• Hemlibra is not approved for the treatment of patients with VWD. The decision on whether to use Hemlibra for patients with VWD lies with the physician and should be based on an appropriate assessment of the likely risk to benefit ratio.
• Published case series on the use of Hemlibra in Type 3 VWD
• A case series of 2 adult and 2 pediatric patients described the use of Hemlibra for type 3 VWD. Outcomes of 1 patient have been reported who experienced a considerable decrease in the number of emergency department visits, hospitalization, and factor doses after the initiation of Hemlibra.
• A case series of two paediatric patients described the use of Hemlibra for type 3 VWD:
• The patient with anti-VWF antibodies underwent surgery for a pseudotumor of the mandible. The patient received Hemlibra 3 mg/kg once-weekly for 4 weeks followed by once every 2 weeks thereafter.
• Patient with recurrent menorrhagia, anemia, and hypovolemic shock was treated with Hemlibra 3 mg/kg once a month.
• At the time of the report both the patients remained free of bleeding episodes with no reports of thrombosis or TMA during treatment with Hemlibra.
• Published case reports on the use of Hemlibra in Type 3 VWD
• A pediatric patient with severe type 3 VWD treated with BPAs was switched to Hemlibra prophylaxis at 3 mg/kg once-weekly for 4 weeks, followed by 1.5 mg/kg once-weekly for 9 months and eventually transitioned to 3 mg/kg every other week.
• An adult patient with type 3 VWD with persistent anti-VWF and pain from left ankle arthropathy initiated Hemlibra prophylaxis at 3 mg/kg once-weekly for 4 weeks, followed by 1.5 mg/kg once-weekly. The patient reported complete relief from pain by the end of the first month and improvement of walking after 6 month of treatment with Hemlibra.
• A pediatric type 3 VWD patient with anti-VWF and anti-FVIII antibodies who experienced repeated severe mucosal bleeding episodes was treated with Hemlibra 3 mg/kg once-weekly for 4 weeks, followed by 1.5 mg/kg once-weekly. Post Hemlibra, the mucocutaneous bleeding events improved. Both VWF and FVIII inhibitors decreased over a treatment duration of 12 months. No AEs related to Hemlibra were reported.
• A pediatric type 3 VWD patient with frequent bleeding and joint deterioration was treated with Hemlibra 3 mg/kg once-weekly for 4 weeks followed by 1.5 mg/kg once-weekly. The patient did not experience any joint bleeds over more than 51 weeks of treatment with Hemlibra. No AEs related to Hemlibra were reported.
• A pediatric patient with type 3 VWD with anti-VWF and anti-FVIII inhibitors received Hemlibra prophylaxis for recurrent episodes of life-threatening oropharyngeal bleeds refractory to conventional therapy. Bleeding improved and inhibitors decreased. Subsequently, the patient experienced bleeding and thromboembolic complications despite peri-operative prophylaxis for a tonsillotomy; Hemlibra was interrupted and later restarted along with plasma derived-VWF and FVIII; anti-VWF and anti-FVIII inhibitors levels continued to decline and no further bleeding events were reported.
• Published case report on the use of Hemlibra in Type 3 AVWS
• One case report described the use of Hemlibra for recurrent GI bleeding in a patient with AVWS and other comorbidities. Patient was started on Hemlibra prophylaxis and experienced increase in hemoglobin. One GI bleed occurred in ~12 months of treatment follow-up. No thrombotic events were noted.

AE(s)=adverse event(s)

AVWS=acquired von Willebrand syndrome

BPA(s)=bypassing agent(s)

BU=biological unit

FVIII=factor VIII

pd-VWF= plasma-derived von Willebrand factor

rFVIIa=recombinant activated factor VII

RA=rheumatoid arthritis

TMA=thrombotic microangiopathy

VWD=von Willebrand disease

VWF=von Willebrand factor

Four patients with symptomatic Type 3 VWD

Vo et al. published a case series on the use of Hemlibra in four patients with symptomatic Type 3 VWD.[1] They reported on patients aged from 2 to 44 years, including two adult female patients and two paediatric patients, aged 2 and 6 years.

Hemlibra treatment

Hemlibra dose was not reported for any of the patients.

Reported outcomes

Outcomes have been reported for one patient.[1] Within one year while on prophylactic Hemlibra the patient experienced a considerable decrease in the number of visits to the emergency department (1 vs. 30), hospitalization (0 vs. 13), and factor doses (1 vs. 54) compared to the five years preceeding Hemlibra treatment.

Two paediatric patients with VWD

Shanmukhaiah et al. published their experience of two paediatric patients with VWD: [2]

• 6-year-old female patient with anti-VWF antibodies underwent surgery for a pseudotumor of the mandible.
• 11-year-old female patient diagnosed with type 3 VWD at 1 year of age and had a historical average annual bleeding rate of 28.

