Pediatric Von Willebrand Disease Medication

Class Summary

Desmopressin is a synthetic analogue of antidiuretic hormone. It is considered the primary treatment for bleeding in individuals with mild von Willebrand disease (VWD). It works by causing release of von Willebrand factor (VWF) from endothelial storage sites.

Desmopressin can be administered intravenously, intranasally, or subcutaneously. The dose for hemostasis is approximately 15 times the dosage used to treat individuals with diabetes insipidus. The regular intranasal preparation (0.1 mg/mL), which is used to treat persons with diabetes insipidus, is too dilute to elicit a hemostatic response. A high-concentration intranasal preparation (ie, Stimate 1.5 mg/mL) has been licensed and has shown a similar response as the intravenous form.

The higher concentration intranasal preparation allows home treatment for bleeding symptoms; however, experience with its use in the surgical setting is limited. Most experience in treating individuals with von Willebrand disease is with intravenous infusion, with which the response is rapid (ie, peak von Willebrand factor levels in approximately 45-90 min of infusion). Doses may be repeated at intervals of 12-24 hours for continued bleeding or for postoperative use. Desmopressin has also been administered subcutaneously with a favorable response.

Desmopressin (Stimate)

Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys.

Test patients for response prior to usage in a bleeding episode. A 2-fold to 5-fold increase in VWF and FVIII commonly is obtained after treatment.

The higher concentration of desmopressin (ie, Stimate 1.5 mg/mL) is prescribed for VWD to provide an adequate dose.

Class Summary

For patients with von Willebrand disease who do not respond to desmopressin, and for individuals with the rare types 2B or 3 von Willebrand disease, plasma-derived factor VIII (FVIII) concentrates that contain von Willebrand factor in high molecular weight can be used. The product used must contain von Willebrand factor in the high–molecular weight form to be effective. However, most available FVIII concentrates do not contain sufficient von Willebrand factor to be used in von Willebrand disease. Cryoprecipitate contains multimeric von Willebrand factor; however, concerns about possible virus transmission have led many clinicians to choose FVIII products that contain multimeric von Willebrand factor and have undergone viral inactivation processes.

Only a minority of currently available FVIII products contain von Willebrand factor; the protein has been eliminated from the others. In general, the dosage of cryoprecipitate or FVIII to be used is calculated on the basis of FVIII units. Other blood products are rarely required for patients with von Willebrand disease. Platelet transfusion may benefit patients with type 3 von Willebrand disease who do not respond to von Willebrand factor–containing concentrates or cryoprecipitate.

Antihemophilic factor/von Willebrand Factor Complex, human (Alphanate, Humate-P)

Some FVIII concentrates (eg, Humate-P, Alphanate) also contain VWF in high molecular weight form. These concentrates are especially useful in types 2B and 3 vWD.

Alphanate is indicated to prevent excessive bleeding for surgical and invasive procedures in vWD in cases in which desmopressin is either ineffective or contraindicated. It is not indicated for patients with severe vWD (ie, Type 3) undergoing major surgery.

Humate-P is indicated for treatment and prevention of spontaneous and trauma-induced bleeding episodes for patients with mild-to-moderate or severe vWD.

Aminocaproic acid (Amicar)

Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. Main problem is that the thrombi that forms during treatment are not lysed and effectiveness is uncertain. Has been used to prevent recurrence of subarachnoid hemorrhage (SAH). Useful in mucous membrane bleeding.