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. Some children may have completely normal screening and yet bleed at procedures in areas with increased fibrinolysis, such as the mouth (ie, tonsillectomy). 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. [9, 10]
The history may reveal the following:
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Increased or easy bruising
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Recurrent epistaxis
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Menorrhagia
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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. [11] 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.
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Family history of a bleeding diathesis - Bleeding from wounds, gingival bleeding, postpartum bleeding
A study by Bowman et al reported that the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease [MCMDM-1 VWD]) Bleeding Questionnaire, as modified into the Pediatric Bleeding Questionnaire, has a strong negative predictive value in addressing bleeding symptoms. [12]
A study by Sanders et al found that out of 113 children with von Willebrand disease (type 1, type 2, or type 3), 44% experienced pediatric-specific bleeding (any of the following: umbilical stump bleeding, cephalohematoma, cheek hematoma, conjunctival bleeding, postcircumcision bleeding, postvenipuncture bleeding). The study also found that children with type 2 or 3 von Willebrand disease had greater frequency of any bleeding, epistaxis, and oral cavity bleeding than did those with type 1 disease, with this frequency linked to von Willebrand factor levels. [13]
Physical
The physical examination findings may be normal, but the following may be present:
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Increased bruises
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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:
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Congenital heart disease [14]
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Angiodysplasia, telangiectasia, connective tissue disorders
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Seizure disorders treated with valproic acid
A meta-analysis by Sahebkar et al of randomized, controlled trials indicated that high-intensity statin therapy can significantly reduce von Willebrand factor antigen levels. This was particularly found in studies lasting 12 weeks or more, with simvastatin and pravastatin showing the greatest lowering effect. [15]
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Structure and domains of von Willebrand factor.
