Severe aplastic anemia (SAA) is a rare blood disorder where the body’s bone marrow stops producing enough new blood cells. The condition is characterized by a failure of the hematopoietic stem cells, the precursor cells for all blood components: red blood cells, white blood cells, and platelets. This causes dangerously low levels of these cells in the bloodstream. The process of diagnosing SAA is a step-by-step investigation that confirms the disease and excludes other serious conditions that may present similarly.
Symptoms Leading to Investigation
The initial signs of SAA are a direct consequence of the shortage of mature blood cells in circulation. Patients often seek medical help because of generalized symptoms of anemia (lack of red blood cells), such as persistent fatigue, weakness, paleness, or shortness of breath. A low platelet count (thrombocytopenia) leads to clotting problems, often causing easy bruising, nosebleeds, or tiny red spots called petechiae. Furthermore, the lack of infection-fighting white blood cells results in recurrent or prolonged infections and fevers. The presence of these symptoms prompts a physician to order initial blood tests.
Screening with Blood Tests
The first formal diagnostic step is a Complete Blood Count (CBC) test, which quantifies the different types of cells in the blood. A characteristic finding in SAA is pancytopenia, a simultaneous reduction in all three major blood cell lines: red cells, white cells, and platelets. The CBC will show low hemoglobin, low absolute neutrophil count, and low platelet count. The reticulocyte count, which measures newly produced red blood cells, is also very low (less than 60,000 per microliter) because the damaged bone marrow cannot respond. This combination strongly suggests a bone marrow problem, and additional blood tests are conducted to rule out other causes of pancytopenia.
Bone Marrow Examination
While blood tests indicate a problem, the definitive diagnosis of SAA requires a direct examination of the bone marrow. This procedure involves both a bone marrow aspiration (liquid sample) and a biopsy (solid core tissue), typically performed on the hip bone. The biopsy assesses the cellularity of the marrow, which is the proportion of blood-forming cells to fat cells. The defining feature of SAA is profound hypocellularity, meaning the marrow cavity is largely replaced by fat instead of active blood-producing tissue. Cellularity is typically found to be less than 25% for a diagnosis of severe aplastic anemia. This examination also helps exclude other conditions causing pancytopenia, such as myelodysplastic syndrome or certain leukemias.
Final Confirmation and Classification
After the diagnosis of aplastic anemia is established by the hypocellular bone marrow and pancytopenia, further testing is required to finalize the classification and inform treatment decisions. One ancillary test is flow cytometry to check for the presence of a Paroxysmal Nocturnal Hemoglobinuria (PNH) clone. The presence of these cells suggests the disease is immune-mediated and influences therapy choice. The final step is classifying the disease severity, which dictates the urgency and type of treatment.
Classification of Severity
The criteria for Severe Aplastic Anemia (SAA) include bone marrow hypocellularity plus at least two of the following: an absolute neutrophil count below 500 per microliter, a platelet count below 20,000 per microliter, or an absolute reticulocyte count below 60,000 per microliter. A patient is classified as having Very Severe Aplastic Anemia (VSAA) if they meet all SAA criteria, but their absolute neutrophil count is below 200 per microliter. This grading system guides the medical team in determining whether the patient requires immunosuppressive therapy or a stem cell transplant.