Aspirin failure in patients presenting with acute cerebrovascular ischaemia

2011 ◽  
Vol 106 (08) ◽  
pp. 240-247 ◽  
Author(s):  
Saeed H. M. Halawani ◽  
David J. P. Williams ◽  
John Webster ◽  
Michael Greaves ◽  
Isobel Ford
Keyword(s):  
Platelet Aggregation ◽  
Ischaemic Stroke ◽  
High Sensitivity ◽  
Adenosine Diphosphate ◽  
Platelet Inhibition ◽  
Antiplatelet Drug ◽  
Platelet Response ◽  
Reactive Protein ◽  
Fibrinogen Binding ◽  
Von Willebrand

SummaryAspirin is the most commonly used antiplatelet drug for prevention of ischaemic stroke. In order to determine the prevalence and nature of aspirin failure, we studied 51 adults admitted with suspected ischaemic stroke and already prescribed daily aspirin. Within 48 hours (h) of onset, blood and urine samples were collected to assess platelet aggregation, activation and aspirin response by a range of methods. All tests were then repeated on a second sample taken 24 h after witnessed administration of 75 mg or 150 mg aspirin. At entry to the study, incomplete response to aspirin, measured by arachidonic acid (AA)-stimulated platelet aggregation, was found in 43% of patients. Following in-hospital aspirin administration, there was a significant decrease in AA-aggregation (p=0.001) suggesting poor adherence to therapy prior to admission. However, residual aggregation (10–15%) persisted in 11 subjects – suggesting alternative causes. In incomplete responders on admission, platelet aggregation with adenosine diphosphate (ADP) was significantly higher compared with responders (p<0.05) but there were no significant differences in collagen aggregation, platelet fibrinogen binding or P-selectin expression, plasma von Willebrand factor, fibrinogen, high-sensitivity C-reactive protein, or the urinary metabolite, 11-dehydro-TxB2. Incomplete platelet inhibition is common around the time of acute cerebrovascular ischaemic events in patients prescribed aspirin. Up to 50% of these observations appear due to incomplete adherence to aspirin therapy. Intervention studies are required to determine the clinical relevance of measured platelet response to aspirin in terms of outcome, and the effectiveness of improved pharmacotherapy for stroke prevention.

Abstract 3473: The Effect of Cigarette Smoking on the Antiplatelet Effect of Clopidogrel: The Smokers Paradox

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paul Gurbel ◽  
Joseph Dichiara ◽  
Kevin P Bliden ◽  
Mark J Antonino ◽  
Lawal Lookman
Keyword(s):  
Platelet Aggregation ◽  
Cigarette Smoking ◽  
Metabolic Activation ◽  
Adenosine Diphosphate ◽  
Platelet Inhibition ◽  
Response Variability ◽  
Light Transmittance ◽  
Prior History ◽  
Platelet Response ◽  
Clopidogrel Therapy

Background: Wide response variability to clopidogrel therapy has been reported. Clopidogrel is a prodrug that requires metabolic activation by hepatic cytochromes (CYP). Cigarette smoking is an inducer of CYP1A2 and may, therefore, enhance the metabolism of clopidogrel. We sought to examine the effect of cigarette smoking on the platelet response to clopidogrel. Methods: Three hundred thirteen consecutive patients undergoing elective coronary stenting were studied. Platelet aggregation (PA) was assessed by light transmittance aggregometry (LTA) stimulated by 5 and 20μ M adenosine diphosphate. One hundred fourteen patients were on chronic clopidogrel therapy, were not reloaded, and had pre-stenting PA measurements. Pre-and post-stenting PA was measured in 199 patients: 60 were loaded with 300mg and 139 were loaded with 600mg. There were 120 current smokers (smoking within 2 weeks of PCI) and 193 non-smokers (no prior history of smoking). Low PA was defined as the lowest two quartiles of 5μM ADP-induced platelet aggregation (≤ 40%). Results: PA was significantly lower (p ≤ 0.008) in smokers on long term chronic clopidogrel treatment (Table ). Relative platelet inhibition (RPI) was higher in smokers treated with either 300mg or 600mg clopidogrel measured by 5 and 20μM ADP-induced PA. In a multivariate analysis, cigarette smoking was an independent predictor of low PA in patients on chronic clopidogrel therapy and in patients loaded with clopidogrel (r=0.3, p=0.0001). Conclusion: Clopidogrel therapy in smokers is associated with increased platelet inhibition and lower aggregation as compared to non-smokers. The mechanism of the smoking effect deserves further study and may be another cause of response variability to clopidogrel. RPI = 100 x ((baseline aggregation-post-treatment aggregation)/(baseline aggregation))

Platelet Function and the Bleeding Time in Progressive Renal Failure

1988 ◽  
Vol 60 (01) ◽  
pp. 083-087 ◽  
Author(s):  
M P Gordge ◽  
R W Faint ◽  
P B Rylance ◽  
G H Neild
Keyword(s):  
Renal Failure ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Bleeding Time ◽  
C Reactive Protein ◽  
Severe Renal Failure ◽  
Reactive Protein ◽  
Thromboxane Production ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryBleeding time and platelet function tests were performed on 31 patients with progressive chronic renal failure (CRF) due to non-immunological (urological) causes, and compared with 22 healthy controls. Patients were classified as mild (plasma creatinine <300 μmol/l), moderate (300-600 μmol/l) or severe renal failure (>600 μmol/l). Bleeding time was rarely prolonged in mild and moderate CRF and mean bleeding time significantly elevated only in severe CRF (p <0.005). Haematocrit was the only index which correlated with bleeding time (r = -0.40). Platelet counts, collagen stimulated thromboxane generation, and platelet aggregation responses to ADP, collagen and ristocetin were all either normal or increased in all three CRF groups, but thromboxane production in clotting blood was reduced. Plasma fibrinogen, C reactive protein and von Willebrand factor (vWF) were elevated in proportion to CRF. We found no evidence that defects in platelet aggregation or platelet interaction with vWF prolong the bleeding time in patients with progressive CRF.

scholarly journals Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1150
Author(s):  
Alberto Zanetto ◽  
Marco Senzolo ◽  
Elena Campello ◽  
Cristiana Bulato ◽  
Sabrina Gavasso ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Compensated Cirrhosis ◽  
Impedance Aggregometry ◽  
Child Class ◽  
Von Willebrand ◽  
Willebrand Factor

Hyper-functional platelets are being proposed as a potential therapeutic target in multiple cancers. Whether this can be considered in patients with cirrhosis and hepatocellular carcinoma (HCC) is unknown as their platelet function has not yet been investigated. We evaluated platelet function in cirrhosis patients with HCC. Patients with cirrhosis with and without HCC were prospectively recruited. Platelet aggregation, a marker of platelet function, was assessed by impedance aggregometry with adenosine diphosphate (ADP), arachidonic acid (ASPI), and thrombin (TRAP) stimulation. Plasmatic levels of Von Willebrand factor antigen (VWF) were also determined. One-hundred patients were recruited (50 cirrhotics with and 50 without HCC). Cirrhosis severity by Child class and platelet count were comparable between cirrhotics with and without HCC. Cirrhotics with HCC had higher ADP- (45 vs. 28; p < 0.001), ASPI- (47 vs. 28; p < 0.001), and TRAP- (85 vs. 75; p = 0.01) induced platelet aggregation than cirrhotics without HCC, all indicative of platelet hyper-function. The relatively increased platelet aggregation in patients with HCC was confirmed after adjusting the analysis for platelet count/severity of thrombocytopenia. Levels of VWF were higher in patients with vs. without HCC (348 vs. 267; p = 0.006), particularly in compensated cirrhosis. In patients with cirrhosis, HCC is associated with increased platelet aggregation and higher VWF. The clinical implications of these findings deserve further investigation.

Ticlopidine Selectively Inhibits Human Platelet Responses to Adenosine Diphosphate

1991 ◽  
Vol 66 (06) ◽  
pp. 694-699 ◽  
Author(s):  
Marco Cattaneo ◽  
Benjaporn Akkawat ◽  
Anna Lecchi ◽  
Claudio Cimminiello ◽  
Anna M Capitanio ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Clot Retraction ◽  
Fibrinogen Binding ◽  
Low Concentrations ◽  
Binding Inhibition ◽  
High Concentrations ◽  
Formalin Fixed

SummaryPlatelet aggregation and fibrinogen binding were studied in 15 individuals before and 7 days after the oral administration of ticlopidine (250 mg b.i.d.). Ticlopidine significantly inhibited platelet aggregation induced by adenosine diphosphate (ADP), the endoperoxide analogue U46619, collagen or low concentrations of thrombin, but did not inhibit platelet aggregation induced by epinephrine or high concentrations of thrombin. Ticlopidine inhibited 125I-fibrinogen binding induced by ADP, U46619 or thrombin (1 U/ml). The ADP scavengers apyrase or CP/CPK, added in vitro to platelet suspensions obtained before ticlopidine, caused the same pattern of aggregation and 125I-fibrihogen binding inhibition as did ticlopidine. Ticlopidine did not inhibit further platelet aggregation and 125I-fibrinogen binding induced in the presence of ADP scavengers. After ticlopidine administration, thrombin or U46619, but not ADP, increased the binding rate of the anti-GPIIb/IIIa monoclonal antibody 7E3 to platelets. Ticlopidine inhibited clot retraction induced by reptilase plus ADP, but not that induced by thrombin or by reptilase plus epinephrine, and prevented the inhibitory effect of ADP, but not that of epinephrine, on the PGE1-induced increase in platelet cyclic AMP. The number of high- and low-affinity binding sites for 3H-ADP on formalin-fixed platelets and their K d were not modified by ticlopidine. These findings indicate that ticlopidine selectively inhibits platelet responses to ADP.

