Laboratory characterization of obligate carriers of type 3 von Willebrand disease with a potential role for Platelet Function Analyzer (PFA‐200)

Abstract

Introduction Type 3 von Willebrand disease (VWD) is a rare autosomal recessive disorder characterized by undetectable von Willebrand Antigen (VWF:Ag). Carriers of type 3 VWD carry one null allele and have von Willebrand factor (VWF) at about 50% of normal. The aim of this study was to characterize type 3 VWD carriers and to study the role of Platelet Function Analyzer (PFA‐200) in this cohort. Methods This was a cross‐sectional study where data were collected from carriers (parents/offspring) of type 3 VWD patients and evaluated with activated partial thromboplastin time, factor VIII, blood group, ristocetin cofactor assay (VWF:RCo), VWF:Ag, and closure time on PFA‐200 with collagen/epinephrine (COL/EPI), and collagen/ADP (COL/ADP). Results One hundred carriers were included in the study of which 85 were included for PFA‐200 analysis. The mean (SD) of VWF:Ag (IU/ml) and VWF:RCo (IU/ml) was 0.63 (0.24) and 0.61 (0.26), respectively. Among the 100 carriers, based on VWF levels (VWF:Ag and/or VWF:RCo) and bleeding history, there were 7 type 1 VWD, 10 type 2 VWD, 25 borderline VWF (0.30–0.50 IU/ml and no bleeding), and 58 normal VWF (>0.50 IU/ml). PFA‐200 was prolonged in 71% of the carriers, all carriers with type 1 and type 2 VWD phenotype, 80% carriers with borderline VWF, and 59% with normal VWF. COL/EPI was more sensitive than COL/ADP and showed better correlation with VWF parameters than COL/ADP. Conclusion Carriers of type 3 VWD can have a variable laboratory phenotype. PFA‐200 showed good sensitivity among the carriers at VWF levels <0.50 IU/ml.

Point-of-Care Testing in Patients with Hereditary Disorders of Primary Hemostasis: A Narrative Review

“…43,52 Normal PFA-100 results are especially rare in patients with abnormal VWF function or a lower quantity of large molecular VWF multimers. 24,26,32,35,60,78,80,81 In cases of mild type 1 VWD the false-negative rate is higher. Sap et al reported a sensitivity of only 29%, specifically in this group of patients.…”

“…PFA-100 is extensively studied in patients with (suspected) VWD. 17 18 19 21 22 23 24 26 27 28 29 30 31 32 33 34 35 36 37 43 51 52 53 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 Favaloro et al reported an overall sensitivity of 83.2% and 91.5% of the ADP and EPI cartridge respectively in a review in 2008. 79 A current analysis including all articles published before and after 2008 yielded similar test performance outcomes, as shown in Fig.…”

Harmonizing platelet function analyzer testing and reporting in a large laboratory network

“…For comparison, some CT NRRs reported in the contemporary 6,16–29 and original literature 30–53 are shown in Figure 3. In most instances, these NRRs differ from each other and also from the manufacturer ranges, especially for C/ADP.…”

“…The Siemens product information CT NRRs are shown by the green horizontal dashed lines. Figure A shows NRRs from some contemporary literature as obtained from the recent literature search (see Methods), and reflecting information from the past 3 years 6,16–29 . Figure B shows NRRs from some early literature as otherwise reviewed in Reference 10 30–53 .…”

“…As an example, the ICPMR laboratory recently , and reflecting information from the past 3 years. 6,[16][17][18][19][20][21][22][23][24][25][26][27][28][29] Figure B shows NRRs from some early literature as otherwise reviewed in Reference 10. Reference numbers identify their place in the reference list.…”