Subscribe to RSS
DOI: 10.1055/s-0037-1615226
A Heparin-coated Circuit Maintains Platelet Aggregability in Response to Shear Stress in an In Vitro Model of Cardiopulmonary Bypass
Publication History
Received
08 December 1997
Accepted after resubmission
13 May 1998
Publication Date:
08 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199803/lookinside/thumbnails/10-1055-s-0037-1615226-1.jpg)
Summary
Alterations in platelet aggregability may play a role in the pathogenesis of qualitative platelet defects associated with cardiopulmonary bypass (CPB). We circulated fresh heparinized whole blood through tubing sets coated with heparin (C group, n = 10) and through non-coated sets (N group, n = 10) as a simulated CPB circuit. Shear stress (108 dyne/cm2)-induced platelet aggregation (hSIPA), plasma von Willebrand factor (vWF) activity and platelet glycoprotein (GP) Ib expression were measured, before, during, and after this in vitro set up of circulation. In the two groups, the extent of hSIPA significantly decreased during circulation and was partially restored after circulation. Decreases in the extent of hSIPA were significantly less with use of heparin-coated circuits. There was an equivalent reduction in plasma vWF activity, in the two groups. Expression of platelet surface GP Ib decreased significantly during circulation and recovered after circulation. Reduction of surface GP Ib expression during circulation was significantly less in the C group than that in the N group. Decrease in surface GP Ib expression correlated (r = 0.88 in either group) with the magnitude of hSIPA, in the two groups. The progressive removal of surface GP Ib was mainly attributed to redistribution of GP Ib from the membrane skeleton into the cytoskeleton. Our observations suggest that use of heparin-coated circuits partly blocks the reduction of hSIPA, as a result of a lesser degree of redistribution of GP Ib.
-
References
- 1 Woodmann RC, Harker LA. Bleeding complications associated with cardiopulmonary bypass. Blood 1990; 76: 1680-97.
- 2 Rinder CS, Mathew JP, Rinder HM, Bonan J, Ault KA, Smith BR. Modulation of platelet surface adhesion receptors during cardiopulmonary bypass. Anesthesiology 1991; 75: 563-70.
- 3 Harker LA, Malpass TW, Branson HE, Hessel EA, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: Acquired transient platelet dysfunction associated with selective α-granule release. Blood 1980; 56: 824-34.
- 4 Boldt J, Knothe C, Welters I, Dapper FL, Hempelmaa DG. Normothermic versus hypothermic cardiopulmonary bypass: Do changes in coagulation differ?. Ann Thorac Surg 1996; 62: 130-5.
- 5 Kondo C, Tanaka K, Takagi K, Shimono T, Shinpo H, Yada I, Yuasa H, Kusagawa M, Akamatsu N, Tanoue K. Platelet dysfunction during cardiopulmonary bypass surgery with special reference to platelet membrane glycoproteins. ASAIO J 1993; 39: M550-3.
- 6 Lavee J, Savion N, Smolinsky A, Goor DA, Mohr R. Platelet protection by aprotinin in cardiopulmonary bypass: Electron microscopic study. Ann Thorac Surg 1992; 53: 477-81.
- 7 Kroll MH, Hellums JD, McIntire LV, Schafer AI, Moake JL. Platelets and shear stress. Blood 1996; 88: 1525-41.
- 8 Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb-IIIa complex. Blood 1988; 71: 831-43.
- 9 Pytela R, Pierschbacher MD, Ginsberg MH, Plow EF, Ruoslahti E. Platelet membrane glycoprotein IIb/IIIa: Member of a family of Arg-Gly-Asp-specific adhesion receptors. Science 1986; 231: 1559-62.
- 10 Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Ando H, Kawai Y, Watanabe K, Itagaki I, Sakai K, Zaverio MR. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest 1991; 87: 1234-40.
- 11 Kroll MH, Harris TS, Moake JL, Handin RI, Schafer AI. von Willebrand factor binding to platelet GP Ib initiates signals for platelet activation. J Clin Invest 1991; 88: 1568-73.
- 12 Nakai K, Hayashi T, Nagaya S, Toyoda H, Yamamoto M, Shiku H, Ikeda Y, Nishikawa M. Shear stress-induced myosin association with cytoskeleton and phosphorylation in platelets. Life Sci 1997; 60: 181-91.
- 13 Adelman B, Michelson AD, Greenberg J, Handin RI. Proteolysis of platelet glycoprotein Ib by plasma is facilitated by plasmin lysine-binding regions. Blood 1986; 68: 1280-4.
- 14 Miller JL, Castella A. Platelet-Type von Willebrand’s Disease: Characterization of a new bleeding disorder. Blood 1982; 60: 790-4.
- 15 Hourdille P, Heimann E, Combrie R, Winckler J, Clemetson KJ, Nurden AT. Thrombin induces a rapid redistribution of glycoprotein Ib-IX complexes within the membrane systems of activated human platelets. Blood 1990; 76: 1503-13.
- 16 Michelson AD, Barnard MR. Thrombin-induced changes in platelet membrane glycoproteins Ib, IX, and IIb-IIIa complex. Blood 1987; 70: 1673-8.
