The understanding of coagulopathies in trauma has increased interest in thromboelastography (TEG®) and thromboelastometry (ROTEM®), which promptly evaluate the entire clotting process and may guide blood product therapy. Our objective was to review the evidence for their role in diagnosing early coagulopathies, guiding blood transfusion, and reducing mortality in injured patients. We considered observational studies and randomized controlled trials (MEDLINE, EMBASE, and Cochrane databases) to February 2014 that examined TEG®/ROTEM® in adult trauma patients. We extracted data on demographics, diagnosis of early coagulopathies, blood transfusion, and mortality. We assessed methodologic quality by using the Newcastle-Ottawa scale (NOS) for observational studies and QUADAS-2 tool for diagnostic accuracy studies. Fifty-five studies (12,489 patients) met inclusion criteria, including 38 prospective cohort studies, 15 retrospective cohort studies, two before-after studies, and no randomized trials. Methodologic quality was moderate (mean NOS score, 6.07; standard deviation, 0.49). With QUADAS-2, only three of 47 studies (6.4%) had a low risk of bias in all domains (patient selection, index test, reference standard and flow and timing); 37 of 47 studies (78.8%) had low concerns regarding applicability. Studies investigated TEG®/ROTEM® for diagnosis of early coagulopathies (n = 40) or for associations with blood-product transfusion (n = 25) or mortality (n = 24). Most (n = 52) were single-center studies. Techniques examined included rapid TEG® (n =12), ROTEM® (n = 18), TEG® (n = 23), or both TEG® and rapid TEG® (n = 2). Many TEG®/ROTEM® measurements were associated with early coagulopathies, including some (hypercoagulability, hyperfibrinolysis, platelet dysfunction) not assessed by routine screening coagulation tests. Standard measures of diagnostic accuracy were inconsistently reported. Many abnormalities predicted the need for massive transfusion and death, but predictive performance was not consistently superior to routine tests. One observational study suggested that a ROTEM® -based transfusion algorithm reduced blood-product transfusion, but TEG®/ROTEM®-based resuscitation was not associated with lower mortality in most studies. Limited evidence from observational data suggest that TEG®/ROTEM® tests diagnose early trauma coagulopathy and may predict blood-product transfusion and mortality in trauma. Effects on blood-product transfusion, mortality, and other patient-important outcomes remain unproven in randomized trials.

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Effect of thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®) on diagnosis of coagulopathy, transfusion guidance and mortality in trauma: descriptive systematic review

The Society for Vascular Surgery clinical practice guidelines on the management of visceral aneurysms.

Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. A wide variety of embolic agents including metallic coils, calibrated microspheres, and liquids are available for clinical practice. Additionally, advances in biomaterials, such as shape-memory foams, biodegradable polymers, and in situ gelling solutions have led to the development of novel preclinical embolic agents. The aim here is to provide a comprehensive overview of current and emerging technologies in endovascular embolization with respect to devices, materials, mechanisms, and design guidelines. Limitations and challenges in embolic materials are also discussed to promote advancement in the field.

Advances in Biomaterials and Technologies for Vascular Embolization

Early brain injury (EBI) following aneurysmal subarachnoid hemorrhage (SAH) is an important predictor of poor functional outcome, yet the underlying mechanism is not well understood. Animal studies suggest that platelet activation and inflammation with subsequent microthrombosis and ischemia may be a mechanism of EBI. A prospective, hypothesis-driven study of spontaneous, SAH patients and controls was conducted. Platelet activation [thromboelastography maximum amplitude (MA)] and inflammation [C-reactive protein (CRP)] were measured serially over time during the first 72 h following SAH onset. Platelet activation and inflammatory markers were compared between controls and SAH patients with mild [Hunt–Hess (HH) 1–3] versus severe (HH 4–5) EBI. The association of these biomarkers with 3-month functional outcomes was evaluated. We enrolled 127 patients (106 SAH; 21 controls). Platelet activation and CRP increased incrementally with worse EBI/HH grade, and both increased over 72 h (all P < 0.01). Both were higher in severe versus mild EBI (MA 68.9 vs. 64.8 mm, P = 0.001; CRP 12.5 vs. 1.5 mg/L, P = 0.003) and compared to controls (both P < 0.003). Patients with delayed cerebral ischemia (DCI) had more platelet activation (66.6 vs. 64.9 in those without DCI, P = 0.02) within 72 h of ictus. At 3 months, death or severe disability was more likely with higher levels of platelet activation (mRS4–6 OR 1.18, 95 % CI 1.05–1.32, P = 0.007) and CRP (mRS4–6 OR 1.02, 95 % CI 1.00–1.03, P = 0.041). Platelet activation and inflammation occur acutely after SAH and are associated with worse EBI, DCI and poor 3-month functional outcomes. These markers may provide insight into the mechanism of EBI following SAH.

