A Review of Coagulation Abnormalities of Autoimmune Acquired Factor V Deficiency with a Focus on Japan

Akitada Ichinose; Tsukasa Osaki; Masayoshi Souri

doi:10.1055/s-0041-1740149

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2022; 48(02): 206-218
DOI: 10.1055/s-0041-1740149

Review Article

A Review of Coagulation Abnormalities of Autoimmune Acquired Factor V Deficiency with a Focus on Japan

Akitada Ichinose

¹Department of Molecular Pathobiochemistry and Pathobiology, Yamagata University School of Medicine, Yamagata, Japan

²The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan

,

Tsukasa Osaki

¹Department of Molecular Pathobiochemistry and Pathobiology, Yamagata University School of Medicine, Yamagata, Japan

²The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan

³Department of Public Health and Hygiene, Yamagata University Graduate School of Medical Science, Iida-Nishi, Yamagata, Japan

,

Masayoshi Souri

¹Department of Molecular Pathobiochemistry and Pathobiology, Yamagata University School of Medicine, Yamagata, Japan

²The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan

³Department of Public Health and Hygiene, Yamagata University Graduate School of Medical Science, Iida-Nishi, Yamagata, Japan

› Author Affiliations

Abstract

Coagulation factor V (or FV for the purpose of medical safety) is an essential cofactor of coagulation factor X in the common pathway of coagulation; severe FV deficiency leads to a bleeding tendency. Although both congenital and acquired FV deficiencies are widely recognized, FV deficiency also presents as an autoimmune disorder. A nationwide survey on autoimmune coagulation factor deficiencies (AiCFDs) conducted in Japan by our Japanese Collaborative Research Group identified 24 new patients with autoimmune FV deficiency (AiFVD) in the past 5 years. Furthermore, our extensive literature search confirmed that 177 AiFVD cases have been reported in previous articles published from Japan. Patients with AiFVD in Japan were predominantly men, with age similar to those with other AiCFDs. AiFVD was confirmed as a relatively mild type of bleeding diathesis, associated with lower mortality rate than that for AiFVD and other AiCFDs reported in previous studies. Patients with AiFVD had variable FV inhibitor titers and both neutralizing anti-FV autoantibodies and nonneutralizing counterparts. Although spontaneous resolution occurs in some patients, timely initiation of hemostatic and immunosuppressive therapies helps arrest the bleeding and eliminate anti-FV antibodies, resulting in a high cumulative recovery rate. Immunological anti-FV antibody detection is recommended to avoid missing AiFVD cases for the presence of nonneutralizing anti-FV autoantibodies. Further investigation is necessary to clarify the long-term prognosis and optimal management of AiFVD.

Keywords

acquired coagulation factor deficiency - autoantibody - bleeding disorder - factor V - inhibitor - nonneutralizing antibody

