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Ann Thorac Surg 1999;67:79-84
© 1999 The Society of Thoracic Surgeons

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Original Articles

Platelet aggregation during cardiopulmonary bypass evaluated by a laser light-scattering method

^a Department of Cardiovascular Surgery, Jichi Medical School, Tochigi, Japan
^b Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan
^c Omiya Medical Center, Jichi Medical School, Saitama, Japan

Accepted for publication June 16, 1998.

Address reprint requests to Dr Kawahito, Department of Cardiovascular Surgery, Jichi Medical School, Yakushiji, Minami-Kawachi, Kawachi, Tochigi 329-04, Japan
e-mail: bza06625{at}niftyserve.or.jp

	Abstract

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Background. In regard to postoperative bleeding, the most important consequence of cardiopulmonary bypass (CPB) is the loss of aggregability. However, the mechanism of platelet aggregation loss during CPB is unclear. Newly developed particle-counting methods that use light scattering can be used to quantify changes in the number of platelet aggregates of different sizes after application of an aggregating stimulus. Using a light-scattering method, we investigated changes in platelet aggregation during cardiac operation.

Methods. Nineteen patients undergoing CPB were evaluated. Blood samples were obtained before the operation, 1 hour after initiation of CPB, at the end of CPB, at the end of the operation, and on day 1 after the operation. Platelet aggregation after stimulation by 2.5 µmol/L adenosine diphosphate and 2.0 µg/mL collagen was determined; small (9 to 25 µm), medium (25 to 50 µm), and large (50 to 70 µm) aggregates were counted.

Results. Generation of medium and large aggregates after stimulation with adenosine diphosphate and collagen were significantly decreased with CPB, whereas, in spite of hemodilution, the quantity of the small aggregates was maintained at the elevated level.

Conclusions. These results reflect the fact that CPB does not affect the first phase of aggregation. It suggests that platelet dysfunction associated with CPB is mainly caused by an inhibition in the development of small aggregates into larger aggregates.

	Introduction

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Bleeding is one of the major complications after cardiopulmonary bypass (CPB). Platelet dysfunction during CPB, which may contribute to postoperative bleeding, has been reported by many authors [1–3] and results from contact activation induced by the extracorporeal circuit [4, 5], shear stress in flowing blood [6, 7], and drugs such as heparin [8, 9] and protamine sulfate [10]. In regard to postoperative bleeding, the most important consequence of CPB is the loss of aggregability [2–4]. However, the aggregation kinetics of platelets of different sizes, especially the pattern of aggregation loss during CPB, has not been fully investigated.

Although platelet aggregation is conventionally evaluated using optical density (OD) changes [11] or impedance analysis [12], these methods do not provide information about temporal changes in the numbers of platelet aggregates of different sizes after stimulation with an aggregation agent. Furthermore, the assumption that platelet aggregation evaluated by OD methods is reflective of in vivo hemostatic function is controversial [3, 13, 14]. The light-scattering (LS) method, which resembles that used in the flow cytometric light-scattering technique, enables selective detection of scattered light from a single aggregate in a defined observation volume. The intensity of scattered light corresponds to particle size and provides greater sensitivity than the OD method. Newly developed particle-counting methods that use light scattering (AG-10 aggregometer; Cowa Co Ltd, Tokyo, Japan) are being used to quantify real-time changes in the number of platelet aggregates of different sizes after the application of an aggregating stimulus [15–17]. This new system makes possible sensitive, continuous in situ evaluations of aggregation by counting and sizing aggregates. Using this system, we quantified aggregates of different sizes after stimulation with aggregating agents and observed their changes with time in patients undergoing cardiac operations.

	Material and methods

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Patients and surgical procedures
The study was conducted at Jichi Medical School Hospital and Omiya Medical Center between September 1996 and March 1998. Nineteen adult patients (14 men and 5 women) undergoing elective cardiovascular operations with CPB were studied. Patient ages ranged from 36 to 72 years (mean, 64 ± 8 years). The types of operations done were coronary artery bypass grafting in 11 patients, double valve replacement in 1 patient, mitral valvoplasty in 1 patient, mitral valve replacement in 2 patients, aortic valve replacement in 2 patients, left atrium myxoma resection in 1 patient, and atrium septal defect closure in 1 patient.

