Thrombocytopenia is common in persons infected with
relapsing fever Borreliae. We previously showed that the
relapsing fever spirochete Borrelia hermsii binds to and activates human platelets in vitro and that, after platelet activation, high-level spirochete-platelet attachment is mediated by
integrin alpha IIb beta 3, a receptor that requires platelet activation for full function. Here we established that B hermsii
infection of the mouse results in severe
thrombocytopenia and a functional defect in hemostasis caused by accelerated platelet loss.
Disseminated intravascular coagulation,
immune thrombocytopenic purpura, or splenic sequestration did not play a discernible role in this model. Instead, spirochete-platelet complexes were detected in the blood of infected mice, suggesting that platelet attachment by bacteria might result in platelet clearance. Consistent with this,
splenomegaly and
thrombocytopenia temporally correlated with spirochetemia, and the severity of
thrombocytopenia directly correlated with the degree of spirochetemia. Activation of platelets and
integrin alpha IIb beta 3 were apparently not required for bacterium-platelet binding or platelet clearance because the bacterium-bound platelets in the circulation were not activated, and platelet binding and
thrombocytopenia during
infection of beta 3-deficient and wild-type mice were indistinguishable. These findings suggest that
thrombocytopenia of
relapsing fever is the result of platelet clearance after beta 3-independent bacterial attachment to circulating platelets.