Clinical use of Haemate (R) P in inherited von Willebrand's disease: a cohort study on 100 Italian patients

Background and Objectives: Plasma-derived concentrates containing von Willebrand factor and factor VIII (VWF/FVIII concentrates) are the mainstay of treatment of patients with inherited von Willebrand's disease (VWD) who are unresponsive or have a contraindication to desmopressin (DDAVP) therapy. Only a few clinical studies are available on the use of these VWF/FVIII concentrates in large numbers of cases and within the same country. The aim of our study was to collect retrospective data on the efficacy and safety of Haemate® P (CSL Behring, Marburg, Germany) in a large cohort of well-characterized VWD patients after the introduction of the guidelines for VWD management in Italy. Design and Methods: A retrospective survey of data records was organized among ten Italian Hemophilia Centers in order to retrieve information on the clinical use of Haemate® P. Data on 100 VWD patients (44 males and 56 females, median age 41.5, range 2-87 years) were available relating to the period from January 2002 to December 2004. All patients were diagnosed according to the criteria proposed by the Italian guidelines for VWD management. Results: Of the 100 VWD patients enrolled, 23 had type 1 VWD, 40 had type 2 (2A=7, 2B=11, 2M=9, 2M Vicenza=13) and 37 had type 3. Seventy-one percent were severely affected, as shown by VWF:RCo levels <10 IU/dL. Fifty-nine patients were treated with Haemate® P because of 280 spontaneous bleeding episodes. These patients required 1,003 infusions of Haemate® P with a median daily dose of 72 (27-135) VWRRCo IU/kg. In 95% of patients, clinical responses were rated as excellent/good. Fifty-six patients underwent major surgery (n=17), minor surgery (n=28), invasive procedures (n=9) or dental procedures (n=19), with a total consumption of 1.97×10 6 IU of VWF:RCo through 366 infusions of Haemate® P The median daily dose was 80 (range, 27-146) VWRRCo IU/kg, with clinical responses rated as excellent/good in 97% of patients. Twelve patients (type 1=1, type 2B=1, type 2M Vicenza=1, type 3=9, with a median age of 34.5, range 11-71 years) also underwent 17 long-term secondary prophylaxis regimens to prevent recurrent bleeding at the same site (47% in the gastrointestinal tract, 35% in joints). During the 4,358 days of prophylaxis, the patients received 1,424 infusions of Haemate® P, given three times (53%) or twice (47%) a week, with clinical responses rated as excellent/good in 100%. No serious adverse events, including thrombosis, were reported in the 370 evaluated treatments. Interpretation and Conclusions: Based on this retrospective study conducted in a large cohort of Italian patients (n=100) and covering a long period of observation (36 months), Haemate® P was shown to be effective and safe for the clinical management of patients with VWD, whether given on demand or as prophylaxis.