Download PDF
Thromb Haemost 2000; 83(01): 54-59
DOI: 10.1055/s-0037-1613757
Commentary
Schattauer GmbH

Hemostatic Parameters and Platelet Activation Marker Expression in Cyanotic and Acyanotic Pediatric Patients Undergoing Cardiac Surgery in the Presence of Tranexamic Acid

Elena Levin
1   Department of Laboratory Medicine, University of British Columbia, Vancouver, Canada
,
John Wu
,
Dana V. Devine
1   Department of Laboratory Medicine, University of British Columbia, Vancouver, Canada
,
John Alexander
,
Clayton Reichart
2   Department of Anaesthesiology, University of British Columbia, Vancouver, Canada
,
Suvro Sett
3   Department of Surgery, University of British Columbia, Vancouver, Canada
,
Michael Seear
› Author Affiliations
Further Information

Publication History

Received December 1998

Accepted after resubmission 27 August 1999

Publication Date:
06 December 2017 (online)

    Permissions and Reprints

Summary

We have investigated hemostatic parameters including platelet activation in 56 pediatric patients with or without cyanosis undergoing cardiopulmonary bypass (CPB) and cardiac surgery to repair congenital defects. Patients were participants in a study assessing the effects of tranexamic acid on surgery-related blood loss. Parameters monitored included blood loss, prothrombin F1.2, thrombin-antithrombin complexes, t-PA, PAI-1, plasminogen, fibrin D-dimer, and plasma factor XIII. Additionally, flow cytometry monitored platelet degranulation (P-selectin or CD63), as well as surface-bound fibrinogen, von Willebrand factor and factor XIIIa. Cyanotic patients had evidence of supranormal coagulation activation as both fibrin D-dimer and PAI-1 levels were elevated prior to surgery. While the extent of expression of Pselectin or CD63 was not informative, platelet-associated factor XIIIa was elevated in cyanotic patients at baseline. In both patient groups, CPB altered platelet activation state and coagulation status irrespective of the use of tranexamic acid.

