Development and Validation of a Nomogram for Predicting Heparin Resistance in Neonates and Young Infants Undergoing Cardiac Surgery
A Retrospective Study
Anesthesia Analgesia
Submitted August 2024 by Dr Marlene Johnson
Read by 170 Journal Watch subscribers
Summary:
This study describes the development of a simple, predictive nomogram using pre-operative variables for heparin resistance in neonates and young infants undergoing cardiac surgery.
Methods:
Heparin resistance was defined as the failure to achieve an ACT of 410 seconds or greater after the administration of 400U/kg heparin. In this single-centre retrospective study of 296 patients, patients were divided into a development cohort (70%), and a validation cohort (30%). The development cohort was used to identify predictors of heparin resistance and to establish a nomogram, whilst the validation cohort was used to test the efficacy of the nomogram.
Key Findings:
The predictors of heparin resistance were identified as:
- Antithrombin activity
- Platelet count
- Fibrinogen level
Using these 3 factors, the prediction model achieved an area under the receiver operating characteristic curve of 0.88 and 0.87 in the development and validation cohorts, indicating the clinical utility of the prediction model. The model performed well in both neonatal and infant sub-groups.
Discussion:
The authors present a simple to use clinical tool that can be used pre-operatively to identify young patients at risk of heparin resistance. The authors argue that their nomogram may help to tailor the heparin dose to the patient, thereby avoiding “over-anticoagulation” (which may lead to heparin rebound and post-operative bleeding) as well as “under-anticoagulation” (which may result in repeated dosing and prolonged overall operative time). They did not provide suggestions for tailored anti-coagulation management, or a threshold for the risk score to trigger active management.
Apart from the usual limitations of a small, single centre, retrospective study, there were several other limitations. First, baseline ACT values were not measured, so the heparin sensitivity index (a more robust method of determining heparin responsiveness) could not be calculated. Second, the authors tried to identify as many “potential predictors” of heparin resistance as possible in the initial stage of the study, before the final three (listed above) were selected. This increases the type I error, or likelihood of a false positive error. Finally, heparin resistance is commonly defined as an ACT >480s. In this study, it was defined as ACT >410s due to differences in their assay equipment and technology, thereby reducing the external validity of their result.
