Today we discussed an unusual case of TTP, and along the way we reviewed the differential for hemolytic anemia and Evans Syndrome in particular. Thank you to our faculty expert, Dr. Cuker, for some amazing teaching! Our patient was a young female previously treated for melanoma who developed thrombocytopenia and hemolytic anemia. There are different frameworks in which to classify hemolytic anemias. Today we thought about immune vs. non-immune mediated processes (which is not perfect, and some etiologies can fall within both categories!). Here is some of the differential that we discussed:
Direct antibody test can be used to determine if there is antibody or complement bound to the patient’s RBCs. In this test, the patient’s RBCs are separated out from the serum and incubated with anti-human IgG; if there is antibody or C3 bound to the patient’s RBCs, then agglutination will occur, resulting in a positive test result. Indirect antibody testing looks at the patient’s serum to test for antibodies to RBCs – the serum is incubated with other RBCs (ie not from the patient), and then anti-human IgG is added. If the serum contains anti-RBC antibodies, they will bind the cells and then agglutination will occur when anti-human IgG is added. (Figure adapted from Wikipedia.org)
Our patient was initially thought to have Evans Syndrome, which is a condition that involves at least two immune-mediated cytopenias, most commonly thrombocytopenia and hemolytic anemia. Corticosteroids are usually the first line of treatment, especially if the patient is presenting with anemia. If the patient is presenting with thrombocytopenia as the primary concern, then IVIg can be considered. These patients typically have relapsing courses, and this can be really difficult to treat.
Our patient initially did really well with steroids, but then had recurrence of thrombocytopenia and hemolytic anemia, this time accompanied by abdominal pain and a peripheral smear with many schistocytes, which had not previously been seen. She was ultimately diagnosed with TTP, which is a form of thrombotic microangiopathy caused by low ADAMTS13 level. In healthy patients, ADAMTS13 cleaves ultralarge Von Willebrand Factor multimers, so when activity is low these multimers can persist. This causes platelet activation and aggregation, which can lead to thrombosis and ischemia to end-organs, and a hemolytic anemia from shearing.
Treatment for TTP has made a dramatic change in mortality of this condition. Patients with suspected TTP should be treated immediately! Plasma exchange should be initiated as soon as possible, along with corticosteroids. There is also growing evidence to support use of rituximab in all patients without contraindications; this can be removed by plasma exchange, so should be dosed following sessions when possible.
References: please see citations underneath figures