Table Info

Table 3.

Suspicious cases of coexistent LA and ant-FV antibodies [5]

No.	Age (years)	Gender	Underlying conditions	FV:C (%)	FV-inhibitor (BU/mL)	Symptoms	LA	Remarks	Reference
VS-1	92	F	HT, HF, Af, PE, erysipelas, leg infection, and antibiotics	1	496	Extensive hematomas	dRVVT: IM	None	Hoffmann et al. [53]
VS-2	87	M	DM	< 1	415	Recurrent bleeding from the hemodyalysis puncture site	dRVVT: IM	None	Ogawa et al. [54]
VS-3	70	M	Unknown	12.4	NR	Subcutaneous hemorrhage and right thigh hematoma	dRVVT: IM	Positive for aCL	Kato et al. [55]

Normal range: FV:C < 60% and anti-FV inhibitor < 1 BU/mL. FV:C: FV activity; HF: heart failure; Af: atrial fibrillation; IM: immeasurable (not clotting); NR: not reported; PE: pulmonary embolism

Supplementary materials

The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/1003103_sup_1.xlsx.

Declarations

Acknowledgments

Thanks are due to Yayoi Ishida of the Health Sciences University of Hokkaido for assistance with this study and Editage (www.editage.com) for the English language editing.

Author contributions

MI: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Funding acquisition, Project administration, Supervision. KO: Data curation, Software. SN: Investigation, Data curation. MY and HS: Investigation. TS and NS: Writing—original draft, Validation. NT: Writing—review & editing, Validation. AI: Writing—review & editing, Funding acquisition, Project administration. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This study was funded in part by a research grant (to Prof. Akitada Ichinose) for the Japanese Nationwide Survey on Autoimmune Coagulation Factor Deficiencies from the Japanese Ministry of Health, Labor and Welfare [21FC1008]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder managed this study and helped write and revise this paper.

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References

Osaki T, Souri M, Ichinose A. Plasma proteomics associated with autoimmune coagulation factor deficiencies reveals the link between inflammation and autoantibody development. Int J Hematol. 2022;115:672–85. [DOI] [PubMed]

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]

Ichinose A, Osaki T, Souri M. A review of coagulation abnormalities of autoimmune acquired factor V deficiency with a focus on Japan. Semin Thromb Hemost. 2022;48:206–18. [DOI] [PubMed]

Ieko M, Yoshida M, Naito S, Ohmura K, Takahashi N. Lupus anticoagulant-hypoprothrombinemia syndrome and similar diseases: experiences at a single center in Japan. Int J Hematol. 2019;110:197–204. [DOI] [PubMed]

Ieko M, Naito S, Yoshida M, Ohmura K, Takahashi N, Sugawara N, et al. Lupus anticoagulant-hypoproaccelerin (factor V) syndrome (LAHPS-V): a new hemorrhagic condition associated with lupus anticoagulant. Int J Hematol. 2022;116:152–4. [DOI] [PubMed]

Jacobs JW, Gisriel SD, Iyer K, Rinder HM. Concomitant factor VIII inhibitor and lupus anticoagulant in an asymptomatic patient. J Thromb Haemost. 2022;53:945–9. [DOI] [PubMed] [PMC]

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;4:295–306. [DOI] [PubMed]

Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, et al. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost. 2009;7:1737–40. [DOI] [PubMed]

Simmons DP, Herskovits AZ, Battinelli EM, Schur PH, Lemire SJ, Dorfman DM. Lupus anticoagulant testing using two parallel methods detects additional cases and predicts persistent positivity. Clin Chem Lab Med. 2018;56:1289–96. [DOI] [PubMed]

10.

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]

11.

Laboratory testing for the lupus anticoagulant; approved guideline [Internet]. Wayne (PA): Clinical and Laboratory Standards Institute; c2014 [cited 2023 Mar 5]. Available from: https://clsi.org/media/1386/h60a_sample.pdf

12.

Devreese KMJ, de Laat B. Mixing studies in lupus anticoagulant testing are required at least in some type of samples. J Thromb Haemost. 2015;13:1475–8. [DOI] [PubMed]

13.

Devreese KMJ. No more mixing tests required for integrated assay systems in the laboratory diagnosis of lupus anticoagulants? J Thromb Haemost. 2010;8:1120–2. [DOI] [PubMed]

14.

Favaloro EJ, Bonar R, Marsden K. Lupus anticoagulant testing – sometimes mixing is required: potential for false negatives without mixing studies. Blood Coagulat Fibrinol. 2013;24:673–6. [DOI] [PubMed]

15.

Favaloro EJ. Coagulatiom mixing studies: utility, algorithmic strategies and limitations for lupus anticoagulant testing or follow up of abnormal coagulation tests. Am J Hematol. 2020;95:117–28. [DOI] [PubMed]

16.

