What is Acquired Hemophilia?
Congenital Hemophilia is an inherited (genetic) bleeding disorder caused by a missing or reduced levels of one of two protein(s), clotting factors VIII (8) or factor IX (9). In a person with normal levels of clotting factors, when an injury occurs, all of the clotting factors work together to form a clot that stops the bleeding. People with congenital hemophilia are born without enough of one of these important clotting factors so bleeding in them continues until treatment is given. Patients with none or reduced factor VIII have congenital hemophilia A (“classic” hemophilia) and those with none or reduced factor IX are known as congenital hemophilia B (Christmas Disease).
Acquired hemophilia is a disorder that is not present at birth, but develops suddenly at some point in your life. It happens due to an abnormality in your immune system like in rheumatoid arthritis or lupus.
Normally, the immune system helps to protect the body from viruses and germs. When a germ enters the body, the immune system sees it as something that does not belong. The immune system will then make an antibody to destroy the germ. The immune system also protects the body from other things that it sees as foreign or as not belonging.
In acquired hemophilia, the immune system makes a mistake and thinks that the body’s clotting factor doesn’t belong. The immune system makes antibodies which destroy this clotting factor and prevents blood from clotting. This is called Acquired Hemophilia or Autoimmune Hemophilia (antibodies against yourself).
Antibodies that block function of a protein are sometimes called inhibitors. Antibodies in congenital and acquired hemophilia are different, even though they might both be called inhibitors. In congenital hemophilia, patients are born with insufficient factor VIII or IX, so replacement factor VIII or IX medication is given. Sometimes this factor treatment is seen as a foreign protein and causes an immune response and antibodies. Whereas, in acquired hemophilia, patients have normal factor VIII and the body just mistakenly develops an immune response against it.
What causes it?
There is no personal or family history of bleeding in patients with acquired hemophilia. Once an inhibitor is present, there can be spontaneous bleeds and it is common to have severe bleeding after invasive procedures.
Each year, acquired hemophilia occurs in only 1 to 1.5 people per 1 million people. In the US (~320 million people), this amounts to about 320-500 patients at any one time. Acquired hemophilia can occur in association with other underlying conditions that involve the immune system, like cancer, other autoimmune diseases, pregnancy or even the use of certain medications (shown in pie chart below). About half of the time, there is no clear medical condition or reason this happened, which we call idiopathic, which is just a big medical term meaning ‘unknown cause’.
Associated Conditions with Acquired Hemophilia
Acquired hemophilia affects both men and women almost equally and almost always occurs in adults. It most often affects the elderly, but can sometimes be seen in women after giving birth (called post-partum period). The median age of onset is approximately 73.9 years (range, ~2–98 years).
Acquired hemophilia is very serious and can be fatal. This is because bleeding can be severe and unexpected and health care professionals may not recognize that an antibody has developed. While it’s unknown just how many patients with acquired hemophilia die as a consequence of the bleeding or other complications, the estimates from some large studies are between 8 and 22 percent.
While acquired hemophilia is straightforward to diagnose with the proper laboratory tests, healthcare professionals who see patients with bleeding symptoms often don’t make the diagnosis immediately. The healthcare provider who might first see a patient with severe bruising or bleeding (emergency medicine, internal medicine, geriatrics, obstetrics/gynecology, and rheumatology) probably have never seen a case of acquired hemophilia before and likely consider the more common reasons for bleeding first, or focus on where their patient is bleeding more than why. Patients with acquired hemophilia might be tested or diagnosed with other diseases or disorders at first but the bleeding continues. At some point a blood specialist (hematologist) would likely become involved, and a diagnosis of acquired hemophilia confirmed by specific testing at a specialized laboratory.
What are the symptoms?
Acquired hemophilia can be difficult to diagnose due to its rare occurrence and lack of awareness by healthcare professionals.
The most common symptoms are:
- Extensive bleeding into the skin (bruising)
- Bleeding into muscle and soft tissues
- Internal bleeding
- Heavy and persistent bleeding after surgery
How is it diagnosed?
The first step in making the diagnosis of a new bleeding disorder is always the medical history, and in acquired hemophilia you likely had no specific bleeding problems prior to this recent episode of spontaneous bleeding, bleeding after surgery or childbirth.
After history, physical examination can show the pattern of bleeding, which is sometimes obvious (extensive bruising, blood in urine). Internal bleeding (in the intestines, muscles, etc.) may require imaging studies (x-rays, and CT or MRI scans).
