A mathematical model of coagulation under flow identifies factor V as a modifier of thrombin generation in hemophilia A.

ABSTRACT:

Background

The variability in bleeding patterns among individuals with hemophilia A, who have similar factor VIII (FVIII) levels, is significant and the origins are unknown.

Objective

To use a previously validated mathematical model of flow-mediated coagulation as a screening tool to identify parameters that are most likely to enhance thrombin generation in the context of FVIII deficiency.

Methods

We performed a global sensitivity analysis (GSA) on our mathematical model to identify potential modifiers of thrombin generation. Candidates from the GSA were confirmed by calibrated automated thrombography (CAT) and flow assays on collagen-tissue factor (TF) surfaces at a shear rate of 100 per second.

Results

Simulations identified low-normal factor V (FV) (50%) as

SUBMITTER: Link KG 

PROVIDER: S-EPMC6994344 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature