Aspirin Resistance in Patients Undergoing Hemodialysis and Effect of Hemodialysis on Aspirin Resistance

Aksu, Hale Ünal; Oner, Ender; Çelik, Ömer; Işıksaçan, Nilgün; Aksu, Hüseyin; Uzun, Sami; Yavuz, Derya; Öztürk, Savaş; Gül, Mehmet; Uslu, Nevzat

doi:10.1177/1076029613489597

Cited by 10 publications

(7 citation statements)

References 22 publications

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“…Most studies report a HTPR rate of approximately 20% using MEA . In patients undergoing haemodialysis, 50% of patients had HTPR . Interestingly, in patients undergoing coronary artery bypass‐graft surgery, the HTPR rate increased postoperatively .…”

Section: Discussionmentioning

confidence: 46%

Acetylsalicylic acid in critically ill patients: a cross‐sectional and a randomized trial

Schoergenhofer

Hobl

Schwameis

et al. 2017

Eur J Clin Investigation

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BackgroundDespite decades of clinical use, the pharmacokinetics and the effects of acetylsalicylic acid (ASA) in critically ill patients remain ill‐defined. We aimed to investigate the pharmacokinetics and the effects of different ASA formulations during critical illness.DesignA cross‐sectional study and a randomized, parallel‐group trial were performed. Critically ill patients under chronic oral ASA treatment (100 mg enteric‐coated) were screened for high ‘on‐treatment’ platelet reactivity (HTPR) according to arachidonic acid‐induced whole‐blood aggregometry. Thirty patients with HTPR were randomized to receive 100 mg ASA intravenously, 100 mg enteric‐coated ASA bid (bis in die) or 81 mg chewable ASA (n = 10 per group). Serum thromboxane B2 (TXB2) levels, ASA and salicylic acid levels were quantified.ResultsOf 66 patients, 85% (95% confidence intervals 74–93%) had HTPR. Compared to baseline infusion of 100 mg, ASA significantly reduced platelet aggregation after 24 h to median 80% (Quartiles: 66–84%). Intake of 81 mg chewable ASA significantly reduced platelet aggregation to 75% (54–86%) after four hours, but increased it to 117% after 24 h (81–163%). Treatment with 100 mg enteric‐coated ASA bid decreased platelet aggregation after 24 h to median 56% (52–113%). Baseline TXB2 levels were median 0·35 ng/mL (0·07–0·94). Infusion of ASA or intake of 100 mg ASA bid reduced TXB2 levels to 0·07–0·18 ng/mL after 24 h, respectively. Chewable ASA reduced TXB2 levels only transiently. Pharmacokinetic analysis revealed highly variable absorption patterns of oral ASA formulations.ConclusionThere is a very high prevalence of HTPR in critically ill patients on peroral ASA therapy, caused by an incomplete suppression of TXB2 and/or by impaired absorption of ASA.

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Section: Discussionmentioning

confidence: 46%

Acetylsalicylic acid in critically ill patients: a cross‐sectional and a randomized trial

Schoergenhofer

Hobl

Schwameis

et al. 2017

Eur J Clin Investigation

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“…In many studies, the relationship between chronic renal failure and AR has been established. 26,27 We also found that the creatinine level was one of the independent predictors of AR (OR: 37.565; 95% CI: 2.21-636.35; P = .012). In vivo and in vitro studies have shown the effect of hyperlipidemia on AR.…”

Section: Discussionmentioning

confidence: 52%

The Relationship Between Aspirin Resistance and Carotid Imaging in Young Patients With ST-Segment Elevated Myocardial Infarction: A Cross-Sectional Study

