# Development and Validation of the PASS Score: A Simplified Tool to Diagnose Acquired Aplastic Anemia in Adults

## TL;DR

Researchers developed a new clinical tool called PASS to quickly and accurately diagnose acquired aplastic anemia in adults, reducing the need for genetic testing.

## Contribution

The PASS score is a novel, validated clinical tool that distinguishes acquired aplastic anemia from inherited bone marrow failure syndromes using common clinical data.

## Key findings

- The PASS model achieved an AUC of 0.990 in the training cohort and 0.977 in external validation.
- A score ≥30 had 100% positive predictive value for diagnosing acquired aplastic anemia.
- The tool rapidly diagnosed 80% of AA cases and is available as an open-access web calculator.

## Abstract

Acquired aplastic anemia (AA) can present similarly to inherited bone marrow failure 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 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 open-access web calculator (https://pennmedicine.shinyapps.io/passcalc/).