Chapter 135. Hemophilias and von Willebrand Disease

The most common hemophilias are caused by genetic deficiencies of factor VIII (hemophilia A) or factor IX (hemophilia B).

Clinical Features

Bleeding complications depend on severity of the disease. Patients with severe disease (factor VIII or factor IX activity level <1%) experience spontaneous bleeds and difficult to control bleeding after trauma. Patients with moderate disease (1% to 5% factor activity level) may bleed spontaneously but more commonly bleed after trauma. Patients with mild disease (5% to 40% factor activity level) usually only bleed after trauma. Easy bruising, recurrent hemarthrosis, and muscle hematomas are the most common clinical manifestations. Mucocutaneous, abdomenal, retroperitoneal, GU and CNS bleeding also occur. Neck hematomas may obstruct the airway. Unless there is another underlying disease, most patients with hemophilia do not have problems with minor cuts or abrasions.

Diagnosis and Differential

Clinically, it is impossible to differentiate between hemophilias A and B. Laboratory testing in patients with hemophilia most often shows a normal prothrombin time (PT), prolonged partial thromboplastin time (PTT), and a normal bleeding time. However, if greater than 30% to 40% of factor activity is present, the PTT may be normal. Specific factor assays may be used to differentiate between the types of hemophilia. Ten percent to 25% of patients with hemophilia A and 1% to 2% of patients with hemophilia B will develop an inhibitor, which is an antibody against the deficient factor. The quantity of inhibitor is measured by the Bethesda inhibitor assay (BIA) and is reported in BIA units. The presence of an inhibitor makes treatment more difficult.

Emergency Department Care and Disposition

The mainstay of therapy is early factor replacement. Replacement factor products are listed in Table 135-1.

1. Determine the type of hemophilia and the presence or absence of inhibitor. See Table 135-2 for factor replacement guidelines. Factor replacement may need to be instituted before definitive imaging after head trauma and other life-threatening injuries. If an inhibitor is present, use therapy as outlined in Table 135-3.

2. Determine the desired factor activity level. Factor activity level determines how much factor replacement is required. Calculate the amount of factor needed using the patient's weight and the desired increase in factor:

   • Factor VIII required = (Target factor – Base line factor)/2 × weight (kg)
   • Factor IX required = (Target factor – Base line factor)/2 × weight (kg)

   For severe hemophilia, assume 0% intrinsic activity.

3. Treat patients with undiagnosed bleeding disorders with fresh frozen plasma (FFP). FFP contains 1 unit of factor VIII/mL. Specific factor assays should guide further therapy.

4. Treat minor bleeding in patients with mild hemophilia A with desmopressin (DDAVP) 0.3 microgram/kilogram IV over 15 to 30 min or DDAVP 150 micrograms single spray in each nostril (for children >5 years, DDAVP 150 micrograms single spray in 1 nostril). Very mild mucosal bleeding can also be treated with antifibrinolytic agents, such as ε-aminocaproic acid(EACA) 75 to 100 milligrams/kilogram (up to 6 grams) IV/PO every 6 hours or tranexamic acid 10 to 25 milligrams/kilogram IV every 6 hours.

5. Indications for admission include bleeding involving the head, neck, pharynx, retropharynx, or retroperitoneum, potential compartment syndrome, inability to control pain; and treatment requiring multiple factor replacement.

Clinical Features

Von Willebrand disease (vWD) is a group of disorders caused by a defect or deficiency of von Willebrand factor (vWF). vWF is a cofactor for platelet adhesion and a carrier protein for factor VIII in the plasma. Type 1 vWD is most common; patients have 20% to 50% of normal vWF levels and usually manifest with skin and mucosal bleeding symptoms. Patients with Type 2 vWF have abnormal and dysfunctional vWF. Patients with Type 3 vWF have complete vWF deficiency and have clinical presentations similar to hemophilia. Patients with mild vWF are frequently unaware of the disease until bleeding occurs after a traumatic episode or surgical procedure.

Diagnosis and Differential

The PT and PTT are usually normal. The bleeding time is prolonged and vWF activity is low. Variability in vWF levels can make it difficult to distinguish vWD from hemophilia A.

Emergency Department Care and Disposition

The treatment of vWD depends on the type of disease and the severity of bleeding. Indications for admission are similar to patients with hemophilia.

1. The mainstay of treatment for bleeding in type 1 vWD is desmopressin(DDAVP) 0.3 microgram/kilogram (up to 20 micrograms) SC/IV every 12 to 24 hours for up to 4 doses or DDAVP 150 micrograms single spray in each nostril (for children >5 years, DDAVP 150 micrograms single spray in 1 nostril). If there is no response to DDAVP, administer factor VIII concentrate or cryoprecipitate as described for type 2 and 3 vWD.

2. Factor VIII concentrate containing vWF is used to treat bleeding in patients with type 2 or 3 disease (Table 135-1).

3. Cryoprecipitate 10 bags IV every 12 to 24 hours can be used for type 1 refractory to DDAVP or type 2 or 3 vWD. There is, however, a risk of viral transmission.

4. Platelet transfusions may benefit patients with type 3 vWD who do not respond to vWF-containing plasma products.

5. Oral contraceptives may help increase vWF levels and limit menstrual bleeding in women with vWD and menorrhagia.

6. Patients who have sustained dental injuries or who require dental procedures may need ε-aminocaproic acid(EACA) 75 to 100 milligrams/kilogram (up to 6 grams) PO every 6 hours or tranexamic acid mouthwash for 5 to 10 days.