Etiology. Hemophilia A (factor 8 deficiency) occurs in 1 in 5000 males. Hemophilia B (factor 9 deficiency) occurs in approximately 1 in 25,000. Clinically the two disorders are indistinguishable other than by their therapy (Table 151-3).The lack of factor 8 or factor 9 delays the generation of thrombin, which is crucial to forming a normal, functional fibrin clot and solidifying the platelet plug that has formed in areas of vascular injury. The severity of the disorder is determined by the degree of clotting factor deficiency.
Table 151-3 Comparison of Hemophilia A, Hemophilia B, and von Willebrand Disease FEATURE HEMOPHILIA A HEMOPHILIA B VON WILLEBRAND DISEASE Inheritance X-linked X-linked Autosomal dominant Factor deficiency Factor 8 Factor 9 vWF, factor 8
Bleeding site(s) Muscle, joint, Muscle, joint, Mucous membranes, skin, surgical surgical surgical, menstrual
Ristocetin-induced platelet Normal Normal Normal, low, or increased at agglutination
PFA, Platelet function analyzer-100; vWF, von Willebrand factor. *Desmopressin (DDAVP) for mild to moderate hemophilia A or type 1 von Willebrand disease.
Clinical Manifestations. Patients with less than 1% (severehemophilia) factor 8 or factor 9 may have spontaneous bleeding or bleeding with minor trauma. Patients with 1% to 5% (moderate hemophilia) factor 8 or factor 9 usually require moderatetrauma to induce bleeding episodes. In mild hemophilia (>5%factor 8 or factor 9), significant trauma is necessary to inducebleeding; spontaneous bleeding does not occur. Mild hemophiliamay go undiagnosed for many years, whereas severe hemophiliamanifests in infancy when the child reaches the toddler stage. Insevere hemophilia, spontaneous bleeding occurs, usually in themuscles or joints (hemarthroses).
Laboratory Studies. The diagnosis of hemophilia is based on a prolonged activated partial thromboplastin time(aPTT). In the aPTT, a surface-active agent activates the intrinsic system of coagulation, of which factors 8 and 9 are crucial components. In factor 8 or factor 9 deficiency, the aPTT is quite prolonged but should correct to normal when the patient’s plasma is mixed 1:1 with normal plasma. When an abnormal aPTT is obtained, specific factor assays are needed to make a precise diagnosis (see Table 151-2) to determine the appropriate factor replacement therapy. Prenatal diagnosis and carrier diagnosis are possible using molecular techniques.
Treatment. Early, appropriate replacement therapy is the hallmark of excellent hemophilia care. Acute bleeding episodes are best treated in the home when the patient has attained the appropriate age and the parents have learned home treatment. Bleeding associated with surgery, trauma, or dental extraction often can be anticipated, and excessive bleeding can be prevented with appropriate replacement therapy. Prophylactic therapy starting in infancy has greatly diminished the likelihood of chronic arthropathy in children with hemophilia. For life-threatening bleeding, levels of 80% to 100% of normal factor 8 or factor 9 are necessary. For mild to moderate bleeding episodes (hemarthroses), a 40% level for factor 8 or a 30% to 40% level for factor 9 is appropriate. The dose can be calculated using the knowledge that 1 U/kg body weight of factor 8 increases the plasma level 2%, whereas 1.5 U/kg of recombinant factor 9 increases the plasma level 1%:
Dose for factor 8=desired level (%)× weight (kg)× 0.5
Dose for recombinant factor 9=desired level (%) × weight (kg) ×1.5