Hemophilia
Hemophilia is a hereditary bleeding disorder resulting from a deficiency of specific clotting factors. After a person with hemophilia forms a platelet plug at a bleeding site, the clotting factor deficiency impairs the blood's capacity to form a stable fibrin clot. Bleeding occurs primarily into large joints, especially after trauma or surgery. Spontaneous intracranial bleeding can occur and may be fatal.
Advances in treatment have greatly improved the prognosis for patients with hemophilia, many of whom live normal life spans. Surgical procedures can be done safely at special treatment centers under the guidance of a hematologist.
Causes and incidence
Both hemophilia A and B are inherited as X-linked recessive traits. This means that female carriers have a 50% chance of transmitting the gene to each daughter, who would then be a carrier, and a 50% chance of transmitting the gene to each son, who would be born with hemophilia. Hemophilia A (classic hemophilia), which affects more than 80% of patients with hemophilia, results from a deficiency of factor VIII-C; hemophilia B (Christmas disease), which affects approximately 15% of patients with hemophilia, results from a deficiency of factor IX-C.
The factor VIII gene is located within the Xq28 region, and the factor IX gene is located within Xq27. Females with one defective factor VIII gene are carriers of hemophilia. A large number of disease-causing mutations have been identified in both genes. A specific inversion mutation in the noncoding region of the factor VIII gene is present in approximately 45% of families with severe hemophilia A. Hemophilia A is the most common X-linked genetic disease, occurring in approximately 1 in 10,000 live male births. It is five times more common than hemophilia B.
Signs and symptoms
Hemophilia produces abnormal bleeding, which may be mild, moderate, or severe, depending on the degree of factor deficiency.
Mild hemophilia commonly goes undiagnosed until adulthood because the patient doesn't bleed spontaneously or after minor trauma but has prolonged bleeding if challenged by major trauma or surgery. Postoperative bleeding continues as a slow ooze or ceases and starts again, up to 8 days after surgery.
Severe hemophilia causes spontaneous bleeding. In many cases, the first sign of severe hemophilia is excessive bleeding after circumcision. Later, spontaneous bleeding or severe bleeding after minor trauma may produce large subcutaneous and deep intramuscular hematomas. Bleeding into joints (hemarthrosis) and muscles causes pain, swelling, extreme tenderness and, possibly, permanent deformity.
Moderate hemophilia causes symptoms similar to severe hemophilia but produces only occasional spontaneous bleeding episodes.
Bleeding near peripheral nerves may cause peripheral neuropathy, pain, paresthesia, and muscle atrophy. If bleeding impairs blood flow through a major vessel, it can cause ischemia and gangrene. Pharyngeal, lingual, intracardial, intracerebral, and intracranial bleeding may all lead to shock and death.
Diagnosis
Development of a large cephalohematoma or intracranial hemorrhage after prolonged labor or delivery by forceps or vacuum extraction may be the first indication of a bleeding problem. After the neonatal period, a history of prolonged bleeding after surgery (including dental extractions) or trauma or of episodes of spontaneous bleeding into muscles or joints usually indicates some defect in the hemostatic mechanism. Hemophilia A and B may be clinically indistinguishable, but specific coagulation factor assays can diagnose the type and severity of the disease. A positive family history, prenatal diagnosis, and carrier testing can also help diagnose hemophilia, but nearly one-third of all patients have no family history.
Characteristic findings in hemophilia A include:
❑ factor VIII-C assay, 0% to 30% of normal
❑ prolonged partial thromboplastin time (PTT)
❑ normal platelet count and function, bleeding time, and prothrombin time.
Characteristics of hemophilia B include:
❑ deficient factor IX-C
❑ baseline coagulation results similar to hemophilia A, with normal factor VIII.
In both types of hemophilia, the degree of factor deficiency determines severity:
❑ mild hemophilia — factor levels 5% to 40% of normal
❑ moderate hemophilia — factor levels 1% to 5% of normal
❑ severe hemophilia — factor levels less than 1% of normal.
Treatment
Hemophilia isn't curable, but treatment can prevent crippling deformities and prolong life expectancy. Correct treatment quickly stops bleeding by increasing plasma levels of deficient clotting factors to help prevent disabling deformities that result from repeated bleeding into muscles and joints. (See Factor replacement products.)
