Platelet reactivity changes with shear stress, which in turn depends on whole blood and plasma viscosity (PV). Platelets interact with fibrinogen during thrombus formation, and fibrinogen is a determinant of PV. The respective role of PV and fibrinogen on platelet function is still unclear.
METHODS:
30 patients undergoing vascular surgery were admitted to this study. In each patient we measured PV using a cone-on-plate viscosimeter, functional fibrinogen using thromboelastometry, and platelet reactivity to thrombin receptor activating peptide (TRAP) stimulation using multi-electrode aggregometry. Routine coagulation parameter were measured.
RESULTS:
At the univariate analysis, platelet reactivity was positively associated with mean platelet volume (R2 = 0.15, P = 0.033) and PV (R2 = 0.35, P = 0.0006), and negatively associated with serum bilirubin (R2 = 0.20, P = 0.013) and international normalized ratio (INR) (R2 = 0.19, P = 0.017). At the multivariable analysis, only PV (P = 0.001) and INR (P = 0.019) remained independent predictors of platelet reactivity.
CONCLUSION:
PV is directly and independently associated with platelet reactivity, whereas functional fibrinogen is not. Aspirin treatment is inadequate to correct thrombin-induced platelet aggregation. In presence of hyperviscosity, patients at high cardiovascular risk, may benefit from more aggressive anti-platelet treatments.
AsherE., FeferP., ShechterM., BeigelR., VaronD., ShenkmanB., SavionN., HodH. and MatetzkyS., Increased mean platelet volume is associated with non-responsiveness to clopidogrel, Thromb Haemost112 (2014), [Epub ahead of print].
2.
BernlochnerI., SteinhublS., BraunS., MorathT., JaitnerJ., StegherrJ., MehilliJ., von BeckerathN.,SchömigA.,KastratiA. and SibbingD., Association between inflammatory biomarkers and platelet aggregation in patients under chronic clopidogrel treatment, Thromb Haemost104 (2010), 1193–1200.
3.
ChenH., AngererJ.I., NapoleoneM., ReiningerA.J., SchneiderS.W., WixforthA., SchneiderM.F. and Alexander-KatzA., Hematocrit and flow rate regulate the adhesion of platelets to von Willebrand factor, Biomicrofluidics7 (2013), 64113.
4.
ChesnuttJ.K. and HanH.C., Platelet size and density affect shear-induced thrombus formation in tortuous arterioles, Phys Biol10 (2013), Epub 2013 Aug 23.
5.
DikmenoğluN., CiftçiB., IleriE., GüvenS.F., SeringeçN., AksoyY. and ErcilD., Erythrocyte deformability, plasma viscosity and oxidative status in patients with severe obstructive sleep apnea syndrome, Sleep Med7 (2006), 255–261.
6.
GotoS., OgawaH., TakeuchiM., FlatherM.D. and BhattD.L., On behalf of the J-LANCELOT (Japanese-Lesson from Antagonizing the Cellular Effect of Thrombin) Investigators. Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease, Eur Heart J31 (2010), 2601–2613.
7.
GremmelT., CalatzisA., SteinerS., KaiderA., SeidingerD., KoppensteinerR., KoppC.W. and PanzerS., Is TRAP-6 suitable as a positive control for platelet reactivity when assessing response to clopidogrel?Platelets21 (2010), 515–521.
8.
HuissoudC., CarrabinN., AudibertF., LevratA., MassignonD., BerlandM. and RudigozR.C., Bedside assessment of fibrinogen level in postpartum haemorrhage by thrombelastometry, BJOG116 (2009), 1097–1102.
9.
JakubowskiJ.A., PayneC.D., WeerakkodyG.J., BrandtJ.T., FaridN.A., LiY.G., NaganumaH., LachnoD.R. and WintersK.J., Dose-dependent inhibition of human platelet aggregation by prasugrel and its interaction with aspirin in healthy subjects, J Cardiovasc Pharmacol49 (2007), 167–173.
10.
JastrzębskaM., ChełstowskiK., WódeckaA., SiennickaA., ClarkJ. and NowackiP., Factors influencing multiplate whole blood impedance platelet aggregometry measurements, during aspirin treatment in acute ischemic stroke: A pilot study, Blood Coagul Fibrinolysis24 (2013), 830–838.
11.
KalinaU., StohrH.A., BickhardH., KnaubS., SiboniS.M., MannucciP.M. and PeyvandiF., Rotational thromboelastography for monitoring of fibrinogen concentrate therapy in fibrinogen deficiency, Blood Coagul Fibrinolysis19 (2008), 777–783.
12.
KésmárkyG., KenyeresP., RábaiM. and TóthK., Plasma viscosity: A forgotten variable, Clin Hemorheol Microcirc39 (2008), 243–246.
