# Distinct Coagulation Phenotypes and Long-Term Neurological Outcomes in Post-Cardiac Arrest Syndrome: A Latent Class Analysis of a 9-Year Single-Center Cohort

## TL;DR

This study identifies three distinct coagulation patterns in cardiac arrest patients and finds that one pattern is strongly linked to worse brain recovery and outcomes.

## Contribution

The study introduces a novel method using latent class analysis to classify coagulation phenotypes in post-cardiac arrest patients and links them to neurological outcomes.

## Key findings

- Three coagulation phenotypes were identified: preserved coagulation, hypercoagulable state, and consumptive coagulopathy.
- Consumptive coagulopathy was independently associated with poor neurological outcomes at 6 months.
- Patients with consumptive coagulopathy showed the lowest gray-to-white matter ratio and highest neuron-specific enolase levels.

## Abstract

Background/Objectives: Post-cardiac arrest syndrome (PCAS) induces systemic ischemia–reperfusion injury accompanied by sepsis-like coagulopathy. This coagulopathy presents heterogeneously, yet distinct coagulation phenotypes and their impact on hypoxic–ischemic brain injury (HIBI) remain poorly defined. We aimed to identify coagulation phenotypes using latent class analysis (LCA) and assess their association with 6-month neurological outcomes. Methods: We retrospectively analyzed adult out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM) between 2011 and 2019 from a prospective registry at a tertiary academic center. LCA was performed using coagulation biomarkers measured at admission and 24 h post-return of spontaneous circulation: D-dimer, fibrinogen, antithrombin III (ATIII), platelet count, and PT-INR. The primary outcome was poor neurological outcome (Cerebral Performance Category 3–5) at 6 months. Secondary outcomes included in-hospital mortality and cerebral edema severity assessed by gray-to-white matter ratio (GWR) on brain CT. Results: Among 325 patients, LCA identified three phenotypes: Class 1 (Preserved Coagulation, 36.9%), Class 2 (Hypercoagulable State, 41.5%) characterized by elevated D-dimer with preserved fibrinogen and ATIII, and Class 3 (Consumptive Coagulopathy, 21.5%) marked by profound D-dimer elevation with fibrinogen <150 mg/dL and ATIII <60%. Class 3 exhibited the lowest GWR and highest neuron-specific enolase levels. In multivariable analysis adjusting for age, low-flow time, initial rhythm, and lactate, Class 3 independently predicted poor neurological outcome (adjusted OR 4.52; 95% CI 2.15–9.48), whereas Class 2 did not. Conclusions: PCAS-related coagulopathy is heterogeneous. A consumptive coagulopathy phenotype identifies a high-risk subgroup associated with severe brain injury and poor long-term neurological outcomes. Early identification of this phenotype may enable targeted prognostication and guide future phenotype-specific interventional strategies.: