Retrospective Audit of a Factor VIII Continuous Infusion Protocol to Examine Inhibitor Formation, Complications and Product Use.
Bibliographic record
Abstract
Abstract Continuous infusion (CI) of factor concentrates has been suggested to decrease both the risk of bleeding and cost in the treatment of bleeding disorders. However, concerns have been raised with regards to the stability and sterility of products administered by CI and the risk of local thrombophlebitis. Most recently, there has been a concern about a potential association between the use of CI and the development of an inhibitor in mild hemophilia. A retrospective chart review was conducted to determine the effectiveness, safety, product use and risk of inhibitor formation of a continuous infusion protocol in the management of hemophilia A. Currently 248 patients are registered with the Provincial Hemophilia Program for Newfoundland and Labrador. These patients include 104 with mild hemophilia A, 3 with moderate hemophilia A and 5 with severe hemophilia A. The charts of twelve hemophilia A patients who received factor VIII (FVIII) by CI a total of 18 times between April 1998 and September 2003 were reviewed. All patients were affected by hemophilia A; 8 patients were diagnosed as mild, 1 as moderate and 3 as severe. The mean age of the cohort was 36.1 years and the patients’ ages ranged from 4 months to 75 years. Continuous infusion was used as treatment for severe bleeds in 12 cases and as prophylaxis for surgical procedures in 6 cases. All patients received recombinant FVIII. Recommended devices such as a syringe pump and mini-pump were unavailable therefore all infusions were carried out by diluting the reconstituted concentrate in saline and delivering via IV infusion. The CI protocol followed required a bolus of 50 U/kg of FVIII followed by CI at an initial rate of 4 U/kg/hr. Based on daily FVIII levels, this maintenance dose could be adjusted, with an initial targeted FVIII level of 1.0 U/L. The maximum initial infusion rate was 6.7 U/kg/hr and the minimum was 3.2 U/kg/hr (mean 4.3 U/kg/hr). The infusion rate was reduced in 8 cases to a minimum of 1.2 U/kg/hr. Adequate FVIII levels were maintained after the reduction of the infusion rate in all cases. The mean low and high FVIII levels were 0.79 U/L and 1.23 U/L, respectively (range 0.05 to 1.82 U/L). Excluding the patient who developed an inhibitor, the FVIII level remained above the minimum acceptable level of 0.3 U/L for the duration of CI in all but one case (low 0.29 U/L). Patients required an average dose of 53,163 units (range 2651–299,137 units) of factor concentrate delivered by continuous infusion over a mean period of 8.1 days (range 2–21 days). FVIII infusion was well tolerated in all cases; there were no documented cases of significant bleeding, adverse reactions, thrombophlebitis or infection. One patient was documented to have a minor bleed from an NG tube despite adequate FVIII levels throughout the period of infusion. One patient with mild hemophilia developed a low titer inhibitor (0.8 BU) approximately 2 years after receiving FVIII by continuous infusion for 8 days. Another mild hemophilia patient was discovered to have a low titer inhibitor (1.3 BU) on the eighth day after the third infusion had begun. It is possible that CI contributed to the development of an inhibitor in this patient. CI was not found to significantly reduce product use. More rapid downward adjustment of infusion rates in response to high FVIII levels might improve product utilization.
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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 | 0.003 | 0.010 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 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".