. Sanfelippo MJ, Joshi A, Schwartz S, Meister JA, Goldberg JW. Antibodies to phosphatidylserine/prothrombin complex in suspected antiphospholipid syndrome in the absence of antibodies to cardiolipin or beta-2-glycoprotein I. Lupus. 2013 Nov;22(13):1349-1352.23989738
43. Fabris M, Giacomello R, Poz A, et al. The introduction of anti-phosphatidylserine/prothrombin autoantibodies in the laboratory diagnostic process of anti-phospholipid antibody syndrome: 6 months of observation. Auto Immun Highlights. 2014 Aug 14;5(2):63-67.26000157
44. Rodríguez-García V, Ioannou Y, Fernández-Nebro A, Isenberg DA, Giles IP. Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review. Rheumatology (Oxford). 2015;54(11):2042-2050.26152548
45. Pregnolato F, Chighizola CB, Encabo S, et al. Anti-phosphatidylserine/prothrombin antibodies: an additional diagnostic marker for APS? Immunol Res. 2013 Jul;56(2–3):432-438.23572433
46. Sciascia S, Baldovino S, Schreiber K, et al. Thrombotic risk assessment in antiphospholipid syndrome: the role of new antibody specificities and thrombin generation assay. Clin Mol Allergy. 2016 Jul 15;14:6.27429595
47. Sciascia S, Radin M, Sanna G, Cecchi I, Roccatello D, Bertolaccini ML. Clinical utility of the global anti-phospholipid syndrome score for risk stratification: a pooled analysis. Rheumatology (Oxford). 2018 Apr 1;57(4):661-665.29342292
48. Nakamura H, Oku K, Amengual O, et al. First-line, non-criterial antiphospholipid antibody testing for the diagnosis of antiphospholipid syndrome in clinical practice: a combination of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin complex antibodies tests. Arthritis Care Res (Hoboken). 2018 Apr;70(4):627-634.28686816
49. Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. GAPSS: the Global Anti-Phospholipid Syndrome Score. Rheumatology (Oxford). 2013 Aug;52(8):1397-1403.23315788
50. Litvinova E, Darnige L, Kirilovsky A, Burnel Y, de Luna G, Dragon-Durey MA. Prevalence and Significance of Non-Conventional Antiphospholipid Antibodies in Patients with Clinical APS Criteria. Front Immunol. 2018 Dec 14;9:2971.30619328
51. Zigon P, Podovsovnik A, Ambrozic A, et al. Added value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome: lessons learned from year-long routine measurements. Clin Rheumatol. 2019 Feb;38(2):371-378.30099654
52. Tonello M, Mattia E, Favaro M, et al. IgG phosphatidylserine/prothrombin antibodies as a risk factor of thrombosis in antiphospholipid antibody carriers. Thromb Res. 2019 May;177:157-160.30903876
53. Vlagea A, Gil A, Cuesta MV, et al. Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential markers of antiphospholipid syndrome. Clin Appl Thromb Hemost. 2013 Jun;19(3):289-296.22387581
54. Bertolaccini ML, Sciascia S, Murru V, Garcia-Fernandez G, Sanna G, Khamashta MA. Prevalence of antibodies to prothrombin in solid phase (aPT) and to phosphatidylserine-prothrombin complex (aPS/PT) in patients with and without lupus anticoagulant. Thromb Haemost. 2013 Feb;109(2):207-213.23254928
55. Kitaori T, Sugiura-Ogasawara M, Oku K, et al. Determination of clinically significant tests for antiphospholipid antibodies and cutoff levels for obstetric antiphospholipid syndrome. Lupus. 2015 Dec;24(14):1505-1519.26162683
56. Hoxha A, Ruffatti A, Tonello M, et al. Antiphosphatidylserine/prothrombin antibodies in primary antiphospholipid syndrome. Lupus. 2012 Jun;21(7):787-789.22635234
