HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Philip R. Belcher Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Belcher, P. R. Articles by Menys, V. C. Search for Related Content PubMed Articles by Belcher, P. R. Articles by Menys, V. C. Related Collections Related Article

Ann Thorac Surg 1999;68:1126
© 1999 The Society of Thoracic Surgeons

---

Correspondence

Platelet studies during cardiopulmonary bypass

^a Department of Cardiac Surgery, University of Glasgow, Royal Infirmary, Glasgow, Scotland, G31 2ER, Scotland, UK

To the Editor

We found the article by Kawahito and colleagues [1] describing the failure of formation of large platelet aggregates during cardiopulmonary bypass, while maintaining preservation of small aggregates, to be a gratifying confirmation of our previous work [2]. The sequence of aggregate formation from shape change to formation of small aggregates (microaggregation) and finally to large aggregates (macroaggregation) was well described in 1988 by Pedvis and associates [3], whom the authors have also not acknowledged. In our own studies we assessed the relative effects on platelet aggregation (microaggregation) by counting single unaggregated platelets in whole blood after agonist stimulation with collagen [4]. The formation of large aggregates (macroaggregation) was assessed by optical aggregometry in platelet-rich plasma. Despite well-preserved microaggregation we discovered the defect in macroaggregation to be present after cardiopulmonary bypass, although recovery was easily apparent within 25 minutes of the end of cardiopulmonary bypass. Subsequent studies in whole blood, using single platelet counting and impedance aggregometry, have confirmed that heparinization for cardiopulmonary bypass is the culprit and that the period of extracorporeal circulation has no extra effect [5]. The aspirin status of the patients in the study by Kawahito and associates is not specified.

We are disturbed by the choice of citrate as an anticoagulant, as findings using adenosine diphosphate (ADP) as the platelet stimulant might be obscured by artifacts associated with low Ca²⁺ concentrations. It has been shown that a low Ca²⁺ level in plasma favors thromboxane A₂ formation and secretion in response to ADP [6, 7]. The exaggerated response to ADP-induced aggregation might be more evident before cardiopulmonary bypass, as during and after cardiopulmonary bypass there is some impairment of largely ADP-dependent "spontaneous" platelet aggregation in stirred normocalcemic blood [2, 8]; Kawahito and colleagues did not measure this. Therefore, hemodilution during cardiopulmonary bypass, in addition to the dilution of samples for preparation of platelet-rich plasma, might have greatly exaggerated the degree of impairment of ADP-induced aggregation reported by them [1]. The use of ethylenediaminetetraacetic acid-anticoagulated samples gives a total platelet count, but because of disaggregation, does not allow estimation of the degree of extant aggregation within the circulation, especially that attributable to heparin [5, 9].

We also consider that the quantity of collagen used (2 µg/mL) was likely to be greater than that required to give a maximal response and therefore, that subtle changes in aggregation would have been missed. The researchers have neither presented dose–effect data nor have they specified their source of collagen. We used collagen (Hormon Chemie, Munich, Germany) 1 µg/mL for platelet studies in platelet-rich plasma and 0.6 µg/mL for studies in whole blood [5, 9, 10], which gave just submaximal responses.

References

1. Kawahito K., Kobayashi E., Iwasa H., Misawa Y., Fuse K. Platelet aggregation during cardiopulmonary bypass evaluated by a laser light-scattering method. Ann Thorac Surg 1999;67:79-84.[Abstract/Free Full Text]
2. Menys V.C., Belcher P.R., Noble M.I.M., et al. Macroaggregation of platelets in plasma, as distinct from microaggregation in whole blood (and plasma), as determined using optical aggregometry and platelet counting respectively, is specifically impaired following cardiopulmonary bypass in man. Thromb Haemost 1994;72:511-518.[Medline]
3. Pedvis L.G., Wong T., Frojmovic M.M. Differential inhibition of the platelet activation sequence. Shape change, micro- and macro-aggregation, by a stable prostacyclin analogue (Iloprost). Thromb Haemost 1988;59:323-328.[Medline]
4. Falcon C., Arnout J., Vermylen J. Platelet aggregation in whole blood—studies with a platelet counting technique—methodological aspects and some applications. Thromb Haemost 1989;61:423-428.[Medline]
5. Milne E.M., Muriithi E.W., Wanikiat P., Armstrong R.A., Wheatley D.J., Belcher P.R. Heparin, neutrophil-platelet interaction, and cardiopulmonary bypass. Clin Sci 1999;96(suppl 40):3.[Medline]
6. Packham M.A., Kinlough-Rathbone R.L., Mustard J.F. Thromboxane A₂ causes feedback amplification involving extensive thromboxane A₂ formation on close contact of human platelets in media with a low concentration of ionized calcium. Blood 1987;70:647-651.[Abstract/Free Full Text]
7. Falcon C.R., Cattaneo M., Ghidoni A., Mannucci P.M. The in vitro production of thromboxane B₂ by platelets of diabetic patients is normal at physiological concentrations of calcium. Thromb Haemost 1993;70:389-392.[Medline]
8. Zilla P., Fasol R., Groscurth P., Klepetko W., Reichenspurner H., Wolner E. Blood platelets in cardiopulmonary bypass operations. J Thorac Cardiovasc Surg 1989;97:379-388.[Abstract]
9. Menys V.C., Smith C.T.T., Belcher P.R., Pillai R. The influence of aspirin on the proaggregatory action of adrenaline after cardiopulmonary bypass in man. Platelets 1995;6:377-380.
10. Menys V.C., Belcher P.R., Noble M.I.M., Drossos G.E., Pillai R., Westaby S. Impaired platelet aggregation following cardiopulmonary bypass in man. Clinical Science 1995;88:269-275.[Medline]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Philip R. Belcher Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Belcher, P. R. Articles by Menys, V. C. Search for Related Content PubMed Articles by Belcher, P. R. Articles by Menys, V. C. Related Collections Related Article