Favaloro E. Mixing studies for lupus anticoagulant: mostly yes, sometimes no. Clin Chem Lab Med. 2020;58:487–91. [DOI] [PubMed]

17.

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;1982–93. [DOI] [PubMed]

18.

Fabris M, Giacomello R, Poz A, Pantarotto L, Tanzi N, Curcio F, 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 Highlight. 2014;5:63–7. [DOI] [PubMed] [PMC]

19.

Triplett DA. Screening for the lupus anticoagulant. Ric Clin Lab. 1989;19:379–89. [DOI] [PubMed]

20.

Bonar R, Favaloro E, Zebeljan D, Rosenfeld D, Kershaw G, Mohammed S, et al. Evaluating laboratory approaches to the identification of lupus anticoagulants: a diagnostic challenge from the RCPA Haematology QAP. Pathology. 2012;44:240–7. [DOI] [PubMed]

21.

Hoxha A, Banzato A, Ruffatti A, Pengo V. Detection of lupus anticoagulant in the era of direct oral anticoagulants. Autoimmun Rev. 2017;16:173–8. [DOI] [PubMed]

22.

Favaloro EJ, Gilmore G, Arunachalam S, Mohammed S, Baker R. Neutralising rivaroxaban induced interference in laboratory testing for lupus anticoagulant (LA): a comparative study using DOAC stop and andexanet alfa. Thromb Res. 2019;180:10–9. [DOI] [PubMed]

23.

Favresse J, Lardinois B, Sabor L, Devalet B, Vandepapeliere J, Braibant M, et al. Evaluation of the DOAC-stop^® procedure to overcome the effect of DOACs on several thrombophilia screening tests. TH Open. 2018;2:e202–9. [DOI] [PubMed] [PMC]

24.

Ratzinger F, Lang M, Belik S, Jilma-Stohlawetz P, Schmetterer KG, Haslacher H, et al. Lupus-anticoagulant testing at NOAC trough levels. Thromb Haemost. 2016;116:235–40. [DOI] [PubMed]

25.

Tripodi A, Mancuso ME, Chantarangkul V, Clerici M, Bader R, Meroni PL, et al. Lupus anticoagulants and their relationship with the inhibitors against coagulation factor VIII: considerations on the differentiation between the 2 circulating anticoagulants. Clin Chem. 2005;51:1883–5. [DOI] [PubMed]

26.

Scully MF, Ellis V, Kakkar VV, Savidge GF, Williams YF, Sterndale H. An acquired coagulation inhibitor to factor II. Br J Haematol. 1982;50:655–64. [DOI] [PubMed]

27.

Wong RS, Lau FY, Cheng G. Successful treatment of acquired hypoprothrombinemia without associated lupus anticoagulant using intravenous immunoglobulin. Haematologica. 2001;86:551. [PubMed]

28.

Mazodier K, Arnaud L, Mathian A, Costedoat-Chalumeau N, Haroche J, Frances C, et al. Lupus anticoagulant-hypoprothrombinemia syndrome: report of 8 cases and review of the literature. Medicine (Baltimore). 2012;91:251–60. [DOI] [PubMed]

29.

Abdi A, Bordbar MR, Hassan S, Rosendaal FR, van der Bom JG, Voorberg J, et al. Prevalence and incidence of non-neutralizing antibodies in congenital hemophilia A— a systematic review and meta-analysis. Front Immunol. 2020;11:563. [DOI] [PubMed] [PMC]

30.

Male C, Lechner K, Eichinger S, Kyrle PA, Kapiotis S, Wank H, et al. Clinical significance of lupus anticoagulants in children. J Pediatr. 1999;134:199–205. [DOI] [PubMed]

31.

Jin J, Zehnder JL. Prozone effect in the diagnosis of lupus anticoagulant for the lupus anticoagulant-hypoprothrombinemia syndrome. Am J Clin Pathol. 2016;146:262–7. [DOI] [PubMed]

32.

Huang JN, Koerper MA. Factor V deficiency: a concise review. Haemophilia. 2008;14:1164–9. [DOI] [PubMed]

33.

Boland F, Shreenivas AV. Acquired factor V inhibitors: a review of literature. Ann Hematol Oncol. 2017;4:1168.

34.

Nakata K, Ueda S, Matsunaga H, Mima F, Ueda H, Yoshioka A, et al. High titer of acquired factor V Inhibitor presenting with a pseudo-deficiency of multiple coagulation factors. Intern Med. 2018;57:393–7. [DOI] [PubMed] [PMC]

35.

Chartier AR, Hillert CJ, Gill H, Jha P. Acquired factor V inhibitor after antibiotic therapy: a clinical case report and review of the literature. Cureus. 2020;12:e9481. [DOI] [PubMed] [PMC]

36.

