What Is Acquired Haemophilia?

Introduction

Definition of acquired haemophilia

Acquired Haemophilia is a rare autoimmune bleeding disorder. In acquired haemophilia, your body creates molecules called autoantibodies to attack certain clotting factors in your blood. Without these factors, your body cannot properly clot (coagulate) your blood, making you bleed uncontrollably. This can be deadly if not treated quickly.¹

Antibodies are usually a good immune response. Your body will create antibodies called IgA and IgM to attack foreign viruses and bacteria in your body to fight off illnesses such as COVID-19 or the common cold. This is crucial for your body to recover. However, in the case of an autoimmune disorder, your body will mistake some of your own body’s cells as foreign and create specific antibodies to attack them, also known as autoantibodies. Some examples of autoimmune disorders include multiple sclerosis, rheumatoid arthritis, and Crohn’s disease.¹

There are two main types of acquired haemophilia: A and B. The type depends on which clotting factor is affected. 

Acquired haemophilia A (AHA)

Haemophilia A is when you don’t have enough clotting factor 8 (VIII) in your blood. This is the most common type of haemophilia in people. Acquired haemophilia is reported to occur in 1.5 cases per 1 million people each year. A majority of the cases occur in those older than 65 and of this group, half have another autoimmune disorder.¹

Acquired haemophilia B (AHB)

Haemophilia B is when you don’t have enough clotting factor 9 (IX) in your blood. This is extremely rare.¹

What are clotting factors?

Imagine when you get a paper cut or scrap your knee, you initially have blood flowing but after a few minutes, the blood stops and your cut dries and eventually scabs over and heals. This is an example of your blood clotting.¹ Your body has 12 clotting factors that work together to clot your blood. Clotting is when your blood turns into a thicker gel-like substance that acts as a barrier when you have damage to your blood vessels to stop the blood from leaking out.¹

Causes and risk factors

Underlying conditions leading to acquired haemophilia

In approximately 50% of diagnosed cases of acquired haemophilia, there is no recognised cause. In the other 50% of cases, there is an identified risk or cause of the disorder. Many underlying causes can lead to acquired haemophilia. Some include:²

Other immune disorders

In approximately 17-18% of the cases with an identified cause, the patient already has another autoimmune disorder. This could include rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, or connective tissue diseases to name a few examples.²

Obstetrical causes

In approximately 8% of the causes, acquired haemophilia is diagnosed in the immediate time after one has given birth, also referred to as the post-partum period. For up to 12 months after giving birth, abnormal bleeding should be checked out as it might be due to acquired haemophilia A.²

Cancer-related

Some cancers can result in acquired haemophilia. Solid tumours, precancerous states, and non-Hodgkins lymphoma can cause this as well as blood cancers such as chronic lymphocytic leukaemia.²

Skin-related
Some conditions such as psoriasis or pemphigus can lead to acquired haemophilia.²

Drug-related

Antibiotics, psychiatric and immunomodulatory drugs such as interferon have been associated with AHA.⁴

Infectious diseases

Including acute hepatitis B and C infections, and other infectious illnesses.⁵

Transplants

This can be a result of rejection from a transplant such as graft versus host disease where the body is attacking the transplant.²

Lung-related

Some cases of asthma and chronic obstructive pulmonary disease(COPD) have been reported as a cause or risk of acquired haemophilia.²

Symptoms

Acquired haemophilia is specific to those who bleed with varying severity without a previous personal or family history of haemophilia. The National Organization for Rare Disease reports that one-third of patients do not require therapy to control the bleeding, however, more than one-third of the patients suffer more than one bleeding episode. 

The bleeding episodes can present in multiple places: 

• Subcutaneous (bruising or ecchymoses): the most common type of bleeding
• Muscle bleeding (haematoma)
• Gastrointestinal (melaena)
• Genitourinary (haematuria)
• Retroperitoneal bleeding
• Intracranial haemorrhage

Commonly, the bleeding occurs without an immediately obvious cause, such as a trauma or cut. Because of the lack of clotting, these episodes of bleeding can become severe depending on location and amount and can become life-threatening fast.

