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Bleeding Disorder Treatments: Von Willebrand Disease

ANTIHEMOPHILIC FACTOR VIII/VON WILLEBRAND FACTOR COMPLEX Alphanate1 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU lyophilized pwd for IV inj after reconstitution Adults: Pre-op: 60 VWF:RCo IU/kg, then 40–60 VWF:RCo IU/kg every 8–12hrs if needed; may reduce dose after 3rd post-op day; treat until healed. Max infusion rate ≤10mL/min.Children: Initially 75 VWF:RCo IU/kg, then 50–75 VWF:RCo IU/kg every 8–12hrs if needed; may reduce dose after 3rd post-op day; treat until healed. Max infusion rate ≤10mL/min. Humate-P 250 IU FVIII + 600 IU VWF, 500 IU FVIII + 1200 IU VWF, 1000 IU FVIII + 2400 IU VWF lyophilized pwd for IV infusion after reconstitution Adults and Children: Type 1 (Mild): major bleed: initially 40–60 IU/kg, then 40–50 IU/kg every 8–12hrs for 3 days, then once daily for a total of 7 days. Type 1 (Moderate or severe): minor bleed: 40–50 IU/kg for 1–2 doses; major bleed: initially 50–75 IU/kg, then 40–60 IU/kg every 8–12hrs for 3 days, then once daily for a total of 7 days. Types 2 and 3: minor bleed: 40–50 IU/kg for 1–2 doses; major bleed: initially 60–80 IU/kg, then 40–60 IU/kg every 8–12hrs for 3 days, then once daily for a total of 7 days. Max infusion rate: 4mL/min. Surgery: see full labeling. Wilate 500 IU FVIII + 500 IU VWF:RCo, 1000 IU FVIII + 1000 IU VWF:RCo pwd for IV inj after reconstitution <5yrs: Contact manufacturer. ≥5yrs: Minor bleed: 20–40 IU/kg once, then 20–30 IU/kg every 12–24hrs as needed. Major bleed: 40–60 IU/kg once, then 20–40 IU/kg every 12–24hrs as needed. Surgery (give loading dose within 3hrs before); Minor: 30–60 IU/kg once, then 15–30 IU/kg (or half the loading dose) every 12–24hrs; Major: 40–60 IU/kg once, then 20–40 IU/kg (or half the loading dose) every 12–24hrs. Routine prophylaxis (≥6yrs): 20–40 IU/kg 2–3 times per week. Monitor and adjust according to VWF:RCo and FVIII activity, and location of bleed; usual treatment duration is 3 days (minor hemorrhage, minor surgery), 5–7 days (major hemorrhage), or ≥6 days (major surgery). DESMOPRESSIN DDAVP2 4mcg/mL soln for inj or IV infusion after dilution Adults and Children: <3mos: not recommended. ≥3mos: 0.3mcg/kg (max 20mcg) IV over 15–30mins. Pre-op: give 30mins before scheduled procedure. If used to reduce spontaneous or traumatic bleeding, may repeat doses after 8–12hrs and once daily thereafter based on clinical response. VON WILLEBRAND FACTOR Vonvendi3 650 IU VWF:RCo, 1300 IU VWF:RCo lyophilized pwd for IV inj after reconstitution Adults: ≥18yrs: Minor bleed:initially 40–50 IU/kg, then every 8–24hrs as needed. Major bleed:initially 50–80 IU/kg, then 40–60 IU/kg every 8–24hrs for 2–3 days as needed. Routine prophylaxis: initially 40–60 IU/kg twice weekly; adjust dose up to 60 IU/kg twice weekly if breakthrough bleeding occurs in joints or if severe bleeding occurs. Surgery: see full labeling. Max infusion rate: 4mL/min.Children: <18yrs: not established. NOTES

Takeda's Bleeding Disorder Drug Veyvondi Backed For NHS Use

NHS England has recommended that patients with von Willebrand disease (VWD) be treated with Takeda's Veyvondi, making it the first and only medicine backed for what is the most common inherited bleeding disorder in the UK.

The decision was taken by the Clinical Priorities Advisory Group (CPAG), which advises NHS England on commissioning services, treatments and new technologies.

Veyvondi (vonicog alfa) – originally developed by Shire before the company was taken over by Takeda last year – has been approved in Europe since 2018.

VWD affects up to 1% of the global population, and is caused by deficiency or dysfunction in the protein known as von Willebrand factor (VWF). Veyvondi is used to treat haemorrhage and surgical bleeding events in adults with VWD, as well as to prevent surgical bleeding, when desmopressin treatment alone is ineffective or not indicated.

The CPAG decision means that adult patients with VWD will now have access to Veyvondi as an alternative to plasma-derived von Willebrand factor (pdVWF) concentrates – another standard therapy for the disease given either alone or with Factor VIII products.

These blood-derived products have theoretical disadvantages compared with synthetic, recombinant drugs like Veyvondi, including reliance on donor availability, the risk of human-derived infections, allergic reactions and variations in the amount of material in the blood to help with clotting.

Also, unlike many pdVWF products, Veyvondi does not contain any clotting Factor VIII, so that co-dosing does not need to be accounted for and the risk of excess factor building up is reduced.

However, current treatments are well-established as being safe and effective, according to a CPAG commissioning proposal document published earlier this year.

[caption id="attachment_72418" align="alignleft" width="135"] Dr Carolyn Millar[/caption]

The decision has been welcomed by Dr Carolyn Millar, a consultant haematologist with Imperial College London, who said Veyvondi "contains only trace amounts of recombinant FVIII."