Full Text

References

Reference
1 Duckers C, Simioni P, Rosing J, Castoldi E. Advances in understanding the bleeding diathesis in factor V deficiency. Br J Haematol 2009; 146 (01) 17-26
2 Lippi G, Favaloro EJ, Montagnana M, Manzato F, Guidi GC, Franchini M. Inherited and acquired factor V deficiency. Blood Coagul Fibrinolysis 2011; 22 (03) 160-166
3 Olson NJ, Ornstein DL. Factor V inhibitors: a diagnostic and therapeutic Challenge. Arch Pathol Lab Med 2017; 141 (12) 1728-1731
4 Ichinose A. [Diagnosis and treatment of acquired factor XIII/13 deficiencies: for all doctors treating the MHLW's designated intractable diseases]. Rinsho Ketsueki 2015; 56 (10) 2110-2122
5 Ichinose A. The present condition of and clinical guidance for autoimmune coagulation factor deficiencies in Japan. J Thromb Haemost 2018; 29: 251-261
6 Ichinose A. [Immune-mediated acquired coagulation factor deficiencies: state-of-the-art in diagnosis and management]. Rinsho Ketsueki 2019; 60 (06) 667-679
7 Ichinose A, Osaki T, Souri M. Autoimmune coagulation factor X deficiency as a rare acquired hemorrhagic disorder: a literature review. Thromb Haemost 2021; (e-pub ahead of print).
8 Ang AL, Kuperan P, Ng CH, Ng HJ. Acquired factor V inhibitor. A problem-based systematic review. Thromb Haemost 2009; 101 (05) 852-859
9 Franchini M, Lippi G. Acquired factor V inhibitors: a systematic review. J Thromb Thrombolysis 2011; 31 (04) 449-457
10 Ichinose A, Kohler HP, Philippou H. Factor XIII and Fibrinogen SSC Subcommittee of the ISTH. Recommendation for ISTH/SSC Criterion 2015 for autoimmune acquired factor XIII/13 deficiency. Thromb Haemost 2016; 116 (04) 772-774
11 Ogawa H, Souri M, Kanouchi K. et al. A high titer of acquired factor V inhibitor in a hemodialysis patient who developed arterial thrombosis. Int J Hematol 2019; 109 (02) 214-220
12 Akashi N, Ogawa Y, Yanagisawa K. et al. [Recurrence of acquired factor V inhibitor after four years of remission]. Rinsho Ketsueki 2019; 60 (01) 46-50
13 Matsumoto A, Ogawa Y, Osaki T. et al. [Successful management of acquired factor V deficiency developing shortly after induction of hemodialysis]. Rinsho Ketsueki 2020; 61 (05) 445-450
14 Kato T, Hanawa T, Asou M, Asakawa T, 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
15 Ochiai T, Misawa K, Iwao N. et al. Corticobasal degeneration that developed autoimmune factor V/5 deficiency triggered by endoscopic gastrostomy. Jap J Thromb Hemost. 2019; 30: 465 [Abstract]
16 Kaneda H, Fukuno K, Horinoue A, et al. Autoimmune acquired coagulation factor V deficiency with hyperfibrinolytic DIC. J Jap Soc Lab Hematol. 2020;21 Academic Meeting:S226. [Abstract] & Kaneda H, Fukuno K, Horinoue A, et al. Coagulation factor V inhibitor negative, non-neutralizing anti-factor V antibody positive autoimmune acquired factor V deficiency. Jap J Thromb Hemost. 2020;31:255. [Abstract]
17 Katsuren H, Taira H, Niisato Y. et al. A case of end-stage renal disease patient with autoimmune acquired coagulation factor V deficiency. J Soc Dialy Med. 2020; 53 (Suppl. 01) 464
18 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 (11) 1831-1832
19 Knöbl P, Lechner K. Acquired factor V inhibitors. Baillieres Clin Haematol 1998; 11 (02) 305-318
20 Favaloro EJ, Posen J, Ramakrishna R. et al. Factor V inhibitors: rare or not so uncommon? A multi-laboratory investigation. Blood Coagul Fibrinolysis 2004; 15 (08) 637-647
21 Ortel TL. Clinical and laboratory manifestations of anti-factor V antibodies. J Lab Clin Med 1999; 133 (04) 326-334
22 Ichinose A. Autoimmune acquired coagulation factor deficiency (designated intractable disease code 288). Thromb. Med. 2021; 11: 27-38
