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Thromb Haemost 1994; 71(01): 078-090
DOI: 10.1055/s-0038-1642388
Review Article
Schattauer GmbH Stuttgart

Adenosine Diphosphate-Induced Aggregation of Human Platelets in Flow Through Tubes: III. Shear and Extrinsic Fibrinogen-Dependent Effects

H L Goldsmith
1   The McGill University, Medical Clinic, Montreal General Hospital, Canada
2   The Departments of Medicine and Physiology, McGill University, Montreal, Canada
,
M M Frojmovic
2   The Departments of Medicine and Physiology, McGill University, Montreal, Canada
,
Susan Braovac
1   The McGill University, Medical Clinic, Montreal General Hospital, Canada
,
Fiona McIntosh
1   The McGill University, Medical Clinic, Montreal General Hospital, Canada
,
T Wong
2   The Departments of Medicine and Physiology, McGill University, Montreal, Canada
› Author Affiliations
Further Information

Publication History

Received: 01 October 1993

Accepted after revision 05 October 1993

Publication Date:
12 July 2018 (online)

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Summary

The effect of shear rate and fibrinogen concentration on adenosine diphosphate-induced aggregation of suspensions of washed human platelets in Poiseuille flow at 23°C was studied using a previously described double infusion technique and resistive particle counter size analysis (1). Using suspensions of multiple-centrifuged and -washed cells in Tyrodes-albumin [3 × 105 μl−1; (17)] with [fibrinogen] from 0 to 1.2μM, the, rate and extent of aggregation with 0.7 μM ADP in Tyrodes-albumin were measured over a range of mean transit times from 0.2 to 43 s, and at mean tube shear rates, Ḡ, = 41.9, 335 and 1,335 s−1. As measured by the decrease in singlet concentration, aggregation at 1.2 μM fibrinogen increased with increasing Ḡ up to 1,335 s1, in contrast to that previously reported in citratcd plasma, in which aggregation reached a maximum at Ḡ = 335 s−1. Without added fibrinogen, there was no aggregation at Ḡ = 41.9 s1; at Ḡ = 335 s1, there was significant aggregation but with an initial lag time, aggregation increasing further at Ḡ = 1,335 s−1. Without added fibrinogen, aggregation was abolished at all Ḡ upon incubation with the hexapeptide GRGDSP, but was almost unaffected by addition of an F(ab’)2 fragment of an antibody to human fibrinogen. Aggregation in the absence of added fibrinogen was also observed at 37°C. The activation of the multiple-washed platelets was tested using flow cytometry with the fluorescently labelled monoclonal antibodies FITC-PAC1 and FITC-9F9. It was shown that 57% of single cells in unactivated PRT expressed maximal GPIIb-IIIa fibrinogen receptors (MoAb PAC1) and 54% expressed pre-bound fibrinogen (MoAb 9F9), with further increases on ADP activation. However, incubation with GRGDSP and the F(ab’)2 fragment did not inhibit the prebound fibrinogen. Moreover, relatively unactivated cells (8% expressing receptor, 14% prebound fibrinogen), prepared from acidified cPRP by single centrifugation with 50 nM of the stable prostacyclin derivative, ZK 36 374, and resuspension in Tyrodes-albumin at 5 × 104 μl−1, aggregated with 2 and 5 μM ADP at Ḡ = 335 and 1,335 s−1 in the absence of added fibrinogen. We therefore postulate that a protein such as von Willebrand factor, secreted during platelet isolation or in flow at sufficiently high shear rates, may yield the observed shear-rate dependent aggregation without fibrinogen.

 

