Thrombin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Thrombin: From Fibrin Sealant Hemostasis to Primary Release Disorder of Platelets
One-Sentence Summary
Thrombin is a clotting protein used in Singapore as a component of fibrin sealant products (topical hemostasis). The TxGNN model predicts it may be useful for primary release disorder of platelets, but no clinical trials and no literature testing thrombin as a treatment for this condition were found. The evidence is model prediction only (0 clinical trials), and the retrieved publications are general background on platelet biology.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the registration records. All three registered products are fibrin sealants, which are used for local hemostasis. |
| Predicted New Indication | Primary release disorder of platelets |
| TxGNN Prediction Score | 96.8% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available for this drug. Thrombin is the enzyme that converts fibrinogen to fibrin. It is also a strong platelet activator that triggers granule release. This is the likely basis for the model linking it to a platelet release (secretion) disorder.
On closer inspection, the link is weak. A platelet secretion defect would not be corrected by adding thrombin, because the problem lies in the platelet's own release machinery. Thrombin is also used as a topical or local agent, not a systemic therapy for platelet function defects. The high score appears to reflect a network association with platelet biology rather than a therapeutic rationale.
For context, one other predicted indication, esophageal disease, has more substantial support. It rests on a Phase 3 trial and a meta-analysis of thrombin injection for bleeding gastric varices (see the conclusion).
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The retrieved papers describe platelet and coagulation biology or related clinical contexts. None tests thrombin as a therapy for this condition.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30986390 | 2019 | Guideline / clinical practice update | Gastroenterology | Expert guidance on altered coagulation in cirrhosis and on the use of anticoagulants and pro-coagulants. It does not address platelet release disorders. |
| 1321709 | 1992 | Review | Dis Mon | Overview of platelet function disorders and the phases of normal platelet function, including secretion. |
| 33749992 | 2021 | Review | Wound Repair Regen | Platelet gels activated with thrombin or calcium are used in chronic wound healing. |
| 11079020 | 2000 | Review | Arch Pathol Lab Med | Pathophysiology, diagnosis and treatment of heparin-induced thrombocytopenia. |
| 12556215 | 2003 | Review | Expert Opin Investig Drugs | Thrombin acts through protease-activated receptors, and PAR-1 antagonists are being explored as therapies. |
| 35226963 | 2022 | Review | Hamostaseologie | Genetic analysis of hereditary hemorrhagic, thrombotic and platelet disorders. |
| 14727968 | 2002 | Review | Am J Cardiovasc Drugs | Platelet activation pathways and new targets for antithrombotic drugs. |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14707P | TISSEEL FIBRIN SEALANT VH S/D (FROZEN) | Solution | Not stated in the registration record |
| SIN16776P | BERIPLAST P COMBI-SET 3ML POWDERS AND SOLVENTS FOR SEALANT | Other | Not stated in the registration record |
| SIN16775P | BERIPLAST P COMBI-SET 1ML POWDERS AND SOLVENTS FOR SEALANT | Other | Not stated in the registration record |
Safety Considerations
Please refer to the package insert for safety information. No drug interaction records were found for thrombin.
For context, the evidence compiled for other predicted indications suggests that systemic exposure to thrombin could carry thrombotic risk. This is a general mechanistic concern and not a label statement.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on model output alone (L5). There are no trials, and the literature describes platelet biology without showing any therapeutic role for thrombin. Mechanistically, a platelet release defect would not be repaired by exogenous thrombin, and a topical agent does not address a systemic defect.
To proceed, the following is needed:
- Package insert warnings and contraindications for the registered products, which are currently unavailable
- Mechanism of action data
- Any preclinical or clinical evidence that thrombin improves platelet secretion or bleeding in this disorder
- A route-of-administration assessment, since the registered products are topical sealants
- Consideration of the better-supported indication, bleeding gastric varices (under "esophageal disease"). It is supported by a small Phase 3 trial (NCT01717612, n=62, status unknown) and a systematic review and meta-analysis. This would need to be assessed as a separate candidate restricted to variceal bleeding.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.