International Journal of Hematology

, Volume 109, Issue 2, pp 214–220 | Cite as

A high titer of acquired factor V inhibitor in a hemodialysis patient who developed arterial thrombosis

  • Hina Ogawa
  • Masayoshi Souri
  • Kazunori Kanouchi
  • Tsukasa Osaki
  • Rie Ohkubo
  • Tomoko Kawanishi
  • Sachiko Wakai
  • Keita Morikane
  • Akitada IchinoseEmail author
Case Report


An 87-year-old man with diabetes mellitus was admitted to control recurrent bleeding from hemodialysis puncture sites. He was a smoker and had been diagnosed with arteriosclerosis obliterans. His PT and APTT were markedly prolonged, and all coagulation factors were markedly decreased (factor V [FV] activity < 1%) or below the measurement threshold, with the exception of fibrinogen and factor XIII. Neither PT nor APTT were corrected upon mixing with normal plasma. A high titer of FV inhibitor was found at 415 BU/mL, and anti-FV autoantibody was detected by both immunoblot assay and ELISA. Prednisolone administration and plasma exchange partially improved prolonged PT and APTT and decreased the FV inhibitor level. Five months later, he manifested symptoms of severe ischemia in both legs. Angiography revealed diffuse stenosis downstream of both common iliac arteries. Endovascular therapy was repeated four times, the prednisolone dose was reduced, and low-dose antiplatelet therapy was initiated. After the final successful endovascular therapy, arterial thrombosis was detected using ultrasound and angiography. Aspiration thrombectomy and thrombolytic therapy failed to achieve recanalization, and necrosis of the legs worsened. Despite the severe coagulation abnormalities, vascular interventions should have been performed with regular-dose antiplatelet therapy, as the patient exhibited multiple risk factors for atherothrombosis.


Anti-factor V autoantibody Bleeding/hemorrhage Thrombosis False multiple factor deficiencies False multiple factor inhibitors 



This study was supported in part by research aids from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Japanese Ministry of Health, Labor and Welfare (MHLW), and a research gran from Japan Agency for Medical Research and Development (AMED). We would like to thank all members of ‘Japanese Collaborative Research Group (JCRG) on Autoimmune Coagulation Factor Deficiencies’ and Ms. Yuriko Shibue and Ms. Eiko Ichinose for their cooperation in conducting a nation-wide survey in Japan from 2009 to 2018.

Author contributions

HO carried out clinical studies and drafted the manuscript, MS, KK and TO performed experimental laboratory examinations and analyzed the results, SO, TK, and SW collected clinical data, KM reviewed the project and the manuscript, and AI designed the project and experiments, analyzed the results and wrote the manuscript. All authors have approved the submitted version.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interests in association with this study.

Supplementary material

12185_2018_2561_MOESM1_ESM.docx (100 kb)
Supplementary material 1 (DOCX 100 KB)


