Platelet testing in flow diversion: a review of the evidence.

OBJECTIVE Although the use of dual antiplatelet therapy with flow diversion is recommended and commonplace, the testing of platelet inhibition is more controversial. METHODS The authors reviewed the medical literature to establish and describe the physiology of platelet adhesion, the pharmacology of antiplatelet medications, and the mechanisms of the available platelet function tests. Additionally, they present a review of the pertinent neurointerventional and interventional cardiology literature. RESULTS Competing reports in the neurointerventional literature argue for and against the use of routine platelet function testing, with adjustments to the dosage or medications based on the results. The interventional cardiology literature has also wrestled with this dilemma after percutaneous coronary interventions, with conflicting reports of the benefits of platelet function testing. CONCLUSIONS Despite its prevalence, the benefits of platelet function testing prior to flow diversion are unproven. This practice will likely remain controversial until the level of evidence improves through more rigorous testing and reporting.

Neurosurgical applications of viscoelastic hemostatic assays.

Patients taking antithrombotic agents are very common in neurosurgical practice. The perioperative management of these patients can be extremely challenging especially as newer agents, with poorly defined laboratory monitoring and reversal strategies, become more prevalent. This is especially true with emergent cases in which rapid reversal of anticoagulation is required and the patient's exact medical history is not available. With an aging patient population and the associated increase in diseases such as atrial fibrillation, it is expected that the use of these agents will continue to rise in coming years. Furthermore, thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and myocardial infarction are common complications of major surgery. These trends, in conjunction with a growing understanding of the hemostatic process and its contribution to the pathophysiology of disease, stress the importance of the complete evaluation of a patient's hemostatic profile in guiding management decisions. Viscoelastic hemostatic assays (VHAs), such as thromboelastography and rotational thromboelastometry, are global assessments of coagulation that account for the cellular and plasma components of coagulation. This FDA-approved technology has been available for decades and has been widely used in cardiac surgery and liver transplantation. Although VHAs were cumbersome in the past, advances in software and design have made them more accurate, reliable, and accessible to the neurosurgeon. VHAs have demonstrated utility in guiding intraoperative blood product transfusion, identifying coagulopathy in trauma, and managing postoperative thromboprophylaxis. The first half of this review aims to evaluate and assess VHAs, while the latter half seeks to appraise the evidence supporting their use in neurosurgical populations.

Laboratory assessments of therapeutic platelet inhibition in endovascular neurosurgery: comparing results of the VerifyNow P2Y12 assay to thromboelastography with platelet mapping.

OBJECTIVEInhibition of platelet aggregation is vital to preventing thromboembolic complications related to stent placement in endovascular neurosurgery, but excessive inhibition potentiates hemorrhagic complications. Recent evidence suggests an ideal inhibition range of 70-150 P2Y12 response units (PRU) as measured on the VerifyNow assay, which relies on photometric measurements of platelet aggregation. Thromboelastography (TEG) with platelet mapping (PM) is an alternative assay that directly measures clot formation and mechanical strength. This study compares the results of PRU to TEG-PM.METHODSPatients with simultaneous or near-simultaneous PRU and TEG-PM results who underwent cervical carotid artery stenting, intracranial stent-assisted aneurysm coiling, or flow diversion at the authors' institution between August 2015 and November 2016 were identified. PRU results were compared with the TEG maximal amplitude (MA) attributable to adenosine diphosphate (ADP) activity (MA-ADP) as measured by TEG-PM. Platelet inhibition was considered therapeutic for MA-ADP values < 50 mm or PRU < 194. The Pearson correlation coefficient was calculated, and the sensitivity and specificity of PRU were calculated assuming that the results of TEG-PM reflected the true degree of platelet inhibition.RESULTSTwenty-three patients were identified with a total of 37 matched sets of TEG-PM and PRU. Three of these pairs were excluded due to anemia outside of the PRU manufacturer's recommended range. The Pearson correlation coefficient for these values was 0.50 (p = 0.0026). The prevalence of clopidogrel nonresponders determined by TEG-PM (9%) matched reported rates (5%-12%); PRU demonstrated much higher prevalence (39%). For detecting a therapeutic level of platelet inhibition, PRU demonstrated a sensitivity of 0.59, specificity of 0.50, positive predictive value of 0.95, and negative predictive value of 0.07. Ideal inhibition was concordant in only 25% of observations in which at least one of the results was ideal.CONCLUSIONSAgreement between TEG-PM and PRU regarding the degree of platelet inhibition is poor. PRU likely overestimates clopidogrel resistance, as 93% of patients with PRU > 194 demonstrate a therapeutic level of platelet inhibition on TEG.

