Last updated:
1/13/2026
Years published: 2026
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for the preparation of this report.
Summary
Acquired hemophilia B is a very rare autoimmune disorder characterized by bleeding that occurs in people with no personal or family history of diseases related to blood-clotting (coagulation) problems.
In acquired hemophilia B, the body produces antibodies (known as inhibitors) that attack clotting factor IX, a protein needed for normal blood clotting.1,2 Autoimmune disorders occur when the body’s immune system mistakenly attacks healthy cells or tissue.
Acquired hemophilia B is associated with autoimmune diseases, certain cancers (malignancies), and some infections such as hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV).3
Symptoms include abnormal, uncontrolled bleeding that can occur spontaneously during surgery, or following trauma. The condition can potentially cause life-threatening bleeding complications in severe cases.1, 4
Treatment is individualized and focuses on stopping the bleeding and eliminating the autoantibodies.
Introduction
Acquired hemophilia B is distinct from both acquired hemophilia A and congenital hemophilia B.
While acquired hemophilia A involves autoantibodies against factor VIII and represents most of the acquired hemophilia cases, acquired hemophilia B involves autoantibodies specifically against factor IX.
Congenital hemophilia B is a genetic disorder caused by changes (variants) in the F9 gene, which provides instructions for making clotting factor IX. Congenital hemophilia B primarily affects males, as it is inherited in an X-linked recessive pattern.
Although both acquired and congenital hemophilia B involve deficiency of the same clotting factor (factor IX), the acquired form develops later in life due to autoimmune processes rather than genetic inheritance.1, 2, 5 This condition is far rarer than acquired hemophilia A, with only a few cases reported in the medical literature.
The symptoms of acquired hemophilia B develop because the blood cannot clot properly due to autoantibodies blocking the normal activity of factor IX. It is characterized by bleeding problems that can range from mild to life-threatening.1-4
Bleeding often occurs without cause (spontaneously) or following minor trauma. Common signs and symptoms include: 3, 6
Bleeding episodes can become life-threatening if not promptly recognized and treated.3, 6 In some people, delayed diagnosis and the presence of additional medical issues make the condition worse.
Because acquired hemophilia B is so rare there is not enough data that allow to have all the information about the signs and symptoms that can occur among the affected people with this condition. Affected individuals are at significant risk of excessive bleeding during surgery or following trauma.1, 4
The course of the condition varies widely, ranging from mild conditions to life-threatening bleeds. Bleeding is limited mainly to the mucosa, skin or muscle; by contrast, bleeding caused by hereditary hemophilia B tends to mainly involve the joints.3
Acquired hemophilia B is an autoimmune disorder that occurs when the immune system produces antibodies that mistakenly attack factor IX, a specialized clotting protein. 1, 2
The immune system normally protects the body by producing specialized proteins called antibodies in response to foreign substances. When antibodies mistakenly target the body’s own healthy tissues, they are known as autoantibodies. In acquired hemophilia B, these autoantibodies are called inhibitors because they block the normal function of clotting factor IX. Researchers believe that a triggering event, such as an infection or an underlying medical condition, may cause the immune system to produce these autoantibodies. 1, 4
About half of cases of acquired hemophilia B may be associated with underlying conditions including autoimmune disorders, malignancies, infections such as hepatitis B (HBV), hepatitis C (HCV) and acquired immunodeficiency syndrome (AIDS) viruses, or drug exposures, while the remaining cases are idiopathic (no identifiable cause). However, specific data on associated conditions in acquired hemophilia B are extremely limited due to the rarity of this disorder.1, 3, 4, 6
Hemostasis is the body’s natural process for stopping bleeding. Blood clotting is a complex, step-by-step process involving many proteins working together. When a blood vessel is injured, the body quickly recognizes the damage and starts a series of steps to prevent too much blood loss. When there is an injury, substances at the injury site signal that clotting is needed. Next, small blood cells called platelets gather and stick together to form an initial plug. Finally, a chain reaction known as the coagulation cascade occurs, in which clotting proteins work together to strengthen the clot and seal the injury. For example, factor VIII and factor IX work together to support clot formation, and problems with either of these factors can lead to bleeding disorders such as hemophilia. Additional proteins help strengthen clots and later break them down once healing has occurred. Factor X and prothrombin (factor II) help produce thrombin, an enzyme that plays a key role in clot formation. Thrombin then converts fibrinogen (factor I) into fibrin, which forms the strong mesh that holds the clot together.