57. Nojima J, Iwatani Y, Suehisa E, Kuratsune H, Kanakura Y. The presence of anti-phosphatidylserine/prothrombin antibodies as risk factor for both arterial and venous thrombosis in patients with systemic lupus erythematosus. Haematologica. 2006 May;91(5):699-702.16627257
58. 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 Dec;10(12):2512-2518.23025466
59. Pengo V, Del Ross T, Ruffatti A, et al. Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns. Thromb Res. 2018 Dec;172:172-178.30466070
60. Otomo K, Atsumi T, Amengual O, et al. Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum. 2012 Feb;64(2):504-512.21953404
61. Kato M, Hisada R, Atsumi T. Clinical profiles and risk assessment in patients with antiphospholipid antibodies. Expert Rev Clin Immunol. 2019 Jan;15(1):73-81.30381978
1. Cifù A, Domenis R, Pistis C, Curcio F, Fabris M. Anti-β2-glycoprotein I and anti-phosphatidylserine/prothrombin antibodies exert similar pro-thrombotic effects in peripheral blood monocytes and endothelial cells. Auto Immun Highlights. 2019 Apr 6;10(1):3.32257059
2. Garcia D, Erkan D. Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med. 2018 May;378(21):2010-2021.29791828
3. Hughes GR. The anticardiolipin syndrome. Clin Exp Rheumatol. Oct-Dec 1985;3(4):285-286.4085158
4. Miyakis S Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306.16420554
5. Peterson LK, Willis R, Harris EN, Branch WD, Tebo AE. Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives. Adv Clin Chem. 2016;73:1-28.26975968
6. Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review. Thromb Haemost. 2014 Feb;111(2):354-364.24172938
7. Bertolaccini ML. Antibodies to prothrombin. Lupus. 2012 Jun;21(7):729-731.22635215
8. Matsuda J, Sanaka T, Nishizawa A, Gotah M, Gohchi K. Two antiprothrombin antibodies against prothrombin and prothrombin-phosphatidyl serine show partial but not total identity. Blood Coagul Fibrinolysis. 2002 Dec;13(8):697-702.12441908
9. Bardin N, Alessi MC, Dignat-George F, et al. Does the anti-prothrombin antibodies measurement provide additional information in patients with thrombosis? Immunobiology. 2007;212(7):557-565.17678713
10. Bertolaccini ML, Atsumi T, Koike T, Hughes GRV, Khamashta MA. Antiprothrombin antibodies detected in two different assay systems. Prevalence and clinical significance in systemic lupus erythematosus. Thromb Haemost. 2005 Feb;93(2):289-297.15711745
11. Bertolaccini ML, Gomez S, Pareja JF, et al. Antiphospholipid antibody tests: spreading the net. Ann Rheum Dis. 2005;64(11):1639-1643.15817655
12. Žigon P, Čučnik S, Ambrožič A, Šemrl SS, Kveder T, Božič B. Antibodies to phosphatidylserine/prothrombin complex as an additional diagnostic marker of APS? Lupus. 2012 Jun;21(7):790-792.22635235
13. Vaarala O, Puurunen M, Mänttäri M, Manninen V, Aho K, Palosuo T. Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men. Thromb Haemost. 1996 Mar;75(3):456-459.8701407
14. Atsumi T, Ieko M, Bertolaccini ML, 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 Sep;43(9):1982-1993.11014348
15. Forastiero R, Martinuzzo M, Pombo G, et al. A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis. J Thromb Haemost. 2005 Jun;3(6):1231-1238.15946213
16. Bizzaro N, Ghirardello A, Zampieri S, et al. Anti-prothrombin antibodies predict thrombosis in patients with systemic lupus erythematosus: a 15-year longitudinal study. J Thromb Haemost. 2007;5(6):1158-1164.17388963
17. 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 Jun;35(6):589-591.8670583
18. 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 May;180(2):218-226.25522978
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References

