Lack of association between aspirin responsiveness and seven candidate gene haplotypes in patients with symptomatic vascular disease

2009 ◽  
Vol 101 (01) ◽  
pp. 123-133 ◽  
Author(s):  
Shirley Williams ◽  
Diane Nugent ◽  
Paul Harrison ◽  
Helen Segal ◽  
Anila Syed ◽  
...  

SummaryWe studied the effect of prophylactic aspirin (ASA) ingestion on platelet function in 463 patients with stroke, transient ischemic attack (TIA) or acute coronary disease (ACD), using the Platelet Function Analyzer-100 (PFA-100). We correlated ASA responsiveness with haplotypes of seven candidate genes, selected for their documented role in platelet function, namely, the genes for integrins α2β1and αIIbβ3 (ITGA2, ITGA2B, and ITGB3), platelet glycoproteins Ibα and VI (GPIBA and GP6), the purinergic receptor P2Y1 (P2RY1), and prostaglandin H synthase 1 (PTGS1 = COX1). Non-responsiveness to ASA was defined as the failure of prior ASA ingestion to prolong the PFA-100 closure time (CT) when blood was perfused through cartridges coated with collagen plus epinephrine (CEPI-CT). ASA non-responsiveness was observed in 114 of 463 patients (24.6 %), but was not associated with haplotypes of any of the seven candidate genes. There was also no association between any haplotypes and the CT when blood was perfused through cartridges coated with collagen plus ADP (CADP-CT). The ASA non-responsive cohort had significantly increased whole blood platelet counts (p = 0.03) and plasma von Willebrand Factor antigen levels (p<0.001), which likely contributes to resistance to the inhibitory effects of ASA in the PFA-100.

2020 ◽  
Vol 22 (12) ◽  
pp. 1214-1218
Author(s):  
Elizabeth C Hiebert ◽  
David L Panciera ◽  
Katie M Boes ◽  
Lara Bartl

Objectives Cats with hyperthyroidism have been reported to develop thromboembolism, with and without echocardiographic abnormalities consistent with hyperthyroidism. The objective of this study was to compare platelet function in cats with hyperthyroidism with euthyroid age-matched cats. We hypothesized that cats with hyperthyroidism have shortened collagen and adenosine diphosphate (C-ADP) closure times as measured with the platelet function analyzer (PFA-100) in comparison with healthy, age-matched controls. Methods Sixteen hyperthyroid and nine euthyroid healthy cats >7 years of age were recruited from the hospital population. Platelet function, measured using the C-ADP closure times by the PFA-100, and platelet count were measured in healthy euthyroid cats and cats with hyperthyroidism. Results Mean ± SD closure times were not significantly different between control (66.3 ± 9.6 s) and hyperthyroid cats (65.9 ± 11.5 s; P = 0.75). The mean ± SD closure times of hyperthyroid cats that either were untreated or received methimazole for ⩽3 weeks (n = 6; mean 68.5 ± 15.4 s) was not different than that of cats treated for >3 weeks (n = 10; mean 64.3 ± 8.9 s; P = 0.57). The mean automated platelet count was higher in the hyperthyroid group than in the control group ( P = 0.023). Conclusions and relevance Platelet function, as measured by closure time under high shear conditions using C-ADP as an agonist, was not affected by hyperthyroidism in this group of cats. Further research is needed to determine if a hypercoagulable state exists in hyperthyroid cats and the potential roles platelets and von Willebrand factor may have.


Platelets ◽  
2018 ◽  
Vol 30 (2) ◽  
pp. 264-270 ◽  
Author(s):  
Isabell Pekrul ◽  
Thorsten Kragh ◽  
Peter L Turecek ◽  
Aaron R Novack ◽  
Helmut W Ott ◽  
...  

1996 ◽  
Vol 2 (4) ◽  
pp. 241-249 ◽  
Author(s):  
Sourav K. Kundu ◽  
Eric J. Heilmann ◽  
Reynaldo Sio ◽  
Carmen Garcia ◽  
Roy A. Ostgaard

A new in vitro system for the evaluation of platelet function, PFA-100 (currently under evaluation) is characterized. The system monitors platelet aggrega tion on a collagen-epinephrine-coated membrane as whole blood sample is aspirated under controlled flow conditions through a microscopic aperture cut into the membrane. The time required for the platelet plug to oc clude the aperture (closure time) is indicative of the plate let function in the sample. Incubation of normal blood samples with antibodies to glycoprotein (GP) Ib, GPIIb- IIIa, von Willebrand factor, or with the peptide Arg-Gly- Asp-Ser, resulted in a concentration-dependent prolonga tion in closure time. An anti-fibrinogen antibody did not impact the closure time. Closure time was also prolonged when the hematocrit or the platelet count was lowered to pathological values. The study indicates that PFA-100 could detect defects in platelet adhesion or aggregation. The simplicity of the test makes PFA-100 unique for rapid screening of a variety of platelet dysfunction.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Lulu Zhang ◽  
Xiaowei Hu ◽  
Juehua Zhu ◽  
Xiuying Cai ◽  
Yan Kong ◽  
...  

