Advertisement

Rheumatology International

, Volume 39, Issue 10, pp 1811–1819 | Cite as

Lupus anticoagulant-hypoprothrombinemia syndrome and immunoglobulin-A vasculitis: a report of Japanese sibling cases and review of the literature

  • Kaori Fujiwara
  • Junya Shimizu
  • Hirokazu Tsukahara
  • Akira ShimadaEmail author
Cases with a Message
  • 56 Downloads

Abstract

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare bleeding disorder caused by antiprothrombin antibodies. LAHPS is associated with systemic lupus erythematosus (SLE) or infections. We describe two Japanese brothers with immunoglobulin-A vasculitis (IgAV) who met the diagnostic criteria of LAHPS. They presented with palpable purpura and abdominal pain, and had a prolonged activated partial thromboplastin time (APTT) and prothrombin deficiency with the presence of lupus anticoagulant. Pediatric LAHPS was reviewed in abstracts from the Japan Medical Abstracts Society that were written in Japanese and PubMed or Web of Science-listed articles in English between 1996 and 2019. Including our cases, pediatric LAHPS has been reported in 40 Japanese and 46 non-Japanese patients. We summarized the clinical and laboratory characteristics of all 86 cases, and found only one Japanese LAHPS case with IgAV, except for our cases. Of the 86 cases, most were associated with infections followed by SLE. The presence of SLE, older age, lower prothrombin levels, severe bleeding symptoms, and positivity of immunoglobulin G anticardiolipin antibodies and anticardiolipin/β2-glycoprotein I antibodies and/or β2-glycoprotein I-dependent anticardiolipin antibodies had higher odds of requiring treatment. Measuring the APTT and prothrombin time (PT) might be required in patients with IgAV when they do not have a typical clinical course or distinctive symptoms. LAHPS should be considered with prolongation of the APTT and/or PT. Additionally, it is important to maintain a balance between the risk of thrombosis and hemorrhage when normalization of the PT and FII levels occurs in LAHPS cases under treatment.

Keywords

Immunoglobulin-A vasculitis Henoch–Schönlein purpura Lupus anticoagulant-hypoprothrombinemia syndrome Hypoprothrombinemia Japanese Pediatric 

Notes

Acknowledgements

We thank Ellen Knapp, PhD, from Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (include name of committee + reference number) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from parents of the patients for publication.

Supplementary material

296_2019_4404_MOESM1_ESM.pptx (121 kb)
Supplementary material 1 (PPTX 121 kb)

