# Dogs with sepsis are more hypercoagulable and have higher fibrinolysis inhibitor activities than dogs with non-septic systemic inflammation

**Authors:** Emily Hill, Yao Zhu, Marjory B. Brooks, Robert Goggs

PMC · DOI: 10.3389/fvets.2025.1559994 · Frontiers in Veterinary Science · 2025-04-30

## TL;DR

Dogs with sepsis show increased blood clotting and reduced fibrinolysis compared to non-septic critically ill dogs, with certain markers potentially predicting survival.

## Contribution

The study identifies unique coagulation and fibrinolysis patterns in septic dogs compared to non-septic ones and links specific markers to survival outcomes.

## Key findings

- Dogs with sepsis had higher fibrinogen and coagulation potential than non-septic dogs.
- Sepsis dogs showed elevated AP and TAFI activities compared to non-septic dogs.
- H3.1 nucleosomes and active PAI-1 concentrations were associated with survival in sepsis dogs.

## Abstract

Hemostatic imbalance in dogs with sepsis is characterized by hypercoagulability and hypofibrinolysis. We aimed to determine whether these abnormalities are unique features of sepsis or are also present in dogs with non-septic critical illness. Secondary aims were to assess relationships between coagulation assay results and circulating markers of neutrophil extracellular traps (NETs), and to relate coagulation assay abnormalities with survival in dogs with sepsis.

This prospective single-center observational cohort study enrolled 55 client-owned dogs that satisfied at least 2 systemic inflammatory response syndrome (SIRS) criteria. Dogs with a bacterial infection were categorized as sepsis, those without evidence of infection were categorized as non-infectious systemic inflammation (nSIRS). Clotting times, fibrinogen and D-dimer concentrations, and activities of antithrombin (AT), antiplasmin (AP), thrombin activatable fibrinolysis inhibitor (TAFI), and total and active plasminogen activator inhibitor-1 (PAI-1) were measured. Thrombin generation and overall hemostasis potential assays were performed and concentrations of cell-free DNA (cfDNA) and H3.1 nucleosomes quantitated.

Compared to dogs with nSIRS, dogs with sepsis had higher fibrinogen concentrations, greater endogenous thrombin potential, higher AP and TAFI activities and greater overall hemostasis and coagulation potential values. H3.1 nucleosome and cfDNA concentrations were strongly correlated and significantly associated with various coagulation variables. In dogs with sepsis, non-survivors had lower AT activity, and higher active PAI-1 and H3.1 nucleosome concentrations.

Relative to non-septic critically ill dogs, dogs with sepsis are hyperfibrinogenemic, hypercoagulable and have higher AP and TAFI activities. Concentrations of H3.1 nucleosomes and active PAI-1 and AT activity might have prognostic value in dogs with sepsis.

## Linked entities

- **Proteins:** antithrombin (antithrombin protein)
- **Species:** Canis lupus familiaris (taxon 9615)

## Full-text entities

- **Genes:** MPO (myeloperoxidase) [NCBI Gene 609986], HMGB1 (high mobility group box 1) [NCBI Gene 403170] {aka HMG1}, SERPINE1 (serpin family E member 1) [NCBI Gene 403476] {aka PAI-1}, F3 (coagulation factor III, tissue factor) [NCBI Gene 490153] {aka TF}, CPB2 (carboxypeptidase B2) [NCBI Gene 1361] {aka CPU, PCPB, TAFI}, PLG (plasminogen) [NCBI Gene 403602], PLAT (plasminogen activator, tissue type) [NCBI Gene 482840] {aka TPA}, CTSS (cathepsin S) [NCBI Gene 403400]
- **Diseases:** abscess (MESH:D000038), coma (MESH:D003128), PT (MESH:D007020), necrotizing hepatitis (MESH:D047508), bacteremia (MESH:D016470), septic (MESH:D001170), burns (MESH:D002056), thrombosis (MESH:D013927), otitis interna (MESH:D007762), mastitis (MESH:D008413), critical illness (MESH:D016638), seizures (MESH:D012640), systemic illness (MESH:D012140), aspiration pneumonia (MESH:D011015), septic peritonitis (MESH:D010538), liver failure (MESH:D017093), pancreatitis (MESH:D010195), volvulus syndrome (MESH:D045822), fibrinolytic (MESH:C565017), Coagulation disturbances (MESH:D001778), anemia (MESH:D000740), OFP (MESH:C537245), babesiosis (MESH:D001404), IMHA (MESH:C567355), bite injuries (MESH:D001733), neoplastic disease (MESH:D004194), bacterial pneumonia (MESH:D018410), septic shock (MESH:D012772), pyometra (MESH:D055112), Sepsis (MESH:D018805), injuries (MESH:D014947), gastric dilatation (MESH:D013271), SIRS (MESH:D018746), lobe torsion (MESH:D050723), multiple organ dysfunction (MESH:D009102), necrotic (MESH:D009336), thrombocytopenia (MESH:D013921), AT (MESH:D020152), Immunothrombosis (MESH:D000090882), cancer (MESH:D009369), -infectious (MESH:D003141), fungal (MESH:D009181), infection (MESH:D007239), NETs (MESH:C536657), disseminated intravascular coagulation (MESH:D004211), intestinal obstruction (MESH:D007415), inflammation (MESH:D007249), death (MESH:D003643), acute respiratory failure (MESH:D012131), hepatopathy (MESH:D020754), hypercoagulability (MESH:D019851), Bacterial sepsis (MESH:D001424)
- **Chemicals:** Citrate (MESH:D019343), saline (MESH:D012965), lactate (MESH:D019344), K2-EDTA (-), EDTA (MESH:D004492), oxygen (MESH:D010100), bilirubin (MESH:D001663), imidazole (MESH:C029899), creatinine (MESH:D003404), sodium citrate (MESH:D000077559), S-2251 (MESH:C018788)
- **Species:** Homo sapiens (human, species) [taxon 9606], Canis lupus familiaris (dog, subspecies) [taxon 9615], Bos taurus (bovine, species) [taxon 9913], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395]

## Full text

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## Figures

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## References

82 references — full list in the complete paper: https://tomesphere.com/paper/PMC12075940/full.md

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Source: https://tomesphere.com/paper/PMC12075940