Acetylsalicylic Acid Medication Research Articles

Risk factor management matters more than pharmaceutical cyclooxygenase-2 inhibition in the prevention of de novo intracranial aneurysms.

Pathophysiological studies of saccular intracranial aneurysm (sIA) disease have shown that inflammation plays a crucial role in sIA development. Pharmaceutical inhibition of COX-2-PGE2-NF-κB signaling (COX-2, cyclooxygenase-2; PGE2, prostaglandin E2; NF-κB, nuclear factor κB) has been shown in animal models to inhibit sIA formation and progression suggesting that use of medication inhibiting COX-2 could reduce intracranial aneurysm formation also in patients. The impact of COX-2 inhibition on de novo sIA formation was studied in two cohorts: in a previously described angiographically followed cohort of 1419 sIA patients and in a cohort of 117 sIA patients treated with stenting or stent-assisted embolization. Patients were identified from our population-based Kuopio Intracranial Aneurysm Database. Data on the use of anti-inflammatory medications and hospital diagnoses were obtained from national registries. Risk factors were identified by univariate and multivariate analyses. De novo sIA patients were younger and more often smokers. Use of COX-2 selective inhibitors or nonsteroidal anti-inflammatory drugs did not significantly reduce de novo sIA formation, but the percentage of patients with de novo sIA formation was smaller in patients with prescribed regular acetylsalicylic acid medication (1.1% vs. 3.6%). In the multivariate analysis, however, neither acetylsalicylic acid use nor other type of pharmaceutical inhibition of COX-2 reduced the formation of de novo sIAs. The risk was mostly affected by age, smoking history and irregular usage of antihypertensive medication regardless of used COX-2 inhibition level. For the prevention of de novo sIA formation, risk factor management with focus on cessation of smoking and treating hypertension adequately seems more important than pharmaceutical COX-2 inhibition.

Impact of acetylsalicylic acid (ASA) on postoperative hemorrhage in spinal lumbar surgery: Should preoperative ASA be discontinued for elective surgery?

ObjectiveThe application of acetylsalicylic acid (ASA) represents high evidence in the aging society due to primary and secondary prevention in cardiovascular disease and stroke. However, this presents a challenge for neurosurgeons in terms of preoperative and postoperative management of care. This study aimed to analyze the risk of bleeding by applying ASA before lumbar spinal surgery. MethodsRetrospective analysis of medical records of 3051 patients was performed from 2008 to 2018 who underwent lumbar surgery at our institution. The risk of postoperative hemorrhage was compared in patients treated with ASA versus patients without ASA treatment. Additionally, the relationship between discontinuation of ASA preoperatively (≥7 days) or no previous history of ASA versus continuation with ASA (<7 days) on postoperative hemorrhage was analyzed. ResultsPostoperative hemorrhagic were observed in 2.1% (n = 63) of all lumbar operations. In 421 patients, the effect of ASA (<7 days) was still persistent at the time of surgery (ASA impact group). Of these, 12 (2.85%) patients had a hemorrhage. No significant differences were found in comparison to the No ASA impact group (p = 0.272). Sex (p = 0.003), hypertension (p = 0.015), recurrent surgery (p = 0.001) and use of hemostatic agents (p = 0.023) had a significant impact on postoperative hemorrhage. ConclusionThe continuation of ASA medication is not associated with increased risk of postoperative hemorrhage after spinal surgery. However, sex, hypertension, recurrent surgery and the use of hemostatic agents under continued ASA treatment were found to be associated with an increased risk of hemorrhage.

