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Abnormal Bleeding Risk in Female Hemophilia A Carriers

Award Number: K08HL159314
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Abnormal Bleeding Risk in Female Hemophilia A Carriers - Project Summary/Abstract This K08 Mentored Clinical Scientist Research Career Development Award application details a 5-year training program to advance Dr. Cygan’s career goal of developing an independent research program in hemostasis focused on bleeding tendency in female Hemophilia A carriers. The scientific proposal seeks to investigate bleeding tendency in Hemophilia A (HA) carriers, which remains largely underrecognized and poorly understood. HA is due to mutations within the F8 gene encoding coagulation Factor VIII (FVIII), and is commonly thought to affect only men, while female HA carriers are thought to be only rarely symptomatic. There are an estimated four female HA carriers for every one HA male, and increasing evidence indicates that decreased FVIII levels and bleeding symptoms in HA carriers are not rare. Many have significant bleeding events despite Factor VIII activity levels considered adequate in males. Current understanding of bleeding tendency in this area is lacking, and research investigating female HA carriers would greatly inform their classification and management. The proposal seeks to develop a risk prediction model for bleeding tendency in HA carriers, using parameters other than standard coagulation testing. In Aim 1, a multivariable risk prediction model will be developed and validated. In Aim 2, a cell culture system to model the HA carrier state will be developed and the role of X-chromosome inactivation (XCI) in altering basal and stimulated levels of FVIII and resulting thrombin generation will be evaluated. In Aim 3, the role that natural anticoagulants alter hemostasis and explain differences in bleeding phenotypes between HA carriers independent of XCI will be investigated. During the award period, Dr. Cygan will continue to develop his expertise in benign hematology, and further expand his abilities in experimental design and implementation. A multidisciplinary mentorship team has been assembled to ensure the success of this project and includes expertise in X chromosome biology, Factor VIII expression, clinical hematology and biostatistics. The mentorship team includes Dr. Laura Carrel, Dr. Valder R. Arruda and Dr. M. Elaine Eyster; they will guide Dr. Cygan in meeting his training objectives through direct research experience, formal didactics, participation in institutional seminars and junior career development opportunities. Dr. Lan Kong, a biostatistician, will contribute to Dr. Cygan’s research and career plan as a collaborator and statistical advisor.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $172,670 )
2025	2025	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	000	5	8/14/2025	NON-COMPETING CONTINUATION	$172,670
														Subtotal = $172,670

Issue Date FY: 2024 ( Subtotal = $172,670 )
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	000	4	9/9/2024	NON-COMPETING CONTINUATION	$172,670
														Subtotal = $172,670

Issue Date FY: 2023 ( Subtotal = $172,670 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	000	3	8/15/2023	NON-COMPETING CONTINUATION	$172,670
														Subtotal = $172,670

Issue Date FY: 2022 ( Subtotal = $172,670 )
2022	2022	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	000	2	8/4/2022	NON-COMPETING CONTINUATION	$172,670
														Subtotal = $172,670

Issue Date FY: 2021 ( Subtotal = $172,670 )
2021	2021	PENNSYLVANIA STATE UNIVERSITY, THE	500 UNIVERSITY AVE RM C1607	HERSHEY	PA	17033	DAUPHIN	USA	Blood Diseases and Resources Research	000	1	8/19/2021	NEW	$172,670
														Subtotal = $172,670

Grand Total All Awards = $863,350

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Abnormal Bleeding Risk in Female Hemophilia A Carriers

Award Number: K08HL159314

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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