Mechanisms through which hyperfibrinogenemia causes more stable thrombi that do not respond to treatment with thrombolytic drugs

 

Trainee:

Bethany Walton

Bethany Walton

Research Mentor:

Dr. Alisa Wolberg

unavailable

Clinical Co-Mentor:

Dr. Nigel Key

unavailable
Department Pathology
Project Description:

Cardiovascular disease is the leading cause of death and disability in the United States. Epidemiological studies have associated elevated levels of fibrinogen, a 340 kDa plasma protein, with both arterial and venous thrombosis. Our lab has recently shown that fibrinogen in causative in these pathologies, and not just a biomarker. However, it remains unclear if the level of γ’ fibrinogen (γA/γ’), a fibrinogen variant containing an alternatively spliced gamma chain, further modulates the risk of thrombus formation. γA/γ’ accounts for 8-15% of fibrinogen in healthy individuals, and has unique functional properties that may either be pro- or anti- thrombotic. Studies have shown that elevated levels of γA/γ’ is associated with arterial thrombosis (coronary artery disease and myocardial infarction), independent of total fibrinogen levels. Another study found an increased γA/γ’ to total fibrinogen ratio in the acute phase of ischemic stroke. Conversely, a decreased γA/γ’ to total fibrinogen ratio has been correlated with deep vein thrombosis and thrombotic microangiopathy. These findings suggest γA/γ’ has specific, but different functions in arterial and venous thrombosis. It is of clinical importance to determine the role of γ’ fibrinogen in thrombosis as it may serve as a diagnostic biomarker and/or direct thrombolytic therapy.