Pegylated Interferon in Myelodysplastic/Myeloproliferative Syndrome with Ringsideroblasts and Thrombocytosis

Background:In 2016 WHO recognized the provisional entity refractory anemia with ring sideroblasts and thrombocytosisas a distinct entity and renamed it myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T). The disease presents hallmarks of both myelodysplastic and myeloproliferative features. Although the diagnostic criteria are well defined and there are several studies of the molecular landscape of the disease, the treatment regimen of these patients remains inconsistent. Due to lack of clinical trials, treatment options are chosen either on MDS- or MPN-based regimens and individual preferences such as patients characteristics and clinical presentation. Prevention of thromboembolic events is a reasonable goal. However, the use of platelet-lowering drugs is still not well studied and treatment related anemia leading to transfusions with accelerated iron overload limits a general use of cytoreductive treatment. To avoid worsening of the anemia while efficiently reducing thrombocytosis we treated 3 patients with pegylated interferon (pIFN) and provide insight in JAK2-allele burden measurement and additional mutations obtained with next generation sequencing (NGS). Results:Three patients with diagnosis of MDS/MPN-RS-T were treated with 135µg pIFN during an observation period between 8 and 34 months. All 3 patients had a JAK2V617F mutation, &gt;15% ringsideroblasts and a thrombocyte count above 600G/l. In the additional NGS analysis, two patients showed a mutation in the SF3B1 gene, one with an additional DNMT3A mutation. In the third case, NGS results revealed a mutation in the splicing factor U2AFI, which is a rare finding in patients with MDS/MPN-RS-T. JAK2-allelel burden was obtained at the beginning and showed a decrease of a mean value of 38% as measured by digital droplet PCR. Anemia was present at initial diagnosis in two patients. During observation period, none of the patient became transfusion dependent, in one case even an improvement in hemoglobin levels was achieved. Side effects of the treatment were only minimal and no thromboembolic as well as major bleeding event occurred under additional acetylsalicylic acid medication. Conclusion: In summary we show that in patients with MDS/MPN-RS-T a therapy with pIFN achieved rapid decrease of thrombocyte values without lowering hemoglobin levels at a maximal dose of 135µg per week. JAK2-allele burden reduction and a low side effect profile further demonstrate the value of this treatment option for these often elderly patients. However, larger studies are needed to confirm our data. Disclosures No relevant conflicts of interest to declare.

In vitro analysis of platelet function in acute aneurysmal subarachnoid haemorrhage.

Platelet function might play an essential role in the pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Thus, impaired platelet function and disturbed primary haemostasis induced by intake of acetylsalicylic acid (ASA) might influence the rate of DCI. Primary haemostasis and platelet function can be measured with in vitro diagnosis (platelet function analyser test, PFA 100). The aim of this study is to evaluate the rate of DCI, haemorrhagic complications and the neurological outcome. Two groups were compared (patients with regular platelet function versus patients with impaired platelet function). This is a retrospective observational study. An initial cohort of 787 patients with SAH has been treated from January 2005 to September 2012. Seventy-nine patients (10%) with aneurysmal SAH, a history of ASA medication and PFA testing within the first 24h after aneurysm rupture have been included. The overall rate of DCI in the present study was 43%. In vitro platelet function testing showed pathological primary haemostasis in 69.6%. The DCI rate was higher in patients with regular tested primary haemostasis (p=0.02, OR=3.16, 95%CI=[1.19; 8.83]). However, outcome assessment by mGOS did not show a significant difference between the groups. Patients with impaired primary haemostasis did not display a higher rate of haemorrhagic complications. Impairment of primary haemostasis resulting from an impairment of platelet function at an early stage after SAH might lead to a lower rate of DCI. In vitro testing of platelet function might be useful to predict the occurrence of DCI in the course.

Influence of acetylsalicylic acid and low-molecular weight heparins on the formation of renal hematoma after shock wave lithotripsy.

