|dc.description.abstract||Introduction/Aims: Patients undergoing interventional neuroradiology (IVN) procedures to treat intracranial aneurysms experience a minor, but potentially life threatening risk of thromboembolic or haemorrhagic complications. Antiplatelet medications, such as clopidogrel and aspirin, are routinely administered pre-operatively for elective IVN procedures to reduce the risk of thromboembolic events. There are known hyper- or hypo-effective responses to these pre-operative antiplatelet medications, notably clopidogrel, which may insufficiently inhibit platelet function in some patients and increase the risk of complication. The point-of-care (POC) Multiplate® analyser was used to assess platelet function (aggregation) at numerous time points. Patient outcome (ie. those who suffered surgical complications, and those who did not) was assessed to establish whether platelet functionality was related to IVN complication. Additionally, analysing platelet response data in patients with and without complications aimed to establish the potential diagnostic value of Multiplate® response for negative clinical outcomes. In addition, platelet aggregation as recorded by Multiplate® analysis was with platelet activation as assessed using flow cytometry in an attempt to compare functional Multiplate® data to sensitive molecular activation markers.
Methods: This project received ethical approval from Griffith University and the Gold Coast University Hospital (GCUH), including amendments for the inclusion of flow cytometric analysis. Demographic and surgical data, as well as blood samples were collected from adult patients admitted to the GCUH for elective or emergent treatment of intracranial aneurysms between March 2015 and April 2018. Blood samples were collected at five separate time points: admission (pre-antiplatelet administration), pre-operatively (post-antiplatelet administration), post-surgically, and at days 1 and 4 post-operatively. The samples of 120 patients and 131 procedures were analysed on Multiplate®, while 12 matched patient samples were also analysed using a BD LSRFortessa™ Cell Analyser for flow cytometric analysis. Samples were collected from elective and emergent (ruptured aneurysm) patients. The main variable of interest were the extent of platelet aggregation/activation at each time point, as well as any peri- or post—surgical complications the patient experienced.
Results: Analysis of the 120 patients showed that pre-operative aspirin and clopidogrel administration significantly reduced platelet aggregation (Multiplate®) and platelet activation (flow cytometry). A total of 26 complications were recorded including ischaemic, haemorrhagic events, vasospasm and evidence of temporary neurological deficit. Elective patients who suffered complications (composite score of all adverse events) had significantly higher pre-operative, ADP-induced Multiplate® scores compared to their non-complication counterparts (P<0.05). There were no significant differences in Multiplate® scores in the elective cohort when comparing the non-complication group to those who suffered ischaemic or haemorrhagic complications specifically (P>0.05). Furthermore, Multiplate® scores did not differ in patients in non-complication versus complications within the emergent cohort.
ROC analysis of pre-operative Multiplate® data demonstrated that a ADP-induced platelet aggregation score of >31.5AUC was a significant predictor of elective complications (i.e. all complications excluding haemorrhagic). This allowed successful identification of 88.89% (i.e. sensitivity) of surgical complications pre-surgically by assessing their platelet aggregation with a 34.62% false positive rate. There were no significant predictors of haemorrhagic complication, or for any type of emergent complication.
Platelet activation recorded by flow cytometry followed a similar trend over time to platelet aggregation as recorded by Multiplate® analyser. “A significant but weak correlation between flow cytometric and Multiplate® analysis was established for agonists including ADP (p=>0.01, r2=0.32) and TRAP-6 (p=0.05, r 2= 0.12).
Conclusion: Elective patients experience significant inhibition of platelet function following antiplatelet administration for IVN procedures as recorded by Multiplate®. Furthermore, this study demonstrated, for the first time, that pre-operative ADP induced platelet aggregation can sensitively predict patients’ risk of experiencing thromboembolic events and/or vasospasm. However, the predictive values established are only reliable for elective patients and do not predict haemorrhagic complications. This is likely due to the small number of patients suffering complication throughout the study. This thesis also presents the first data to compare and potentially validate Multiplate® recorded platelet aggregation against flow cytometry analysis for platelet activation.||