What is Acquired Hemophilia?
Hemophilia, with its roots in the words ‘hemo’ (meaning blood) and ‘philia’ (meaning love), is known as the most common and harsh bleeding disorder. It comes in three types – A, B, and C, each caused by a lack or malfunction of certain blood factors, specifically factors VIII, IX, and XI. Hemophilia is often inherited, but in some rare cases, it can be acquired. This acquisition comes from the body creating antibodies that fight against a clotting factor, most commonly factor VIII. This is typically referred to as ‘acquired hemophilia A’.
Patients who have these antibodies might experience severe bleeding. However, they typically don’t have a history of bleeding problems or disorders. Diagnosing hemophilia can be tough because it’s not common and there is a complex process behind lab testing. This report goes over the symptoms and biological features of this disease, as well as treatment plans.
When it comes to symptoms, they can range from severe, life-threatening bleeds to mild or even no bleeding incidents. The life-threatening situations usually occur within the initial few weeks, however, they can occur at any stage if the right treatment is not started.
What Causes Acquired Hemophilia?
In about half of the patients diagnosed with acquired hemophilia, no cause can be found. For the rest, there are certain triggers or underlying conditions. Many factors can contribute to acquired hemophilia A development, including:
Immunological disorders: These includes conditions such as lupus, rheumatoid arthritis, Sjogren syndrome, diseases of the connective tissues, autoimmune thyroiditis, Grave’s disease, antiphospholipid syndrome, multiple sclerosis, temporal arteritis, myasthenia gravis, Goodpasture syndrome, and other autoimmune diseases.
Obstetrical causes: This refers to complications after childbirth. This is one of the most common causes of acquired hemophilia contributing to 8.4% of total cases. Unexpected bleeding up to 12 months after delivery could indicate acquired hemophilia A. Autoantibody development typically happens after delivery, but it can also be detected during labor and may cause severe bleeding, potentially requiring the removal of the uterus.
Hematological and Oncological Causes: Conditions related to blood or cancer, including cancer diagnosis, precancerous states, tumors in the lungs, prostate, pancreas, breasts, leukemia, multiple myeloma, lymphoproliferative malignancies, and non-Hodgkin lymphoma can precede acquired hemophilia A.
Dermatologic Disorders: Skin conditions such as psoriasis, pemphigus, and epidermolysis bullosa may also be related.
Pharmacological Causes: Certain medications, such as various types of antibiotics, interferons, clopidogrel, anti-inflammatory drugs, amiodarone, rivastigmine, sunitinib, heparin, phenytoin, chloramphenicol, methyldopa, and fludarabine can cause acquired hemophilia A.
Infectious Diseases: Some infections such as acute hepatitis B and C could be a trigger.
Transplant-Related Disorders: Conditions such as chronic graft versus host disease after a transplant.
Gastroenterological Diseases: Conditions such as inflammatory bowel disease.
Pulmonary Diseases: Conditions like asthma and chronic obstructive pulmonary disease (COPD).
Transfusion of blood products can also play a role.
Risk Factors and Frequency for Acquired Hemophilia
Acquired hemophilia is not common and mostly affects adults, especially those above 65 years old, more than children. It has an equal occurrence in both men and women. Interestingly, women between 20 and 40 years old tend to be diagnosed more often, likely due to the risk associated with pregnancy and the period after giving birth.
- Acquired hemophilia is a rare condition with a frequency of 1.5 cases per million per year.
- The disease’s incidence changes with age – it’s far less common in children under 16 (0.045 per million per year) compared to adults over 85 (14.7 per million per year).
- About 80% of people diagnosed with this condition are over the age of 65.
- The median age of those affected ranges from 73.9 years to 78 years.
- There isn’t any genetic pattern associated with it.
- Women aged 20 to 40 and men over 85 are the groups typically affected more frequently.
- The higher incidence in females between 20 and 40 could be linked to the increased risk during pregnancy and up to 12 months post-delivery.
