Klinische und in vitro-Untersuchungen zur therapeutischen Breite von Acetylsalicylsäure zur Thromboseprophylaxe

Zusammenfassung Acetylsalicyl-lysin wurde in den Dosierungen 0,9 g/48 h, 1,8 g/24 h und 3,6 g/24 h in drei nacheinander folgenden Studien zur Thromboseprophylaxe bei Hüftgelenksoperationen anhand des Radio-Fibrinogen-Tests untersucht. Mit den drei AS-lysin-Dosierungen wurde keine Verminderung von Thrombosen (TVT) gefunden.Die Kollagen-induzierte Thrombozytenaggregation war in allen drei Gruppen signifikant gesenkt. Unter den niedrigen AS-lysin-Dosen war die Aggregation beim Auftreten einer TVT weniger stark gehemmt als beim Ausbleiben einer TVT. Bei der 3,6 g-Dosis war die Aggregation maximal ohne signifikante Unterschiede vom Thrombosevorkommen gehemmt.Die Befunde ergeben keinen therapeutischen Bereich für die Acetylsalicylsäure zur Verhütung venöser Thrombosen.     

The effect of aspirin on the response to the rabbit ear artery

Aspirin significantly potentiated the response of the rabbit ear artery to intraluminal noradrenaline and electrical stimulation. The response to methoxamine and extraluminal noradrenaline was unaffected. Treatment of the artery with cocaine partially inhibited these effects of aspirin.     

Leukotriene-related gene polymorphisms in patients with aspirin-intolerant urticaria and aspirin-intolerant asthma: differing contributions of ALOX5 polymorphism in Korean population

The pathogenesis of aspirin (acetylsalicylic acid, ASA)-intolerant urticaria (AIU) is still poorly understood but it has recently been suggested that it is associated with the overproduction of leukotriene (LT). This is supported by evidence that cyclooxygenase 2 inhibitor is given safely to patients with AIU. The present study was designed to investigate the role of genetic polymorphism of LT related genes in the pathogenesis of AIU via a case-control study. We screened single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in leukotriene synthesis in the Korean population with AIU (n = 101), ASA-intolerant asthma (AIA, n = 95) and normal healthy controls (n = 123). Genotype was determined by primer extension reactions using the SNapShot ddNTP primer extension kit. Among 8 SNPs of four LT related genes, the polymorphism of ALOX5 at positions of -1708 G > A showed significant difference in genotype frequency between AIU and AIA (p = 0.01). Furthermore, there were significant differences observed in the frequencies of two ALOX5 haplotypes between the AIU group and AIA group (p < 0.05). However, there were no differences in allele, genotype, or haplotype frequencies of ALOX5 between the AIU group and the normal control group. These results suggested that ALOX5 has a differing contribution in two major clinical pathogenesis related to ASA-sensitivity.     

Aspirin Treatment for Neonatal Infectious Endocarditis

We describe a term female neonate with Serratia marcescens endocarditis. Despite adequate antibiotic therapy for 8 days, the bacteremia persisted and there was an increase in vegetation size. Treatment with aspirin was initiated, with resolution of the bacteremia and a gradual decrease in vegetation size. We conclude that in neonatal endocarditis, aspirin may be beneficial additional treatment.     

Gauze packing for aspirin-induced hemorrhage in vaginal hysterectomy

Intra-abdominal packing has been used to control massive hemorrhage in many difficult situations. Gynecologists are finding it increasingly useful in controlling persistent hemorrhage in a variety of situations. Recently we found it necessary to use packing for persistent brisk bleeding during vaginal hysterectomy in a patient on aspirin therapy for heart disease. We could find no similar report in the literature and now describe our experience.Abbreviations INR International normalized ratio     

Pharmacodynamic profile of antiplatelet agents: marked differences between single versus costimulation with platelet activators

BACKGROUND: In pharmacodynamic studies with antiplatelet agents, platelets are usually activated in vitro with single agonists (e.g., ADP) solely. We questioned whether differences occur between single and combined stimulation of platelets [involving the major thrombin-receptors, protease-activated receptors (PAR)1 and PAR4], and whether the pharmacodynamic response to common antiplatelet drugs vary when a combined stimulus is applied instead of a single agonist. METHODS: We investigated the influence of different antiplatelet agents (aspirin [500 mg]) in vivo, the P2Y12-antagonist AR-C 69931MX (4 nM) and the GPII/IIIa-antagonist (abciximab ([5 microg/ml] in vitro) on the degranulation response (CD62) and expression of the activated GPIIb/IIIa-receptor (PAC-1) after stimulation with ADP (2 microM), collagen (4 microg/ml), a PAR1-activating peptide (3 microM TRAP) and a PAR4-activating peptide (200 microM AYPGKF) alone or in a combination of each two agonists by flow cytometry in healthy subjects. RESULTS: (1) Combined activation of TRAP with AYPGKF resulted in synergistic CD62 and PAC-1 expression. Only AYPGKF but neither TRAP nor ADP acted synergistically with collagen. (2) AR-C 69931MX inhibited platelet degranulation (CD62) in all inducer combinations with ADP or the combination TRAP with AYPGKF. The effect was considerably smaller or absent for the combination of collagen with a second inducer. (3) Aspirin intake reduced platelet degranulation and PAC-1 expression only for AYPGKF costimulation with collagen. CONCLUSION: Because a variety of different agonists influence platelet activation and its distinct functions at a time, investigations which regard the concert of these agonists might be closer to the in vivo situation and better reflect the pharmacodynamic profile of an antiplatelet agent than using one single inducing agent.     

