Acquired hemophilia (AH) is a rare bleeding disorder that develops when the body’s own immune system mistakenly attacks its blood clotting system. Unlike inherited hemophilia, which is a genetic condition present from birth, AH is an acquired, non-genetic condition that typically affects older adults who previously had no bleeding issues. This condition occurs when the immune system develops proteins that neutralize the function of necessary clotting factors, leading to unpredictable and sometimes severe hemorrhage. The onset is often sudden, demanding immediate diagnosis and specialized management to prevent potentially life-threatening bleeding episodes.
The Autoimmune Mechanism
Acquired hemophilia is classified as an autoimmune condition where the body’s immune system produces autoantibodies, commonly called inhibitors, that target healthy proteins. In the vast majority of AH cases, these inhibitors target coagulation Factor VIII (FVIII), a protein fundamental to the blood clotting cascade. Factor VIII normally works with other proteins to form a stable blood clot, but the presence of the inhibitor prevents this process from happening effectively.
The autoantibodies bind directly to the circulating FVIII molecules. This neutralization severely impairs the blood’s capacity to form a clot. The severity of the bleeding disorder correlates directly with the amount of functional Factor VIII remaining in the bloodstream. The body is unable to maintain sufficient levels of the clotting factor needed for normal hemostasis because the immune system continues to produce these inhibitors.
Who is at Risk and Common Symptoms
Acquired hemophilia affects approximately 1.5 people per million each year. It is most often found in the elderly population, with the median age for presentation typically between 60 and 80 years, though it can appear at any age. Unlike inherited hemophilia, which predominantly affects males, AH affects men and women with roughly equal frequency.
AH is frequently associated with pre-existing conditions, including various autoimmune disorders such as lupus or rheumatoid arthritis, certain cancers, and skin diseases. The clinical presentation of AH is notably distinct from the inherited forms, which are known for causing bleeds into the joints. Patients with AH typically present with sudden, extensive bleeding into the skin, muscles, or soft tissues. Bleeding from mucous membranes, such as the gastrointestinal or urinary tracts, is also common and may result in blood found in the urine or stool.
Confirming the Diagnosis
Diagnosis of acquired hemophilia often begins with routine laboratory tests when a patient presents with sudden, unexplained bleeding. A coagulation panel will typically show an isolated prolongation of the activated partial thromboplastin time (aPTT). The prothrombin time (PT) and platelet count, however, remain normal. This pattern of prolonged aPTT with a normal PT strongly suggests a deficiency in an intrinsic clotting factor, like Factor VIII, or the presence of an inhibitor.
The next step is performing a mixing study to distinguish between a factor deficiency and an inhibitor. In this test, the patient’s plasma is mixed with an equal volume of normal plasma, which contains all clotting factors. If the aPTT corrects to normal, it indicates a factor deficiency. If the aPTT remains prolonged, it confirms the presence of an inhibitor, as the autoantibodies neutralized the Factor VIII supplied by the normal plasma.
Two specific assays are performed to measure the level and strength of the inhibitor. A specific Factor VIII activity assay measures the amount of functional FVIII remaining in the patient’s blood. The Bethesda assay, or a similar modification, quantifies the strength of the inhibitor in Bethesda units (BU).
Managing Bleeding and Eradicating Inhibitors
Treatment for acquired hemophilia involves two simultaneous objectives: immediate control of acute bleeding and long-term eradication of the autoantibodies. Acute bleeding episodes are managed using hemostatic agents that bypass the need for functional Factor VIII. These bypassing agents include recombinant Factor VIIa (rFVIIa) or activated prothrombin complex concentrates (APCC). These agents allow bleeding to be controlled even while the inhibitor is still present.
For the ultimate cure, the immune system must be suppressed to stop the production of the FVIII inhibitor. This is achieved through immunosuppressive therapy. First-line eradication therapy typically involves the use of corticosteroids, often combined with a cytotoxic agent such as cyclophosphamide.
If the first-line therapy fails, or for patients with high inhibitor titers, a monoclonal antibody called rituximab may be used. Rituximab targets B-cells, which are responsible for producing the inhibitors. Throughout this eradication phase, doctors monitor Factor VIII activity levels and inhibitor titers to confirm that the autoantibodies have been successfully eliminated and that normal clotting function has been restored.