Nojima J, Kuratsune H, Suehisa E, Kitani T, Iwatani Y, Kanakura Y. Strong correlation between the prevalence of cerebral infarction and the presence of anti-cardiolipin/beta2-glycoprotein I and anti-phosphatidylserine/prothrombin antibodies--Co-existence of these antibodies enhances ADP-induced platelet activation in vitro. Thromb Haemost. 2004 May;91(5):967-976.15116258
Nojima J, Motoki Y, Hara K, Sakata T, Ichihara K. Novel enzyme immunoassay system for simultaneous detection of six subclasses of antiphospholipid antibodies for differential diagnosis of antiphospholipid syndrome. Blood Coagul Fibrinolysis. 2017 Jun;28(4):316-322.27676644
Sciascia S, Amigo MC, Roccatello D, Khamashta M. Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances. Nat Rev Rheumatol. 2017 Sep;13(9):548-560.28769114
Sciascia S, Khamashta MA, Bertolaccini ML. New tests to detect antiphospholipid antibodies: antiprothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies. Curr Rheumatol Rep. 2014 May;16(5):415.24609824
Sciascia S, Radin M, Cecchi I, et al. Reliability of Lupus Anticoagulant and Anti-phosphatidylserine/prothrombin Autoantibodies in Antiphospholipid Syndrome: A Multicenter Study. Front Immunol. 2019 Mar 5;10:376.30891041
Tsutsumi A, Hayashi T, Chino Y, et al. Significance of antiprothrombin antibodies in patients with systemic lupus erythematosus: clinical evaluation of the antiprothrombin assay and the antiphosphatidylserine/prothrombin assay, and comparison with other antiphospholipid antibody assays. Mod Rheumatol. 2006;16(3):158-164.16767554
Nojima J, Kuratsune H, Suehisa E, Kitani T, Iwatani Y, Kanakura Y. Strong correlation between the prevalence of cerebral infarction and the presence of anti-cardiolipin/beta2-glycoprotein I and anti-phosphatidylserine/prothrombin antibodies--Co-existence of these antibodies enhances ADP-induced platelet activation in vitro. Thromb Haemost. 2004 May;91(5):967-976.15116258
Nojima J, Motoki Y, Hara K, Sakata T, Ichihara K. Novel enzyme immunoassay system for simultaneous detection of six subclasses of antiphospholipid antibodies for differential diagnosis of antiphospholipid syndrome. Blood Coagul Fibrinolysis. 2017 Jun;28(4):316-322.27676644
Sciascia S, Amigo MC, Roccatello D, Khamashta M. Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances. Nat Rev Rheumatol. 2017 Sep;13(9):548-560.28769114
Sciascia S, Khamashta MA, Bertolaccini ML. New tests to detect antiphospholipid antibodies: antiprothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies. Curr Rheumatol Rep. 2014 May;16(5):415.24609824
Sciascia S, Radin M, Cecchi I, et al. Reliability of Lupus Anticoagulant and Anti-phosphatidylserine/prothrombin Autoantibodies in Antiphospholipid Syndrome: A Multicenter Study. Front Immunol. 2019 Mar 5;10:376.30891041
Tsutsumi A, Hayashi T, Chino Y, et al. Significance of antiprothrombin antibodies in patients with systemic lupus erythematosus: clinical evaluation of the antiprothrombin assay and the antiphosphatidylserine/prothrombin assay, and comparison with other antiphospholipid antibody assays. Mod Rheumatol. 2006;16(3):158-164.16767554

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
117994 Antiphosphatidylserine IgG/M/A 117910 Antiphosphatidylserine IgM Units 14246-3
117994 Antiphosphatidylserine IgG/M/A 117926 Antiphosphatidylserine IgA APS Units 13069-0
117994 Antiphosphatidylserine IgG/M/A 117927 Antiphosphatidylserine IgG Units 14245-5

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