Somuncu

Demir

Karakurt

et al. 2018

Clin Appl Thromb Hemost

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The presence of carotid atherosclerosis accompanied by coronary artery disease is associated with poor prognosis. A subset of patients who take aspirin continue to have recurrent cardiovascular events, which may be due to aspirin resistance (AR). Also, carotid plaques may cause turbulent flow which in turn may lead to platelet activation and poor antiplatelet response. In our study, we aimed to show the prevalence of AR and its relationship between high-risk carotid images in young patients with ST-segment elevated myocardial infarction (STEMI). In our study, we included 112 patients younger than 45 years with STEMI. Aspirin response test was evaluated 1 hour after aspirin intake using multiplate platelet function analyzer, and carotid ultrasonography has been performed to determine carotid intima-media thickness (CIMT) and the presence of carotid plaque. We identified 30.3% AR in young patients with STEMI. Carotid intima-media thickness ( P = .002), carotid plaque ( P = .012), and high-risk carotid image ( P = .015) values are significantly high in patients who have AR. Independent of other risk factors, the presence of carotid plaque and being in the high-risk carotid group were associated with 3.7 times and 3.2 times increased odds for AR, respectively. In young patients with STEMI, physicians should be careful about AR, especially in patients who have carotid plaque and thicker CIMT.

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“…This could be explained by aspirin resistance, which is known to occur to a higher degree in patients on HD than in other patient populations. 56 Our patient sample was too small to adequately evaluate the response to ASA in patients on HD. To our knowledge, a link between carbamylation and ASA resistance has not been investigated before.…”

Section: Discussionmentioning

confidence: 97%

Carbamylation of Integrin α IIb β 3: The Mechanistic Link to Platelet Dysfunction in ESKD

Binder

Chruścicka-Smaga

Bergum

et al. 2022

JASN

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BackgroundBleeding diatheses, common among patients with ESKD, can lead to serious complications, particularly during invasive procedures. Chronic urea overload significantly increases cyanate concentrations in patients with ESKD, leading to carbamylation, an irreversible modification of proteins and peptides.MethodsTo investigate carbamylation as a potential mechanistic link between uremia and platelet dysfunction in ESKD, we used liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to quantify total homocitrulline, and biotin-conjugated phenylglyoxal labeling and Western blot to detect carbamylated integrin αIIbβ3 (a receptor required for platelet aggregation). Flow cytometry was used to study activation of isolated platelets and platelet-rich plasma. In a transient transfection system, we tested activity and fibrinogen binding of different mutated forms of the receptor. We assessed platelet adhesion and aggregation in microplate assays.ResultsCarbamylation inhibited platelet activation, adhesion, and aggregation. Patients on hemodialysis exhibited significantly reduced activation of αIIbβ3 compared with healthy controls. We found significant carbamylation of both subunits of αIIbβ3 on platelets from patients receiving hemodialysis versus only minor modification in controls. In the transient transfection system, modification of lysine 185 in the β3 subunit was associated with loss of receptor activity and fibrinogen binding. Supplementation of free amino acids, which was shown to protect plasma proteins from carbamylation-induced damage in patients on hemodialysis, prevented loss of αIIbβ3 activity in vitro.ConclusionsCarbamylation of αIIbβ3—specifically modification of the K185 residue—might represent a mechanistic link between uremia and dysfunctional primary hemostasis in patients on hemodialysis. The observation that free amino acids prevented the carbamylation-induced loss of αIIbβ3 activity suggests amino acid administration during dialysis may help to normalize platelet function.

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Aspirin Resistance in Patients Undergoing Hemodialysis and Effect of Hemodialysis on Aspirin Resistance

Cited by 10 publications

References 22 publications

Acetylsalicylic acid in critically ill patients: a cross‐sectional and a randomized trial

Acetylsalicylic acid in critically ill patients: a cross‐sectional and a randomized trial

The Relationship Between Aspirin Resistance and Carotid Imaging in Young Patients With ST-Segment Elevated Myocardial Infarction: A Cross-Sectional Study

Carbamylation of Integrin α IIb β 3: The Mechanistic Link to Platelet Dysfunction in ESKD

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