A single-center study of patients with rare isolated acquired clotting factor deficiencies other than acquired hemophilia A

Abstract

Background: Isolated acquired clotting factor deficiencies (ACFDs) are mainly caused by the existence of anti-factor antibodies or adsorption of clotting factors onto substances such as amyloid. Besides acquired factor (F)VIII deficiency (acquired hemophilia A), the remaining factor deficiencies are rare and diverse, posing challenges in both diagnosis and management.

Objectives: To describe different features of isolated ACFDs to improve our understanding of these diseases and provide practical recommendations for their management.

Methods: Clinical characteristics of patients with isolated acquired FII, FV, FIX, FX, FXI, FXII, FXIII, and von Willebrand factor deficiencies were collected from a single center between July 1997 and December 2021 and analyzed retrospectively.

Results: A total of 54 rare isolated ACFD patients were enrolled in our study, mainly including 20 acquired FV deficiency patients and 16 acquired FX deficiency patients. The median age at diagnosis of all rare isolated ACFD patients was 55 years. The median time to diagnose all rare isolated ACFD patients was 60 days. Ten (18.5%) rare isolated ACFD patients had no bleeding and 2 (3.7%) rare isolated ACFD patients showed venous thromboembolism. Hemostatic treatment was applied to 41 (41/54; 75.9%) rare isolated ACFD patients. Thirty-seven (68.5%) rare isolated ACFD patients received immunosuppressive therapy, and 10 (18.5%) rare isolated ACFD patients received chemotherapy targeting primary diseases. Twenty-two (61.9%) rare isolated ACFD patients achieved complete remission, and 9 (21.4%) rare isolated ACFD patients died.

Conclusion: Rare isolated ACFDs are underestimated, associated with delayed diagnosis, and lack effective therapy. Clinicians should raise awareness for recognizing and managing rare isolated ACFD patients to avoid morbidity and mortality.

Keywords: acquired clotting factor deficiency; bleeding; diagnosis; immunosuppression; inhibitor.

Figure 1

Laboratory test and bleeding presentations of patients with isolated acquired clotting factor deficiency (ACFD). (A) The number of patients with isolated ACFD who have different factor activity levels. (B) The number of patients with isolated ACFD who had been found with or without neutralizing factor inhibitors. (C) The diverse bleeding presentations of patients with isolated ACFD. (D) The bleeding score (BS) of patients with isolated ACFD. AFIID, acquired factor II deficiency; AFIXD, acquired factor IX deficiency; AFVD, acquired factor V deficiency; AFXD, acquired factor X deficiency; AFXID, acquired factor XI deficiency; AFXIID, acquired factor XII deficiency; AFXIIID, acquired factor XIII deficiency; AVWD, acquired von Willebrand disease