Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-β2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.

Department of Hemato Oncology Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc 77900 Olomouc Czech Republic

Department of Immunology Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc 77900 Olomouc Czech Republic

Department of Internal Medicine 3 Nephrology Rheumatology and Endocrinology Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc 77900 Olomouc Czech Republic

Laboratory for Inherited Metabolic Disorders Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc 77900 Olomouc Czech Republic

Laboratory of Molecular and Cellular Immunology Institute of Molecular Biology NAS RA Yerevan 0014 Armenia

Masaryk Hospital Usti nad Labem Department Clinical Hematology 40113 Usti nad Labem Czech Republic

See more in PubMed

Hughes G.R. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br. Med. J. (Clin. Res. Ed.) 1983;287:1088–1089. doi: 10.1136/bmj.287.6399.1088. PubMed DOI PMC

Lopez-Pedrera C., Barbarroja N., Patiño-Trives A.M., Collantes E., Aguirre M.A., Perez-Sanchez C. New Biomarkers for Atherothrombosis in Antiphospholipid Syndrome: Genomics and Epigenetics Approaches. Front. Immunol. 2019;10:764. doi: 10.3389/fimmu.2019.00764. PubMed DOI PMC

Radic M., Pattanaik D. Cellular and Molecular Mechanisms of Anti-Phospholipid Syndrome. Front. Immunol. 2018;9:969. doi: 10.3389/fimmu.2018.00969. PubMed DOI PMC

Schreiber K., Sciascia S., de Groot P.G., Devreese K., Jacobsen S., Ruiz-Irastorza G., Salmon J.E., Shoenfeld Y., Shovman O., Hunt B.J. Antiphospholipid syndrome. Nat. Rev. Dis. Primers. 2018;4:17103. doi: 10.1038/nrdp.2017.103. PubMed DOI

Cervera R. Antiphospholipid syndrome. Thromb. Res. 2017;151((Suppl. S1)):S43–S47. doi: 10.1016/S0049-3848(17)30066-X. PubMed DOI

Liu L., Sun D. Pregnancy outcomes in patients with primary antiphospholipid syndrome: A systematic review and meta-analysis. Medicine. 2019;98:e15733. doi: 10.1097/MD.0000000000015733. PubMed DOI PMC

Whitaker K.L. Antiphospholipid antibody syndrome: The difficulties of diagnosis. JAAPA Off. J. Am. Acad. Physician Assist. 2017;30:10–14. doi: 10.1097/01.JAA.0000526771.67820.59. PubMed DOI

Miyakis S., Lockshin M.D., Atsumi T., Branch D.W., Brey R.L., Cervera R., Derksen R.H., DE Grrot P.G., Koike T., Meroni P.L., et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) J. Thromb. Haemost. JTH. 2006;4:295–306. doi: 10.1111/j.1538-7836.2006.01753.x. PubMed DOI

Devreese K.M.J., Ortel T.L., Pengo V., de Laat B. Laboratory criteria for antiphospholipid syndrome: Communication from the SSC of the ISTH. J. Thromb. Haemost. JTH. 2018;16:809–813. doi: 10.1111/jth.13976. PubMed DOI

Pengo V., Banzato A., Bison E., Bracco A., Denas G., Ruffatti A. What have we learned about antiphospholipid syndrome from patients and antiphospholipid carrier cohorts? Semin. Thromb. Hemost. 2012;38:322–327. doi: 10.1055/s-0032-1304719. PubMed DOI

Pengo V., Ruffatti A., Del Ross T., Tonello M., Cuffaro S., Hoxha A., Banzato A., Bison E., Denas G., Bracco A., et al. Confirmation of initial antiphospholipid antibody positivity depends on the antiphospholipid antibody profile. J. Thromb. Haemost. JTH. 2013;11:1527–1531. doi: 10.1111/jth.12264. PubMed DOI

Pengo V., Ruffatti A., Legnani C., Gresele P., Barcellona D., Erba N., Testa S., Marongiu F., Bison E., Denas G., et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J. Thromb. Haemost. JTH. 2010;8:237–242. doi: 10.1111/j.1538-7836.2009.03674.x. PubMed DOI