Since many situations requiring VWF replacement do not also require Factor VIII, the drug "offers clinicians the flexibility to dose vonicog alfa with or without [recombinant Factor VIII] based on the patient's individual needs," she added.

Access to Veyvondi will be primarily via Haemophilia Comprehensive Care Centres (CCC), according to the CPAG.

[caption id="attachment_72416" align="alignright" width="137"] Jo Traunter[/caption]

"Until now, adults living with VWD have not had a recombinant treatment option, so we are delighted to share this news with our members," said Jo Traunter, a Haemophilia Society UK Trustee, who has VWD herself and has two children with the disease.

"It is a significant development in access to treatment and shows that our successful 'Recombinant for All campaign' which started almost 20 years ago is just as important for our community today," she added.

Nigeria: Blood On The Line - The Impact Of Undiagnosed Bleeding Disorders On Mothers, Infants, And Children

Bleeding disorders remain a huge challenge to maternal, newborn and child health (MNCH) worldwide, with the burden higher in low-resource countries like Nigeria. These disorders result from the inability of the body to stop bleeding and, if undiagnosed and untreated, may result in life-threatening complications during childbirth and early childhood. This issue calls for medical attention to address it and ensure that such care is accessible, especially for families who can't afford it.

Bleeding disorders are mainly inherited and include disorders such as haemophilia, von Willebrand disease, and platelet function disorders that affect the clotting process, leading to excessive bleeding. This burden of bleeding disorders in Nigeria is increased by a lack of awareness, limited availability of diagnostics, and shortage of adequate treatment products, with significant, far-reaching implications for the health and financial stability of families.

Maternal mortality remains a serious global problem, with postpartum haemorrhage (PPH) accounting for 27.1% of deaths. Undiagnosed bleeding disorders in women may result in complications such as heavy menstrual bleeding, complications during pregnancy, and PPH during or after childbirth. It is therefore a public health concern.

For instance, women who are haemophilia 'carriers' may remain asymptomatic but go through excessive bleeding at delivery. In many health settings in Nigeria, obstetricians and midwives may not often consider bleeding disorders as the cause of PPH, resulting in delayed or inappropriate interventions. Stigma remains another reason many women go through symptoms in silence, dismissing them as normal or fearing societal judgment.

Impact of bleeding disorders on child health

Life-threatening conditions in newborns, such as intracranial haemorrhage, prolonged bleeding from circumcision, or delayed healing of the umbilical cord stump, could be the first manifestations of a bleeding disorder. In 2022, sub-Saharan Africa accounted for 57 per cent of bleeding disorders with Nigeria reportedly having 34.3 % in the same year, putting it amongst the highest globally. The absence of routine screening for bleeding disorders leaves many cases undiagnosed, with many families remaining unaware of the condition until a major bleeding episode occurs that may lead to disability or death.

For children who have bleeding disorders and remain undiagnosed, the dangers extend beyond infancy into life. Minor injuries can mean long-term bleeding or joint damage because of recurring internal bleeding. These challenges greatly affect the quality of the child's life, limiting his or her ability to engage in normal activities like school. If not managed properly, families can often experience repeated visits to the hospital, loss of income, and social isolation. In most instances, parents use traditional remedies or do not seek care at all, putting the child's health in further jeopardy.

Over the past five years, the Haemophilia Foundation of Nigeria (HFN) has been a beacon of hope for families affected by bleeding disorders. Their work spans awareness, advocacy, diagnosis, and access to treatment. Recognising the special challenge that bleeding disorders pose to MNCH, HFN has prioritised efforts to address this gap using various strategies.

HFN, with partners like the World Federation of Hemophilia (WFH) and Novo Nordisk Haemophilia Foundation (NNHF), provides training for healthcare practitioners on managing bleeding disorders during pregnancy, childbirth, and early childhood. They also conduct awareness programs and support laboratories with training and diagnostic tools. Through the WFH Humanitarian Aid Programme, HFN has improved access to anti-haemophilia factor concentrates and other treatment products. HFN collaborated with healthcare providers, stakeholders, and policymakers to advocate for the inclusion of bleeding disorders in the National NCD policy in August 2024. The organisation organises activities like the annual Camp Bravehearts for children and youths supported by Save One Life Inc and the Red Heart workshops for women and girls with bleeding disorders supported by NNHF.

Collaboration by all relevant stakeholders will help strengthen MNCH outcomes in Nigeria by ensuring undiagnosed bleeding disorders are identified early before they result in life-threatening complications.

Expanding diagnostic reach through mobile units ensures early diagnosis of bleeding disorders, reducing complications during childbirth and neonatal care. Joint training workshops for health workers in rural and urban areas can help integrate bleeding disorders into routine maternal and child health care.

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Collaborative policy advocacy and engagements can help increase funding, treatment subsidies, and inclusion of bleeding disorders in MNCH programs and health insurance. Joint community education will help amplify messages, address stigma, and empower families to seek care and adhere to treatment.

Addressing bleeding disorders in maternal, neonatal, and child health is a lifeline that can be given to Nigerian families. Awareness, access to diagnosis and treatment, and integration of bleeding disorder care into maternal, neonatal and child health programmes can reduce mortality and ensure a better quality of life for thousands of families.

The journey ahead requires multisectoral collaboration. The rewards are healthier mothers, thriving children, and resilient families.

No family in Nigeria, a country of such diversity and great resources, need to suffer the tragedy of the prevented death of a loved one from an undiagnosed or untreated bleeding disorder. It is now time to act.

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