nd 73.five IU/kg FVIII for surgeries using a higher and moderate threat of bleeding, respectively. Therapy wasABSTRACT703 of|PB0943|Atypical Presentation of VWD Resulting in Discovery of Novel VWF Mutation T. van de Berg1; A.M Todaro1; J. van Beers2; K. Wichapong1; F. Heubel-Moenen3; E. Castoldi1; Y. Henskens2; E. Beckers1PB0944|The von CB1 Modulator Gene ID Willebrand IL-6 Antagonist review Disease-Woman (VWD-Woman) Trial: A Pilot Research Evaluating Recombinant von Willebrand Component (rVWF) plus Tranexamic Acid (TA) vs. rVWF Alone during the Prevention of Postpartum Hemorrhage in Women with von Willebrand Disease N. Machin1; S. Caritis1,2; C. Seaman1,three; M. Brooks1; D. Vehec1,three; M. Rode1,3; D. Ivanco1,3; D. Fischer2; D. Zowacki2; M. Ragni1,Cardiovascular Research Institute Maastricht, Division of2Biochemistry, Maastricht, Netherlands; Central Diagnostic Laboratory, MUMC+, Maastricht, Netherlands; Department of Hematology, MUMC+, Maastricht, Netherlands Background: Von Willebrand Aspect (VWF) is often a multimeric protein largely involved in both key and secondary hemostasis. The diagnosis and classification of von Willebrand Condition (VWD) individuals might be tough. Atypical presentations of VWD could benefit from extra genetic evaluation. Aims: Characterization of the VWD patient having a disproportionately severe bleeding phenotype. Approaches: Regimen evaluation for VWD was performed. Genetic screening was carried out by exome sequencing of hemostasis associated genes. VWF mRNA analysis was carried out by RT-PCR and Sanger sequencing. Effects: Schedule evaluation showed PFA-ADP and PFA EPI 300 seconds, VWF:ACT of 37 which has a VWF:AG of 36 . Collagen binding and FVIII-binding had been 46 and 28 respectively. Genetic evaluation with the VWF gene disclosed 2 heterozygous variants of unknown significance (VUS): c.2771 GA (exon 21, p.Arg924. Gln) features a one.5 population prevalence and has been previously described in form 1 and 2N VWD. The other VUS (c.2278 CA; exon 17) can be a novel mutation predicting a major amino acid substitution (p.Arg760Ser) while in the D2-domain of VWF. Sequencing of exons 17 and 21 inside the patient’s VWF mRNA exposed homozygosity for that mutated allele at each mutation internet sites, indicating the two variants are in cis and the `normal’ allele will not be expressed at mRNA level. Additionally, an aberrantly spliced mRNA was identified which lacks exon 17, resulting in a frameshift in addition to a premature stop codon in exon 18. Structural evaluation showed the Arg760Ser mutation may lessen the affinity of furin to the VWF pro-peptide cleavage internet site. Conclusions: The patient carried two VUS within the only VWF allele that was expressed at the mRNA level. The Arg760Ser mutation potentially interferes pro-peptide cleavage by furin. The cause from the silencing in the `normal’ allele, the phenotypic impact with the exon 17 variant as well as practical affect of your mutations are at present beneath investigation.University of Pittsburgh, Pittsburgh, Usa; 2UPMC Magee-Womens Hospital, Pittsburgh, United states of america; 3Hemophilia Center of Western Pennsylvania, Pittsburgh, Usa Background: Von Willebrand ailment (VWD) is usually a quantitative or qualitative deficiency of von Willebrand component (VWF) that may be linked having a one.5-fold improved odds of postpartum hemorrhage (PPH). This risk persists in spite of VWF substitute and might be lifethreatening, cause hysterectomy, and call for blood transfusion with its attendant risk. We hypothesize the increased bleeding chance is because of physiologic postpartum fibrinolysis inside the setting of VWF