Research Studies

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. 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.

This study will evaluate hemophilia treatment center (HTC) services provided to women with hemophilia A or B (Factor VIII or Factor IX level [ 50%). The American Thrombosis and Hemostasis Network (ATHN) maintains a confidential national database for patients with bleeding and clotting disorders. Utilizing this existing ATHNdataset, the study will analyze the effect of gender on the delivery of comprehensive care in patients with hemophilia A and B. The project will focus on how gender impacts three specific components of care: identification of patients with factor VIII or IX deficiency, inclusion of patients in the comprehensive care model, and monitoring of joint bleeding as a key component of comprehensive care provided by HTCs. Demonstrating gender-based disparities in comprehensive care would provide evidence for making changes to improve the clinical care provided to women with hemophilia. This study will add to the knowledge regarding the care of women with hemophilia, helping to inform future studies of this under-researched population.

Klaus Bonazza received his Ph.D. in chemistry from Vienna University of Technology. He is currently a postdoctoral researcher at Boston Children's Hospital and appointed at Harvard Medical School, mentored by Dr. Timothy Springer. His field of interest is the ultra-large concatemeric protein von Willebrand factor (VWF), which accounts for the adaptability of hemostasis to different flow conditions in the blood vessels.

At moderate, physiological flow VWF has a packed, "bird nest's" shape whereas strong elongational flow conditions, occurring downstream of vascular restrictions or injuries, induce a transition to a threat-like, elongated state. On top of this overall unpacking, tensile forces, which are exerted on the chain and transmitted by its A1 domain, cause local conformational changes which activate binding of thrombocyte receptor Glycoprotein Ib (GPIbα) to initiate coagulation. With his JGP fellowship award, Dr. Bonazza will pioneer a new method to obtain structural insights into force dependent VWF unpacking, A1 deformation and GPIbα binding based on hydrogendeuterium exchange under elongational flow conditions.

Objective:

Hepatitis C virus (HCV) infection is a significant health problem for patients with bleeding disorders due to the absence of highly effective HCV screening of blood products prior to the early 1990s. The aim of this analysis was to evaluate the safety and efficacy of the ribavirin-free regimen of glecaprevir/pibrentasvir (G/P) among patients with a history of bleeding disorders.

Methods:

Data from 11 Phase 2 and 3 registrational studies conducted across 18 countries worldwide were included. HCV genotype (GT) 1–6-infected patients with compensated liver disease received G/P for 8, 12 or 16 weeks. The sustained virologic response 12 weeks after end of treatment (SVR12) rate and safety are reported.

Results:

Sixty-two patients with history of bleeding disorders were identified, the most common disorder being hemophilia (37%, [23/62]). The remaining 63% (39/62) of patients had other disorders, including Von Willebrand disease. The cohort was 76% (47/62) male and 89% (54/62) white race with a mean age of 50.5 years (standard deviation ± 12.1). Additionally, 23% (14/62) had compensated cirrhosis. The HCV genotype breakdown among the patients was: GT1, 39%; GT2, 18%; GT3, 21%; GT4, 13%, GT5, 8%; GT6, 2%. In addition to bleeding disorders, a medical history of anemia was reported in 16% (10/62) of patients. SVR12 was achieved in 100% (62/62) of patients. Adverse events (AEs) were reported in 68% (42/62) of patients, and 37% (23/62) of patients experienced an AE assessed as possibly related to study drugs. Serious AEs (SAE) were reported in 3 (5%) patients, none being assessed as related to the study drugs; 2 of these SAEs (1 per patient) were associated with the underlying bleeding disorder. There was 1 (2%) AE leading to discontinuation of study drug (dyspepsia); the patient went on to achieve SVR12. There was 1 (2%) non-treatment emergent death reported, occurring 60 days after the last dose of study drug. Post-baseline grade ≥3 laboratory abnormalities occurred in 3 patients: one each in hemoglobin, aspartate aminotransferase and bilirubin (all n = 1; 2%), without concurrent elevations in alanine aminotransferase.

Conclusions:

G/P achieved a 100% SVR12 rate in patients with a history of bleeding disorders and demonstrated a favorable safety profile, thus providing support for treatment of chronic HCV infection with the G/P regimen in this patient population.