A 69-year-old morbidly obese woman with a history of osteoarthritis presented to a community hospital for a routine left, total knee arthroplasty. Postoperatively, diffuse diarrhea developed and was diagnosed as Clostridium difficile colitis. Despite appropriate treatment, she decompensated clinically with toxic megacolon developing requiring subtotal colectomy with ileostomy. Her postoperative course was complicated by septic shock, respiratory failure, and acute renal failure requiring renal replacement therapy. On hospital day 15, thrombocytopenia developed that was progressive and complicated by bleeding most notably at venipuncture sites, requiring RBC transfusion. Her platelet count remained severely depressed despite multiple platelet transfusions. She had been treated with broad-spectrum IV antibiotics, vasopressor support, and corticosteroids for septic shock during her hospitalization. Her hemodynamics ultimately improved allowing discontinuation of the vasopressors. Due to her refractory thrombocytopenia and multiple acute medical problems, she was transferred to our ICUs for further management on hospital day 31.