Exploration of Immunology

From: Generation and pathogenicity of autoantibodies associated to thrombosis and hemostasis

Table 2. Major reported autoantibodies, inducing bleeding complications, and their laboratory interference

Targeted autoantigen	Clinical context	Biological effect	Interference in laboratory assays
PT	Bleeding, bruise, peripheral thrombosis	Accelerated FII clearance, inhibition of coagulation cascade	LA, apparent FII, V, VII, IX, X, XI, XII deficiencies
FV	Severe bleeding (ultra-rare; association with antibiotics)	Decreased FV activity, coagulation cascade inhibition	LA, apparent FV, VII, IX, X, XI, XII deficiencies
FVII	Asymptomatic to severe bleeding (ultra-rare)	FVII inhibition	Prolonged PT, FVII deficiency
FVIII	Severe recurrent hemorrhages (frequent in hemophilia A)	FVIII inhibition	Prolonged APTT and mixing tests, FVIII deficiency
FIX	Severe bleeding (can occur in hemophilia B)	FIX inhibition	Prolonged APTT and mixing tests, FIX deficiency
FX	Ultra-rare, bruise	FX inhibition	Prolonged APTT, FX deficiency
FXIII	Delayed bleeding (can be fatal)	Delayed bleeding, intracranial hemorrhages	Decreased FXIII activity, variable FXIII-A antigen
AT	Enhanced AT activity, bleeding tendency	“Heparin-like” behavior enhances AT activity	Prolonged thrombin time
vWF	Severe bleeding	Reduced Plt adhesiveness	Decreased vWF activity (collagen binding)
GP-IIb-IIIa	Thrombocytopenia, bruise, bleeding	ITP	MAIPA assay, Plt count, flow cytometry
GP1b-IX	Thrombocytopenia, bruise, bleeding	ITP	MAIPA assay, Plt count, flow cytometry
GPVI	Bruise, bleeding	ITP	MAIPA assay, Plt count, flow cytometry

Return to article view

APTT: activated partial thromboplastin time; AT: antithrombin; ITP: immune thrombocytopenic purpura; MAIPA: monoclonal antibody-specific immobilization of Plt antigens

Declarations

Author contributions

JA: Conceptualization, Writing—original draft, Writing—review & editing.

Conflicts of interest

JA is consultant for HYPHEN BioMed SAS.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Franchini M, Mannucci PM. Inhibitors of propagation of coagulation (factors VIII, IX and XI): a review of current therapeutic practice. Br J Clin Pharmacol. 2011;72:553–62. [DOI] [PubMed] [PMC]

Chang HH, Chiang BL. The diagnosis and classification of autoimmune coagulopathy: an updated review. Autoimmun Rev. 2014;13:587–90. [DOI] [PubMed]

Favaloro EJ, Pasalic L, Lippi G. Autoimmune diseases affecting hemostasis: a narrative review. Int J Mol Sci. 2022;23:14715. [DOI] [PubMed] [PMC]

Mingot-Castellano ME, Rodríguez-Martorell FJ, Nuñez-Vázquez RJ, Marco P. Acquired haemophilia a: a review of what we know. J Blood Med. 2022;13:691–710. [DOI] [PubMed] [PMC]

Amiral J. Immunomodulation, autoimmunity and haemostatic dysfunctions. Transfus Sci. 1997;18:361–5. [DOI] [PubMed]

Takei M, Kitamura N, Nagasawa Y, Tsuzuki H, Iwata M, Nagatsuka Y, et al. Are viral infections key inducers of autoimmune diseases? Focus on Epstein–Barr virus. Viruses. 2022;14:1900. [DOI] [PubMed] [PMC]

Olsen NJ. Drug-induced autoimmunity. Best Pract Res Clin Rheumatol. 2004;18:677–88. [DOI] [PubMed]

Puel A, Bastard P, Bustamante J, Casanova JL. Human autoantibodies underlying infectious diseases. J Exp Med. 2022;219:e20211387. [DOI] [PubMed] [PMC]

Aliyath A, Eni-Olotu A, Donaldson N, Trivedi P. Malignancy-associated immune responses: lessons from human inborn errors of immunity. Immunology. 2023;170:319–33. [DOI] [PubMed]

10.

von Boehmer H. Self recognition by the immune system. Eur J Biochem. 1990;194:693–8. [DOI] [PubMed]

11.

