Potential supplementary utility of combined PFA-100 and functional von Willebrand factor testing for the laboratory assessment of desmopressin and factor concentrate therapy in von Willebrand disease

Blood Coagulation &Amp; Fibrinolysis

Mohammed

Koutts

2009

Self Cite

We report an investigation of type 2N von Willebrand disease (VWD), covering the past 7 years and evaluating 1031 plasma samples from over 500 patients. Samples included specific requests for investigation of possible type 2N VWD (including family studies) and samples from 'hemophilia' or nonspecified VWD investigations that could unknowingly be type 2N VWD. In total, 13 new patients with type 2N VWD were identified, four of whom initially presented with normal levels of factor VIII and only three of whom (i.e. 23%) derived from specific clinical requests for investigation of type 2N VWD. Furthermore, type 2N VWD was excluded in 91% of specific clinical requests for type 2N VWD investigations. Poststudy evaluation indicates that type 2N VWD in this geographic region has an incidence rate similar to that in other westernized regions, accounting for around 1-2% of all identified VWD cases and about 13% of all type 2 VWD cases. In conclusion, this study highlights that clinicians requesting laboratory investigations related to a bleeding tendency often fail to appropriately recognize the possibility of type 2N VWD, that a normal plasma factor VIII will not exclude type 2N VWD, and although a relatively uncommon form of VWD overall, type 2N VWD represents a significant qualitative disorder.

Section: Assessment Of Prevalence Of Type 2n Von Willebrand Diseasementioning

confidence: 93%

Identification and prevalence of von Willebrand disease type 2N (Normandy) in Australia

Blood Coagulation &Amp; Fibrinolysis

Mohammed

Koutts

2009

Self Cite

“…In summary, the differentiation of types 1 and 2M VWD will remain problematic when laboratories do not incorporate a VWF:CB assay and run a VWF:RCo assay insensitive to low levels of VWF. Globally, most 2M VWD cases are currently inappropriately identified as type 1 (Favaloro, 2011), which has significant management implications because postdesmopressin functional VWF responses tend to be suboptimal, compared with classical type 1 VWD patients with similar levels of VWF:Ag (Favaloro et al. , 2009a,b).…”

Section: Discussionmentioning

confidence: 99%

“…Using retrospective data, our laboratory recently highlighted a test process to help discriminate types 1 and 2M VWD using laboratory testing that incorporates VWF collagen binding (VWF:CB) and the PFA‐100 ® (Siemens, Marburg, Germany), supplemented by repeat testing and a desmopressin trial (Favaloro et al. , 2009a,b).…”

Section: Introductionmentioning

confidence: 99%

Distinguishing types 1 and 2M von Willebrand disease

Forsyth

Koutts

2011

Int J Lab Hematology

Discrimination of types 1 and 2M von Willebrand disease (VWD) is problematic. Type 1 VWD represents a quantitative deficiency of von Willebrand factor and type 2M a qualitative disorder. 2M VWD is considered a potentially more serious bleeding disorder than type 1 VWD and may also require a differential management approach given the higher bleeding risk and that desmopressin may be less effective. We describe a case of 2M VWD 'masquerading' as type 1 and show how the differential diagnosis can be obtained using standard laboratory assays. The case was genetically confirmed as a 3943C>T mutation, leading to R1315C.

“…There is additional but generally underrecognized utility in assessing data from DDAVP trials for the diagnosis and typing of VWD, given that the response profile is often VWD-type characteristic. 13,24,25,[51][52][53] In brief, FVIII and all VWF test parameters will rise post-DDAVP in type 1, and both RCo:Ag and CB:Ag ratios will be >0.7 before and after DDAVP. In type 2A, FVIII and VWF:Ag will rise post DDAVP, but VWF:RCo and VWF:CB will not, or their response is weak and/or transient; therefore pre-DDAVP RCo:Ag and CB:Ag ratios typically <0.7 will remain <0.7 after DDAVP.…”

Section: Additional Useful Investigative Approaches To Help Overcome mentioning

confidence: 99%

von Willebrand Disease: Local Diagnosis and Management of a Globally Distributed Bleeding Disorder

2011

Semin Thromb Hemost

von Willebrand disease (VWD) is the most common inherited bleeding disorder and arises from deficiencies and/or defects in the plasma protein von Willebrand factor (VWF). The current report overviews the diagnosis and management of VWD as reflected by differential processes applied within centers around the world. The prevalence of VWD, as well as the frequency of different VWD types, is also reported. VWD prevalence data varies according to methodology used, with epidemiological/population screening estimates approximating 1% of the population (or 10,000 cases per million population), several orders of magnitude higher than estimates from bleeding disorders registry data or regional/center analysis (which instead range from <1 to ~450 cases per million population). Frequency of different VWD types also varies according to source and analysis, with type 1 VWD identified as the clear dominant type in most developed countries (ranging from 40% to 90% of all VWD cases), whereas type 3 VWD predominates in developing countries such as India and Iran. The frequency of qualitative (i.e., type 2) VWD also varies considerably among different reports, ranging from 3% to >50% of all VWD cases, as does the frequency of specific qualitative VWD types (i.e., 2A, 2B, 2M, and 2N). Although type 2A VWD is considered the most common form of type 2 VWD, in some reports workers consider type 2M VWD to be as, or more, common. Although not considered to be a "true" VWD, given its platelet origin, platelet-type VWD is only rarely identified. Finally, management of VWD also differs according to geographic region. Most developed countries use standard therapy, employing desmopressin (DDAVP) wherever possible, factor concentrate in other situations, and antifibrinolytic therapy as required. In contrast, the relative high cost and unavailability of factor concentrates in developing countries, and sometimes the unavailability of DDAVP, requires different management strategies to be applied.