References

  1. 1.
    Male C, Lechner K, Eichinger S, Kyrle PA, Kapiotis S, Wank H, Kaider A, Pabinger I (1999) Clinical significance of lupus anticoagulants in children. J Pediatr 134:199–205CrossRefGoogle Scholar
  2. 2.
    Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306CrossRefGoogle Scholar
  3. 3.
    Bajaj SP, Rapaport SI, Fierer DS, Herbst KD, Schwartz DB (1983) A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome. Blood 61:684–692Google Scholar
  4. 4.
    Mazodier K, Arnaud L, Mathian A, Costedoat-Chalumeau N, Haroche J, Frances C, Harlé JR, Pernod G, Lespessailles E, Gaudin P, Charlanne H, Hachulla E, Niaudet P, Piette JC, Amoura Z (2012) Lupus anticoagulant-hypoprothrombinemia syndrome: report of 8 cases and review of the literature. Medicine (Baltimore) 91:251–260CrossRefGoogle Scholar
  5. 5.
    Rapaport SI, Ames SB, Duvall BJ (1960) A plasma coagulation defect in systemic lupus erythematosus arising from hypoprothrombinemia combined with antiprothrombinase activity. Blood 15:212–227Google Scholar
  6. 6.
    González LM, Janniger CK, Schwartz RA (2009) Pediatric Henoch–Schönlein purpura. Int J Dermatol 2009(48):1157–1165CrossRefGoogle Scholar
  7. 7.
    Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, Al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A (2010) EULAR/PRINTO/PRES criteria for Henoch–Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Ann Rheum Dis 69:798–806CrossRefGoogle Scholar
  8. 8.
    Shimizu T, Ishiguro A, Takayanagi T, Matsui T, Tonegawa N, Maekawa T, Itabashi K (2014) A case of lupus anticoagulant hypoprothrombinemia syndrome following adenovirus gastroenteritis and mycoplasma pneumonia. Nihon Rinsho Meneki Gakkai Kaishi 37:55–60 (Japanese) CrossRefGoogle Scholar
  9. 9.
    Mizumoto H, Maihara T, Hiejima E, Shiota M, Hata A, Seto S, Atsumi T, Koike T, Hata D (2006) Transient antiphospholipid antibodies associated with acute infections in children: a report of three cases and a review of the literature. Eur J Pediatr 165:484–488CrossRefGoogle Scholar
  10. 10.
    Morinaga S, Ide Y, Kusumoto M, Ogata M, Takaki K, Matsumoto E (2012) Lupus anticoagulant-hypoprothrombinemia syndrome with a false-positive test for coagulation factor inhibitors. Rinsho Ketsueki 53:716–720 (Japanese) Google Scholar
  11. 11.
    Amiral J, Aronis S, Adamtziki E, Garoufi A, Karpathios T (1997) Association of lupus anticoagulant with transient antibodies to prothrombin in a patient with hypoprothrombinemia. Thromb Res 86:73–78CrossRefGoogle Scholar
  12. 12.
    Anderson AK, Mohan U, Liesner R (2003) Transient lupus anticoagulant: an unusual cause of bruising in children. Emerg Med J 20:E6CrossRefGoogle Scholar
  13. 13.
    Appert-Flory A, Fischer F, Amiral J, Monpoux F (2010) Lupus anticoagulant -hypoprothombinemia syndrome (HLAS): report of one case in familial infectious context. Thromb Res 126:e139–e140.  https://doi.org/10.1016/j.thromres.2009.11.025 CrossRefGoogle Scholar
  14. 14.
    Baca V, Montiel G, Meillón L, Pizzuto J, Catalán T, Juan-Shum L, Nieva B (2002) Diagnosis of lupus anticoagulant in the lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature. Am J Hematol 71:200–207CrossRefGoogle Scholar
  15. 15.
    Becton DL, Stine KC (1997) Transient lupus anticoagulants associated with hemorrhage rather than thrombosis: the hemorrhagic lupus anticoagulant syndrome. J Pediatr 130:998–1000CrossRefGoogle Scholar
  16. 16.
    Carvalho C, Viveiro C, Maia P, Rezende T (2013) Acquired antiprothrombin antibodies: an unusual cause of bleeding. BMJ Case Rep.  https://doi.org/10.1136/bcr-2012-007948 Google Scholar
  17. 17.
    Cȏté HC, Huntsman DG, Wu J, Wadsworth LD, MacGillivray RT (1997) A new method for characterization and epitope determination of a lupus anticoagulant-associated neutralizing antiprothrombin antibody. Am J Clin Pathol 107:197–205CrossRefGoogle Scholar
  18. 18.