Sciascia S., Murru V., Sanna G., Roccatello D., Khamashta M.A., Bertolaccini M.L. Clinical accuracy for diagnosis of antiphospholipid syndrome in systemic lupus erythematosus: Evaluation of 23 possible combinations of antiphospholipid antibody specificities. J. Thromb. Haemost. JTH. 2012;10:2512–2518. doi: 10.1111/jth.12014. PubMed DOI

De Groot P.G., Derksen R.H. Pathophysiology of the antiphospholipid syndrome. J. Thromb. Haemost. JTH. 2005;3:1854–1860. doi: 10.1111/j.1538-7836.2005.01359.x. PubMed DOI

Douxfils J., Morimont L., Delvigne A.S., Devel P., Masereel B., Haguet H., Bouvy C., Dogné J.M. Validation and standardization of the ETP-based activated protein C resistance test for the clinical investigation of steroid contraceptives in women: An unmet clinical and regulatory need. Clin. Chem. Lab. Med. 2020;58:294–305. doi: 10.1515/cclm-2019-0471. PubMed DOI

Albay A., Artim-Esen B., Pericleous C., Wincup C., Giles I., Rahman A., McDonnell T. Domain I of β2GPI is capable of blocking serum IgA antiphospholipid antibodies binding in vitro: An effect enhanced by PEGylation. Lupus. 2019;28:893–897. doi: 10.1177/0961203319851571. PubMed DOI PMC

Cervera R., Conti F., Doria A., Iaccarino L., Valesini G. Does seronegative antiphospholipid syndrome really exist? Autoimmun. Rev. 2012;11:581–584. doi: 10.1016/j.autrev.2011.10.017. PubMed DOI

Conti F., Capozzi A., Truglia S., Lococo E., Longo A., Misasi R., Alessandri C., Valesini G., Sorice M. The mosaic of “seronegative” antiphospholipid syndrome. J. Immunol. Res. 2014;2014:389601. doi: 10.1155/2014/389601. PubMed DOI PMC

Salle V. Seronegative antiphospholipid syndrome: Myth or reality? Rev. Med. Interne. 2020;41:265–274. doi: 10.1016/j.revmed.2020.02.005. PubMed DOI

Conti F., Andreoli L., Crisafulli F., Mancuso S., Truglia S., Tektonidou M.G. Does seronegative obstetric APS exist? “pro” and “cons”. Autoimmun. Rev. 2019;18:102407. doi: 10.1016/j.autrev.2019.102407. PubMed DOI

Ortona E., Capozzi A., Colasanti T., Conti F., Alessandri C., Longo A., Garofalo T., Margutti P., Misasi R., Khamashta M.A., et al. Vimentin/cardiolipin complex as a new antigenic target of the antiphospholipid syndrome. Blood. 2010;116:2960–2967. doi: 10.1182/blood-2010-04-279208. PubMed DOI

Misasi R., Capozzi A., Longo A., Recalchi S., Lococo E., Alessandri C., Conti F., Valesini G., Sorice M. “New” antigenic targets and methodological approaches for refining laboratory diagnosis of antiphospholipid syndrome. J. Immunol. Res. 2015;2015:858542. doi: 10.1155/2015/858542. PubMed DOI PMC

Tripodi A. Laboratory testing for lupus anticoagulants: A review of issues affecting results. Clin. Chem. 2007;53:1629–1635. doi: 10.1373/clinchem.2007.089524. PubMed DOI

Chaturvedi S., McCrae K.R. Diagnosis and management of the antiphospholipid syndrome. Blood Rev. 2017;31:406–417. doi: 10.1016/j.blre.2017.07.006. PubMed DOI PMC

Meroni P.L., Tincani A., Harris E.N., Valesini G., Hughes G.R., Balestrieri G. The pathophysiology of anti-phospholipid antibodies. Clin. Exp. Rheumatol. 1989;7((Suppl. S3)):S81–S84. PubMed

Liu T., Gu J., Wan L., Hu Q., Teng J., Liu H., Cheng X., Ye J., Su Y., Sun Y., et al. “Non-criteria” antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort. Arthritis Res. Ther. 2020;22:33. doi: 10.1186/s13075-020-2131-4. PubMed DOI PMC

De Groot P.G., Meijers J.C. β(2)-Glycoprotein I: Evolution, structure and function. J. Thromb. Haemost. JTH. 2011;9:1275–1284. doi: 10.1111/j.1538-7836.2011.04327.x. PubMed DOI

Perdan-Pirkmajer K., Žigon P., Boc A., Podovsovnik E., Cucnik S., Mavri A., Rotar Ž., Ambrozic A. The Predictive Value of the aCL and Anti-β2GPI at the Time of Acute Deep Vein Thrombosis—A Two-Year Prospective Study. Biomedicines. 2021;9:901. doi: 10.3390/biomedicines9080901. PubMed DOI PMC

Chayoua W., Kelchtermans H., Moore G.W., Musiał J., Wahl D., de Laat B., Devreese K.M.J. Identification of high thrombotic risk triple-positive antiphospholipid syndrome patients is dependent on anti-cardiolipin and anti-β2glycoprotein I antibody detection assays. J. Thromb. Haemost. JTH. 2018;16:2016–2023. doi: 10.1111/jth.14261. PubMed DOI

Decavele A.S., Schouwers S., Devreese K.M. Evaluation of three commercial ELISA kits for anticardiolipin and anti-beta2-glycoprotein I antibodies in the laboratory diagnosis of the antiphospholipid syndrome. Int. J. Lab. Hematol. 2011;33:97–108. doi: 10.1111/j.1751-553X.2010.01259.x. PubMed DOI

Gebhart J., Posch F., Koder S., Quehenberger P., Perkmann T., Kuessel L., Ay C., Pabinger I. High risk of adverse pregnancy outcomes in women with a persistent lupus anticoagulant. Blood Adv. 2019;3:769–776. doi: 10.1182/bloodadvances.2018026948. PubMed DOI PMC

Pierangeli S.S., Favaloro E.J., Lakos G., Meroni P.L., Tincani A., Wong R.C., Harris E.N. Standards and reference materials for the anticardiolipin and anti-β2glycoprotein I assays: A report of recommendations from the APL Task Force at the 13th International Congress on Antiphospholipid Antibodies. Clin. Chim. Acta Int. J. Clin. Chem. 2012;413:358–360. doi: 10.1016/j.cca.2011.09.048. PubMed DOI

Willis R., Lakos G., Harris E.N. Standardization of antiphospholipid antibody testing--historical perspectives and ongoing initiatives. Semin. Thromb. Hemost. 2014;40:172–177. doi: 10.1055/s-0033-1364207. PubMed DOI

Ahluwalia J., Sreedharanunni S. The Laboratory Diagnosis of the Antiphospholipid Syndrome. Indian J. Hematol. Blood Transfus. Off. J. Indian Soc. Hematol. Blood Transfus. 2017;33:8–14. doi: 10.1007/s12288-016-0739-y. PubMed DOI PMC

Janek D., Slavik L., Ulehlova J., Krcova V., Hlusi A., Prochazkova J. Validation of a New Panel of Automated Chemiluminescence Assays for Anticardiolipin Antibodies in the Screening for Antiphospholipid Syndrome. Clin. Lab. 2016;62:1309–1315. doi: 10.7754/Clin.Lab.2015.151129. PubMed DOI

Bizzaro N., Ghirardello A., Zampieri S., Iaccarino L., Tozzoli R., Ruffatti A., Villalta D., Tonutti E., Doria A. Anti-prothrombin antibodies predict thrombosis in patients with systemic lupus erythematosus: A 15-year longitudinal study. J. Thromb. Haemost. JTH. 2007;5:1158–1164. doi: 10.1111/j.1538-7836.2007.02532.x. PubMed DOI

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;10:3. doi: 10.1186/s13317-019-0113-9. PubMed DOI PMC

Sciascia S., Khamashta M.A., Bertolaccini M.L. New tests to detect antiphospholipid antibodies: Antiprothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies. Curr. Rheumatol. Rep. 2014;16:415. doi: 10.1007/s11926-014-0415-x. PubMed DOI

