Sticha, Benjamin J.

Little is known about mechanisms by which bacterial infection contributes to thrombotic risk. Experiments were designed to identify the relationship between toll‐like receptor 4 (TLR4) activation by bacterial lipopolysaccharide (LPS) and circulating procoagulant (phosphatidylserine (PS) positive) microvesicles (MV). Blood from wild type (WT), and TLR4‐ gene deleted (dTLR4) female mice was collected prior to and following exposure to either saline or LPS 20ng/g body weight administered as a single intravenous injection (acute exposure) or after administration by subcutaneous osmotic pump (chronic exposure). MV were isolated from blood by differential centrifugation and identified by flow cytometry. MV thrombin generating capacity was measured by solid phase fluorescent assay. Procoagulant MV were significantly lower in dTLR4 compared to WT mice (P<0.007). Platelet derived MV were the most prominent MV in saline treated mice. Following LPS‐treatment, counts of procoagulant MV increased (P<0.006) significantly only in WT mice. The increase was greater after chronic compared to acute exposure. Thrombin generating capacity positively correlated (r 2 =0.9) with PS expression. These results suggest that increased procoagulant MV through TLR4 activation and thus explain in part increased thrombotic risk with bacterial infection. This work is supported by AHA‐SDG 30503Z and Mayo Foundation.