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

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.

A Review of Autoimmune Acquired von Willebrand Factor Deficiency in Japan

“…Furthermore, since there is no compartment syndrome, the chance of receiving emergency medical care may be less than that of other AiCFDs. Moreover, 15% (6/40 cases) of cases had no bleeding symptoms, which was approximately half to that of AiFVD 27 and twice that of AiFXD. 28 The average number of bleeding events per patient was 1.6, which was approximately one-half that of AiFVD and nearly the same as AiFXD (2.0 per patient).…”

“…3A), which is also evidently different from other AiCFD. 27,28 Bleeding Sites or Symptoms and Severity…”

Acquired factor V inhibitor with erythema and eosinophilia in a patient with end-stage renal disease

“…3 c) [ 3 ]. Thus, the patient was ‘definitely diagnosed’ with AiFVD in accordance with the diagnostic criteria enacted by the Japanese Ministry of Health, Labor, and Welfare [ 2 , 4 ]. Factor V inhibitor and anti-factor V autoantibodies were not detected on day 73 and 94, likely because of antibody eradication treatment using PSL alone (Fig.…”

“…Further, immunological remission was confirmed on days 73 by the absence of anti-factor V autoantibodies on ELISA and factor V inhibitor. We previously reported that 73% of Japanese patients with AiFVD initially received PSL for antibody eradication, while 13.5% patients received a pulse PSL regimen, with success rates of 74.7% and 70.8%, respectively [ 2 ]. The success rate of PSL alone (85.1%) is higher than that of overall PSL (74.7%).…”

“…Autoimmune factor V deficiency (AiFVD) is a rare bleeding disorder caused by factor V inhibitors and loss of the coagulation factor due to rapid removal of the immune complex with each coagulation factor. In Japan, the reported incidence of AiFVD is 0.04 [ 2 ], and due to its low incidence, its diagnosis is challenging, compared to the diagnosis of acquired hemophilia A.…”