Sciascia S., Radin M., Sanna G., Cecchi I., Roccatello D., Bertolaccini M.L. Clinical utility of the global anti-phospholipid syndrome score for risk stratification: A pooled analysis. Rheumatology. 2018;57:661–665. doi: 10.1093/rheumatology/kex466. PubMed DOI

Conti F., Alessandri C., Spinelli F.R., Capozzi A., Martinelli F., Recalchi S., Misasi R., Valesini G., Sorice M. TLC immunostaining for detection of “antiphospholipid” antibodies. Methods Mol. Biol. 2014;1134:95–101. doi: 10.1007/978-1-4939-0326-9_8. PubMed DOI

Yin D., de Laat B., Devreese K.M.J., Kelchtermans H. The clinical value of assays detecting antibodies against domain I of β2-glycoprotein I in the antiphospholipid syndrome. Autoimmun. Rev. 2018;17:1210–1218. doi: 10.1016/j.autrev.2018.06.011. PubMed DOI

Rand J.H. Antiphospholipid antibody-mediated disruption of the annexin-V antithrombotic shield: A thrombogenic mechanism for the antiphospholipid syndrome. J. Autoimmun. 2000;15:107–111. doi: 10.1006/jaut.2000.0410. PubMed DOI

Bertolaccini M.L., Amengual O., Atsumi T., Binder W.L., de Laat B., Forastiero R., Kutteh W.H., Lambert M., Matsubayashi H., Murthy V., 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;20:191–205. doi: 10.1177/0961203310397082. PubMed DOI

Chandler W.L., Roshal M. Optimization of plasma fluorogenic thrombin-generation assays. Am. J. Clin. Pathol. 2009;132:169–179. doi: 10.1309/ajcp6ay4htraajfq. PubMed DOI

Duarte R.C.F., Ferreira C.N., Rios D.R.A., Reis H.J.D., Carvalho M.D.G. Thrombin generation assays for global evaluation of the hemostatic system: Perspectives and limitations. Rev. Bras. Hematol. Hemoter. 2017;39:259–265. doi: 10.1016/j.bjhh.2017.03.009. PubMed DOI PMC

Hron G., Kollars M., Binder B.R., Eichinger S., Kyrle P.A. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA. 2006;296:397–402. doi: 10.1001/jama.296.4.397. PubMed DOI

Billoir P., Miranda S., Levesque H., Benhamou Y., Le Cam Duchez V. Hypercoagulability Evaluation in Antiphospholipid Syndrome without Anticoagulation Treatment with Thrombin Generation Assay: A Preliminary Study. J. Clin. Med. 2021;10:2728. doi: 10.3390/jcm10122728. PubMed DOI PMC

Heit J.A., Sobell J.L., Li H., Sommer S.S. The incidence of venous thromboembolism among Factor V Leiden carriers: A community-based cohort study. J. Thromb. Haemost. JTH. 2005;3:305–311. doi: 10.1111/j.1538-7836.2004.01117.x. PubMed DOI

Liestøl S., Sandset P.M., Mowinckel M.C., Wisløff F. Activated protein C resistance determined with a thrombin generation-based test is associated with thrombotic events in patients with lupus anticoagulants. J. Thromb. Haemost. JTH. 2007;5:2204–2210. doi: 10.1111/j.1538-7836.2007.02734.x. PubMed DOI

Jiang D., Lim W., Crowther M., Garcia D. A systematic review of the association between anti-β-2 glycoprotein I antibodies and APS manifestations. Blood Adv. 2021;5:3931–3936. doi: 10.1182/bloodadvances.2021005205. PubMed DOI PMC

Pastori D., Bucci T., Triggiani M., Ames P.R.J., Parrotto S., Violi F., Pignatelli P., Farcomeni A. Immunoglobulin G (IgG) anticardiolipin antibodies and recurrent cardiovascular events. A systematic review and Bayesian meta-regression analysis. Autoimmun. Rev. 2019;18:519–525. doi: 10.1016/j.autrev.2019.03.005. PubMed DOI