Hemlibra treatment

Both patients received treatment with Hemlibra: [2]

• 6-year-old patient — Hemlibra 3 mg/kg once weekly for 4 weeks, followed by 3 mg/kg every-other-week thereafter.
• 11-year-old patient — Hemlibra 3 mg/kg once-a-month.

Reported outcomes 

At the time of the report both the patients remained free of bleeding episodes.[2]

Neither patient had any thrombosis or TMA during treatment with Hemlibra.[2]

Several case reports on the use of Hemlibra in Type 3 VWD have been published.

Paediatric male patient with anti-VWF antibodies

Wayland et al. published a case report of a 7-year-old male patient with VWD and alloantibodies, previously treated with prophylactic BPAs and on-demand rFVIIa.[3]

Hemlibra treatment

The patient recieved Hemlibra at

• a loading dose of 3 mg/kg once-weekly for 4 weeks
• followed by 1.5 mg/kg once-weekly for approximately 9 months, and then
• transitioned to 3 mg/kg every-other-week.[3]

Reported outcomes 

The author reported improved bleed prevention with Hemlibra prophylaxis.[3] No bleeding events or bleeding symptomatology was experienced by the patient for the 9 month period that they were treated with the 1.5 mg/kg once-weekly schedule. Since transitioning to every-other-week schedule, one trauma-induced soft tissue hematoma occurred and was managed with rFVIIa.

No safety outcomes were reported.[3]

Adult female patient with persistent anti-VWF antibodies

Sigaud et al. reported a 48-year-old female patient with Type 3 VWD with persistent anti-VWF antibodies and pain from left ankle arthropathy.[4,5] The patient had previously received treatment with on-demand recombinant FVIII.

Hemlibra treatment

The patient received Hemlibra 3 mg/kg once-weekly for 4 weeks, followed by 1.5 mg/kg once-weekly.[4,5]

Reported outcomes

The patient reported complete relief from pain by the end of the first month and improvement of walking after 6 month of treatment with Hemlibra.[4,5]

Thrombin Generation Assays showed significant improvement and there were no biological sign of neutralizing anti-drug antibodies after measurement of plasmatic concentration of Hemlibra.[4,5]

Paediatric male patient with anti-VWF and anti-FVIII inhibitors

Cefalo et al. reported on the case of a 2-year-old male child with VMD with anti-VWF and anti-FVIII inhibitors.[6] The patient experienced repeated severe mucocutaneous bleeding episodes and sporadic episodes of minor joint bleeding.

Hemlibra treatment

The patient received Hemlibra 3 mg/kg once-weekly for 4 weeks, followed by 1.5 mg/kg once-weekly.[6]

Reported outcomes

After beginning Hemlibra, the patient 

• experienced fewer and less severe mucocutaneous bleeding events
• did not require hospitalization or RBC transfusions, and
• had no new episodes of spontaneous joint bleeding.[6]

Reductions in both anti-VWF and anti-FVIII inhibitors (65 and 2 BU/mL, respectively) were observed over a treatment duration of 12 months.

No adverse events related to Hemlibra were observed.

Paediatric male patient with sporadic Type 3 VWD

Barg et al. reported on a 9-year-old child patient with sporadic Type 3 VWD, recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy.[7]

Hemlibra treatment

The patient received Hemlibra 3 mg/kg once-weekly for 4 weeks, followed by 1.5 mg/kg once-weekly.[7] 

Reported outcomes

Thrombin generation was low prior to starting Hemlibra, increased after the first loading dose, and increased further after 5 weeks of Hemlibra prophylaxis, with peak height approximately 175 nM.[7] 

At the time of the report, the patient had received 51 weeks of Hemlibra without any joint bleeds. 

No adverse events associated with Hemlibra were reported.

Paediatric patient with anti-VWF and anti-FVIII inhibitors

Luciani et al. reported on a 6-year old paediatric patient who underwent a tonsillotomy for obstructive sleep apnea.[8]

Hemlibra prophylaxis had been initiated at the age of 2 due to recurrent episodes of life-threatening oropharyngeal bleeds refractory to conventional therapy, and complicated by the development of anti-VWF and anti-FVIII inhibitors.

Hemlibra treatment

Hemlibra dose was not reported.

Reported outcomes

Improvement in bleeding and a reduction of both inhibitors had been observed after Hemlibra had been initiated.[8] 

At the time of the tonsillotomy the patient received peri-operative prophylaxis, however they still experienced a severe pharyngeal bleed that required ICU admission. Pd-VWF/FVIII concentrate and rFVIIa were administered. 

