# Therapeutic Effects of Single and Combined Anti-Disseminated Intravascular Coagulation (DIC) Drugs in a Rat Venom-Induced Consumption Coagulopathy (VICC) Model Using Yamakagashi (Rhabdophis tigrinus) Venom

**Authors:** Akihiko Yamamoto, Takashi Ito, Toru Hifumi

PMC · DOI: 10.3390/toxins18030151 · Toxins · 2026-03-23

## TL;DR

Researchers tested drug combinations to treat coagulopathy caused by yamakagashi snake venom in rats, finding that a mix of recombinant thrombomodulin α and tranexamic acid improved survival and coagulation.

## Contribution

The study identifies a novel combination therapy using recombinant thrombomodulin α and tranexamic acid for treating venom-induced coagulopathy.

## Key findings

- Tranexamic acid or antithrombin III alone did not improve survival or coagulation markers in venom-treated rats.
- Combining recombinant thrombomodulin α with tranexamic acid extended survival and partially restored coagulation markers.
- Antithrombin III combined with thrombomodulin α did not show significant therapeutic benefits.

## Abstract

Yamakagashi (Rhabdophis tigrinus) is a widely distributed snake species in Japan. Yamakagashi causes venom-induced consumption coagulopathy (VICC) when the amount of infused venom is high, and bites can be fatal if antivenom treatment is delayed. However, yamakagashi antivenom is an unapproved treatment, and its storage capacity is limited, preventing its prompt administration. Therefore, we investigated the application of commercially available drugs, namely tranexamic acid and antithrombin III, in the treatment of VICC caused by yamakagashi venom in a rat model. Furthermore, we investigated the combination of each drug with recombinant thrombomodulin α. Administration of tranexamic acid or antithrombin III alone failed to extend rat survival or correct changes in blood coagulation markers, such as prothrombin time, fibrinogen concentrations, and D-dimer levels, in yamakagashi venom-treated rats. However, combined administration of recombinant thrombomodulin α and tranexamic acid extended rat survival and partially restored blood coagulation markers. Therefore, the combination of recombinant thrombomodulin α and tranexamic acid might represent a useful therapeutic regimen for yamakagashi venom exposure.

## Linked entities

- **Proteins:** SERPINC1 (serpin family C member 1)
- **Chemicals:** tranexamic acid (PubChem CID 5526)
- **Diseases:** disseminated intravascular coagulation (MONDO:0001243)
- **Species:** Rhabdophis tigrinus (taxon 126484), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Serpinc1 (serpin family C member 1) [NCBI Gene 304917], F2 (coagulation factor II, thrombin) [NCBI Gene 29251], A2m (alpha-2-macroglobulin) [NCBI Gene 24153] {aka A2MAC1, A2m1, A2maa, A2mb, Mam}, Proc (protein C, inactivator of coagulation factors Va and VIIIa) [NCBI Gene 25268], Plg (plasminogen) [NCBI Gene 85253] {aka Ab1-346}, Pros1 (protein S) [NCBI Gene 81750] {aka Pros}
- **Diseases:** blood clotting disorders (MESH:D013927), anaphylaxis (MESH:D000707), bite injuries (MESH:D001733), snakebites (MESH:D012909), pulmonary edema (MESH:D011654), poisoning (MESH:D011041), hypercoagulable (MESH:D019851), Infectious Diseases (MESH:D003141), cancer (MESH:D009369), sepsis (MESH:D018805), hypo- or afibrinogenemia (MESH:D000347), Coagulopathy (MESH:D001778), Venom (MESH:D000092422), acute renal failure (MESH:D058186), bleeding tendency (MESH:C536965), Snake Venom (MESH:C000719210), serum sickness (MESH:D012713), deficiency in FIB (MESH:D007153), toxicity (MESH:D064420), platelet aggregation (MESH:D001791), deaths (MESH:D003643), deficiency of FIB coagulation factors (MESH:D020147), cerebral hemorrhage (MESH:D002543), infections (MESH:D007239), bleeding (MESH:D006470), injury to (MESH:D014947), PT (MESH:D007020), DIC (MESH:D004211)
- **Chemicals:** water (MESH:D014867), isoflurane (MESH:D007530), TXA (MESH:D014148), D (MESH:D003903), sodium citrate (MESH:D000077559), Ci-Trol (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Rhabdophis tigrinus (Tiger keelback, species) [taxon 126484], Equus caballus (domestic horse, species) [taxon 9796], Homo sapiens (human, species) [taxon 9606], Serpentes (snakes, infraorder) [taxon 8570], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

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## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC13030296/full.md

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Source: https://tomesphere.com/paper/PMC13030296