Schlee M, Hartmann G. Discriminating self from non-self in nucleic acid sensing. Nat Rev Immunol. 2016;16:566–80. [DOI] [PubMed] [PMC]

12.

Apcher S, Vojtesek B, Fahraeus R. In search of the cell biology for self- versus non-self- recognition. Curr Opin Immunol. 2023;83:102334. [DOI] [PubMed]

13.

Chayoua W, Nicolson PLR, Meijers JCM, Kardeby C, Garcia-Quintanilla L, Devreese KMJ, et al. Antiprothrombin antibodies induce platelet activation: a possible explanation for anti-FXa therapy failure in patients with antiphospholipid syndrome? J Thromb Haemost. 2021;19:1776–82. [DOI] [PubMed] [PMC]

14.

Borrell M, Tirado I, Mateo J, Oliver A, Santamaría A, Fontcuberta J. IgM anti-protein S antibodies as a risk factor for venous thrombosis. Haematologica. 2008;93:1115–7. [DOI] [PubMed]

15.

Rossetto V, Spiezia L, Franz F, Salmaso L, Pozza LV, Gavasso S, et al. The role of antiphospholipid antibodies toward the protein C/protein S system in venous thromboembolic disease. Am J Hematol. 2009;84:594–6. [DOI] [PubMed]

16.

Yasuda S, Atsumi T, Ieko M, Koike T. β₂-Glycoprotein I, anti-β₂-glycoprotein I, and fibrinolysis. Thromb Res. 2004;114:461–5. [DOI] [PubMed]

17.

Liu Q, Miao H, Li S, Zhang P, Gerber GF, Follmann D, et al. Anti-PF4 antibodies associated with disease severity in COVID-19. Proc Natl Acad Sci U S A. 2022;119:e2213361119. [DOI] [PubMed] [PMC]

18.

Knight JS, Kanthi Y. Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome. Semin Immunopathol. 2022;44:347–62. [DOI] [PubMed] [PMC]

19.

Yatim KM, Lakkis FG. A brief journey through the immune system. Clin J Am Soc Nephrol. 2015;10:1274–81. [DOI] [PubMed] [PMC]

20.

Xiao ZX, Miller JS, Zheng SG. An updated advance of autoantibodies in autoimmune diseases. Autoimmun Rev. 2021;20:102743. [DOI] [PubMed]

21.

Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015;278:369–95. [DOI] [PubMed]

22.

Poole BD, Scofield RH, Harley JB, James JA. Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus. Autoimmunity. 2006;39:63–70. [DOI] [PubMed]

23.

Rojas M, Restrepo-Jiménez P, Monsalve DM, Pacheco Y, Acosta-Ampudia Y, Ramírez-Santana C, et al. Molecular mimicry and autoimmunity. J Autoimmun. 2018;95:100–23. [DOI] [PubMed]

24.

Rodriguez-Perez AI, Labandeira CM, Pedrosa MA, Valenzuela R, Suarez-Quintanilla JA, Cortes-Ayaso M, et al. Autoantibodies against ACE2 and angiotensin type-1 receptors increase severity of COVID-19. J Autoimmun. 2021;122:102683. [DOI] [PubMed] [PMC]

25.

Casciola-Rosen L, Thiemann DR, Andrade F, Trejo-Zambrano MI, Leonard EK, Spangler JB, et al. IgM anti-ACE2 autoantibodies in severe COVID-19 activate complement and perturb vascular endothelial function. JCI Insight. 2022;7:e158362. [DOI] [PubMed] [PMC]

26.

Amiral J, Busch MH, Timmermans SAMEG, Reutelingsperger CP, van Paassen P. Development of IgG, IgM, and IgA autoantibodies against angiotensin converting enzyme 2 in patients with COVID-19. J Appl Lab Med. 2022;7:382–6. [DOI] [PubMed]

27.

