CLINICAL STUDY
Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction
Mark I. Furman, MD, FACC*,
Marc R. Barnard, MS ,
Lori A. Krueger, BA,
Marsha L. Fox, RN, MS,
Elizabeth A. Shilale, RN, MS ,
Darleen M. Lessard, MS*,
Peter Marchese, BA,
A. L. Frelinger, III, PhD,
Robert J. Goldberg, PhD* and
Alan D. Michelson, MD
* Center for Platelet Function Studies, Division of Cardiovascular Medicine, Worcester, Massachusetts, USA
Center for Platelet Function Studies, Division of Pediatric Hematology/Oncology, Departments of Medicine, Pediatrics, Worcester, Massachusetts, USA
Center for Platelet Function Studies, Division of Emergency Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Manuscript received December 6, 2000;
revised manuscript received May 25, 2001,
accepted June 15, 2001.
Reprint requests and correspondence: Dr. Mark I. Furman, Division of Cardiovascular Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655
Mark.Furman{at}umassmed.edu
OBJECTIVES
We investigated whether elevated levels of circulating monocyte-platelet aggregates (MPA) can be used to identify patients with acute myocardial infarction (AMI).
BACKGROUND
Commonly used blood markers of AMI reflect myocardial cell death, but do not reflect the earlier pathophysiologic processes of plaque rupture, platelet activation and resultant thrombus formation. Circulating MPA form after platelet activation.
METHODS
In a single center between October 1998 and November 1999, we measured circulating MPA in a blinded fashion by whole blood flow cytometry in 211 consecutive patients who presented to the emergency department (ED) with chest pain and were admitted to rule out AMI. Acute myocardial infarction was diagnosed by a CK-MB fraction greater than three times control.
RESULTS
Patients with AMI (n = 61), as compared with those without AMI (n = 150), had significantly higher numbers of circulating MPA (11.6 ± 11.4 vs. 6.4 ± 3.6, mean ± SD, p < 0.0001). After controlling for age, the adjusted odds of developing AMI for patients in the 2nd, 3rd and 4th quartiles of MPA, in comparison with patients in the lowest quartile (odds ratio = 1.0), were 2.1 (95% confidence interval [CI]: 0.7, 6.8), 4.4 (95% CI: 1.5, 13.1) and 10.8 (95% CI: 3.6, 32.0), respectively. The number of circulating MPA in patients with AMI presenting within 4 h of symptom onset (14.4) was significantly greater than those presenting after 4 h (9.4) and after 8 h (7.0), (p < 0.001). Of the 61 patients with AMI, 35 (57%) had a normal creatine kinase isoenzyme ratio at the time of presentation to the ED, but had high levels of circulating MPA (13.3).
CONCLUSIONS
Circulating MPA are an early marker of AMI.
|
Abbreviations and Acronyms
| | AMI | = acute myocardial infarction | | CI | = confidence interval | | CK-MB | = creatine kinase isoenzyme | | ED | = emergency department | | FITC | = fluorescein isothiocyanate | | MPA | = monocyte-platelet aggregates | | PSGL-1 | = P-selectin glycoprotein ligand-1 |
|
This article has been cited by other articles:
|
|
|
|
 
E. Shantsila and G. Y.H. Lip
Monocytes in Acute Coronary Syndromes
Arterioscler Thromb Vasc Biol,
October 1, 2009;
29(10):
1433 - 1438.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. van Gils, J. J. Zwaginga, and P. L. Hordijk
Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases
J. Leukoc. Biol.,
February 1, 2009;
85(2):
195 - 204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bournazos, J. Rennie, S. P. Hart, K. A.A. Fox, and I. Dransfield
Monocyte Functional Responsiveness After PSGL-1-Mediated Platelet Adhesion Is Dependent on Platelet Activation Status
Arterioscler Thromb Vasc Biol,
August 1, 2008;
28(8):
1491 - 1498.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Catellier, N. Aleksic, A. R. Folsom, and E. Boerwinkle
Atherosclerosis Risk in Communities (ARIC) Carotid MRI Flow Cytometry Study of Monocyte and Platelet Markers: Intraindividual Variability and Reliability
Clin. Chem.,
August 1, 2008;
54(8):
1363 - 1371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. O'Donoghue, D. A. Morrow, C. P. Cannon, W. Guo, S. A. Murphy, C. M. Gibson, and M. S. Sabatine
Association between baseline neutrophil count, clopidogrel therapy, and clinical and angiographic outcomes in patients with ST-elevation myocardial infarction receiving fibrinolytic therapy
Eur. Heart J.,
April 2, 2008;
29(8):
984 - 991.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. I. Sternberg, D. Shimbo, S. M. Kawut, J. Sarkar, G. Hurlitz, F. D'Ovidio, D. J. Lederer, J. S. Wilt, S. M. Arcasoy, D. J. Pinsky, et al.
