# Total thrombus formation system exploration of primary hemostasis in cirrhotic patients

## TL;DR

Cirrhotic patients have impaired blood clotting, and a new system called T-TAS 01 reveals these issues more clearly than traditional tests.

## Contribution

The study introduces T-TAS 01 as a novel method to assess primary hemostasis in cirrhotic patients under flow conditions.

## Key findings

- Cirrhotic patients showed significantly impaired thrombus formation compared to controls using T-TAS 01.
- Elevated von Willebrand Factor levels in cirrhotic patients did not compensate for hemostatic impairments.
- Platelet-mimicking nanoparticles had only partial effects on improving hemostasis in cirrhotic samples.

## Abstract

Primary hemostasis is impaired in cirrhosis, characterized by thrombocytopenia, platelet dysfunction, elevated von Willebrand Factor (VWF) levels, and reduced a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) activity. Current clinical hemostasis tests assess biological parameters individually or use static clot formation models.

We aimed to study thrombus formation in patients with cirrhosis in whole blood under flow conditions with the Total Thrombus Formation Analysis System (T-TAS 01). We also investigated whether synthetic platelet-mimicking nanoparticles (PMNPs) could improve primary hemostatic function in cirrhotic samples.

This observational study included 60 participants (30 patients with cirrhosis and 30 controls). All patients underwent blood cell counts, VWF profiling (antigen, activity, propeptide levels, and multimer analysis), ADAMTS13 activity measurement, and T-TAS 01 analysis using collagen-coated PL chips. In cirrhotic samples, T-TAS 01 assays were also performed after adding PMNPs to evaluate their hemostatic efficacy.

Patients with cirrhosis had significantly lower platelet counts (97 vs 218 G/L, P < .0001), higher VWF antigen levels (310% vs 119%, P < .0001), and reduced ADAMTS13 activity (77% vs 100%, P < .01) compared with controls. T-TAS 01 showed prolonged occlusion start time (5:08 vs 2:21 min:sec, P < .0001) and occlusion time (10:00 vs 5:00, P < .0001), with reduced AUC at 10 minutes (96 vs 382, P < .0001). These impairments were more pronounced in patients with higher Child-Pugh scores. PMNPs showed only partial effects on T-TAS 01 parameters.

T-TAS 01 effectively detects hemostatic impairment in patients with cirrhosis, which apparently is not compensated by the presence of elevated VWF levels. This approach may therefore serve as a valuable tool for assessing clinical and biological monitoring in patients with cirrhosis.

•Patients with cirrhosis suffer from impaired primary hemostasis and thrombocytopenia.•Current clinical tests do not provide a full overview of their hemostatic function.•T-TAS01 is an innovative method to assess primary hemostasis of these patients.•Synthetic platelet-mimicking nanoparticles failed to improve hemostasis as measured by T-TAS01.

Patients with cirrhosis suffer from impaired primary hemostasis and thrombocytopenia.

Current clinical tests do not provide a full overview of their hemostatic function.

T-TAS01 is an innovative method to assess primary hemostasis of these patients.

Synthetic platelet-mimicking nanoparticles failed to improve hemostasis as measured by T-TAS01.