PB0202 - The Impact of Iron Deficiency Anemia on Activation of Coagulation in Hereditary Hemorrhagic Telangiectaisa

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

SG

Shatadal Ghosh

Post-doctoral research fellow
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States

Co-Author(s)

Kimberley Youkhana, MD

Hematology Fellow
Department of Medicine, University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, United States
Steven P. Grover, PhD

Research Assistant Professor
Division of Hematology and Blood Research Center, University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, United States
SO

Suk Paul Oh

Professor
Barrow Neurological Research Institute
Phoenix, Arizona, United States
KS

Karen Smith

Research Coordinator
University of North Carolina
Chapel Hill, North Carolina, United States
Brandi N. Reeves, MD

Assistant Professor of Medicine
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Rafal Pawlinski, PhD

Professor of Medicine
Division of Hematology and Blood Research Center, University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States

Co-Author(s)

RK

Raj S. Kasthuri

Professor of Medicine
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare inherited bleeding disorder caused by mutations in endoglin, activin receptor-like kinase 1, or their downstream transcription factor SMAD4. These lead to dysregulated angiogenesis resulting in formation of mucocutaneous telangiectasias and visceral arteriovenous malformations. Recurrent epistaxis and gastrointestinal bleeding are common and cause iron deficiency anemia (IDA). HHT has also been associated with an increased risk for thrombosis. The mechanism(s) remains unclear and a correlation with low iron levels has been observed.

Aims: (1) Determine evidence of coagulation activation in HHT plasma; (2) Assess impact of IDA on coagulation activation in HHT plasma; (3) Develop a mouse model of HHT and IDA to facilitate further investigation.

Methods: Five groups of human subjects were enrolled: HHT with and without IDA, HHT with anemia without ID, non-HHT IDA, healthy controls. Clinical data were recorded and plasma collected. CBC, ferritin, D-dimer, E-selectin and vascular endothelial growth factor (VEGF) were measured. Differential expression of 55 angiogenesis-related proteins in HHT vs control determined using a protein array assay. HHT mice (ALK-1 +/-) and wild-type littermate controls were placed on an iron deficient or normal diet for 3 months and development of IDA assessed.

Results: Fifty-eight subjects enrolled. D-dimer levels were significantly higher in all study groups compared to control (Figure 1a). VEGF levels were higher in both HHT groups but E-selectin levels were comparable. Angiogenesis array identified differentially expressed proteins ( ≥ 50% of control) (Table). Iron deficient diet resulted in reliable development of IDA after 12 weeks in HHT mice (Figure 1b).

Conclusion(s): Our study confirms coagulation activation in patients with HHT and suggests this is further increased by IDA. Angiogenesis array identified differentially expressed proteins that can be independently evaluated. Coagulation activation in HHT is currently being evaluated using various thrombosis models in the HHT IDA mice to discern underlying mechanism(s).