  1. 1.
    Boggio LN, Green D. Acquired hemophilia. Rev Clin Exp Hematol. 2001;5:389–404.CrossRefGoogle Scholar
  2. 2.
    Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, et al. 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.CrossRefGoogle Scholar
  3. 3.
    Favaloro EJ. Posen J. Ramakrishna R. Solatani S. McRae S. Just S, et al. Factor V inhibitors: rare or not so uncommon? A multi-laboratory investigation. Blood Coagul Fibrinolysis. 2004;8:637–47.CrossRefGoogle Scholar
  4. 4.
    Ang A. Kuperan P. Ng C. Ng HJ. Acquired factor V inhibitor. A problem-based systematic review. J Thromb Haemost. 2009;101:852–9.CrossRefGoogle Scholar
  5. 5.
    Olson NJ, Ornstein DL. Factor V, Inhibitors. A diagnostic and therapeutic challenge. Arch Pathol Lab Med. 2017;141:1728–31.CrossRefGoogle Scholar
  6. 6.
    Ortel TL. Clinical and laboratory manifestations of anti-factor V antibodies. J Lab Clin Med. 1999;133:326–34.CrossRefGoogle Scholar
  7. 7.
    Knobl P, Lechner K. Acquired factor V inhibitors. Baillières Clin Haematol. 1998;11:305–8.CrossRefGoogle Scholar
  8. 8.
    Ortel TL, Moore KD, Quinn-Allen MA, Okamura T, Sinclair AJ, Lazarchick J, et al. Inhibitory anti-factor V antibodies bind to the factor V C2 domain and are associated with hemorrhagic manifestations. Blood. 1998;91:4188–96.Google Scholar
  9. 9.
    Kadohira Y, Yamada S, Hayashi T, Morishita E, Asakura H, Ichinose A. A discrepancy between prothrombin time and Normotest (Hepaplastintest) results is useful for diagnosis of acquired factor V inhibitors. Int J Hematol. 2018;108(2):145–50.CrossRefGoogle Scholar
  10. 10.
    Tracy PB, Eide LL, Bowie EJ, Mann KG. Radioimmunoassay of factor V in human plasma and platelets. Blood. 1982;60:59–63.Google Scholar
  11. 11.
    Kapur A, Kelsey PR, Isaacs PE. Factor V inhibitor in thrombosis. Am J Hematol. 1993;42:384–8.CrossRefGoogle Scholar
  12. 12.
    Koyama T, Saito T, Kusano T, Hirosawa S. Factor V inhibitor associated with Sjögren’s syndrome. Br J Haematol. 1995;89:893–6.CrossRefGoogle Scholar
  13. 13.
    George S, Nagabhushana MS, Cyran EM. Coagulopathy due to an acquired factor V inhibitor and subsequently thrombosis. Am J Hematol. 1995;49:98–100.CrossRefGoogle Scholar
  14. 14.
    Kamphuisen PW, Haan J, Rosekrans PC, Van Der Meer FJ. Deep-vein thrombosis and coumarin skin necrosis associated with a factor V inhibitor with lupus-like features. Am J Hematol. 1998;57:176–8.CrossRefGoogle Scholar
  15. 15.
    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.CrossRefGoogle Scholar
  16. 16.
    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.CrossRefGoogle Scholar
  17. 17.
    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.CrossRefGoogle Scholar
  18. 18.
    Gavva C, Yates SG, Rambally S, Sarode R. Transfusion management of factor V deficiency: three case reports and review of the literature. Transfusion. 2016;56:1745–9.CrossRefGoogle Scholar
  19. 19.
    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.CrossRefGoogle Scholar
  20. 20.
    Dahlbäck B. Novel insights into the regulation of coagulation by factor V isoforms, tissue factor pathway inhibitorα, and protein S. J Thromb Haemost. 2017;15:1241–50.CrossRefGoogle Scholar
  21. 21.
    Kalafatis M, Simioni P, Tormene D, Beck DO, Luni S, Girolami A. Isolation and characterization of an antifactor V antibody causing activated protein C resistance from a patient with severe thrombotic manifestations. Blood. 2002;99:3985–92.CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Hina Ogawa
    • 1
  • Masayoshi Souri
    • 2
    • 3
    • 5
  • Kazunori Kanouchi
    • 2
    • 4
  • Tsukasa Osaki
    • 2
    • 3
    • 5
  • Rie Ohkubo
    • 1
  • Tomoko Kawanishi
    • 1
  • Sachiko Wakai
    • 1
  • Keita Morikane
    • 2
    • 4
  • Akitada Ichinose
    • 2
    • 3
    Email author
  1. 1.Department of NephrologyOhkubo HospitalTokyoJapan
  2. 2.Japanese Collaborative Research Group on Autoimmune Coagulation Factor Deficiencies (JCRG supported by the Japanese Ministry of Health, Labor and Welfare)YamagataJapan
  3. 3.Department of Molecular Patho-Biochemistry and Patho-BiologyYamagata University School of MedicineYamagataJapan
  4. 4.Department of Clinical Laboratory MedicineYamagata University School of MedicineYamagataJapan
  5. 5.Department of Public HealthYamagata University School of MedicineYamagataJapan

Personalised recommendations