The disclosure relates to methods of managing blood coagulation and pharmaceutical compositions related thereto. In certain embodiments, the disclosure relates to methods of managing the coagulation of blood in a patient undergoing surgery comprising administering combinations of a direct thrombin inhibitor and a coagulation factor inhibitor. In some embodiments, the disclosure relates to treating or preventing clotting by administering compositions disclosed herein to a subject at risk for, exhibiting symptoms of, or diagnosed with a blood clot.