Pires Da Rosa G., Rodríguez-Pintó I., Cervera R., Espinosa G. Management of patients with antiphospholipid antibodies: What to do in laboratory scenarios that do not fit the guidelines. Expert Rev. Hematol. 2021;14:457–466. doi: 10.1080/17474086.2021.1923474. PubMed DOI

Truglia S., Mancuso S., Capozzi A., Recalchi S., Riitano G., Longo A., De Carolis S., Spinelli F.R., Alessandri C., Ceccarelli F., et al. ‘Non-criteria antiphospholipid antibodies’: Bridging the gap between seropositive and seronegative antiphospholipid syndrome. Rheumatology. 2022;61:826–833. doi: 10.1093/rheumatology/keab414. PubMed DOI

Zhu R., Cheng C.Y., Yang Y., Denas G., Pengo V. Prevalence of aPhosphatidylserine/prothrombin antibodies and association with antiphospholipid antibody profiles in patients with antiphospholipid syndrome: A systematic review and meta-analysis. Thromb. Res. 2022;214:106–114. doi: 10.1016/j.thromres.2022.04.021. PubMed DOI

Egri N., Bentow C., Rubio L., Norman G.L., López-Sañudo S., Mahler M., Pérez-Isidro A., Cervera R., Viñas O., Espinosa G., et al. Anti-Phosphatidylserine/Prothrombin Antibodies at Two Points: Correlation With Lupus Anticoagulant and Thrombotic Risk. Front. Immunol. 2021;12:754469. doi: 10.3389/fimmu.2021.754469. PubMed DOI PMC

Slavik L.J.D., Ulehlova J., Krcova V., Hlusi A. Detection of Anti-Domain I β-2 Glycoprotein I Antibodies as New Potential Target in Antiphospholipid Syndrome Diagnosis. J. Hematol. Thromboembolic Dis. 2017;5:276. doi: 10.4172/2329-8790.1000276. DOI

Guo H., Zhang Y., Li A., Wang C., Yang S., Zhang Y., Zhang J., Qiao R. Anti-domain 1 of beta2-glycoprotein I aids risk stratification in lupus anticoagulant-positive patients. Clin. Exp. Med. 2019;19:339–345. doi: 10.1007/s10238-019-00555-w. PubMed DOI

Slavik L., Jacova J., Friedecky D., Ulehlova J., Tauber Z., Prochazkova J., Hlusi A., Palova M. Evaluation of the DOAC-Stop Procedure by LC-MS/MS Assays for Determining the Residual Activity of Dabigatran, Rivaroxaban, and Apixaban. Off. J. Int. Acad. Clin. Appl. Thromb. Hemost. 2019;25 doi: 10.1177/1076029619872556. PubMed DOI PMC

Pengo V., Tripodi A., Reber G., Rand J.H., Ortel T.L., Galli M., De Groot P.G. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J. Thromb. Haemost. JTH. 2009;7:1737–1740. doi: 10.1111/j.1538-7836.2009.03555.x. PubMed DOI

McDonnell T.C.R., Willis R., Pericleous C., Ripoll V.M., Giles I.P., Isenberg D.A., Brasier A.R., Gonzalez E.B., Papalardo E., Romay-Penabad Z., et al. PEGylated Domain I of Beta-2-Glycoprotein I Inhibits the Binding, Coagulopathic, and Thrombogenic Properties of IgG From Patients With the Antiphospholipid Syndrome. Front. Immunol. 2018;9:2413. doi: 10.3389/fimmu.2018.02413. PubMed DOI PMC

Linnemann B. Antiphospholipid syndrome-an update. VASA Z. Fur Gefasskrankh. 2018;47:451–464. doi: 10.1024/0301-1526/a000723. PubMed DOI

Devreese K.M.J. How to Interpret Antiphospholipid Laboratory Tests. Curr. Rheumatol. Rep. 2020;22:38. doi: 10.1007/s11926-020-00916-5. PubMed DOI

