First guideline released for von Willebrand Disease

"This is the first readily available resource that is comprehensive," Barbara A. Konkle, M.D., told Drug Topics. Konkle, an associate professor of medicine at the University of Pennsylvania, said that prior to this, there were other sources of information available to practitioners but not in one place.

According to the new guide, the goal to treating VWD is to stop bleeding or to provide prophylaxis for surgical procedures. But prior to treatment, persons suspected of having VWD should have a laboratory-confirmed diagnosis of the type and severity of disease. Patients with Type I, the most common and mildest form which accounts for 75% of cases, may have a low level of VWF and may also have lower-than-normal levels of FVIII. Type II patients may exhibit normal VWF levels but the protein is ineffective at promoting hemostasis. Patients with Type III, the most serious kind but more rare, usually have no VWF and low levels of FVIII.

Fluid restriction in persons receiving DDAVP should be considered to avoid hyponatremia and seizures, and can be done without laboratory monitoring unless high-dose desmopressin (Stimate, CSL Behring) or DDAVP is used more than three times within 72 hours.

According to Konkle, who is also the director of the Penn Comprehensive Hemophilia and Thrombosis Program, patients must first be tested to see if they will respond to DDAVP since the drug works by releasing VWF into the circulation. "If a patient has Type III VWD, they have no VWF, and so DDAVP isn't going to work," she explained. Persons with more than 10 IU/dL VWF ristocetin cofactor activity (VWF:RCo) and more than 20 IU/dL Factor VIII activity levels should be given a trial with desmopressin while in a non-bleeding state.

Antifibrinolytics, such as aminocaproic acid and tranexamic acid, are helpful for treatment of mild mucocutaneous bleeding in VWD. Antifibrinolytics plus desmopressin may be necessary, and are recommended for oral surgery in mild to moderate VWD. VWF replacement therapy with VWF concentrate products, such as Humate-P (CSL Behring) and Alphanate SD/HT (Grifols), should be available for persons who cannot tolerate desmopressin or who bleed excessively despite combination therapy, according to the new guidelines. It should be noted, however, that these products are not interchangeable due to differing ratios of FVIII to VWF. According to the guide, plasma-derived concentrates that contain FVIII, but little or no VWF, are usually not useful for treating VWD. Fibrin sealant or bovine thrombin are recommended as useful adjuncts in oral surgery if necessary.

"Patients undergoing major surgery need to have their VWF levels elevated prior to the procedure to avoid bleeding," Konkle pointed out. In fact, according to the guidelines, for treatment of severe bleeding or for prophylaxis of major surgery, initial target VWF:RCo and FVIII activity levels should be at least 100 IU/dL, followed by trough levels of more than 50 IU/dL for at least seven to 10 days. VWF:RCo and FVIII levels should not exceed 200 IU/dL and 250 IU/dL, respectively, to decrease the risk for perioperative thrombosis.

"Von Willebrand patients should avoid anything that inhibits platelet function," Konkle reminds pharmacists. "This includes aspirin, NSAIDs, and some over-the-counter products, such as ginkgo biloba." In addition, the new guide suggests any patient with VWD over two years of age be vaccinated against hepatitis A and B.

NHLBI's The Diagnosis, Evaluation and Management of von Willebrand Disease can be accessed online at http://www.nhlbi.nih.gov/guidelines/vwd/ and in Haemophilia 2008; 14:171-232.