To investigate the risk of renal hematoma (RHT) after shock wave lithotripsy (SWL) among patients on acetylsalicylic acid (ASA) or low-molecular-weight heparin (LMWH). Retrospective analysis of 434 patients treated with SWL for nephrolithiasis and ureterolithiasis of the proximal ureter. Primary endpoint was detection of RHT by ultrasound the day after SWL. Secondary outcome variables included transfusion of erythrocyte concentrate(s), interventions, hospital readmission or death due to RHT within 30days of SWL. Binary logistic regression analysis was used including a post hoc one-way analysis. Of 434 patients, 33 (7.6%) and 67 (15.4%) patients were medicated with ASA and LMWH, respectively. RHT was detected in 20 of 434 (4.6%) patients. Of those, 3 (20%) were on ASA, 6 (35%) were on LMWH, 1 (5%) was on ASA and LMWH, and 10 (50%) had no anticoagulation. Univariate analysis showed a statistically significant higher risk for RHT among patients on ASA (p=0.04) and LWMH (p=0.02) with an untreated urinary tract infection (UTI) (p=0.008) and history of cardiovascular disease (p=0.028). On multivariate analysis, ASA medication, untreated UTI (OR 4.4, 95% CI 1.31-14.75, p=0.016 and OR 5.79, 95% CI 1.65-20.32, p=0.03) and a therapeutic dose of LMWH (OR 10.4, 95% CI 1.74-62.27, p=0.01) were independent predictors for RHT. Before SWL, a patient risk profile should be evaluated. If feasible, LMWH in therapeutic dosing should be avoided, and ASA should be discontinued. UTI should be treated before SWL in any case. http://www.clinicaltrials.gov ; Identifier NCT02875717.

Antithrombotic therapy in patients undergoing TAVI with concurrent atrial fibrillation. One center experience.

Aim of the present study was to record the antithrombotic approach in AF and non-AF patients undergoing TAVI, and to compare the efficiency of the used regimens combination. Antithrombotic approach of patients undergoing TAVI remains a challenging dispute. It becomes even more complex when need for anticoagulant treatment is required due to concurrent atrial fibrillation. Consecutive patients with severe symptomatic aortic stenosis treated with TAVI, were retrospectively studied. All patients were divided into two groups, matched to age, depending on the existence of atrial fibrillation. The primary end-point was the composite of MACE, while the secondary end-point was the occurrence of major bleeding at follow-up. A total of 80 patients were included in the study. Out of them, 20 patients (80.2 ± 5.4 years) suffered from concurrent atrial fibrillation. This group was matched with 20 patients (80.6 ± 3.7 years) with no need for anticoagulation. AF-group patients were treated with clopidogrel plus acenocoumarol for 3 months. Following that, acetylsalicylic acid plus acenocoumarol were prescribed. Non-AF patients were treated with 3 months clopidogrel plus acetylsalicylic acid followed by single acetylsalicylic acid medication. No statistical significant differences in MACE between AF and non-AF group were identified (p = 0.705, phi coefficient = 0.06) (mean follow-up 23.4 ± 14 months). Similarly, there was no statistical significant difference for bleedings among the AF and non-AF patient group (p = 0.658, phi coefficient = 0.14). In patients undergoing TAVI with CoreValve, with concurrent AF, treatment with clopidogrel plus acenocoumarol for 3 months, followed by acetylsalicylic acid plus acenocoumarol, seems safe and effective enough in long-term follow-up.

Monitoring of acetyl salicylic acid-induced platelet inhibition with impedance aggregometry in children with systemic-to-pulmonary shunts

Shunt thrombosis after implantation of systemic-to-pulmonary shunts in paediatric patients is common. Acetyl salicylic acid is used for anti-thrombotic treatment; however, the effect is rarely monitored, although it is known that the response varies. The aim was to determine the effects of acetyl salicylic acid medication on platelet aggregation in children with systemic-to-pulmonary shunts. A total of 14 children – median age 12 days; ranging from 3 to 100 days – were included in a prospective observational longitudinal study. All children were treated with oral acetyl salicylic acid (3–5 milligrams per kilogram once daily) after shunt implantation. Acetyl salicylic acid-dependent platelet aggregation in whole blood was analysed with impedance aggregometry (Multiplate®) after addition of arachidonic acid. Analyses were carried out before the primary operation, before and 5 and 24 hours after the first acetyl salicylic acid dose, and after 3–6 months of treatment. The therapeutic range for acetyl salicylic acid was defined as a test result less than 60 units. Acetyl salicylic acid reduced the arachidonic acid-induced platelet aggregation in all but one patient. Of the patients, 93% were in the therapeutic range 5 hours after acetyl salicylic acid intake, 86% were in the range after 24 hours, and 64% after 3–6 months. Acetyl salicylic acid reduces platelet aggregation after shunt implantation in paediatric patients, but a considerable percentage of the children are outside the therapeutic range. Monitoring of platelet aggregation has the potential to improve anti-platelet treatment after shunt implantation by identifying children with impaired acetyl salicylic acid response.

