Hemophilia

HEMOPHILIA

Hemophilia is usually an inherited, congenital bleeding disorder characterized by a lack of blood clotting factors, especially factors VIII and IX. It is an X-linked disorder primarily affecting males; females act as carriers. Occurs in 1 in 5,000 males. There is no racial predilection, and hemophilia is found in all ethnic groups.

 80% to 85% have factor VIII deficiency or hemophilia A (classic hemophilia).

 15% to 20% have factor IX deficiency or hemophilia B (Christmas disease).

 Few have factor XI deficiency or hemophilia C.

Transmission of Hemophilia

GENOTYPE OF PARENTS PROBABILITY OF ABNORMALITY IN OFFSPRING

FEMALE MALE

Normal Carrier Hemophiliac Normal Hemophiliac

Female carrier/normal male 50% 50% 0 50% 50%

Noncarrier female/+ male 0 100% 0 100% 0

Female carrier/+ male 0 50% 50% 50% 50%

Pathophysiology and Etiology

1. Hereditary (approximately 80% of patients)

a. Sex-linked, recessive trait--- caused by a gene carried on the X chromosome.

b. Transmitted by asymptomatic females.

c. Appears in males who have the hemophilic gene on their X chromosome.

d. Affected males may pass the gene to female offspring, making them carriers.

e. May appear in females if a female carrier bears offspring w/ a hemophiliac male (rare).

2. Spontaneous mutations may cause the condition when the family history is negative for the disease (about 30% of patients).

3. The basic defect is in the intrinsic phase of the coagulation cascade. The blood clotting factors are necessary for the formation of prothrombin activator, which acts as a catalyst in the conversion of prothrombin to thrombin.

a. The rate of formation of thrombin from prothrombin is almost directly proportional to the amount of prothrombin activator available.

b. The rapidity of the clotting process is proportional to the amount of thrombin formed.

4. The result is an unstable fibrin clot.

5. Platelet number and function are normal; therefore, small lacerations and minor hemorrhages are usually not a problem.

Clinical Manifestations

1. Seldom diagnosed in infancy unless excessive bleeding is observed from the umbilical cord or after circumcision.

2. Usually diagnosed when the child becomes active.

3. Varies in severity, depending on the plasma level of the coagulation factor involved.

a. Level of less than 1% of normal--- severe hemophilia; commonly severe clinical bleeding, with a tendency for spontaneous bleeds.

b. Level of 1% to 5% of normal--- moderately afflicted; may be free from spontaneous bleeding and may not manifest severe bleeding until trauma occurs.

c. Level of 6% to 30% of normal--- mildly afflicted; patients usually lead normal lives and bleed only with severe injury or surgery.

d. Degree of severity tends to be constant within a given family. Within an individual severity does not vary over time unless inhibitor (autoantibody to infused factor) develops.

4. Signs and symptoms of abnormal bleeding include:

a. History of prolonged bleeding episodes such as after circumcision.

b. Easily bruised.

c. Prolonged bleeding from the mucous membranes of the nose and mouth from lacerations.

d. Spontaneous soft tissue hematomas.

e. Hemorrhages into the joints (hemarthrosis) --- especially elbows, knees, and ankles, causing pain, swelling, and limitation of movement.

f. Spontaneous hematuria.

g. GI bleeding.

h. Cyclic bleeding episodes may occur with periods of little bleeding, followed by periods of severe bleeding.

i. Head trauma, resulting in intracranial hemorrhage.

Diagnostic Evaluation

1. Prothrombin time and bleeding time are normal.

2. Partial thromboplastin time--- prolonged.

3. Prothrombin consumption--- decreased.

4. Thromboplastin--- increased.

5. Assays for specific clotting factors--- abnormal.

6. Gene analysis--- to detect carrier state, for prenatal diagnosis.

Management of disease

1. Prompt, early, appropriate treatment is the key to preventing most complications.

2. Must replace missing coagulation factor (VIII or IX) through the administration of type-specific Coagulation concentrates during bleeding episodes.

a. Factor VIII--- made from cryoprecipitate that has been viral inactivated, monoclonal