This chapter discusses the cell-based model of coagulation, regulation of coagulation, and bleeding disorders. The disorders include congenital disorders and acquired disorders such as thrombocytopenia, disseminated intravascular coagulation (DIC) and microangiopathic haemolytic anaemia. Thrombocytopenia may occur because of impaired production, sequestration, increased consumption, and enhanced degradation. Activated protein C has been shown to reduce mortality in sepsis especially in patients with DIC and multi-organ failure. During the resuscitation of patients who have suffered a major haemorrhage, factors that can contribute to associated coagulopathy are: hypothermia, metabolic acidosis, and consumption of clotting products. Heparin-induced thrombocytopenia (HIT) usually occurs 5-10 days following exposure to heparin. It is a pro-thrombotic disorder and can lead to significant venous and arterial thrombosis. HIT usually resolves following the discontinuation of heparin over a few days. Management includes the prompt removal of all heparin containing medication and the substitution of a direct thrombin inhibitor to control clotting.