Dose Of ASA Research Articles

Visible light assisted photooxidative facile degradation of azo dyes in water using a green method.

In this study, the methyl orange (MO) dye has been degraded after screening several azo dyes due to its effective results and being toxic and carcinogenic to aquatic life and humans. An environmentally friendly, economical, and green method for water purification was used in this study using the photooxidative method. Several organic acids were screened for oxidative applications against various azo dyes but due to better results, methyl orange was selected for the whole study. Ascorbic acid, also known as vitamin C, was found to be best for photodegradation due to its high oxidative activity among various organic acids utilized. A newly developed photoreactor box has been used to conduct the photooxidation process. To evaluate the degradation efficiency of AsA, photooxidative activity was monitored periodically. When the dose of AsA was used at a contact time of 180 minutes, degradation efficiency was 96%. The analysis of degraded products was performed using HPLC and GC-MS. The nucleophilicity of HOMO-LUMO and MEPs was confirmed using density functional theory. For the optimization of the process, central composite design (CCD) in Response Surface Methodology (RSM) was utilized.

Analysis of Platelet Function Testing in Children Receiving Aspirin for Antiplatelet Effects.

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children.

Novel Dosing and Monitoring of Aspirin in Infants With Systemic-to-Pulmonary Artery Shunt Physiology: the SOPRANO Study.

Provision of pulmonary blood flow with a systemic-to-pulmonary artery shunt is essential in some patients with cyanotic congenital heart disease. Traditionally, aspirin (ASA) has been used to prevent thrombosis. We evaluated ASA dosing with 2 separate antiplatelet monitoring tests for accuracy and reliability. This is a retrospective, pre-post intervention single center study. Two cohorts were evaluated; the pre-intervention group used thromboelastography platelet mapping (TPM) and post-intervention used VerifyNow aspirin reactivity unit (ARU) monitoring. The primary endpoint was to compare therapeutic effect of TPM and ARU with regard to platelet inhibition. Inadequate platelet inhibition was defined as TPM <50% inhibition and ARU >550. Data from 49 patients were analyzed: 25 in the TPM group and 24 in the ARU group. Baseline characteristics were similar amongst the cohorts. The TPM group had significantly more patients with inadequate platelet inhibition (14 [56%] vs 2 [8%]; p = 0.0006) and required escalation with additional thromboprophylaxis (15 [60%] vs 5 [21%]). There was no difference in shunt thrombosis (1 [2%] vs 0 [0%]; p = 0.32), cyanosis requiring early re-intervention (9 [36%] vs 14 [58%]; p = 0.11), or bleeding (15 [60%] vs 14 [58%]; p = 0.66). With similar cohorts and the same ASA-dosing nomogram, ARU monitoring resulted in a reduced need for escalation of care and concomitant thromboprophylaxis with no difference in adverse outcomes. Our study suggests ARU monitoring compared with TPM may be a more reliable therapeutic platelet inhibition test for determining ASA sensitivity in children with congenital heart disease requiring systemic-to-pulmonary artery shunt.

Comparison of the effectiveness and safety of 2 aspirin doses in secondary prevention of cardiovascular outcomes in patients with chronic kidney disease: A subgroup analysis of ADAPTABLE

Among patients with established cardiovascular disease, the ADAPTABLE trial found no significant differences in cardiovascular events and bleeding rates between 81 mg and 325 mg of aspirin (ASA) daily. In this secondary analysis from the ADAPTABLE trial, we studied the effectiveness and safety of ASA dosing in patients with a history of chronic kidney disease (CKD). ADAPTABLE participants were stratified based on the presence or absence of CKD, defined using ICD-9/10-CM codes. Within the CKD group, we compared outcomes between patients taking ASA 81 mg and 325 mg. The primary effectiveness outcome was defined as a composite of all cause death, myocardial infarction, or stroke and the primary safety outcome was hospitalization for major bleeding. Adjusted Cox proportional hazard models were utilized to report differences between the groups. After excluding 414 (2.7%) patients due to missing medical history, a total of 14,662 patients were included from the ADAPTABLE cohort, of whom 2,648 (18%) patients had CKD. Patients with CKD were older (median age 69.4 vs 67.1 years; P < .0001) and less likely to be white (71.5% vs 81.7%; P < .0001) when compared to those without CKD. At a median follow-up of 26.2 months, CKD was associated with an increased risk of both the primary effectiveness outcome (adjusted HR 1.79 [1.57, 2.05] P < .001 and the primary safety outcome (adjusted HR 4.64 (2.98, 7.21), P < .001 and P < .05, respectively) regardless of ASA dose. There was no significant difference in effectiveness (adjusted HR 1.01 95% CI 0.82, 1.23; P=.95) or safety (adjusted HR 0.93; 95% CI 0.52, 1.64; P=.79) between ASA groups. Patients with CKD were more likely than those without CKD to have adverse cardiovascular events or death and were also more likely to have major bleeding requiring hospitalization. However, there was no association between ASA dose and study outcomes among these patients with CKD.

