The diagnostic utility of PNH^Gran clones, acquired 6p CN-LOH^MHC, and clonal TRG rearrangement for acquired AA. Following initial hematologic evaluation, which includes a complete blood count (CBC) with differential, a bone marrow aspirate and biopsy, and cytogenetics analysis, the diagnostic evaluation of patients with suspected AA should include upfront testing for AA-specific laboratory findings using peripheral blood flow cytometry to detect PNH and single-nucleotide polymorphism array testing of bone marrow or peripheral blood DNA to detect acquired 6p CN-LOH^MHC in addition to exclusion of alternative etiologies of pancytopenia. The presence of PNH clones or acquired 6p CN-LOH^MHC is predictive of AA, which may allow clinicians to bypass extensive IBMFS testing. In the absence of these findings, AA diagnosis is established by excluding alternative etiologies of marrow aplasia, including exclusion of telomere biology disorders via telomere-length measurements and FA via chromosome breakage testing. Select patients suspected of having other IBMFSs may require comprehensive genetic testing. As PNH and acquired 6p CN-LOH^MHC are clonal changes that emerge in response to autoimmune attack on the bone marrow, their prevalence may rise over the disease course. Thus, serial testing for these markers (along with repeating a bone marrow biopsy with cytogenetic analysis and genetic testing for unrecognized germline mutations) may increase the diagnostic yield later in disease. This may be particularly helpful for patients who are refractory to IST, for whom there may be lingering concerns that failure to respond to IST could indicate a mistaken diagnosis of immune-mediated AA, and that a patient’s marrow failure is caused by other, non–immune-mediated etiologies such as IBMFSs. LDH, lactate dehydrogenase.