Fibrinolytic Treatment Research Articles

P1455 Succesfully surgical management of "transit thrombus"

Abstract A 74-year-old woman was admitted in the emergency department in November 2018 for dyspnea, sudden chest pain and hemodynamic instability. Se had a previous history of pelvic fracture in September 2018, complicated with subdural hematoma secondary to therapeutic anticoagulation that wassurgically managed in October 2018. A through pulmonary arteries CT revealed massive pulmonary thromboembolism with right ventricle overload and pulmonary infarction. Because of history of cerebral hemorrhage, fibrinolytic treatment was ruled out and surgical approach of pulmonary embolism was decided. An intraoperative transesophageal echocardiogram demonstrates a thrombus in the right atrium (Figure 1A, yellow arrow), with invasion through the interatrial septum through a patent foramen ovale (Figure 1B, yellow arrow) with extension to mitral valve plane in the left ventricle (Figure 1C, yellow arrow). "Transit thrombus" was removed, patent foramen ovale was closed and bilateral pulmonary embolectomy was performed. In postoperative transesophageal echocardiography, no residual thrombus in cardiac chambers was seen and the closure of the foramen ovale was checked (Figure 1D). During the postoperative period, the patient presented cardiac tamponade, treated with pericardial drainage. Once this complication was overcome, the evolution was satisfactory and the patient could be discharged. This case demonstrates that performing a transesophageal echocardiogram before a surgical embolectomy in the setting of pulmonary embolism is essential. It allows detect the presence of cardiac thrombi, assess the interatrial septum integrity (where the CT has limitations), and allows to guide the surgical treatment. Abstract P1455 Figure.

Legal medicine implications in fibrinolytic therapy of acute ischemic stroke

BackgroundBefore the advent of fibrinolytic therapy as a gold standard method of care for cases of acute ischemic stroke in Romania, issues regarding legal medicine aspects involved in this area of medical expertise were already presented and, in the majority of cases, the doctors seem to be unprepared for these situations.Main textThe present research illustrates some of the cases in which these aspects were involved, that adressed a clinical center having 6 years of professional experience in the application of fibrinolytic treatment for stroke. The following cases report either situations in which the afore mentioned therapy was not rightfully administrated or legal aspects regarding the obtainment of informed consent.ConclusionObtaining informed consent is a mandatory procedure, which takes time, to the detriment of application of fibrinolytic treatment.

Evaluation of D‐dimer levels in aqueous humor of rabbit eyes with and without induced intraocular fibrin and fibrinolytic treatment

To analyze D-dimer concentrations in aqueous humor (AH) of rabbit eyes under physiological conditions, after induction of fibrin clots, and following fibrinolytic therapy. Prospective study measuring D-dimers in aqueous humor of rabbit eyes with induced fibrin clots (n=44). Rabbits were purchased in two groups, which led to two temporally separated experimentation groups. Different treatment protocols were compared for their efficacy in fibrin reduction (slit-lamp examination, high-resolution ultrasound). AH was taken from left eyes before clot induction (baseline, day 1), 24hours later after clot establishment/prior to drug administration (post-induction, day 2) and 48hours after clot induction (post-treatment, day 3). An enzyme-linked immunosorbent assay (ELISA) was performed to measure intraocular D-dimer concentrations RESULTS: D-dimer concentrations were measurable in all samples. There were no differences in D-dimer levels across time points or treatments within the arrival groups. However, a significant difference in mean D-dimer levels was observed between the two arrival groups (group 1:3.1µg/mL; group 2:6.1µg/mL; P<.0001), which made a direct comparison of treatment groups impossible. Clinically, all eyes displayed fibrin clots in the anterior chamber and different treatment types led to significant differences in clot resolution (clot size reduction after intracameral treatment: 98%, topical treatment: 60%, no treatment: 40%). D-dimers were identified in all AH samples of rabbits with large variability between samples. D-dimer levels were neither predictive for differences in induced fibrin formation nor for drug efficacy.

