Thromb Haemost 1998; 80(02): 225-230
DOI: 10.1055/s-0037-1615177
Rapid Communication
Schattauer GmbH

Measurement of Platelet Microparticles during Cardiopulmonary Bypass by Means of Captured ELISA for GPIIb/IIIa

Shinji Miyamoto
1   Harrison Department of Surgical Research, Department of Surgery, School of Medicine, University of Pennsylvania
,
Cezary Marcinkiewicz
2   Sol Sherry Thrombosis Research Center
3   Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA
,
L. Henry Edmunds
1   Harrison Department of Surgical Research, Department of Surgery, School of Medicine, University of Pennsylvania
,
Stefan Niewiarowski
2   Sol Sherry Thrombosis Research Center
3   Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA
› Author Affiliations
Further Information

Publication History

Received 19 August 1997

Accepted after resubmission 22 April 1998

Publication Date:
08 December 2017 (online)

Summary

A captured enzyme-linked immunosorbent assay (ELISA) using the disintegrin, kistrin, is described and used to measure platelet microparticles (PMP) generated during open heart surgery. This ELISA detects 75 ng/ml of glycoprotein IIb/IIIa (GPIIa/IIIa) in solution and is more sensitive and less variable than flow cytometry and radioimmunoassay. By ELISA, mean values of GPIIb/IIIa in PMP are 14.2 ± 7.9 μg/ml for outdated platelets and 0.28 ± 0.1 μg/ml in fresh blood from healthy donors. Normal washed platelets (108) contain 8.8 μg of GPIIb/IIIa.

In 12 cardiac surgical patients, PMP measured by ELISA significantly increased (p = 0.039) to 0.58 ± 0.3 μg/ml at the end of cardio-pulmonary bypass, but the increase measured by flow cytometry (1207 to 1447 events in PMP gate) was not significant. Neither heparin nor protamine alter PMP. After cardiopulmonary bypass, PMP concentrations return to baseline values before protamine is given. Concentrations of PMP in pericardial blood are greater than in simultaneous perfusate. This ELISA is more sensitive and accurate than alternate methods for measuring PMP and shows the PMP production and rapid clearance during open cardiac surgery.

Present address: Dr. Shinji Miyamoto, Department of Cardiovascular Surgery, Oita Medical University, 1-1 Idaigaoka, Oita, Japan