Desmopressin (DDAVP — 1-deamino-8-d-arginine vasopressin) administered I.V. or intranasally is usually sufficient to manage bleeding episodes of children and adolescents with mild hemophilia A. Persons with moderate to severe hemophilia A require commercially prepared factor VIII concentrates to treat bleeding episodes. Concentrates derived from human plasma are virally attenuated by one or more available methods significantly minimizing the risk for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B, and hepatitis C contamination. However, no currently available method has been successful in eradicating parvovirus B 19 from blood products. Factor VIII concentrate derived from recombinant technology (rFVIII) has been shown in multiple clinical trials to be as effective as virally attenuated plasma-derived concentrate. Risk for viral contamination is essentially nonexistent in preparations of rFVIII that avoid human serum albumin as a stabilizer.
In hemophilia B, administration of factor IX concentrate during bleeding episodes increases factor IX levels.
The U.S. National Hemophilia Foundation first recommended prophylaxis with factor concentrates in 1994 after investigators in Sweden demonstrated repeated success with this approach. The ultimate goal is to prevent irreversible destructive arthritis that results from repeated hemarthrosis and synovial hypertrophy. Prophylaxis of persons with hemophilia A or B may begin as early as age 1 or 2.
A person with hemophilia who undergoes surgery needs careful management by a hematologist with expertise in hemophilia care. The patient will require replacement of the deficient factor before and after surgery, possibly even for minor surgery such as a dental extraction. (DDAVP may be given before dental extractions and surgery to prevent bleeding.) In addition, epsilon-aminocaproic acid is commonly used for oral bleeding to inhibit the active fibrinolytic system present in the oral mucosa.
Development of factor VIH or factor XI inhibitors occurs in up to 3.5% of children with severe hemophilia A and up to 3% of those with hemophilia B. Studies indicate that certain gene mutations predispose to an increased risk for inhibitor development. Patients with hemophilia who can't achieve hemostasis after use of previously effective factor concentrate doses should be evaluated for factor inhibitors.
Preventive measures include teaching the patient how to avoid trauma, manage minor bleeding, and recognize bleeding that requires immediate medical intervention. Genetic counseling helps carriers understand how this disease is transmitted. (See Managing hemophilia, page 28.)
Special considerations
During bleeding episodes:
❑ Give clotting agents as ordered. The body uses up factor VIII in 48 to 72 hours, so repeat infusions, as ordered, until bleeding stops.
❑ Apply cold compresses or ice bags and raise the injured part.
❑ To prevent recurrence of bleeding, restrict activity for 48 hours after bleeding is under control.
❑ Control pain with an analgesic, such as acetaminophen, propoxyphene, codeine, or meperidine, as ordered. Avoid I.M. injections because of possible hematoma formation at the injection site. Aspirin and aspirin-containing medications are contraindicated because they decrease platelet adherence and may increase the bleeding. Caution should be used when trying other nonsteroidal anti-inflammatory drugs, for example, ibuprofen or ketoprofen.
If the patient has bled into a joint:
❑ Immediately elevate the joint.
❑ To restore joint mobility, begin range-of-motion exercises, if ordered, at least 48 hours after the bleeding is controlled. Tell the patient to avoid weight bearing until bleeding stops and swelling subsides.
After bleeding episodes and surgery:
❑ Watch closely for signs of further bleeding, such as increased pain and swelling, fever, or symptoms of shock.
❑ Closely monitor PTT.
❑ Teach parents special precautions to prevent bleeding episodes.
❑ Refer new patients to a hemophilia treatment center for evaluation. The center will devise a treatment plan for such patients' primary physicians and is a resource for other medical and school personnel, dentists, and others involved in their care.
❑ Persons who have been exposed to HIV through contaminated blood products need special support.
❑ Refer patients and carriers for genetic counseling.
Pictures
Book Source Details
- Book Title: Professional Guide to Diseases (Eighth Edition)
- Author(s): Springhouse
- Year of Publication: 2005
- Copyright Details: Professional Guide to Diseases (Eighth Edition), Copyright © 2005 Lippincott Williams & Wilkins.
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Copyright Details: Professional Guide to Diseases (Eighth Edition), Copyright © 2008 Williams & Wilkins.
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