A 22 year old female is referred to your clinic for a lifelong history of easy bruising and heavy menstrual bleeding starting at menarche.
- Is this bleeding history significant? Are there any clinical prediction rules that may help in defining pre-hemostatic test probability?
Yes, this bleeding history is significant. Heavy menstrual bleeding starting at menarche and a low ferritin are two very sensitive markers that suggest the significance of a bleeding history.
There are numerous bleeding questionnaires that have been developed and validated to aid in the diagnosis of von Willebrand disease. Please see below for the history of bleeding questionnaires that help in the diagnosis of bleeding disorders.
These bleeding questionnaires have a very powerful negative predictive value and can, with a negative score, eliminate the need for von Willebrand screening. This is extremely important as the diagnosis of von Willebrand is rife with confounding factors, including pre-analytical laboratory variables that can lead to its excessive and improper diagnosis.
- She is found to have von Willebrand disease on hemostatic testing. What is von Willebrand disease?
Von Willebrand disease (VWD) is also inherited, but unlike hemophilia, it is not gender linked. It is inherited predominantly in an autosomal dominant fashion and has a prevalence of 1%. There are exceptions, however, as well as variable penetrance in some subtypes.
- What is the initial screen for von Willebrand disease? What are the subsequent tests required to further define the diagnosis?
VWD presents as bleeding in the mucous membranes and also as bleeding in joints/muscles among the few individuals with a severe form of the disorder.
There are 3 broad types of VWD:
- Type 1 (partial quantitative defect). Type 1 VWD is the most common form.
- Type 2 (qualitative defect),
- Type 3 (complete qualitative absence).
VWD is caused by insufficient or impaired function of a protein called von Willebrand factor (VWF). VWF is synthesized by endothelial cells and megakaryocytes. It is stored in the Weibel-Palade bodies of endothelial cells and alpha granules of platelets. VWF exists in various forms – from dimers to larger multimers. The larger the VWF molecule, the more active it is in primary hemostasis – i.e. the better it helps with platelet function.
VWF has two major hemostatic roles:
- Platelet adhesion and aggregation,
- Chaperoning and prolonging the half-life of coagulation factor VIII.
VWF is therefore important for both primary and secondary hemostasis.
Sadler, JE. Low von Willebrand factor: sometimes a risk factor and sometimes a disease. Hematology Am Soc Hematol Educ Program. 2009:106-12. doi: 10.1182/asheducation-2009.1.106.