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Elevated platelet reactivity in stable angina pectoris without significant coronary flow obstruction
Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
2008 (English)In: Journal of Cardiovascular Medicine, ISSN 1558-2027, Vol. 9, no 2, 129-130 p.Article in journal (Refereed) Published
Abstract [en]


There are many different causes of angina pectoris without significant coronary flow obstruction in major coronary arteries. Examples include Prinzmetal angina and small vessel atherosclerotic disease.


We investigated individuals with stable angina pectoris subject to elective coronary angiography. To keep the study group as homogeneous as possible, patients with diabetes mellitus were excluded. Subjects with normal coronary angiograms (n = 13) or insignificant (< 50%) coronary flow obstruction(s) (n = 4) were grouped together. The remaining cohort (n = 96) with at least one significant (> or = 50%) flow obstruction in at least one major coronary artery served as controls.


Before angiography, platelet activity in vitro on stimulation with a thrombin-receptor activating peptide (TRAP-6) (57 micromol/l and 74 micromol/l) and ADP (1.7 micromol/l and 8.5 micromol/l) was determined. Angina pectoris individuals without significant flow obstruction in major coronary arteries had enhanced platelet reactivity both when stimulated with TRAP-6 and ADP (P < 0.01 for both TRAP-6 concentrations and P < 0.05 for both ADP concentrations, respectively.


It is concluded that angina pectoris without significant flow impediment in major epicardial arteries is associated with augmented platelet reactivity.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2008. Vol. 9, no 2, 129-130 p.
Keyword [en]
angina pectoris; flow cytometry; platelets; platelet reactivity
National Category
Cardiac and Cardiovascular Systems
URN: urn:nbn:se:liu:diva-44108DOI: 10.2459/JCM.0b013e3280c56d46PubMedID: 18192803Local ID: 75552OAI: diva2:264969
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2014-01-07Bibliographically approved
In thesis
1. Platelets: with special reference to platelet density subpopulations, stable coronary heart disease and atrial fibrillation
Open this publication in new window or tab >>Platelets: with special reference to platelet density subpopulations, stable coronary heart disease and atrial fibrillation
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The current thesis was divided into two parts. Basic platelet research is the topic of the first section. The subsequent clinical part examines platelet reactivity in stable angina pectoris (AP) and in atrial fibrillation.

Platelet heterogeneity was investigated in the first section (papers 1 and 2). The cells were separated according to density using linear Percoll™ (a density medium) gradients. The latter contained EDTA, prostaglandin E1 and theophylline to prevent platelet in vitro activity. The platelet population was then divided into density subpopulations (n = 16 - 20). Membrane attached fibrinogen was determined with a flow cytometer technique and used as a marker reflecting platelet in vivo activity. Platelet P-Selectin content was employed to estimate the quantity of platelet α-granules. Paper I examined healthy blood donors (n = 3). The second report (paper II) compared healthy volunteers (n = 2) and subjects with essential thrombocythemia (ET) (n = 2). The latter is a clonal disease being characterized by an excessive platelet production. Platelet counts were determined in all fractions. In manuscripts I and II determination of surface bound fibrinogen and intracellular P-Selectin was carried out in 12 and 16 platelet density fractions, respectively.

High density platelets displayed more surface bound fibrinogen indicating in vivo activity. They also contained less P-Selectin. The latter finding implies platelet in vivo release reactions. Low density platelets circulated with more surface bound fibrinogen as well. Compared with peak density platelets, lighter cells contained more P-Selectin. ET was characterized by a similar platelet density pattern in that high and low density platelets displayed more surface bound fibrinogen. The similarity may explain why severe bleedings do not occur more frequently in ET. It is also obvious from the current thesis that the significance of platelet heterogeneity remains unclear and stimulates to further research. In particular, future work must involve more patients.

The second part (papers III-VI) of the thesis was devoted to stable AP and atrial fibrillation. Determination of platelet reactivity i.e. platelet bound fibrinogen after stimulation was carried out in whole blood. A flow cytometer technique was employed (papers III-VI). Adenosine diphosphate (ADP) (1.7 and 8.5 μmol/L) and a thrombin-receptor activating peptide (TRAP-6) (57 and 74 μmol/L) were used as stimulating agents. Determination of peak platelet density (kg/L) was utilized as a further measure reflecting platelet reactivity (paper V). Surface bound and soluble P-Selectin were employed as platelet activity markers (paper VI).

Gender differences with respect to platelet reactivity were investigated in paper III. Paper IV examined platelets in stable AP without significant coronary flow obstruction(s) as determined by coronary angiography. In a following study platelet reactivity was analysed in diabetes type II complicated by stable AP (paper V). Finally, long-term (more than 2 years) outcome of atrial fibrillation was related to platelet reactivity and activity (paper VI). In this study the subjects were investigated at the initial electrical cardioversion and the analysis were repeated after more than 2 years.

Postmenopausal women with stable AP demonstrated more reactive platelets when stimulating with TRAP-6. They had higher platelet counts (paper III) as well. Stable AP without significant coronary flow obstruction(s) was associated with elevated platelet reactivity (paper IV). Diabetes type II was linked to higher peak platelet density and elevated platelet reactivity (paper V). Augmented platelet reactivity proved to be a feature of subjects remaining in atrial fibrillation more than 2 years after the electrical cardioversion (paper VI). In contrast, the irregular heart rhythm did not affect platelet activity.

It is to assume that platelets at least partly are responsible for the sometimes atypical symptoms of females with stable AP. It is also conceivable to speculate that platelets contribute to chest pain in AP free from significant coronary flow obstruction(s). Theoretically, enhanced platelet reactivity could at least partly explain why diabetes type II affects the prognosis of coronary heart disease. The thesis further shows a possible theoretical link between atrial fibrillation, increased platelet reactivity and clot formation.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 85 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1220
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-62630 (URN)978-91-7393-272-1 (ISBN)
Public defence
2010-12-10, K3, Campus Norrköping, Linköpings univeristet, Norrköping, 13:00 (Swedish)
Available from: 2010-12-01 Created: 2010-12-01 Last updated: 2010-12-01Bibliographically approved

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Järemo, PetterMilovanovic, MichaLindahl, TomasRichter, Arina
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Department of Internal Medicine in NorrköpingDivision of Health, Activity and CareFaculty of Health SciencesClinical ChemistryDepartment of Clinical ChemistryCardiologyDepartment of Cardiology
Cardiac and Cardiovascular Systems

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