Acral ischemia as a presenting manifestation of essential thrombocythemia

A 74-year-old male presented with a 6-week history of rapidly progressive acral ischemia. Clinical examination revealed livid discoloration of his toes and fingertips. All peripheral pulses were palpable, and ankle brachial pressure indices were normal. Laboratory tests revealed thrombocytosis of 710,000/ll (normal range 140,000– 320,000/ll), while red blood cells were within normal range and leukocytes were moderately elevated, indicating neutrophilia but otherwise normal differential blood count. Angiography showed obliteration of all digital arteries (top right panel). There were no proximal stenoses or plaques. A cardiac source of embolism was excluded by transesophageal echocardiography. Despite intravenous and intraarterial administration of prostaglandin E1 and acetylsalicylic acid medication, the ischemic areas rapidly M. Hanoun F.-E. Brock Department of Angiology, University Hospital, University of Duisburg-Essen, Essen, Germany

A randomised controlled trial to evaluate and optimize the use of antiplatelet agents in the perioperative management in patients undergoing general and abdominal surgery- the APAP trial (ISRCTN45810007)

BackgroundDue to the increase of cardiovascular diseases acetylsalicylic acid (ASA) has become one of the most frequently prescribed drugs these days. Despite the rising number of patients with ASA medication presenting for elective general and abdominal surgery and the potentially increased risk of hemorrhage in these patients, there are no clear, evidence-based guidelines for the perioperative use of antiplatelet agents. The present randomised controlled trial was designed to evaluate the safety and optimize the use of ASA in the perioperative management of patients undergoing general and abdominal surgery.Methods/DesignThis is a two-arm, monocenter randomised controlled trial. Patients scheduled for elective surgical treatment (i.e. inguinal hernia repair, cholecystectomy and colorectal resections) with ASA as a permanent medication are randomised equally to perioperative continuation or discontinuation of ASA. Patients who are randomised in the discontinuation group stop the administration of ASA five days prior to surgical treatment and start intake of ASA on postoperative day 5. Fifty-two patients will be enrolled in this trial. The primary outcome is the incidence of postoperative bleeding and cardiovascular events at 30 days after surgery. In addition a set of general as well as surgical variables are analysed.DiscussionThis is a randomised controlled two-group parallel trial designed to assess the safety and optimize the use of ASA in the perioperative management of patients undergoing general and abdominal surgery. The results of this pilot study build the basis for a confirmative randomised controlled trial that may help to clarify the use and potential risk/benefits of perioperative ASA medication in patients undergoing elective surgery.Trial registrationThe trial is registered with Current Controlled Trials ISRCTN45810007.

Individual variability of response and non-response to acetyl salicylic acid after cardiac surgery

Insufficient inhibition of platelet function by acetyl salicylic acid (ASA) or other platelet inhibitors is a risk factor for arterial thrombosis in cardiovascular patients. We wanted to collect and analyse information on the frequency and probable causes of non-response to ASA in patients prior to and after cardiac surgery. One hundred and one patients (mean age 68 ± 9 years) undergoing cardiac surgery (98 patients with coronary bypass grafting, 18 cases had combined valve replacement, and three patients with only valve replacement) were enrolled. Post-operatively all patients received metamizole for analgesia. Platelet aggregation in platelet-rich plasma was induced by arachidonic acid (AA; 1.6 mM) or ADP (3 mM) in the absence and presence of exogenous ASA (100 µM). ASA non-response was defined as a maximum AA-induced aggregation of >30%. Eighty eight patients had pre-operative medication with ASA (100 mg/d), and ASA non-response was found in 24%. Irrespective of whether or not ASA medication was continued immediately after surgery, incidence of non-response increased to 55% at the first post-operative day. During continuous post-operative ASA medication (100 mg/d), 65% of patients were non-responder at fifth–7th post-operative day. When estimated on the basis of exogenously added ASA, non-response was observed pre-operative in 10%, at first post-operative day in 53% and at fifth–7th post-operative day in 39% of the patients. Twenty six of the 52 patients who did not adequately respond to exogenous ASA at the first post-operative day became responders when tested at the fifth–7th post-operative day, and 13 of the 46 responders became non-responders. The conversions were not due to small changes around the threshold of 30% aggregation but due to a highly significant decrease or increase in the extend of aggregation. Neither extracorporal circulation nor co-medication with clopidogrel had any significant influence on the platelet response to ASA medication or exogenously added ASA. Some non-steroidal analgesics, including metamizole, have been suggested to prevent inhibition of platelet cylcooxygenase by ASA. However, in 10 healthy volunteers we did not observe any interference of metamizole with the response to ASA. In conclusion, platelet response to ASA is markedly decreased after cardiac surgery. The underlying mechanisms and the clinical consequences of the post-operative instability of non-response to ASA need further evaluation.

