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Thromb Haemost 1999; 81(03): 373-377
DOI: 10.1055/s-0037-1614480
Review Article
Schattauer GmbH

Circulating Platelets Show Increased Activation in Patients with Acute Cerebral Ischemia

Joern A. Zeller
,
Diethelm Tschoepe
1   Diabetes Research Institute, Heinrich-Heine-University, Düsseldorf, Germany
,
Christof Kessler
2   Department of Neurology, Ernst-Moritz-Arndt-University, Greifswald, Germany
› Author Affiliations
Further Information

Publication History

Received14 August 1998

Accepted after revision24 November 1998

Publication Date:
09 December 2017 (online)

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Summary

Platelet activation plays a central role in acute arterial stenosis as has been shown in coronary heart disease. Likewise it can be assumed to be of importance in the evolution of acute cerebral ischemia (ACI), particularly in patients with large vessel disease. Flow cytometric detection of platelet adhesion molecules as a marker of platelet activation in a group of patients with ACI and different etiologies has not been evaluated. In 72 patients with ACI and 72 controls, the exposure of activation-dependent adhesion molecules was determined using flow cytometry after immunostaining with monoclonal antibodies against CD 62, CD 63 and thrombospondin. The extent of platelet activation differed as a function of the etiology of ACI: platelets from patients with atherosclerosis of brain-supplying arteries expressed significantly more activation markers than did controls, whereas patients with cardioembolic stroke did not. By analyzing platelet adhesion molecules it is possible to describe platelet activation profiles in patients with acute cerebral ischemia. This diagnostic procedure will be useful for monitoring individualized anti-platelet therapy and may enable distinguishing different subgroups of stroke patients.

 

