Impaired ABCG5/ABCG8 heterodimer function in Abcg5^−/− or Abcg8^−/− hepatocytes and enterocytes leads to increased plasma sterol levels. Sterols accumulate in the platelet membrane, resulting in calpain activation, reduced αIIbβ3 surface expression, loss of the GPIbα-FlnA linkage, microparticle formation, and poor hemostatic functions.