Quality in hemostasis and thrombosis - part IV.

Abstract

bleeding symptoms, macrothrombocytopenia, mild spontaneous platelet aggregation, positive RIPA at 0.3 and 0.4 mg/mL, von Willebrand factor (VWF) ristocetin cofactor (VWF:RCo) to antigen (VWF:Ag) ratio of T located at nucleotide 3805 in the g.DNA of the patient’s GP1BA gene, resulting in a Trp to Leu amino acid change at residue 246 (p.W246L). This mutation was absent in his unaffected mother and also in the 100 controls and was predicted as damaging by in silico analysis. The residue W246 is located within the VWF binding region and exists in a strongly conserved position in the phylogenetic tree, which is expected to be unable to tolerate substitutions without changing its functional characteristics. These findings argue strongly in favor of the view that this substitution does not represent a polymorphism, and therefore, is responsible for the PT-VWD phenotype of the patient. The accompanying editorial by Othman and Emsley 5 highlights the importance of this new work, and it alsoextends the analysis of the proposed mutation by molecular modeling. The second editorial, 7 along with the accompanying highlighted articles, 8,9 deal with recent initiatives in the standardization and harmonization of antiphospholipid antibody (aPL) testing, essential for the appropriate diagnosis and management of patients with antiphospholipid syndrome (APS) and other hypercoagulable states. 14 The leading issues in aPL testing include high vulnerability to preanalytical, analytical as well as postanalytical problems, the heterogeneous sensitivity of tests and reagents, high intermethod and interlaboratory variability, the clinically meaningful rate of false-negative and false-positive results, an absence of