Managing Postpneumonic Empyema Thoracis in Children: Comparison of Different Treatment Options

Objectives: To compare various treatment methods of postpneumonic empyema (PPE) in children. Methods: Six hundred eighty one (302 females and 379 males) pediatric PPE patients were studied at two different centers between 2000 and 2016. The average age was 4.8 years that ranged from 30 days to 15 years. The patients were considered in six groups. The initial treatments, thoracentesis (group A), chest tube drainage (group B), fibrinolytic therapy (group C), decortication following chest tube drainage (group D), video-assisted thoracoscopic surgery (VATS) (group E) and primary operation without chest tube drainage (group F), were applied to the patients. Results: Success rates were 100%, 47.3%, 82.7%, 100%, 100%, and 100% for thoracentesis, chest tube drainage, fibrinolytic treatment, chest tube drainage, decortication following chest tube drainage, VATS and primer operation, respectively. The overall response rate of fibrinolytic therapy was 82.7% (n = 67). Fourteen of 81 (17.2%) patients who went through fibrinolytic instillation did not respond to treatment; these recovered after the application of thoracotomy and VATS. In addition to decortication pulmonary resections were performed in 15 patients. Overall mortality rate was 1.32%. There was no operative mortality. Postoperative morbidity included wound infection in 22, delayed expansion in 17, and atelectasis in 40 patients. Conclusions: Chest tube drainage can be said to be an efficient and safe primary treatment for PPE in children. In cases when chest tube drainage fails to satisfy, decortication with thoracotomy can be applied well with low mortality and morbidity rates.

A bioinspired hyperthermic macrophage-based polypyrrole-polyethylenimine (Ppy-PEI) nanocomplex carrier to prevent and disrupt thrombotic fibrin clots

Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot prevention and reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs could be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to prevent and lyse fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments. Statement of SignificanceFibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs can be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to disintegrate fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments.

Pleural Thickening after Pleural Effusion: How can we Follow-Up in Children?

No clear information exists about the factors affecting pleural thickening following parapneumonic effusion in children. We aimed to investigate factors that affect the resolving time of pleural thickening after parapneumonic effusion. Between the years of 2007-18, 91 patients, which were followed due to diagnosis of pleural thickening after parapneumonic effusion, were assessed. Ages, complaints, physical examination findings, laboratory results, chest x-ray and ultrasonography findings, treatments, duration of treatment and recovery time of the patients were examined terms in of pleural thickening resolving time. The mean age of patients was 7.5 ± 5.0 years. Pleural thickening resolving time was 151 ± 6.8 days. The resolving time for pleural thickening was delayed with older ages, longer duration of complaints, fever before hospital admission and treatment, lower oxygen saturation at the time of admission, crackles in the physical examination, higher white blood cell count and pleural fluid density (p = 0.018, p = 0.001, p = 0.021, p = 0.020, p = 0.024, p = 0.025, p = 0.021, p = 0.019). In addition, the amount of effusion measured by thorax ultrasonography, fibrinolytic usage, and complications had a role in the delayed resolving time (p = 0.034, p = 0.001, p = 0.034). Pleural thickening resolved in 80% of the patients. In this report, 80% of pleural thickening, following parapneumonic effusion resolved within 5 months. Patients who do not have a complication during follow-up are not required to monitor with frequent chest x-ray. Patients with a higher amount of pleural effusion, complications and need for fibrinolytic treatment should be followed more carefully.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease (VWD). The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. This is an update of a previously published Cochrane Review. Primarily, we aim to assess the efficacy of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or VWD undergoing oral or dental procedures.Secondary objectives are to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or VWD and to establish the effects of these agents on bleeding in oral or dental procedures for each of these patient populations. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched PubMed, Embase, Cinahl and the Cochrane Library. Additional searches were performed in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP).Date of last search of the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 01 March 2019. Randomised and quasi-randomised controlled trials in people with haemophilia or VWD undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid or epsilon aminocaproic acid (EACA)) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained for potentially relevant abstracts and two authors independently assessed these for inclusion based on the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardised forms. While there were no eligible trials in people with VWD identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of EACA published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference (RD) of -0.64 (95% confidence interval (CI) -0.93 to - 0.36) and the EACA trial a RD of -0.50 (95% CI 0.77 to -0.22). The combined RD of both trials was -0.57 (95% CI -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping EACA (combined RD of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the EACA trial, but overall the risk of bias appeared to be low for both trials. Despite the discovery of a beneficial effect of systemically administered tranexamic acid and EACA in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with VWD.

