DYNAMIC MONITORING OF ADAMTS 13 ACTIVITY FOR DIFFERENTIAL DIAGNOSIS ACROSS THE SPECTRUM OF SEPSIS ASSOCIATED WITH THROMBOTIC MICROANGIOPATIES

Adamts 13 and Sepsis Associated with Thrombotic Thrombocytopenic Purpura

Background: In the ICU, distinguishing immune‑mediated thrombotic thrombocytopenic purpura (iTTP) from sepsis‑associated thrombotic microangiopathy (TMA) is time‑critical. We tested whether serial ADAMTS‑13 combined with targeted coagulation and inflammation markers improves iTTP risk stratification in a Sepsis‑3 ICU cohort and whether a pragmatic rule‑out is feasible.

Methods: Prospective single‑center study of adults meeting Sepsis‑3 with thrombocytopenia and schistocytes ≥ 1% or LDH > 2× ULN within 24 h of ICU admission. ADAMTS‑13 activity and VWF: Ag were assayed at 0/24/48/72 h alongside a thrombo‑inflammatory panel. We derived a Dynamic ADAMTS‑13 Index (DAI), a Coagulation Consumption Index (CCI) anchored to ISTH DIC and fibrinogen/antithrombin III, and an Inflammation Index (IL‑6/HBP). The prespecified main rule‑out required a ≥ 15% ADAMTS‑13 rise by 48 h plus low CCI. A prespecified RCV‑anchored sensitivity analysis required ≥ 35% relative rise or ≥ 10 absolute %-points plus low consumption. For decision‑making, pre‑treatment (pre‑plasma exchange, PEx) analyses are emphasized. Intent‑to‑diagnose (care‑embedded) analyses are exploratory, and internal validation used bootstrap optimism correction.

Results: Of 1,274 screened, 330 were included (iTTP = 34). Discrimination improved from baseline ADAMTS‑13 (AUROC 0.78) to DAI (0.93), with smaller gains after adding CCI (0.95) and the Inflammation Index (0.96). With the main rule‑out (≥ 15% + low CCI) in the intent‑to‑diagnose analysis, sensitivity was 97.1%, specificity was 86.1%, and NPV was 99.6%. the RCV‑anchored sensitivity analysis preserved 100.0% sensitivity and NPV with 76.0% specificity. A 72‑h phenotype (ADAMTS‑13 < 10% with high IL‑6/HBP) was associated with higher 28‑day mortality (adjusted HR 2.6).

Conclusions: In Sepsis‑3 ICU patients with TMA features, serial ADAMTS‑13 plus targeted coagulation/inflammation markers enhance early iTTP risk stratification and supports a pragmatic rule‑out framework. The ≥ 15% + low CCI rule‑out achieved high sensitivity and NPV, while an RCV‑anchored threshold ensured 100% sensitivity/NPV at reduced specificity. External validation and implementation studies remain essential.