Laboratory misdiagnosis of von Willebrand disease in post- menarchal females: A multi- center study

Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off- site laboratory processing, instead of a coagulation facility with onsite processing. Off- site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off- site and onsite specimen processing for VWD in this multicenter, retrospective study. We enrolled females aged 12 to 50- years who had off- site specimen processing for VWF assays, and repeat testing performed at a consulting institution with onsite coagulation phlebotomy and processing. A total of 263 females from 17 institutions were included in the analysis. There were 251 subjects with both off- site and onsite VWF antigen (VWF:Ag) processing with 96 (38%) being low off- site and 56 (22%) low onsite; 223 subjects had VWF ristocetin co- factor (VWF:RCo), 122 (55%) were low off- site and 71 (32%) were low onsite. Similarly, 229 subjects had a Factor VIII (FVIII) assay, and 67 (29%) were low off- site with less than half, 29 (13%) confirmed low with onsite processing. Higher proportions of patients demonstrated low VWF:Ag, VWF:RCo, and/or FVIII with off- site processing compared to onsite (McNemarʼs test P- value <.0005, for all assays). These results emphasize the need to decrease delays from sample procurement to processing for VWF assays. The VWF assays should ideally be collected and processed at the same site under the guidance of a hematologist.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156476/2/ajh25869.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156476/1/ajh25869_am.pd

Differential lipid response to statins is associated with variants in the BUD13-APOA5 gene region

Genetic variants within the BUD13-APOA5 gene region are known to be associated with high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. Recent studies suggest that single nucleotide polymorphisms (SNPs) within this region affect HDL-C response to statin-fibrate combination therapy and low-density lipoprotein cholesterol (LDL-C) response to statin therapy. We hypothesized that SNPs within the BUD13-APOA5 region are associated with TG, HDL-C, and LDL-C response to statin therapy. We examined 1520 observations for 1086 patients from the Personalized Medicine Research Project, a large biorepository at the Marshfield Clinic Research Foundation, who had received statin therapy and been previously genotyped for polymorphisms in the 11q23 chromosomal region. A significant differential response to statin therapy was observed for 3 SNPs. The minor allele at rs11605293 significantly attenuated TG-lowering response to pravastatin (P = 0.000159), whereas the minor allele at rs12806755 was associated with a similar response to lovastatin (P = 0.000192). Genotypes at rs947990 significantly attenuated LDL-C reduction to atorvastatin therapy (P = 0.000668) with some patients with the minor allele having LDL-C increase after therapy. No SNPs within the BUD13-APOA5 region were associated with a significant effect on HDL-C reduction in response to statin therapy. In conclusion, this study suggests that common SNPs within the BUD13-APOA5 can affect TG and LDL-C response to statin therapy in a North American population