Insufficient platelet inhibition and thromboembolic complications in patients with intracranial aneurysms after stent placement.

OBJECT Insufficient platelet inhibition has been associated with an increased incidence of thromboembolic complications in cardiology patients undergoing percutaneous coronary intervention. Data regarding the relationship between insufficient platelet inhibition and thromboembolic complications in patients undergoing neurovascular procedures remain controversial. The purpose of this study was to assess the relationship of insufficient platelet inhibition and thromboembolic complications in patients with intracranial aneurysm undergoing stent treatment. METHODS The authors prospectively recruited patients with intracranial aneurysms undergoing stent treatment and maintained the data in a database. MRI with diffusion-weighted sequences was performed within 24 hours of stent insertion to identify acute ischemic lesions. The authors used thromboelastography to assess the degree of platelet inhibition in response to clopidogrel and aspirin. Univariate and multivariate logistic regression analysis was used to identify potential risk factors of thromboembolic complications. RESULTS One hundred sixty-eight patients with 193 aneurysms were enrolled in this study. Ninety-one of 168 (54.2%) patients with acute cerebral ischemic lesions were identified by diffusion-weighted MRI. In 9 (5.4%) patients with ischemic lesions, transient ischemic attack or stroke was found at discharge, and these complications were found in 11 (6.5%) patients during the follow-up period. The incidence of periprocedural thromboembolic complications increased with resistance to antiplatelet agents, hypertension, hyperlipidemia, complete occlusion, and aneurysm of the anterior circulation. The multivariate regression analysis demonstrated that the anterior circulation and adenosine diphosphate (ADP) inhibition percentage were independent risk factors of perioperative thromboembolic complications. The maximum amplitude and ADP inhibition percentage were independent risk factors for thromboembolic complications during the follow-up period. CONCLUSIONS The ADP inhibition percentage is related to thromboembolic complications after stent placement for intracranial aneurysms. The increase of the ADP inhibition may decrease the risk of thromboembolic complications.

Use of blood-sparing surgical techniques and transfusion algorithms: association with decreased blood administration in children undergoing primary open craniosynostosis repair.

OBJECT Craniofacial reconstruction surgery (CFR) is often associated with significant blood loss, coagulopathy, and perioperative blood transfusion. Due to transfusion risks, many different approaches have been used to decrease allogeneic blood transfusion for these patients during the perioperative period. Protocols have decreased blood administration during the perioperative period for many types of surgeries. The object of this study was to determine if a protocol involving blood-sparing surgical techniques and a transfusion algorithm decreased intraoperative blood transfusion and blood loss. METHODS A protocol using transfusion algorithms and implementation of blood-sparing surgical techniques for CFR was implemented at Vanderbilt University on January 1, 2013. Following Institutional Review Board approval, blood loss and transfusion data were gathered retrospectively on all children undergoing primary open CFR, using the protocol, for the calendar year 2013. This postprotocol cohort was compared with a preprotocol cohort, which consisted of all children undergoing primary open CFR during the previous calendar year, 2012. RESULTS There were 41 patients in the preprotocol and 39 in the postprotocol cohort. There was no statistical difference between the demographics of the 2 groups. When compared with the preprotocol cohort, intraoperative packed red blood cell transfusion volume decreased from 36.9 ± 21.2 ml/kg to 19.2 ± 10.9 ml/kg (p = 0.0001), whereas fresh-frozen plasma transfusion decreased from 26.8 ± 25.4 ml/kg to 1.5 ± 5.7 ml/kg (p < 0.0001) following implementation of the protocol. Furthermore, estimated blood loss decreased from 64.2 ± 32.4 ml/kg to 52.3 ± 33.3 ml/kg (p = 0.015). Use of fresh-frozen plasma in the postoperative period also decreased when compared with the period before implementation of the protocol. There was no significant difference in morbidity and mortality between the 2 groups. CONCLUSIONS The results of this study suggested that using a multidisciplinary protocol consisting of transfusion algorithms and implementation of blood-sparing surgical techniques during major CFR in pediatric patients is associated with reduced intraoperative administration of blood product, without shifting the transfusion burden to the postoperative period.