Signs and Symptoms of Acquired Hemophilia
If someone has unexplained bleeding, especially if they are elderly or have recently given birth, doctors may suspect a condition called Acquired Hemophilia A (AHA). This condition can occur in anyone, but it’s often found in people with immune system diseases, those taking certain medications, or those with other medical conditions that make them more likely to get AHA. It’s important to note that about half the people diagnosed with this condition won’t have any clear reason why they have it.
When diagnosing AHA, doctors will take into account the patient’s age, gender, symptoms, medical history, past surgeries, and current medications. Key signs of AHA include sudden, unusual bleeding, even if it seems minor to begin with. This bleeding can get serious quickly, leading to dangerous health risks, like severe bleeding events.
It’s also important to note that AHA can be hard to diagnose because it’s quite rare and can easily be mistaken for other conditions. A complete physical examination and various tests are needed to make a sure diagnosis.
- AHA often shows itself through bruises or discoloration of the skin (known as purpura) and bleeding into soft tissues.
- More serious bleeding complications can also occur.
- Unlike the inherited types of hemophilia, patients with AHA rarely have joint bleeds (hemarthrosis).
Testing for Acquired Hemophilia
If a doctor thinks a person might have acquired hemophilia based on their medical history and current symptoms, they will arrange for a complete blood count and a coagulation profile, which are special blood tests, to confirm it. Contrary to what you might expect, the complete blood test could show a normal platelet count for a person with acquired hemophilia. However, the coagulation profile, which measures how long it takes for blood to clot, will often reveal a much longer clotting time – about 2 to 3 times the norm.
The long clotting time could be down to lower levels of certain blood clotting factors, or because someone has developed antibodies that neutralise these factors. To find out the cause, doctors carry out something known as a mixing study, where they mix the patient’s plasma (a component of blood) with normal plasma in equal measure.
If the clotting time normalizes after this mix, it indicates that the patient is lacking in the blood clotting factors. If the clotting time still remains long, it implies that there are antibodies present that are interfering with the clotting process. To conduct the mixing study, the doctor will need to let the plasma incubate for 1 or 2 hours first.
Once these steps are completed, other tests will be conducted to measure the level of these clotting factors and antibodies in the patient’s blood. In acquired hemophilia, the levels of one of the clotting factors (FVIII) are typically lower whereas the antibodies that act against this factor are usually higher.
The level of these antibodies is expressed in something called the Bethesda unit (BU), a measure of how much of the antibody it takes to neutralise 50% of the FVIII activity. The measurement process has been improved by a modification from Nijmegen, which has made sure that the pH level and protein concentration of the test mixture are always the same, meaning the test’s results are more reliable.
In severe cases where the patient has lost a lot of blood, the complete blood count may show that they have lower than normal levels of hemoglobin. Also, while it’s rare, some patients might not have an extended clotting time, despite having acquired hemophilia. In such cases, the doctor and their team will have to rely on their professional judgement and collaboration to make the diagnosis.
Treatment Options for Acquired Hemophilia
Treating patients diagnosed with acquired hemophilia A (AHA) relies on the expertise of medical providers, as there isn’t a standard international agreement on its management yet. The treatment mainly involves two simultaneous approaches:
1. Managing bleeding.
2. Getting rid of the Inhibitor that sparks the condition.
In managing bleeding, treatment varies based on how severe the bleeding is and where it’s happening. It’s important to note that the severity of bleeding doesn’t directly correspond with the levels of autoantibodies in the blood.
For patients with minor bleeding who have autoantibody levels equal to or less than five BU and don’t require immediate surgery, observation is usually enough. Sometimes the autoantibodies disappear on their own within a few months. If treatment is necessary, it’s usually focused on stopping medications linked to bleeding and avoiding surgery. Medication to increase the levels of factor VIII, a protein that helps your blood clot, might also be used.
For patients with severe bleeding, quick and appropriate treatment is essential. If the autoantibody levels are low, treatments including medication to increase factor VIII or Desmopressin might be used. If the autoantibody levels are high, the first treatment is typically to use bypassing agents, which help to clot the blood by avoiding the need for factor VIII. Either of these agents can be chosen based on patient history, preference and availability. If the first agent is not effective, the other one can be tried.
