Variable Platelet Response to Aspirin in Patients with Ischemic Stroke

Hohlfeld, Thomas; Weber, Artur‐Aron; Junghans, Ulrich; Schumacher, Marc; Boucher, Marc; Schrör, Karsten; Siebler, Mario

doi:10.1159/000103115

Cited by 33 publications

(24 citation statements)

References 68 publications

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“…In a recent review on response variability to aspirin, a significantly higher prevalence of aspirin resistance was seen in patients with a long treatment period [16]. Loss of the antiplatelet effect of aspirin due to prolonged administration (tachyphylaxis) has been proposed [12,14]. There was a high rate of patients with signs of prothrombotic disorders in both groups in our study.…”

Section: Discussionsupporting

confidence: 49%

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Aspirin Resistance in Patients with Hemodynamic Cerebral Ischemia Undergoing Extracranial-Intracranial Bypass Surgery

Jussen¹,

Horn²,

Vajkoczy³

2013

Cerebrovasc Dis

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Background: Aspirin (acetylsalicylic acid, ASA) is the treatment of choice for prevention of vascular events in symptomatic steno-occlusive cerebrovascular disease (CVD). Cerebral revascularization using standard extracranial-intracranial (EC-IC) bypass surgery may be used to revert hemodynamic compromise. Aspirin is prescribed as standard medication in order to avoid bypass failure. Accumulating evidence of an increased risk of major adverse clinical events led to this study, in which we aimed to assess the prevalence of aspirin resistance and prothrombotic disorders among patients scheduled for EC-IC bypass surgery, and the effectiveness of aspirin dose escalation. Methods: We prospectively screened patients with circumscribed high-grade stenosis or occlusion of brain-supplying vessels fulfilling the hemodynamic criteria for EC-IC bypass surgery for aspirin resistance using a platelet function analyzer (PFA-100®) test. We also determined their smoking habits and screened for prothrombotic disorders and comorbidities. The patients were divided into 2 major groups: group A had atherosclerotic steno-occlusive CVD and group B consisted of patients with nonatherosclerotic steno-occlusive CVD (moyamoya disease) and a subgroup of pediatric moyamoya patients (pediatric subgroup). Bypass patency was documented via digital subtraction angiography. Standard initial ASA dose applied was 100 mg/day. In cases of aspirin resistance, doses were increased and the PFA-100 test was repeated. Results: A total of 56 patients were included over a time period of 6 months. In group A (n = 25), we found a ratio of 40% of patients with primary resistance to aspirin 100 mg/day. In contrast, in group B (n = 25), only 20% of the patients were resistant to aspirin 100 mg/day; in the pediatric population (n = 6), there was no primary aspirin resistance. After a dose escalation to 300 mg/day, the ratio of aspirin resistance was reduced to 20% in group A and to 0% in group B. Altogether 5 patients with atherosclerotic steno-occlusive CVD remained aspirin-resistant despite the dose escalation; 2 of them suffered an early bypass failure. Smoking habits and diabetes mellitus were positively correlated with aspirin resistance. Moreover, 25% of all patients had laboratory signs of a prothrombotic disorder, but this had no influence on aspirin response or bypass patency. Conclusions: Aspirin resistance is common in the population of patients with hemodynamic cerebral ischemia scheduled for cerebral revascularization. It may have an adverse impact on the outcome of surgery. Screening and treatment via dose escalation of aspirin is a straightforward and sensible routine for patients undergoing EC-IC bypass surgery.

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Section: Discussionsupporting

confidence: 49%

“…There is still controversy regarding aspirin resistance and the optimal dosing of aspirin [8]. More than 20% of the normal population and even more in populations with former vascular events show resistance to aspirin medication in low doses [12,13,14]; this increases the risk for further ischemic events [15,16,17]. …”

Section: Introductionmentioning

confidence: 99%

Aspirin Resistance in Patients with Hemodynamic Cerebral Ischemia Undergoing Extracranial-Intracranial Bypass Surgery

Jussen¹,

Horn²,

Vajkoczy³

2013

Cerebrovasc Dis

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“…A broad range of responses from partial to complete inhibition of aggregation was observed; we can only speculate on the influence of genetics, the current status of the organism in terms of infection, organ functions and metabolism, or external circumstances. Higher thrombocytic excitability has also been repeatedly reported in acute stroke [8,9], but its role as a consequence or underlying cause of acute stroke has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Different Doses and Different Routes of Acetylsalicylic Acid Administration on Platelet Aggregation in Healthy Volunteers and Ischemic Stroke Patients

Chylova

Moťovská

Osmančík

et al. 2014

Transl. Stroke Res.

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The purpose was to assess the effect of different doses and different routes of acetylsalicylic acid (ASA) administration on platelet aggregation and the comparison between platelet aggregation after the single and the repetitive administration of ASA in healthy individuals and in patients after ischemic stroke. The study group consists of 22 healthy individuals and 30 patients with documented ischemic stroke. Platelet aggregation was measured in healthy individuals: (a) twice before ASA and (b) 2 h after different single doses and different routes of ASA administration-(b1) 500 mg orally, (b2) 500 mg intravenously, and (b3) 100 mg orally. We measured aggregability in healthy individuals after five consecutive days of 100 mg of ASA q.d. and in patients on chronic ASA 100 mg q.d. The VerifyNow was used with results expressed in aspirin reaction units (ARU). In healthy individuals, the dose-(b1) 500 mg orally-reduced the aggregability to mean (SD) 392 (36) ARU (p < 0.001), (b2) 500 mg intravenously to 428 (46) (p < 0.001) and (b3) 100 mg orally to 460 (76) (p < 0.001). The suppression of aggregation after 500 mg was (p = 0.029) higher after the oral compared to intravenous administration, and the same is true for the suppression after single dose of 500 mg orally and 100 mg orally (p = 0.011). Oral dose 100 mg for 5 days in healthy individuals reduced aggregation to 405 (37) and in post-stroke patients to 433 (54). All doses of ASA, both orally and intravenously, have produced a significant reduction of platelet aggregation. Preference of the parenteral to oral application has not been established.

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“…However, the pharmacodynamic response to antiplatelet medication varies significantly between individuals [2]. Insufficient response is defined as high on-treatment platelet reactivity (HTPR) [3]. Several factors are known to be associated with impaired pharmacodynamic response to antiplatelet medication, like drug-drug interactions, genetic polymorphisms, enhanced platelet turnover, incompliance to medication, and comorbidities like chronic kidney disease or diabetes [4,5,6].…”

Section: Introductionmentioning

confidence: 99%

Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin

Mohring

Piayda²,

Dannenberg³

et al. 2017

Pharmacology

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Platelet inhibition by aspirin is indispensable in the secondary prevention of cardiovascular events. Nevertheless, impaired aspirin antiplatelet effects (high on-treatment platelet reactivity [HTPR]) are frequent. This is associated with an enhanced risk of cardiovascular events. The current gold standard to evaluate platelet hyper-reactivity despite aspirin intake is the light-transmittance aggregometry (LTA). However, pharmacologically, the most specific test is the measurement of arachidonic acid (AA)-induced thromboxane (TX) B2 formation. Currently, the optimal cut-off to define HTPR to aspirin by inhibition of TX formation is not known. Therefore, in this pilot study, we aimed to calculate a TX formation cut-off value to detect HTPR defined by the current gold standard LTA. We measured platelet function in 2,507 samples. AA-induced TX formation by ELISA and AA-induced LTA were used to measure aspirin antiplatelet effects. TX formation correlated nonlinearly with the maximum of aggregation in the AA-induced LTA (Spearman's rho R = 0.7396; 95% CI 0.7208-0.7573, p < 0.0001). Receiver operating characteristic analysis and Youden's J statistics revealed 209.8 ng/mL as the optimal cut-off value to detect HTPR to aspirin with the TX ELISA (area under the curve: 0.92, p < 0.0001, sensitivity of 82.7%, specificity of 90.3%). In summary, TX formation ELISA is reliable in detecting HTPR to aspirin. The calculated cut-off level needs to be tested in trials with clinical end points.

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Variable Platelet Response to Aspirin in Patients with Ischemic Stroke

Cited by 33 publications

References 68 publications

Aspirin Resistance in Patients with Hemodynamic Cerebral Ischemia Undergoing Extracranial-Intracranial Bypass Surgery

Aspirin Resistance in Patients with Hemodynamic Cerebral Ischemia Undergoing Extracranial-Intracranial Bypass Surgery

The Effect of Different Doses and Different Routes of Acetylsalicylic Acid Administration on Platelet Aggregation in Healthy Volunteers and Ischemic Stroke Patients

Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin

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