Franchini M, Lippi G. Acquired factor V inhibitors: a systematic review. J Thromb Thrombolysis. 2011;31:449–57. [DOI] [PubMed]

37.

Tessier-Marteau A, Croquefer S, Meziani F, Cau S, Asfar P, Macchi L. Acquired factor V inhibitor in a context of sepsis and disseminated intravascular coagulation. Am J Hematol. 2010;85:145–6. [DOI] [PubMed]

38.

Yamada Y, Miyakawa Y, Sawano M, Okano Y. Successful treatment of severe lung hemorrhage caused by acquired factor V inhibitor with rituximab. Intern Med. 2014;53:1083–5. [DOI] [PubMed]

39.

Aljohani NI, Matthews JH. Acquired factor V inhibitor in a patient with mantle cell lymphoma presenting with hematuria followed by thrombosis: a case report. Int Med Case Rep J. 2014;7:27–30. [DOI] [PubMed] [PMC]

40.

Guglielmone H, Jarchum G, Minoldo S. Successful treatment with intravenous immunoglobulin (IVIg) in a patient with an acquired factor V inhibitor after liver transplantation. Thromb Haemost. 2011;106:985–6. [DOI] [PubMed]

41.

Higuchi T, Okamoto T, Kou T, Takeuchi T, Koyamada R, Okada S. Deep vein thrombosis associated with factor V inhibitor followed by immune thrombocytopenia. Ann Hematol. 2012;91:1831–2. [DOI] [PubMed]

42.

Kapur A, Kelsey PR, Isaacs PE. Factor V inhibitor in thrombosis. Am J Hematol. 1993;42:384–8. [DOI] [PubMed]

43.

Mima F, Minami R, Asako M, Matsunaga H, Fujita Y, Takimoto Y, et al. Acquired factor V inhibitor complicated with immune thrombocytopenia. Intern Med. 2022;61:91–5. [DOI] [PubMed] [PMC]

44.

Ieko M, Ohmura K, Naito S, Yoshida M, Saito M, Kiyohara K, et al. Measurement of coagulation factor antibody levels is useful for diagnosis and determining therapeutic efficacy in hemorrhagic patients with autoantibodies to coagulation factor VIII and factor V: results from a single center in Japan. Int J Hematol. 2022;115:11–20. [DOI] [PubMed]

45.

Kamphuisen PW, Haan J, Rosekrans PC, Van Der Meer FJM. Deep-vein thrombosis and coumarin skin necrosis associated with a factor V inhibitor with lupus-like features. Am J Hematol. 1998;57:176–8. [DOI] [PubMed]

46.

Van den Berg SAA, Verwer PE, Idema RN, Van Guldener C. Transient cefuroxime/metronidazole treatment induced factor V antibodies. BMI Case Rep. 2014;2014:bcr2014205523. [DOI] [PubMed] [PMC]

47.

Donohoe K, Levine R. Acquired factor V inhibitor after exposure to topical human thrombin related to an otorhinolaryngological procedure. J Thromb Haemost. 2015;13:1787–9. [DOI] [PubMed]

48.

Rief P, Hackl G, Hafner F, Raggam RB, Wölfler A, Brodmann M, et al. Venous thromboembolism in a patient with persistent inhibitor to coagulation factor V - a case report. Clin Chem Lab Med. 2016;54:e269–71. [DOI] [PubMed]

49.

Sridharan M, Fylling KA, Ashrani AA, Chen D, Marshall AL, Hook CC, et al. Clinical and laboratory diagnosis of autoimmune factor V inhibitors: a single institutional experience. Thromb Res. 2018;171:14–21. [DOI] [PubMed]

50.

Olson NJ, Robert D, Hedayat AA, Liu X, Ornstein DL. Fatal hemorrhage due to a spontaneous factor V inhibitor with lupus anticoagulant properties. Blood Coagul Fibrinolysis. 2017;28:407–10. [DOI] [PubMed]

51.

Yokota Y, Inatomi O, Nakagawa M, Kakuda K, Hiroe K, Sakai S, et al. Acquired coagulation factor V inhibitor that was successfully treated with oral corticosteroid therapy. Intern Med. 2021;60:2663–6. [DOI] [PubMed] [PMC]

52.

Favaloro EJ, Posen J, Ramakrishna R, Soltani S, McRae S, Just S, et al. Factor V inhibitors: rare or not so uncommon? A multi-laboratory investigation. Blood Coagul Fibrinolysis. 2004;15:637–47. [DOI] [PubMed]

53.

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]

54.

Ogawa H, Souri M, Kanouchi K, Osaki T, Ohkubo R, Kawanishi T, et al. A high titer of acquired factor V inhibitor in a hemodialysis patient who developed arterial thrombosis. Int J Hematol. 2019;109;214–20. [DOI] [PubMed]

55.