23 Collins PW, Hirsch S, Baglin TP. 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 (05) 1870-1877
24 Ichinose A. Japanese Collaborative Research Group on AH13. Autoimmune acquired factor XIII deficiency due to anti-factor XIII/13 antibodies: A summary of 93 patients. Blood Rev 2017; 31 (01) 37-45
25 Matsubara F, Nomura H, Okeda T. A case of factor V deficiency that developed in old age. Mutual Aid Med Bulletin 2007; 56 (suppl.): 111[Abstract]
26 Yamaguchi M, Yamamoto A, Yasutomi Y. et al. Experience in treating ingrown toenail in patients with factor V deficiency. Dermatol Clin 2019; 61: 423-426
27 Sato S, Mizutani Y, Osawa M. et al. A case of autoimmune acquired factor V deficiency caused by dabigatran administration. J Jap Soc Lab Hematol 2020; 21: S225
28 Oshiro M, Kawaji Y, Fujino T. et al. A case of drug-induced acquired F5 inhibitors against multiple antiplatelet drugs. Rinsho Ketsueki 2015; 56: 1656
29 Okajima A, Horii M, Nasu Y. et al. [Factor V inhibitor with double cancer]. Rinsho Ketsueki 1989; 30 (04) 514-519
30 Yusa J, Owada K. A case of an 83-year-old man with intractable bleeding tendency. Chiba Med J. 2018; 94: 145-146
31 Peyvandi F, Palla R, Menegatti M. et al; European Network of Rare Bleeding Disorders Group. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost 2012; 10 (04) 615-621
32 Koyama T, Saito T, Kusano T, Hirosawa S. Factor V inhibitor associated with Sjögren's syndrome. Br J Haematol 1995; 89 (04) 893-896
33 Yamanouchi J, Hato K. A case of acquired coagulation factor V inhibitor in which prednisolone was remarkably effective. Journal of Japanese Society for Thrombosis and Hemostasis. 2010; 21: 391-394
34 Okuno S, Kajiguchi T, Ono T. Suzuki. Prednisolone restored acquired factor V inhibitor in a patient with lung tuberculosis. Rinsho Ketsueki 2013; 54: 1467 [Abstract]
35 Goto H, Ikoma Y, Takada E. et al. Clinical analysis of acquired coagulation factor inhibitors including acquired hemophilia. Rinsho Ketsueki 2014; 55: 1625 [Abstract]
36 Yamada T. Coagulation disorders and thrombosis that may be encountered on a daily basis: A patient with factor V inhibitor discovered in the wake of cerebral infarction. Med Exam. 2014; 63 (special issue): 69
37 Suzuki Y, Uemura Y, Nagae C. et al. Acquired factor V inhibitor case with extensive subcutaneous bleeding and deep vein thrombosis of the lower extremities during the course. Jap J Thromb Hemost. 2017; 28: 241 [Abstract]
38 Yanagiya R, Kanouchi K, Toubai T. et al. Plasma exchange as an initial treatment for severe bleeding induced by acquired factor V deficiency: a case report and mini literature review. Acta Haematol 2021; 144 (01) 82-87
39 Matsumoto T, Nogami K, Shima M. Coagulation function and mechanisms in various clinical phenotypes of patients with acquired factor V inhibitors. J Thromb Haemost 2014; 12 (09) 1503-1512
40 Váradi K, Rosing J, Tans G, Schwarz HP. Influence of factor V and factor Va on APC-induced cleavage of human factor VIII. Thromb Haemost 1995; 73 (04) 730-731
41 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 (07) 1241-1250
42 Cramer TJ, Griffin JH, Gale AJ. Factor V is an anticoagulant cofactor for activated protein C during inactivation of factor Va. Pathophysiol Haemost Thromb 2010; 37 (01) 17-23
43 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 (02) 145-150
44 Takagi F, Nakano K, Ito Y, et al. A case of factor V deficiency who underwent endoscopic submucosal dissection for gastric adenoma. Rinsho Ketsueki. 2019;60:1475. [Abstract] & Shinozawa K, Amano K, Kaneko M, et al. An elderly patient with Factor V deficiency who showed coagulation factor deficiency in a cross-mixed study but did not detect a clear etiological gene mutation. Clin Pathol. 2019;67 Suppl.;252. [Abstract]