 
  • References

  • 1 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.
  • 2 Abrams CS, Ellison N, Budzynski AZ, Shattil SJ. Direct activation platelets and platelet-derived microparticles in humans.. Blood 1990; 75: 128-38.
  • 3 Warkentin TE, Hayward CPM, Boshkov LK, Santos AV, Sheppard J-A, Bode AP, Kelton JG. Sera from patients with heparin induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia.. Blood 1994; 84: 3691-9.
  • 4 Lee YJ, Jy W, Hortman LL, Janania J, Reyes Yolanda, Kelley RE, Ahn YS. Elevated platelet microparticles in transient ischemic attacks, lacunar infarcts, and multi-infarct dementias.. Thromb Res 1993; 72: 295-304.
  • 5 Miyazaki Y, Nomura S, Miyake T, Kagawa H, Kitada C, Taniguchi H, Komiyama Y, Fujimura Y, Ikeda Y, Fukuhara S. High shear stress can initiate both platelet aggregation and shedding of procoagulant containing microparticles.. Blood 1996; 88: 3456-64.
  • 6 Holme PA, Orvim U, Hamers MJAG, Solum NO, Brosstad FR, Barstad RM, Sakariassen KS. Shear-induced platelet activation and platelet micro-particle formation at blood flow conditions as in arteries with a severe stenosis.. Arterioscler Thromb 1996; 17: 646-53.
  • 7 Sims PJ, Faioni EM, Wiedmer T, Shattil SJ. Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity.. J Biol Chem 1988; 263: 18205-12.
  • 8 Tans G, Rosing J, Christella M, Thomassen LGD, Reeb MJ, Zwaal RFA, Griffin JH. Comparison of anticoagulant and procoagulant activities of stimulated platelets and platelet derived microparticles.. Blood 1991; 77: 2641-8.
  • 9 Jy W, Horstman LL, Arce M, Ahn YS. Clinical significance of platelet microparticles in autoimmune thrombocytopenias.. J Lab Clin Med 1992; 119: 334-45.
  • 10 Nomura S, Komiyama Y, Matsuura E, Xie GL, Katsura K, Miyake T, Miyazaki Y, Kagawa H, Koike T, Fukahara S. Participation of αIIbβ3 in platelet microparticle generation by collagen plus thrombin.. Haemostasis 1996; 26: 31-7.
  • 11 Jy W, Mao W-W, Horstman LL, Tao J, Ahn YS. Platelet microparticles bind, activate and aggregate neutrophils in vitro.. Blood Cell Molecules and Diseases 1995; 21: 217-31.
  • 12 Gemmell CH, Ramirez SM, Yeo EL, Sefton MV. Platelet activation in whole blood by artificial surfaces; identification of platelet-derived micro-particles and activated platelet binding to leukocytes as material-induced activation events.. J Lab Clin Med 1995; 125: 276-87.
  • 13 Sloand E, Alyono D, Yu M, Klein H. Platelet membrane glycoproteins and microvesicles in blood from postoperative salvage: a study in cardiac bypass patients.. Transfusion 1995; 35: 738-44.
  • 14 Iwamoto S, Kawasaki T, Kambayashi J, Ariyoshi H, Monden M. Platelet microparticles: a carrier of platelet-activating factor?. Biochem Biophys Res Comm 1996; 218: 940-4.
  • 15 Sims PJ, Wiedmer T, Esmon CT, Weiss HJ, Shattil SJ. Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome; an isolated defect in platelet procoagulant activity.. J Biol Chem 1989; 264: 117049-57.
  • 16 Pasquet JM, Dachary-Prigent J, Nurden AT. Calcium influx is a determining factor of calpain activation and microparticles formation in platelets.. Eur J Biochem 1996; 239: 647-54.
  • 17 Holme PA, Roger M, Solum NO, Brosstad F, Larsen AM, Hovig T. Glycoprotein IIb/IIIa on platelet-derived microparticles, and microparticle structures studied by electron microscopy, confocal laser microscopy and cross-radioimmuno-electrophoresis.. Platelet 1996; 7: 207-14.
  • 18 Williams J, Rucinski B, Holt JC, Niewiarowski S. Elegantin and albolabrin purified peptides from viper venoms. Homologies with the RGDS domain of fibrinogen and von Willebrand factor.. Biochem Biophys Acta 1990; 1039: 81-9.
  • 19 Cook JJ, Trybulec M, Lasz EC, Khan S, Niewiarowski S. Binding of glycoprotein IIIa-derived peptide 217-231 to fibrinogen and von Wille-brand factors and its inhibition by platelet glycoprotein IIb/IIIa complex.. Biochim Biophys Acta 1992; 1119: 312-21.
  • 20 Marcinkiewicz C, Rosenthal LA, Mosser DM, Kunicki TJ, Niewiarowski S. Immunological characterization of eristostatin and echistatin binding sites on αIIbβ3 integrins.. Biochemical J 1996; 317: 817-25.
  • 21 Nieuwland R, Berckmans RJ, Rotteveel-Eijkman RC, Maquelin KN, Roozendaal KJ, Jansen PGM, Ten Have K, Eijsman L, Hack CE, Sturk A. Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant.. Circulation 1997; 96: 3534-41.
  • 22 Dennis MS, Henzel WJ, Pitti RM, Lipari MT, Napier MA, Deisher TA, Bunting S, Lazarus RA. Platelet glycoprotein IIb/IIIa protein antagonists from snake venoms. Evidence for a family of platelet-aggregation inhibitors.. Proc Natl Acad Sci USA 1990; 87: 2471-5.
  • 23 Gould RI, Polokoff MA, Friedman PA, Huang TF, Holt JC, Cook JJ, Niewiarowski S. Disintegrins. A family of integrin inhibitory proteins from viper venoms.. Proc Soc Exp Biol Med 1990; 195: 168-71.
  • 24 Huang TF, Holt JC, Lukasiewicz H, Niewiarowski S. Trigramin: A low molecular weight peptide inhibiting fibrinogen interaction with platelet receptors expressed on glycoprotein IIb-IIIa complex.. J Biol Chem 1987; 262: 16157-63.
  • 25 McLane MA, Kowalska MA, Silver L, Shattil SJ, Niewiarowski S. Interaction of disintegrins with the αIIbβ3 receptor on resting and activated human platelets.. Biochem J 1994; 301: 429-36.
  • 26 Juliano D, Wang Y, Marcinkiewicz C, Rosenthal LA, Stewart GJ, Niewiarowski W. Disintegrin interaction with αvβ3 integrin on human umbilical vein endothelial cells: expression of ligand-induced binding site on β3 subunit.. Exper Cell Res 1996; 225: 132-42.
  • 27 Coller BS, Cheresh DA, Asch E, Seligsohn U. Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthenia in Israel.. Blood 1991; 77: 75-83.
  • 28 Cierniewski CS, Niewiarowski S, Hershock D, Rucinski B, Schmaier AH. Quantitation and characterization of human platelet glycoprotein IIIa by radioimmunoassay.. Biochim Biophys Acta 1987; 924: 216-24.
  • 29 Holme PA, Solum NO, Brosstad F, Roger M, Abdelnoor M. Demonstration of platelet-derived microvesicles in blood from patients with activated coagulation and fibrinolysis using a filtration technique and western blotting.. Thromb Haemost 1994; 72: 666-71.
  • 30 Edmunds Jr LH. Why cardiopulmonary bypass makes patients sick; strategies to control the blood-synthetic surface interface.. In: Advances in Cardiac Surgery. Volume 6. Mosby Year Book, Inc.; St. Louis: 1995. pp 131-67.
  • 31 Wenger RW, Lukasiewicz H, Mikuta BS, Niewiarowski S. Edmunds Jr. LH. Loss of platelet fibrinogen receptors during clinical cardiopulmonary bypass.. J Thorac Cardiovasc Surg 1989; 97: 235-9.
  • 32 Musial J, Niewiarowski S, Hershock D, Morinelli TA, Colman RW. Edmunds, Jr. LH. Loss of fibrinogen receptors from the platelet surface during simulated extracorporeal circulation.. J Lab Clin Med 1985; 105: 514-22.
  • 33 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.
  • 34 Chung BA, Gikakis N, Rao AK, Drake TA, Colman RW. Edmunds Jr. LH. Pericardial blood activates the extrinsic coagulation pathway during clinical cardiopulmonary bypass.. Circulation 1996; 93: 2014-8.
  • 35 Tabuchi N, Haan J, Boonstra PW, van Oeveren W. Activation of fibrinolysis in the pericardial cavity during cardiopulmonary bypass.. J Thorac Cardiovasc Surg 1993; 106: 828-33.
  • 36 Miyamoto S, Kowalska MA, Marcinkiewicz C, Mosser D, Edmunds Jr. LH, Niewiarowski S. Interaction of platelet microparticles with leukocytes.. Thromb Haemost. (submitted) 1998.