    Davey AL, Foxton SJ, Bala P, Richards M, Cuthbert A (2007) Bruising: when it is spontaneous and not idiopathic thrombocytopenia purpura. J Paediatr Child Health 43:310–311CrossRefGoogle Scholar
  19. 19.
    Foord A, Baca N, Buchbinder D, Mahajerin A (2017) Lupus anticoagulant hypoprothrombinemia syndrome associated with severe thrombocytopenia in a child. Pediatr Blood Cancer 64:e26357.  https://doi.org/10.1002/pbc.26357 CrossRefGoogle Scholar
  20. 20.
    Grau E, Real E, Pastor E, Ivorra J, Quecedo E (1997) Prothrombin deficiency and hemorrhage associated with a lupus anticoagulant. Am J Hematol 54:85CrossRefGoogle Scholar
  21. 21.
    Hudson N, Duffy CM, Rauch J, Paquin JD, Esdaile JM (1997) Catastrophic haemorrhage in a case of paedatric primary antiphospholipid syndrome and factor II deficiency. Lupus 6:68–71CrossRefGoogle Scholar
  22. 22.
    Indolfi G, Poggi GM, Regoli M, Bartolini E, Nesi A, Resti M (2013) A coeliac child presenting with bleeding. Acta Paediatr 102:e191–e192.  https://doi.org/10.1111/apa.12171 CrossRefGoogle Scholar
  23. 23.
    Kim JS, Kim MJ, Bae EY, Jeong DC (2014) Pulmonary hemorrhage in pediatric lupus anticoagulant hypoprothrombinemia syndrome. Korean J Pediatr 57:202–205CrossRefGoogle Scholar
  24. 24.
    Knobe K, Tedgård U, Ek T, Sandström PE, Hillarp A (2012) Lupus anticoagulants in two children-bleeding due to nonphospholipid-dependent antiprothrombin antibodies. Eur J Pediatr 171:1383–1387CrossRefGoogle Scholar
  25. 25.
    Lee MT, Nardi MA, Hadzi-Nesic J, Karpatkin M (1996) Transient hemorrhagic diathesis associated with an inhibitor of prothrombin with lupus anticoagulant in a 1 1/2-year-old girl: report of a case and review of the literature. Am J Hematol 51:307–314CrossRefGoogle Scholar
  26. 26.
    Moser KA, Puetz J (2015) Challenging hemostasis scenarios in pediatric patients-two cases studies. Int J Lab Hematol 37(Suppl 1):72–77.  https://doi.org/10.1111/ijlh.12355 CrossRefGoogle Scholar
  27. 27.
    Mulliez SM, De Keyser F, Verbist C, Vantilborgh A, Wijns W, Beukinga I, Devreese KM (2015) Lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature. Lupus 24:736–745CrossRefGoogle Scholar
  28. 28.
    Sarker T, Roy S, Hollon W, Raipurkar M (2015) Lupus anticoagulant hypoprothrombinemia syndrome in childhood: two distinct patterns and review of the literature. Haemophilia 21:754–760CrossRefGoogle Scholar
  29. 29.
    Schmugge M, Tȏlle S, Marbet GA, Laroche P, Meili EO (2001) Gingival bleeding, epistaxis and haematoma three days after gastroenteritis: the haemorrhagic lupus anticoagulant syndrome. Eur J Pediatr 160:43–46CrossRefGoogle Scholar
  30. 30.
    Sreedharanunni S, Ahluwalia J, Kumar N, Bose S, Dhawan R, Malhotra P (2017) Lupus anticoagulant-hypoprothrombinemia syndrome: a rare cause of intracranial bleeding. Blood Coagul Fibrinolysis 28:416–418CrossRefGoogle Scholar
  31. 31.
    Taddio A, Brescia AC, Lepore L, Rose CD (2007) Steady improvement of prothrombin levels after cyclophosphamide therapy in pediatric lupus anticoagulant hypoprothrombinemia syndrome (LAHPS). Clin Rheumatol 26:2167–2169CrossRefGoogle Scholar
  32. 32.
    Yacobovich JR, Uziel Y, Friedman Z, Radnay J, Wolach B (2001) Diffuse muscular haemorrhage as presenting sign of juvenile systemic lupus erythematosus and lupus anticoagulant hypoprothrombinemia syndrome. Rheumatology (Oxford) 40:585–587CrossRefGoogle Scholar
  33. 33.
    AlMoshary M, Alswayyed A, Salamah BB (2019) A case report of lupus anticoagulant hypoprothrombinemia syndrome. Int J Med Dev Countries 3:395–397CrossRefGoogle Scholar
  34. 34.
    Mediwake H, Robertson J, Beggs J, Mason J (2018) Anaphylaxis following human prothrombin complex concentrate in a child with lupus anticoagulant hypoprothrombinemia syndrome: a cautionary tale. TH Open. 02:e25–e27.  https://doi.org/10.1055/s-0038-1624567 CrossRefGoogle Scholar
  35. 35.
    Pilania RK, Suri D, Jindal AK, Kumar N, Sharma A, Sharma P, Guleria S, Rawat A, Ahluwalia J, Singh S (2018) Lupus anticoagulant hypoprothrombinemia syndrome associated with systemic lupus erythematosus in children: report of two cases and systematic review of the literature. Rheum J Pediatr 123(6):937–939Google Scholar
  36. 36.
    Bhowmick R, Agarwal I, Arumugam V, Kumar TS (2018) Lupus anticoagulant-hypoprothrombinemia syndrome. Indian J Pediatr 85:392–393CrossRefGoogle Scholar
  37. 37.
    Cetin Gedik K, Siddique S, Aguiar CL (2018) Rituximab use in pediatric lupus anticoagulant hypoprothrombinemia syndrome—report of three cases and review of the literature. Lupus 27:1190–1197CrossRefGoogle Scholar
  38. 38.
    Jin J, Zehnder JL (2016) Prozone effect in the diagnosis of lupus anticoagulant for the lupus anticoagulant-hypoprothrombinemia syndrome. Am J Clin Pathol 146:262–267CrossRefGoogle Scholar
  39. 39.
    Komvilaisak P, Wisanuyotin S, Jettrisuparb A, Wiangnon S (2017) Lupus anticoagulant-hypoprothrombinemia syndrome (LAC-HPS) in children with systemic lupus erythematosus: report of 3 cases. J Pediatr Hematol Oncol 39:e521–e524.  https://doi.org/10.1097/MPH.0000000000000891 CrossRefGoogle Scholar
  40. 40.
    Moellman JJ, Bernstein JA, Lindsell C, Banerji A, Busse PJ, Camargo CA Jr, Collins SP, Craig TJ, Lumry WR, Nowak R, Pines JM, Raja AS, Riedl M, Ward MJ, Zuraw BL, Diercks D, Hiestand B, Campbell RL, Schneider S, Sinert R, American College of Allergy, Asthma & Immunology (ACAAI); Society for Academic Emergency Medicine (SAEM) (2014) A consensus parameter for the evaluation and management of angioedema in the emergency department. Acad Emerg Med 21:469–484CrossRefGoogle Scholar
  41. 41.
    Chen O, Zhu XB, Ren P, Wang YB, Sun RP, Wei DE (2013) Henoch Schonlein Purpura in children: clinical analysis of 120 cases. Afr Health Sci 13:94–99Google Scholar
  42. 42.
    Saulsbury FT (1999) Henoch–Schönlein purpura in children. Report of 100 patients and review of the literature. Medicine (Baltimore) 78:395–409CrossRefGoogle Scholar
  43. 43.
    Kamitsuji H, Tani K, Yasui M, Taniguchi A, Taira K, Tsukada S, Iida Y, Kanki H, Fukui H (1987) Activity of blood coagulation factor XIII as a prognostic indicator in patients with Henoch–Schönlein purpura. Efficacy of factor XIII substitution. Eur J Pediatr 146:519–523CrossRefGoogle Scholar
  44. 44.
    Lin Q, Min Y, Li Y, Zhu Y, Song X, Xu Q, Wang L, Cheng J, Feng Q, Li X (2012) Henoch–Schönlein purpura with hypocomplementemia. Pediatr Nephrol 27:801–806CrossRefGoogle Scholar
  45. 45.
    Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR (2002) Incidence of Henoch–Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet 360:1197–1202CrossRefGoogle Scholar
  46. 46.
    Chiu HY, Muo CH, Sung FC (2018) Associations of chronic urticaria with atopic and autoimmune comorbidities: a nationwide population-based study. Int J Dermatol 57:822–829CrossRefGoogle Scholar
  47. 47.
    Hočevar A, Rotar Ž, Žigon P, Čučnik S, Ostrovršnik J, Tomšič M (2018) Antiphospholipid antibodies in adult IgA vasculitis: observational study. Clin RheumatolGoogle Scholar
  48. 48.
    Yang YH, Huang MT, Lin SC, Lin YT, Tsai MJ, Chiang BL (2000) Increased transforming growth factor-beta (TGF-β)-secreting T cells and IgA anti-cardiolipin antibody levels during acute stage of childhood Henoch–Schönlein purpura. Clin Exp Immunol 122:285–290CrossRefGoogle Scholar
  49. 49.
    Kawakami T, Yamazaki M, Mizoguchi M, Soma Y (2008) High titer of serum antiphospholipid antibody levels in adult Henoch–Schönlein purpura and cutaneous leukocytoclastic angiitis. Arthritis Rheum 59:561–567CrossRefGoogle Scholar
  50. 50.
    Vinet E, Rich E, Senécal JL (2006) Thromboembolism complicating the treatment of lupus anticoagulant hypoprothrombinemia syndrome. J Rheumatol 33:2088–2090Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PediatricsOkayama University HospitalOkayamaJapan
  2. 2.Department of Pediatric Hematology/OncologyOkayama University HospitalOkayamaJapan
  3. 3.Department of PediatricsNational Hospital Organization Okayama Medical CenterOkayamaJapan

Personalised recommendations