Evaluation of Plasma-Derived FVII Efficacy for the Treatment of Bleeding in a Murine Model of Hemophilia a
Bibliographic record
Abstract
Background Recombinant human activated factor VII (rhFVIIa) has been used successfully to treat hemophilic patients with neutralizing antibodies to FVIII or FIX. High doses of FVIIa are known to be effective in opposing bleeding in hemophilia B mice and in a mouse model of antibody-induced hemophilia A. The therapeutic indications for human plasma-derived coagulation factor VII (pdFVII) include the prophylaxis and treatment of bleeding disorders in isolated congenital or acquired factor VII deficiency. These preparations are considered to be ineffective in hemophilia A in the presence of inhibitors as they do not contain activated factor VII and therefore cannot be used in haemophiliac patients with inhibitors. Aim Here, we investigated the potential use of pdFVII to induce hemostasis in a mouse model of congenital hemophilia A with high-titer inhibitors and antibody-induced hemophilia A in wild-type mice. Methods F8 KO mice were given 2 IU recombinant human FVIII intravenously weekly for 4 weeks. All mice that developed high-titer inhibitors (>5 BU/ml) were selected to be used in tail transection experiments. Additionally, a model of antibody-induced hemophilia was used by injecting C57BL/6 wild-type mice with 2 doses of murine plasma containing high-titer inhibitors. Mice were anesthetized and tails transected at a cross-sectional diameter of 1.5 mm; the tail was immediately placed in thermostated saline, and the duration of active bleeding was recorded. Bleeding was monitored for 10 minutes. Blood loss was determined by measuring the amount of released haemoglobin in the saline. Mice were pre-treated 15 minutes before haemostatic challenge with a single i.v. injection of saline, rhFVIIa (4 mg/kg) or pdFVII (500 IU/kg). Results Administration of both rhFVIIa and pdFVII corrected the bleeding tendency in both animal models. In particular, pdFVII and rFVIIa treatments caused a marked reduction in the mean bleeding index score of hemophilia A mice with inhibitors in comparison to mice treated with vehicle only (vehicle, mean=5750, s.e.m.= 438; pdFVII, mean=1301, s.e.m.= 819; rFVIIa, mean=1101, s.e.m.=565; P Conclusions Our results provide evidence that pharmacological doses of both rFVIIa and pdFVII are effective in promoting hemostasis in animal models of congenital hemophilia A with inhibitors and antibody-induced hemophilia A in wild-type mice. Disclosures No relevant conflicts of interest to declare.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".