Additional symptoms may include:

• Bleeding gums
• Pain and stiffness in the joints (due to internal bleeding)

Diagnosis

Laboratory tests used to confirm acquired haemophilia

To diagnose acquired haemophilia, laboratory tests are needed to measure how the clotting system is functioning.³ Prolonged clotting factor expression, like the factor being “always on”, can tell the doctor if something is missing or wrong with the cycle. The doctors will run what is called a haemostatic assay. In this, they will be able to measure:³

• Prothrombin time (PT) - This factor is sensitive to the clotting factors produced in the liver
• Thrombin time (TT) - This test shows how long it takes the blood plasma to clot, due to the conversion of fibrinogen into fibrin
• Activated partial thromboplastin time (aPTT) - This factor is sensitive to certain clotting factors including factors 8 and 9

These measures are important for understanding how long it takes for your blood to coagulate. In patients with acquired haemophilia, the assay should report normal PT and prolonged aPTT levels. After this assay, they will run other tests to rule out other causes of prolonged aPTT, such as the presence of Lupus or a deficiency of clotting factors 7 (VII) and/or 11 (XI).³

Your doctor will most likely run an antibody titre test. This is used to detect the strength of the immune response against your own body’s tissues. For this test, your doctor will draw your blood and can run many tests on it. One such test is called an enzyme-linked immunoassay (ELISA). This laboratory test is used to identify the presence of a certain antibody. The sample is prepared and if the test turns a colour, typically purple, this is a positive indication that the antibody is present. This is done to identify the autoantibodies that deactivate the clotting factors.

It is important to properly diagnose acquired haemophilia. Improper diagnosis can cause adverse effects from improper treatment. Acquired haemophilia can commonly be mistaken for congenital haemophilia or antiphospholipid syndrome.³

Treatment and management

Because acquired haemophilia is rare, treatment is personalized to the patient. Not enough studies have been conducted to create a “gold standard” treatment plan. It is important to have a detailed discussion with your physician and other medical professionals on the best course of treatment. Factors that are included in the direction of treatment include:¹

• Past medical history including previous disorders and response to certain medications
• Current symptoms present
• Age and overall health
• Personal preference for treatment

There have been reported cases of remission during the post-partum period, allergic reactions to drugs, and those with low levels of inhibitors during the titre test.

There are three goals for treatment: stop the bleeding, prevent future bleeding, and treat the underlying cause, if there is one.

Haemostatic management is for patients who experience severe bleeding and decreased haemoglobin, a protein responsible for delivering oxygen through the blood. This is done by administering haemostatic agents to bypass the missing clotting factor that has been taken away by the autoantibodies. This can be done with certain plasma derivatives or complexes, such as Cryoprecipitated Antihaemophilic Factor (Cryo), that help clot the blood.²

Inhibitor eradication is an immunosuppressive (IST) therapy using glucocorticoids and other agents. This treatment's goal is to eradicate, or destroy, the autoantibodies to resolve the risk of life-threatening bleeds. Some of the medication includes prednisone alone or with cyclophosphamide, as the use of both is correlated with better patient outcomes. Success is dependent on the results of the antibody titre and measured levels of the affected clotting factor. While the goal is the eradicate the autoantibody, there are still reports of relapses, so it is important to follow up with your medical team when necessary.²

What is the fatality rate?

Without diagnosis and proper treatment, acquired haemophilia has a high morbidity and mortality rate. Those with this disease can have catastrophic uncontrollable bleeding. For acquired haemophilia A, the mortality rate is between 8-22%. In cases where acquired haemophilia A is present in the post-partum period, the recovery rate is 97%.¹

Summary

Acquired haemophilia is a rare autoimmune disorder that causes uncontrollable bleeding. Without proper diagnosis and treatment, this disorder can be deadly. There are 2 main types of acquired haemophilia: A and B. A is the most common type, with an antibody targeting clotting factor 8, and B, the rare form, targeting clotting factor 9. 

The main symptom of acquired haemophilia is bleeding in varying severity and locations without an underlying cause or trauma that induces the bleeding. Acquired haemophilia can be diagnosed with several laboratory tests that will help the doctor understand what is wrong with the blood and identify the presence of the autoantibodies. 

Only occurring approximately once in every million people per year, this disorder has no one-size-fits-all treatment and is mainly based on symptoms, progression, health, and personal medical history. Treatment is focused on stopping and preventing major bleeding and eradicating the autoantibodies from the system.