RBC-diff schistocyte counts improve diagnostic evaluation of TMAs. (A) TMA cohort inclusion criteria and study design. (B) RBC-diff schistocyte counts according to TMA etiology. (C,D) RBC-diff counts for iTTP (C), and all other TMA etiologies (D). The interrupted y-axis shows a single outlier (93% spiculated, DIC case). For box plots (B,C,D), center lines show the medians; box limits indicate the 25th to 75th percentiles; whiskers extend 1.5× the interquartile range; and dots represent outliers. (E) The sensitivity and specificity of diagnosis of iTTP and/or HUS against all other TMA etiologies using schistocyte count with (light blue) and without (dark blue) predominance (requirement that schistocyte count be higher than that for other abnormal cell types) and using morphology grading flags (brown diamonds). An equivalent plot of the validation cohort is shown in supplemental Figure 13. (F) Sensitivity, specificity, and positive predictive value (PPV) of the RBC-diff cell count criteria for the diagnosis of iTTP and/or HUS in derivation and validation cohorts (supplemental Figure 7). Sensitivity and PPV using the joint criteria were significantly higher than those using morphology grading flags (P < 1e-5; exact binomial test). (G) Volcano plot indicating the statistical significance and fold changes of CBC indices, RBC-diff counts, and ADAMTS13 activity, each for iTTP compared with non-iTTP/HUS TMA cases. P values using Bonferroni-corrected 2-sided Student t test. DIC, disseminated intravascular coagulation; Hgb, hemoglobin; Plt, platelet count.