Background. The correlation between platelet function and recurrent ischemic stroke or TIA remains uncertain. Objective. To investigate two inductive agents to detect platelet functions and assess associations with recurrent ischemic stroke/TIA. Method. The study included 738 ischemic stroke/TIA patients. On days 0, 3, and 9 after antiplatelet therapy, platelet function tests were determined by maximum aggregation rate (MAR) using a PL-11 platelet function analyzer and phase matching reagents. Two induction agents were used: arachidonic acid (AA) and adenosine diphosphate (ADP). At 3-month follow-up, recurrence of stroke/TIA was recorded. Result. Cut-off values of adequate platelet function inhibition were MARADP < 35% and MARAA < 35%. Data showed that antiplatelet therapy could reduce the maximum aggregation rate. More importantly, adequate platelet function inhibition of either MARADP or MARAA was not associated with the recurrence of stroke/TIA, but adequate platelet function inhibition of not only MARADP but also MARAA predicts lower recurrence (0/121 (0.00%) versus 18/459 (3.92%), P = 0.0188). Conclusion. The platelet function tested by PL-11 demonstrated that adequate inhibition of both MARADP and MARAA could predict lower risk of ischemic stroke/TIA recurrence.


1995 ◽  
Vol 21 (S 02) ◽  
pp. 106-112 ◽  
Author(s):  
Sourav Kundu ◽  
Eric Heilmann ◽  
Reynaldo Sio ◽  
Carmen Garcia ◽  
Rosa Davidson ◽  
...  

A new in vitro system for the detection of platelet dysfunction, PFA-100™* has been developed. It provides a quantitative measure of platelet function in anticoagulated whole blood. The system comprises a microprocessor-controlled instrument and a disposable test cartridge containing a biologically active membrane. The instrument aspirates a blood sample under constant vacuum from the sample reservoir through a capillary and a microscopic aperture cut into the membrane. The membrane is coated with collagen and epinephrine or adenosine 5’-diphosphate. The presence of these biochemical stimuli, and the high shear rates generated under the standardized flow conditions, result in platelet attachment, activation, and aggregation, slowly building a stable platelet plug at the aperture. The time required to obtain full occlusion of the aperture is reported as the m“closure time.” We have found that impairment of von Willebrand factor, or inhibition of platelet receptors glycoprotein Ib or IIblIIIa with monoclonal antibodies or peptides, resulted in abnormal closure times. An antifibrinogen antibody, in contrast, failed to show any effect. The test appears to be sensitive to platelet adherence and aggregation abnormalities. The PFA-100™ system has potential applications in routine evaluation of platelet function in the clinical setting because of its accuracy, ease of operation, and rapid turnaround of results. * Under evaluation


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4054-4054
Author(s):  
Eric Bush ◽  
Shannon Smiley ◽  
Linda Belling ◽  
Zale P. Bernstein

Abstract Menorrhagia is a common problem among women. The pathophysiology has been attributed to Von Willebrand’s disease in some patients. The lab diagnosis and confirmation of this condition in these women is often difficult. The need for easily reproducible, validated lab investigations is recognized. The platelet function analyzer (PFA-100) (described below) has recently been used as an adjunct for lab diagnosis of this condition. Use of this device is relatively recent, thus clinical correlation with its results have been lacking. Therefore, we initiated a study to determine if a correlation could be established between pictorial blood assessment chart (PBAC), PFA-100, and Von Willebrand’s screening (VWF antigen and co-factor activity levels). Materials and methods: After obtaining informed consent 15 female patients with a diagnosis of von Villebrand’s disease were enrolled in the above study. All received verbal and written instructions of how to record their tampon/pad use on the PBAC. The PBAC was then scored on a validated and well-established point system for lightly (1point), moderately (2points) and heavily (3points) soiled pads or tampons. In addition their blood samples were analyzed for von Willebrand antigen, Ristocetin Co-Factor and on the PFA-100 (pre and post DDAVP). The PFA-100, is a high shear-inducing device which simulates primary hemostasis after injury to small vessel, which consists of a reservoir for whole blood and a small capillary surmounted by a collagen-coated membrane with a central aperture. Platelet agonist which is either epinephrine or ADP is present on the membrane. Closure time is reported as a variable which describes von Willebrand factor function. All blood samples were forwarded to Children’s Hospital of Buffalo Special Coagulation lab for examination of the PFA-100(pre and post DDAVP),and von Willebrand panel. Conclusion: There was correlation between the number of points self-assessed on the PBAC and the PFA-100. Summary Data Patient # Age # points/PBAC VWF Ristocetin Co Factor Factor VIII PFA 100 Pre DDAVP 1 48 10 56 52 70 104 2 47 23 73 53 138 90 3 21 9 69 70 63 151 4 47 180 75 51 120 280 5 44 25 107 68 114 124 6 49 47 102 93 74 63 7 25 12 74 51 84 177 8 26 8 30 28 77 216 9 30 24 47 64 115 125 10 27 11 76 45 60 118 11 25 10 66 49 79 136 12 48 11 51 48 121 117 13 25 9 59 42 44 99 14 23 41 33 11 34 275 15 46 84 3 2 11 300


2013 ◽  
Vol 60 (7) ◽  
pp. 1184-1187 ◽  
Author(s):  
Swati Naik ◽  
Jun Teruya ◽  
Jennifer E. Dietrich ◽  
Purvi Jariwala ◽  
Esther Soundar ◽  
...  

2004 ◽  
Vol 191 (2) ◽  
pp. 449-455 ◽  
Author(s):  
Andra H. James ◽  
Andrea S. Lukes ◽  
Leo R. Brancazio ◽  
Elizabeth Thames ◽  
Thomas L. Ortel

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