PracticeUpdate Conference Series - ANZAN 2018

tissue-type plasminogen activator fails in more than 60% of patients with acute ischemic stroke. Risks associated with recombinant tissue-type plasminogen activator include symptomatic intracra- nial hemorrhage, even in patients who recanalize. While thrombus location, etiology, and infarct size can affect the likelihood of successful thrombolysis, other factors that distinguish patients who recanalize from those who do not have yet to be fully elucidated. The ability of recombi- nant tissue-type plasminogen activator to promote thrombolysis depends on its capacity to generate plasmin. Dr. Levi and colleagues set out to test this capacity ex vivo. They hypothesized that patients with low plasmin-generating capacity would be less likely to recana- lize following treatment recombinant tissue-type plasminogen activator. Plasma was obtained from 90 patients with acute ischemic stroke up to 1 h before thrombolysis and screened for baseline levels of plasminogen, antiplasmin, and plasmin-antiplasmin complexes. The degree of inducible plasmin gener- ation was determined using amidolytic assays following ex vivo addition of recombinant tissue-type plasminogen activator for 1 h. Enzyme-linked immunosorbent assay was also used to quantify the increase in plasmin-antiplasmin complex levels after treatment with recombinant tissue-type plasminogen activator. Plasmin-antiplasmin complex levels that were induced by recombinant tissue-type plasminogen activator, a surrogate for the capacity to generate plasmin from plasminogen, varied dramatically among patients. The ratio of post-thrombolysis plasmin- antiplasmin complex to prethrombolysis plasmin-antiplasmin complex ranged from 3.4 to 105.9 within the examined cohort. Multivariate regression analyses revealed that each fold increase in plasmin-antiplasmin complex levels was associated with a 4.2% increase in the odds of recanalization (P = .035) when corrected for blood glucose levels. Dr. Levi concluded that this was the first report of ex vivo-inducible plasmin gener- ation as a predictor of thrombolysis. The predictive power of this screening assay for symptomatic intracerebral hemor- rhage remains under investigation.

most appropriate hospital, which may not be the closest.” Ambulance Victoria paramedics assessed ACT-FAST in all suspected stroke patients prior to hospital arrival in metropolitan Melbourne and in the Royal Melbourne Hospital emergency department since 2017. Algorithm results were validated against a comparator of internal carotid artery/ middle cerebral artery/proximal (M1) middle cerebral artery occlusion on CT angiography with National Institutes of Health stroke scale ≥6 (class 1 indications for endovascular thrombectomy). Data were available from 119 assessments (emergency department n=68, prehospi- tal n=51). Diagnoses were large vessel occlusion (n=20, 15.6%), non-large vessel occlusion infarcts (n=45, 38.5%, intracer- ebral hemorrhage (n=10 (8.3%), and no stroke on imaging (n=44, 37.6%). ACT-FAST exhibited 85% sensitivity, 88.9% specificity, 60.7% (72% excluding intracerebral hemorrhage) positive predictive value, and 96.7% negative predictive value for large vessel occlusion. Of 10 false–positive results, 4 received thrombectomy for non-class 1 indications (basilar/distal [M2] middle cerebral artery 2 occlusions/cervical dissection), 3 were intracerebral hemorrhages, and 1 was a tumor. A total of 3 false–negatives were large vessel occlusions with milder syndromes. Dr. Campbell concluded that the ongo- ing ACT-FAST algorithm validation study showed high accuracy for clinical rec- ognition of large vessel occlusions. The streamlined algorithmic approach with just two examination items provides a more practical option for implementation in large emergency service networks. Accurate prehospital recognition of large vessel occlusions will allow for bypass to endovascular centers and early activation of neuro-intervention services to expedite endovascular thrombectomy. “Results so far look very promising,” Dr. Campbell noted. “Paramedics can dis- tinguish patients with severe stroke using this simple algorithm. We are testing ACT- FAST across Victoria to further establish its accuracy in the field and to assess the likely impact of taking ACT-FAST-positive patients directly to a clot retrieval hospital.” Plasmin assay Chris Levi, MD, of the John Hunter Hospital in Newcastle, NSW, explained that thrombolysis with recombinant

It was designed to improve specificity and paramedic assessment reliability vs exist- ing triage scales. ACT-FAST sequentially assesses: ƒ ƒ Unilateral arm fall to stretcher <10 s ƒ ƒ Severe language disturbance (right arm weak) or severe gaze deviation/ hem-neglect assessed by shoulder tap (left arm weak) ƒ ƒ Clinical eligibility questions Dr. Campbell presented results of the ongoing Ambulance Victoria paramedic validation study on behalf of Henry Zhao, MBBS, also of the Royal Melbourne Hospital. “Getting the best outcomes for stroke patients,” Dr. Campbell told Elsevier’s PracticeUpdate , “requires opening blocked arteries as soon as possible. Treatment is delayed by the need to transfer patients between hospitals for clot retrieval.” He continued, “Studies have shown that interhospital transfer adds an approximately 2-h delay, even though driving time between hospitals may be only 15–20 minutes. The ultimate aim of ACT-FAST is to empower paramedics to (1) identify patients likely to need clot retrieval when they arrive on the scene, and (2) take those patients directly to the

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ANZAN 2018 • PRACTICEUPDATE CONFERENCE SERIES 21