Prophylaxis of thromboembolic complications after the Fontan operation (total cavopulmonary anastomosis)

Thrombotic events have been reported as a major cause of morbidity after the Fontan procedure. There is no consensus concerning the postoperative mode and duration of anticoagulation prophylaxis. In a retrospective study, we evaluated the results of a prophylactic regimen on the basis of the surgical technique, potentially predisposing risk factors, and specific sequelae. We evaluated 142 surviving patients after total cavopulmonary anastomosis (mean follow-up was 91.1 +/- 43.9 months). Prophylactic antithrombotic treatment was initiated in 86 patients with partial prosthetic venous pathway with acetylsalicylic acid; 45 patients with complete autologous tissue venous pathway or partial prosthetic venous pathway received no anticoagulation, and 11 patients received warfarin sodium (Coumadin). During long-term follow-up, 22 patients (12 after acetylsalicylic acid medication) crossed over to warfarin. Thrombotic events occurred in 10 patients (7%), with systemic venous thrombus formation in 8 (5.6%), stroke in 2 (1.4%), and a peak incidence during the first postoperative year. Eight of 10 patients were receiving heparin therapy mainly for prolonged postoperative immobilization. During follow-up, none of the 74 patients receiving acetylsalicylic acid and 1 of 40 patients without medication presented with thrombus formation. Under warfarin medication, 1 of 28 patients had an asymptomatic thrombus. Expected freedom from a thromboembolic event was 92% at 5 years and 79% at 10 years. There was no association with coagulation factor abnormalities. Protein-losing enteropathy was present in 4 of 10 patients. A prophylactic anticoagulation strategy that considers the surgical technique and potential predisposing circumstances proved effective in the prevention of late thrombotic complications after total cavopulmonary anastomosis. There is no need for routine anticoagulation during long-term follow-up after Fontan-type surgery in pediatric patients.

Acetylsalicylic Acid and Microembolic Events Detected by Transcranial Doppler in Symptomatic Arterial Stenoses

Background: In patients with symptomatic carotid artery stenosis, high-intensity transient signals detected by transcranial Doppler (TCD) have been related to particulate microemboli originating at the stenotic lesion. The occurrence of these microembolic events within the Doppler spectrum should be influenced by antithrombotic agents of proven efficacy in these patients mainly by reducing cerebral embolism. Methods: Seventy-four of 192 consecutive patients with symptomatic arterial stenosis in the anterior circulation and clinical symptoms within the last 30 days underwent 1-hour bilateral TCD monitoring. Patients were selected, if they presented temporal bone windows enabling transcranial insonation, revealed normal Doppler CO₂ test excluding hemodynamic impairment, had not received antithrombotic therapy other than acetylsalicylic acid (ASA) before sonographic examination, and gave informed consent to 1-hour monitoring which could be performed immediately on admission/presentation of the patient at the Department of Neurology. Results: Microembolic events were detected in 38 patients (51%). The proportion of patients with events among 26 patients without antithrombotic medication was 73% as compared with 40% in 48 patients receiving ASA at the time of TCD monitoring (p = 0.023). Multivariate analysis including time from ischemia to TCD, presence and start of ASA prevention, degree and localization of stenosis, and presence of a single or recurrent ischemia revealed that absence of an ASA prevention (odds ratio OR 7.1, 95% confidence interval CI 1.6–31.4, p = 0.010), recurrent ischemic events (OR 7.1, 95% CI 1.6–32.7, p = 0.011), and extracranial localization of the stenosis (OR 3.8, 95% CI 1.1–13.2, p = 0.038) were independent predictors for microembolic events. Conclusion: In patients with symptomatic arterial stenosis, the absence of an ASA medication is associated with the occurrence of TCD-detected microembolic events, suggesting a relation between these events and ASA-sensitive microemboli from the stenotic lesion.