Key words

Platelet activation markers - pediatric cardiac surgery - factor XIII
 

  • References

  • 1 Zonis Z, Seear M, Reichert C, Sett S, Allen C. The effect of preoperative tranexamic acid on blood loss after cardiac operations in children. J Thoracic Cardiovasc Surg 1996; 111: 982-7.
    CrossrefPubMedGoogle Scholar
  • 2 Turner-Gomes SO, Nitschmann EP, Nroman GR, Andrew ME, Williams WG. Effect of heparin loading during congenital heart operation on thrombin generation and blood loss. Ann Thorac Surg 1997; 63: 482-8.
    CrossrefPubMedGoogle Scholar
  • 3 Devine DV, Carter CJ. Profibrinolytic and antifibrinolytic effects of platelets. Coronary Art Dis 1995; 06: 915-22.
    PubMedGoogle Scholar
  • 4 Becker RC, Tracy RP, Bovill EG, Mann KG, Ault K. The clinical use of flow cytometry for assessing platelet activation in acute coronary syndromes. Coronary Art Dis 1994; 05: 339-45.
    CrossrefPubMedGoogle 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.
    CrossrefPubMedGoogle Scholar
  • 6 Langford EJ, Parfitt A, de Belder AJ, Marrinan MT, Martin JF. A study of platelet activation during human cardiopulmonary bypass and the effect of S-nitrosoglutathione. Thromb Haemost 1997; 78: 1516-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Cox AD, Devine DV. Factor XIIIa binding to activated platelets is mediated through activation of glycoprotein IIb/IIIa. Blood 1994; 83: 1006-16.
    PubMedGoogle Scholar
  • 8 Janes SL, Janes SL, Wilson DJ, Chronos N, Goodall AH. Evaluation of whole blood flow cytometric detection of platelet bound fibrinogen on normal subjects and patients with activated platelets. Thromb Haemost 1993; 70: 659-66.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Cahill MR, Macey MG, Newland AC. Fixation with formaldehyde induces expression of activation dependent platelet membrane glycoproteins, P selectin (CD62) and GP53 (CD63). Br J Haematol 1993; 84: 527-9.
    CrossrefPubMedGoogle Scholar
  • 10 Adelman B, Michelson AD, Handin RI, Ault KA. Evaluation of platelet glycoprotein Ib by fluorescence flow cytometry. Blood 1985; 66: 423-7.
    PubMedGoogle Scholar
  • 11 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80: 1998-2005.
    PubMedGoogle Scholar
  • 12 Chan AKC, Leaker M, Burrows FA, Williams WG, Gruenwald CE, Whyte L, Adams M, Brooker LA, Adams H, Mitchell L, Andrew M. Coagulation and fibrinolytic profile of pediatric patients undergoing cardiopulmonary bypass. Thromb Haemost 1997; 77: 270-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Turner-Gomes SO, Mitchell L, Williams WG, Andrew M. Thrombin regulation in congenital heart disease after cardiopulmonary bypass operations. J Thorac Cardiovasc Surg 1994; 107: 562-8.
    PubMedGoogle Scholar
  • 14 Petaja J, Peltola K, Sairanen H, Jeijala M, Kekomaki R, Valhtera E, Siimes MA. Fibrinolysis, anti-thrombin III, and protein C in neonates during cardiac operations. J Thorac Cardiovasc Surg 1996; 112: 665-71.
    CrossrefPubMedGoogle Scholar
  • 15 Suarez CR, Menendez CE, Greffin AJ, Ow EP, Walenga JM, Fareed J. Cyanotic congenital heart disease in children: Hemostatic disorders and relevance of molecular markers of hemostasis. Sem Thromb Hemost 1984; 10: 285-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Maurer HM, McCue CM, Robertson LW, Haggins JC. Correction of platelet dysfunction and bleeding in cyanotic congenital heart disease by simple red cell volume reduction. Am J Cardiol 1975; 35: 831-5.
    CrossrefPubMedGoogle Scholar
  • 17 Olgun N, Uysal KM, Irken G, Unal N, Undar B, Akkoc N, Akcoral A, Sarialioglu F, Cevik N. Platelet activation in congenital heart disease. Acta Paed Japonica 1997; 39: 566-9.
    PubMedGoogle Scholar
  • 18 Waldman JD, Czapek EE, Paul MH, Schwartz AD, Levin DL, Schindler S. Shortened platelet survival in cyanotic heart disease. J Peds 1975; 87: 77-9.
    CrossrefPubMedGoogle Scholar
  • 19 Inenacho HNC, Breeze GR, Fletcher DJ, Stuart J. Consumption coagulopathy in congenital heart disease. Lancet 1973; 01: 231-6.
    PubMedGoogle Scholar
  • 20 Chandler WL, Fitch JC, Wall MH, Verrier ED, Cochran RP, Soltov LO. Individual variations in the fibrinolytic response during and after cardiopulmonary bypass. Thromb Haemost 1995; 74: 1293-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Sonntag J, Dahnert I, Stiller B, Hetzer R, Langer PE. Complement and contact activation during cardiovascular operations in infants. Ann Thorac Surg 1998; 65: 525-31.
