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Hemophilia, Type A
Updated: Oct 6, 2008
Introduction
Background
Hemophilia A is an inherited, X-linked, recessive disorder resulting in deficiency of functional plasma coagulation factor VIII. Significant rates of spontaneous mutation and acquired immunologic processes can result in this disorder as well.
Morbidity and death are primarily the result of hemorrhage, although infectious diseases (eg, HIV, hepatitis) became prominent, particularly in patients who received blood products prior to 1985.
For related information, see Medscape's Hematology-Oncology Resource Center.
Pathophysiology
Factor VIII deficiency, dysfunctional factor VIII, or factor VIII inhibitors lead to the disruption of the normal intrinsic coagulation cascade, resulting in spontaneous hemorrhage and/or excessive hemorrhage in response to trauma.
Hemorrhage sites include joints (eg, knee, elbow), muscles, CNS, GI system, genitourinary system, pulmonary system, and cardiovascular system. Intracranial hemorrhage is most common in patients younger than 18 years and can be a fatal event.
Patients who acquired HIV, hepatitis, or other viruses suffer from maladies associated with those infections.
Frequency
United States
An estimated 17,000 people were affected with hemophilia A in the United States in 2003.
Approximately 1 per 5,000-10,000 males are born with hemophilia A.
Mortality/Morbidity
The death rate for those affected with hemophilia A is not reported. The life span approaches that of the healthy population, excluding individuals infected with HIV.- Severe disease, defined as less than 1% factor VIII activity, presents in children younger than 1 year and accounts for 43-70% of those with hemophilia A.
- Moderate disease, defined as 1-5% factor VIII activity, presents in children aged 1-2 years and accounts for 15-26% of those with hemophilia A.
- Mild disease, defined as greater than 5% factor VIII activity, presents in children older than 2 years and accounts for 15-31% of those with hemophilia A.
Race
Hemophilia occurs in all races and ethnic groups. Rates of hemophilia among whites, African Americans, and Hispanic males in the US are similar.
Sex
- Because hemophilia is an X-linked, recessive condition, it occurs predominantly in males.
- Occasionally, cases are reported in females; however, females usually are asymptomatic carriers.
Age
Patients often present in infancy or childhood.
Clinical
History
For patients in whom hemophilia is suspected, ascertain the history of hemorrhage disproportionate to trauma, spontaneous hemorrhage, familial hemorrhage, concomitant illness (eg, chronic inflammatory disorders, autoimmune diseases, hematologic malignancies [acquired form], allergic drug reactions), and pregnancy.
For individuals with documented hemophilia, ascertain the type of deficiency (eg, VIII, IX, von Willebrand), percent factor deficiency, known presence of inhibitors, and HIV/hepatitis status. For patients with mild-to-moderate disease, determine responsiveness to desmopressin acetate (DDAVP).
- Hemorrhage
- General - Weakness and orthostasis
- Musculoskeletal (joints) - Tingling, cracking, warmth, pain, stiffness, and refusal to use joint (children)
- CNS - Headache, stiff neck, vomiting, lethargy, irritability, and spinal cord syndromes
- GI - Hematemesis, melena, frank red blood per rectum, and abdominal pain
- Genitourinary - Hematuria, renal colic, and postcircumcision bleeding
- Other - Epistaxis, oral mucosal hemorrhage, hemoptysis, dyspnea (hematoma leading to airway obstruction), compartment syndrome symptoms, and contusions; excessive bleeding with routine dental procedures
- Infectious disease
- HIV/AIDS-related symptoms
- Hepatitis-related symptoms
Physical
- General signs of hemorrhage
- Tachycardia
- Tachypnea
- Hypotension
- Orthostasis
- Organ system–specific signs of hemorrhage
- Musculoskeletal (joints) - Tenderness, pain with movement, decreased range of motion, effusion, and warmth
- CNS - Abnormal neurologic exam findings, altered mental status, and meningismus
- GI - Can be painless, hepatic/splenic tenderness, and peritoneal signs
- Genitourinary - Bladder spasm/distension/pain and costovertebral angle pain
- Other - Hematoma leading to location-specific signs (eg, airway obstruction, compartment syndrome)
- Infectious disease
- HIV/AIDS-related signs
- Hepatitis-related signs
Causes
Hemophilia A is caused by an inherited or acquired genetic mutation or an acquired factor VIII inhibitor.
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References
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Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Found. Recommendations regarding the use of recombinant factor VIII in the treatment of hemophilia A. Medical Bulletin # 232. 1995;1-2.
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Further Reading
Keywords
hemophilia type A, hemophilia A, deficiency of functional plasma coagulation factor VIII, factor VIII deficiency, dysfunctional factor VIII, factor VIII inhibitors, disruption of the normal intrinsic coagulation cascade