The most helpful testing is some screening coagulation laboratory tests that measure how your blood clots, often just called “coags” tests. There are two of these tests, the prothrombin time or PT, and the activated partial thromboplastin time or aPTT. Both tests measure the number of seconds that it takes your blood to clot compared with the normal range. The aPTT is the test that is sensitive to abnormalities in factor VIII, and in congenital and acquired hemophilia the aPTT is higher than normal (your blood takes more seconds to clot). The PT test will be normal.
A prolonged aPTT test can be due to a decreased amount of Factor VIII (congenital hemophilia) or because an antibody or anticoagulant is blocking the clotting process. The next step will be the aPTT mixing study, where your blood is mixed with normal blood to see if the aPTT results change. If your factor level is only low, adding the normal blood allows clotting to occur. If you have an antibody that blocks factor from working, the aPTT might start to show clotting, but then the inhibitor begins to inactivate the normal factor over a couple of hours and the aPTT remains prolonged.
To confirm a diagnosis of acquired hemophilia, you will have a factor VIII test to measure the amount of factor in your blood. A second specific test will be performed to determine the amount of antibody, called a Bethesda inhibitor assay (also inhibitor titer or Bethesda titer). Unlike congenital hemophilia, the exact factor VIII level and inhibitor titer do not predict frequency or severity of bleeding in acquired hemophilia.
Most commonly, a hematologist specialized in bleeding disorders becomes involved in confirming the diagnosis and making the treatment plan.
How is it treated?
When a person is diagnosed with acquired hemophilia, their treatment has two aims:
- Bleeding – Stop the current bleeding or prevent bleeding during a surgical procedure by using agents that can bypass the factor VIII antibody.
- Remove inhibitor – Block the immune system from making antibodies to factor VIII (immunosuppression).
The diagnosis and clinical management of each person’s situation is challenging due to severe bleeding and the limited laboratory tests that can be used to guide treatment.
There are different types of treatments that can be used to control bleeding, depending on the seriousness of the bleeding episode. Factor VIII replacement is not the recommended treatment for acquired hemophilia. For bleeds requiring treatment, guidelines recommend bypassing agents, products that can help blood to clot by bypassing the steps that require factor VIII. During treatment with bypassing agents, people should be monitored closely to make sure the blood is not clotting too much or clotting in the wrong place in the body. If you are older or already have risk factors for cardiovascular disease or blood clots, there is a higher risk of clotting in the wrong place (thrombosis) and this can lead to additional complications.
Blood transfusions are sometimes necessary for anemia (low blood counts) after losing a significant amount of blood.
Patients remain at risk of life-threatening bleeding as long as the antibody persists, regardless of the factor or inhibitor level. Elective surgeries and procedures should be delayed until the antibody is gone. Guidelines recommend bypassing agents be used prior to major or minor invasive procedures that cannot be postponed. Even with proper use of bypassing agents, there can be serious bleeding. Blood transfusions may be needed.
Because antibodies can re-occur over time, you should make sure to check with your hematologist prior to undergoing any major or minor procedures. You may need to have blood tests prior to having any surgery to see if you have an active antibody.
Acquired hemophilia means that a person’s immune system is confused and it is attacking their blood factors which would normally help them clot. Immunosuppressive therapy is used to relax or suppress the immune system, which then leads to fewer antibodies attacking the factor.
Guidelines recommend all patients diagnosed with acquired hemophilia should receive immunosuppressive therapy immediately. Unlike inhibitors with congenital hemophilia who develop inhibitors after receiving replacement factor, acquired antibody levels and the factor levels do not predict a person’s bleeding risk. So, immune therapy is started to reduce the risk of life-threatening bleeds.
Tips for staying healthy
To help you manage your acquired hemophilia, it is important to find a hematologist or Hemophilia Treatment Center (HTC) specializing in bleeding disorders. Because there may also be other conditions associated with acquired hemophilia, you should make sure that all of your healthcare professionals know about the inhibitor and all your conditions and are coordinating with one another.
Antibodies can re-occur or relapse, often in association with a reoccurrence or worsening of an underlying immune condition. You should check with your hematologist prior to undergoing any major or minor procedures. You may need to have blood tests before any surgery to see if there is active antibody even if it had gone away with earlier treatment.