  • References

  • 1 Schultheiss HP, Tschoepe D, Esser J, Schwippert B, Roesen P, Nieuwenhuis HK, Schmidt-Soltau C, Strauer B. Large platelets continue to circulate in an activated state after myocardial infarction. Eur J Clin Invest 1994; 24: 243-7.
    CrossrefPubMedSearch in Google Scholar
  • 2 Gawaz M, Neumann FJ, Ott I, Schiessler A, Schomig A. Platelet function in acute myocardial infarction treated with direct angioplasty. Circulation 1996; 93: 229-37.
    CrossrefPubMedSearch in Google Scholar
  • 3 Nurden AT, Macchi L, Bihour C, Durrieu C, Besse P, Nurden P. Markers of platelet activation in coronary heart disease patients. Eur J Clin Invest 1994; 24 (Suppl. 01) Suppl 42-5.
    PubMedSearch in Google Scholar
  • 4 Itoh T, Nakai K, Ono M, Hiramori K. Can the risk for acute cardiac events in acute coronary syndrome be indicated by platelet membrane activation marker P-selectin?. Coron Artery Dis 1995; 6: 645-50.
    CrossrefPubMedSearch in Google Scholar
  • 5 Tschoepe D, Schultheiss HP, Kolarov P, Schwippert B, Dannehl K, Nieuwenhuis HK, Kehrel B, Strauer B, Gries FA. Platelet membrane activation markers are predictive for increased risk of acute ischemic events after PTCA. Circulation 1993; 88: 37-42.
    CrossrefPubMedSearch in Google Scholar
  • 6 Neumann FJ, Ott I, Gawaz M, Puchner G, Schomig A. Neutrophil and platelet activation at balloon-injured coronary artery plaque in patients undergoing angioplasty. J Am Coll Cardiol 1996; 27: 819-24.
    CrossrefPubMedSearch in Google Scholar
  • 7 Kolarov P, Tschoepe D, Nieuwenhuis HK, Gries FA, Strauer B, Schultheiß HP. PTCA: Periprocedural Platelet Activation. Eur Heart J 1996; 17: 1-7.
    CrossrefPubMedSearch in Google Scholar
  • 8 Harker LA, Malpass TW, Branson HE, Hessel EA, 2nd Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass. Blood 1980; 56: 824-34.
    PubMedSearch in Google Scholar
  • 9 Tschoepe D, Roesen P, Schwippert B, Gries FA. Platelets in diabetes: The role in the hemostatic regulation in atherosclerosis. Semin Thromb Hemost 1993; 19: 122-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Tschoepe D, Driesch E, Schwippert B, Niewenhuis HK, Gries FA. Exposure of adhesion molecules on activated platelets in patients with newly diagnosed IDDM is not normalized by near-normoglycemia. Diabetes 1995; 44: 890-5.
    CrossrefPubMedSearch in Google Scholar
  • 11 Nagao T, Hamamoto M, Kanda A, Tsuganesawa T, Ueda M, Kobayashi K, Miyazaki T, Terashi A. Platelet activation is not involved in acceleration of the coagulation system in acute cardioembolic stroke with nonvalvular atrial fibrillation. Stroke 1995; 26: 1365-8.
    CrossrefPubMedSearch in Google Scholar
  • 12 Iwamoto T, Kubo H, Takasaki M. Platelet activation in the cerebral circulation in different subtypes of ischemic stroke and Binswanger’s disease. Stroke 1995; 26: 52-6.
    CrossrefPubMedSearch in Google Scholar
  • 13 Feinberg WM, Erickson LP, Bruck D, Kittelson J. Hemostatic markers in acute ischemic Stroke. Stroke 1996; 27: 1296-300.
    CrossrefPubMedSearch in Google Scholar
  • 14 Koudstall PJ, Ciabattoni G, van Gijn J, Nieuwenhuis HK, de Groot PG, Sixma JJ, Patrono C. Increased thromboxane biosynthesis in patients with acute cerebral ischemia. Stroke 1993; 24: 219-23.
    CrossrefPubMedSearch in Google Scholar
  • 15 van-Kooten F, Ciabattoni G, Patrono C, Schmitz I P, Koudstall PJ. Evidence for episodic platelet activation in acute ischemic stroke. Stroke 1994; 25: 278-81.
    CrossrefPubMedSearch in Google Scholar
  • 16 Konstantopoulos K, Grotta JC, Sills C, Wu KK, Hellums JD. Shear-induced platelet aggregation in normal subjects and stroke patients. Thromb Haemost 1995; 74: 1329-34.
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Feinberg WM, Albers GW, Barnett HJM, Biller J, Caplan LR, Carter LP, Hart RJ, Hobson RW, Kronmal RA, Moore WS, Robertson JT, Adams Jr HP, Mayberg M. Guidelines for the management of transient ischemic attacks. Stroke 1994; 25: 1320-35.
    CrossrefPubMedSearch in Google Scholar
  • 18 Valet G, Tschöpe D, Gabriel H, Valet M. Standardized, self learning flow cytometric list mode data. Classifier: Classif 1 for thrombocyte and lymphocyte immune phenotyping. Ann NY Acad Sci 1993; 677: 233-51.
    CrossrefPubMedSearch in Google Scholar
  • 19 Larsen E, Celi A, Gilbert GE, Furie BC, Erban JK, Bonfanti R, Wagner DD, Furie B. PAGDEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 1989; 59: 305-12.
    CrossrefPubMedSearch in Google Scholar
