Acquired Hemophilia - Causes, Signs, Diagnosis, and Treatment

Introduction

Acquired hemophilia differs from congenital hemophilia, a group of rare genetic disorders caused by mutations in genes encoding specific clotting factors. The main form of hemophilia is hemophilia A (classical hemophilia). This is an X-related disorder that primarily affects men but can also affect women. It is caused by a deficiency or inactivation of factor VIII, the same clotting factor that affects most people with acquired hemophilia. Both diseases are associated with deficiencies of the same clotting factors, but the bleeding patterns are quite different. The reasons for the different bleeding patterns among these diseases are not fully understood.

What Is Acquired Hemophilia?

Acquired hemophilia is an autoimmune disease in which the immune system attacks blood clotting factor VIII, shutting it down and causing excessive bleeding. Autoimmune diseases occur when the body's immune system mistakenly attacks healthy cells and tissues.

The disease affects men and women equally but usually begins later in life.

What Causes Acquired Hemophilia?

• Acquired hemophilia is an autoimmune disease. It occurs when the immune system mistakenly produces antibodies that attack healthy tissue, specifically specialized proteins known as clotting factors, most commonly clotting factor VIII.

• Acquired hemophilia is an autoimmune disease. It occurs when the immune system mistakenly produces antibodies that attack healthy tissue, specifically specialized proteins known as clotting factors, most commonly clotting factor VIII.

• When antibodies target healthy tissue, they are called autoantibodies. Researchers believe that a triggering event (such as an infection or underlying disease) may prompt the immune system to produce autoantibodies. AH, autoantibodies are called inhibitors because they block the function of the affected clotting factors.

Acquired hemophilia is primarily a disease of the elderly. In about 50 % of patients, no underlying disease or precipitating event can be identified (idiopathic form). The remaining have coexisting diseases or conditions, including autoimmune diseases such as,

• Lupus.

• Rheumatoid arthritis.

• Multiple sclerosis.

• Sjögren's syndrome

• Temporal arteritis.

• Inflammatory bowel disease or ulcerative colitis.

• Infections.

• Diabetes.

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• Hepatitis.

• Respiratory or dermatological disease.

• Hematological cancer (blood cancer) or certain solid tumors.

Acquired hemophilia has also been pointed out to be associated with drugs such as Penicillin and Interferon, and its association with pregnancy has also been reported mainly in the postpartum period.

What Signs and Symptoms Are Seen With Acquired Hemophilia?

People with acquired hemophilia may have no bleeding, minor or life-threatening bleeding. Most patients present with bleeding in the skin, muscles, soft tissues, and mucous membranes. Episodes of joint bleeding are rare. Specific symptoms include nosebleeds (epistaxis), bruising all over the body, hard swellings of clotted blood (hematoma), hematuria, and bleeding in the digestive or genitourinary tract.

How Is Acquired Hemophilia Diagnosed?

Acquired hemophilia should be suspected on the basis of clinical presentation and confirmed by prominent coagulation studies. Diagnosis should be considered in patients with recent abnormal bleeding and isolated prolongation of activated partial thromboplastin time (aPTT), especially in older women and prenatal and postpartum women.

How Is Acquired Hemophilia Treated?

Treatment options for acquired hemophilia include:

• Eliminate or help eliminate inhibitors by treating underlying conditions or discontinuing interfering drugs.

• Clinically relevant bleeding can be treated with recombinant porcine FVIII sequences (rpFVIII) if the baseline anti-porcine FVIII inhibitor titer is ≤20 BU. Recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrate (APCC).

• The availability and cost of the active ingredient drive the choice and, in the case of rpFVIII, the baseline titer of the anti-porcine FVIII inhibitor and the ability to monitor rpFVIII.

• Human FVIII concentrate can be used for hemostasis if the patient has low FVIII inhibitor levels (<5 BU) and no other options are available. However, dosage guides are not available, and large dosages may be required.

• Human FVIII concentrate can be used for hemostasis if the patient has low FVIII inhibitor levels (<5 BU) and no other options are available. However, dosage guides are not available, and large dosages may be required.

• Eradication of inhibitors by immunosuppression should begin as soon as acquired hemophilia is diagnosed.

• First-line therapy to eradicate inhibitors is Corticosteroids alone or in combination with Rituximab or Cyclophosphamide.

• Cyclosporine salvage therapy is particularly effective in patients with underlying systemic lupus erythematosus.

What Are the Clinical Conditions Associated With Acquired Hemophilia?

Acquired hemophilia results from the formation of autoantibodies (usually immunoglobulin G [IgG]) against clotting factors. Many diseases are associated with acquired FVIII inhibitors. FVIII autoantibodies rarely occur as an idiosyncratic response to drugs. However, approximately 50 % of cases are idiopathic and occur without associated comorbidities or medications.

FVIII autoantibodies rarely occur as an idiosyncratic response to drugs. However, approximately 50 % of cases are idiopathic, occurring without associated comorbidities or medications.

• Autoimmune disease.

• Pregnancy.

• Inflammatory bowel disease and ulcerative colitis.

• Skin diseases (psoriasis, pemphigus, etc.).

• Respiratory diseases (asthma, chronic obstructive pulmonary disease, etc.).

• Allergic drug reaction.

• Diabetes.

• Acute hepatitis B infection.

• Acute hepatitis C infection.

• Malignant tumors - Solid tumors (prostate, lung, colon, pancreas, stomach, bile duct, head and neck, cervix, breast, skin, kidney).

• Hematologic malignancy.

Autoimmune diseases include:

• Rheumatoid arthritis.

• Systemic lupus erythematosus.

• Multiple sclerosis.

• Temporal arteritis

• Sjögren's syndrome.

• Autoimmune hemolytic anemia.

• Goodpasture syndrome.

• Myasthenia gravis.

• Basedow's disease.

• Autoimmune hypothyroidism.

Allergic drug reactions can occur for the following reasons:

• Penicillin and its derivatives.

• Sulfamide.

• Phenytoin.

• Chloramphenicol.

• Methyldopa.

• Thioxanthene deposits.

• Interferon alpha.

• Fludarabine.

• Vaccination against BCG.

• Desvenlafaxine.

Hematologic malignancies include:

• Chronic lymphocytic leukemia

• Non-Hodgkin's lymphoma.

• Multiple myeloma.

• Waldenstrom macroglobulinemia.

• Myelodysplastic syndrome.

• Myelofibrosis.

• Erythroleukemia.

Conclusion

Acquired hemophilia (AH) is a rare autoimmune disease characterized by bleeding in patients with no personal or family history of coagulation or clotting-related disorders. In AH, the body produces antibodies that attack clotting factors, most commonly factor VIII which causes complications related to abnormal and uncontrolled bleeding which can be life-threatening. Approximately 50 % of patients have an identifiable underlying medical condition. The remaining 50 % are of unknown cause (idiopathic).