相対的適応で実施した血液透析で致死量摂取のアスピリン中毒を治療した1例(A case of successful treatment with hemodialysis after ingestion of a lethal dose of aspirin)

服毒自殺目的に大量摂取されたアスピリン［アセチルサリチル酸（acetylsalicylic acid: ASA）］が通常の半減期を大幅に延長していたが，血液透析により著明な症状改善を得た1例を経験したため，若干の考察とともに報告する。症例は20歳の男性，2日間にわたりASAを過量摂取（各13.2g，26.4g）し，発熱などを主訴に2回目の摂取から約8時間経過して救急外来を受診した。来院時は頻呼吸・頻脈・耳鳴症状を認め，活性炭投与，大量補液，アルカリ化利尿などの保存的治療を行ったが，症状改善に乏しく，難聴の出現，呼吸性アルカローシスと凝固機能の悪化を認めたためsalicylic acid（SA）の除去目的に血液透析を行った。初回および再検査の血中SA濃度から半減期が20.3時間と過延長していたが，2回の血液透析により，自覚症状の改善と採血結果の改善を認め，第7病日に聴力検査したところ感音難聴は改善した。中毒学的には2回目のみで考えても致死的の517mg/kgを摂取，予測最高血中濃度は1,045μg/mLと重症例であったが，血液透析により速やかな血中濃度減少を認め，有効な治療であったと考えられる。 We report a case of attempted suicide by aspirin (acetylsalicylic acid: ASA) poisoning that was markedly improved by hemodialysis. After ingesting a large dose of ASA on two days (13.2g and 26.4g, respectively), a 20–year–old man came to the emergency department on his own about 8 hours after the second intake. His chief complaint was fever, but tachypnea, tachycardia, and tinnitus were also observed at admission. Conservative treatments such as administration of activated charcoal, supplemental fluids, and alkaline diuresis were performed, but his symptoms did not improve. There was hearing loss and deteriorated coagulation function deteriorated, the patient underwent hemodialysis to remove salicylic acid (SA). The initial and subsequent blood SA concentration showed that the half–life of SA was increased to 20.3 hours; however, two hemodialysis sessions improved subjective symptoms and blood sample results, and a hearing test on the seventh day showed improvement in sensorineural hearing loss. Although the patient was severely poisoned and had a calculated maximum blood concentration of SA of 1,045μg/mL, hemodialysis effectively decreased the concentration of SA in blood. アスピリンは代表的な非ステロイド性消炎薬（NSAIDs）として処方箋なしで手に入る解熱・鎮痛剤であるとともに，抗血小板作用により虚血性心疾患や虚血性脳血管疾患の再発予防薬として有効 1であるため，広く利用されている薬剤である。その結果，自殺目的にしばしば大量服用されることがあるが，乳幼児の誤食や湿布薬と内服薬の併用などによる中毒報告もある 2, 3（Table 1）。 この論文は患者本人の同意を得て作成しており，個人情報保護法に基づいた匿名化がなされている。また，倫理委員会の承諾が必要ない発表である。 患 者：20歳の男性，体重51kg 主 訴：発熱，耳鳴，嘔気 既往・併存症・家族歴：特記事項なし 病 歴：自殺目的に2日間にわたり2回にわけてバファリンA®（ASA）を過量服薬（各40錠，80錠。330mg/錠）。2回目の内服後約8時間経過したところで発熱と嘔気，耳鳴を主訴に救急外来を独歩で受診した。 来院時の身体所見は意識清明，心拍数92bpm，血圧112/56mmHg，呼吸数28/分，SpO2 98%（室内気），体温37.0℃，発汗著明であった。呼吸音や心音に明らかな異常を認めなかった。 血液検査結果では軽度の凝固機能障害（PT–INR 1.55，APTT 32.7秒）を認めたものの，肝腎機能障害を認めず（AST 31，ALT 34，BUN 17.8，Cre 0.94)，CT検査で胃内容物を認めなかったため胃洗浄は行わなかった。通常の半減期であれば症状軽快傾向に向かうと判断し，保存的治療として大量補液，炭酸水素ナトリウム投与，経鼻胃管から活性炭，クエン酸マグネシウムを投与した。来院後6時間後の採血でPT–INR 2.88，APTT 61.7秒と凝固系の異常延長と呼吸性アルカローシスの悪化を認め（Table 2），難聴症状が明らかとなり，中毒が進行していると考え積極的な治療介入が必要と判断した。初回血液透析を施行（4時間，中空糸管であるPMMA（NF）膜2.1m2，血液流量150mL/min，抗凝固薬ナファモスタット）し，自覚症状として耳鳴は消失するも難聴症状が残存しており，聴力検査でも両側感音難聴を呈していたため翌日にも血液透析を前回と同条件で4時間施行した。第3病日の採血では凝固能を含め，明らかな異常値を呈することなく，精神状態も安定しており，希死念慮がないことを確認して退院した。第7病日に外来で聴力検査を再検査し，難聴が改善していることを確認できた（Fig. 1）。後に血中SA濃度結果が出たところで半減期が常用量では2～3時間であるのに対し，本症例では20.3時間と過延長していたことがわかった（Fig. 2, 3）。 Hearing test. 左：初回血液透析後，右：退院後（第7病日） Changes in blood SA consentration. 来院時と初回透析前の2値からFig. 3を用いて半減期を推定。その半減期を基に2回目の内服後4時間後を血中濃度のピークと仮定し，ピーク値を推定。また，初回透析後，2回目透析前からの予想半減期曲線を描いた。初回透析後にほぼ中毒レベル以下になったが半減期は初期と変わらずに延長したままである。 