At the same time, the body has other controls to prevent excessive clotting. Normal blood flow helps wash away activated clotting proteins, and the lining of blood vessels releases substances, such as nitric oxide and prostacyclin, that reduce platelet activity. Other protective proteins, including proteins C and S, antithrombin, and plasmin, help slow down or break down clots once they are no longer needed.³
Acquired coagulation inhibitors are antibodies that develop in the bloodstream and interfere with normal blood clotting. Antibodies are immune system proteins that usually protect against infections, but in this case, they mistakenly target clotting factors. Acquired hemophilia B occurs when antibodies develop against factor IX. In acquired hemophilia B, the immune system produces specific types of antibodies that block or reduce the function of factor IX, preventing normal blood clotting.³
Acquired hemophilia B is extremely rare, with only few case reports in medical literature. 1, 2, 4
Due to the extreme rarity of acquired hemophilia B, precise epidemiological data about age, sex and other demographic characteristics are not well established. Based on the general pattern of acquired coagulation factor inhibitors, the condition could affect people of any age, though acquired autoimmune bleeding disorders are more commonly seen in elderly populations and occasionally in association with pregnancy.1, 4, 6
One documented case of acquired hemophilia involving both factor VIII and factor IX inhibitors has been reported, demonstrating that autoantibodies can rarely target multiple clotting factors simultaneously.7
Acquired hemophilia B should be suspected in people with new-onset abnormal bleeding and who do not have a personal or family history of bleeding disorders, especially when laboratory testing shows specific changes in blood clotting tests.
The firsts tests are usually routine blood clotting tests. Two common tests are the activated partial thromboplastin time (aPTT) and the prothrombin time (PT), which measure how long it takes blood to clot through different clotting pathways. These tests measure how long it takes for blood to clot through different clotting pathways. In people with acquired hemophilia B, the aPTT is longer than normal, meaning the blood takes more time to clot, while the PT remains normal. This pattern is also seen in acquired hemophilia A and helps guide further testing.1, 4, 5
To better understand the cause of the abnormal aPTT, doctors perform an aPTT mixing test. In this test, the patient’s blood plasma (the liquid part of blood) is mixed with normal plasma from a healthy person. This helps determine whether the problem is due to a missing clotting factor or the presence of an inhibitor. If the clotting time returns to normal, it suggests a factor deficiency, meaning the body is not making enough of a clotting protein. If the clotting time does not improve, it indicates a factor inhibitor, which is an antibody that blocks the clotting factor from working.1, 5
Once an inhibitor is suspected, specific factor tests are used to measure the level of factor IX, the clotting protein affected in acquired hemophilia B. Doctors can also measure how strong the inhibitor is using a test called the Bethesda assay, which measures how strongly the antibody blocks the clotting factor. These tests help confirm the diagnosis and distinguish acquired hemophilia B from acquired hemophilia A, which affects factor VIII, and from other conditions that can also cause a prolonged aPTT.1, 5
Treatment
Treatment of acquired hemophilia B has two main goals, stopping active bleeding and removing the harmful antibodies, inhibitors, that interfere with normal blood clotting.
To control acute bleeding (sudden or active bleeding), doctors use medications called bypassing agents, which help the blood clot without using factor IX. These medicines help the blood clot by working around the blocked clotting factor. The preferred treatment is recombinant activated factor VII (rFVIIa), a laboratory-made clotting protein. rFVIIa is preferred over activated prothrombin complex concentrate (APCC) because APCC contains factor IX, which may cause allergic reactions or increase antibody levels in patients who already have antibodies against factor IX.⁸ Both forms of rFVIIa have been shown to be effective in stopping bleeding by helping the body generate thrombin, an enzyme essential for forming blood clots, without relying on factor IX.⁹
The second part of treatment focuses on eliminating the inhibitor, which is the antibody causing the problem. This is done using immunosuppressive therapy, which calms the immune system to reduce antibody production. The standard first-line treatment includes corticosteroids, often combined with cyclophosphamide, a medication that suppresses immune system activity. Most affected people achieve partial or complete improvement within six months of treatment.10, 11 If this approach is not effective, another medication called rituximab, which targets specific immune cells, may be used and has shown benefit in some patients.11 Because acquired hemophilia B is extremely rare, there are limited clinical studies and no widely established treatment guidelines specific to this condition.
The National Bleeding Disorders Foundation provides up-to-date information about FDA-approved therapies to treat bleeding disorders.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
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