Clinically significant autoantibodies to coagulation factor deficiencies are uncommon but can produce life-threatening bleeding episodes and death. The most commonly targeted coagulation factor in autoimmunity is factor VIII. Acquired hemophilia A, which results from these antibodies, can be either idiopathic or associated with older age, other autoimmune disorders, malignancy, the postpartum period, or a drug reaction. Treatment options to prevent or stop bleeding in acquired hemophilia A include factor VIII–bypassing agents, anti-inhibitor coagulant complex and recombinant factor VIIa, and recombinant porcine factor VIII. The underlying autoimmune disorder frequently responds to immunosuppressive medication. Antiprothrombin antibodies usually are found in patients with antiphospholipid antibody syndrome and can be associated with bleeding. Antibodies of von Willebrand factor are found in patients with type 3 von Willebrand disease in response to infusion of von Willebrand factor. Antibodies to factor V can occur as autoantibodies or as cross-reacting anti-bovine factor V antibodies that develop after exposure to bovine thrombin products that are contaminated with factor V. Pathogenic autoantibodies also have been described that target thrombin, factor IX, factor XI, factor XIII, protein C, protein S and the endothelial cell protein C receptor.
Acronyms and Abbreviations
aPTT, activated partial thromboplastin time; BU, Bethesda unit; DAMPs, damage associated molecular patterns; IU, international unit; MZ, marginal zone; PAMPS, pathogen associated molecular patterns.
Antibodies directed against coagulation factors can develop as an acquired, autoimmune phenomenon. These “circulating anticoagulants” or “inhibitors” were recognized as early as 1906 as a cause of an acquired bleeding disorder.1 The key feature that distinguishes antibody mediated from other acquired coagulation factor deficiencies, such as impaired synthesis (eg, as a result of vitamin K deficiency) or increased consumption (eg, in disseminated intravascular coagulation), is the inability of normal plasma to correct the coagulation defect of the patient’s plasma.
The most common coagulation factor targeted in autoimmunity is factor VIII, producing a condition called acquired hemophilia A. Factor VIII is the most commonly targeted coagulation factor in autoimmunity, which is remarkable because factor VIII circulates at lower concentrations than the other coagulation factors. Inhibitory anti–factor VIII antibodies also can develop after factor VIII infusions in patients with congenital hemophilia A (Chap. 122). The identification of a bleeding patient with hemophilia-like plasma coagulation defect secondary to a circulating anticoagulant was described by Lozner and colleagues in 1940.2 This condition became known as acquired hemophilia and the circulating anticoagulant subsequently was identified as an antibody.
The incidence of acquired hemophilia A is 1.5 cases per million people per year.3 Although acquired hemophilia A is rare, results from several large series and registries have been published, allowing a comprehensive picture of the clinical characteristics and demographics of the disorder.4–10 Approximately 50% of patients with acquired hemophilia A have underlying ...