Determinants of bleeding before and during immune tolerance in 222 boys with severe hemophilia A and inhibitors >5 BU
Bibliographic record
Abstract
ABSTRACT: Prevention of bleeding and its consequences is the main goal of hemophilia treatment and determines treatment choices for patients who develop inhibitors. To assess bleeding before and during immune tolerance induction (ITI) and its association with ITI regimen and inhibitor titer, we selected and analyzed data on patients receiving high-titer inhibitors from the international prospective PedNet cohort study. In total, 222 patients with severe hemophilia A and inhibitor titers of >5 Bethesda units (BU) were followed from the first positive to the first negative inhibitor result (median overall follow-up, 1.7 years). Mean annual (joint) bleeding rates (AJBR) and 95% confidence intervals (CIs) were compared according to treatment and inhibitor titer using multivariable negative binomial regression. Before ITI, 115 patients showed an ABR of 6.1 (5.0-7.4) and an AJBR 2.6 (2.1-3.2). Bleeding was independent of inhibitor titer. During ITI, 202 patients had an ABR of 4.4 (3.9-5.1) and an AJBR of 1.7 (1.5-2.0). AJBR during ITI increased with inhibitor titer (hazard ratio [HR] for ≥200 BU vs 5 to 39 BU [4.9; CI, 3.2-7.4]) and decreased with daily ITI infusions (HR, 0.4; CI, 0.3-0.6) or activated prothrombin complex concentrate prophylaxis (HR, 0.4; CI, 0.2-0.8), whereas ITI dose and recombinant activated factor VII prophylaxis did not independently affect bleeding. These data provide evidence for a protective effect of repeated FVIII infusions (ITI) on bleeding in patients who have developed inhibitors; these data should be used to plan ITI and/or serve as a comparator for prophylaxis with nonreplacement therapy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".