Inhibitors to Von Willebrand Factor in Type 3 Von Willebrand Disease (VWD)
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2017, Vol 1, Issue 3
Abstract
Introduction: Type 3 VWD is the least common and most severe among the three types of VWD. The incidence was estimated at 5-3/million and the severity is thought to be similar to mild or moderate hemophilia A. A recent report from the UK showed that failing to perform all required assays for the diagnosis of VWD Type 3, may occasionally result in giving a wrong diagnosis such as mild or moderate hemophilia A, a practice occasionally used by some hemostasis laboratories.[1] Type 3 VWD is usually associated with a clinical course that combines the mucous membranes bleeding features seen in patients with VWD as well as the deep muscle and joint bleeding encountered in patients with mild to moderate hemophilia. The lack of VWF, which usually protects and delays the degradation of FVIII result in very low level of FVIII activity, which contributes to the bleeding severity. The treatment of this condition is somewhat similar to that of patients with hemophilia which consists of infusions to replace the missing factors as on demand regimen using plasma derived (PD) products which contains both FVIII and VWF. Furthermore, many of the patients are currently on some form of prophylaxis to eliminate or decrease the frequency of bleeding episodes. 7.5-9.5 % of the patients develop inhibitors to VWF becoming non- responsive to replacement therapy, and prone to develop severe anaphylactic and life threatening reactions when exposed to any product that contains VWF [2]. A previous exposure to VWF , extent of the exposure, as well as mutations causing a null-allele or deletion of the gene are all known predisposing factors for the development of inhibitors in patients with type 3 VWD. Clinical course variability in type 3 VWD is attributed to the different antigenic regions on the gene and the potency of the inhibitor. Bleeding manifestations could be very severe in some patients presenting with long refractory and recurrent epistaxis, GI bleed, joint bleeds or formation of pseudo tumor in various tissues. It is somewhat surprising that very few reports on inhibitors in type 3 VWD were published in the USA in comparison to the European literature. The neutralizing antibodies are usually polyclonal IgG class which precipitates VWF in normal plasma without any effect on purified FVIII unless it is bound to VWF, and for this reason, recombinant FVIII is usually effective in controlling the bleeds , keeping in mind that its half-life in such patients is very short at approximately 3 hours [3,4].To describe the clinical course in patients with type 3 VWD who develop inhibitor to the factor, and the circumstances leading to the diagnosis of neutralizing antibodies in type 3 VWD, the diagnostic tests required, and the treatment options.
Authors and Affiliations
Hassan M Yaish, Robert D Christensen, Jessica Meznarich, Walid K Salah, George M Rodgers, Richard S Lemons
Keywords
Related Articles
- EP ID EP569504
- DOI 10.26717/BJSTR.2017.01.000242
- Views 162
- Downloads 0
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