    CrossrefPubMedGoogle Scholar
  • 22 Ashraf SS, Tian Y, Zacharrias S, Cowan D, Martin P, Watterson K. Effect of cardiopulmonary bypass on neonatal and pediatric inflammatory profiles. Eur J Cardiothoracic Surg 1997; 12: 862-8.
    CrossrefPubMedGoogle Scholar
  • 23 Rinder C, Fitch J. Amplication of inflammatory response: adhesion molecules associated with platelet/ white cell responses. J Cardiovasc Pharmacol 1996; 27 (Suppl. 01) s6-12.
    CrossrefPubMedGoogle Scholar
  • 24 Gelb AB, Roth RI, Levin J, London MJ, Noall RA, Hauck WW, Mangano DT. Changes in blood coagulation during and following cardiopulmonary bypass. Am J Clin Pathol 1996; 106: 87-99.
    CrossrefPubMedGoogle Scholar
  • 25 Ereth MH, Nutall GA, Klindworth JT, Macveigh I, Santrach PJ, Orzulak TA, Harmsen WS, Oliver WCJ. Does the platelet-activated clotting test (Hemo-STATUS) predict blood loss and platelet dysfunction associated with cardiopulmonary bypass?. Anaesthes Analgesia 1997; 85: 259-64.
    PubMedGoogle Scholar
  • 26 Woodman RC, Harker LA. Bleeding complications associated with cardiopulmonary bypass. Blood 1990; 50: 675-83.
    PubMedGoogle Scholar
  • 27 Fedderick W. Campbell The contribution of platelet dysfunction to postbypass bleeding. J Cardiothorac Vasc Anesth 1991; 05 (Suppl. 01) 8-12.
    CrossrefPubMedGoogle Scholar
  • 28 Rinder CS, Bonnert J, Rinder HM, Mitchell J, Ault K, Hillman RS. Platelet activation and aggregation during cardiopulmonary bypass. Anasthesiology 1991; 74: 388-93.
    PubMedGoogle Scholar
  • 29 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.
    CrossrefPubMedGoogle Scholar
  • 30 Rinder CS, Gaal D, Student LA, Smith BR. Platelet-leucocyte activation and modulation of adhesion receptors in pediatric patients with congenital heart disease undergoing cardiopulmonary surgery. J Thorac Cardiovasc Surg 1994; 107: 280-8.
    PubMedGoogle Scholar
  • 31 Kestin A, Valeri CR, Khuri SF, Loscalso J, Ellis PA, MacGregor, Birjiniuk V, Ouimet H, Pasche B, Nelson MJ, Benoit SE, Rodino LJ, Bernard MR, Michelson AD. The platelet function defect of cardiopulmonary bypass. Blood 1993; 82: 107-17.
    PubMedGoogle Scholar
  • 32 Devine DV, Andestad G, Nugent D, Carter CJ. Platelet-associated factor XIII as a marker of platelet activation in patients with severe peripheral vascular disease. Arterioscler Thrombos 1993; 13: 857-63.
    PubMedGoogle Scholar
  • 33 Levin E, Maharaj M, Carter CJ, Devine DV. Platelet-associated factor XIII as a marker of platelet activation in patients with unstable angina or myocardial infarction. Thromb Haemost 1997; 77 (suppl.): 32 (abstr.).
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Greenberg CS, Shuman MA. Specific binding of blood coagulation factor XIIIa to thrombin stimulated platelets. J Biol Chem 1984; 259: 14721-6.
    PubMedGoogle Scholar
  • 35 Vahba A, Black G, Koksch M, Rothe G, Preuner J, Schmitz G, Birnbaum DE. Cardiopulmonary bypass leads to a preferential loss of activated platelets. A flow cytometric assay of platelet surface antigens. Eur J Card Thorac Surg 1996; 10: 768-73.
    CrossrefPubMedGoogle Scholar
  • 36 Ammar T, Fisher CF. The effects of heparinase 1 and protamine on platelet reactivity. Anesthesiology 1997; 86: 1382-6.
    CrossrefPubMedGoogle Scholar
  • 37 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.
    CrossrefPubMedGoogle Scholar
  • 38 Holada K, Simak J, Kusera V, Roznova L, Eckschlager T. Platelet membrane receptors during short cardiopulmonary bypass – a flow cytometry study. Perfusion 1996; 11: 401-6.
    CrossrefPubMedGoogle Scholar
  • 39 Gemmell CH, Ramirez SM, Yeo EL, Sefton MV. Platelet activation in whole blood by artificial surfaces: identification of platelet-derived microparticles and activated platelet binding to leukocytes as material-induced activation events. J Lab Clin Med 1995; 125: 276-87.
    PubMedGoogle Scholar
  • 40 Michelson AD, Barnard MR, Hechtman HB, MacGregor H, Connolly RJ, Loscalzo J, Valeri CR. In vivo tracking of platelets: Circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function. Proc Nat Acad Sci (USA) 1996; 93: 11877-82.
    CrossrefPubMedGoogle Scholar
  • 41 Ferraris VA, Ferraris SP, Singh A, Fuhr W, Koppel D, McKenna D, Rodriguez E, Reich H. The platelet thrombin receptor and postoperative bleeding. Ann Thorac Surg 1998; 65: 352-8.
    CrossrefPubMedGoogle Scholar