J Haem Pract 2016; 3(2):1 - 3. doi: 10.17225/jhp00068

Authors: S Jenkins, Manuel Carcao, Vanessa Bouskill

S Jenkins
Lawrence Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada

Manuel Carcao
Department of Paediatrics, Division of Haematology/Oncology, and Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

Vanessa Bouskill
Department of Paediatrics, Division of Haematology/Oncology, and Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. E-mail:


Developing an inhibitor to von Willebrand factor (VWF) is extremely uncommon. Consequently, patients with von Willebrand disease (VWD) tend not to be routinely evaluated for inhibitors, leading to the possibility of delay in inhibitor diagnosis. We present such an occurrence to raise awareness, with a view to avoiding such delays. A 1-year-old male with no family history of bleeding disorders or parental consanguinity presented with a tongue bleed lasting three days. Investigations confirmed a diagnosis of Type 3 VWD. Over the next few months, the patient received seven exposures to Humate-P (a plasma derived FVIII containing von Willebrand factor concentrate), but developed an anaphylactic reaction necessitating adrenalin and Benadryl (diphenhydramine). The reaction quickly abated and did not recur with further exposure to Humate-P. In 2013, due to recurrent epistaxis and tonsillar bleeding, the patient was commenced on prophylaxis receiving Humate-P 50 RCo U/kg twice weekly. Despite this regimen, he continued to experience recurrent epistaxis, leading to escalation of prophylaxis to 3/week. In November 2014, he showed persistent tonsillar bleeding, despite having received two doses of Humate-P (each 40 RCo U/kg) in the previous 12 hours. Testing revealed reduced VWF:Ag, VWF:RCo and FVIII:C recoveries. Further testing revealed an anti-VWF antibody (2.6 BU) of unspecified Ig type. Since diagnosis of the inhibitor, he has received 100 RCo U/kg daily for prophylaxis and immune tolerance. He is now bleed-free; however, monthly inhibitor testing shows that his inhibitor persists. Given the limited experience and literature on inhibitors in VWD, the prognosis for such cases is unknown.


Special acknowledgements to the National Program for Hemophilia Mutation Testing, Queen’s University, Kingston, Ontario (Dr David Lillicrap, Dr Paula James, and Dr Mackenzie Bowman) and St. Justine Hospital, Montreal, Quebec (Dr Georges Rivard and Dr Arnaud Bonnefoy) for the specialized VWF inhibitor testing and molecular genetics.




  1. Bergamaschini L, Mannucci P, Federici A, et al. Post-transfusion anaphylactic reactions in a patient with severe von Willebrand disease: role of complement and alloantibodies to von Willebrand factor. J Lab Clin Med 1995; 125: 348-55.
  2. James P, Lillicrap D, Mannucci P. Alloantibodies in von Willebrand disease. Blood 2013; 122: 636-40.
  3. Jokela V, Lassila R, Szanto T, et al. Phenotypic and genotypic characterization of 10 Finnish patients with von Willebrand disease type 3: discovery of two main mutations. Haemophilia 2013; 19, 344-8.
  4. Bergamaschini L, Santegelo T, Fariciotti A, et al. Study of complement-mediated anaphylaxis in humans. The role of IgG subclasses (IgG1 and/or IgG4) in the complement-activating capacity of immune complexes. J Immunol 1996; 156:1256-61.
  5. Franchini M, Gandini G, Giuffrida A, et al. Treatment for patients with type 3 von Willebrand disease and alloantibodies: a case report. Haemophilia 2008; 14: 645-6.
  6. Mannucci P, Ruggeri Z, Ciavarella N, et al. Precipitating antibodies to factor VIII/von Willebrand factor in von Willebrand’s disease: effects on replacement therapy. Blood 1981; 57: 25-31.
  7. Pergantou H, Xafaki P, Adamtziki E, et al. The challenging management of a child with type 3 von Willebrand disease and antibodies to von Willebrand factor. Haemophilia 2012; 18: e66-7.
  8. CSL Behring Canada, Inc. Humate-P® antihemophilic factor / von Willebrand factor complex (human), dried, pasteurized. Product monograph. 2014. Available from: (accessed 22 April 2016).

The Journal of Haemophilia Practice is published by Haemnet.

Haemnet is a registered charity that brings together and gives a voice to haemophilia nurses, physiotherapists and allied health care professionals, providing forums for collaborative research, educational activities and support.