Research Studies

Objective:

Evaluate clinical characteristics, hemostasis management, and clinical outcomes regarding menstruation, child birth, surgical procedures, dental care, and spontaneous and traumatic bleeds of women and girls with factor VIII (FVIII; hemophilia A) or factor IX (FIX; hemophilia B) deficiency (WGFD).

Methods:

A retrospective chart review is ongoing at three US hemophilia treatment centers (HTC) to collect data on WGFD (obligate or potential carriers of FVIII or FIX deficiency, with or without genetic confirmation). Data are collected on patients who had at least two HTC visits and underwent medical or surgical interventions for hemostasis management between April 2012 and November 2018, with the outcome available in medical charts.

Summary:

Interim results as of April 5, 2019 include charts from two HTCs on 26 (89.7%) patients with FVIII deficiency and 3 (10.3%) patients with FIX deficiency. The median (range) age at factor deficiency diagnosis was 18.5 (0.1–72.0) years. Twenty-four (82.8%) and 8 (27.6%) patients had a family history of hemophilia and other bleeding disorders, respectively. A total of 17 (58.6%) patients initially visited the HTC due to family history/genetic counseling. Other reasons for visiting an HTC were heavy menstrual bleeding (n=12 [41.4%]) or spontaneous or traumatic bleeds (n=12 [41.4%]), including 7 (24.1%) patients reporting both heavy menstrual bleeding and spontaneous or traumatic bleeds. Of the 12 patients with spontaneous or traumatic bleeds, 4 (33.3%) patients had joint bleeds, 6 (50.0%) patients had excessive nose bleeds, and 9 (75.0%) patients had easy bruising. For those with FVIII deficiency, the median (range) FVIII level at diagnosis was 32.5 (2.0–101.1) IU/dL (n=24), median (range) baseline hemoglobin was 12.9 (5.4–14.8) g/dL (n=19), and median (range) baseline von Willebrand factor ristocetin cofactor was 70 (40–150) IU/mL (n=16). The median (range) number of documented bleeds was 1.0 (0.0–24.0) in the first year at the HTC. Final results of this chart review, including data from those with FIX deficiency, HTC interventions, and outcomes for hemostasis management, will be presented.

Conclusions:

This chart review provides further insights into the clinical presentation and hemostasis management of WGFD evaluated at HTCs in the US. Results may contribute to the design of future prospective studies evaluating treatment options for this patient group.

Dr. Meeks is an Associate Professor of Pediatrics in the Department of Pediatrics at the Emory University School of Medicine and the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta. She obtained a Bachelor of Science in Mathematics from Duke University where she was elected to Phi Beta Kappa. After earning her medical degree from the University of Mississippi, she completed her clinical training at the University of Virginia and Emory University. Dr. Meeks has a basic, translational, and clinical research interest in the development of inhibitors in hemophilia A. Her work has focused on the early immune response to factor VIII and the diversity of the B-cell response to factor VIII. She is a former NHF clinical fellow who currently has funding to pursue these projects from the Hemostasis and Thrombosis Research Society and the National Institutes of Health.

Dr. Staber received her undergraduate e degree in biochemistry from the University of Iowa. She received her MD from the Carver College of Medicine at the University of lowa. She received strong mentorship under the guidance of Drs. Paul McCray and Steven Lentz during her post-doctoral research in gene therapy and hemophilia studies. She was subsequently appointed a faculty position at the University of Iowa Children's Hospital in 2010 and became Assistant Professor of Pediatrics in the Division of Hematology/Oncology in 2013.

Dr. Jill Johnsen is scientist and physician at the Washington Center for Bleeding Disorders in Seattle, WA.  She is an Associate Member at the Bloodworks Research Institute and also an Associate Professor of Medicine in the Division of Hematology at the University of Washington. Her research focuses on the study of hereditary and acquired modifiers of blood traits, with particular emphasis on the genetics and biology of variation in blood group and coagulation factors such as factor VIII, factor IX, and von Willebrand Factor.  Dr. Johnsen is honored by this award and grateful for this support that will further the development of a test to enable patients and providers to determine factor levels much more quickly without needing to send blood to a lab.

Dr. Patricia Zerra is currently completing her pediatric hematology/oncology fellowship at Emory University/Children's Healthcare of Atlanta (CHOA) and will begin an additional fellowship in Transfusion Medicine focusing on coagulation in July 2017. Dr. Zerra graduated from Connecticut College followed by two years of research at Boston Children's Hospital. She received her M.D. from Jefferson Medical College in Philadelphia and completed pediatrics residency at the University of Miami/Jackson Memorial Hospital where she served as chief resident with an additional year practicing general pediatrics. As an NHF-Shire Clinical Fellow, Dr. Zerra will work under the mentorship of Dr. Robert Sidonio, Pediatric Director of the Emory/CHOA Hemophilia Treatment Center to focus on the clinical management of children with bleeding disorders. She will also continue her current research under the mentorship of Drs. Shannon Meeks and Sean Stowell, focusing on the immune response to FVIII in an effort to identify initiating immune events that can serve as targets to prevent FVIII inhibitor formation. Her goal is to serve as a pediatric hematologist and clinical/translational researcher focusing on the care of pediatric patients at risk for developing inhibitors.

Dr. Karen Zimowski is a pediatric hematology/oncology fellow at Emory University/Children's Healthcare of Atlanta (CHOA). Dr. Zimowski received her BS in Biochemistry from Clemson University and her MD from the Medical College of Georgia. She completed pediatric residency at Johns Hopkins University. As a NHF-Shire Clinical Fellow, she will receive clinical training under the guidance of Drs. Robert Sidonio and Shannon Meeks in the Comprehensive Bleeding Disorders Clinic at CHOA and Special Coagulation Laboratory at Emory University. In addition, she will continue her current research projects, investigating the structure-function relationships of both coagulation factor V and factor VIII. Dr. Zimowski aims to become an expert physician-scientist in the field of pediatric hemostasis and thrombosis. She seeks to apply the knowledge gained through laboratory analysis to the clinical setting and provide the highest level of medical care to patients with bleeding and coagulation disorders.

Dr. Megan Rost is a postdoctoral fellow at the University of Michigan. She received a B.S in biochemistry and biotechnology from Michigan State University, and her Ph.D. in molecular and developmental biology at the University of Cincinnati - Cincinnati Children's Hospital Medical Center. Her graduate work focused on understanding vascular endothelial development using zebrafish as a model organism. In July 2015, she joined the lab of Dr. Jordan Shavit in the Department of Pediatrics and Hematology/Oncology at University of Michigan. For her 2016 JGP research fellowship project, she will be using the zebrafish model to analyze blood clot structure and function in the presence and absence of von Willebrand Factor. In studying this, Dr. Rost will be elucidating how arterial thrombus formation occurs in the absence of VWF, aiding in uncovering possible new therapeutic targets for VWD treatment.