Introduction
Acquired hemophilia and rheumatic diseases are autoimmune disorders where the immune system attacks the body’s healthy cells and tissues. In the year 2022, a study found that individuals with rheumatoid arthritis often have more than one autoimmune disease (such as acquired hemophilia).
What Is Rheumatic Disease?
Rheumatic disease is an autoimmune, inflammatory disease that occurs as a result of the immune system attacking healthy cells and tissues of muscles, joints, bones, and organs.
What Is Acquired Hemophilia?
Hemophilia is a clotting disorder that can be congenital or acquired. Congenital hemophilia is a bleeding disorder caused by a genetic mutation that subsequently causes a deficiency or inactivation of clotting factor VIII. Acquired hemophilia is a rare autoimmune bleeding disorder that occurs due to antibodies attacking the clotting factors, most often clotting factor VIII.
This condition has been reported in association with autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, and Sjögren’s syndrome) and also in healthy elderly postpartum women, individuals with malignant neoplasia, and related with the use of some drugs (such as Penicillin).
What Are the Symptoms of Acquired Hemophilia?
Clotting factors are specialized proteins that help the blood form a plug to stop bleeding at the site of a wound. An attack on the clotting factor by the body’s immune system can disrupt the clotting mechanism and cause episodes of bleeding. The severity of bleeding varies among individuals, some may not require any therapy, while others may suffer multiple bleeding episodes. Some of the symptoms include the following:
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Subcutaneous Bleeding (Ecchymoses) - Leaking of blood into the subcutaneous layer underlying the skin.
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Muscle Bleeding (Hematoma) - Spontaneous bleeding into the muscle spaces without a cause (injury).
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Gastrointestinal (Melena) - Blood in feces.
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Genitourinary (Hematuria) - Bleeding in the bladder, kidneys, ureters, urethra, and prostate (in men).
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Retroperitoneal Bleed - Bleeding into the space behind the abdomen, where the esophagus, aorta, inferior vena cava, kidneys, ureters, adrenals, rectum, parts of the duodenum, parts of the pancreas, and parts of the colon are present.
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Intracranial Hemorrhage - This can be fatal and rare.
Bleeding into the soft tissues can progress rapidly, potentially causing increased pressure on muscles due to damage caused by compression of nerves and blood vessels. Affected individuals are also at risk of excessive bleeding during surgery, following trauma, or postpartum.
What Causes Acquired Hemophilia in Rheumatic Diseases?
Several studies believe that the immune system gets triggered to produce autoantibodies (antibodies that target healthy tissue) due to an infection or an underlying disorder (rheumatoid arthritis). Autoantibodies in acquired hemophilia are called inhibitors because they inhibit the function of the affected clotting factor.
Who Is at Risk for Acquired Hemophilia?
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Children are rarely affected and acquired hemophilia is most common among the elderly (40 to 60 years of age).
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Pregnant women tend to have a higher tendency of risk for acquired hemophilia.
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A majority of the individuals have a deficiency of factor VIII which is the most common cause of acquired hemophilia, nevertheless, deficiency of factor IX (acquired hemophilia B) and other factors have also been reported.
How to Diagnose Acquired Hemophilia Associated With Rheumatic Diseases?
An individual known to have rheumatic diseases with a sudden onset of bleeding abnormalities suggests that hemophilia is associated with rheumatic diseases. Rheumatic disease is diagnosed using:
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X-rays.
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Magnetic Resonance Imaging (MRI).
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Blood Tests- Such as erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), antinuclear antibody (ANA), anti-cyclic citrullinated peptides (anti-CCP), complete blood count (CBC), and C-reactive protein (CRP).
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Biopsy.
Acquired hemophilia is confirmed with abnormal coagulation tests. Such tests are as follows:
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Prothrombin Time (PT) - It measures the clotting ability of factors I, II, V, VII, and X. Deficiency of any of these factors in the blood can prolong the clotting time. Individuals with acquired hemophilia have normal prothrombin time.
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Activated Partial Thromboplastin Time (aPTT) - It measures the clotting ability of factors VIII, IX, XI, and XII. A deficiency of any of these factors in the blood can prolong the clotting time. Individuals with acquired hemophilia have an isolated prolonged activated partial thromboplastin time.
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Other Tests- Additional tests to rule out other probable causes of isolated prolonged aPTT such as checking for inhibitors in the blood (for example, lupus anticoagulant) or if the person is on any medication (Heparin therapy) that can affect the results.
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aPTT Mixing Tests - This test is performed by measuring the aPTT in the individual's plasma, which is then mixed with an equal volume of the individual's plasma and normal pooled plasma (NPP) to create a sample. An aPTT test of this sample is done immediately and after one hour of incubation. A mixing study differentiates genetic factor deficiencies from factor inhibitors. In individuals with a factor deficiency, the normal plasma restores the test value to normal; in individuals with a factor inhibitor, it does not. This test can further confirm the diagnosis of acquired hemophilia.
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Tests to Measure Factors Inhibitor Levels - Acquired factor VIII inhibitors are autoantibodies that bind to native factor VIII in a person without congenital hemophilia A. Antibody binding leads to functional FVIII deficiency.
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Signs of Clotting Factor VIII inhibitors - Acquired factor VIII inhibitors are autoantibodies that bind to native factor VIII in an individual without congenital hemophilia A. Antibody binding leads to low activity levels of clotting factor VIII and may suggest acquired hemophilia.
How to Treat Acquired Hemophilia Associated With Rheumatic Diseases?
Treatment modalities differ among individuals based on age, the onset of the condition, the presence of rheumatic diseases, and the severity of bleeding episodes. The primary goal, however, should be to control bleeding episodes. Some of the treatment measures include the following:
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Control Bleeding - This is necessary to reduce morbidity and mortality of individuals. Administration of clotting factor replacement therapy, such as factor VIII concentrates, to replace the deficient clotting factors. Anti-hemorrhagic treatment using bypassing agents (concentrates of factors that bypass the acquired deficiency) or strategies to increase factor VIII levels are recommended in cases of severe bleeding. The bypassing agents are recombinant activated factor VII or activated prothrombin complex concentrate, however, they may not necessarily be effective for all individuals.
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Immunosuppressive Therapy - The presence of factor inhibitors can cause spontaneous bleeding and put the individual at risk of morbidity and mortality. Immunosuppressive therapy helps to eradicate the inhibitor. Corticosteroids may be used to suppress the immune system and prevent the production of antibodies against clotting factors (inhibitors). Other immunosuppressive agents, such as Cyclophosphamide or Rituximab, may also be used. A combination of Methylprednisolone and Cyclophosphamide prevents the immune system from attacking healthy cells.
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Supportive Care - In severe cases, supportive care, such as blood transfusions, may be indicated to manage bleeding episodes and prevent complications.
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Surgery - In severe cases, surgery may be required to control bleeding, particularly if bleeding occurs in the muscles or joints.
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Treatment of Underlying Rheumatic Disease - Treating the underlying rheumatic disease, such as lupus or rheumatoid arthritis, may also help to improve the symptoms of acquired hemophilia. This may involve the use of disease-modifying antirheumatic drugs (DMARDs) or biologic agents.
Conclusion
Acquired hemophilia along with debilitating rheumatic diseases is a life-threatening condition if not diagnosed and treated early. Cases of relapse of acquired hemophilia have also been reported in individuals once immunosuppressive therapy is stopped or if the dose is reduced. Unfortunately, long-term immunosuppressive therapy is not recommended due to the adverse side effects. Individuals with acquired hemophilia need to be closely monitored for prompt treatment.