Abstract WP174: Frequency, Predicators, and Outcomes of Pre-Intervention Thrombus Migration in Patients With Acute Ischemic Stroke Due to Large Vessel Occlusion

Background: In patients presenting with acute ischemic stroke (AIS) due to large vessel occlusion (LVO), between initial CTA/MRA and catheter angiography performed for intervention, the occlusive thrombus may persist unchanged, fragment and migrate distally, or resolve completely, with or without bridging intravenous fibrinolytic treatment. The frequency, predictors, and outcomes of pre-intervention thrombus migration not been well delineated. Methods: We analyzed a prospectively maintained registry of AIS-LVO patients at an academic medical center over a 2.8 year period (Dec 2014-Oct 2017). Comparing occlusion sites on arrival CTA/MRA with immediately following interventional angiogram, patients were classified as having: 1) thrombus persistence (TP), 2) thrombus migration (TM), or 3) thrombus resolution (TR). Results: In the 220 patients, mean age was 70.7, 42.7% were female, NIHSS was 13.8, onset to first imaging was 156 minutes, and initial occlusion sites on MRA/CTA were: ICA-20.5%; MCA-67.3%; VA/BA-12.3%. Frequencies of thrombus evolution patterns were: TP-59.5%; TM-30.5%; TR-10.0%. On multivariate analysis, independent predictors of TM were: higher NIHSS (OR 1.06 per 1 pt), cardioembolic mechanism (OR 2.40), and longer time from last known well to first CTA/MRA imaging (OR 1.08 per 60 min). While rates of substantial reperfusion (TICI 2b-3) were similar (85.2% vs 83.7%), patients with TM rather than TP had lower rates of excellent reperfusion (TICI 2C-3), 24.1% vs 44.2%, p = 0.02. Symptomatic intracranial hemorrhage occurred more often in TM than TP, 17.9% vs 8.4%, p = 0.05. In multivariate analysis, TM was independently associated with reduced rates of good functional outcome (mRS 0-2), both at discharge (OR 0.41, 95% CI 0.19 to 0.90; p=0.03) and at 3 months (OR 0.43, 95% CI 0.19 to 0.94; p=0.03). Conclusions: Early TM between initial noninvasive imaging and interventional angiography occurs in nearly one-third of patients, is paradoxically associated with poorer outcomes, including more symptomatic hemorrhage and reduced final functional independence. Better understanding of dynamic clot changes early after arrival and their effects on outcome may aid further development of reperfusion therapeutics.

Timing of Coronary Angiography After Successful Fibrinolytic Therapy in ST-Segment Elevated Myocardial Infarction.

BackgroundWe aimed to compare outcomes of patients received successful fibrinolytic treatment (FT) for ST-segment elevated myocardial infarction (STEMI) and performed coronary angiography (CAG) within 24 - 72 h or after 72 h.MethodsBetween March 2013 and November 2014, 76 STEMI patients received successful FT and performed CAG > 24 h were included in the study. Patients were divided into two groups according to the time-interval from FT admission to CAG performing (Group-1, 24 - 72 h (n = 29), Group-2, > 72 h (n = 47)). The primary end point was major adverse cardiac events (MACE) defined as cardiovascular death, non-fatal myocardial infarction, and heart failure.ResultsThe mean age of patients were 56 ± 11.4 years old (27.6% female). CAG was performed within mean 2.17 ± 0.38 days in the Group-1 and 2.9 ± 11.5 days in the Group 2 (P < 0.001). At short-term follow-up (6 months), MACE rate was higher in Group-2 (21.3%) than Group-1(13.8%), but it was not statistically significant (P = 0.661). The rate of MACE was 37.9% in Group-1 and 38.3% in Group-2 (P = 0.974) in the long-term follow-up (median: 57 months). Overall cardiac mortality rate was 7.9%, the re-infarction rate was 19.7% and heart failure was 17.1% in long-term follow-up, and there were no significant difference between groups.ConclusionsPresent study has shown that performance of CAG after 24 h of successful FT, within 24 - 74 h or > 72 h, did not shown any difference in term of MACE both in short and long-term follow-up.

