Revisiting clinical scoring tools for the diagnosis of thrombotic thrombocytopenic purpura (TTP).

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening hematologic emergency that leads to increased complexities and mortality due to diagnostic delays. Therapeutic plasma exchange (TPE) along with immunosuppressants is life-saving in cases with severe ADAMTS13 deficiency. Routine ADAMTS13 activity testing is unavailable in many diagnostic centers. Clinical heterogeneity also complicates the early differentiation of TTP from TTP-like syndromes. To critically examine the efficacy of contemporary clinical scoring systems used in the prediction of severe ADAMTS13 deficiency and guide early TPE initiation in the absence of ADAMTS13 activity testing. A literature search was made in PubMed, Embase, Scopus, and Cochrane Library databases from inception till December 2025. Only those studies evaluating PLASMIC, French, and Bentley scores in comparison with standard ADAMTS13 activity assays were included. Existing clinical scoring tools demonstrate high sensitivity in selected cohorts; their real-world utility is limited by modest specificity, population-dependent variability, and misclassification in complex clinical settings such as critical illness, pregnancy, malignancy, renal dysfunction, and old age. Clinical scoring systems facilitate early decision-making, but insufficient as stand-alone diagnostic tools. Overestimation of TTP risk may lead to unnecessary TPE exposure and increased healthcare cost. Emerging strategies, including rapid ADAMTS13 assays, biomarkers, and machine-learning approaches, may permit early TTP diagnosis and prompt management.