von Willebrand’s disease is a hereditary deficiency of von Willebrand’s factor (VWF), causing platelet dysfunction. Bleeding tendency is usually mild. Screening tests show a normal platelet count and, possibly, a slightly prolonged PTT. Diagnosis is based on low levels of VWF antigen and abnormal ristocetin cofactor activity. Treatment involves control of bleeding with replacement therapy (cryoprecipitate or pasteurized intermediate-purity factor VIII concentrate) or desmopressin.
There are three types of Von Willebrand disease:
- Type 1 – a quantitative deficiency of VWF, which is the most common form and is an autosomal dominant disorder,
- Type 2 – a qualitative impairment in synthesis of VWF that can result from various genetic abnormalities and is also an autosomal dominant disorder, and
- Type 3 – a rare autosomal recessive disorder in which homozygotes have no detectable VWF.
Desmopressin may be a useful treatment depending on the type of VWD a patient has. It is an analog of antidiuretic hormone (vasopressin) that stimulates the release of VWF into the plasma and may increase levels of factor VIII. Desmopressin may be helpful for type 1 VWD but is usually of no value in other types and may even be harmful in some.
To ensure adequate response to the drug, a test dose is typically given and the response of VWF antigen is measured. Desmopressin 0.3μg/kg given in 50 mL 0.9% saline solution IV over 15 to 30 min may enable patients to undergo minor procedures (e.g., tooth extraction, minor surgery) without needing replacement therapy. If a replacement product is needed, desmopressin may reduce the required dose. One dose of desmopressin is effective for about 8 to 10 hours. About 48 hours must elapse for new stores of VWF to accumulate, permitting a second injection of desmopressin to be as effective as the initial dose.
Introduction to von Willebrand
vWD is as common as hemophilia A, autosomal dominant non-sex-linked. vWF is a glycoprotein that adheres to vessels after injury and causes activation and adhesion of platelets. 85% of vWD is type I (decreased amount of vWF). Type II is a functional problem of vWF, and type III is no vWF. Nose bleeds are common, PTT and bleeding time are long. Desmopressin increases plasma levels of vWF, helps in type I and II. Cryo (contains vWF) if Desmopressin not helping.
What causes vWD?
An abnormality, either quantitative or qualitative, of the von Willebrand factor
What is vWF?
A large multimeric glycoprotein that functions as the carrier protein for factor VIII.
- Functions of VWF
- Required for normal platelet adhesion
- Attaches to platelets by glycoprotein Ib and acts as a bridge between platelets and damaged subendothelium
- Secondary hemostasis, protects FVIII from degradation and delivers it to the site of injury
Types of vWD
- Type I VWD
- 70-80% of cases
- Partial quantitative decrease of qualitatively normal von Willebrand factor and FVIII
- Mild Sx
- AD inheritance, varied penetrance
Type II VWD
- Either autosomal dominant or autosomal recessive
- 50% are younger than 35 years
- 4 described type II von Willebrand disease subtypes (type 2A is by far the most common)
Type III VWD
- Marked deficiencies of both von Willebrand factor and FVIIIc in the plasma, the absence of von Willebrand factor from both platelets and endothelial cells, and a lack of response to DDAVP
- Most severe form
- Autosomal recessive
1. H and P:
- Increased or easy bruising
- Recurrent epistaxis
- Postoperative bleeding (particularly after tonsillectomy or dental extractions)
- Family history of a bleeding diathesis
- Bleeding from wounds
- Gingival bleeding
- Postpartum bleeding
- Mucosal bleeding and bruises
2. xs bleeding time, prolonged PTT in some cases
3. low vwF assays
- Minor bleeding problems in patients with von Willebrand disease, such as bruising or a brief nosebleed, may not require specific treatment
- More serious bleeding,
- desmopressin (1-deamine-8-D-arginine vasopressin [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.
- can be used to treat bleeding complications or to prepare patients with von Willebrand disease for surgery.
- 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.
Route: IV, intranasal, sc
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.