Characteristics of the stroke alert process attended by 061 ARAGON assistance units from 2010 to 2016. Factors influencing times of response and access to fibrinolytic treatment

To study the response times of stroke code assistance by care units of 061 ARAGON, analyzing factors involved and their relationship with availability to fibrinolytic treatment in the hyperacute phase. Transversal descriptive study on outpatient care from the registry of cases attended by 061 ARAGON health care units to patients with stroke code during the period 2010-2016. A total of 1743 patients were attended (54.6% males), with a mean age of 72.83 ± 13.1 years. There was a higher number of strokes attended in 2015 and 2016 (372 and 366 respectively), compared to the average of 201 strokes per year in the rest of the years. 27,2% of patients were treated between 08:00-11:59 h, the most frequent time interval. Regarding the time, it took to take care of the patient, the average was 71.93 ± 33.64 minutes with a longer response time in Teruel. When influence of the hour interval on the percentage of cases treated with fibrinolysis was analyzed, a higher rate of fibrinolysis was observed when it was activated between 12:00-15:59 h (28.1%). In 55,3% of patients, the 061 response time was greater than 60 minutes, but this time were not conditioned by the activation time. However, there were differences in the percentage of cases fibrinolysed in the different time intervals, suggesting that factors other than the response time of 061 influence the indication of fibrinolytic treatment.

Surgical Treatment in Central Retinal Vein Occlusion

Retinal vein occlusion (RVO) is the second most common vascular disease after diabetic retinopathy. Central retinal vein occlusion (CRVO) is less common than branched retinal vein occlusion. There are different aspects of the mechanisms underlying etiology and optimal treatment strategies in CRVO. There are various treatment modalities for CRVO including observation, systemic treatments, intravitreal agents, laser photocoagulation, fibrinolytic treatment, and surgical approaches. Despite most of the treatment strategies are directed at secondary complications of CRVO that affect vision including macular edema and retinal neovascularization, some treatment options also have the ability to create a bypass around the obstructed retinal vein and to decrease the raised venous hydrostatic pressure. The aim of this review is to describe the outcomes of surgical treatment modalities for CRVO.

Mechanism Underlying a Role for Factor XIII (FXIII) Polymorphism in Sickle Cell Disease-Associated Priapism

Background: The pathophysiology of priapism in sickle cell disease (SCD) is poorly understood. While blood stasis is essential to tumescence, most research in SCD-associated priapism to date has focused on the potential role of abnormal signaling pathways. We have previously observed that a coding sequence single nucleotide polymorphism (rs5988) of the transglutaminase factor XIII gene (FXIII) is strongly associated with SCD priapism, with an odds ratio of 2.52 [C.I. 1.27 -5.03] for the risk genotype (G/G, expressing only FXIII E652) vs the most common non-risk genotype (G/C, expressing both FXIII E652 and FXIII Q652). We therefore explored the effect of the rs5988 polymorphism on various aspects of FXIII function.Methods: Recombinant FXIII (rFXIII) E652 and rFXIII Q652 were expressed by 293 kidney cells and isolated from serum-free tissue culture supernatant. Before use in assays, activation of rFXIII by thrombin was confirmed by generating activated rFXIII (rFXIIIa) with thrombin (10 U/ml), followed SDS-PAGE, western blotting for FXIII, and densitometry for quantitation. Whole blood samples and plasmas were obtained from previously genotyped subjects with SCD under an IRB-approved protocol. Plasma FXIII and rFXIII transglutaminase activity was measured by the ability to catalyze 5-(biotinamido)pentylamine incorporation into a suitable substrate. Plasma FXIII antigen was assayed by ELISA. Clot contraction was measured after tissue factor-initiated clotting of recalcified whole blood. Clot resistance to lysis was measured after exposure to tissue plasminogen activator (tPA).Results: Transglutaminase activity of each rFXIII was measured using fibrinogen and fibronectin as substrates. At 20 minutes, rFXIIIa E652 showed 1.44-fold more transglutaminase (crosslinking) activity toward fibrin(ogen) than rFXIIIa Q652 (p=0.027), and a nonsignificant trend toward more activity (1.32-fold, p=0.079) toward fibronectin. Kinetic assays also showed that rFXIII E652 had significantly greater activity toward both matrices (p=0.006 and 0.012, respectively), suggesting the risk genotype (homozygosity for the G allele) enhances fibrin(ogen) and/or fibronectin crosslinking. FXIII activity in the plasma of 18 genotyped SCD patients (3 CC, 7 GC, 8 GG) demonstrated a consistent, but not significant, trend toward increased FXIII activity with increasing presence of G alleles (80.01% CC, 98.90% CG, and 107.20% GG). Although results were not adjusted for genotype at other loci reported to affect FXIII expression, there was no significant difference in FXIII antigen among genotypes. Compared to contracted whole blood clots from patients with only one or no risk alleles, clots from SCD patients with two copies of the risk allele (GG, expressing only FXIII E652) did not differ in either RBC retention within clots or clot mass (weight). Moreover, inhibition of transglutaminase activity with T101 significantly increased RBC release and decreased clot weight to a similar degree in contracted clots from patients with either the GC or GG genotype. In clots formed from FXIII-deficient plasma supplemented with rFXIIIa E652 or rFXIIIa Q652 and ABO-compatible donor RBCs, clots containing rFXIIIa E652 were 14% more resistant to lysis than clots containing rFXIIIa Q652 (p=0.016). Parallel studies with SCD patient plasma samples also showed that clots containing only FXIII E652 were more resistant to lysis than clots containing both FXIII E652 and FXIII Q652(p=0.0001).Conclusions: These data suggest the FXIII rs5988 polymorphism does not alter protein expression or clot contraction but may regulate clot stability via slightly increased transglutaminase activity and enhanced resistance to lysis. These effects may predispose patients to formation of microclots during tumescence, thus impairing blood egress and increasing risk of priapism. Further studies should be conducted to determine if anticoagulation or fibrinolytic treatments are viable preventative or treatment strategies for SCD patients with the risk FXIIIGG genotype and recurrent priapism. DisclosuresTelen:Pfizer, Inc.: Consultancy, Research Funding. Wolberg:GlaxoSmithKline: Employment; Novo Nordisk: Research Funding.

Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator.

Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections.

Dual-Targeted Theranostic Delivery of miRs Arrests Abdominal Aortic Aneurysm Development.

Abdominal aortic aneurysm (AAA) is an often deadly disease without medical, non-invasive treatment options. The upregulation of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium provides an early target epitope for a novel biotechnological theranostic approach. MicroRNA-126 was used as a therapeutic agent, based on its capability to downregulate VCAM-1 expression in endothelial cells and thereby reduces leukocyte adhesion and exerts anti-inflammatory effects. Ultrasound microbubbles were chosen as carriers, allowing both molecular imaging as well as targeted therapy of AAA. Microbubbles were coupled with a VCAM-1-targeted single-chain antibody (scFvmVCAM-1) and a microRNA-126 mimic (M126) constituting theranostic microbubbles (TargMB-M126). TargMB-M126 downregulates VCAM-1 expression in vitro and in an in vivo acute inflammatory murine model. Most importantly, using TargMB-M126 and ultrasound-guided burst delivery of M126, the development of AAA in an angiotensin-II-induced mouse model can be prevented. Overall, we describe a unique biotechnological theranostic approach with the potential for early diagnosis and long-sought-after medical therapy of AAA.

Abstract WMP108: Defining Optimal Thresholds for Achieving Clinical Benefit in Spontaneous Intraventricular Hemorrhage