Nakamura H., Oku K., Amengual O., Ohmura K., Fujieda Y., Kato M., Bohgaki T., Yasuda S., Atsumi T. First-Line, Non-Criterial Antiphospholipid Antibody Testing for the Diagnosis of Antiphospholipid Syndrome in Clinical Practice: A Combination of Anti-β(2)-Glycoprotein I Domain I and Anti-Phosphatidylserine/Prothrombin Complex Antibodies Tests. Arthritis Care Res. 2018;70:627–634. doi: 10.1002/acr.23310. PubMed DOI

Zhou J., Hou X., Zhang H., Wang T., Cui L. The Clinical Performance of a New Chemiluminescent Immunoassay in Measuring Anti-β2 Glycoprotein 1 and Anti-Cardiolipin Antibodies. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2018;24:6816–6822. doi: 10.12659/MSM.910369. PubMed DOI PMC

Aydin S. A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides. 2015;72:4–15. doi: 10.1016/j.peptides.2015.04.012. PubMed DOI

Kohl T.O., Ascoli C.A. Immunometric Double-Antibody Sandwich Enzyme-Linked Immunosorbent Assay. Cold Spring Harb. Protoc. 2017;2017:pdb.prot093724. doi: 10.1101/pdb.prot093724. PubMed DOI

Kohl T.O., Ascoli C.A. Indirect Immunometric ELISA. Cold Spring Harb. Protoc. 2017;2017:396–401. doi: 10.1101/pdb.prot093708. PubMed DOI

Tebo A.E., Jaskowski T.D., Phansalkar A.R., Litwin C.M., Branch D.W., Hill H.R. Diagnostic performance of phospholipid-specific assays for the evaluation of antiphospholipid syndrome. Am. J. Clin. Pathol. 2008;129:870–875. doi: 10.1309/6MPULFBL24FM9B50. PubMed DOI

Tripodi A. Thrombin Generation Assay and Its Application in the Clinical Laboratory. Clin. Chem. 2016;62:699–707. doi: 10.1373/clinchem.2015.248625. PubMed DOI

Depasse F., Binder N.B., Mueller J., Wissel T., Schwers S., Germer M., Hermes B., Turecek P.L. Thrombin generation assays are versatile tools in blood coagulation analysis: A review of technical features, and applications from research to laboratory routine. J. Thromb. Haemost. JTH. 2021;19:2907–2917. doi: 10.1111/jth.15529. PubMed DOI PMC

Binder N.B., Depasse F., Mueller J., Wissel T., Schwers S., Germer M., Hermes B., Turecek P.L. Clinical use of thrombin generation assays. J. Thromb. Haemost. JTH. 2021;19:2918–2929. doi: 10.1111/jth.15538. PubMed DOI PMC

Devreese K.M.J., Zuily S., Meroni P.L. Role of antiphospholipid antibodies in the diagnosis of antiphospholipid syndrome. J. Transl. Autoimmun. 2021;4:100134. doi: 10.1016/j.jtauto.2021.100134. PubMed DOI PMC

Fabris M., Giacomello R., Poz A., Pantarotto L., Tanzi N., Curcio F., Tonutti E. 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;5:63–67. doi: 10.1007/s13317-014-0061-3. PubMed DOI PMC

Meroni P.L., Chighizola C.B., Rovelli F., Gerosa M. Antiphospholipid syndrome in 2014: More clinical manifestations, novel pathogenic players and emerging biomarkers. Arthritis Res. Ther. 2014;16:209. doi: 10.1186/ar4549. PubMed DOI PMC

Radin M., Barinotti A., Foddai S.G., Cecchi I., Rubini E., Roccatello D., Menegatti E., Sciascia S. Cerebrovascular events in patients with isolated anti-phosphatidyl-serine/prothrombin antibodies. Immunol. Res. 2021;69:372–377. doi: 10.1007/s12026-021-09208-1. PubMed DOI PMC

Shi H., Zheng H., Yin Y.F., Hu Q.Y., Teng J.L., Sun Y., Liu H.L., Cheng X.B., Ye J.N., Su Y.T., 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;56:614–624. doi: 10.1515/cclm-2017-0502. PubMed DOI

Determining Thrombogenicity: Using a Modified Thrombin Generation Assay to Detect the Level of Thrombotic Event Risk in Lupus Anticoagulant-Positive Patients