- 17 Toyoda H, Nakai K, Omay SB, Shima H, Nagao M, Shiku H, Nishikawa M. Differential association of protein Ser/Thr phosphatase types 1 and 2A with the cytoskeleton upon platelet activation. Thromb Haemost 1996; 76: 1053-62.
- 18 Michelson AD, Benoit SE, Kroll MH, Li J-M, Rohrer MJ, Kestin AS, Barnard MR. The activation-induced decrease in the platelet surface expression of the glycoprotein Ib-IX complex is reversible. Blood 1994; 83: 3562-73.
- 19 Michelson AD, Ellis PA, Barnard MR, Matic GB, Viles AF, Kestin AS. Downregulation of the platelet surface glycoprotein Ib-IX complex in whole blood stimulated by thrombin, adenosine diphosphate, or an in vivo wound. Blood 1991; 77: 770-9.
- 20 Rinder CS, Bohnert J, Rinder HM, Mitchell J, Ault K, Hillman R. Platelet activation and aggregation during cardiopulmonary bypass. Anesthesiology 1991; 75: 388-93.
- 21 George JN, Pickett EB, Saucerman S, McEver RP, Kunicki TJ, Kieffer N, Newman PJ. Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery. J Clin Invest 1986; 78: 340-8.
- 22 van Oevern W, Harder MP, Roozendaal KJ, Eijsman L, Wildevuur CRH. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990; 99: 788-97.
- 23 Sloand EM, Alyono D, Klein HG, Chang P, Yu M, Lightfoot FG, Kessler C. 1-Deamino-8-D-Arginine Vasopressin (DDAVP) increases platelet membrane expression of glycoprotein Ib in patients with disorders of platelet function and after cardiopulmonary bypass. Am J Hematol 1997; 46: 199-207.
- 24 Coller BS, Kalomiris E, Steinberg M, Scudder LE. Evidence that glycocalicin circulates in normal plasma. J Clin Invest 1984; 73: 794-9.
- 25 Nurden P. Bidirectional trafficking of membrane glycoproteins following platelet activation in suspension. Thromb Haemost 1997; 78: 1305-15.
- 26 Pardhan MJ, Fleming JS, Nkere UU, Arnold J. Clinical experience with heparin-coated cardiopulmonary bypass. Perfusion 1991; 6: 235-42.
- 27 Bannan S, Danby A, Cowan D, Ashraf S, Martin PG. Low heparinization with heparin-bonded bypass circuits: It is a safe strategy?. Ann Thorac Surg 1997; 63: 663-8.
- 28 Gorman RC, Ziats NP, Rao AK, Gikakis N, Sun L, Khan MMH, Stenach N, Sapatnekar S, Chouhan V, Gorman III JH, Niewiarowski S, Colman RW, Anderson JM, Edmunds Jr LH. Surface-bound heparin fails to reduce thrombin formation during clinical cardiopulmonary bypass. J Thorac Cardiovasc Surg 1996; 111: 1-12.
- 29 Nakajima T, Osawa S, Ogawa M, Sasaki T, Izumoto H, Yagi Y, Kawazoe K. Clinical study of platelet function and coagulation/fibrinolysis with Duraflo II heparin coated cardiopulmonary bypass equipment. ASAIO J 1996; 42: 301-5.
- 30 Tanaka K, Tani K, Morimoto T, Yada I, Yuasa H, Kusagawa M. Hemostatic analysis for patients undergoing open heart surgery by molecular marker assays – with special reference to thrombin-antithrombin III complex and α2-plasmin inhibitor-plasmin complex. Artif Organ 1992; 2: 127-35.
- 31 Sobel M, McNeill PM, Carison PL, Kermode JC, Adelman B, Conroy R, Marques D. Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo. J Clin Invest 1991; 87: 1787-93.
- 32 Salzman EW, Rosenberg RD, Smith MH, Lindon JN, Favreau L. Effect of heparin and heparin fractions on platelet aggregation. J Clin Invest 1980; 65: 64-73.
- 33 Westwick J, Scully MF, Poll C, Kakkar VV. Comparisons of the effects of low molecular weight heparin and unfractionated heparin on activation of human platelets in vitro. Thromb Res 1986; 42: 435-47.
- 34 Kawano K, Ikeda Y, Handa M, Kamata T, Anbo H, Akai Y, Kawai Y, Watanabe K, Itagaki I, Kawakami K, Fukuyama M, Sakai K. Enhancing effect by heparin or shear-induced platelet aggregation. Semin Thromb Haemost 1990; 16: S60-5.
- 35 Lindon JN, Salzman EW, Merrill EW, Dincer AK, Labarre D, Bauer KA, Rosenberg RR. Catalytic activity and platelet reactivity of heparin covalently bonded to surfaces. J Lab Clin Med 1985; 105: 219-26.
- 36 Borowiec JW, Bylock A, van der Linden J, Thelin S. Heparin coating reduces blood cell adhesion to arterial filters during coronary bypass: a clinical study. Ann Thorac Surg 1993; 55: 1540-5.