Determining the true cause of thrombocytopenia is a difficult and challenging clinical problem. Thrombocytopenia results from various causes, but ultimately occurs when platelets are destroyed, sequestered in the body, or not produced. The differential diagnosis of thrombocytopenia is extensive and complex, and there is a significant overlap among disorders. The advanced practice nurse must take a holistic approach to the patient, eliciting a detailed history and performing a comprehensive physical examination with special emphasis on the skin, abdominal, lymph node and neurologic consideration.