Amiral J, Seghatchian J. Autoimmune complications of COVID-19 and potential consequences for long-lasting disease syndromes. Transfus Apher Sci. 2023;62:103625. [DOI] [PubMed] [PMC]

28.

Fudala R, Krupa A, Matthay MA, Allen TC, Kurdowska AK. Anti-IL-8 autoantibody:IL-8 immune complexes suppress spontaneous apoptosis of neutrophils. Am J Physiol Lung Cell Mol Physiol. 2007;293:L364–74. [DOI] [PubMed]

29.

Nielsen CH, Bendtzen K. Immunoregulation by naturally occurring and disease-associated autoantibodies. Adv Exp Med Biol. 2012;750:116–32. [DOI] [PubMed] [PMC]

30.

Shih HP, Ding JY, Yeh CF, Chi CY, Ku CL. Anti-interferon-γ autoantibody-associated immunodeficiency. Curr Opin Immunol. 2021;72:206–14. [DOI] [PubMed]

31.

Quiros-Roldan E, Sottini A, Signorini SG, Serana F, Tiecco G, Imberti L. Autoantibodies to interferons in infectious diseases. Viruses. 2023;15:1215. [DOI] [PubMed] [PMC]

32.

Berndt MC, Castaldi PA. Drug-mediated thrombocytopenia. Blood Rev. 1987;1:111–8. [DOI] [PubMed]

33.

Amiral J, Meyer D. 12 Heparin-induced thrombocytopenia: diagnostic tests and biological mechanisms. Baillieres Clin Haematol. 1998;11:447–60. [DOI] [PubMed]

34.

Vayne C, Guéry EA, Rollin J, Baglo T, Petermann R, Gruel Y. Pathophysiology and diagnosis of drug-induced immune thrombocytopenia. J Clin Med. 2020;9:2212. [DOI] [PubMed] [PMC]

35.

Amiral J. Antigens involved in heparin-induced thrombocytopenia. Semin Hematol. 1999;36:7–11. [PubMed]

36.

Chong BH, Du XP, Berndt MC, Horn S, Chesterman CN. Characterization of the binding domains on platelet glycoproteins Ib-IX and IIb/IIIa complexes for the quinine/quinidine-dependent antibodies. Blood. 1991;77:2190–9. [DOI] [PubMed]

37.

Chang A, Kowalewska J, Smith KD, Nicosia RF, Alpers CE. A clinicopathologic study of thrombotic microangiopathy in the setting of IgA nephropathy. Clin Nephrol. 2006;66:397–404. [DOI] [PubMed]

38.

Qi F, Li D, Zhang Z. The kinetics of chemokine autoantibodies in COVID-19. Nat Immunol. 2023;24:567–9. [DOI] [PubMed]

39.

Gwynne PJ, Clendenen LH, Turk SP, Marques AR, Hu LT. Antiphospholipid autoantibodies in Lyme disease arise after scavenging of host phospholipids by Borrelia burgdorferi. J Clin Invest. 2022;132:e152506. [DOI] [PubMed] [PMC]

40.

Amiral J, Peynaud-Debayle E, Wolf M, Bridey F, Vissac AM, Meyer D. Generation of antibodies to heparin-PF4 complexes without thrombocytopenia in patients treated with unfractionated or low-molecular-weight heparin. Am J Hematol. 1996;52:90–5. [DOI] [PubMed]

41.

Amiral J, Wolf M, Fischer A, Boyer-Neumann C, Vissac A, Meyer D. Pathogenicity of IgA and/or IgM antibodies to heparin–PF4 complexes in patients with heparin-induced thrombocytopenia. Br J Haematol. 1996;92:954–9. [DOI] [PubMed]

42.

Greinacher A, Kohlmann T, Strobel U, Sheppard JA, Warkentin TE. The temporal profile of the anti-PF4/heparin immune response. Blood. 2009;113:4970–6. [DOI] [PubMed]

43.

Martirosyan A, Aminov R, Manukyan G. Environmental triggers of autoreactive responses: induction of antiphospholipid antibody formation. Front Immunol. 2019;10:1609. [DOI] [PubMed] [PMC]

44.

