Development and validation of the predictive aplastic score system (PASS): a simplified tool to diagnose acquired aplastic anemia in adults

Acquired aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… (AA) can present similarly to inherited bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… syndromes (IBMFS) but treatment differs. AA diagnosis relies on excluding IBMFS; however, genetic testing is not always available, may delay care or be inconclusive. We developed the Predictive Aplastic Score System (PASS), a clinical tool using readily available data to distinguish AA from IBMFS in adults. The training cohort included 212 adults (162 AA, 50 IBMFS). Compared to IBMFS, AA patients were older and more likely to have acute-onset, severe cytopenias. Using logistic regression with LASSO, we selected seven clinical variables for model inclusion: severity, acuity, age, IBMFS red flags, AA-associated conditions, AA-associated somatic changes, and telomere telomere: A telomere is the end of a chromosome. Telomeres are made of repetitive sequences of non-coding DNA that protect the chromosome from damage. Each time a cell divides, the telomeres become shorter. EVvntually, the telomeres become so short that the cell can no longer divide. lengths. The model achieved AUC of 0.990 (95% CI: 0.982-0.999), with 100% positive predictive value (PPV) for AA for scores ≥30. 86.8% of patients with scores <0 had IBMFS. We validated PASS in 716 patients from four external cohorts with AUC of 0.977 (95% CI: 0.968-0.987). Threshold analysis confirmed 100% PPV for scores ≥30, rapidly diagnosing 80% of AA cases. PASS is a practical and accurate clinical tool that can rapidly distinguish AA from IBMFS for most adult patients. To promote clinical adoption, we developed an open-access web calculator ( https://pennmedicine.shinyapps.io/passcalc/ ).