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The Role of Platelet Activation and Inflammation in Early Brain Injury Following Subarachnoid Hemorrhage.

Previous studies proved that melatonin protected against secondary brain damage by modulating oxidative stress after experimental subarachnoid hemorrhage (SAH), but it has not been evaluated yet about its effects on inflammatory pathway and secondary cognitive dysfunction in SAH model. This study was undertaken to evaluate the influence of melatonin on toll-like receptor 4 (TLR4) signaling pathway and neurobehavioral tests after SAH. Adult SD rats were divided into four groups: control group (n = 20), SAH group (n = 20), SAH+vehicle group (n = 20), and SAH+melatonin group (n = 20). The rat SAH model was induced by injection of 0.3 mL fresh arterial, nonheparinized blood into the prechiasmatic cistern in 20 s. In SAH+melatonin group, melatonin was administered i.p. at 150 mg/kg at 2 and 24 hr after the induction of SAH. Cognitive and memory changes were investigated in the Morris water maze. Treatment with melatonin markedly decreased the expressions of TLR4 pathway-related agents, such as high-mobility group box 1 (HMGB1), TLR4, nuclear factor-κB (NF-κB), myeloid differentiation factor 88 (MyD88), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS). Administration of melatonin following SAH significantly ameliorated spatial learning and memory deficits in this prechiasmatic blood injection model. Staining of apoptosis and necrosis indicated that fewer positive cells appeared in melatonin-treated group than SAH+vehicle group. In conclusion, melatonin may attenuate neurobehavioral dysfunction in this SAH model, and melatonin exhibits neuroprotection possibly not only through anti-oxidative pathway but also anti-inflammatory signaling after experimental SAH.

Melatonin alleviates secondary brain damage and neurobehavioral dysfunction after experimental subarachnoid hemorrhage: possible involvement of TLR4-mediated inflammatory pathway.

Background The Raymond–Roy Occlusion Classification (RROC) is the standard for evaluating coiled aneurysms (Class I: complete obliteration; Class II: residual neck; Class III: residual aneurysm), but not all Class III aneurysms behave the same over time. Methods This is a retrospective review of 370 patients with 390 intracranial aneurysms treated with coil embolization. A Modified Raymond–Roy Classification (MRRC), in which Class IIIa designates contrast within the coil interstices and Class IIIb contrast along the aneurysm wall, was applied retrospectively. Results Class IIIa aneurysms were more likely to improve to Class I or II than Class IIIb aneurysms (83.34% vs 14.89%, p Conclusions We propose the MRRC to further differentiate Class III aneurysms into those likely to progress to complete occlusion and those likely to remain incompletely occluded or to worsen. The MRRC has the potential to expand the definition of adequate coil embolization, possibly decrease procedural risk, and help endovascular neurosurgeons predict which patients need closer angiographic follow-up. These findings need to be validated in a prospective study with independent blinded angiographic grading.

https://jnis.bmj.com/content/neurintsurg/7/7/496.full.pdf

An update to the Raymond–Roy Occlusion Classification of intracranial aneurysms treated with coil embolization

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1538-7836.2012.04651.x

Early platelet activation, inflammation and acute brain injury after a subarachnoid hemorrhage: a pilot study

