Clinical Aspects of and Therapy for Hemophilia A. Incidence. Clinical Severity, страница 6

Doses can be calculated by multiplying the recipient plasma volume in milliliters by the desired increment of factor VIII in units per milliliter. A simpler and reproducible dose calculation is that each unit of factor VIII infused per kilogram of body weight yields a 2% rise in plasma factor VIII level (i.e., 0.02 U/ml). An example of therapy for a 50-kg patient with an extensive laceration would include maintenance of a 30% factor VIII level in vivo until healing is complete. This can be accomplished by an initial infusion to the 60% level with 1,500 U (30 1 50 kg) of factor VIII, followed by 750 U every 12 hours thereafter for 7–10 days, with dose adjustments being made every few days as indicated by factor VIII assays.

For patients with major or life-threatening lesions, the laboratory measurement of in vivo factor VIII activity is advisable because of variations that result from the responses of patients to such infusions. 33 Substitution of the activated partial thromboplastin time or another screening test for a formal factor VIII assay should be avoided because the results may be misleading.

Antihemophilic factor may be given on a variety of schedules to keep the amount of in vivo factor VIII above a fixed level, thus converting a patient with severe deficiency to one with a mild or moderate deficiency. Prophylactic factor used on a regular basis in small children is being explored as a method of preventing later costly joint deterioration. Such a program can dramatically reduce the incidence of hemorrhages, but it can also increase the expense, the drain on plasma resources, and possibly the side effects as well. Indications for such prophylactic use include intensive physical therapy, recurrent hemorrhage in a single joint or chronic synovitis, or learning a new physical activity.

Indications For  Infusion

Guidelines for doses of replacement therapy are  variable from treater to treater, and there should be room  for upward dose modification when the clinician is  concerned that lesions are advanced or more threatening  than usual. Below is a link to a table of typical initial doses of  replacement therapy used at our hemophilia treatment  center.

Table Table

Other Therapeutic Principles

Acute hemarthrosis should be treated with early infusion therapy, which will minimize the risk of chronic synovitis or progressive arthropathy and avoid the need for excessive pain medication or for arthrocentesis. Aspiration of the joint during an acute hemorrhage should be avoided unless the swelling and pain are very severe or a septic joint is suspected. The total consumption of factor concentrate and health care costs are the same in patients so treated as in those in whom advanced hemorrhagic lesions develop, and the health of the patient is clearly improved. MLID75089203  34

Chronic hemophilic arthropathy can improve remarkably from several weeks or months of intensive physical therapy for muscle building and increased joint stability, intervals of avoiding weight bearing to allow for the regression of synovitis, and the correction of flexion contractures by wedging casts, night splints, or traction. 35 Regular prophylactic infusions of factor VIII can also be used to prevent traumatic bleeding.

Chronic synovitis should be treated with intensive factor VIII replacement plus conservative orthopaedic and physical therapy measures, a program that produces a medical synovectomy in about one-half of the treated joints. 36 Surgical synovectomy has been suggested for patients with nonhealing chronic synovitis or with frequently recurring hemarthrosis and the progressive development of severe chronic arthropathy; it has also been successful in preventing long-term sequelae. 37 Surgical synovectomy is associated not only with a marked decrease in the frequency of hemorrhage in the joint, but also with some loss of joint motion, which may not be fully regained despite physical therapy. More recently, radioactive synovectomies, performed by injecting radioactive dysprosium into a joint, have been done successfully. Such a procedure can be considered for patients who are poor surgical risks.