Investigation into the effect of prasugrel versus clopidogrel on platelet thromboelastography (TEG) analysis in paediatric patients on Ventricular Assistance Devices (VAD)
Aims Currently there are no published reports on the use of prasugrel in paediatric patients. Literature search using Embase and Medline databases for ‘PAEDIATRICS’ and ‘PRASUGREL’ with no limits retrieves no published articles on this topic (13 July 2012). Our aims are to:
▸ Document our experience of using prasugrel in paediatric patients on Ventricular Assistance Devices (VADs)
▸ Compare the responses seen between clopidogrel and prasugrel
Methods Data was collected retrospectively (over last 12 months) from all patients who had received prasugrel as part of their anti-platelet therapy whilst on a VAD. Data was collated from drug charts filed in patient notes for dosing information and the electronic pathology system for thromboelastography (TEG) results.
Results In total, two patients were identified as having received prasugrel as part of their anti-platelet therapy whilst on a VAD. Our VAD anticoagulation protocol states a loading dose of 1 mg/kg (no maximum) followed by 0.1 mg/kg (max 5 mg) maintenance, adjusted to achieve TEG ADP inhibition of >70%.1
The mean age was 11 months (range 5–18 months) and mean weight 8.5 kgs (range 6–11 kgs). Both patients were female. Mean duration of treatment was 57 days (range 24–90 days). The mean loading dose was 1.04 mg/kg (0.91–1.17 mg/kg) and the mean maintenance dose was 0.30 mg/kg (0.21–0.49 mg/kg). The mean ADP inhibition was 64.0% (range 59.4–68.7%).
Additionally, in these two patients the mean dose of clopidogrel used prior to initiating prasugrel was 0.8 mg/kg (range 0.64–0.96 mg/kg). The previous mean ADP inhibition achieved on clopidogrel was 48.6% (range 40.8–56.5%). The average duration of treatment was 22 days (range 20–24 days).
The mean time taken to achieve an ADP inhibition of >70% was 10 days (range 4–16 days) and 15.5 days (range 13–18 days) for prasugrel and clopidogrel respectively.
Conclusions The response seen in our patients to prasugrel is similar to studies conducted in adults where prasugrel achieves a greater ADP inhibition than clopidogrel.2 Additionally the time take to achieve effective ADP inhibition was faster. One of the possible causes of this is likely to be due to the different expression of metabolising enzymes in individual patients as both drugs are metabolised in vivo to form their active substrates.3
As prasugrel gives more effective ADP inhibition than clopidogrel, the risk of bleeding events will also be higher. This has been observed in adult clinical trials.2 The intra- and inter-patient variation in TEG response observed supports routine monitoring using TEG analysis to guide dosing and manage side effects such as bleeding.
Effective anticoagulation is imperative to prevent complications on VAD including cerebrovascular accidents that occur in about 30% of patients.4 The management of these patients highlights the importance of prescribers to have access to high quality medicines information to guide dosing, avoid interactions and ensure therapy is optimised.