Effects of Sulodexide on Hemostatic Factors, Lipid Profile, and Inflammation in Chronic Peritoneal Dialysis Patients

2007 ◽  
Vol 27 (4) ◽  
pp. 456-460 ◽  
Author(s):  
Soon Bae Kim ◽  
Su Hee Kim ◽  
Moo Song Lee ◽  
Jai Won Chang ◽  
Sang Koo Lee ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Dermatan Sulfate ◽  
High Sensitivity ◽  
Blood Levels ◽  
Chronic Peritoneal Dialysis ◽  
Dialysis Patients ◽  
Reactive Protein ◽  
Hemostatic Factors ◽  
Bleeding Episodes ◽  
Von Willebrand

Sulodexide, a standardized extractive glycosaminoglycan containing 80% “fast moving” heparin and 20% dermatan sulfate, decreased plasma D-dimer, a marker of intravascular coagulation, and fibrinogen levels in chronic peritoneal dialysis patients. Blood levels of von Willebrand factor, lipid, and high-sensitivity C-reactive protein were not significantly changed. No bleeding episodes were reported. These results suggest that sulodexide was effective in partially reversing the thrombogenic coagulation profile without increasing the risk of bleeding.

scholarly journals Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein IIb-IIIa with conformation-specific monoclonal antibodies

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 2017-2023 ◽  
Author(s):  
MH Ginsberg ◽  
AL Frelinger ◽  
SC Lam ◽  
J Forsyth ◽  
R McMillan ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ligand Binding ◽  
Cell Activation ◽  
Flow Cytometric Analysis ◽  
Adenosine Diphosphate ◽  
Receptor Activation ◽  
Affinity Column ◽  
Primary Defect ◽  
Fibrinogen Receptor ◽  
Fibrinogen Binding

Abstract Normal primary platelet aggregation requires agonist-mediated activation of membrane GPIIb-IIIa, binding of fibrinogen to GPIIb-IIIa, and cellular events after ligand binding. PAC1 monoclonal antibody distinguishes between resting and activated states of GPIIb-IIIa, and other antibodies preferentially recognize GPIIb (PMI-1) or IIIa (anti- LIBS1) after the binding of fibrinogen or fibrinogen-mimetic peptides, such as GRGDSP. Using these antibodies and platelet flow cytometry, we studied two distinct persistent platelet aggregation abnormalities. Platelets from a thrombasthenic variant, which contained near-normal amounts of GPIIb-IIIa, failed to aggregate or bind PAC1 in response to agonists. In addition, GRGDSP, which binds to normal GPIIb-IIIa without prior cell activation, failed to increase the binding of PMI-1 or anti- LIBS1 to the thrombasthenic platelets, suggesting a primary defect in ligand binding. Chromatography of detergent-solubilized platelets on a KYGRGDS affinity column confirmed that the patient's GPIIb-IIIa lacked the fibrinogen binding site. In another patient with myelofibrosis and defective aggregation, PAC1 failed to bind to adenosine diphosphate- stimulated platelets, but did bind when protein kinase C was directly activated with phorbol myristate acetate. Furthermore, the binding of PMI-1 and anti-LIBS1 increased in response to GRGDSP, confirming a defect in agonist-mediated fibrinogen receptor activation rather than in fibrinogen binding or events distal to binding. These studies indicate that this immunochemical approach is useful in classification of clinical abnormalities of platelet aggregation as defects in either (a) fibrinogen receptor activation, (b) fibrinogen binding, or (c) postoccupancy events.

scholarly journals Screening for von Willebrand Disease With a New Analyzer Using High Shear Stress: A Study of 60 Cases

Blood ◽  
1998 ◽  
Vol 91 (4) ◽  
pp. 1325-1331 ◽  
Author(s):  
Edith Fressinaud ◽  
Agnès Veyradier ◽  
Florence Truchaud ◽  
Isabelle Martin ◽  
Catherine Boyer-Neumann ◽  
...  
Keyword(s):  
Shear Stress ◽  
High Sensitivity ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
Von Willebrand Disease ◽  
High Shear ◽  
High Shear Stress ◽  
Platelet Disorder ◽  
Von Willebrand