Platelet activation in the postoperative period after lung transplantation
J. Thorac. Cardiovasc. Surg.,
March 1, 2008;
135(3):
679 - 684.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. E. May, P. Seizer, and M. Gawaz
Platelets: Inflammatory Firebugs of Vascular Walls
Arterioscler Thromb Vasc Biol,
March 1, 2008;
28(3):
s5 - s10.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Schmidt, A. Bultmann, S. Fischel, A. Gillitzer, P. Cullen, A. Walch, P. Jost, M. Ungerer, N. D. Tolley, S. Lindemann, et al.
Extracellular Matrix Metalloproteinase Inducer (CD147) Is a Novel Receptor on Platelets, Activates Platelets, and Augments Nuclear Factor {kappa}B-Dependent Inflammation in Monocytes
Circ. Res.,
February 15, 2008;
102(3):
302 - 309.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bournazos, J. Rennie, S. P. Hart, and I. Dransfield
Choice of Anticoagulant Critically Affects Measurement of Circulating Platelet-Leukocyte Complexes
Arterioscler Thromb Vasc Biol,
January 1, 2008;
28(1):
e2 - e3.
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Goubareva, E. Gkaliagkousi, A. Shah, L. Queen, J. Ritter, and A. Ferro
Age decreases nitric oxide synthesis and responsiveness in human platelets and increases formation of monocyte-platelet aggregates
Cardiovasc Res,
September 1, 2007;
75(4):
793 - 802.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Michelson and P. E. Newburger
Platelets and leukocytes: aggregate knowledge
Blood,
August 1, 2007;
110(3):
794 - 795.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Steinhubl, J. J. Badimon, D. L. Bhatt, J.-M. Herbert, and T. F. Luscher
Clinical evidence for anti-inflammatory effects of antiplatelet therapy in patients with atherothrombotic disease
Vascular Medicine,
May 1, 2007;
12(2):
113 - 122.
[Abstract]
[PDF]
|
|
|
|
|
|
|
E. Lupia, O. Bosco, S. Bergerone, A. E. Dondi, A. Goffi, E. Oliaro, M. Cordero, L. Del Sorbo, G. Trevi, and G. Montrucchio
Thrombopoietin Contributes to Enhanced Platelet Activation in Patients With Unstable Angina
J. Am. Coll. Cardiol.,
December 5, 2006;
48(11):
2195 - 2203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Htun, S. Fateh-Moghadam, B. Tomandl, R. Handschu, K. Klinger, K. Stellos, C. Garlichs, W. Daniel, and M. Gawaz
Course of Platelet Activation and Platelet-Leukocyte Interaction in Cerebrovascular Ischemia
Stroke,
September 1, 2006;
37(9):
2283 - 2287.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. C. Strike, K. Magid, D. L. Whitehead, L. Brydon, M. R. Bhattacharyya, and A. Steptoe
Pathophysiological processes underlying emotional triggering of acute cardiac events.
