The Diagnosis, Evaluation, and Management of von Willebrand desease. National Institute of Health, National Heart, Lung, and Blood Institute, 2007.
Shoshana Revel-Vilk, Markus Schmugge, Manuel D Carcao, Phillip Blanchette, Margaret L Rand, Victor S Blanchette
Desmopressin (DDAVP) responsiveness in children with von Willebrand disease.
J Pediatr Hematol Oncol. 2003 Nov;25(11):874-9.
Abstract/Text
PURPOSE: To determine the pattern and predictors of response to desmopressin (DDAVP) in children with von Willebrand disease (VWD).
METHODS: The authors reviewed the hospital records of all children with type 1 (n = 70) and type 2A (n = 5) VWD who were followed in the institution's Bleeding Disorders Clinic from January 1989 to June 2001 and who had a DDAVP challenge test after diagnosis. The major outcome evaluated was response to DDAVP, defined as an increase of greater than twofold over baseline of von Willebrand factor, ristocetin cofactor (VWF:RCo), and factor VIII coagulant (FVIII:C) and levels above 0.3 IU/mL.
RESULTS: Response to DDAVP was observed in 56 (80%) of the 70 children with type 1 VWD. Age and baseline VWF:RCo and FVIII:C levels were positively associated with DDAVP response. A total of 36 children (28 responders, 8 nonresponders) with type 1 VWD were treated for bleeding episodes or for prophylaxis; of these 75% (6/8) of the nonresponders compared with 7% (2/28) of the responders to a DDAVP challenge test received blood component therapy (P < 0.01). One of the five children with type 2A VWD responded to DDAVP.
CONCLUSIONS: DDAVP challenge tests are recommended in children with newly diagnosed VWD to identify responders in whom DDAVP may be used for the prevention or treatment of bleeding, thus avoiding exposure to blood products. The association of DDAVP response with age merits further investigation.
D Lillicrap, M C Poon, I Walker, F Xie, B A Schwartz, Association of Hemophilia Clinic Directors of Canada
Efficacy and safety of the factor VIII/von Willebrand factor concentrate, haemate-P/humate-P: ristocetin cofactor unit dosing in patients with von Willebrand disease.
Thromb Haemost. 2002 Feb;87(2):224-30.
Abstract/Text
The present study was initiated to evaluate the safety and efficacy of Haemate-P (Humate-P in North America) (anti-hemophilic FVIII/VWF complex [human] dried, pasteurized) dosed in ristocetin cofactor units (VWF:RCo) in the treatment of von Willebrand disease (VWD) patients in Canada. This retrospective data collection reviewed the medical records of VWD patients treated under the Canadian Emergency Drug Release Program from November 22, 1991, to April 30, 1996. Data collection was accomplished by on-site retrieval from source data for 97 patients. Dosing was based on the German package insert, which lists only Factor VIII:C (FVIII:C) units, which were converted in the study analysis to VWF:RCo units based on the analysis of the individual manufactured lots of product used in these patients (average ratio of 2.6 IU VWF:RCo per IU FVIII:C). Twenty five different lots of Haemate-P/Humate-P were used to treat 437 different events in the 97 study patients (344 hemorrhagic events, 73 surgical interventions and 20 prophylactic infusion cycles). Overall, the median dose of concentrate per infusion used to treat surgical events was 69.1 IU VWF:RCo/kg (range 11.9-222.8); bleeding events 55.3 IU VWF:RCo/kg (range 17.1-227.5) and prophylaxis 41.6 IU VWF:RCo/kg (range 34.6-81.0). Treatment periods varied, with the majority of events treated for < or = 10 days (91%). Fifty percent of events that were treated longer than 10 days were given for prophylactic reasons. Efficacy was determined in a standardized manner by the physician, based on dosing in VWF:RCo activity. An overall clinical result of "excellent" or "good" was reported in 97% (424/437) of treatment events. A pediatric sub-population analysis of the patient population reported "excellent/good" efficacy in 100% (17/17) of treatment events in infants, 95% (155/164) in children, and 94% (76/81) in adolescent patients. Related adverse events (AEs) were observed in only 4 (4%) patients and were not deemed to be serious. The findings in this study confirm the safety and efficacy of Haemate-P/Humate-P using VWF:RCo dosing in pediatric and adult patients with various types of VWD.
W Kreuz, D Mentzer, S Becker, I Scharrer, B Kornhuber
Haemate P in children with von Willebrand's disease.
Haemostasis. 1994 Sep-Oct;24(5):304-10.
