A polymorphism in the cytochrome P450 3A4 (CYP3A4) gene influences platelet activation and response to clopidogrel in patients with coronary artery disease

2006 ◽  
Vol &NA; (1554) ◽  
pp. 10
Author(s):  
&NA;
Author(s):  
Carolin Langnau ◽  
Anne-Katrin Rohlfing ◽  
Sarah Gekeler ◽  
Manina Günter ◽  
Simone Pöschel ◽  
...  

Objective: Patients with coronary artery disease (CAD) are at increased risk for cardiac death and respiratory failure following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Platelets are crucially involved in pathogenesis of CAD and might also contribute to pathophysiology of SARS-CoV-2 infection. Approach and Results: We enrolled a cohort of 122 participants from February 2020 to July 2020 including 55 patients with preexisting CAD and acute SARS-CoV-2 infection (CAD-SARS-CoV-2 positive ), 28 patients with CAD and without SARS-CoV-2 (CAD-SARS-CoV-2 negative ), and 39 healthy controls. Clinical and cardiac examination of the CAD-SARS-CoV-2 positive group included blood sampling, echocardiography, and electrocardiography within 24 hours after hospital admission. Phenotyping of platelets was performed by flow cytometry; plasma levels of chemokines were analyzed by ELISA. Respiratory failure of patients was stratified by the Horovitz index as moderately/severely impaired when Horovitz index <200 mm Hg. The clinical end point was defined as Horovitz index <200 mm Hg with subsequent mechanical ventilation within a follow-up of 60 days. CAD-SARS-CoV-2 positive patients display a significant enhanced platelet activation and hyper-inflammation early at time of hospital admission. Circulating platelet/leukocyte co-aggregates correlate with plasma levels of cytokines/chemokines like IL (interleukin)-6, CCL2, and CXCL10 as well as activation of platelets is associated with CCL5 and elevation of pulmonary artery pressure. Furthermore, furin is stored and released from activated platelets. High furin plasma levels are associated with poor clinical prognosis in CAD-SARS-CoV-2 positive patients. Conclusions: Patients with CAD and SARS-CoV-2 infection exhibit elevated systemic platelet activation and enhanced plasma levels of the subtilisin-like proprotein convertase furin, which may contribute to an unfavorable clinical prognosis.


Circulation ◽  
2004 ◽  
Vol 110 (15) ◽  
pp. 2132-2136 ◽  
Author(s):  
Martin Spiecker ◽  
Harald Darius ◽  
Thomas Hankeln ◽  
Muhidien Soufi ◽  
Alexander M. Sattler ◽  
...  

2015 ◽  
Vol 57 (1) ◽  
pp. 109-119 ◽  
Author(s):  
Akinyemi Oni-Orisan ◽  
Matthew L. Edin ◽  
John Andrew Lee ◽  
Michael A. Wells ◽  
Erin S. Christensen ◽  
...  

2008 ◽  
Vol 100 (10) ◽  
pp. 626-633 ◽  
Author(s):  
Christoph arenhorst ◽  
Stefan James ◽  
John T. Brandt ◽  
Joseph A. Jakubowski ◽  
Kenneth J. Winters ◽  
...  

SummaryPrasugrel, a novel P2Y12 ADP-receptor antagonist, has been reported to achieve greater inhibition of platelet aggregation compared to clopidogrel as assessed by light transmission aggregometry. It was the objective of this study to investigate the effect of prasugrel on alternative markers of platelet activation in comparison to a high loading dose and the approved maintenance dose of clopidogrel. One hundred ten aspirintreated patients with stable coronary artery disease were randomized to a loading dose (LD, day 1)/ maintenance dose (MD, days 2–29) of prasugrel 60 mg/10 mg or clopidogrel 600 mg/75 mg. Platelet activation markers were analyzed by whole blood flow cytometry pre-dose and at 2 and 24 hours after LD and pre-dose at 14 and 29 days. After stimulation with 20 µM ADP, 2 hours after LD, significantly lower expression of activated GPIIb/IIIa (4.3 vs. 21.8 [mean fluorescent intensity (MFI)], p < 0.001) and P-selectin (2.0 vs. 11.7 MFI, p < 0.001) along with decreased formation of platelet-monocyte aggregates (16.4% vs.29.6% positive cells, p < 0.001) was observed with prasugrel versus clopidogrel. All these effects were maintained through 24 hours and during the MD period. In conclusion, prasugrel 60 mg LD and 10 mg MD inhibit several markers of platelet activation and the formation of platelet-monocyte aggregates more effectively than a 600 mg LD and 75 mg MD of clopidogrel. Attenuated platelet aggregation and reduced expression of platelet procoagulant and pro-inflammatory markers with prasugrel suggest the potential to reduce cardiovascular events both in the acute setting and in longterm treatment.


2009 ◽  
Vol 71 (4) ◽  
pp. 438-445 ◽  
Author(s):  
Graham J. Reid ◽  
Peter H. Seidelin ◽  
Willem J. Kop ◽  
M Jane Irvine ◽  
Bradley H. Strauss ◽  
...  

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