Fibrinogen Human
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
FIBRINOGEN HUMAN: From Fibrinogen Replacement to Hemoglobinopathy
One-Sentence Summary
Human fibrinogen is a plasma-derived clotting protein marketed in the US as fibrinogen concentrates (Fibryga and RiaSTAP). The approved indication text is not included in the source data. The TxGNN model predicts it may be effective for hemoglobinopathy, but 1 registered trial (not linked to fibrinogen) and 20 publications (mostly observational or mechanistic) provide no direct support. This prediction is most likely a knowledge-graph artifact, and fibrinogen replacement could raise thrombotic risk in these patients.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the source data |
| Predicted New Indication | Hemoglobinopathy |
| TxGNN Prediction Score | 99.12% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 4 (all BLA biologics licenses) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Fibrinogen is a coagulation glycoprotein that is converted to fibrin during clot formation, and the marketed products supply it as a replacement. The source data does not list the approved indications.
The literature does not support a therapeutic link to hemoglobinopathies such as sickle cell disease and beta-thalassemia. It treats fibrinogen as a biomarker of a hypercoagulable, inflammatory state in these conditions. Reports describe elevated fibrinogen, altered thromboelastometry and thrombotic complications. One study also found that sickle red blood cell adhesion to ICAM-1 is mediated by fibrinogen.
Giving more fibrinogen to patients who already have elevated thrombotic risk could therefore be harmful rather than beneficial. The high TxGNN score probably reflects proximity between coagulation and hemoglobin-related nodes in the knowledge graph. It does not reflect a real therapeutic relationship.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03673085 | Phase 1 | Completed | 32 | First-in-human single-ascending-dose safety and PK study of CN128 tablets in thalassemia patients aged 16 and above. Relevance grade C: the record does not mention fibrinogen, and a first-in-human design is unusual for a marketed plasma product. It is not counted as direct evidence. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31648337 | 2019 | Review | Blood Adv | Coagulation activation is a key part of sickle cell disease pathophysiology and drives chronic inflammation |
| 14693325 | 2003 | Review | Am J Med | Sickle cell disease shows activation of coagulation and platelets (a hypercoagulability paradox) |
| 33026614 | 2020 | Review | Mol Biol Rep | Exogenous fibrinogen reduces surgical bleeding but may carry pro-inflammatory and cardiovascular risk |
| 24609765 | 2014 | Observational | Int J Hematol | Thromboelastometry profile in children with beta-thalassemia, who have a hypercoagulable state and higher thrombosis risk |
| 35417875 | 2022 | Review/Observational | Georgian Med News | Thrombotic complications and latent hypercoagulation in beta-thalassemia |
| 40883664 | 2025 | Observational | BMC Nephrol | Fibrinogen-to-albumin ratio and NGAL as indicators of kidney disease in sickle cell patients (Ghana case-control study) |
| 32777069 | 2020 | Laboratory study | Blood Adv | Red blood cell adhesion to ICAM-1 is mediated by fibrinogen in sickle cell disease (17 patients) |
| 27723451 | 2017 | Laboratory study | Blood Transfus | Platelet procoagulant properties and the effect of transfusion in beta-thalassemia |
| 39441287 | 2024 | Observational | Georgian Med News | Protein C and S in beta-thalassemia major and their correlation with D-dimer and other markers |
| 1203541 | 1975 | Observational | Blut | Hypercoagulability and hypofibrinolysis in 52 sickle cell patients, with higher-than-normal fibrinogen levels |
None of these studies tested fibrinogen as a treatment for hemoglobinopathy. Their study types were inferred from titles and abstracts.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| BLA125612 | Fibryga (Octapharma USA Inc) | Powder, for solution | Not listed in source data |
| BLA125612 | Fibryga (Octapharma USA Inc) | Powder, for solution | Not listed in source data |
| BLA125317 | Riastap (CSL Behring GmbH) | Injection, solution | Not listed in source data |
| BLA125317 | RiaSTAP (CSL Behring GmbH) | Injection, powder, lyophilized, for solution | Not listed in source data |
Safety Considerations
Please refer to the package insert for safety information.
One risk comes from the literature rather than labeling. Patients with sickle cell disease and beta-thalassemia already have a hypercoagulable state and elevated fibrinogen. Additional fibrinogen could increase thrombotic risk.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (99.12%), but no study supports fibrinogen as a treatment for hemoglobinopathy. The only registered trial is unrelated to fibrinogen, and the literature points to a possible harmful direction of effect (thrombosis). Evidence is at L4, and the repurposing rationale is weak.
To proceed, the following is needed:
- Package insert warnings and contraindications, which are required for safety screening
- Approved indications and mechanism of action from DrugBank
- Preclinical or clinical evidence that fibrinogen supplementation has any benefit in a hemoglobinopathy setting
- A thrombosis risk assessment for hypercoagulable hemoglobinopathy patients
- Verification of the NCT03673085 registry record, to confirm whether fibrinogen is involved at all
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.