Desmopressin acetate is a synthetic vasopressin analog with minimal vasopressor effect. Desmopressin triples or quadruples the initial factor 8 level of a patient with mild or moderate (not severe) hemophilia A, but has no effect on factor 9 levels. When adequate hemostatic levels can be attained, desmopressin is the treatment of choice for individuals with mild and moderate hemophilia A. Aminocaproic acid is an inhibitor of fibrinolysis that may be useful for oral bleeding.
Patients treated with older factor 8 or 9 concentrates derived from large pools of plasma donors were at high risk for hepatitis B, C, and D and HIV. Recombinant factor 8 and factor 9 concentrates are safe from virally transmitted illnesses. Acquiredimmunodeficiency syndrome (AIDS) is the most common causeof death in older hemophilia patients (who received plasma-derived factors). Many older patients also have chronic hepatitis C.
Inhibitors are IgG antibodies directed against transfusedfactor 8 or factor 9 in congenitally deficient patients. Inhibitorsarise in 15% of severe factor 8 hemophiliacs but are less common in factor 9 hemophiliacs. They may be high or low titerand show an anamnestic response to treatment. The treatmentof bleeding patients with an inhibitor is difficult. For low titerinhibitors, options include continuous factor 8 infusions. Forhigh titer inhibitors, it is usually necessary to administer a product that bypasses the inhibitor, preferably recombinant factor 7a.Activated prothrombin complex concentrates, used in the pastto treat inhibitor patients, paradoxically increased the risks ofthrombosis, resulting in fatal complications, such as myocardial infarction. For long-term treatment of inhibitor patients, induction of immune tolerance by repeated infusion of the deficientfactor with or without immunosuppression may be beneficial.
Early institution of factor replacement and continuous prophylaxis beginning in early childhood should prevent the chronic joint disease associated with hemophilia.
Etiology. Von Willebrand disease is a common disorder (1% ofthe population) caused by a deficiency of vWF, an adhesive protein that serves two functions: acting as a bridge between sub-endothelial collagen and platelets and binding and protectingcirculating factor 8 from rapid clearance from circulation. Von Willebrand disease usually is inherited as an autosomal dominanttrait and rarely as an autosomal recessive trait. vWF may be eitherquantitatively deficient (partial = type 1 or absolute = type 3) orqualitatively abnormal (type 2 = dysproteinemia). Approximately80% of patients with von Willebrand disease have classic (type 1)disease (i.e., a mild to moderate deficiency of vWF). Several othersubtypes are clinically important, each requiring different therapy.
Clinical Manifestations. Mucocutaneous bleeding, epistaxis, gingival bleeding, cutaneous bruising, and menorrhagia occur in patients with von Willebrand disease. In severe disease, factor 8 deficiency may be profound, and the patient may also have manifestations similar to hemophilia A (hemarthrosis). Findings in classic von Willebrand disease differ from findings in hemophilia A and B (see Table 151-3).
Laboratory Testing. vWF testing involves measurement ofthe amount of protein, usually measured immunologically as thevWF antigen (vWF:Ag). vWF activity (vWF:Act) is measuredfunctionally in the ristocetin cofactor assay (vWFR:Co), whichuses the antibiotic ristocetin to induce vWF to bind to platelets.