von Willebrand Disease Treatment & Management

The 2 main treatment options for patients with von Willebrand disease (vWD) are desmopressin (DDAVP) and transfusion therapy. With regard to the latter therapy, platelet transfusions may be helpful in some patients with vWD whose disease is refractory to other therapies. Cryoprecipitate and fresh frozen plasma contain functional von Willebrand factor (vWF) but should be avoided whenever possible because of the potential transmission of viral disease. An additional drawback of fresh frozen plasma is the large infusion volume most often required.^{[4, 5]}

For prophylaxis in major surgery or for treatment of serious bleeding episodes, vWF-containing FVIII concentrates are the treatment of choice. Following a literature review, however, Franchini et al advised that the need for thromboprophylaxis with vWF/FVIII concentrates in patients with vWD who undergo major surgery should be individually assessed, after a careful risk/benefit analysis.^[6]

Even so, the investigators noted that only 11 cases have been reported in which venous thromboembolic complications occurred in surgical vWD patients who were prophylactically treated with such concentrates, with most happening during orthopedic procedures.^[6]

vWF in pregnancy

During pregnancy, the von Willebrand factor (vWF) level increases in most patients with non–type III vWD. Thus, in patients with functionally normal vWF, labor and delivery usually proceed normally.

However, patients with type II disease may experience hemorrhagic problems. In particular, patients with type IIB may experience thrombocytopenia due to the increased plasma levels associated with abnormal vWF. All patients should be monitored for excessive bleeding, particularly during the first week postpartum.

Hemostasis

Particular attention to hemostasis is advised once the hemostatic defect has been corrected medically.

Consultations

Seek the opinion of a hematologist experienced in the management of bleeding disorders prior to all surgical/dental procedures.

Activity

Patients should be wary of any physical activity associated with an increased risk of hemorrhage.

Outpatient care

Because of the effects of stress on the expression of vWF, laboratory testing should be repeated in patients with newly diagnosed vWD.

Deterrence

Advise patients to avoid aspirin-containing compounds.

vWD type I

DDAVP is the treatment of choice for individuals with vWD type I. DDAVP is a synthetic analogue of the antidiuretic hormone vasopressin; it has enhanced antidiuretic activity and no pressor activity related to vasopressin. The infusion of DDAVP into healthy individuals and individuals with vWD type I results in a rapid increase in circulating levels of vWF:Ag and FVIII and RCoF activity.

Typically, a maximal rise of vWF and FVIII is observed in 30-60 minutes. The typical maximal rise is 2- to 4-fold for vWF and 3- to 6-fold for FVIII. Additionally, hemostatic levels of both factors are usually maintained for at least 6 hours.

DDAVP can be administered not only through intravenous infusion but also via a highly concentrated nasal spray; 300mcg intranasally produces levels comparable to those observed with an intravenous infusion. Intranasal treatment is particularly useful for home therapy of menorrhagia and recurrent epistaxis.

vWD type II

Responses to DDAVP are variable in patients with type II disease. A trial infusion may be performed to evaluate the potential efficacy for a particular patient.

Many individuals with vWD type IIA have a response to DDAVP, with peak vWF and FVIII levels at 30-60 minutes. This is similar to responses observed in patients with vWD type I. However, rapid loss of vWF, FVIII, and, particularly, RCoF activity, occurs as the high ̶ molecular weight multimers are degraded, with return to baseline levels at 4 hours post infusion. Although the response is transient, it may be adequate therapy in certain clinical situations.

DDAVP trials may be contraindicated in patients with type IIB, because of thrombocytopenia and possible thrombotic complications. DDAVP is probably not effective in patients with type IIM and is rarely effective in patients with type IIN.

Individuals with vWD type III have a virtually complete deficiency of vWF. Thus, the fact that DDAVP, an agent that causes the release of stored vWF, has no effect in patients with vWD type III is not surprising.

The treatment of choice for patients with vWD type III (and other vWD types unresponsive to DDAVP) is virus-inactivated, vWF-containing FVIII concentrates that contain a near-normal complement of high ̶ molecular weight vWF multimers.^[7] Most experience reported in the literature has been with the use of Humate-P, a plasma-derived product of intermediate purity. Two other FVIII concentrates, Alphanate and Koate-HP, have been reported to be efficacious in the treatment of vWD. Too little vWF is present in monoclonally purified FVIII concentrates and recombinant FVIII concentrates to allow their use in the treatment of vWD.

Alloantibody formation occurs in 10-15% of patients with type III disease. Therefore, the possibility of this complication must be managed appropriately, because patients are at increased risk for life-endangering anaphylactic reactions to vWF-FVIII preparations. With hemostatic stress in emergency situations, infusion of FVIII preparations devoid of vWF, while adjusting for the markedly decreased FVIII half-life, may be necessary.