Approach to the treatment, characterization and diagnosis of an acquired auto‐antibody directed against factors prothrombin, factor X and factor IX: a case report and review of the literature

Abstract

Bleeding disorders secondary to acquired non-inhibitory antibodies directed against vitamin K-dependent coagulation proteins are rare. In this report, the authors describe a patient with a low grade lymphoma who presented with a fatal acquired bleeding manifestation and abnormal hemostatic studies resulting from deficiencies in both prothrombin and factor X. Patient plasma samples were collected and studied for the presence of an acquired inhibitor. Levels of plasma coagulation proteins were measured using immunoassay. Patient anti-prothrombin immunoglobulin G was isolated and binding to prothrombin, prothrombin F1.2, factors IX and X was evaluated using immunoblots and competition immunoassay. Prolongation in the prothrombin time and activated partial thromboplastin time suggested a factor deficiency in the common pathway of coagulation. Functional and antigenic levels of both prothrombin and factor X were decreased. An IgG subtype-4 antibody was isolated from patient plasma using affinity chromatography on prothrombin-sepharose. This antibody was found to bind to a common metal-ion-dependent conformational epitope found on the γ-carboxyglutamic acid (Gla) domain of prothrombin, factor X and factor IX. This report represents the first description of an acquired bleeding disorder resulting from a unique cross-reactive auto-antibody against a common metal-ion-dependent antigenic structure on the Gla-domain of the vitamin K-dependent proteins.