Introduction: Fibrinolytic therapy for spontaneous intraventricular hemorrhage (IVH) appears to reduce mortality with uncertain benefit on long-term functional outcomes. Threshold for volume of IVH which responds to intraventricular fibrinolytic therapy with therapeutic benefit has not been determined. Methods: CLEAR III, a randomized, multi-center, double-blinded, placebo-controlled trial was conducted to determine if pragmatically employed external ventricular drainage (EVD) plus intraventricular Alteplase improved outcome, in comparison to EVD plus saline. We analyzed of IVH volume strata from study randomization: Large IVH: volume ≥50 mL; small IVH: volume&lt;20 mL. We assessed clinical variables and outcomes by IVH volume group. Outcome measures were blinded assessment of modified Rankin score (mRS) at 30, 180 and 365 days, (with mRS&gt;3 signifying poor outcome). We performed logistic regression to evaluate outcomes by IVH volume group. Results: Among the 500 patients enrolled, 55 (11%) had IVH volumes &gt;50 mL and 222 (44.4%) had IVH volume &lt;20mL. Subjects with large volume IVH were older (mean, 62.3 vs. 58.1 years; p=0.01), had smaller ICH volume (6.1 vs. 9.9 mL; p&lt;0.001), less thalamic ICH (16.4% vs. 63.6%; p&lt;0.001), more pre-admission use of anticoagulants and antiplatelet agents and greater proportion of high intracranial pressure readings during monitoring at all thresholds (&gt;20, 30, 40 mmHg), compared to those with IVH volume &lt;50mL. Day 180 mortality and poor mRS were 49.1% and 81.8% in large volume IVH compared to 13.1% and 43.3% in small volume IVH. In logistic regression models adjusted for confounders, drainage of &gt;85% IVH volume was significantly associated with higher odds of good outcome (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3) and lower odds of mortality (OR, 0.3; 95% CI, 0.1-0.8) compared to &lt;85% drainage, in patients with baseline volumes &lt;50mL. Removal of &gt;85% IVH volume (n=3/55) was not associated with improved outcomes in patients with large IVH. Conclusions: IVH volume &gt;50mL may represent a cohort without identified benefit from fibrinolytic treatment. Defining an upper limit for IVH volume would benefit from a larger sample and other methods of achieving IVH reduction.

Regional QT Interval Dispersion as an Early Predictor of Reperfusion in Patients with Acute Myocardial Infarction after Fibrinolytic Therapy.

BackgroundPatients with ST-elevation acute myocardial infarction attending primary care centers, treated with pharmaco-invasive strategy, are submitted to coronary angiography within 2-24 hours of fibrinolytic treatment. In this context, the knowledge about biomarkers of reperfusion, such as 50% ST-segment resolution is crucial.ObjectiveTo evaluate the performance of QT interval dispersion in addition to other classical criteria, as an early marker of reperfusion after thrombolytic therapy.MethodsObservational study including 104 patients treated with tenecteplase (TNK), referred for a tertiary hospital. Electrocardiographic analysis consisted of measurements of the QT interval and QT dispersion in the 12 leads or in the ST-segment elevation area prior to and 60 minutes after TNK administration. All patients underwent angiography, with determination of TIMI flow and Blush grade in the culprit artery. P-values < 0.05 were considered statistically significant.ResultsWe found an increase in regional dispersion of the QT interval, corrected for heart rate (regional QTcD) 60 minutes after thrombolysis (p = 0.06) in anterior wall infarction in patients with TIMI flow 3 and Blush grade 3 [T3B3(+)]. When regional QTcD was added to the electrocardiographic criteria for reperfusion (i.e., > 50% ST-segment resolution), the area under the curve increased to 0.87 [(0.78-0.96). 95% IC. p < 0.001] in patients with coronary flow of T3B3(+). In patients with ST-segment resolution >50% and regional QTcD > 13 ms, we found a 93% sensitivity and 71% specificity for reperfusion in T3B3(+), and 6% of patients with successful reperfusion were reclassified.ConclusionOur data suggest that regional QTcD is a promising non-invasive instrument for detection of reperfusion in the culprit artery 60 minutes after thrombolysis.

Optical coherence tomography guided successful fibrinolytic treatment without the need for percutaneous coronary intervention in a patient with acute ST-segment elevation myocardial infarction.

Optical coherence tomography guided successful fibrinolytic treatment without the need for percutaneous coronary intervention in a patient with acute ST-segment elevation myocardial infarction.

Aspiration Thrombectomy for Treatment of Acute Massive and Submassive Pulmonary Embolism: Initial Single-Center Prospective Experience