Pender MP. Infection of autoreactive B lymphocytes with EBV, causing chronic autoimmune diseases. Trends Immunol. 2003;24:584–8. [DOI] [PubMed]

45.

Bach JF. Infections and autoimmune diseases. J Autoimmun. 2005;25:74–80. [DOI] [PubMed]

46.

Franchini M, Veneri D. Acquired coagulation inhibitor-associated bleeding disorders: an update. Hematology. 2005;10:443–9. [DOI] [PubMed]

47.

Lleo A, Invernizzi P, Gao B, Podda M, Gershwin ME. Definition of human autoimmunity – autoantibodies versus autoimmune disease. Autoimmun Rev. 2010;9:A259–66. [DOI] [PubMed]

48.

Kizilocak H, Young G. Diagnosis and treatment of hemophilia. Clin Adv Hematol Oncol. 2019;17:344–51. [PubMed]

49.

Linari S, Castaman G. Concomitant use of rFVIIa and emicizumab in people with hemophilia A with inhibitors: current perspectives and emerging clinical evidence. Ther Clin Risk Manag. 2020;16:461–9. [DOI] [PubMed] [PMC]

50.

Peyvandi F, Kavakli K, El-Beshlawy A, Rangarajan S. Management of haemophilia A with inhibitors: a regional cross-talk. Haemophilia. 2022;28:950–61. [DOI] [PubMed] [PMC]

51.

Zanon E. Acquired hemophilia A: an update on the etiopathogenesis, diagnosis, and treatment. Diagnostics (Basel). 2023;13:420. [DOI] [PubMed] [PMC]

52.

López-Jaime FJ, Benítez O, Díaz Jordán BL, Montaño A, Coll J, Quintana París L, et al. Expert opinion paper on the treatment of hemophilia A with emicizumab. Hematology. 2023;28:2166334. [DOI] [PubMed]

53.

Galanakis DK, Henschen-Edman A, Weisel J, Spitzer S. Antifibrinogen IgG, fibrinogen, and Clq complexes circulating in a hypodysfibrinogenemic proband. Ann N Y Acad Sci. 2001;936:611–6. [DOI] [PubMed]

54.

Amengual O, Atsumi T, Koike T. Antiprothombin antibodies and the diagnosis of antiphospholipid syndrome. Clin Immunol. 2004;112:144–9. [DOI] [PubMed]

55.

Souri M, Osaki T, Shimura Y, Ichikawa S, Mori M, Ogawa Y, et al. Identification of non-neutralizing anti-factor X autoantibodies in three Japanese cases of autoimmune acquired factor X deficiency. Haemophilia. 2023;29:555–63. [DOI] [PubMed]

56.

Mulliez SM, Devreese KM. Isolated acquired factor VII deficiency: review of the literature. Acta Clin Belg. 2016;71:63–70. [DOI] [PubMed]

57.

Hoffmann C, Amiral J, Rezig S, Kerspern H, Jantzem H, Robin S, et al. A very potent factor V inhibitor interferes with the levels of all coagulation factors and causes a fatal hemorrhagic syndrome. Eur J Haematol. 2019;103:137–9. [DOI] [PubMed]

58.

Goulenok T, Vasco C, Faille D, Ajzenberg N, De Raucourt E, Dupont A, et al.; RAVI study group. Acquired factor V inhibitor: a nation-wide study of 38 patients. Br J Haematol. 2021;192:892–9. [DOI] [PubMed]

59.

Nitu-Whalley IC, Lee CA. Acquired von Willebrand syndrome – report of 10 cases and review of the literature. Haemophilia. 1999;5:318–26. [DOI] [PubMed]

60.

Michiels JJ, Budde U, van der Planken M, van Vliet HH, Schroyens W, Berneman Z. Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management. Best Pract Res Clin Haematol. 2001;14:401–36. [DOI] [PubMed]

61.

Muszbek L, Pénzes K, Katona É. Auto- and alloantibodies against factor XIII: laboratory diagnosis and clinical consequences. J Thromb Haemost. 2018;16:822–32. [DOI] [PubMed]

62.

