Successful Desensitization of a Patient with Possible IgE-Mediated Anaphylactic Reaction to FVIII/VWF Concentrate

Abstract

Background: Type 3 von Willebrand disease (VWD) is a severe bleeding disorder with a prevalence of 1:1 million live births. There are several von Willebrand factor (VWF) replacement products used in the treatment of acute bleeding episodes or as prophylaxis. Patients who receive multiple transfusions have an increased risk of developing antibodies against these products. These antibodies can lead to life-threatening anaphylactic reactions. Previous studies have identified immune complex formation and complement activation as the trigger for anaphylaxis, rather than IgE. IgE-mediated anaphylaxis against VWF concentrates has not yet been published. Case: A 4-year-old female patient with type 3 VWD was referred to our hospital because of an anaphylactic reaction during FVIII/VWF concentrate (Immunate Ò) infusion. She had previously received FVIII/VWF concentrate (Haemate P Ò) infusions 8 times without any complications. She did not have antibodies against VWF and FVIII, and serum IgA level was normal. Since she needed factor replacement therapy as a result of a growing hematoma on her scalp, we performed skin prick and intradermal tests 2 days after the reaction. The prick test, with FVIII/VWF (Immunate), was negative, but the intradermal test was positive. We administered a 12-step desensitization protocol with FVIII/VWF concentrate (Immunate) successfully without any reactions. Conclusion: Anaphylactic reaction to factor replacement products is a major problem for patients with VWD, especially type 3 VWD requiring multiple factor infusions. We achieved a successful desensitization with FVIII/VWF concentrate in a patient who had an anaphylactic reaction during the infusion of this product. Our patient is important since she represents the first case of IgE-mediated anaphylaxis against VWF concentrate reported in the literature.

Immune complications and their management in inherited and acquired bleeding disorders

“…The literature contains 1 case where there was evidence of complement activation and another in which there was indirect evidence of an IgE-mediated acute hypersensitivity reaction. 48,49 …”

A rare case of an anaphylactic reaction to plasma and recombinant blood coagulation factor VIII in a child with severe hemophilia A

“…Протокол десенсибилизации к используемому лекарственному средству (pdFVIII), адаптированный нами для пациента с тяжелой формой гемофилии А на основании материалов, приведенных в публикации В. Beken и соавт. [11]…”

Recombinant von Willebrand factor for perioperative bleeding management in pediatric patient with allergy to plasma‐derived von Willebrand factor

“…3 While plasma-derived von Willebrand factor (pdVWF) and recombinant von Willebrand factor (rVWF) are efficacious and have similar safety profiles, there are some notable differences between the two classes (Table 1 dren with history of anaphylaxis to pdVWF would undergo pdVWF desensitization. 4 There are very limited data on the use of rVWF in children, 5 particularly in the setting of anaphylaxis. Herein, we present the case of a pediatric patient with VWD and history of anaphylaxis to Humate-P who received vonicog alpha prior to elective orthopedic surgery.…”

“…Drawbacks with factor desensitization are that it may require more time and can be more costly, and still poses a risk of further potentially serious allergic reactions. 4,7 rVWF provides exogenous VWF to correct the deficiency without introducing additional FVIII that may lead to an increased risk of thrombosis. rVWF has been used off label to successfully treat bleeds in pediatric patients who are refractory to pdVWF.…”