Cutaneous reactions to aspirin and nonsteroidal antiinflammatory drugs

Soon after the introduction of aspirin for the treatment of pain, fever, and inflammation more than a century ago, clinicians were challenged by the frequent observation of ASA-triggered allergic and pseudoallergic reactions occurring in the skin. This problem was further enhanced by the development of a number of other analgesic and antiinflammatory drugs that, having different chemical structures, cross-reacted with acetilsalycilic acid in many patients. This paper reviews the information presently available for the management of individuals who develop urticaria and angioedema when exposed to drugs that inhibit cyclooxygenase isoenzymes. The immune and nonimmunologic mechanisms leading to the pathogenesis of such reactions, their prevalence in selected groups of the population, clinical picture, and useful diagnostic approaches are described, and current guidelines used in our institutions for the clinical orientation of the patients, taking advantage of the recent introduction of various new and more selective NSAIDS that inhibit preferentially the COX-2 enzyme, are proposed.     

Does aspirin protect against Alzheimer's dementia? A study in a Swedish population-based sample aged > or =80 years

Objective It has been reported that aspirin and other non-steroidal anti-inflammatory drugs (NSAID) may protect against dementia of Alzheimer's type and/or vascular dementia. However, co-morbidity and the dose of aspirin may be critical. A major indication for low-dose aspirin is prophylaxis after stroke and transient ischaemic attacks, conditions that may obscure an anti-dementia effect by the drug. Alternatively, low-dose aspirin may be insufficient if the protective effect is due to an anti-inflammatory mechanism. The aim of this study was to assess whether high-dose or low-dose aspirin may protect against Alzheimer's dementia in subjects aged 80 years. For comparison, effects of (other) NSAID, paracetamol and d-propoxyphene were studied.Methods Global, cross-sectional, and longitudinal (1991–2000) epidemiological analyses of clinical, cognitive and drug treatment data on 702 individuals 80 years old or more (351 twin pairs of same sex), all alive at inclusion: mean age 83.9 years (80–99 years). Calculations were made with logistic regression of associations between use of various analgesics and cognitive function, after adjustment for age, gender, and cardiovascular and cerebrovascular diseases.Results Users of high-dose aspirin had significantly lower prevalence of Alzheimer's dementia and better-maintained cognitive function than non-users. There were numerically similar but not significant associations with use of low-dose aspirin and other NSAID. There were no such associations with use of either paracetamol or d-propoxyphene.Conclusion Aspirin might protect against Alzheimer's disease, but controlled trials are warranted.     

社区门诊高血压患者抗栓治疗情况的调查

目的：调查社区门诊高血压患者使用阿司匹林抗栓治疗的情况，分析其使用现状。方法：在社区门诊随机抽取50例需要抗栓治疗的高血压患者，调查其阿司匹林使用情况，分析未使用及使用剂量不足的原因。结果：在50例患者中，22％未使用过阿司匹林，16％曾间断使用，未坚持，28％使用剂量不足。阿司匹林使用不当的原因主要为：社区医生认识不清或重视不够；担心不良反应；慢性病管理制度不完善；社区医生对患者健康教育不够，患者的治疗依从性差：医生忽略询问具体使用情况。结论：社区门诊高血压患者的抗栓治疗中存在阿司匹林使用率较低及使用剂量不当的问题。应进一步加大宣传，提高使用率。     

阿司匹林对冠状动脉粥样硬化性心脏病血清C-反应蛋白水平的干预以及临床意义

目的探讨血清C反应蛋白(C-reactive protein,CRP)与不同临床类型冠状动脉粥样硬化性心脏病(Coronary Atherosclerotic Herat Disease,CAHD)的关系,以及阿司匹林对CRP水平的干预作用.方法前瞻性地对首次确诊的96例不同类型的CAHD与23例对照者抽取空腹静脉血,测定血清CRP;96例CAHD给予30d的阿司匹林肠溶片口服(每日100mg)后再次测量血清CRP.结果初诊患者与对照组相比,各组CAHD的CRP均有不同程度地升高,其中急性心肌梗死组与不稳定型心绞痛组升高最为显著(P＜0.05);口服30d阿司匹林肠溶片后,各组CAHD的CRP均有不同程度地降低,其中急性心肌梗死组与不稳定型心绞痛组降低最为显著(P＜0.05),但仍显著高于对照组.结论血清CRP与CAHD的发生、进展及不良事件的产生相关,口服阿司匹林可通过降低血清CRP,减少CAHD不良事件的发生.