Ichinose A, Osaki T, Souri M. Pathological coagulation parameters in as many as 54 patients with autoimmune acquired factor XIII deficiency due to anti–factor XIII autoantibodies. Haemophilia. 2021;27:454–62. [DOI] [PubMed]

63.

Berruyer M, Amiral J, Ffrench P, Belleville J, Bastien O, Clerc J, et al. Immunization by bovine thrombin used with fibrin glue during cardiovascular operations. Development of thrombin and factor V inhibitors. J Thorac Cardiovasc Surg. 1993;105:892–7. [DOI] [PubMed]

64.

Ortel TL, Charles LA, Keller FG, Marcom PK, Oldham HN Jr, Kane WH, et al. Topical thrombin and acquired coagulation factor inhibitors: clinical spectrum and laboratory diagnosis. Am J Hematol. 1994;45:128–35. [DOI] [PubMed]

65.

Martínez-Martínez I, González-Porras JR, Cebeira MJ, de Arriba F, Espín S, Bohdan N, et al. Identification of a new potential mechanism responsible for severe bleeding in myeloma: immunoglobulins bind the heparin binding domain of antithrombin activating this endogenous anticoagulant. Haematologica. 2016;101:e423–6. [DOI] [PubMed] [PMC]

66.

Baglin TP, Langdown J, Frasson R, Huntington JA. Discovery and characterization of an antibody directed against exosite I of thrombin. J Thromb Haemost. 2016;14:137–42. [DOI] [PubMed]

67.

Davidson SJ, Burman JF, Nicholson AG, Jones DW, Dusmet ME. Factor XII auto-antibodies present in a patient with a B-cell lymphoma. Blood Coagul Fibrinolysis. 2005;16:365–7. [DOI] [PubMed]

68.

Salomon O, Zivelin A, Livnat T, Seligsohn U. Inhibitors to factor XI in patients with severe factor XI deficiency. Semin Hematol. 2006;43:S10–2. [DOI] [PubMed]

69.

Elsheikh S, Tidbury N, Lip GYH. A review of emerging factor XI inhibitors. Expert Opin Emerg Drugs. 2023;28:43–53. [DOI] [PubMed]

70.

Winkelhorst D, Oepkes D. Foetal and neonatal alloimmune thrombocytopenia. Best Pract Res Clin Obstet Gynaecol. 2019;58:15–27. [DOI] [PubMed]

71.

Porcelijn L, Schmidt DE, Oldert G, Hofstede-van Egmond S, Kapur R, Zwaginga JJ, et al. Evolution and utility of antiplatelet autoantibody testing in patients with immune thrombocytopenia. Transfus Med Rev. 2020;34:258–69. [DOI] [PubMed]

72.

Davidson A, Diamond B. Autoimmune diseases. N Engl J Med. 2001;345:340–50. [DOI] [PubMed]

73.

Legendre P, Régent A, Thiebault M, Mouthon L. Anti-endothelial cell antibodies in vasculitis: a systematic review. Autoimmun Rev. 2017;16:146–53. [DOI] [PubMed]

74.

Audia S, Mahévas M, Nivet M, Ouandji S, Ciudad M, Bonnotte B. Immune thrombocytopenia: recent advances in pathogenesis and treatments. Hemasphere. 2021;5:e574. [DOI] [PubMed] [PMC]

75.

Carmi O, Berla M, Shoenfeld Y, Levy Y. Diagnosis and management of catastrophic antiphospholipid syndrome. Expert Rev Hematol. 2017;10:365–74. [DOI] [PubMed]

76.

Cervera R. Antiphospholipid syndrome. Thromb Res. 2017;151:S43–7. [DOI] [PubMed]

77.

Cervera R, Rodríguez-Pintó I, Espinosa G. The diagnosis and clinical management of the catastrophic antiphospholipid syndrome: a comprehensive review. J Autoimmun. 2018;92:1–11. [DOI] [PubMed]

78.

de Groot PG, Oosting JD, Derksen RH. 8 Antiphospholipid antibodies: specificity and pathophysiology. Baillieres Clin Haematol. 1993;6:691–709. [DOI] [PubMed]

79.