The effectiveness of the treatment is usually monitored by observing the patient’s symptoms, as there are no approved lab tests for checking the success of the treatment. If there’s bleeding in the mucous membranes, medications to prevent blood clots from breaking down can be used at the same time.
The second part of the treatment is to eradicate the inhibitors causing AHA. This is crucial as patients with these autoantibodies are at risk of serious, possibly life-threatening bleeding. To do this, prednisone might be used alone or in conjunction with another medication, cyclophosphamide. If this therapy is successful, the autoantibody levels should be undetectable, and factor VIII levels return to normal. However, sometimes the disease may relapse, necessitating long-term monitoring. Other medications, like Rituximab and 2-chlorodeoxyadenosine, may be useful in managing acquired hemophilia, especially in cases resistant to standard therapy.
What else can Acquired Hemophilia be?
Bleeding caused by acquired hemophilia can be hard to distinguish from other bleeding disorders. The main conditions doctors consider include:
- Congenital hemophilia A, B, and C (tests involve mixing studies and factor assays)
- Factor XII deficiency (tests involve measuring factor activity and inhibitor levels)
- Drug-related bleeding due to medications like unwrapped heparin, warfarin, thrombin inhibitors, and factor Xa inhibitors (doctors consider medication history and coagulation profile)
- Antiphospholipid syndrome (tests include lab assays for certain antibodies and checking for lupus anticoagulant)
In these cases, the correct diagnosis is confirmed by performing appropriate tests based on the suspected condition.
What to expect with Acquired Hemophilia
Three large-scale studies found that the death rate for acquired hemophilia A (AHA) ranged from 8% to 22%. However, newer studies have indicated lower death rates due to treatments designed to stop bleeding.
Having a low level of Factor VIII, a protein that helps blood to clot, is related to a lower chance of full recovery and survival. Other risk factors for passing away include getting older and having cancer. Interestingly, in congenital hemophilia (inherited from birth), the creation of antibodies that fight against foreign substances in the body doesn’t relate to the death rate. This is different compared to acquired hemophilia where the production of autoantibodies, antibodies that attack our own cells, does influence it.
On a positive note, acquired hemophilia A has a very high success rate of recovery, approximately 97%, for patients who develop the condition after childbirth. In many cases, there is a spontaneous recovery where the autoantibodies disappear on their own, on average in about 30 months.
Possible Complications When Diagnosed with Acquired Hemophilia
If not treated properly and promptly, acquired hemophilia can result in various complications, including:
- Severe Intramuscular Bleeding: This can lead to a condition known as compartment syndrome or even tissue death due to the pressure on nerves and blood vessels.
- Mucosal Bleeding: This includes bleeding in the nose (also known as epistaxis), digestive system, urinary system (resulting in blood in urine), and respiratory system (resulting in coughing up blood).
- Bleeding From the Wound/Operative Site: Any invasive procedure, like surgeries or procedures that involve puncturing arteries, can make a person with acquired hemophilia potentially vulnerable to severe, uncontrolled bleeding.
- Seldom occurrences of intracranial hemorrhages i.e., bleeding inside the skull.
Unlike congenital (hereditary) hemophilia, people with acquired hemophilia often don’t experience frequent episodes of bleeding inside their joints. Large, spontaneous collections of blood under the skin, known as subcutaneous hematomas, are also a possibility.
Preventing Acquired Hemophilia
It’s crucial that patients understand the importance of taking their medication as prescribed and are aware of potential complications. They should also know how important it is to regularly check in with their healthcare provider. This is because acquired hemophilia can return, so patients should seek medical advice quickly if they notice any bleeding. This allows for the disease to be caught and treated sooner. Also, patients should have clear written guidelines on activities that could potentially cause bleeding, like shaving or brushing teeth. This will help them get the best possible health results.
