Thrombus stability explains the factor V Leiden paradox: a mouse model

Area of Science:

• Biomedical Science
• Hematology
• Thrombosis Research

Background:

• Factor V Leiden (FVL) variant carriers have a fivefold higher risk of venous thrombosis.
• A paradox exists where deep vein thrombosis (DVT) incidence is disproportionately higher than pulmonary embolism (PE) in FVL carriers.

Purpose of the Study:

• To investigate the hypothesis that FVL carriers develop more stable thrombi, leading to clinically significant DVTs more frequently than non-carriers.
• To elucidate the mechanisms behind the FVL paradox by comparing thrombus stability and embolization in FVL and wild-type models.

Main Methods:

• Induced femoral vein thrombi in wild-type (WT), heterozygous (F5L/+), and homozygous (F5L/L) mice.
• Utilized intravital microscopy to visualize thrombus size and embolization.
• Quantified emboli in the lungs to assess pulmonary embolism (PE) burden.

Main Results:

• Femoral vein thrombi were larger and embolized less in FVL (F5L/+) and homozygous (F5L/L) mice compared to WT mice.
• Homozygous FVL (F5L/L) mice exhibited significantly decreased total and large embolic events and reduced PE burden.
• The percentage of thrombus that embolized was significantly lower in FVL mice.

Conclusions:

• FVL variant leads to more stable thrombi with reduced embolization, contributing to a higher incidence of symptomatic DVT.
• Less embolization in FVL carriers allows thrombi to grow, potentially causing symptomatic DVT, whereas in non-carriers, embolization may prevent small thrombi from becoming clinically significant.