Gris JC, Amadio C, Mercier E, Lavigne-Lissalde G, Déchaud H, Hoffet M, et al. Anti-protein Z antibodies in women with pathologic pregnancies. Blood. 2003;101:4850–2. [DOI] [PubMed]

80.

Amiral J, Aronis S, Adamtziki E, Garoufi A, Karpathios T. Association of lupus anticoagulant with transient antibodies to prothrombin in a patient with hypoprothrombinemia. Thromb Res. 1997;86:73–8. [DOI] [PubMed]

81.

de Groot PG, Horbach DA, Simmelink MJ, van Oort E, Derksen RH. Anti-prothrombin antibodies and their relation with thrombosis and lupus anticoagulant. Lupus. 1998;7:S32–6. [DOI] [PubMed]

82.

Galli M, Barbui T. Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome. Blood. 1999;93:2149–57. [DOI] [PubMed]

83.

Atsumi T, Koike T. Clinical relevance of antiprothrombin antibodies. Autoimmun Rev. 2002;1:49–53. [DOI] [PubMed]

84.

Bertolaccini ML. Antibodies to prothrombin. Lupus. 2012;21:729–31. [DOI] [PubMed]

85.

Bertolaccini ML, Atsumi T, Caliz AR, Amengual O, Khamashta MA, Hughes GR, et al. Association of antiphosphatidylserine/prothrombin autoantibodies with HLA class II genes. Arthritis Rheum. 2000;43:683–8. [DOI] [PubMed]

86.

Luliano A, Galeazzi M, Sebastiani GD. Antiphospholipid syndrome’s genetic and epigenetic aspects. Autoimmun Rev. 2019;18:102352. [DOI] [PubMed]

87.

Amiral J, Legros E, Vivant M, Rossi D, Renaud G. Vaccine induced thrombotic thrombocytopenia: development and reactivity of anti-platelet factor 4 antibodies and immune pathogenic mechanisms. Explor Immunol. 2022;2:604–21. [DOI]

88.

Greinacher A, Warkentin TE. Platelet factor 4 triggers thrombo-inflammation by bridging innate and adaptive immunity. Int J Lab Hematol. 2023;45:11–22. [DOI] [PubMed]

89.

Amiral J, Seghatchian J. An update on evidence based diagnostic and confirmatory testing strategies for heparin induced thrombocytopenia using combined immunological and functional assays. Transfus Apher Sci. 2018;57:804–11. [DOI] [PubMed]

90.

Vissac AM, Amiral J. Mechanisms involved in heparin-induced thrombocytopenia and associated thrombosis. Semin Thromb Hemost. 2008;34:018–26. [DOI]

91.

Amiral J, Vissac AM. Update on mechanisms, pathogenicity, heterogeneity of presentation, and laboratory diagnosis of heparin-induced thrombocytopenia. In: Kelleni M, editor. Anticoagulation drugs. Rijeka: IntechOpen; 2019. pp. 1–20.

92.

O’Brien JR, Etherington MD, Pashley M. Intra-platelet platelet factor 4 (IP.PF4) and the heparin-mobilisable pool of PF4 in health and atherosclerosis. Thromb Haemost. 1984;51:354–7. [DOI] [PubMed]

93.

Lewandowski K, Elikowski W, Turowiecka Z, Zozulińska M, Przybył L, Zawilska K. Low molecular weight heparin and the heparin mobilisable pool of platelet factor 4 are reduced in young survivors of myocardial infarction. Thromb Res. 1996;81:615–22. [DOI] [PubMed]

94.

Amiral J, Baglin TP, Magnani HN, Mikhailidis DP. Consensus overview. Platelets. 1997;8:83. [DOI]

95.

Warkentin TE. HIT paradigms and paradoxes. J Thromb Haemost. 2011;9:105–17. [DOI] [PubMed]

96.

Amiral J, Pouplard C, Vissac AM, Walenga JM, Jeske W, Gruel Y. Affinity purification of heparin-dependent antibodies to platelet factor 4 developed in heparin-induced thrombocytopenia: biological characteristics and effects on platelet activation. Br J Haematol. 2000;109:336–41. [DOI] [PubMed]

97.

Kanack AJ, Bayas A, George G, Abou-Ismail MY, Singh B, Kohlhagen MC, et al. Monoclonal and oligoclonal anti-platelet factor 4 antibodies mediate VITT. Blood. 2022;140:73–7. [DOI] [PubMed] [PMC]

98.

Warkentin TE, Arnold DM, Sheppard JI, Moore JC, Kelton JG, Nazy I. Investigation of anti-PF4 versus anti-PF4/heparin reactivity using fluid-phase enzyme immunoassay for 4 anti-PF4 disorders: classic heparin-induced thrombocytopenia (HIT), autoimmune HIT, vaccine-induced immune thrombotic thrombocytopenia, and spontaneous HIT. J Thromb Haemost. 2023;21:2268–76. [DOI] [PubMed]

99.

Desprez D, Desprez P, Tardy B, Amiral J, Droulle C, Ducassou S, et al. Anti-PF4 antibodies and thrombophlebitis in a child with cerebral venous thrombosis. Ann Biol Clin (Paris). 2010;68:725-8. French. [PubMed]

100.

Wang M, Zhang CM, Ma Y, Tang K, Zhang XY, Jia XZ, et al. Anti-platelet factor 4/heparin antibodies in patients with Hantaan virus infection. Res Pract Thromb Haemost. 2022;6:e12813. [DOI] [PubMed] [PMC]

101.

Amiral J, Marfaing-Koka A, Wolf M, Alessi MC, Tardy B, Boyer-Neumann C, et al. Presence of autoantibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated thrombocytopenia. Blood. 1996;88:410–6. [DOI] [PubMed]

102.

de Maistre E, Regnault V, Lecompte T, Scheid P, Martinet Y, Bellou A, et al. Antibodies to interleukin-8 and paraneoplastic catastrophic recurrent thromboses. Am J Med. 2001;111:580–1. [DOI] [PubMed]

103.

Panzer S, Schiferer A, Steinlechner B, Drouet L, Amiral J. Serological features of antibodies to protamine inducing thrombocytopenia and thrombosis. Clin Chem Lab Med. 2015;53:249–55. [DOI] [PubMed]

104.

Bakchoul T, Zöllner H, Amiral J, Panzer S, Selleng S, Kohlmann T, et al. Anti-protamine-heparin antibodies: incidence, clinical relevance, and pathogenesis. Blood. 2013;121:2821–7. [DOI] [PubMed]

105.

Pouplard C, Leroux D, Rollin J, Amiral J, May MA, Gruel Y. Incidence of antibodies to protamine sulfate/heparin complexes in cardiac surgery patients and impact on platelet activation and clinical outcome. Thromb Haemost. 2013;109:1141–7. [DOI] [PubMed]

106.

Froissart A, Veyradier A, Hié M, Benhamou Y, Coppo P, French Reference Center for Thrombotic Microangiopathies. Rituximab in autoimmune thrombotic thrombocytopenic purpura: a success story. Eur J Intern Med. 2015;26:659–65. [DOI] [PubMed]

107.

Cid J, Pérez-Valencia AI, Torrente MÁ, Ávarez-Larrán A, Díaz-Ricart M, Esteve J, et al. Successful management of three patients with autoimmune thrombotic thrombocytopenic purpura with paradigm-changing therapy: caplacizumab, steroids, plasma exchange, rituximab, and intravenous immunoglobulins (CASPERI). Transfus Apher Sci. 2021;60:103011. [DOI] [PubMed]

108.

Kaul A, Jawad A, Hughes G. Antiphospholipid syndrome, thrombosis and multidisciplinary management. Trends Urol Mens Health. 2023;14:31–5. [DOI]

109.

Zöller B, Li X, Sundquist J, Sundquist K. Autoimmune diseases and venous thromboembolism: a review of the literature. Am J Cardiovasc Dis. 2012;2:171–83. [PubMed] [PMC]

110.