Half–life calculation. ASAは化学式C9H8O4，分子量180.16g/molである。主に胃・十二指腸から吸収されて肝臓でサリチル酸（salicylic acid: SA）に加水分解される 3, 4。SAは全身の組織および体液中に広く分布し，中枢神経系や母乳，胎児組織にも分布する 4, 5。タンパク結合率は血中濃度依存性を示し，低濃度域（<100μg/mL）では約90%であるのに対し，高濃度域（>400μg/mL）では約75～30%と低下する 5, 6。主に尿から排泄（80～100%）され，半減期は低用量のときは2～3時間である 3が，高容量のときは胃石を生ずることがあり持続的に吸収される 3, 4ことによったり，血中濃度の上昇に伴い代謝能が飽和し，全身クリアランスが低下したりすることで15～30時間に延長することもある 5。本症例では胃石を認めなかったが，半減期は約20時間と延長しており血中濃度上昇によりクリアランスが低下していたものと考えられる。主な中毒症状は初期症状として耳鳴，めまい，頭痛，嘔吐，難聴，軽度の頻呼吸など 3があり，血中濃度の上昇に伴い過度の過呼吸，呼吸性アルカローシス，代謝性アシドーシス，けいれん，昏睡，呼吸不全などが認められ，とくに過換気，耳鳴，嘔吐は古典的三徴とされる（Fig. 4）。処置は催吐，胃洗浄，活性炭投与，大量輸液，アシドーシス是正，重炭酸ナトリウム投与によるアルカリ化利尿，血液透析を必要に応じて行う。 Relationship between blood SA concentration and side effects/poisoning symptom. 中毒量は摂取量が150mg/kgを超えると耳鳴などの軽度の中毒症状が出現し，240mg/kgを超えると重篤となり，致死量は500mg/kgと言われている 5, 7。本症例では2日目の26.4g摂取だけで考えても517mg/kgであり致死量の摂取があったと考えられる。血中濃度の観点からみると，中毒症状はSA濃度に依存している 8とされ，200μg/mL以上で初期症状である耳鳴が出現し，270μg/mL以上で延髄の化学受容体が刺激され，悪心，嘔吐，さらに高濃度では過換気から呼吸性アルカローシスやテタニー様のけいれんを認めたりする。500～700μg/mLを超える中毒量では酸素消費と代謝速度が増すことで発熱や脱水，電解質異常などで循環不全や意識障害が出現し，最終的に腎不全に至ることもある 9。750μg/mL以上では中枢神経症状，脳浮腫，非心原生肺水腫などのリスクもある。血液透析の適応として絶対適応は900μg/mL以上 3，相対的適応は難治性アシドーシスや重篤な中枢神経症状，臨床症状の悪化などとされている 4。終了については190μg/mL以下まで継続することが望ましい 10とあり，これは蝸牛症状（難聴・耳鳴・めまい）の出現濃度にほぼ一致する。本症例では血中濃度で絶対的適応となるが，後日報告であったため来院直後の透析適応の判断はできなかったが，呼吸性アルカローシスや難聴症状，凝固機能の増悪を臨床症状の悪化と判断し，相対的適応として血液透析を施行した。 透析性については一般的に分子量が3,000以下，水との親和性が大きい，タンパク結合能が小さい，分布容積が小さいものは透析が有効とされている 11。ASA，SAについては分子量［180.16（ASA），138.12（SA）］，水溶性，分布容積が小さいため有効である。血漿タンパク結合能は治療量では80～90%と高値であるが，中毒量以上ではほとんどが遊離状態にあるため透析性は高いとされている 3。本症例では来院時852μg/mLと血液透析前606μg/mLの2値点から半減期は約20.3hrと考えられる。これを基に予測および実測血中SA濃度推移のグラフをFig. 2に示す。初回および2回目の血液透析終了時の実測値と予測血中濃度により血液透析が有効な治療法であることがわかる。また，初回血液透析後の血中濃度が211μg/mLと低値になっているにも関わらず翌日の血液透析まで半減期は変わらず約20時間で経過している。これは本症例での代謝能力が思った以上に低いことを示唆している。 SAにはビタミンK依存性凝固因子活性が抑制されることでPT時間の延長を来すこともわかっている。容量依存的にSAがビタミンKの代謝において間接的にビタミンKエポキシド還元を阻害し，還元型ビタミンKが産生できず凝固因子の合成ができないためである 12。さらに，ビタミンK依存性凝固因子は遅発性に障害される可能性がLoewらにより報告されており 13，本症例の経過にも一致する。このため，PT時間は経過観察が肝要であり，延長傾向がみられた際にはビタミンKの投与が望ましい。本症例においてはPT時間の延長理由を治療段階では判断できなかったものの，経過からSA中毒による所見と判断し，血液透析を行うことによりSA濃度を低下させることでPT時間の改善を認めた。 SAによる難聴は可逆性薬剤性難聴であり，両側に水平型の感音難聴を呈する 14。過量服薬だけでなく，各種疾患に対しての処方薬に加え湿布薬や市販の感冒薬の屯用などによる意図しない複合摂取や常用摂取だけでも難聴症状が出現することがある 3。ASAは蝸牛神経線維や有毛細胞に作用するという報告 15があり，蝸牛神経や有毛細胞の興奮性を低下させることで症状が出現しているものと考えられている 16, 17。また，難聴の程度はSA濃度に正の相関を示し 4, 18，150～200μg/mLになると難聴症状が出現し，400μg/mLまでは濃度依存的に増悪するが，それ以上になると難聴症状は進行しないとされている 19。本症例では初回血液透析後（211μg/mL）では自覚症状の改善を認めるものの症状残存，翌朝（125μg/mL）には自覚難聴症状ほぼ消失という臨床経過であった。聴力検査は血液透析後のものであるが，両側で気導・骨導とも低下しており感音難聴を呈していたが，退院後の第7病日に再検査したところ難聴所見は改善していた（Fig. 1）。 アスピリン（アセチルサリチル酸）を致死量内服し，遅発性凝固機能障害と薬剤性感音難聴を来した1例に対し血液透析を行い，救命と速やかな症状改善を認めた。本症例では摂取後から約8時間経過して来院しており，通常の半減期で考えれば血中濃度は低下し，快方に向かうと考えられたため内科的に治療を試みたが，入院後に難聴症状が明らかとなり，採血検査結果で呼吸性アルカローシスや遅発性の凝固機能異常の増悪を来したために臨床症状の悪化と判断し，相対的適応と判断して血液透析を施行するに至った。 大量摂取で摂取後数時間は徴候や症状が軽いかほとんどないこともあるが，有症状時は中毒濃度にあることから代謝が律速となり半減期は過延長している可能性が高く，代謝量＜吸収量の場合，血中濃度が上昇し，症状が悪化する。そのため，血液透析治療開始の閾値を下げて薬物を速やかに除去することにより重篤な毒性作用を回避することができるかもしれない。本症例においても脳出血などの重篤な出血合併症を来すことなく救命し得た。また，凝固機能の経過観察も必要で，増悪時にはビタミンKの投与や血液透析により速やかな改善が期待できると考える。最後に，本症例はこまめに血中濃度測定を実施することで，血液透析の実際の効果を知ることができた貴重な症例である。 本論文の投稿にあたり，開示すべきCOIはない。

Acetylsalicylic acid in primary and secondary prevention of atherosclerotic cardiovascular disease

The article is devoted to an urgent problem - primary and secondary prevention of atherosclerotic cardiovascular diseases. Modern approaches to management tactics depending on age and the appointment of antiplatelet therapy with acetylsalicylic acid in low doses from 75 to 150 mg/day are presented. At the same time, the relatively high effectiveness of the use of ASA for primary prevention in men 40-69 years old without an increased risk of bleeding from the gastrointestinal tract is shown. Low doses of ASA provide little benefit in reducing the risk of CVD in people 40 years and older, when there is no history of CVD, but at the same time they are at increased risk of CVD.

Abstract 14286: Comparison of Enteric Coated Aspirin With Plain Aspirin on Effectiveness and Safety in the ADAPTABLE Trial

Introduction: Many clinicians recommend enteric coated aspirin (EC-ASA) to decrease gastrointestinal bleeding (GIB) in secondary cardiovascular (CV) protection even though studies suggest decreased platelet inhibition with EC-ASA compared to uncoated “plain” formulations (P-ASA). ADAPTABLE was a large, pragmatic study, showing no difference in ischemic events or bleeding between 81-mg and 325-mg ASA and provides a large population to assess effectiveness and safety of EC-ASA versus P-ASA in CV patients. Methods: Participants (pts) from ADAPTABLE were re-grouped according to type and dose of reported ASA use at baseline. The primary effectiveness endpoint was the composite of myocardial infarction (MI), stroke, or death from any cause and the primary safety endpoint was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage) analyzed between groups by ASA type and within groups by dose using multivariable Cox proportional hazards. Results: 15,076 pts were randomized to 81-mg or 325 -mg ASA were followed for a median of 26.2 months of whom 10,678 reported ASA type at baseline. Of pts reporting ASA type used, 69% used EC-ASA and were slightly older, more likely to be in the 81-mg cohort, be nonsmokers, have slightly more coronary artery disease, and have a slightly lower prior MI rate (Table). No other significant differences between the 2 cohorts were noted. There was no significant difference in the effectiveness or safety outcomes between the EC-ASA and P-ASA cohorts (Table). Within EC-ASA and P-ASA, ASA dose had no effect on effectiveness (interaction p = 0.41) or safety (interaction p = 0.07). Conclusion: Enteric coating did not significantly affect the primary effectiveness or safety endpoints in ADAPTABLE, regardless of ASA dose. More research is needed to confirm whether enteric coated aspirin formulations or newer formulations will improve ischemic and bleeding outcomes in patients with CV disease.

Experimental study of the antiulcer effect of cryopreserved placenta extract on a model of acetylsalicylic acid-induced ulcerogenesis

Abstract Introduction. The gastrotoxicity of nonsteroidal anti-inflammatory drugs is a leading side effect that significantly limits their clinical use, among other types of their toxicity (nephrotoxicity, hepatotoxicity, cardiotoxicity, etc.). Cryopreserved placenta extract has drawn our attention as a potential modifier of the ulcerogenic action of nonsteroidal anti-inflammatory drugs. Aim. To characterize the cytoprotective properties of cryopreserved placenta extract by the condition of the mucous membrane of the proximal (esophagus and stomach) and distal (small and large intestine) parts of the gastrointestinal (GI) tract on the model of ASA-induced ulcerogenesis. Material and methods. The study was performed using 28 male rats weighing 200-220 g. Subchronic ASA-induced ulcerogenesis of the digestive tract was reproduced by intragastrically administration to rats of ASA in a dose of 150 mg/kg. The effect of the studied drugs on the condition of the mucous membrane of the digestive tract was assessed macroscopically by the following criteria: edema, redness and hemorrhage on the surface of the mucous membrane. The ulcer index for each group of animals was calculated. Results and discussion. Five doses of ASA 150 mg/kg cause damage to the esophagus, stomach, small and large intestines in all of the rats. The use of the proton pump inhibitor esomeprazole has pronounced gastrocytoprotective properties, but does not affect the ulcerogenic effect in the small intestine, and in the colon, it enhances it. This is indicated by ulcerative lesions of the colon in 57.1% of all rats administered ASA and esomeprazole, as well as in the folding of the gastric mucosa. In contrast, mild hyperemia of the gastric mucosa was seen in 28.6% of all rats and moderate hemorrhage in 57.1% of all rats due to the combined use of ASA and cryoextract placenta. Conclusions. The use of cryopreserved placenta extract is statistically significantly (p &lt;0.05) inferior to the antiulcer activity of esomeprazole in the stomach. Thus, the ulcer index on the background of the use of ASA and cryopreserved placenta extract was 0.97, and on the background of the use of ASA and esomeprazole – 0.39. In the distal parts of the GI tract cryoextract placenta showed cytoprotective properties against the background of induced ASA ulcerogenesis, in contrast to esomeprazole.

