eMedicine Specialties > Pediatrics: General Medicine > Hematology
Von Willebrand Disease: Treatment & Medication
Updated: May 21, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
Evidence-based guidelines for the diagnosis and management of von Willebrand disease (VWD) have been established.2,3
Minor bleeding problems in patients with von Willebrand disease, such as bruising or a brief nosebleed, may not require specific treatment. For more serious bleeding, medications that can raise the von Willebrand factor (VWF) level and, thereby, limit bleeding are available. The goal of therapy is to correct the defect in platelet adhesiveness (by raising the level of effective von Willebrand factor) and the defect in blood coagulation (by raising the factor VIII [FVIII] level). In recent years, desmopressin (1-deamine-8-D-arginine vasopressin [DDAVP]) has become a mainstay of therapy for most patients with mild von Willebrand disease. At appropriate doses, DDAVP causes a 2-fold to 5-fold increase in plasma von Willebrand factor and FVIII concentrations in individuals who are healthy and patients who are responsive. DDAVP can be used to treat bleeding complications or to prepare patients with von Willebrand disease for surgery.
In general, a patient's responsiveness to DDAVP prior to its use for these purposes can be determined. Once determined, such responsiveness is generally consistent in patients over time and within families. In patients with serious bleeding, prompt treatment is important in order to decrease the possibility of complications.
Remember that in type IIB von Willebrand disease, DDAVP may cause a paradoxical drop in the platelet count and should not be used in a therapeutic setting without prior testing to see how the patient responds.
Consultations
Consult a pediatric or adult hematologist.
Activity
No evidence suggests that extensive activity restrictions are necessary for most patients with mild type1 von Willebrand disease. Patients with more severe forms of von Willebrand disease should follow guidelines developed for patients with severe hemophilia.
Medication
Vasopressin analogues
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.
Adult
Pediatric
0.3 mcg/kg IV or 1-2 inhalations of nasal spray; use high concentration product (1.5 mg/mL)
Coadministration with demeclocycline and lithium decrease effects; fludrocortisone and chlorpropamide increase effects of desmopressin
Documented hypersensitivity; platelet-type von Willebrand disease; no response in previous testing; thrombocytopenia may occur in patients with Type IIB VWD
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Restrict free-water intake to avoid hyponatremia; mild facial flushing and headache may occur; tachyphylaxis develops with repeated usage; may cause thrombocytopenia in patients with Type IIB VWD
Plasma products
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.
Adult
Note: Ratio of vWF:RCoF activity and FVIII potency contained in each vial of Alphanate or Humate-P is on vial's label; this ratio varies by lot, so dosage should be reevaluated whenever lot selection is changed
Alphanate: Preoperative dose: 60 vWF:RCoF IU/kg IV
Subsequent infusions: 40-60 vWF:RCof IU/kg IV q8-12h prn
Dose may be reduced after postoperative day 3; continue treatment until healing is complete; maintain vWF activity of 40-50% during at least 1-3 d postoperation for minor procedures and at least 3-7 d postoperation for major procedures
Humate-P: Type I disease
Minor bleeding: 40-50 U/kg (1 or 2 doses) IV
Major bleeding: Loading dose of 40-75 U/kg IV, then 40-60 U/kg q8-12h for 3 d to keep RCoF activity nadir >50%; then 40-50 U/kg qd for up to 7 d
Type 2 and 3 disease
Minor bleeding: 40-50 U/kg (1 or 2 doses) IV
Major bleeding: Loading dose of 60-80 U/kg IV, then 40-60 U/kg q8-12h for 3 d to keep RCoF activity nadir >50%; then 40-50 U/kg IV qd for up to 7 d; monitor FVIII levels
Pediatric
Alphanate:
Initial dose: 75 vWF:RCof IU/kg IV
Subsequent infusions: 50-75 vWF:RCof IU/kg IV q8-12h prn
Dose may be reduced after postoperative day 3; continue treatment until healing is complete
Humate-P: 20-50 U/kg IV; base dose on patient weight, baseline FVIII level, and bleeding severity
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Viral contamination and infection are remotely possible but unlikely due to prescreening; may induce anamnestic response; monitor patients for signs or symptoms of any allergic reactions by monitoring vital signs including pulse rate; reduce rate of administration or discontinue AHF concentrate if significant change in vital signs occur and are thought to be due to allergic reaction and not to continuing active bleeding; immune tolerance regimens can be associated with nephrotic syndrome, which requires discontinuation of product
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.
Adult
Pediatric
100 mg/kg/dose PO q4-6h
Coadministration with estrogens may cause increase in clotting factors, leading to a hypercoagulable state
Documented hypersensitivity; evidence of active intravascular clotting process; since aminocaproic acid can be fatal in patients with disseminated intravascular coagulation (DIC), it is important to differentiate between hyperfibrinolysis and disseminated intravascular coagulation
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not administer unless a definite diagnosis of hyperfibrinolysis has been made; caution in cardiac, hepatic, or renal disease
More on Von Willebrand Disease |
| Overview: Von Willebrand Disease |
| Differential Diagnoses & Workup: Von Willebrand Disease |
 Treatment & Medication: Von Willebrand Disease |
| Follow-up: Von Willebrand Disease |
| Multimedia: Von Willebrand Disease |
| References |
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References
Tosetto A, Castaman G, Rodeghiero F. Evidence-based diagnosis of type 1 von Willebrand disease: a Bayes theorem approach. Blood. Apr 15 2008;111(8):3998-4003. [Medline].
[Guideline] Nichols WL, Hultin MB, James AH, et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia. Mar 2008;14(2):171-232. [Medline].
[Guideline] Nichols WL, Rick ME, Ortel TL, et al. Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines. Am J Hematol. Mar 16 2009;[Medline].
Batlle J, Torea J, Rendal E, Fernandez MF. The problem of diagnosing von Willebrand's disease. J Intern Med Suppl. 1997;740:121-8. [Medline].
Carcao MD, Blanchette VS, Dean JA, et al. The Platelet Function Analyzer (PFA-100): a novel in-vitro system for evaluation of primary haemostasis in children. Br J Haematol. Apr 1998;101(1):70-3. [Medline].
Federici AB, Mannucci PM. Management of inherited von Willebrand disease in 2007. Ann Med. 2007;39(5):346-58. [Medline].
[Guideline] Lee CA, Brettler DB. Guidelines for the diagnosis and management of von Willebrand disease. Haemophilia. 1997;3:1-25.
Nichols WC, Ginsburg D. von Willebrand disease. Medicine (Baltimore). Jan 1997;76(1):1-20. [Medline].
Sadler JE, Budde U, Eikenboom JC, et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost. Oct 2006;4(10):2103-14. [Medline].
Werner EJ. von Willebrand disease in children and adolescents. Pediatr Clin North Am. Jun 1996;43(3):683-707. [Medline].
Zhang Z, Blomback M, Anvret M. Understanding von Willebrand's disease from gene defects to the patients. J Intern Med Suppl. 1997;740:115-9. [Medline].
Further Reading
Keywords
von Willebrand disease, VWD, von Willebrand factor, VWF, congenital bleeding disorder, intramuscular bleeding, hemarthrosis, bruising, menorrhagia, wound bleeding, excessive bleeding, Wilms tumor, congenital heart disease, systemic lupus erythematosus, angiodysplasia, hypothyroidism, treatment, diagnosis
