Download PDF
Thromb Haemost 1996; 75(05): 827-832
DOI: 10.1055/s-0038-1650374
Original Article
Schattauer GmbH Stuttgart

Reduced Effect of Aspirin on Thrombus Formation at High Shear and Disturbed Laminar Blood Flow

R Marius Barstad
The Nycomed Pharma AS, Oslo, Norway
,
Una Ørvim
The Nycomed Pharma AS, Oslo, Norway
,
Maria J A.G Hamers
The Nycomed Pharma AS, Oslo, Norway
,
Geir E Tjønnfjord
1   The Medical Department A, The National Hospital, University of Oslo, Oslo, Norway
,
Frank R Brosstad
1   The Medical Department A, The National Hospital, University of Oslo, Oslo, Norway
,
Kjell S Sakariassen
The Nycomed Pharma AS, Oslo, Norway
› Author Affiliations
Further Information

Publication History

Received 05 October 1995

Accepted after revision 22 January 1996

Publication Date:
10 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Aspirin is the most commonly used antithrombotic drug in primary and secondary prophylaxis against cardio- and cerebrovascular disease. In previous studies from our laboratory it was demonstrated that the effect of aspirin on collagen-induced thrombus formation in a parallelplate perfusion device with laminar blood flow is shear rate dependent. Although aspirin did not affect collagen-induced thrombus formation at 650 s-1 (medium sized arteries), a significant inhibition of thrombus formation by approximately 38% at 2,600 s-1 (moderately stenoses in medium sized arteries) was observed. At present we have extended these studies to thrombus formation at the apex of eccentric stenoses in a parallel-plate perfusion chamber device. The stenoses reduced the cross-sectional area of the blood flow channel of the perfusion chambers by 60 or 80%, introducing disturbed laminar flow and apex wall shear rates of 2,600 and 10,500 s-1, respectively. The corresponding wall shear stresses were 80 and 315 dynes/cm2, respectively.

Aspirin reduced the platelet thrombus volume at the 60% stenosis by 45% (p <0.03), and the fibrin deposition by 70% (p <0.004). However, none of these parameters were affected by aspirin at the 80% stenosis. These observations may at least partly explain why aspirin has a limited clinical effect in preventing arterial thrombus formation in atherosclerotic vessels at high shear and disturbed blood flow. In contrast, thrombus formation in blood from one patient with Glanzmann’s thrombasthenia and two patients with von Willebrand disease subtype 2M was almost abolished at this blood flow condition. Thus, blocking the function of either von Willebrand factor or glycoprotein IIb/IIIa may represent better antithrombotic approaches for such critical events than blocking the prostaglandin metabolism by aspirin. The lack of effect of aspirin on thrombus formation at the 80% stenosis may reflect shear-induced platelet activation at the stenosis inlet region, since shear-induced platelet aggregation in rotational viscometers is not affected by aspirin at shear stresses exceeding 100 dynes/cm2.

 