AbstractWe have evaluated the performance of a new analyzer using high shear stress, the PFA-100 (Platelet Function Analyzer, Dade International, Massy, France), for screening of patients with von Willebrand disease (vWD). Whole citrated blood is aspirated through a capillary to the central aperture of a membrane coated with collagen and with a platelet agonist (either epinephrine or adenosine diphosphate [ADP]). The time required to obtain occlusion of the aperture by a platelet plug is defined as the closure time (CT). We studied 60 patients with different types of vWD and 96 normal subjects. Fourteen subjects with hemophilia and 15 patients with a platelet disorder were also analyzed. When omitting results from two patients with type 2N, the 58 other patients with type 1, type 2A, type 2B, type 3, or acquired vWD all exhibited an abnormal occlusion with collagen-ADP (sensitivity, 100%) and 56 of 58 had an abnormal CT with collagen-epinephrine (sensitivity, 96.5%). Only two patients with mild type 1 were not detected with collagen-epinephrine. In comparison, the bleeding time (BT) was normal in 20 patients: 17 with type 1, two with type 2A, and one with acquired vWD (sensitivity, 65.5%). The specificity of the PFA-100 was over 95% with both types of cartridges. Thus, the analyzer is well adapted to routine testing, as it has the advantages of simplicity and ease of execution, and demonstrates a high sensitivity, clearly superior to that of BT, for the screening of patients with vWD.

Comparison of Cationic Propyl Gallate and Adenosine Diphosphate for the Meassurement of Aspirin Effectivity with Optical Aggregometry.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3943-3943 ◽  
Author(s):  
Zuzana Motovska ◽  
Zdenka Sujanova ◽  
Sona Wimmerova ◽  
Jan Ardo ◽  
Marcela Skrakova ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Propyl Gallate ◽  
Treated Patient ◽  
High Sensitivity ◽  
Adenosine Diphosphate ◽  
Close Correlation ◽  
Light Transmittance ◽  
Measured Parameter ◽  
Control Group ◽  
Statistical Parameters

Abstract Background. The goal of our interest is to bring attention to standardisation of the aspirin effectiveness examination in patients profiting from (life)long antithrombotic terapy. Optical platelet aggregation tests have been most widely used. Examination with endogenous inductors of platelet aggregation - thrombin, colagen, arachidonic acid, adenosine diphosphate (ADP) has a low specificity and reproducibility. Aim. To compare a newer inductor of platelets aggregation cationic propyl gallate (CPG) with ADP for the examination of aspirin (ASA) efffectivity with optical aggregometry. Methods. We prospectively enrolled 116 consecutive patiens with a stable cardiovascular disease on ASA 100mg/day for ≥ 1 month. The controll group was formed from 62 healthy volunteers, without antithrombotic treatment. Analysis. We investigated platelet aggregation by optical aggregometry (aggregometer LASER 4x, BIOART). CPG and ADP were added as aggregating agents. The measured parameter were: CPG-slope (this parameter expresses steepness of the aggregation curve and also the speed of aggregation (%/minutes)) and ADP-max (the maximum percent change in light transmittance from baseline). Results. Definition. First, we determined the CPG-slope cut-off value for the definition of ASA-non-effective treated patient. We established it on the ground of CPG-slope values in the control group. The values from controll group followed a normal distribution (test Shapiro - Wilk). We calculated the cut-off value using the 95% - confidence interval. The CPG-slope cut-off value was 79 %/min for ASA-effective treated patient. We marked the patients as ASA-non efffective treated when the CPG-slope was ≥ 79%/min. The same way we used to define the cut-off value for ADP-max. We identified the aspirin treatment as uneffective when the value of ADP-max had been > 62%. Comparison. The values of CPG-slope and ADP-max were in a close correlation in the group of patients treated with aspirin. The correlation index (r = 0,671) was highly significant. By CPG-induced optical aggregation were 33,6% ASA-non-effective treated patients. While using both inductors (CPG, ADP) were the proportion of ASA-non-effective treated patients 25%. By both tests (CPG, ADP) were equally divided 71,6% patients. ASA-non-effective treated patients were more commonly obese (46,2%) with hypertension (94,9%) and hypercholesterolemia (73,7%) and were less commonly treated with statins (30,8%) as the aspirin effective treated patients (42,%, 88,2%, 59,2% resp.42,1%). Conclusion. Meassurement of a platelet aggregation by CPG is reproducible with high sensitivity and specificity. The study has also brought attention to the importance of control the cardiovascular risk factors. Figure. Statistical parameters Figure. Statistical parameters

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