Analysis of Platelet Function Testing in Children Receiving Aspirin for Antiplatelet Effects

<h3>Purpose</h3> VerifyNow Aspirin assay (VN) assesses platelet response to ASA, with therapeutic effect defined as ≤ 549 aspirin reaction units (ARU). We aim to evaluate its clinical efficacy in children of all ages, by identifying biochemical resistance (> 549 ARU) and association with clinical thrombosis or bleeding. <h3>Methods</h3> Single-center, observational, analysis of 195 children (< 21 yo) who underwent first VN between 2015-2020 after receiving ≥ 1 enteral ASA dose. Primary outcome was proportion of these patients with ASA biochemical resistance. Secondary outcomes included incidence of new clinical thrombotic and bleeding events in 113 patients receiving ASA monotherapy for ≤ 1 year from VN. Patients receiving concomitant anticoagulation (n=61), dual antiplatelet therapy (n=7), had no follow-up (n=8), or had ASA held (n=6) were excluded from secondary outcome analysis. <h3>Results</h3> Of 195 patients, 56% were male and 53% were Caucasian. At time of VN, median age was 1.8 yrs (IQR 0.08 - 11.9), weight 10 kg (3.5 - 39.1), and BSA 0.47 m² (0.23 - 1.25). Indications for ASA included single ventricle with shunt (36.4%), ischemic stroke (22.6%), Glenn/Fontan (9.7%), vascular disease (7.2%), valvular heart disease (6.7%), VAD (6.2%), coronary disease (2%), RV-PA conduit (3.1%), intracardiac thrombus (2%), ventricular dysfunction (1.5%), and other (2.6%). Median ASA dose before VN was 4.6 (2.6 - 5.8) mg/kg/day; 36% received 1 and 64% ≥ 2 doses. Mean VN was 471 ARU (±66). 14.4% (n=28) had VN > 549 ARU. There were no significant differences in age, weight, BSA, ASA dose, platelet count, hemoglobin, or hematocrit between patients with VN ≤ 549 vs > 549 ARU. Of 113 patients receiving ASA only, mean VN was 471 (±69). Over a median of 252 days (89 - 365), 14 (12.4%) had a thrombotic event after 9 days (3.5-118) and 9 (8%) had a bleeding event after 80 days (25-150) from VN. Mean VN was significantly higher at initial testing in thrombotic (516 ARU, p=0.03) but not bleeding groups (472 ARU, p=0.97). 20% of patients in thrombotic and 33% in bleeding groups had repeat VN performed, with results not significantly different from the group as a whole (482 ARU, p=0.45, and 461 ARU, p=0.39, respectively). <h3>Conclusion</h3> VN platelet function testing identifies biochemical resistance in 14.4% of children. Higher ARU at initial testing may be associated with thrombosis; in contrast, there was no association between ARU and bleeding.

Protective Value of Aspirin Loading Dose on Left Ventricular Remodeling After ST-Elevation Myocardial Infarction.

AimsLeft ventricular (LV) remodeling after ST-elevation myocardial infarction (STEMI) is a complex process, defined as changes of LV volumes over time. CMR feature tracking analysis (CMR-FT) offers an accurate quantitative assessment of LV wall deformation and myocardial contractile function. This study aimed to evaluate the role of myocardial strain parameters in predicting LV remodeling and to investigate the effect of Aspirin (ASA) dose before primary coronary angioplasty (pPCI) on myocardial injury and early LV remodeling.Methods and ResultsSeventy-eight patients undergoing CMR, within 9 days from symptom onset and after 6 months, were enrolled in this cohort retrospective study. We divided the study population into three groups based on a revised Bullock's classification and we evaluated the role of baseline CMR features in predicting early LV remodeling. Regarding CMR strain analysis, worse global circumferential and longitudinal strain (GCS and GLS) values were associated with adverse LV remodeling. Patients were also divided based on pre-pPCI ASA dosage. Significant differences were detected in patients receiving ASA 500 mg dose before pPCI, which showed lower infarct size extent and better strain values compared to those treated with ASA 250 mg. The stepwise multivariate logistic regression analysis, adjusted for covariates, indicated that a 500 mg ASA dose remained an inverse independent predictor of early adverse LV remodeling.ConclusionGCS and GLS have high specificity to detect early LV adverse remodeling. We first reported a protective effect of ASA loading dose of 500 mg before pPCI on LV myocardial damage and in reducing early LV adverse remodeling.