45 Mihara M, Ogawa Y, Kobayashi N. et al. A case of acquired factor V inhibitor who achieved remission by immunosuppressive therapy. Rinsho Ketsueki 2014; 55: 1626
46 Bingo S, Suzuki T, Shinozawa K. et al. Two cases of acquired factor V inhibitor diagnosed with congenital deficiency in a cross-mixed trial early in the disease. Jap J Thromb Hemost. 2018; 29: 379-388
47 Koga S, Zaizen K, Tagawa K. et al. A case of acquired factor V inhibitor that could be detected early by a cross-mixing test. J Jap Soc Lab Hematol 2016; 17Academic Meeting issue: S148
48 Inai K, Yamaguchi H, Kaito Y. et al. A case of acquired factor V deficiency that was difficult to diagnose due to fresh frozen plasma replacement. Rinsho Ketsueki 2019; 60: 520-521
49 Kawakami T, Takigawa Y, Iwai M. et al. A patient of FV inhibitor associated with colorectal cancer. J Tohoku Hemost Thromb Study Group 2004; XVII: 1-3
50 Endo H, Kawauchi K, Tomimatsu M. et al. Acquired factor V inhibitor responsive to corticosteroids in a patient with double cancers. Intern Med 2007; 46 (09) 621-625
51 Kitazawa A, Misawa H, Nagahori K. et al. Acquired factor V inhibitors in a patient with end-stage renal disease. Intern Med 2016; 55 (23) 3505-3509
52 Hachinohe M, Okura Y, Fujinami K. et al. A case of maintenance dialysis patient showing abnormal coagulation due to low titer factor V inhibitor. Med Exam. 2011; 60: 531 [Abstract]
53 Cortier D, Van Dreden P, Adam M, Bironien R, François D, Vasse M. Transient Factor V deficiency associated with Factor V-immunoglobulin complexes but without evidence of a classical inhibitor. Thromb Res 2016; 147: 10-12
54 Wada H, Yada K, Nakanishi H. et al. Successful management of severe intraperitoneal hemorrhage by platelet transfusion in a patient with acquired factor V inhibitor. Kawasaki Med J. 2003; 29: 81-87
55 Tomisaka T, Hanaoka N, Mine A. et al. Acquired factor V inhibitor with severe bleeding successfully treated with high-dose steroid therapy and platelet transfusion. J Jap Soc Blood Transf Cell Therapy. 2015; 61: 539-545
56 Tracy PB, Eide LL, Bowie EJ, Mann KG. Radioimmunoassay of factor V in human plasma and platelets. Blood 1982; 60 (01) 59-63
57 Sakai M, Amano K, Ogawa Y. et al. Guidelines for the management of acquired hemophilia A: 2017 revision. Jap J Thrombus Hemostasis. 2017; 28: 715-747
58 Yamane T, Hino M, Ota K. et al. [Clinical cases of acquired coagulation inhibitors]. Rinsho Byori 2000; 48 (12) 1093-1101
59 Hashimoto H, Mannoji K, Kuno H. et al. Acquired coagulation factor V inhibitor (FVI) cases with eosinophilia. Rinsho Ketsueki 2013; 54: 237 [Abstract]
60 Yoshimura T, Sakai T, Hosokawa Y, et al. A case of factor V inhibitor whose recurrence was thought to be caused by antibiotic administration. The 626th Annual Meeting of Kanto Region of Jap Soc Intern Med. 2016; 63. [Abstract] & Hyodo M, Udagawa T, Hosokawa Y, et al. A case of hemodialysis patient who recurred acquired factor V inhibitor due to administration of β-lactam antibiotic during treatment of pneumonia and presented with abnormal blood coagulation. J Jap Soc Dialy Therapy 2018;51 Suppl.1:555. [Abstract]
61 Kibe S, Ogino T, Kawamoto M. et al. A case of drug-induced acquired factor V deficiency after surgery for metastatic pancreatic cancer. The 68th Annual Meeting of the Japanese Society of Gastroenterology. P-53–9, 2013
62 Ichinose A. The actual condition of autoimmune coagulation factor deficiency in Japan. J Jap Soc Intern Med. 2017; 106 (suppl.): 183
63 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 (03) 454-462