There are about 1.5 individuals per million people that are diagnosed with acquired hemophilia every year. Acquired hemophilia can affect men and women of all ethnicities and backgrounds with equal prevalence, however the risk increases with age and the development of other autoimmune disorders. About 50% of AH cases are caused by an underlying autoimmune condition, while the other 50% have an unknown cause. About ⅓ of individuals diagnosed with AH will not require treatment to control their bleeding, but another ⅓ of individuals will suffer multiple bleeding episodes. There are also about 1-5% of cases of AH reported in women during or following pregnancy (postpartum period) wherein they develop severe bleeding episodes.

The rare disease acquired hemophilia (AH) is caused by the body’s immune system producing autoantibodies that target clotting factors instead of foreign antigens for degradation or destruction. The reduction of properly functioning clotting factors prevents blood from clotting aat crucial damaged sites within the body. Individuals with a reduced efficiency of clotting factor VIII have acquired hemophilia A, while those with reduced efficiency of clotting factor IX have the much more rare form of acquired hemophilia B. About 50% of individuals with AH acquired the disorder due to another autoimmune disorder or immune-triggering event that produced autoantibodies that began targeting their clotting factors. These autoimmune disorders include lupus, rheumatoid arthritis, multiple sclerosis, Sjogren syndrome, temporal arteritis, IBS, ulcerative colitis, infection, diabetes, hepatitis, respiratory or dermatological diseases, blood cancer or certain solid tumors. In some cases, a prescribed therapeutic such as penicillin or interferons have been associated with an individual’s development of acquired hemophilia. Additionally, some women have been diagnosed with AH during pregnancy or postpartum if they develop episodes of severe bleeding with no other known cause.

There are different types and locations that may be affected by acquired hemophilia and thus prone to uncontrolled bleeding. These types of bleeding may include subcutaneous (ecchymoses) as the most common, muscle bleeding (hematoma), gastrointestinal (melena), genitourinary (hematuria), retroperitoneal, intracranial hemorrhage (rare but fatal), and while rare some cases of joint bleeding (hemarthrosis) which is more common in individuals with congenital hemophilia. These symptoms of uncontrolled bleeding may cause compartment syndrome in the soft tissue, pressure exerted on the muscles, nerves, and blood vessels that may cause other complications. Signs of this uncontrolled bleeding that an individual should be aware of are developments of nosebleeds (epistaxis), bruising, solid swelling of congealed blood deposits (hematomas), blood in urine (hematuria), and gastrointestinal or urogenital bleeding.

A clinician may test for acquired hemophilia following initial inspection of an individual with abnormal bleeding, especially if the person is elderly (between 60-80 years old) or a woman in postpartum period. Reports of the signs and symptoms may also prompt testing for a diagnosis of AH. 

The diagnostic tests for acquired hemophilia require determining that the uncontrolled bleeding is due to lack of clotting factor VIII, and that this decrease in clotting factors is due to high levels of autoantibodies targeting FVIII. The following is a list of tests and explanations about how they establish AH and rule out other causes:

1. Coagulation tests aPTT and PT - The measurement of the coagulation time of the blood can be achieved using activated partial thromboplastin time (aPTT) and/or prothrombin time (PT). aPPT is dependent on the proper functioning of factors VIII, IX, XI< and XII and thus tests for AHA, while PT is dependent on factors II, VII, and IX and thus tests for AHB. A 25-35% reduction of factor VIII will cause a noticeable change in aPTT time and is typical of a diagnosis of AHA. 

2. aPTT mixing test - An individual’s blood can be mixed with a sample of a healthy person’s blood that contains the proper clotting factors. If the aPTT time decreases (blood clots faster than patient’s blood alone), then the disorder is due to a lack of coagulation factors and can be corrected with the addition of coagulation factors (congenital hemophilia or other disorder). If, however, the coagulation time does not improve, the disorder is due to factor inhibitors actively decreasing the amount of FVIII in the blood (acquired hemophilia).

3. Titer count of factor inhibitors present in the blood determines the overall concentration and severity of the disease

4. Bethesda assay - Developed to determine the amount of VIII autoantibodies in the blood, the Bethesda assay defines a unit of Bethesda unit (BU) that indicates the amount of inhibiting autoantibodies that are needed to destroy 50% of a sample of factor VIII. 

Treatment is highly dependent on the individual case due to the differences between acquired and congenital hemophilia, the scarcity of this disease, and also the different symptoms that may be experienced by the individual. These different symptoms may be due to the possible underlying cause of the acquired disorder, the age of the individual, tolerance and/or allergies to certain treatments, and other factors that must be considered before providing care. The three main goals in treatment strategies for acquired hemophilia are the management of bleeding, the elimination of inhibiting antibodies that target the coagulation factors, and treating any underlying diseases that may have caused the autoimmune response.

1. Bleeding management – Anti-hemorrhagic treatments such as bypassing agents or increased concentration of coagulation factors (often VIII) may be administered at the site of heavy bleeding. Bypassing agents are recombinantly (synthetically) produced factor VII proteins that replace those attacked by autoimmune function, including rFVIIa, NovoSeven® RT, or Sevenfact. Activated prothrombin complex concentrate (aPCC) is a complex composed of clotting factors that are already activated and do not require factor VIII, often depleted in the presence of inhibiting autoantibodies.

2. Elimination of Inhibitors – This is often a form of immunosuppressive therapy aimed to deplete the autoantibodies targeting and destroying coagulation factors. One common treatment combination is corticosteroids with cyclophosphamide, but due to different individuals’ responses to immunosuppressive treatments others are available such as cyclosporine A, azathioprine, vincristine, mycophenolate mofetil, and 2-chlorodeoxyadenosine. Plasmapheresis can also be implemented to replace an individual’s plasma containing autoantibodies with a healthy person’s plasma that contains normal levels of coagulation factors and no autoantibodies.

3. Treatment of other disorders – Rituximab is currently being studied for its efficacy in targeting autoantibodies in individuals with many autoimmune diseases, including acquired hemophilia.

Cases of acquired hemophilia vary in their symptoms and severity from person to person. Often, the prognosis of the individual is also dependent on other factors, such as age of onset, other autoimmune disorders that may have caused the inhibition of coagulation factors, and the affected tissues that are prone to uncontrolled bleeding. Some cases have been reported to improve, such as women experiencing post-partum acquired hemophilia that may go into remission within a few months following their delivery. Additionally, individuals with AH caused by an underlying autoimmune disease can be treated with immunosuppressing agents (IST), with about 60-80% of cases in remission over a period of days to months. These individuals should monitor their symptoms and dosage to prevent reappearance or drug resistance. Individuals on immunosuppressants should also be monitored for signs of infection, a side effect associated with lowering the antibodies capable of responding to foreign agents. Individuals without underlying autoimmune disorders or who do not seek treatment could be subject to severe bleeding episodes and hemorrhaging, which can be life-threatening and fatal if left untreated.

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