Dual antiplatelet therapy improves functional recovery and inhibits inflammation after cerebral ischemia/reperfusion injury

BackgroundDual antiplatelet therapy with aspirin and clopidogrel (ASA + CPG) during the first 21 days has been shown to reduce the risk of major ischemic events in patients with transient ischemic attack (TIA) or minor stroke. However, the mechanisms underlying combination treatment with ASA + CPG in experimental ischemic stroke has not been fully elucidated.MethodsMinor cerebral ischemia was induced in mice by transient distal middle cerebral artery occlusion (tdMCAO). Two doses of ASA + CPG (12 and 24 mg/kg/day) or vehicle were administered by gavage daily. Neurological behaviors were assessed using the modified Garcia scores, Rotarod test, Y maze, and open field test. Platelet function was assessed in vitro by flow cytometry and in vivo by bleeding and clotting time. The neutrophil ratio and the levels of inflammatory cytokines were measured by flow cytometry and the Meso Scale Discovery (MSD) electrochemilunimescence, respectively.ResultsSensorimotor function was partially recovered with ASA + CPG treatment after ischemia. Anxiety levels and cognitive functions showed improvement in the ASA + CPG group at 12 mg/kg/day after 21 days. Both tail bleeding time and flow cytometry showed significantly decreased platelet function after ASA + CPG treatment. Notably, ASA + CPG at 12 mg/kg/day prolonged clotting time at 28 days after injury. Furthermore, the ratio of neutrophils, an indicator of inflammation, was reduced with 12 mg/kg/day ASA + CPG treatment in the bone marrow (BM) at 21 days and in the peripheral blood (PB) at 21 and 28 days after tdMCAO. Both doses of ASA + CPG decreased pro-inflammatory cytokine interleukin (IL)-6 expression 21 days after stroke. Taken together, these results demonstrated that combination treatment with ASA + CPG improved long-term neurological function after stroke and may inhibit platelet-neutrophil interaction by decreasing the concentration of pro-inflammatory cytokine, IL-6.ConclusionsThese findings indicate a neuroprotective effect of combination treatment with ASA + CPG for a duration of 21 days in an experimental acute minor stroke model. These findings provide further evidence that dual antiplatelet therapy may be a viable neuroprotective treatment to decrease the recurrence of stroke.

Abstract WP56: 2021 Comparison Of International Stroke Guidelines For Acute Ischemic Stroke

Background: Many countries/regions have formal Acute Ischemic Stroke (AIS) management guidelines. Variations between guidelines may showcase differences in demographic epidemiology and practice that correspond to the regional or national priorities. Methods: We systemically searched for guideline recommendations on AIS management published between January 1, 2004, and August 20, 2021. With only the latest guideline for each country selected, 11 guidelines from countries/regions of the world were identified and reviewed: United States (2018), Japan (2013), Europe (2018), Australia (2012), Brazil (2012), China (2019), Korea (2019), Canada (2018), India (2011), South Africa (2010), and Malaysia (2006). Results: Urgent imaging guidelines, such as CT or MRI, for initial evaluation are similar across countries; nevertheless, initial intravascular imaging guidelines greatly differ. Of the eleven countries reviewed, the majority recommend a standard tPA dose of 0.9mg/kg, while Japan and China recommend a lower tPA dose of 0.6mg/kg in select patients. While time to initiation of aspirin (ASA) post IV thrombolysis is widely accepted, consensus on the appropriate ASA dose, and possible addition of other antiplatelet therapies does not exist. Mechanical thrombectomy is overall endorsed within 6 hours or between 6-16 hours of symptom onset with causative occlusion, but countries such China and Canada have found validity extending the timeframe to 24hrs and beyond, using imaging modality recommendations. Inpatient management of nutrition, DVT prophylaxis, and rehabilitation differ between the various guidelines. Conclusion: Variations between guidelines exist that highlights those components with a lack of an evidence-based consensus. With further international collaboration, reconciliation of guidelines between countries or regions may be achievable.

Acetylsalicylic acid-induced alterations in male reproductive parameters in Wistar rats and the effect of sprint interval training.

The present study investigated the effect of a 5-week ASA treatment on male reproductive parameters in Wistar rats; moreover, the potential benefits of a 4-week sprint interval training (SIT) on these measures following ASA treatment were investigated. A total of 25 male rats were obtained and randomly assigned to the control group (C, n=10) and the ASA treatment group (EP, n=15). After 5weeks, five rats from each group were killed and the effect of ASA treatment on the reproductive parameters was assessed. Then, the ASA treatment terminated and the remaining 10 ASA-treated rats were divided into the non-treatment group (NT, n=5) and the exercise training group (ET, n=5), which performed SIT 3 sessions/week for 4weeks. Five weeks of ASA treatment resulted in a statistically significant decrease in serum testosterone level, Leydig cell number, sperm count, sperm motility, sperm viability, TDI, SI and RI, and it resulted in a significant increase in sperm nucleus maturity and sperm DNA fragmentation (p˂0.05). Furthermore, 4weeks of SIT reversed all the ASA-induced changes in male reproductive parameters (p<0.05), but not the number of seminiferous tubules and the sperm motility (p>0.05). A subchronic dose of ASA could lead to adverse alterations in male reproductive parameters and SIT is beneficial in reversing those alterations.

Aspirin and omega-3 polyunsaturated fatty acid use and their interaction in cardiovascular diseases and colorectal adenomas.

Aspirin (acetylsalicylic acid, ASA) is inexpensive and is established in preventing cardiovascular disease (CVD) and colorectal adenomas. Omega-3 (n3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have also shown benefit in preventing CVD. The combination could be an effective preventative measure in patients with such diseases. ASA and n3 PUFA reduced the risk of CVD in ASA-resistant or diabetic patients. EPA- and DHA-deficient patients also benefited the most from n3 PUFA supplementation. Synergistic effects between ASA and EPA and DHA are 'V-shaped' such that optimal ASA efficacy is dependent on EPA and DHA concentrations in blood. In colorectal adenomas, ASA (300 mg/d) and EPA reduced adenoma burden in a location- and subtype-specific manner. Low doses of ASA (75-100 mg/d) were used in CVD prevention; however, ultra-low doses (30 mg/d) can also reduce thrombosis. EPA-to-DHA ratio is also important with regard to efficacy. DHA is more effective in reducing blood pressure and modulating systemic inflammation; however, high-dose EPA can lower CVD events in high-risk individuals. Although current literature has yet to examine ASA and DHA in preventing CVD, such combination warrants further investigation. To increase adherence to ASA and n3 PUFA supplementation, combination dosage form may be required to improve outcomes.

