Successful treatment of a noninhibitory antibody‐mediated acquired factor X deficiency in a patient with marginal‐zone lymphoma

Abstract

Key Clinical MessageProlonged clotting times were observed in a patient with spontaneous hemorrhage. Analysis showed severe factor X deficiency due to clearance by a noninhibitory antibody. Lymphadenopathy identified on imaging led to diagnosis of marginal B-cell lymphoma. Treatment of lymphoma with rituximab and chlorambucil resulted in complete disappearance of the bleeding disorder.

Complete remission in a bleeding patient with idiopathic autoimmune factor X deficiency caused by non‐neutralizing anti‐factor X autoantibody

“…Multiple FFP doses usually show little or no effect upon coagulation abnormalities, F10 levels or ongoing bleeding, as was observed in our case. A temporary and partial PT and APTT response to the initial FFP administration was also reported in the first AiF10D case caused by a non‐neutralizing F10 autoantibody . The large FFP doses may provide excessive coagulation factors, resulting in a minimal shortening of the prolonged PT and APTT, but the amount of F10 was not enough to overcome the patient's anti‐F10 autoantibody and increase F10 activity.…”

“…Because non‐neutralizing autoantibodies cannot be detected by functional assays, including cross‐mixing tests and the Bethesda method, patients may be overlooked. Thus, we recommend that physicians conduct immunological antibody detection assays, including crossed immunoelectrophoresis, Western blotting, ELISA (this report) and radioimmunoassay, when they encounter patients with severe AcF10D, especially those without F10 inhibitor.…”

“…Our literature search identified only five reported AiF10D cases in whom both anti‐F10 autoantibodies and F10 inhibitors were identified, indicating that they had neutralizing autoantibodies. However, to date, Meenhuis et al reported the only case of AiF10D caused by a non‐inhibitory (ie, non‐neutralizing) autoantibody. In their report, the F10 antigen level measured by ELISA was only 7% in parallel with extremely low F10 activity (3%‐4%), as was also observed in our patient.…”

Successful Treatment of Life-threatening Bleeding Caused by Acquired Factor X Deficiency Associated with Respiratory Infection

“…Among autoantibodies for coagulation factors, it is assumed that in addition to neutralizing antibodies that bind the functional regions, non-neutralizing antibodies that bind nonfunctional regions also promote clearance (13,14). To our knowledge, only two cases of AFXD in which non-neutralizing antibody was demonstrated have ever been reported (8,9). Neutralizing antibodies were not detected via the functional Bethesda assay in either of those cases.…”

“…AFXD develops in approximately 10% of patients with systemic light-chain amyloidosis, and in such cases, it is probably caused by absorption of FX by amyloid fibrils (2)(3)(4). In contrast, AFXD without amyloidosis is extremely rare, and only a small number of cases have been described in the literature (5)(6)(7)(8)(9)(10)(11). In the majority of cases AFXD is presumed to be caused by autoimmunity towards FX, and a specific FX inhibitor has been identified in some cases (5,8).…”