On the degree of platelet, coagulation and fibrinolysis activation after cerebral infarction and cerebral haemorrhage and the clinical outcome.

Thrombocytic, haemostatic and fibrinolytic quantities were investigated in 47 patients with cerebral infarction and 34 patients with cerebral haemorrhage. Sixteen of the infarction patients and ten patients of the haemorrhage group were on acetylsalicylic acid medication. Of the remaining 55 patients without acetylsalicylic medication 21/31 = 67.7% of the patients in the infarction group and 9/24 = 37.5% of the patients in the bleeding group had unphysiologically enhanced ADP-induced platelet aggregation. With regard to the coagulation and fibrinolysis markers no significant differences were found between the two groups. In both groups, coagulation activity markers (fibrin monomer and thrombin-antithrombin III), as well as D-dimers were significantly higher than in controls in a high proportion of cases. In 5/47 of the infarction patients and in 3/34 of the haemorrhage patients the fibrin monomer levels were elevated to such an extent, that it can be considered as low grade disseminated intravascular coagulation. In the cerebral haemorrhage group, 80.3% of the patients who subsequently died showed a significantly enhanced fibrin monomer concentration, compared with 28.6% of those who survived. The corresponding frequencies for D-dimer were 100% compared with 66.7%. In the cerebral infarction group, the only analytical quantity showing a significant difference between patients with a fatal outcome and those with a non-fatal outcome was ADP (2 mumol/l) induced platelet aggregation (83.3% in the fatal group, 40.0% in the non-fatal group).

Gastric retention of enteric‐coated aspirin tablets in beagle dogs

Administration of acetylsalicylic acid (ASA) in the dog may cause gastric mucosal damage. Enteric-coated tablets protect the canine stomach during oral ASA medication. A therapeutic plasma salicylate concentration can be attained using enteric-coated ASA tablets at a dose rate of 25 mg/kg body wt, administered every 8 h. Six beagle dogs were given enteric-coated ASA tablets (500 mg) orally, in a 5-day cross-over experiment on two different feeding regimens: i.e. feeding once daily (Group I) or 8 hourly (Group II). Results demonstrate that feeding regimen strongly influences the plasma salicylate concentration pattern. Subtherapeutic mean plasma salicylate concentrations were found in both groups. In Group II the standard deviation (SD) of the mean plasma salicylate concentration was larger than that of Group I. The minimal plasma salicylate concentration never reached detectable levels in Group II. In both groups large numbers of tablets were vomited. Gastric evacuation of the ASA tablets is comparable to indigestible solid particles; their removal was dependent on the interdigestive gastric motility. It is concluded that large enteric-coated ASA tablets are not suitable for therapeutic use in small dogs.

Duration of the effect of acetylsalicylic acid on circulating platelet aggregates in cerebral infarct patients

The number of "circulating platelet aggregates" was examined in 33 patients who had suffered a cerebral infarct. Examination was done before onset of treatment with acetylsalicylic acid (ASA), 2 hours after ASA medication, and 12 hours after ASA medication, employing a modification of the platelet function measuring method according to the authors Wu and Hoak. The significant increase in the number of circulating platelet aggregates, compared with healthy persons, was found to be significantly reduced 2 and 12 hours after ASA medication. After 2 hours, we found in only 6% of the patients an increase in the number of circulating platelet aggregates above the mean value + triple (simple) standard deviation for n = 71 healthy controls. 12 hours after ASA administration 30% of the patients had again passed beyond the liberally defined standard level of the method.