Preparation and Evaluation of Extemporaneously Compounded Aspirin Capsules from Crushed Aspirin Tablets

Aims: Extemporaneous preparations of medications might bring about technical and clinical consequences due to formulation failures. Therefore, all such prepared formulas should undergo valid and reliable procedures supported by solid data. Otherwise, patients can experience significant risk due to microbial contamination or physical or chemical changes during the preparation process. Thus, effective extemporaneous preparation relies on correct calculations to avoid extra and serious harm. Therefore, because 50-mg aspirin capsules are not available in Saudi Arabia, this study aimed to formulate 50-mg capsules from available 100-mg aspirin tablets.&#x0D; Methodology: Quality control tests of the preparations were carried out at the time of preparation and after one month of storage at 25 °C and at 40 °C and 75% relative humidity. All tests were carried out according to the British and United States pharmacopeia monograph of aspirin.&#x0D; Results: The drug content assay and uniformity test indicated that the aspirin capsules were within the pharmacopeial limits. The disintegration time for all aspirin capsules was within the pharmacopeial limits of 30 minutes. The aspirin release profile showed that approximately 90% of the aspirin dissolved after 10 minutes.&#x0D; Conclusion: The results indicated that the extemporaneous preparation of ASA capsules complied with the quality control tests for freshly prepared capsules and after one month of storage at room temperature and at 40 °C and 75% relative humidity. The dissolution profile of these capsules indicates immediate and high release of ASA, which is essential to ensure the required absorption. This study is of great importance for patients who need to take this dose of ASA. Pharmacists can prepare good-quality capsules with the desired ASA content using a 100-mg ASA tablet as a source of the active ingredient.

A Less Than 81mg of Aspirin in Heart Mate 3 is Safe Irrespective of Amount of Platelet Inhibition

Purpose Optimal dose of aspirin for Heartmate 3 (HM 3) LVAD patients is still not known. Recently low dose aspirin (81mg compared to 325mg) has shown to be efficacious. Randomized control trial with no dose aspirin is underway. However, platelet inhibition can be still achieved with less than low dose aspirin. So we looked into safety and efficacy of a very low dose aspirin ( Methods We did retrospective analysis of HM3 patients implanted in our institution (2015- 2020). Patients who were on less than 81mg of aspirin/day were identified. Thromboelastogram (TEG) was used to assess response to aspirin. We compared the number of thromboembolic events, bleeding events, LDH, and hematocrit before and after the dose change, with the patients being their own controls, using paired t test. Results In our program, we follow 35 patients on HM3. Most of them 24(68.6%) receive > 81 mg of aspirin daily. We Identified 11 patients on less than 81mg of aspirin. The mean age of this cohort was 51.18 years, 7 were Male. Out of the 11, 3 patients were on aspirin 40.5 mg every other day, 3 on 40.5 mg every day, 4 on 81mg every other day and one patient was not on any aspirin. Reason for dose alteration was adequate inhibition noted on TEG in 5 patients and bleeding in 6 patients (4 out of 6 for gastrointestinal bleed). Mean duration of follow up was 22.57±18months. Six patients in this cohort were on standard warfarin protocol with the INR goal 2-3 and one patient was not on any warfarin. The follow-up on a very low ASA dose was 13.7±8.6 months. There were no pump thrombosis or other thromboembolic events either before or after the dose change. There was no significant difference in LDH levels before (225.2±24.3) or after (220.1±27.8) p=0.7, hematocrit before 33.6+/-9.9 or after 35.0+/-8.1, P=0.08, aspirin dose change. Arachidonic Acid inhibition on thromboelastogram was less than 80% in 7 patients and 5 of them had inhibition less than 50%. Conclusion A very low dose of aspirin (

Oral aspirin or low dose of intravenous lysine acetylsalicylate in ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

To compare the pharmacodynamic effect of an oral loading dose of 'noncoated' ASA 300 mg vs. an intravenous bolus injection of lysine acetylsalicylate 150 mg in patients with STEMI undergoing pPCI. This was a prospective single-center, open label, pharmacodynamic study, including nonconsecutive patients presenting at our catheterization laboratory with STEMI undergoing pPCI and not receiving ASA within the previous 7 days. Pharmacodynamic analyses were performed at five time points: baseline, and 1, 2, 4 and 12 h after the loading dose, and measured as ASA reaction units (ARU) by the Verify Now System. An ARU more than 550 was considered as nonresponsiveness to study drugs. The primary end point was the different rate of patients with ARU more than 550 at 2 h after the loading dose of oral vs. intravenous ASA. Secondary end points included the comparison of ARU more than 550 at the other time points and the comparison of continuous ARU at each time point. The study was planned with a sample size of 68 patients, but it was prematurely stopped due to slow enrollment after the inclusion of 23 patients, 12 randomized to oral ASA and 11 to intravenous lysine acetylsalicylate. At 2 h the rate of patients with ARU more than 550 was numerically but not significantly higher in patients receiving oral ASA as compared with intravenous lysine acetylsalicylate (33 vs. 14.2%; Δ -0.19, 95% confidence interval -0.59-0.21, P = 0.58). The difference over time was NS (P = 0.98), though the prevalence of ARU more than 550 was higher at the other time points. Both routes of administration reduced ARU values over time, though with no overall significant difference between profiles (P overall = 0.48). In patients with STEMI undergoing pPCI the rate of nonresponsiveness to ASA was not different comparing an oral 'noncoated' loading dose of ASA with an intravenous bolus injection of lysine acetylsalicylate. However, as patient enrollment was prematurely terminated, this study is underpowered to draw a definite conclusion.

