College

Buchtel College of Arts and Sciences

Date of Last Revision

2025-06-04 12:48:33

Major

Biomedical Science

Honors Course

BIOL 499

Number of Credits

4

Degree Name

Bachelor of Science

Date of Expected Graduation

Spring 2025

Abstract

Factor XI (FXI) deficiency, also known as Hemophilia C, is characterized by mild to moderate bleeding symptoms. However, the factors that modify bleeding severity in FXI deficiency are not fully understood. In this study, we investigated whether components of the contact activation pathway can act as modifiers of bleeding in the context of FXI deficiency. Using a tail vein transection (TVT) model in rats, we assessed bleeding in four experimental groups: wild-type Sprague-Dawley rats, Prekallikrein knockout (PKK-/-) rats, rats treated with a FXI-inhibiting antibody, and PKK-/- rats treated with the FXI antibody.

Under anesthesia, each rat underwent a standardized incision on the lateral tail vein. The procedure lasted 30 minutes and consisted of three 10-minute intervals, initiated either by the incision or by mechanical agitation (wiping) of the wound. Bleeding time was recorded during each interval, and total blood loss was collected. Following red blood cell lysis, hemoglobin concentration was measured spectrophotometrically to quantify blood loss. Hemoglobin levels were also confirmed via terminal inferior vena cava (IVC) collection and analysis using a Hemavet.

Results showed that total bleeding time was modestly prolonged in PKK-/- rats, FXI-inhibited rats, and in those with both PKK-/- and FXI inhibition. Notably, the combination of PKK-/- and FXI inhibition led to a significant increase in hemoglobin loss compared to controls. These findings suggest that Prekallikrein may serve as an alternative activator of downstream coagulation factor IX, thereby modifying hemostatic function in the absence of FXI of coagulation function.

Research Sponsor

Brian Bagatto

First Reader

Joseph Palumbo

Second Reader

Rachel Olson

Honors Faculty Advisor

Brian Bagatto

Proprietary and/or Confidential Information

No

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