Clinical Aspects of and Therapy for Hemophilia A. Incidence. Clinical Severity, страница 7

Joint replacement has been performed with excellent results for advanced hip arthropathy. MLID89209501  38 Although total knee replacements have now been performed in many patients, orthopaedists have generally restricted this procedure to patients with such severe knee pain that fusion is the only alternative (Fig. 106-11). Other joint prosthesis procedures, such as total shoulder replacements, are also successfully performed in persons with hemophilia.

Dental care should begin with preventive dentistry early in life to minimize expense and subsequent morbidity. Restorative dentistry can now be performed with adequate local anesthesia, including the use of mandibular block, under coverage of factor VIII replacement. MLID78172062  39 For oral surgery, the use of fibrinolysis inhibitors such as e-aminocaproic acid or tranexamic acid markedly reduces the amount of coagulation factor replacement needed for hemostasis. MLID78172062  39 When e-aminocaproic acid is given orally at full therapeutic doses for 7–10 days, a single factor VIII infusion of 40 U/kg just prior to the oral surgery is often sufficient for normal hemostasis. If persistent, severe oozing occurs, another factor VIII infusion may be needed.

Therapy for Mild Hemophilia A

Patients with mild hemophilia A (factor VIII levels >5%) do not bleed spontaneously, but usually only after trauma or surgical procedures. The current treatment of choice for patients with factor VIII levels >10% is DDAVP (Stimate), a synthetic analogue of vasopressin. MLID89027065  40 Although its exact mechanism of action is not understood, it is thought to stimulate release of factor VIII from storage sites. MLID81134059  41 The routine dosage is 0.3 ug/kg in 50 ml of normal saline given intravenously over a period of 30–40 minutes. In a factor VIII-deficient patient, DDAVP will usually increase the factor VIII level threefold. 42 Thus, it may not be helpful in patients with factor VIII levels of <10%.

In order to assess how an individual patient will respond to DDAVP, a staging test should be done. When the patient is not bleeding, a baseline factor VIII level is obtained and then the dose of DDAVP is administered. Thirty to 45 minutes after the infusion stops, a second factor VIII level is checked. The factor VIII level should rise at least threefold. If the levels rise to >80%, the response is adequate for major surgery. In some patients DDAVP can only be used for minor hemorrhages since the factor VIII levels do not rise sufficiently. DDAVP can also be used with factor concentrate in mild hemophiliacs to obtain high levels of factor VIII if needed. When DDAVP is used for major surgery, it should be given 1 hour before surgery and then every 12 hours. Tachyphylaxis may occur after repeated doses secondary to depletion of factor VIII from storage sites. MLID89027065  40 Thus factor VIII levels should be checked frequently after the first 2 days. If tachyphylaxis does occur, factor concentrate must be substituted.

If a patient with mild hemophilia has an inadequate response to DDAVP, cryoprecipitate or factor concentrate must be used when the patient has surgery or encounters trauma. Since plasma-derived concentrates undergo effective virucidal procedures while cryoprecipitate cannot (and recombinant concentrate is now available), the use of factor concentrates is recommended.

Although DDAVP is usually administered in a hospital or emergency room setting, a protocol can be adapted for home use. Equivalent results with subcutaneous DDAVP can be obtained, which would make home therapy much simpler. MLID88178538  43 Unfortunately, no subcutaneous preparation of DDAVP is available in the United States. Intranasal DDAVP in formulations concentrated enough to increase factor VIII levels as efficaciously as intravenous DDAVP is now available, making home management simpler.