Abstract/Text
In our center, 289 children with von Willebrand's disease (vWD) have been diagnosed since 1982. The majority of cases (n = 198) were congenital vWD whereas 91 patients suffered from vWD induced by valproate (VPA). We overview bleeding episodes in 45 children and 64 operative procedures requiring therapeutic intervention. The aim of therapeutic and prophylactic procedures in vWD is correcting the hemostatic disorder and normalization of bleeding time. This can be achieved by application of Haemate P leading to an elevation of plasma levels of von Willebrand parameters together with normalization of bleeding time. In patients with vWD type I, DDAVP will be preferred if contraindications can be excluded and efficacy has been shown. Severe bleeding complications could be prevented in a total of 50 surgical procedures in children with vWD type I by prophylactic treatment with DDAVP or Haemate P. Two children initially treated with DDAVP had to be substituted with Haemate P in the follow-up because of continuous bleeding. In type IIa and type III vWD as well as in VPA-induced vWD, the use of Haemate P was essential for sufficient hemostasis in all bleeding and operations. We conclude that Haemate P provides effective bleeding prophylaxis and treatment in all types of vWD except platelet-type.
I Scharrer, T Vigh, E Aygören-Pürsün
Experience with Haemate P in von Willebrand's disease in adults.
Haemostasis. 1994 Sep-Oct;24(5):298-303.
Abstract/Text
The virally inactivated pasteurized FVIII concentrate Haemate P contains nearly intact vWF multimers. It is currently the treatment of choice to achieve satisfactory hemostasis for moderate to severe vWD and for patients with variants of vWD that cannot be adequately treated with DDAVP or for whom DDAVP is contraindicated. Therefore, we treated patients with type Ia, type IIa, type IIb and type III vWD with Haemate P. A correction of the hemostatic defect was seen in all patients. The type of bleeding events included 24 gastrointestinal, 18 other mucosal, 5 central nervous system, 15 orthopedic and 4 other. 28 dental surgical procedures, 9 operative deliveries, 5 tonsillectomies, 17 orthopedic and 11 miscellaneous surgeries were performed under the cover of Haemate P.
P M Mannucci, G Tamaro, G Narchi, G Candotti, A Federici, D Altieri, F Tedesco
Life-threatening reaction to factor VIII concentrate in a patient with severe von Willebrand disease and alloantibodies to von Willebrand factor.
Eur J Haematol. 1987 Nov;39(5):467-70.
Abstract/Text
A 16-yr-old girl with severe von Willebrand disease complicated by the development of precipitating alloantibodies to von Willebrand factor (anti-VWF) had a life-threatening anaphylactoid reaction immediately after the infusion of a commercial plasma concentrate of factor VIII/von Willebrand factor. An early post-infusion activation of the complement system was demonstrated by the appearance of C3 split products and by the drop of serum CH50 activity, occurring in parallel with a post-infusion drop in the anti-VWF antibody levels. Immune complexes remained unchanged in the early post-infusion period and rose to a moderate extent only after 24 h. We conclude that biologically active products of the complement system contributed to the onset of this life-threatening reaction which occurred after concentrate infusion.
P M Mannucci, Z M Ruggeri, F I Pareti, A Capitanio
1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases.
Lancet. 1977 Apr 23;1(8017):869-72.
Abstract/Text
1-Deamino-8-d-arginine vasopressin (D.D.A.V.P.) infusion causes a marked increase in factor-VIII (antihaemophilic-factor)-related properties in patients with moderate and mild haemophilia and von Willebrand's disease (vWd). The possibility was therefore evaluated that such an autologous factor-VII response might be haemostatically effective, allowing patients to undergo surgery without plasma concentrates. 0.3 microng/kg of D.D.A.V.P. given before dental surgery and repeated in the early postoperative period was followed by a two to three fold rise in factor-VIII coagulant activity (VII C.A.) in four patients with moderate and mild haemophilia. In two, there was no abnormal bleeding after dental extraction, whereas plasma concentrates were necessary to control oozing from the sockets in the remaining two patients. A higher D.D.A.V.P. dosage (0.4-0.5 microng/kg) in patients with higherstarting VII C.A. (9% or more) was followed by a more marked response (four to six fold). VII C.A. levels up to 100% of average normal were achieved and dental extraction and major surgery (such as cholecystectomy, thoracotomy, and two tonsillectomies) were carried out successfullly in six patients with mild haemophilis and in two with vWd. The mean half-life of autologous VII C.A. was 9.4 h (range 7.5-11.6). Plasma and urine osmolality showed no consistent variation after drug administration. Thus D.D.A.V.P. appears a promision pharmacological alternative to plasma concentrates in the management of some patients with haemophilis and vWd.
