Acquired Haemophilia

Acquired haemophilia is a rare but potentially life-threatening bleeding disorder that can appear suddenly in people who have never had bleeding problems before. Unlike the inherited form of haemophilia, this condition develops when the body’s immune system mistakenly attacks its own clotting factors.

Table of contents

• What is Acquired Haemophilia?
• Causes and Associated Conditions
• Who is Affected?
• Signs and Symptoms
• Diagnosis
• Treatment
• Outlook and Survival

What is Acquired Haemophilia?

Acquired haemophilia is a rare bleeding disorder caused by the development of autoantibodies (proteins made by the immune system) that attack the body’s own blood clotting factors. These autoantibodies are also called inhibitors because they prevent the clotting factors from working properly^[1].

Most commonly, these antibodies target factor VIII, which is an essential protein needed for blood to clot normally. This specific form is known as acquired haemophilia A^[3]. Unlike inherited haemophilia, which people are born with, acquired haemophilia develops later in life in people who previously had normal blood clotting^[4].

The condition is extremely rare, affecting only about 1.5 people per million each year^[5][7]. It is not hereditary and cannot be passed from parents to children^[3].

Causes and Associated Conditions

In approximately half of all cases, doctors cannot identify a specific cause for acquired haemophilia. These cases are called idiopathic, meaning the cause is unknown^[1][5].

In the other half of cases, acquired haemophilia is associated with certain underlying conditions or situations^[1]:

• Autoimmune diseases (conditions where the immune system attacks the body): These include systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, and other similar conditions^[1].
• Pregnancy and childbirth: Acquired haemophilia can develop during pregnancy or within one year after giving birth. This accounts for about 8 to 10% of cases^[1][6].
• Cancer: Both solid tumors and blood cancers can be associated with acquired haemophilia^[7].
• Medications: Certain drugs may trigger the development of autoantibodies^[7].

The exact reason why the body loses its normal tolerance to clotting factors remains unclear, but it may involve genetic factors and changes in certain immune cells^[7].

Who is Affected?

Acquired haemophilia can affect both men and women equally, which is different from inherited haemophilia that primarily affects males^[3]. The condition can occur at any age, but it shows a distinct pattern^[6][9]:

There are two peak periods when the condition is most commonly diagnosed. The first peak occurs in younger adults, particularly women between ages 20 and 30, and is mainly related to pregnancy and childbirth. The second and larger peak occurs in older adults between ages 68 and 80, with no difference between men and women in this age group^[7][9].

The majority of patients are elderly, which means they often have other health conditions and may be taking medications that can affect bleeding risk^[6].

Signs and Symptoms

The bleeding pattern in acquired haemophilia differs significantly from inherited haemophilia. People with this condition typically present with bleeding symptoms they have never experienced before, with no personal or family history of bleeding problems^[6][10].

The severity of bleeding varies widely. Some people may have only mild bleeding, while others experience severe, life-threatening bleeding episodes^[1][3]. Approximately 10% of patients may not have any bleeding at all when first diagnosed^[6].

Common bleeding symptoms include^[1][4][7]:

• Large hematomas (collections of blood under the skin) and extensive bruising
• Bleeding into muscles and soft tissues
• Bleeding from mucous membranes, including nosebleeds
• Gastrointestinal bleeding (from the stomach or intestines)
• Blood in the urine
• Abnormal vaginal bleeding in women, especially after childbirth

Unlike inherited haemophilia, bleeding into joints is uncommon in acquired haemophilia^[3][4][7]. Life-threatening bleeds often involve the gastrointestinal tract or can occur in vital organs^[4].

Most bleeding occurs spontaneously without obvious cause, though it can also happen after surgery or minor injuries^[7].

Diagnosis

Diagnosing acquired haemophilia can be challenging because of its rarity and the complexity of laboratory testing^[1]. The condition should be suspected in anyone who develops new bleeding symptoms without a previous bleeding history, especially in elderly people or women who have recently given birth^[7].

The key laboratory finding is a prolonged activated partial thromboplastin time (aPTT), which is a blood test that measures how long it takes for blood to clot. Other basic clotting tests, including the bleeding time, prothrombin time (PT), and platelet count, typically remain normal^[4][7].

To confirm the diagnosis, doctors perform several specific tests^[4][7]:

• A mixing study: The patient’s blood is mixed with normal blood. If the prolonged clotting time does not correct, it suggests the presence of an inhibitor rather than a simple factor deficiency.
• Factor VIII level testing: This shows reduced levels of factor VIII in the blood.
• Bethesda assay or Nijmegen modification: These specialized tests detect and measure the level of autoantibodies against factor VIII.

The diagnosis is confirmed when reduced factor VIII levels are found along with evidence of neutralizing antibodies^[6][9].

Treatment

Treatment for acquired haemophilia has two main goals: controlling active bleeding and eliminating the autoantibodies to prevent future bleeding^[4][11].

Controlling Bleeding

When bleeding occurs, immediate treatment is essential. Several medications can be used to stop bleeding^[4][6]:

• Recombinant activated factor VII (rFVIIa): A laboratory-made clotting factor that helps blood clot by bypassing the missing factor VIII.
• Activated prothrombin complex concentrate (APCC): A medication containing several clotting factors that work together to stop bleeding.
• Recombinant porcine factor VIII: Factor VIII derived from pigs, which may not be recognized by the human antibodies.

The choice of treatment depends on several factors, including the severity of bleeding, the level of inhibitors, availability of medications, and individual patient circumstances^[6].

Eliminating the Autoantibodies

The ultimate goal is to eliminate the autoantibodies and restore normal factor VIII levels. This is achieved through immunosuppressive therapy, which means using medications that reduce the activity of the immune system^[3][4].

Common immunosuppressive treatments include^[6][11]:

• Corticosteroids (such as prednisone): Medications that suppress the immune system
• Cyclophosphamide: A chemotherapy drug that reduces antibody production
• Rituximab: A medication that targets specific immune cells

These treatments can be used alone or in combination. About 60 to 80% of patients achieve remission (meaning the antibodies disappear) after a median of 5 to 6 weeks of treatment, though this varies considerably between individuals^[6][11].

If an underlying condition is identified, treating that condition may help eliminate the inhibitor^[4]. In pregnancy-related cases, the condition often resolves on its own with appropriate treatment^[1].

Prevention and Monitoring

Until the antibodies are eliminated, patients should avoid activities with significant risk of injury. Even minor medical procedures should be postponed when possible^[11]. Patients with acquired haemophilia should be monitored by specialists at a haemophilia treatment center^[3][7].

Outlook and Survival

Acquired haemophilia is a serious condition with significant health risks. The mortality rate ranges from 8 to 22%, with death potentially resulting from severe bleeding, underlying diseases, or complications from infections related to treatment^[7][10].

Several factors can help predict outcomes^[6][9]:

• Factor VIII levels at the time of diagnosis
• The level of inhibitor antibodies
• The type of autoantibodies present

With prompt diagnosis and appropriate treatment, many patients can achieve remission and return to normal life. However, early recognition and treatment are crucial to prevent life-threatening bleeding complications^[1][6].

A prolonged clotting time test should never be ignored before any invasive procedures, as this could be the first sign of acquired haemophilia^[6][9].