  • References

  • 1 Bell DN, Spain S, Goldsmith HE. The ADP-induced aggregation of human platelets in flow through tubes: I. Measurement of the concentration and size of single platelets and aggregates. Biophys J 1989; 56: 817-28
    CrossrefPubMedSearch in Google Scholar
  • 2 Bell DN, Spain S, Goldsmith HE. The ADP-induced aggregation of human platelets in flow through tubes: II. Effect of shear rate, donor sex. and ADP concentration. Biophys J 1989; 56: 819-43
    PubMedSearch in Google Scholar
  • 3 Bell DN, Spain S, Goldsmith HE. Extracellular Ca2+ accounts for the sex difference in the aggregation of human platelets in citrated platelet-rich plasma. Thromb Res 1990; 58: 47-60
    CrossrefPubMedSearch in Google Scholar
  • 4 Goldsmith HE, Turitto VT. Rheological aspects of thrombosis and haemostasis: Basic principles and applications. Thromb Haemost 1986; 55: 415-35
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Phillips DR, Baughan AK. Fibrinogen binding to human platelet plasma membranes. J Biol Chem 1985; 285: 10240-6
    PubMedSearch in Google Scholar
  • 6 Phillips DR, Charo JF, Parise EV, Fitzgerald LA. The platelet membrane glycoprotein IIb-IIIa, complex. Blood 1988; 71: 831-43
    PubMedSearch in Google Scholar
  • 7 Frojmovic MM, Wong T, van de Ven T. Dynamic measurements of the platelet membrane glycoprotein Ilb-IIIa receptor for fibrinogen by flow cy tometry. I. Methodology, theory and results for two distinct activators. Biophys J 1991; 59: 815-27
    CrossrefPubMedSearch in Google Scholar
  • 8 Frojmovic MM, O’Toole TE, Plow EF, Loft us JC, Ginsberg M. Platelet glycoprotein IIb-IlIa (α11bβ3 integrin) confers fibrinogen- and activation-dependent aggregation on heterologous cells. Blood 1991; 78: 369-76
    PubMedSearch in Google Scholar
  • 9 Sung P-L, Frojmovic MM, O’Toole TE, Zhu C, Ginsberg M, Chien S. Determination of adhesion force between single cell pairs generated by activated GpIIb-IIIa receptors. Blood 1993; 81: 419-23
    PubMedSearch in Google Scholar
  • 10 Gugler E, Eiischer EF. Platelet function in congenital afib-rinogenaemia. Thromb Diath Haemorrh 1965; 14: 361-73
    PubMedSearch in Google Scholar
  • 11 Inceman S, Caen J, Bernard J. Aggregation, adhesion and viscous metamorphosis of platelets in congenital fibrinogen deficiencies. J Lab Clin Med 1966; 69: 21-32
    PubMedSearch in Google Scholar
  • 12 Soria J, Soria C, Borg JY, Mirashahi M, Piguet H, Tron P, Lessard C, Caen JP. Platelet aggregation occurs in congenital afibrinogenaemia despite the absence of fibrinogen or its fragments in plasma and platelets, as demonstrated by immunoenzymology. Br J Haematol 1985; 60: 503-14
    CrossrefPubMedSearch in Google Scholar
  • 13 Weiss HJ, Rogers J. Fibrinogen and platelets in the primary arrest of bleeding. Studies in two patients with congenital afibrinogenemia. N Engl J Med 1971; 285: 369-74
    CrossrefPubMedSearch in Google Scholar
  • 14 Cattaneo M, Kinlough-Rathbone RL, Lecchi A, Bevilacqua C, Packham MA, Mustard JF. Fibrinogen-independent aggregation and deaggregation of human platelets: Studies in two afibrogenemic patients. Blood 1987; 70: 221-6
    PubMedSearch in Google Scholar
  • 15 Cross MJ. Effect of fibrinogen on the aggregation of platelets by adenosine diphosphate. Thromb Diathes Haemorrh 1964; 12: 524-7
    PubMedSearch in Google Scholar
  • 16 Bang NU, Heidenreich RO, Trygstad CW. Plasma protein requirements for human platelet aggregation. Ann NY Acad Sci 1972; 201: 280-99
    CrossrefPubMedSearch in Google Scholar
  • 17 Mustard JF, Perry DF, Ardlie NG, Packham MA. Preparation of suspensions of washed platelets from humans. Br J Haematol 1972; 22: 193-204
    CrossrefPubMedSearch in Google Scholar
  • 18 Mustard JF, Packham MA, Kinlough-Rathbone RL, Perry DW, Regoeczi E. Fibrinogen and ADP-induced platelet aggregation. Blood 1978; 52: 453-66
    PubMedSearch in Google Scholar
  • 19 Timmons S, Hawiger J. Von Willebrand factor can substitute for plasma fibrinogen in ADP-induced platelet aggregation. Trans Assoc Am Phys 1986; 99: 226-35
    PubMedSearch in Google Scholar
  • 20 De Marco L, Girolami A, Zimmermann TS, Ruggeri Z. Von Willebrand factor interaction with the glycoprotein Ilb/IIIa complex; its role in platelet function as demonstrated in patients with congenital afibrinogenemia. J Clin Invest 1986; 77: 1272-7
    CrossrefPubMedSearch in Google Scholar
  • 21 Frojmovic MM, Milton JG, Duchtastel A. Microscopic measurements of platelet aggregation reveal a low ADP-dependent process distinct from turbidometrically measured aggregation. J Lab Clin Med 1983; 101: 964-76