  • 20 Nieuwenhuis HK, van Ouosterhout JJG, Rozemuller E, van Iwaarden F, Sixma JJ. Studies with a monoclonal antibody against activated platelets. Evidence that a secreted 53,000-molecular weight lysosome-like granule protein is exposed on the surface of activated platelets in the circulation. Blood 1987; 70: 838-45.
    PubMedSearch in Google Scholar
  • 21 Metzelaar MJ, Sixma JJ, Nieuwenhuis HK. Detection of platelet activation using activation specific monoclonal antibodies. Blood Cells 1990; 16: 85-93.
    PubMedSearch in Google Scholar
  • 22 Aiken ML, Ginsberg MH, Plow EF. Mechanisms for expression of thrombospondin on the platelet cell surface. Semin Thromb Hemost 1987; 13: 307-16.
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Fisher M, Meiselman HJ. Hemorheological factors in cerebral ischemia. Stroke 1991; 22: 1164-9.
    CrossrefPubMedSearch in Google Scholar
  • 24 Shammas NW, Cunningham MJ, Pomerantz RM, Francis CW. Markers of hemostatic activation in affected coronary arteries during angioplasty. Thromb Haemost 1994; 72: 672-5.
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Fitzgerald DJ, Roy L, Catella F, FitzGerald GA. Platelet activation in unstable coronary artery disease. N Engl J Med 1986; 315: 983-9.
    CrossrefPubMedSearch in Google Scholar
  • 26 Oates JA, FitzGerald GA, Branch RA, Jackson EK, Knapp HR. Clinical implications of prostaglandin and thromboxane A2 formation (1). N Engl J Med 1988; 319: 689-98 and (2) 319: 761-7.
    CrossrefPubMedSearch in Google Scholar
  • 27 Lassila R, Badimon JJ, Vallabhajosula S, Badimon L. Dynamic monitoring of platelet deposition on severely damaged vessel wall in flowing blood: effects of different stenosis on thrombus growth. Arteriosclerosis 1990; 10: 306-15.
    CrossrefPubMedSearch in Google Scholar
  • 28 Savage B, Saldivar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand Factor. Cell 1996; 84: 289-97.
    CrossrefPubMedSearch in Google Scholar
  • 29 Scharf RE, Tomer A, Marzec UM, Teirstein PS, Ruggeri ZM, Harker LA. Activation of platelets in blood perfusing angioplasty-damaged coronary arteries. Flow cytometric detection. Arterioscler Thromb 1992; 12: 1475-87.
    CrossrefPubMedSearch in Google Scholar
  • 30 Gralnick HR, Vail M, Williams S, McKeown L, Shafer B, Hansmann K. Platelet alpha granule release is not inhibited by aspirin and is mediated by myosin light chain kinase and protein C kinase. Blood 1990; 75: 128-38.
    PubMedSearch in Google Scholar
  • 31 Chronos NAF, Wilson DJ, Janes SL, Hutton RA, Büller NP, Goodall AH. Aspirin does not affect the flow cytometric detection of fibrinogen binding to, or release of α-granules or lysosomes from, human platelets. Clinical Science 1994; 87: 575-80.
    CrossrefPubMedSearch in Google Scholar
  • 32 Santos MT, Valles J, Aznar J, Marcus AJ, Broekman MJ, Safier LB. Prothrombotic effects of erythrocytes on platelet reactivity. Circulation 1997; 95: 63-68.
    CrossrefPubMedSearch in Google Scholar
  • 33 Schmitz G, Rothe G, Ruf A, Barlage S, Tschoepe D, Clemetson KJ, Good-all AH, Michelson AD, Nurden AT, Shankey TV. European working group on clinical cell analysis: Consensus protocol for the flow cytometric characterisation of platelet function. Thromb Haemost 1998; 79: 885-96.
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Furman MI, Benoit SE, Barnard MR, Valeri CR, Borbone ML, Becker RC, Hechtmann HB, Michelson AD. Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J Am Coll Cardiol 1998; 31: 352-8.
    PubMedSearch in Google Scholar
  • 35 Celi A, Pellegrini G, Lorenzet R, DeBlasi A, Ready N, Furie BC, Furie B. P-selectin induces the expression of tissue factor on monocytes. Proc Natl Acad Sci 1994; 91: 8767-71.
    CrossrefPubMedSearch in Google Scholar
  • 36 Weyrich AS, Elstad MR, McEver RP, McIntyre TM, Moore KL, Morrissey JH, Prescott SM, Zimmermann GA. Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 1996; 97: 1525-34.
    CrossrefPubMedSearch in Google Scholar
  • 37 Neumann FJ, Marx N, Gawaz M, Brand K, Ott I, Rokitta C, Sticherling C, Meinl C, May A, Schomig A. Induction of cytokine expression by binding of thrombin-stimulated platelets. Circulation 1997; 95: 2387-94.
    CrossrefPubMedSearch in Google Scholar
  • 38 The EPIC Investigators. Use of a monoclonal antibody against the platelet glycoprotein IIb/IIIa receptor in high risk coronary angioplasty. N Engl J Med 1994; 330: 956-61.
    CrossrefPubMedSearch in Google Scholar
  • 39 The EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. Lancet 1998; 352: 87-92.
    CrossrefPubMedSearch in Google Scholar