Pediatric Von Willebrand Disease Clinical Presentation
- Author: John D Geil, MD; Chief Editor: Max J Coppes, MD, PhD, MBA more...
History
Many children with von Willebrand disease (VWD) are asymptomatic and are diagnosed as a result of a positive family history or during routine preoperative screening (eg, prolonged bleeding time). Importantly, remember that a wide variation in clinical manifestations is observed, even for members of the same family.
The diagnosis of von Willebrand disease can be challenging and depends on an accurate personal and family bleeding history, as well as demonstration of a low von Willebrand factor (VWF) level.[2]
The history may reveal the following:
- Increased or easy bruising
- Recurrent epistaxis
- Menorrhagia
- Postoperative bleeding (particularly after tonsillectomy or dental extractions): Medical records of 99 patients younger than 18 years with von Willebrand disease who underwent tonsillectomy were compared with 99 patients without von Willebrand disease in the same age group; subjects were matched for age, year of surgery, type of surgery, and indication for surgery.[3] The study concluded that children with von Willebrand disease have a postoperative bleeding rate similar to that of a matched group. However, the sample size was insufficient to eliminate any clinically important difference between the two groups.
- Family history of a bleeding diathesis
- Bleeding from wounds
- Gingival bleeding
- Postpartum bleeding
Physical
The physical examination findings may be normal, but the following may be present:
- Increased bruises
- Mucosal bleeding
Causes
von Willebrand disease is caused by an inherited defect that results in a deficiency or dysfunction of von Willebrand factor. The gene for von Willebrand factor is on the short arm of chromosome 12. It spans approximately 180 kilobases (kb) and is composed of 52 exons. Exons range in size from 40 base pairs (bp) to 1.4 kb. Various point mutations, insertions, and deletions at the von Willebrand factor locus have been described.
In some cases, von Willebrand disease is believed to result from other pathologic processes; however, because of the relatively high prevalence of von Willebrand disease, its concomitant occurrence with other disease states may be coincidental.
Nevertheless, acquired forms of von Willebrand disease can be observed in the following conditions:
- Congenital heart disease
- Angiodysplasia
- Seizure disorders treated with valproic acid
Bowman M, Hopman WM, Rapson D, Lillicrap D, Silva M, James P. A prospective evaluation of the prevalence of symptomatic von Willebrand disease (VWD) in a pediatric primary care population. Pediatr Blood Cancer. Mar 8 2010;[Medline].
Tosetto A, Castaman G, Rodeghiero F. Evidence-based diagnosis of type 1 von Willebrand disease: a Bayes theorem approach. Blood. Apr 15 2008;111(8):3998-4003. [Medline].
Rodriguez KD, Sun GH, Pike F, et al. Post-tonsillectomy bleeding in children with von Willebrand disease: a single-institution experience. Otolaryngol Head Neck Surg. May 2010;142(5):715-21. [Medline].
[Guideline] Nichols WL, Hultin MB, James AH, et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia. Mar 2008;14(2):171-232. [Medline].
[Guideline] Nichols WL, Rick ME, Ortel TL, et al. Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines. Am J Hematol. Mar 16 2009;[Medline].
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Federici AB, Mannucci PM. Management of inherited von Willebrand disease in 2007. Ann Med. 2007;39(5):346-58. [Medline].
[Guideline] Lee CA, Brettler DB. Guidelines for the diagnosis and management of von Willebrand disease. Haemophilia. 1997;3:1-25.
Nichols WC, Ginsburg D. von Willebrand disease. Medicine (Baltimore). Jan 1997;76(1):1-20. [Medline].
Sadler JE, Budde U, Eikenboom JC, et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost. Oct 2006;4(10):2103-14. [Medline].
Werner EJ. von Willebrand disease in children and adolescents. Pediatr Clin North Am. Jun 1996;43(3):683-707. [Medline].
Zhang Z, Blomback M, Anvret M. Understanding von Willebrand's disease from gene defects to the patients. J Intern Med Suppl. 1997;740:115-9. [Medline].
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