Characterizing Complications Among Infants and Toddlers With von Willebrand Disease

A new report published in Blood Advances describes the experiences of infants and toddlers living with von Willebrand disease (VWD), highlighting the role and importance of a family history on the diagnosis of VWD and identifying several factors associated with early diagnosis.

“While VWD can be diagnosed at any age, diagnosis among infants and toddlers <2 years of age is difficult since hemostatic challenges are rare and bruising of extremities and head trauma is common, especially in toddlers as they learn to crawl and walk,” explained study authors, led by Brandi Dupervil, DHSc, MPH, from the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention.

To better understand characteristics and bleeding complications of VWD in young children, Dr. Dupervil and colleagues analyzed data from 105 patients diagnosed with VWD before age 2 who were enrolled in the United States Hemophilia Treatment Center Network (USHTCN). Data were collected at enrollment and at six-month intervals at routine clinic visits. This information, the researchers noted, could help guide obstetric practices for women with VWD and neonatal practices for their potentially affected infants.

Among the 105 enrolled patients, 61 were male (58%) and 44 were female (42%). Type 1 VWD was the most common (63%), followed by Types 2 and 3 (28% and 9%, respectively). For the patients who had available birth and delivery data, the researchers found that most infants and toddlers were born at full term (86%), were a normal weight (82%) and length (89%), and were delivered vaginally (63%).

Notably, 79% of the participants had a family history of bleeding disorders; in 68% of cases, the family history of VWD prompted the initial diagnostic testing. When looking at family history by VWD type, patients with type 2 disease were more likely to have a family history (93%), compared with type 1 (77%) and type 3 (44%; p=0.02).

The mean age at diagnosis was seven months, ranging from prenatal to 22 months, while the mean age at enrollment was 14 months. Patients with type 2 disease tended to be diagnosed earlier than those with other types (p=0.04), and those with a family history of VWD were diagnosed approximately four months earlier than those without (p<0.001).

In addition, patients born to mothers who were known carriers of VWD were diagnosed earlier than those with other family members who had a bleeding disorder. “As expected because of the relationship between family history and Hemophilia Treatment Center (HTC) contact, HTC contact prior to delivery was also associated with earlier diagnosis (p<0.001),” the researchers added.

In the 70% of patients who experienced a bleeding event during the surveillance period, the most common bleeding sites were oral mucosa, followed by circumcision-related and head bleeds (TABLE). “Data on common bleed sites in infants and toddlers with VWD is particularly important because it is an area that previously has not been well studied,” the authors noted.

A large portion of the initial bleeds (41%) occurred before 6 months of age, and approximately two-thirds occurred before the age 1. Looking at patterns and rates of bleeding, there was no significant difference according to patient sex or VWD type.

Approximately 64% of infants and toddlers used treatment products to either prevent perioperative bleeding or to treat a bleeding episode. Treatment approaches included:

  • plasma-derived von Willebrand factor–containing factor VIII concentrates (47%)
  • aminocaproic acid (32%)
  • intravenous or intranasal desmopressin (14%)

No patients in our study used topical hemostatic agents.

They also stressed the vital role of specialized HTCs in offering multidisciplinary care to provide early diagnosis and optimal care of patients with young children with VWD. “[This includes] genetic counselors throughout the prepartum period to increase expectant mothers’ understanding of the risks associated with having a child with VWD, and adult and pediatric hematologists, obstetrician-gynecologists, genetic counselors, nurses, and social workers throughout the pre- and postpartum period to optimize outcomes and disease management,” they concluded.

The researchers noted some potential limitations of this analysis, including an overrepresentation of white patients compared with the distribution of race and ethnicity among children in the U.S.

Reference

Dupervil B, Abe K, O’Brien S, et al. Characteristics, complications, and sites of bleeding among infants and toddlers less than 2 years of age with VWD. Blood Adv. 2021;
5(8):2079-2086.