During hospitalization, the patient developed a pulmonary embolism and subsequently sepsis. Hemlibra was interrupted and enoxaparin was initiated. 3 months later Hemlibra was resumed, along with pd-VWF/FVIII concentrate, as the thromboembolic parameters had improved. Anti-VWF and anti-FVIII inhibitors levels continued to decline and no further bleeding events were reported.

Elderly female patient with RA, Parkinson's disease and AVWS

Escobar et al. reported on the use of Hemlibra for AVWS in a 70-year-old female patient with RA and Parkinson’s disease following recurrent GI bleeding that was minimally responsive to VWF replacement.[9]

Hemlibra treatment

The patient received Hemlibra prophylaxis of 1.5 mg/kg once-weekly after waning response to maintenance intravenous immunoglobulin.[9]

Reported outcomes

The patient experienced increased hemoglobin and reported no bleeding events within the first 6 months of Hemlibra treatment despite unchanged coagulation studies from baseline.[9] 

In the 7th month, the patient experienced a duodenal arteriovenous malformation bleed requiring intravenous immunoglobulin and VWF/FVIII infusion. 

There were no thrombotic complications noted in the patient in approximately 12 months of treatment follow-up.

1. Vo K, Braunstein K, Michals J, et al. Prophylactic Subcutaneous Emicizumab-kxwh in Adults and Children with Symptomatic Type 3 von Willebrand Disease. Presented at the International Society on Thrombosis and Haemostasis 2021 July 17-21, 2021. ISTH Oral presentation. https://abstracts.isth.org/abstract/prophylactic-subcutaneous-emicizumab-kxwh-in-adults-and-children-with-symptomatic-type-3-von-willebrand-disease/
2. Shanmukhaiah C, Jijina F, Kannan S, et al. Efficacy of Emicizumab in von Willebrand Disease (VWD) Patients with and without Alloantibodies to von Willebrand Factor (VWF): Report of Two Cases and Review of Literature. Haemophilia 2022;https://www.ncbi.nlm.nih.gov/pubmed/35014121
3. Weyand A, Flood V, Shavit J, et al. Efficacy of emicizumab in a pediatric patient with type 3 von Willebrand disease and alloantibodies. Blood Adv 2019;3:2748-2750. https://www.ncbi.nlm.nih.gov/pubmed/31540901
4. Sigaud M, Fouassier M, Ternisien C, et al. Treatment with Emicizumab Leads to Clinical Improvement in a Type 3 von Willebrand Disease Patient with Inhibitor Suffering from a Left Ankle Arthropathy. Presented at the International Society on Thrombosis and Haemostasis Virtual Congress; July 12-14, 2020. ISTH Abstract #PB1556. https://abstracts.isth.org/abstract/treatment-with-emicizumab-leads-to-clinical-improvement-in-a-type-3-von-willebrand-disease-patient-with-inhibitor-suffering-from-a-left-ankle-arthropathy/
5. Sigaud M, Fouassier M, Ternisien C, et al. Treatment with Emicizumab Leads to Clinical Improvement in a Type 3 von Willebrand Disease Patient with Inhibitor Suffering from a Left Ankle Arthropathy. Presented at the International Society on Thrombosis and Haemostasis Virtual Congress; July 12-14, 2020. ISTH Poster.
6. Cefalo MG, Ronco F, Di FG, et al. Effectiveness of emicizumab in preventing life-threatening bleeding complications in type 3 von Willebrand disease with inhibitors: A paediatric report. Haemophilia. E-pub Date: November 2020. DOI # 10.1111/hae.14209. https://onlinelibrary.wiley.com/doi/10.1111/hae.14209
7. Barg A, Avishai E, Budnik I, et al. The potential role of emicizumab prophylaxis in severe von Willebrand disease. Blood Cells Mol Dis 1987;87:https://pubmed.ncbi.nlm.nih.gov/33341070
8. Luciani M, Iavarone S, Di Felice G, et al. Emicizumab in paediatric patient with type 3 von Willebrand disease with inhibitors: from "prophylaxis" to "perioperative management". Presented at the The European Association for Haemophilia and Allied Disorders Annual Meeting in Manchester, UK; February 7-10, 2023. EAHAD Abstract #PO228. https://doi.org/10.1111/hae.14715
9. Escobar M, Aboshady I, Montanez N. Emicizumab use in Acquired von Willebrand Disease: Single Case Report. Presented at the International Society on Thrombosis and Haemostasis in London, UK; July 9-13, 2022. ISTH Abstract #PB0167. https://abstracts.isth.org/abstract/emicizumab-use-in-acquired-von-willebrand-disease-single-case-report/