Predictors of uptake of aspirin (ASA) chemoprevention in Lynch syndrome (LS).

49 Background: Substantial data support efficacy of ASA in colorectal adenoma and cancer (CRC) chemoprevention. In 2011, the CaPP2 Phase 3 trial showed benefit of 600 mg ASA daily for prevention of LS-associated CRC (HR 0.41,p=0.02) in persons w/ASA adherence &gt;2 yrs. Anecdotally, uptake of ASA by LS pts has been low, but few data exist. We examined uptake and predictors of ASA chemoprevention among LS pts receiving follow-up at our center since 2011. Methods: Pts evaluated by Fox Chase’s Risk Assessment Program receive in-person medical recommendations and written information about cancer (CA) prevention measures including ASA. Medical records of 127 LS pts were retrospectively reviewed. Demographics, gene affected, personal Hx of CA, ASA use, and ASA dose were collected. Majority (94.5%) of cohort had documentation of ongoing LS endoscopic screening at our center—only 3.2% had no recent follow-up (past 3 yrs) and 2.4% had recently died (past 3 yrs). Chi-square tests and multivariable logistic regression were used in analyses. Results: Overall 24.4% (31/127) of pts reported ASA use for chemoprevention (see Table). Nearly half (48.4%) of ASA users took 81 mg ASA daily, and only 22.6% reported taking &gt;600 mg ASA daily. ASA use was associated with older age, MLH1/ MSH2+ vs MSH6/ PMS2+, and personal Hx of CRC. In the multivariable logistic model, older age (OR 2.80, p=0.04) and MLH1/ MSH2+ (OR 2.64,p=0.07) were significant and borderline significant, respectively. Adding race/ethnicity and gender strengthened the effect of age&gt;60 (OR 3.11, p=0.03), and improved fit (pseudoR2=16.8%). Conclusions: Uptake of ASA chemoprevention by LS pts is overall modest, but older age is associated with ASA uptake for chemoprevention. Among ASA users, fewer than 1 in 4 take the 600 mg daily dose shown effective in CaPP2. Confirmatory trials as well as efforts to elucidate barriers to ASA chemoprevention in LS are needed. [Table: see text]

Intranasal ketorolac, diagnosis, and desensitization for aspirin-exacerbated respiratory disease

BackgroundIntranasal ketorolac has been proposed as a diagnostic test for aspirin-exacerbated respiratory disease (AERD) and a faster, safer, and reliable addition to facilitating aspirin (ASA) desensitization. ObjectiveWe conducted the first prospective study to dissect the impact of intranasal ketorolac incorporation during ASA desensitization vs standard oral protocols in concert with evaluating its diagnostic use for AERD. MethodsPatients with AERD were enrolled in a prospective open-label observational study between November 2006 and August 2013. Participants selected either one of the following desensitization protocols: intranasal ketorolac 1 day before oral ASA (group 1, combined) or ketorolac challenge with greater than 2 weeks elapsing until oral ASA (group 2, washout). All patients were on a leukotriene-modifying drug (montelukast) for at least 1 week before the challenge. ResultsA total of 20 patients were enrolled: 13 in group 1 and 7 in group 2. No significant differences were seen for baseline symptom scores or forced expiratory volume in 1 second. Group 1 exhibited significant increases for the threshold dose of ASA (P = .009), the likelihood of having silent ASA desensitization (P = .01), and decreased reaction severity to oral ASA (P = .04). There were no significant differences in reaction forced expiratory volume in 1 second, the incidence of extrapulmonary symptoms, limited nasoocular reactions, rescue treatment requirements, or time to symptom resolution. There was 100% concordance between reactions to intranasal ketorolac and oral ASA for group 2, supporting its use as a diagnostic test for AERD. ConclusionIntranasal ketorolac is a useful diagnostic test and adjunct within the combined ketorolac/ASA protocol to achieve effective, efficient, and perhaps safer desensitization to ASA for patients with AERD.

Frequency of complications due to sedation in patients undergoing gastrointestinal endoscopy

Aim: Non-operating room anesthesia is frequently used in all areas. Gastrointestinal endoscopy is one of the procedures requiring sedation outside the operating room. This study aimed to investigate the drugs used for sedation and the complications during gastrointestinal procedures in our hospital.Materials and Methods: The files of the patients who underwent anesthesia for gastrointestinal endoscopy between 01.01.2018- 31.12.2018 in our hospital were retrospectively reviewed. ASA score, age, gender, vital signs, drugs, doses, complications, and need for intensive care were evaluated.Results: A total of 508 patients were sedated. The 187 cases (36.3%) were male, and 321 (63.2%) were female. The mean age was 54.9 ± 15.6 years. Two hundred fifty-two cases (49.6%) were found to be ASA II. Colonoscopy was performed in 134 cases (26.4%), gastroscopy in 270 cases (53.1%), both colonoscopy and gastroscopy in 99 cases (19.5%), and PEG in 5 cases (1%). The most frequently used anesthetic drug in sedated patients was observed to be propofol. Complications occurred in 28 patients (5.5%).Conclusions: Drug selection becomes crucial in non-operating room anesthesia applications in terms of early recovery and patient safety. In this study, it was seen that the most used drug was propofol, and accordingly, it was concluded that mortal complications were not observed.