Platelet reactivity

Iron-stimulated free radical-mediated processes are not limited to the promotion of peroxidative reactions. For example, Pratico et al. [188] demonstrated that erythrocytes are able to modulate platelet reactivity in response to collagen via the release of free iron, which supposedly catalyzes hydroxyl radical formation by the Fenton reaction. This process resulted in an irreversible blood aggregation and could be relevant to the stimulation by iron overload of atherosclerosis and coronary artery disease. 

Phillips WT, Klipper R, Fresne D, et al. Platelet reactivity with liposome-encapsulated hemoglobin in the rat. Exp Hematol 1997 25 1347. 

Bougie DW, Birenbaum J, Rasmussen M, Poncz M, Aster RH. (2008) Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia. Blood 113 1105-1111. 

Dipyridamole is a platelet adhesion inhibitor, although the mechanism of action has not been fully elucidated. The mechanism may relate to 1) Inhibition of red blood cell uptake of adenosine, itself an inhibitor of platelet reactivity, 2) phosphodiesterase inhibition leading to increased cyclic-3 , 5 -adenosine monophosphate within platelets and, 3) inhibition of thromboxane A2 formation,... 

Grotemeyer 180 Stroke 1500 1 yr Platelet reactivity Normal PR index 33.3 40% of AR... 

Abbreviations-. AA, arachidonic acid AMI, acute myocardial infarction AR, aspirin resistance ASA, aspirin CABG, coronary artery bypass graft surgery CAD, coronary artery disease CK-MB, creatinine kinase-MB CVA, cerebrovascular accident EPI, epinephrine HS, healthy subjects LTA, light transmittance aggregometry mm, millimolar PAR, platelet activity ratio PCI, percutaneous coronary intervention PR, platelet reactivity RPFA, rapid platelet function analyzer TXA2, thromboxane A2. 

It has been shown that patients with diabetes exhibit platelet activation and increased reactivity to agonists. The heightened platelet reactivity may be related to the increased prevalence of nonresponders and occurrence of ischemic events reported in patients with diabetes (106,107). It has also been reported that patients with a high body mass index (BMI) exhibited a suboptimal platelet response with the standard 300 mg loading dose (108). 

All of the data mentioned earlier strongly support insufficient metabolite generation as the primary explanation for nonresponsiveness rather than genetic polymorphisms of platelet receptors or intracellular signaling mechanisms. The latter mechanisms may be relevant in those patients who may remain resistant and with high platelet reactivity to ADP even after treatment with high doses of clopidogrel. 

PLATE LETS-lb studies, a 600 mg loading dose was associated with increased platelet inhibition compared to a 300 mg loading dose, In turn, increased platelet inhibition was accompanied by a decrease in the release of myocardial necrosis and inflammation (19,20). In a very recent study of 106 patients undergoing stenting, high post-treatment platelet reactivity was asso-ciated with an increased risk of recurrent cardiovascular events (22). 

Reports of high incidences of aspirin resistance may be due to laboratory measurements based on nonspecific methods that do not isolate the response of platelet COX-1 to aspirin or due to an inadequate dose required to fully inhibit the COX-1 in selected patients. Clopidogrel nonresponsiveness is a consistent phenomenon observed in research studies conducted at multiple medical centers around the world. Data from small studies support that patients with high ex vivo platelet reactivity to ADP during and after percutaneous intervention may be at greatest risk for subsequent ischemic events. 

I 5 Gurbel PA, Bliden KR Samara W, et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis results of the CREST Study. J Am Coll Cardiol 2005 46 1827-1832. 

Cuisset T Frere C, Quilici J, et al, High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome, J Thromb Haemost 2006 4 542-549. 

Watala C, Blood platelet reactivity and its pharmacological modulation in (people with) diabetes mellitus. Curr Pharm Des 2005 I 1 233 1-2365. Review. 

Valles J, Santos MT, Aznar J, et al. Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity. Circulation 1998 97 35CA355. 

Gurbel PA, Bliden KR Hiatt BL, O Connor CM. Clopidogrel for coronary stenting response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003 107 2908-2913. 

Samara WM, Bliden KR Tantry US, Gurbel PA, The difference between clopidogrel responsiveness and posttreatment platelet reactivity. Thromb Res 2005 I I 5 89-94,... 

Other effects Reduced platelet reactivity Increased t-PA and decreased plasminogen activator inhibitor-1 Increased circulating endothelial progenitor cells... 

Famdale RW, Baines MJ The platelet reactivity of synthetic peptides based on the collagen III fragment al(III)CB4. Evidence for an integrin a2 31 recognition site involving residues 522 52 of the al(in) collagen chain. J Biol Chem 272 11044-11048,1997... 

Barnes MJ, Knight CG, Famdale RW The use of collagen-based model peptides to investigate platelet-reactive sequences in collagen. Biopolymers 40 383-397,1996... 

The methylxanthines, theophylline and caffeine, act primarily as antagonists for both adenosine A, and Aj receptors (65-68). Caffeine is a relatively weak adenosine antagonist as compared to foeophylline (69). Studies to examine these methylxanthines as adenosine antagonists on platelet ftinction have been limited. Both theophylline and caffeine are shown to stimulate platelet reactivity in vitro and in vivo studies (49,50,67,69,70). Platelets from subjects after chronic consumption of caffeine show decreased antiplatelet activity of the adenosine analog NECA on thrombin-induced... 

Ammaturo, V, Petricome, C, Cananio, A, Ripaldi, M, Ruggiano, A, Zuccarelli, B, Monti, M, Caffeine stimulates in vivo platelet reactivity, Acta Med Scand, 1988,224 245-247. 

Bordeaux MK, Weiss RC, Toivio-Kinnucan, Cox N, Spano JS. Enhanced platelet reactivity in cats experimentally infected with feline infectious peritonitis virus. Vet Pathol 1990 27 269-273... 

In this chapter, literature dealing with altered platelet function in hypertension will be reviewed to develop a better imderstanding of the role of agonist-receptor mediated signal transduction and Ae ensuing biochemical reactions that may be responsible for altered platelet reactivity in hypertension. 

---