    PubMedSearch in Google Scholar
  • 22 Frojmovic MM, Milton JG, Gear AR. Platelet aggregation measured in vitro by microscopic and electronic particle counting. Methods Enzymol 1989; 169: 134-49
    PubMedSearch in Google Scholar
  • 23 Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Anbo H, Kawai Y, Watanabe K, Itagaki I, Sakai K, Ruggeri X. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest 1991; 87: 1234-40
    CrossrefPubMedSearch in Google Scholar
  • 24 Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Heliums JD. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest 1986; 78: 1456-61
    CrossrefPubMedSearch in Google Scholar
  • 25 Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Heliums JD. Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate and is resistant to aspirin. Blood 1988; 71: 1366-74
    PubMedSearch in Google Scholar
  • 26 Shor K, Darius H, Matzky R, Ohlendort R. The antiplatelet and cardiovascular actions of a new carbacyclic derivative (ZK 36374) – equipotent to PGI2 in vitro. Arch Pharm 1981; 316: 252-5
    CrossrefPubMedSearch in Google Scholar
  • 27 Marguerie GA, Plow EF, Edgington TS. Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chcm 1979; 254: 5357-63
    PubMedSearch in Google Scholar
  • 28 Pcerschkc EI, Zuekei MB, Grant RA, Egan JJ, Johnson MM. Correlation between fibrinogen binding to human platelets and platelet aggregability. Blood 1980; 55: 841-7
    PubMedSearch in Google Scholar
  • 29 Marguerie GA, Plow EF. Interaction of fibrinogen with the platelet receptor: Kinetics and effect of pH and temperature. Biochem 1981; 20: 1074-80
    CrossrefPubMedSearch in Google Scholar
  • 30 Lawrie JJ, Ross J, Kemp G. Purification of fibrinogen and the separation of its degradation products in the presence of calcium ions. Biochem Soc Trans 1987; 7: 693-4
    PubMedSearch in Google Scholar
  • 31 Plow EF, Pierschbacher MD, Ruoslathi E, Marguerie GA, Ginsberg MH. The effect of Arg-Gly-Asp-containing peptides on fibrinogen and von Willebrand factor binding to platelets. Proc Nat Acad Sci USA 1985; 82: 8057-61
    CrossrefPubMedSearch in Google Scholar
  • 32 Shattil SJ, Cunningham M, Hoxie JA. Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. Blood 1987; 70: 307-15
    PubMedSearch in Google Scholar
  • 33 Abrams CS, Ellison N, Budzynski AZ, Shattil SJ. Direct detection of activated platelets and platelet-derived microparticles in humans. Blood 1990; 75: 128-38
    PubMedSearch in Google Scholar
  • 34 van de Ven TG M, Mason SG. The microrheology of colloidal dispersions. VII. Orthokinetic doublet formation of spheres. Colloid Polymer Sci 1977; 255: 468-79
    CrossrefPubMedSearch in Google Scholar
  • 35 Swift DL, Friedlander SK. The coagulation of hydrosols by Brownian motion and laminar shear flow. J Colloid Sci 1964; 19: 621-47
    CrossrefPubMedSearch in Google Scholar
  • 36 Bell DN, Spain S, Goldsmith HL. The effect of red blood cells on the ADP-induced aggregation of human platelets in flow through tubes. Thromb Haemost 1990; 63: 112-21
    Thieme ConnectPubMedSearch in Google Scholar
  • 37 Valdorf-Hansen JF, Zucker MB. Effect of temperature and inhibitors on serotonin-14C release from human platelets. Am J Physiol 1971; 220: 105-11
    PubMedSearch in Google Scholar
  • 38 Gralnick HR, Williams SN, Mc Keown L, Connaghan G, Shafer B, Hausmann K, Vail M, Fenton J. Endogenous platelet fibrinogen surface expression on activated platelets. J Lab Clin Med 1991; 118: 604-13
    PubMedSearch in Google Scholar
  • 39 Hsu-Lin S-C, Berman CL, Furie BC, August D, Furie B. A platelet membrane glycoprotein expressed during platelet activation and secretion: Studies using a monoclonal antibody specific for thrombin-activated platelets. J Biol Chcm 1984; 259: 9121-6
    PubMedSearch in Google Scholar
  • 40 Mc Ever RP, Martin MN. A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem 1984; 259: 9799-804
    PubMedSearch in Google Scholar
  • 41 Aasch AS, Barnwell J, Silverstein RL, Nachman RL. Isolation of the thrombospondin membrane receptor. J Clin Invest 1987; 79: 1054-61
    CrossrefPubMedSearch in Google Scholar
  • 42 Frojmovic MM, Mooney RF, Wong T. Platelet aggregation requires maximal expression of GPIIb-IIIa adhesive receptors on each platelet determined by the activating ADP concentration. Circulation 1984; 84: II689
    PubMedSearch in Google Scholar
  • 43 Peerschke EL. Irreversible platelet fibrinogen interactions. J Lab Clin Med 1988; 11: 84-92
    PubMedSearch in Google Scholar