Borjas-Howard JF, Leeuw K, Rutgers A, Meijer K, Tichelaar VYIG. Risk of recurrent venous thromboembolism in autoimmune diseases: a systematic review of the literature. Semin Thromb Hemost. 2019;45:141–9. [DOI] [PubMed]

111.

Bello N, Meyers KJ, Workman J, Marcano Belisario J, Cervera R. Systematic literature review and meta-analysis of venous thromboembolism events in systemic lupus erythematosus. Rheumatol Ther. 2023;10:7–34. [DOI] [PubMed] [PMC]

112.

Amiral J, Peyrafitte M, Dunois C, Vissac AM, Seghatchian J. Anti-phospholipid syndrome: current opinion on mechanisms involved, laboratory characterization and diagnostic aspects. Transfus Apher Sci. 2017;56:612–25. [DOI] [PubMed]

113.

de Groot PG, Derksen RH. Pathophysiology of the antiphospholipid syndrome. J Thromb Haemost. 2005;3:1854–60. [DOI] [PubMed]

114.

Kelchtermans H, Pelkmans L, de Laat B, Devreese KM. IgG/IgM antiphospholipid antibodies present in the classification criteria for the antiphospholipid syndrome: a critical review of their association with thrombosis. J Thromb Haemost. 2016;14:1530–48. [DOI] [PubMed]

115.

Devreese KMJ, de Groot PG, de Laat B, Erkan D, Favaloro EJ, Mackie I, et al. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2020;18:2828–39. [DOI] [PubMed]

116.

Meijide H, Sciascia S, Sanna G, Khamashta MA, Bertolaccini ML. The clinical relevance of IgA anticardiolipin and IgA anti-β2 glycoprotein I antiphospholipid antibodies: a systematic review. Autoimmun Rev. 2013;12:421–5. [DOI] [PubMed]

117.

Merashli M, Alves JD, Gentile F, Ames PRJ. Relevance of antiphospholipid antibodies in multiple sclerosis: a systematic review and meta analysis. Semin Arthritis Rheum. 2017;46:810–8. [DOI] [PubMed]

118.

Kreimann M, Brandt S, Krauel K, Block S, Helm CA, Weitschies W, et al. Binding of anti-platelet factor 4/heparin antibodies depends on the thermodynamics of conformational changes in platelet factor 4. Blood. 2014;124:2442–9. [DOI] [PubMed]

119.

Juhl D, Eichler P, Lubenow N, Strobel U, Wessel A, Greinacher A. Incidence and clinical significance of anti-PF4/heparin antibodies of the IgG, IgM, and IgA class in 755 consecutive patient samples referred for diagnostic testing for heparin-induced thrombocytopenia. Eur J Haematol. 2006;76:420–6. [DOI] [PubMed]

120.

Houen G. Nonspecific binding in immunoassays for autoantibodies. Methods Mol Biol. 2019;1901:13–7. [DOI] [PubMed]

121.

Jacobs JFM, Bossuyt X. Standardization and harmonization of autoimmune diagnostics. Clin Chem Lab Med. 2018;56:1563–7. [DOI] [PubMed]

122.

González-Buitrago JM. Multiplexed testing in the autoimmunity laboratory. Clin Chem Lab Med. 2006;44:1169–74. [DOI] [PubMed]

123.

Hess EV. Environmental chemicals and autoimmune disease: cause and effect. Toxicology. 2002;181–182:65–70. [DOI] [PubMed]

124.

Li M, Zhou Y, Feng G, Su SB. The critical role of Toll-like receptor signaling pathways in the induction and progression of autoimmune diseases. Curr Mol Med. 2009;9:365–74. [DOI] [PubMed]

125.

Zhao CN, Xu Z, Wu GC, Mao YM, Liu LN, Wu Q, et al. Emerging role of air pollution in autoimmune diseases. Autoimmun Rev. 2019;18:607–14. [DOI] [PubMed]

126.

Amiral J, Bouveyron N, Legros E, Kobayashi K. Standardization of HIT diagnostic assays, with K070, a chimeric human-mouse antibody, mimicking heparin dependent pathogenic antibodies. Arch Med Res. 2023;11. [DOI]