  • References

  • 1 Goodnight SH. Antiplatelet therapy with aspirin: from clinical trials to practice. Thromb Haemost 1995; 74: 401-405
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Roth GJ, Majerus PW. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J Clin Invest 1975; 56: 624-632
    CrossrefPubMedGoogle Scholar
  • 3 Roald HE, Ørvim U, Bakken IJ, Barstad RM, Kierulf P, Sakariassen KS. Modulation of thrombotic responses in moderately stenosed arteries by cigarette smoking and aspirin ingestion. Arteriosclerosis Thrombosis 1994; 14: 617-621
    CrossrefPubMedGoogle Scholar
  • 4 Hardwich RA, Heliums JD, Peterson DM, Moake JL, Olson JD. The effects of ASA, PGEj, PGI2 and theophylline on the response of platelets subjected to shear stress. Blood 1981; 58: 678-681
    PubMedGoogle Scholar
  • 5 Konstantopoulos K, Wu KK, Udden MM, Banez EI, Shattil SJ, Heliums JD. Flow cytometric studies of platelet responses to shear stress in whole blood. Biorheology 1995; 32: 73-93
    CrossrefPubMedGoogle Scholar
  • 6 Davies MJ. Mechanisms of thrombosis in atherosclerosis. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice Colman RW, Hirsh J, Marder VJ, Salzman EW. eds J. B. Lippincott Company; Philadelphia: 1994. 62: pp 1225-1237
  • 7 Barstad RM, Roald HE, Cui Y, Turitto VT, Sakariassen KS. A perfusion chamber developed to investigate thrombus formation and shear profiles in flowing native human blood at the “apex” of well-defined stenoses. Arterioscl Thromb 1994; 14: 1984-1991
    CrossrefPubMedGoogle Scholar
  • 8 Roux SP, Sakariassen KS, Turitto VT, Baumgartner HR. Effect of aspirin and epinephrine on experimentally induced thrombogenesis in dogs. A parallelism between in vivo and ex vivo thrombosis models. Arterioscl Thromb 1991; 111: 1182-1191
    PubMedGoogle Scholar
  • 9 Sakariassen KS, Barstad RM. Mechanisms of thromboembolism at arterial plaques. Blood Coag Fibrinolysis 1993; 4: 615-625
    CrossrefPubMedGoogle Scholar
  • 10 Strony J, Beaudoin A, Brands D, Adelman B. Analysis of shear stress and hemodynamic factors in a model of coronary artery stenosis and thrombosis. Am J Physiol 1993; 265: 1787-1796
    PubMedGoogle Scholar
  • 11 Fabris F, Casanotto A, Randi ML, Luzanotto G, De Silvestro G, Ongasro G, Girolami A. The use of fluorescence flow cytometry in characterization of Bemard-Soulier syndrome and Glanzmann’s Thrombasthenia. Haemato-logica 1989; 74: 39-44
    PubMedGoogle Scholar
  • 12 Sadler JE. A revised classification of von Willebrand disease. Thromb Haemost 1994; 71: 520-525
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Miller EF, Rhodes RK. Preparation and characterization of the different types of collagen. Methods Enzymol 1982; 82: 33-64
    PubMedGoogle Scholar
  • 14 Bruns RR, Gross J. High resolution analysis of the quarter stagger model of the collagen fibril. Biopolymers 1977; 13: 931-941
    PubMedGoogle Scholar
  • 15 Sakariassen KS, Muggli R, Baumgartner HR. Measurements of platelet interaction with components of the vessel wall in flowing blood. Methods Enzymol 1989; 169: 37-70
    PubMedGoogle Scholar
  • 16 Sakariassen KS, Joss R, Muggli R, Kuhn H, Tschopp TB, Sage H, Baumgartner HR. Collagen type III induced ex vivo thrombogenesis in humans: role of platelets and leukocytes in deposition of fibrin. Arteriosclerosis 1990; 10: 276-284
    CrossrefPubMedGoogle Scholar
  • 17 Baumgartner HR. Effects of anticoagulation on the interaction of human platelets with subendothelium in flowing blood. Schweiz Med Wochenschr 1976; 106: 1367-1368
    PubMedGoogle Scholar
  • 18 Lee JS, Fung YC. Flow in locally constricted tubes at low Reynolds numbers. J Appl Mech 1970: 09-16
    PubMedGoogle Scholar
  • 19 Baumgartner HR, Muggli R. Adhesion and aggregation: morphological demonstration and quantitation in vivo and in vitro. In: Platelets in Biology and Pathology Gordon JL. (ed) Elsevier/North-Holland; Amsterdam: 1976: 23-60
  • 20 Sakariassen KS, Muggli R, Baumgartner HR. Growth and stability of thrombi in flowing citrated blood: assessment of platelet surface interactions with computer-assisted morphometry. Thromb Haemost 1988; 60: 390-398
    PubMedGoogle Scholar
  • 21 O’Brien JR, Salmon GP. Shear stress activation of platelet glycoprotein Ilb/IIIa plus von Willebrand factor causes aggregation: Filter blockage and the long bleeding time in von Willebrand’s disease. Blood 1987; 70: 1354-1361
    PubMedGoogle Scholar
  • 22 Veen G, Meyer A, Verheugt FW, Werter CJ, de-Swart H, Lie KI, van der Pol JM, Michels HR, van Einige MJ. Culprit lesion morphology and stenosis severity in the prediction of reocclusion after coronary thrombolysis: Angiographic results of the APRICOT study. J Am Coll Cardiol 1993; 22 (01) 1755-1762
    CrossrefPubMedGoogle Scholar
  • 23 Sakariassen KS, Baumgartner HR. Axial dependence of platelet-collagen interaction in flowing blood: upstream thrombus growth impairs downstream platelet adhesion. Arteriosclerosis 1989; 9: 33-42
    CrossrefPubMedGoogle Scholar
  • 24 Roald HE, Sakariassen KS. Axial dependence of collagen-induced thrombus formation in flowing non-anticoagulated human blood. Thromb Haemost 1995; 73: 126-131
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Tschopp TB, Weiss HJ, Baumgartner HR. Interaction of thrombasthénie platelets with subendothelium: normal adhesion, absent aggregation. Experientia 1975; 31: 113-116
    CrossrefPubMedGoogle Scholar
  • 26 Sakariassen KS, Nievelstein PFEM, Coller BS, Sixma JJ. The role of platelet membrane glycoprotein Ib and IIb-IIIa in platelet adherence to human artery subendothelium. Br J Haemat 1986; 63: 681-691
    CrossrefPubMedGoogle Scholar
  • 27 Weiss H, Turitto VT, Baumgartner HR. Role of shear rate and platelets in promoting fibrin formation on rabbit subendothelium: studies utilizing patients with quantitative and qualitative platelet defects. J Clin Invest 1986; 78: 1072-1082
    CrossrefPubMedGoogle Scholar
  • 28 Weiss HJ, Turitto VT, Baumgartner HR. Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. Shear-dependent decrease of adhesion in von Willebrand’s disease and the Bernard Soulier Syndrome. J Lab Clin Med 1978; 92: 750-764
    PubMedGoogle Scholar
  • 29 Fressinaud E, Sakariassen KS, Rothschild C, Baumgartner HR, Meyer D. Shear rate-dependent impairment of thrombus growth on collagen in nonanticoagulated blood from patients with von Willebrand disease and Hemophilia A. Blood 1992; 80: 988-994
    PubMedGoogle Scholar