Prophylactic Use of Emicizumab for Type III Von Willebrand Disease Patients: Our Experience

Background:

There are three major types of von Willebrand Disease (VWD): Type 3 is the most severe type due to the absence or severe reduction of VWF. Emicizumab is a monoclonal antibody miming Factor VIII and is approved for patients with hemophilia A. Although off-label, some literature has shown that Emicizumab can potentially improve hemostasis for patients with VWD type III.

Aim:

To report the effectiveness of prophylactic use of Emicizumab in VWD type 3 patients in preventing bleeding symptoms.

Method:

We presented two cases and discussed the outcomes of VWD type III patients who received prophylactic Emicizumab at Alaziziyah Children's Hospital in Jeddah, Saudi Arabia, over six months starting in November 2023.

Case report:

Case 1:

An 8-year-old girl was referred from an orthopedic clinic due to frequent hematomas and new onset swelling in her right ankle joint that did not improve with conservative treatments when she was 2 years old. At that time, she was diagnosed with VWD type 3, with a factor VIII level of 6% and VWF level of 3%. She had multiple hospital visits and developed a target joint in her right ankle. As a result, she began receiving prophylactic doses of human plasma-derived von Willebrand factor twice weekly and on demand. Despite the treatment, her annual bleeding rate (ABR) was 3.1, with one target joint in the right ankle. It was decided to start her on Emicizumab with a loading dose, followed by 6mg/kg once every 4 weeks, and gradually taper off the hemophilic Factor/von Willebrand factor Complex over 2 weeks

Case 2:

A 2-year, 9-month-old boy first presented with recurrent gum bleeding and easy bruising after minor injuries. His family history and laboratory tests revealed 1% factor VIII and 3% VWF, confirming the diagnosis of severe von Willebrand disease (VWD). As the family lives far from the city and has difficulty with medication, the boy received weekly prophylactic treatment with human plasma-derived von Willebrand factor. Over three consecutive months, he experienced three traumatic forehead bruises, leading to CT scans and hospital admissions for factor replacement. Ultimately, due to the challenges with IV access and other issues, the decision was made to start him on prophylactic Emicizumab. Consent was obtained from the father, and consultation was carried out. He was put on the same treatment plan that was initiated for his sister on the same day. The parents are first-degree cousins with no other children, and there is no family history of the same problem.

We have taught the mother how to administer the subcutaneous injection; however, she has not yet demonstrated the capability to carry out the procedure effectively.

The six-month therapy significantly improved the daughter's right ankle joint and fixed her limp, with no traumatic or spontaneous bleeding requiring FFP, factor transfusion, or hospital visits. The results led to a notable improvement in patient satisfaction.

The son is also doing well, with no traumatic or spontaneous bleeding or bruises requiring FFP or factor therapy.

Both patients have an ABR of 0, and the parents were satisfied with emicizumab therapy. The serial laboratory exams, including complete blood count (CBC) and liver and renal function tests, showed normal results for the two patients.

For both the daughter and the son, the use of emicizumab was not only effective in preventing bleeding but also remarkably safe, with no side effects or thrombotic events noticed during treatment.

Conclusion:

Based on our limited experience using prophylactic emicizumab in severe VWD patients with frequent bleeding symptoms, this medication remarkably improves the prevention of bleeding, thus maintaining a good safety profile and achieving patient satisfaction.

No relevant conflicts of interest to declare.

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