13.
KesmarkyG., TothK., HabonL., VajdaG. and JuricskayI., Hemorheological parameters in coronary artery disease, Clin Hemorheol Microcirc18 (1998), 245–251.
14.
Kilicli-CamurN., DemirtuncR., KonuralpC., EskiserA. and BasaranY., Could mean platelet volume be a predictive marker for acute myocardial infarction?Med Sci Monit11 (2005), CR387–CR392.
15.
KwaanH.C., Role of plasma proteins in whole blood viscosity: A brief clinical review, Clin Hemorheol Microcirc44 (2010), 167–176.
MangiacapraF., PeaceA., BarbatoE., PattiG., GattoL., RicottiniE., De BruyneB., Di SciascioG. and WijnsW., Thresholds for platelet reactivity to predict clinical events after coronary intervention are different in patients with and without diabetes mellitus, Platelets (2013). [Epub ahead of print].
18.
MartonZ., HorvathB., AlexyT., KesmarkyG., GyevnarZ., CzopfL., HabonT., KovacsL., PappE., MezeyB., RothE., JuricskayI. and TothK., Follow-up of hemorheological parameters and platelet aggregation in patients with acute coronary syndromes, Clin Hemorheol Microcirc29 (2003), 81–94.
19.
MaxwellM.J., DopheideS.M., TurnerS.J. and JacksonS.P., Shear induces a unique series of morphological changes in translocating platelets: Effects of morphology on translocation dynamics, Arterioscler Thromb Vasc Biol26 (2006), 663–669.
20.
Rahe-MeyerN., PichlmaierM., HaverichA., SolomonC., WinterhalterM., PiepenbrockS. and TanakaK.A., Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: A pilot study, Br J Anaesth102 (2009), 785–792.
21.
RenemanR.S., ArtsT. and HoeksA.P., Wall shear stress: An important determinant of endothelial cell function and structure in the arterial system in vivo. Discrepancies with theory, J Vasc Res43 (2006), 251–269.
22.
RourkeC., CurryN., KhanS., TaylorR., RazaI., DavenportR., StanworthS. and BrohiK., Fibrinogen levels during trauma hemorrhage, response to replacement therapy and association with patient outcomes, J Thromb Haemost10 (2012), 1342–1351.
23.
SenenK., TopalE., KilincE., ten CateH., TekI., KarakocY. and YetkinE., Plasma viscosity and mean platelet volume in patients undergoing coronary angiography, Clin Hemorheol Microcirc44 (2010), 35–41.
24.
SheriffJ., SoaresS., XenosM., JestyJ., SlepianM.J. and BluesteinD., Evaluation of shear-induced platelet activation models under constant and dynamic shear stress loading conditions relevant to devices, Ann Biomed Eng41 (2013), 1279–1296.
25.
SolomonC., BaryshnikovaE., TripodiA., SchlimpC.J., SchöchlH., CadamuroJ., WinstedtD., AsmisL. and RanucciM., Fibrinogen measurement in cardiac surgery with cardiopulmonary bypass: Analysis of repeatability and agreement of Clauss method within and between six different laboratories, Thromb Haemost13 (2014), 112.
26.
SteinerS., JaxT., EversS., HennersdorfM., SchwalenA. and StrauerB.E., Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk, Cardiology104 (2005), 92–96.
27.
SzaparyL., BagolyE., KoverF., FeherG., PozsgaiE., KoltaiK., HantoK., KomolyS., DocziT. and TothK., The effect of carotid stenting on rheological parameters, free radical production and platelet aggregation, Clin Hemorheol Microcirc43 (2009), 209–217.
28.
ThomasS., Platelet membrane glycoproteins in haemostasis, Clin Lab48 (2002), 247–262.
29.
TousoulisD., PapageorgiouN., AndroulakisE., BriasoulisA., AntoniadesC. and StefanadisC., Fibrinogen and cardiovascular disease: Genetics and biomarkers, Blood Rev25 (2011), 239–245.
30.
TsiaraS., ElisafM., JagroopI.A. and MikhailidisD.P., Platelets as predictors of vascular risk: Is there a practical index of platelet activity?Clin Appl Thromb Hemost9 (2003), 177–190.
31.
van HoltenT.C., WaandersL.F., de GrootP.G., VissersJ., HoeferE., PasterkampG., PrinsM.W. and RoestM., Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses, PLoS One8 (2013), e62080.
32.
WismanP.P., RoestM., AsselbergsF.W., de GrootP.G., MollF.L., van der GraafY. and de BorstG.J., Platelet-reactivity tests identify patients at risk of secondary cardiovascular events: A systematic review and meta-analysis, J Thromb Haemost12 (2014), 736–747.