Background and purpose The Penumbra Coil 400 System (PC 400) is the newly introduced platinum coil system designed specifically to enhance filling efficiency by increasing coil diameter. Our goal was to study the packing and treatment advantage of the PC 4009s unique geometric configuration compared with conventional coils (controls). Materials and methods 16 aneurysms embolized with the PC 400 in 2011 were compared with 79 equally matched aneurysms embolized with conventional coils from 2004 to 2011. Primary outcomes assessed were acute packing density, embolization time, and the number of coils required for aneurysm occlusion. Results Aneurysm embolization with the PC 400 achieved a higher packing density (36.8% vs 28.1%; p Conclusions Compared with conventional coils, the PC 400 is more efficient in the embolization of cerebral aneurysms, achieving greater packing density with fewer coils and less time without compromising safety.

Initial experience with Penumbra Coil 400 versus standard coils in embolization of cerebral aneurysms: a retrospective review

Onyx embolization of cerebral arteriovenous malformations (AVM) has become increasingly common We explored the risk of seizures after Onyx useA retrospective review was conducted of 20 patients with supratentorial brain arteriovenous malformation (AVM) who received Onyx embolization between 2006 and 2009 Baseline demographics, clinical history, seizure history, AVM characteristics and treatment were compared between those who developed post-onyx seizure and those who did not MRIs were reviewed for edema following Onyx treatmentOf 20 patients who underwent Onyx embolization, the initial AVM presentation was hemorrhage in 40% (N=8) The median number of embolizations was two (range 1-4) and the median final obliteration amount was 90% (range 50-100%) A history of seizure was present in 50% (N=10) of patients pre-embolization and 12 (60%) patients received seizure medications (treatment or prophylaxis) prior to embolization Seizur post-Onyx embolization occurred in 45% (N=9) The median time to seizur post-Onyx was seven days (range 03-210) Four patients (20%) with seizures post-Onyx had no seizure history Two of these patients (10%) had no other identifiable cause for seizure other than recent Onyx embolization Seizures in these two patients occurred within 24 hours of Onyx administration Among patients with post-Onyx seizures, there was a trend toward larger AVM size (P=0091) and lower percent obliteration (P=0062) Peri-AVM edema was present in 75% of MRIs performed within one month of Onyx treatment and may represent a possible etiology for seizuresNew onset seizures post-Onyx embolization are not uncommon Further study of seizure prevention is warranted

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Seizures after Onyx embolization for the treatment of cerebral arteriovenous malformation.

Background The initial experience with the large diameter Penumbra Coil 400 (PC400) system has been positive regarding safety, efficacy, improved packing density and cost effectiveness, but follow-up data are limited. Methods This is a single-center retrospective review of 76 aneurysms treated with PC400 coils compared with 301 aneurysms treated with a variety of different bare platinum and bioactively coated coils. Atypical and giant aneurysms were excluded as well as those that had undergone previous treatment. Occlusion classification was determined immediately after the procedure and at short-term follow-up. Results Compared with controls, in the PC400 group fewer coils were used (3.53 vs 5.44, p Conclusions Large diameter PC400 coils can be used to safely treat cerebral aneurysms with fewer coils, decreased procedure time and increased packing density compared with standard coils. The early angiographic outcome is similar to that achieved with standard coils.

https://jnis.bmj.com/content/neurintsurg/7/2/126.full.pdf

Analysis of early angiographic outcome using unique large diameter coils in comparison with standard coils in the embolization of cerebral aneurysms: a retrospective review

A Patel

Papers

An update to the Raymond–Roy Occlusion Classification of intracranial aneurysms treated with coil embolization

Early platelet activation, inflammation and acute brain injury after a subarachnoid hemorrhage: a pilot study

Initial experience with Penumbra Coil 400 versus standard coils in embolization of cerebral aneurysms: a retrospective review

Seizures after Onyx embolization for the treatment of cerebral arteriovenous malformation.

Analysis of early angiographic outcome using unique large diameter coils in comparison with standard coils in the embolization of cerebral aneurysms: a retrospective review