PNAS,
March 14, 2006;
103(11):
4322 - 4327.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D J H McCabe, P Harrison, I J Mackie, P S Sidhu, G Purdy, A S Lawrie, H Watt, S J Machin, and M M Brown
Increased platelet count and leucocyte-platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis
J. Neurol. Neurosurg. Psychiatry,
September 1, 2005;
76(9):
1249 - 1254.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. del Conde, F. Nabi, R. Tonda, P. Thiagarajan, J. A. Lopez, and N. S. Kleiman
Effect of P-Selectin on Phosphatidylserine Exposure and Surface-Dependent Thrombin Generation on Monocytes
Arterioscler Thromb Vasc Biol,
May 1, 2005;
25(5):
1065 - 1070.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yokoyama, H. Ikeda, N. Haramaki, H. Yasukawa, T. Murohara, and T. Imaizumi
Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates
J. Am. Coll. Cardiol.,
April 19, 2005;
45(8):
1280 - 1286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. S. Coller
Leukocytosis and Ischemic Vascular Disease Morbidity and Mortality: Is It Time to Intervene?
Arterioscler Thromb Vasc Biol,
April 1, 2005;
25(4):
658 - 670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Michelson
Platelet Function Testing in Cardiovascular Diseases
Circulation,
November 9, 2004;
110(19):
e489 - e493.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Steiner-Boker, M. Cejna, C. Nasel, E. Minar, and C. W. Kopp
Successful Revascularization of Acute Carotid Stent Thrombosis by Facilitated Thrombolysis
AJNR Am. J. Neuroradiol.,
September 1, 2004;
25(8):
1411 - 1413.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. C. Strike, K. Magid, L. Brydon, S. Edwards, J. R. McEwan, and A. Steptoe
Exaggerated Platelet and Hemodynamic Reactivity to Mental Stress in Men With Coronary Artery Disease
Psychosom Med,
July 1, 2004;
66(4):
492 - 500.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Xiao and P. Theroux
Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome
J. Am. Coll. Cardiol.,
June 2, 2004;
43(11):
1982 - 1988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Haseruck, W. Erl, D. Pandey, G. Tigyi, P. Ohlmann, C. Ravanat, C. Gachet, and W. Siess
The plaque lipid lysophosphatidic acid stimulates platelet activation and platelet-monocyte aggregate formation in whole blood: involvement of P2Y1 and P2Y12 receptors
Blood,
April 1, 2004;
103(7):
2585 - 2592.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Ashman, M. G. Macey, S. L. Fan, U. Azam, and M. M. Yaqoob
Increased platelet-monocyte aggregates and cardiovascular disease in end-stage renal failure patients
Nephrol. Dial. Transplant.,
October 1, 2003;
18(10):
2088 - 2096.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Steiner, D. Seidinger, K. Huber, C. Kaun, E. Minar, and C. W. Kopp
Effect of Glycoprotein IIb/IIIa Antagonist Abciximab on Monocyte-Platelet Aggregates and Tissue Factor Expression
Arterioscler Thromb Vasc Biol,
September 1, 2003;
23(9):
1697 - 1702.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tsiara, M. Elisaf, I. A. Jagroop, and D. P. Mikhailidis
Platelets as Predictors of Vascular Risk: Is There a Practical Index of Platelet Activity?
Clinical and Applied Thrombosis/Hemostasis,
July 1, 2003;
9(3):
177 - 190.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. E. Freedman
CD40 Ligand -- Assessing Risk Instead of Damage?
N. Engl. J. Med.,
March 20, 2003;
348(12):
1163 - 1165.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Califf and D. L. DeMets
Principles From Clinical Trials Relevant to Clinical Practice: Part II
Circulation,
August 27, 2002;
106(9):
1172 - 1175.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Freedman and J. Loscalzo
Platelet-Monocyte Aggregates: Bridging Thrombosis and Inflammation
Circulation,
May 7, 2002;
105(18):
2130 - 2132.
[Full Text]
[PDF]
|
|
|
|
