Research Studies

Dr. Michael H. White is a pediatric hematology and oncology fellow at Emory University/CHOA. He earned his undergraduate degree in biology from Harding University and completed his medical degree at the University of Texas Southwestern Medical School. He went on to complete his general pediatrics residency training at Vanderbilt University in Nashville, TN. He is currently pursuing a Master of Science degree in Clinical Research at Emory University and has received a TL1 research training grant (also known as a "Linked Training Award"), through the National Institutes of Health for his focus on multidisciplinary clinical and translational science. Dr. White is also the Chair-Elect of the Hemostasis and Thrombosis Research Society (HTRS) Fellows Network and serves as a board member for the International Health Care Foundation. As an NHF-Shire clinical fellow, Dr. White will receive specialized clinical training in the Comprehensive Bleeding Disorders Clinic and Women and Girls' Bleeding Clinic at CHOA under the mentorship of Drs. Robert Sidonio and Shannon Meeks. In addition to his clinical focus treating patients with disorders of hemostasis and thrombosis, Dr. White will pursue his clinical research characterizing the management and outcomes of heavy menstrual bleeding in adolescents with bleeding disorders and in those who are taking anticoagulant or antiplatelet medications.

While an NHF-Shire Clinical Fellow, Dr. Hanny Al-Samkari will acquire a clinical and research expertise in hemophilia and rare bleeding disorders under the mentorship of Dr. Stacy Croteau at Boston Children's Hospital and Drs. Eric Grabowski and Larissa Bornikova at Massachusetts General Hospital (MGH). Dr. Al-Samkari received his medical degree from Washington University in St. Louis, where he was elected to AOA (Alpha Omega Alpha is a national medical honor society). He completed his residency in internal medicine at the University of Pennsylvania, where he served as Chief Medical Resident. He completed his fellowship in hematology and medical oncology at the Dana-Farber Cancer Institute and Massachusetts General Hospital (MGH) combined program. During this fellowship, he strengthened his passion for classical hematology, and his research was focused on novel indications for thrombopoietin receptor agonists. Dr. Al-Samkari will lead the Hereditary Hemorrhagic Telangiectasia (HHT) clinic at MGH under the mentorship of Dr. David Kuter. He is also a dedicated medical educator, having worked as a member of the American Society of Hematology's Benign Hematology Curriculum Initiative, and he has continued to be active in teaching medical students, residents and physician assistants.

People with bleeding disorders are often connected to and with various community members such as local and national foundations/associations, their home health company, nurses , pharmaceutical representatives, etc. While people are often encouraged to wear medic alert ID, they do not know anyone in the EMS system who may be caring for them in case of an emergency. Through this project, EMS providers will receive education regarding bleeding disorders and the treatment required in an emergency. This project will seek to connect the HTC's with the EMS systems locally and regionally to coordinate the education with the EMS professionals to provide care.

Objective:

Immune tolerance induction (ITI) is the standard of care for inhibitor eradication and restoration of factor VIII (FVIII) responsiveness in subjects with severe hemophilia who develop high-titer inhibitors. Retrospective data support the use of recombinant FVIII Fc fusion protein (rFVIIIFc) in ITI (Carcao et al. Haemophilia. 2018) but this has yet to be confirmed in prospective studies. This study presents preplanned interim results of verITI-8 (NCT03093480).

Methods:

VerITI-8 is a single-arm, nonrandomized, open‐label, ethics-approved study of rFVIIIFc (200 IU/kg/day) for first-time ITI. Eligible subjects had a history of high-titer inhibitors (historical peak ≥5 Bethesda units [BU]/mL) and provided informed consent. The primary endpoint is time to tolerization, defined by negative inhibitor titer (<0.6 BU/mL) at two consecutive visits; incremental recovery ≥66% of expected at two consecutive visits; and rFVIIIFc half‐life ≥7 hours. ITI failure is defined as not meeting the above criteria by Week 48. This interim analysis was planned when ≥10 subjects had received ≥6 months of rFVIIIFc ITI.

Summary:

Fifteen subjects were screened as of the December 5, 2018 cutoff, while 14 subjects enrolled and had received ≥1 dose of rFVIIIFc for ITI. The median (range) age at start of ITI was 2.6 (0.8–16.0) years and historical peak inhibitor titer was 29.6 (6.2–256.0) BU/mL. Six subjects have been successfully tolerized, with a median (range) time to first negative titer, normal incremental recovery, and tolerization of 2.3 (1.7–15.6), 6.0 (4.3–28.1), and 11.7 (8.1–32.0) weeks, respectively. Seven subjects continue to receive rFVIIIFc ITI (median [range] time on ITI: 16.0 [0.1–35.6] weeks) and 1 subject has failed. No adverse events related to rFVIIIFc have been reported.

Conclusions:

Early results from this prospective/ongoing study of first-time ITI indicate that rFVIIIFc may offer rapid time to tolerization in some subjects with severe hemophilia A and high-titer inhibitors. Achieving tolerance faster can improve quality of life and reduce costs.
 

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.