The hemophilias are a group of diseases which manifest as an increased bleeding tendency. These inherited diseases are secondary to a deficiency of clotting factors. In hemophilia A, the deficient clotting factor is factor VIII, and in hemophilia B (Christmas disease), factor IX is deficient. Rosenthal’s disease refers to a deficiency of factor XI and is a rare bleeding disorder seen mostly in Ashkenazi Jews. Rosenthal’s disease is generally not as severe clinically as the other hemophilias. The degree of clotting factor deficiency determines how severe the symptoms manifest. When levels are less than one percent (severe hemophilia), clinical symptoms are severe and generally manifest early in life. In patients with factor activity levels of between one and five percent (moderate hemophilia) their risk of bleeding increases only after surgery or trauma and generally are not subject to spontaneous hemorrhaging. Hemophilia patients with factor activity levels between six and 24 percent (mild disease) are only at risk for complications with major surgery or severe trauma.
This disorder is transmitted via the X-linked chromosome, and therefore the disorder is seen almost exclusively in males. However, women may inherit the abnormal gene (all daughters of a hemophiliac male will be affected) and serve as carriers with their sons having a 50% chance of having the disease and their daughters have a 50% chance of being carriers. Prenatal evaluation with restriction fragment length polymorphisms (RFLPs) can identify carriers.
Symptoms include bleeding (epistaxis, hematuria, gastrointestinal bleeding or intracerebral hemorrhaging), hemarthrosis and bleeding into soft tissues with hematoma formation. In hemarthrosis, large joints are affected, bleeding generally resolves spontaneously, but patients are subject to repetitive episodes that results in joint damage and severe arthritis. Since intracerebral hemerrohage is a frequent cause of death in afflicted patients, headaches and any type of head trauma must be aggressively evaluated.
The only abnormality noted on screening labs is a prolonged aPTT. Diagnosis and disease severity are established by measuring factor VIII activity in hemophilia A and factor IX in hemophilia B. Since a prolonged aPTT may also be seen with inhibitors, the patient’s plasma is mixed with normal plasma and the aPTT is remeasured. A complete or partial correction after mixing indicates hemophilia; whereas, an aPTT that is unaffected by mixing indicates the presence of an inhibitor.
Treatment of hemophilia A entails either factor replacement with cryoprecipitate or purified factor VIII. Patients may be trained to self administer therapy at home in cases of minor bleeds. Patients with minor disease (level greater than six percent) may also respond to therapy with desmopressin (DDAVP) 0.3 micrograms/kg over 30 minutes. Stimate is a highly concentrated form of intranasal desmopressin that may be used in hemophilia A patients. Approximately 10 percent of patients receiving factor replacement may develop an inhibitor. Patients who develop and inducible inhibitor may require porcine factor VIII. Recombinant factor IX replacement should be administered in cases of hemophilia B. Generally, hemophilia patients should be followed by a hematologist.
When patients present for emergency therapy for a bleeding episode or after trauma, speed is the most important factor. Factor concentrate therapy should not be delayed while the patient undergoes diagnostic procedures. Factor replacement therapy is given intravenously at a rate of 3 cc/minute for adults and 100 units/minute for children. With factor VIII therapy, each 1 unit/kg body weight will increase the factor level by 2%. With factor IX replacement therapy, the factor level will rise by 1% for each 1.2 units/kg administered. The half lives for factors VIII and IX replacement therapies are 12 and 18 hours, respectively. The target level of serum factor during replacement therapy depends on the type hemophilia and the type of hemorrhage as follows:
TYPE OF HEMORRHAGE TARGET FACTOR LEVEL
HEMOPHILIA A joint or muscle except iliopsoas, and soft tissue 40-50% (25units/kg)
nasal or oral mucosa 20-30% (15 units/kg)
iliopsoas, CNS, throat, neck, GI, ophthalmic,
surgical or traumatic 80-100% (50 units/kg)
renal or deep laceration >50% (25 units/kg)
HEMOPHILIA B joint or muscle except iliopsoas, and soft tissue 40-50% (60 units/kg)
nasal or oral mucosa 20-30% (35 units/kg)
iliopsoas, CNS, throat, neck, GI, ophthalmic,
surgical or traumatic 80-100% (120 units/kg)
renal or deep laceration >40% (50 units/kg)
Epsilon-amino-caproic acid should also be administered to patients with epistaxis and oral mucosal bleeding to prevent rapid clot lysis. Epsilon-amino-caproic acid may be administered without factor replacement for superficial mucosal injuries. The dosage is 75 mg/kg for pediatric patients and 6 grams every six hours for adults.