Approach to the patient with refractory ITP. We begin by reassessing the diagnosis of ITP and excluding nonautoimmune causes of thrombocytopenia and secondary ITP. After ITP has been affirmed, we consider whether treatment is indicated. Observation alone is appropriate for most adults with a platelet count >20 to 30 × 10⁹/L and no bleeding or impaired HRQoL and for most children without bleeding or impaired HRQoL. For patients who require treatment, we treat with a Tier 1 agent (Table 2). We select an agent based on age, comorbidities, drug availability, cost, and patient preference. In patients who do not respond to or cannot tolerate a Tier 1 agent, we move on to another Tier 1 agent. In patients who have exhausted all options in Tier 1, we consider enrollment in a clinical trial. If a suitable trial is not available, we initiate a Tier 2 agent (Table 3). We often use Tier 2 agents in combination with Tier 1 or other Tier 2 agents with different mechanisms of action. For the rare patient with serious bleeding who does not achieve an acceptable response with Tier 2 agents, we again consider enrollment in a clinical trial or initiation of a Tier 3 treatment (Table 4).