What if a patient with thalassemia major starts to have a high bilirubin?

That is expected: Bilirubin is released in the blood stream after red blood cells break down. There is a rapid breakdown of red blood cells in patients with thalassemia major, and thus high bilirubin in the blood stream is expected. But there are other casues that would raise bilirubin level, and thus if your bilirubin level is higher than usual, i would suggest to go to your doctor.

Several reasons: Many patients with thalassemia will have elevated bilirubin from the start. This can be made worse here and there from certain experiences which cause the body to breakdown blood cells more rapidly (infection, new medications). Also, if the bilirubin has been climbing, i would check the health of the liver. This can be done with blood tests, mris and possibly biopsies.