What Are Acquired Factor VIII Inhibitors?
Hemophilia A, or classical hemophilia is a rare disorder that affects blood clotting. In affected individuals, after an injury, bleeding time will be more. Blood clotting is a process that requires 12 clotting factors which are proteins, and factor VIII is one among them. The deficiency of this factor can manifest as hemophilia.
In most cases, the cause is congenital; the disorder is passed down from parents to children. However, there are some cases of hemophilia which have no family history. It can occur due to causes other than hereditary. Such cases of hemophilia are known as acquired hemophilia or acquired factor VIII inhibitor. It can cause life-threatening bleeding and is difficult to manage.
The acquired factor VIII inhibitors are autoantibodies that bind to factor VIII. The antibodies present in the body generally destroy any foreign substance that enters the body. But when antibodies destroy healthy tissues, they are known as autoantibodies. This binding of autoantibodies leads to the functional deficiency of factor VIII. Its incidence is very rare; however, with an increase in age, the incidence of the condition can increase. It can affect both males and females equally. It is often associated with autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus, malignancy, dermatological disorders, etc. However, the association of the disorder with these conditions decreases with an increase in age.
What Causes the Development of Acquired Factor VIII Inhibitors?
Acquired factor VIII inhibitor is often associated with several underlying pathologies like;
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Autoimmune disorders like myasthenia gravis, rheumatoid arthritis, multiple sclerosis, autoimmune hypothyroidism, etc.
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Solid cancers of the lung, colon, prostate, pancreas, stomach, head, neck, etc.
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Inflammatory diseases of the bowel like ulcerative colitis.
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Dermatologic disorders like psoriasis and pemphigus.
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Acute hepatitis B and C infection.
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Respiratory diseases like asthma.
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Blood cancer.
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Usage of drugs like Penicillin, Phenytoin, Levodopa, etc.
However, even though 50% of the cases are associated with these conditions, the rest of the reported cases remain idiopathic.
What Are the Clinical Features Resulting From Acquired Factor VIII Inhibitor?
The main clinical features of acquired hemophilia are;
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Common sites of bleeding include subcutaneous tissue, muscle, gastrointestinal tract, and genitourinary tract leading to ecchymoses (dark purple color spot or bruise), hematoma (collection of blood outside the blood vessels), melena (dark tarry stools indicating the presence of blood in stool), and hematuria (blood in urine) respectively.
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Intracranial hemorrhage in some cases.
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Hemarthrosis (bleeding into the joint after an injury) is rare compared to congenital hemophilia.
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Prolonged partial thromboplastin time (time for the blood to form the clot) presented with or without bleeding.
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Spontaneous bleeding without cause.
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The rapid progress of bleeding in soft tissues leads to compartment syndrome (A severe painful condition that occurs due to the increase in pressure of blood vessels, nerves, and muscles, especially those in arms and legs, which can damage these structures).
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Increased genital bleeding after childbirth in affected women.
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Risk of excessive bleeding during surgery or trauma.
How to Diagnose Disorders Involving Acquired Factor VIII Inhibitor?
The diagnosis of the disorder includes the clinical history of the patient and laboratory tests. The patient should be referred for laboratory tests if there is a recent history of abnormal bleeding. Coagulation tests like activated partial thromboplastin time (aPTT) and prothrombin time (PT) can be taken. Affected individuals may have prolonged aPTT with normal PT. Some other conditions, like heparin therapy, may also have prolonged aPTT. So tests must be conducted to rule out other causes. Tests for identifying reduced factor VIII levels due to factor VIII inhibitor activity (Bethesda assay or Nijmegen modification) can also be performed.
What Are the Differential Diagnosis of Acquired Factor VIII Inhibitors?
The differential diagnosis includes;
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Congenital hemophilia A
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Hemophilia B
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Hemophilia C
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Von Willebrand disease.
Hemophilia A, hemophilia B, and hemophilia C are the three types of inherited hemophilia. Hemophilia B is due to clotting factor IX, and hemophilia C is due to the absence of clotting factor XI. Von Willebrand disease is also an inherited disorder that can occur due to the absence of the Von Willebrand factor. This factor is involved in the early stages of blood clotting.
How to Treat the Complications From Acquired Factor VIII Inhibitor?
The treatment for acquired factor VIII inhibitors can vary for each individual. The primary aim of the treatment is to treat acute bleeding episodes, eradication and prevent the recurrence of antibodies, and treat underlying conditions.
Treatment of Acute Bleeding - To control acute bleeding, the available options are bypassing agents and measures to increase the level of factor VIII. Bypassing agents are the first-line treatment option. The bypassing agents are those agents which bypass the deficient clotting factor and help the body to form clots. The available bypass agents are recombinant activated factor VII or activated prothrombin complex concentrate. In order to increase levels of factor VIII, the affected individuals are treated with recombinant human factor VIII or Desmopressin. The effectiveness of these two treatment options will vary for each individual.
Inhibitor Eradication - The eradication of autoantibodies that cause the disorder can be done with the help of immunosuppression therapy (corticosteroids alone or in combination with Cyclophosphamide). There are chances that relapse can occur once the immunosuppression therapy is stopped. Due to potential side effects, long-term usage of this therapy is not recommended. High-dose intravenous immunoglobulin is also used. In individuals with high levels of inhibitors, a procedure called plasmapheresis is recommended.
The diagnosis and treatment of the underlying pathology play a crucial role in treating acquired hemophilia.
The novel treatment options include the treatment with Rituximab. Rituximab is a monoclonal antibody (antibodies produced in the laboratory by cloning a particular white blood cell). This is usually preferred as a second line of treatment along with steroids. The effectiveness of this drug is still under study.
Conclusion:
Acquired hemophilia is a rare and life-threatening disorder if not treated promptly. There are chances that the condition may go underdiagnosed or misdiagnosed. Awareness about this disease should be established. The individuals at risk of this disorder should refrain from activities that may cause trauma. There are specialized centers available for treating individuals with hemophilia. These centers provide comprehensive care. With the help of novel therapeutic strategies, a promising cure is being established for acquired hemophilia.
