Table IV.
Evidence-based recommendations on the treatment of von Willebrand disease.
| Treatment | Level of evidence |
|---|---|
| a) Autologous replacement therapy (DDAVP) | |
| - A DDAVP test infusion measuring FVIII:C and VWF:RCo levels at 1 hour (peak) and 4 hours (clearance) is recommended before the clinical use of the drug, owing to within-patient consistency in response | Grade B, level III |
| - Bleeding episodes and surgical or invasive procedures should be covered with DDAVP in responsive patients unless contraindicated | Grade B, level III |
| - In type 1 with baseline VWF:RCo and FVIII:C levels > 10 U/dL, DDAVP is usually an effective treatment | Grade B, level III |
| - In type 2A, DDAVP may be used if a test infusion indicates an adequate response | Grade B, level III |
| - In type 2B, DDAVP is contraindicated | Grade B, level III |
| - In type 2M, DDAVP may be used if a test infusion indicates response | Grade C, level IV |
| - In type 2N, DDAVP may be effective but the half-life of FVIII is shortened | Grade C, level IV |
| - In type 3, DDAVP is ineffective | Grade B, level III |
| - In patients treated repeatedly with DDAVP, it is preferable to measure the FVIII:C and VWF:RCo responses in order to monitor the development of tachyphylaxis | Grade C, level IV |
| - DDAVP should be used cautiously in children < 2 years, due to the risk of hyponatremia (fluid intake should be limited); and in elderly patients with atherosclerosis due to the risk ischemic complications. Adults should limit fluid intake (< 1 liter) for 24 hours after DDAVP | Grade C, level IV |
| - Pregnant VWD women responsive to DDAVP can be safely treated (0.3 μg/kg for 3–4 days) at the time of parturition to avoid excessive bleeding. The same schedule should be adopted in pregnant women at the time of villocentesis and amniocentesis | Grade C, level IV |
| b) Allogeneic replacement therapy (VWF/FVIII or VWF concentrates) | |
| - Patients unresponsive to DDAVP or in whom DDAVP is contraindicated (inadequate response or prediction of prolonged treatments with risk of tachyphilaxis), should be treated with virus-inactivated plasma-derived VWF/FVIII concentrates | Grade B, level III |
| - Treatment of spontaneous bleeding episodes: daily doses of 20–60 IU/kg of VWF/FVIII to maintain FVIII:C levels > 30 U/dL until bleeding stops (usually 2–4 days)1 | Grade B, level III |
| - Prophylaxis for major surgery: daily doses of 50 IU/kg of VWF/FVIII to maintain FVIII:C levels > 50 U/dL until healing is complete (usually 5–10 days)1 | Grade B, level III |
| - Prophylaxis for minor surgery: daily or every other day doses of 30–60 IU/kg of VWF/FVIII to maintain FVIII:C level > 30 U/dL until healing is complete (usually 2–4 days)1 | Grade B, level III |
| - Prophylaxis for dental extractions or invasive procedures: single dose of 30 IU/kg of VWF/FVIII to maintain FVIII:C level > 50 U/dL for 12 hours1 | Grade B, level III |
| - Prophylaxis for delivery and puerperium: daily doses of 50 IU/kg to maintain FVIII:C level > 50 U/dL for 3–4 days | Grade B, level III |
| - Surgical procedures: measure plasma levels of FVIII:C and VWF:RCo every 12 hours on the day of surgery, then every 24 hours. | Grade B, level III |
| - A dosing pharmacokinetic study should be considered before major surgery, particularly for type 3 VWD patients | Grade B, level III |
| - In surgical VWD patients at high risk of venous thrombosis a thrombo-prophylactic treatment with LMWH should be implemented during treatment with VWF/FVIII concentrates, at the same doses and schedules that are recommended for non-VWD patients undergoing similar procedures | Grade C, level IV |
| - Long-term secondary prophylaxis with VWF/FVIII concentrates may be considered for patients with severe VWD and recurrent bleeding in dangerous sites (i.e., gastrointestinal bleeding, hemarthroses, epistaxis in children) | Grade C, level IV |
| - Possible indications for VWF concentrates devoid of FVIII include elective major surgery, particularly when repeated infusions are foreseen in patients at high risk for thrombosis (old age, cancer surgery, orthopedic surgery) and long-term prophylaxis (i.e., for target joints, recurrent gastrointestinal bleeding, recurrent epistaxis in children) | Grade B, level III |
| - All plasma concentrates containing VWF must be avoided in type 3 VWD patients with alloantibodies because of the risk of anaphylactic reactions. Possible therapeutic approaches for these patients are recombinant FVIII, administered at very high doses by continuous intravenous infusion, or recombinant activated factor VII | Grade B, level III |
| c) Adjunctive and adjuvant therapies | |
| - Platelet infusions should be considered if bleeding occurs after adequate VWF/FVIII replacement therapy, particularly for gastrointestinal bleeding | Grade C, level IV |
| - Antifibrinolytic amino acids (i.e., tranexamic acid and epsilon aminocaproic acid) may be sufficient for the management of less severe forms of mucosal bleeding, menorrhagia, epistaxis, or dental procedures. They can also be used in association with replacement therapy (DDAVP or VWF/FVIII plasma concentrates) for treatment or prevention of mucosal-associated bleeding or for minor/major surgery involving mucosal surfaces | Grade B, level III |
| - Estrogens-progestogen preparations are useful in reducing the degree of menorrhagia in VWD women | Grade B, level III |
1These dosage are indicated for VWD patients with severely reduced FVIII:C/VWF:RCo levels (less than 10 U/dL).