PurposeTo evaluate the feasibility of aspiration thrombectomy in patients with acute massive or submassive pulmonary embolism (PE). Materials and MethodsThis prospective study analyzed patient demographic data, procedural details, and outcomes in 18 consecutive patients (8 men and 10 women; mean age, 60.1 y; range, 36–80 y), 10 with acute submassive PE and 8 with massive PE, treated with an Indigo Continuous Aspiration Mechanical Thrombectomy Catheter between January 2016 and February 2017. Three patients underwent concomitant systemic fibrinolytic treatment with 100 mg tissue plasminogen activator. Technical success was defined as successful placement of devices and initiation of aspiration thrombectomy. Clinical success was defined as stabilization of hemodynamic parameters; improvement in pulmonary hypertension, right heart strain, or both; and survival to hospital discharge. Complications were also analyzed. ResultsThe procedure was considered a technical success in 17 patients (94.4%) and a clinical success in 15 (83.3%). Echocardiography showed significant improvements in right ventricle size (46.36 mm ± 2.2 before treatment vs 41.79 mm ± 7.4 after; P = .041), tricuspid annular plane systolic excursion (16 ± 3 before treatment vs 18.57 ± 3.9 after; P = .011), and systolic wave (10 ± 2.1 before treatment vs 13.1 ± 3.8 after; P = .020). Two patients died of massive PE, and 1 died of submassive PE. Two patients who received systemic fibrinolytic agents experienced intracranial bleeding, and abdominal bleeding developed in 1. ConclusionsAspiration thrombectomy is a feasible option for the treatment of acute massive or submassive PE in patients with hemodynamic compromise or right ventricular dysfunction.

Fibrinolytic for treatment of intraventricular hemorrhage: A meta-analysis and systematic review.

Background Intraventricular hemorrhage is a significant cause of mortality and morbidity worldwide. Treating intraventricular hemorrhage with intraventricular fibrinolytic therapy via a catheter is becoming an increasingly utilized intervention. Aims This meta-analysis aimed to investigate the role of intraventricular fibrinolytic treatment in hypertensive intraventricular hemorrhage patients and evaluate the effect sizes for survival as well as level of function at differing time points. Summary of review PubMed, CNKI, VIP, and Wanfang were searched using the terms "IVH" and "IVH and ICH" for human studies with adult patients published between January 1950 and July 2016. Seventeen publications were selected. Data analysis showed lower rates of mortality in the treatment group at 30 days ( P < 0.001), 180 days ( P = 0.001), 365 days ( P = 0.40), and overall ( P < 0.001). Pooling modified Rankin Scale and Glasgow outcome scale data, the treatment group had more good functional outcomes at 30 days ( P = 0.38), 90 days ( P = 0.04), 180 days ( P = 0.31), 365 days ( P = 0.76), and overall ( P = 0.02). Good functional outcome was defined as modified Rankin Scale score of 0 to 3 or a Glasgow outcome scale score of 3 to 5. Conclusions Intraventricular fibrinolytic for treatment of hypertensive intraventricular hemorrhage reduces mortality and potentially leads to an increased number of good functional outcomes. Different functional outcome scales (modified Rankin Scale or Glasgow outcome scale) produce different effect sizes. Intraventricular fibrinolytic treatment may offer intraventricular hemorrhage patients a targeted therapy that produces meaningful mortality benefit and possible functional outcome benefits.

A real life registry to evaluate patient profile, diagnostic and practice patterns in Acute Coronary Syndrome in Turkey: TURK-AKS study

Background and objectiveEvaluation of patient characteristics and the patterns of diagnostic therapeutic practices of acute coronary syndromes (ACS) in Turkey. MethodsA total of 3695 ACS patients (mean age: 60±12years, 73% males) were included in this prospective, multicenter, non-interventional registry. ResultsST-segment elevation and non-ST segment elevation myocardial infarction (NSTEMI) were identified in 57% and 43% of patients, respectively. In 65% of cases admission was directly to the index hospital. Ambulance transport was higher in rural sites comparing to urban areas (53.4 vs. 38.4%, p<0.001).Admission to a hospital within the first 2h of symptom onset was 42% while after 12h was 24%. Spontaneous anginal relief (44%) was the leading cause of late hospital admission. Fibrinolytic treatment was administered in 23% of the patients. The most common in-hospital interventions were coronary angiography for NSTEMI (18%), primary percutaneous transluminal coronary angioplasty for STEMI (17.5%) and coronary angiography after lytic therapy (12.1%). ConclusionsIn a representative sampling for Turkish population five years ago, this registry of ACS revealed the predominancy of male gender, urban settlement, and presentation with STEMI. The delay between onset of symptoms and hospital admission was more prominent in rural sites, among females and in NSTEMI patients when compared to urban areas, males and STEMI patients.