Kato T, Hanawa T, Asou M, Sakamaki H, Araki M. Autoimmune factor V deficiency that took 16 years to diagnose due to pseudodeficiency of multiple coagulation factors. Case Rep Med. 2021;2021:4657501. [DOI] [PubMed] [PMC]

56.

Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, et al. UK Haemophilia Centre Doctors’ Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors’ Organisation. Blood. 2007;109:1870–7. [DOI] [PubMed]

57.

Baudo F, Collins P, Huth-Kühne A, Lévesque H, Marco P, Nemes L, et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood. 2012;120:39–46. [DOI] [PubMed]

58.

Kessler CM, Nemers L. Acquired inhibitors to factor VIII. In: Rodringuez EC, Lee CA, editors. Inhibitors in patients with haemophilia. Oxford: Blackwell Publishing; 2002. pp. 98–112.

59.

Hay CR, Baglin TP, Collins PW, Hill FG, Keeling DM. The diagnosis and management of factor VIII and IX inhibitors: a guideline from the UK Haemophilia Centre Doctors’ Organization (UKHCDO). Br J Haematol. 2000;111:78–90. [PubMed]

60.

Collins PW, Chalmers E, Hart DP, Liesner R, Rangarajan S, Talks K, et al. Diagnosis and treatment of factor VIII and IX inhibitors in congenital haemophilia: (4th edition). Br J Haematol. 2013;160:153–70. [DOI] [PubMed]

61.

Ballard HS, Nyamuswa G. Life-threatening haemorrhage in a patient with rheumatoid arthritis and a lupus anticoagulant coexisting with acquired autoantibodies against factor VIII. Br J Rheumatol. 1993;32:515–7. [DOI] [PubMed]

62.

Biron C, Durand L, Lemkecher T, Dauverchain J, Meunier L, Meynadier J, et al. Simultaneous occurrence of lupus anticoagulant, factor VIII inhibitor and localized pemphigoid. Am J Hematol. 1996;51:250–1. [DOI] [PubMed]

63.

Großmann R, Wankmüller H, Schwender S, Krischner J, Mansouri-Taleghani B, Keller P, et al. The diagnosis and therapy of acquired factor-VIII inhibitors in combination with lupus anticoagulants. Dtsch Med Wochenschr. 1996;121:906–10. German. [DOI] [PubMed]

64.

Ghirarduzzi A, Silingardi M, D’Incà M, Tincani E. The antiphospholipid syndrome during chronic lymphatic leukemia. An association with anti-factor VIII antibodies. Ann Ital Med Int. 1999;14:46–50. Italian. [PubMed]

65.

Saxena R, Mishra DK, Kashyap R, Choudhry VP, Mahapatra M, Bhargava M. Acquired haemophilia – a study of ten cases. Haemophilia. 2000;6:78–83. [DOI] [PubMed]

66.

Liozon E, Loustaud V, Jauberteau MO, Jaccard A, Soria P, Bordessoule D, et al. Non-simultaneous malignant lymphoma and antiphospholipid syndrome: 4 cases. Rev Med Interne. 2001;22:360–70. French. [DOI] [PubMed]

67.

Brings HA, Waas JK, McCrae KR, Baele HR, Goldstone J. Successful management of life-threatening hemorrhage in a patient with synchronous lupus anticoagulant and factor VIII inhibitor. J Vasc Surg. 2002;36:853–5. [DOI] [PubMed]

68.

Wullen B, Mühlhöfer A, Luz H, Zoller WG. Acquired hemophilia A after an early abortion. Dtsch Med Wochenschr. 2002;127:1075–8. German. [DOI] [PubMed]

69.

Taher A, Abiad R, Uthman I. Coexistence of lupus anticoagulant and acquired haemophilia in a patient with monoclonal gammopathy of unknown significance. Lupus. 2003;12:854–6. [DOI] [PubMed]

70.

Dreisbach JD, Dreisbach LP, Young DE, Dreisbach PB. Acquired factor VIII inhibitor and lupus anticoagulant presenting with prolonged aPTT: a case report. Grand Rounds. 2010;10:19–24.

71.

Spencer A, Pearce MI, Ames PR. Sequential thrombosis and bleeding in a woman with a prolonged activated partial thromboplastin time. Thromb J. 2011;9:16. [DOI] [PubMed] [PMC]

72.

Seethala S, Collins NP, Comerci G. An unusual etiology for elevation of activated partial thromboplastin time (aPTT) in SLE: acquired hemophilia and lupus anticoagulant. Case Rep Hematol. 2013;2013:521785. [DOI] [PubMed] [PMC]

73.

Gupta D, Chatterjee T, Sharma A, Ganguli P, Das S, Sharma S. Rare case of acquired haemophilia and lupus anticoagulant. Indian J Hematol Blood Transfus. 2014;30:197–200. [DOI] [PubMed] [PMC]