Platelets activation markers

Platelets PF-4, p-TG, thromboxane B2 Platelet activation markers Platelet microparticles Gamma imaging of radiolabeled platelets, ln-labeled platelet survival Platelet function analysis Platelet count/adhesion Platelet aggregation... 

In vitro experiments with whole blood showed that cocoa procyanidin trimers and pentamers increased expression of platelet activation markers (librogen binding conformation of GPIIb-IIIa and P-selectin) in unstimulated platelets but suppressed platelet activation response to epinephrine [110]. Both short-term (2-6 h) studies and a long-term (28 day) study with human subjects demonstrated that consumption of proanthocyanidin-rich cocoa beverage lowered P-selectin expression and platelet aggregation (ADP-, collagen-, epinephrine induced) in ex vivo experiments [110, 111]. 

Of the four markers just mentioned, the expression of P-selectin on the activated platelets is the most widely studied. However, CD62P may not be the ideal marker for detection of circulating degranulated platelets, because they may rapidly lose their surface P-selectin but yet may continue to function. The decrease in the platelet surface expression of the GPIb-IX-V complex (CD42) perhaps represents a more sensitive marker of in vivo platelet activation. Apparently platelet activation related to strenuous exercise is more readily detected using CD42 than other markers (99). 

Many of the coagulation factors measured by global coagulation tests have limited stability, and the time and temperature of storage of sample will affect their measurements. Concepts of analyte stability and half-life in plasma extend to markers measured by immunoassay. Markers of platelet activation are affected by artifactual activation in vitro upon collection of the blood specimen. This section will highlight some of the nonanalytical variables that, if uncontrolled, can lead to spurious results and thus affect the interpretation of laboratory data. 

Cystic fibrosis is the most common lethal autosomal-recessive disease, in which oxidative stress takes place at the airway surface [274]. This disease is characterized by chronic infection and inflammation. Enhanced free radical formation in cystic fibrosis has been shown as early as 1989 [275] and was confirmed in many following studies (see references in Ref. [274]). Contemporary studies also confirm the importance of oxidative stress in the development of cystic fibrosis. Ciabattoni et al. [276] demonstrated the enhanced in vivo lipid peroxidation and platelet activation in this disease. These authors found that urinary excretion of the products of nonenzymatic lipid peroxidation PGF2 and TXB2 was significantly higher in cystic fibrotic patients than in control subjects. It is of importance that vitamin E supplementation resulted in the reduction of the levels of these products of peroxidation. Exhaled ethane, a noninvasive marker of oxidative stress, has also been shown to increase in cystic fibrosis patients [277]. 

These authors have demonstrated that plasma levels of P-thromboglobulin and soluble P-selectin, two markers of platelet activation, are elevated in hypertensive patients. 

Gurney D, Lip GY, Blann AD. A reliable plasma marker of platelet activation does it exist Am J Hematol 2002 70 139-44. 

Other parameters include the release of markers of platelet activation, such as jff-throm-boglobulin (Towler 1985). Electron microscopy is a sensitive indicator of platelet activation, manifested as pseudopodia formation (Badenhorst et al. 1982 Figs. 8.8 and 8.9). However, all the available in vitro tests failed to predict correctly collection and labeling injury, showing their hmited practical value, and take a long time, which results in functional platelet deterioration and excludes their routine application (Sinzinger et al. 1987 a). 

The panel smdies of Delfino et al. (2008, 2009) measured pollutants inside and outside the Los Angeles homes of non-smoking elderly subjects with a history of coronary artery disease. Health endpoints examined included various markers of inflammation, platelet activation, and anti-oxidant capacity. Pollutants included hourly concentrations of EC, BC, primary OC, SOA, particle number, CO, ozone, and NO2, and daily size-fractionated PM. Thus these two studies had very good subject exposure and included a large number of health-relevant pollutants. 

Freese R, Vaarala O, Turpeinen AM, Mutanen M. No difference in platelet activation or inflammation markers after diets rich or poor in vegetables, berries and apple in healthy subjects. Eur J Nutr. 2004 43(3) 175—182. 

Other enzymes are involved in biodegradation of OPs some are hydrolases such as prolidases, senescence marker protein (SMP), and platelet-activating factor (PAF-AH) others are oxidases, such as cytochromes... 

By far the most widely measured marker of hemostatic activation is D-dimer, which is a product formed by the action of plasmin on cross-linked fibrin (95). D-dimer levels in plasma are generally elevated in DIC. The consumption of platelets and coagulation proteins as a result of thrombin generation leads to the deposition of fibrin thrombi at multiple organ sites. This triggers fibrinolysis with an increase in the formation of fibrin degradation products, which can cause bleeding at multiple sites. Because DIC can have a variety of causes and may coexist with systemic fibrinolysis, such as in pulmonary embolism or deep vein thrombosis, the d-Dimer test is not specific for DIC (95). 

CD36 or GP IV is a marker that is expressed on both resting and activated platelets. Labeled antibodies can be used that exhibit increased binding to activated platelets. 

CD42 represents the GPIb-IX-V complex, which is a receptor for von Wille-brand factor that is critical for the adhesion of platelets to damaged blood vessels. This marker is down-regulated on activation of platelets. 

Peripheral tissue markers include high-molecular-weight complex biomolecules (receptors) and enzyme systems that can be obtained from outside the CNS (e.g., in platelets, lymphocytes, skin fibroblasts, and erythrocytes) and are thought to reflect or parallel central neuronal activity. 

Flow cytometric determinations of P-selectin and activated GPIIb/llla receptor expression following ADP stimulation have been used to assess platelet inhibition by clopidogrel. Flow cytometry is also a cumbersome method and requires sophisticated instrumentation and well-trained technicians. The phosphorylation state of vasodilator-stimulated phos-phoprotein (VASP) is a specific intracellular marker of clopidogrel-induced P2Y 2 receptor inhibition and can also be measured by flow cytometry. Permeation of the membrane and the use of monoclonal antibodies specific for phosphory-lated VASP are required in this method (15,88). 

---