Pharmacokinetic strategies for achieving precise factor VIII control with susoctocog alfa in acquired hemophilia A
Bibliographic record
Abstract
BACKGROUND: Recombinant porcine factor (F)VIII (rpFVIII, susoctocog alfa) is used to treat bleeding in patients with acquired hemophilia A (AHA), yet pharmacokinetic (PK) parameters and dosing needs vary widely. OBJECTIVES: To explore the precision of PK-guided bolus dosing and continuous infusion of rpFVIII in AHA. METHODS: We enrolled all AHA patients considered for rpFVIII treatment from 2016 to 2023 at our institution. A user-friendly calculation tool was used to estimate noncompartmental PK parameters from 2 measurements after the initial bolus of rpFVIII, projecting FVIII activity levels for different dosing regimens. PK information was used to guide bolus dosing and continuous infusion, and resulting peak and trough levels were recorded during treatment. RESULTS: Out of 22 patients enrolled, 21 received rpFVIII for severe bleeding. After the initial bolus, the median incremental recovery was 1.33 U/dL per U/kg (IQR, 0.73-1.90), with a half-life of 3.8 hours (IQR, 1.9-7.6) and clearance of 0.10 dL/h/kg (IQR, 0.06-0.47). Subsequent PK-guided treatment included bolus dosing (n = 9) or continuous infusion (n = 12), both were clinically effective. Continuous infusion provided stable FVIII levels over time in most patients. PK parameters remained consistent, with a slight increase in half-life over the first 10 days. CONCLUSION: PK estimates from limited sampling effectively guided rpFVIII bolus and continuous infusion dosing. Continuous infusion provided steady FVIII levels and may offer a practical alternative to bolus dosing.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".