All received a similar balanced anesthesia, including high-dose sulfentanyl citrate and a neuromuscular blocking agent. All CPB procedures were done at moderate hypothermia (25° to 30°C) with cold-blood cardioplegia. The CPB system included a roller pump (Stöckert Instruments, Munich, Germany), a cardiotomy reservoir (William/Harvey; Bard, Tewksbury, MA), and a membrane oxygenator (Affinity, Avecor, Plymouth, MN). Bypass tubing included of standard silicone rubber components and polycarbonate connectors. The extracorporeal circuit was primed with crystalloid solution. Before cannulation, patients received heparin at a dose of 2.5 mg/kg body weight. Activated clotting time was maintained for more than 450 seconds during the CPB. Bypass was conducted at a flow rate of 2.4 L · min^-1 · m^-2, and mean arterial pressure was maintained at 50 to 70 mm Hg. After initiation of CPB, lung ventilation was discontinued and was subsequently resumed at the end of the period of aortic cross-clamping. After discontinuation of CPB, heparin was neutralized with protamine sulfate.

The duration of cardioplegic arrest varied from 25 to 164 minutes (mean, 100 ± 42 minutes), and CPB times ranged from 89 to 239 minutes (mean, 151 ± 44 minutes).

Platelet aggregation studies
Platelet-rich plasma (PRP) aggregation was simultaneously determined by evaluating maximal percent decrease in OD and by assessing the LS intensity using the AG-10 aggregometer. In the OD method, the output from the aggregometer was adjusted so that the difference in light transmittance between the PRP and the platelet-poor plasma (PPP) was 100%. Using the LS method, variations in particle size and concentration in PRP are measured by detecting the respective scattered light intensities passing through a laser beam. The principles of the LS method have been described previously [15–17]. Briefly, a He-Ne laser beam with a diameter of 40 µm was passed through 300 µm of PRP rotated in a cylindrical glass cuvette with a 5-mm internal diameter. Light scattered from the observation volume (48 x 140 x 20 µm) was detected with a four-channel photodiode array, with light intensity corresponding to particle size. Each of the four photodiodes detected the light-scattering particles in its corresponding observation volume (one photodiode for each observation volume). The intensity of the scattered light in the direction perpendicular to the optical axis from a particle passing through a laser beam is detected by a photodiode array through an objective lens and it is described as the millivolts. According to the algorithm derived by Lentz from the Mie scattering theory [18], the relationship between the scattered light intensity, I, and the particle size, d, is approximately represented as I = Kd², where K is a constant that specifies the value of scattered light intensity corresponding to a certain particle size. After eliminating high-frequency noise from the output signal using low-pass filters with a cut-off frequency of 10 kHz, the amplitudes and frequency of alternating current signals were analyzed on a personal computer (PC-98 As2; NEC, Tokyo, Japan). The signal frequency was recorded at 10-second intervals.

Data were expressed as the change with time in the number of aggregates of each of three sizes (determined by light intensity, expressed in millivolts). The total light intensities of small, medium, and large aggregates were determined as follows. Particles with an intensity of 25 to 400 mV were counted as small aggregates (9 to 25 µm); an intensity of 400 to 1,000 mV indicated medium aggregates (25 to 50 µm); and an intensity of 1,000 to 2,048 mV indicated large aggregates (50 to 70 µm). Data were recorded on a two-dimensional graph showing the change with time of total light intensity expressed as a cumulative summation at 10-second intervals of scattered light intensity (I_i) and the number of particles corresponding to that intensity (N_i) in terms of particle size (intensity) (S I_i N_i) (volts x counts/10 s). Total intensity was recorded at 10-second intervals for 8 minutes. Quantitative estimation was performed by determining the area under the curve, representing the sum of measurements of the LS intensity.

Measurements
Blood samples from a radial artery catheter were collected at the following observation times: before the operation, 1 hour after initiation of CPB, at the end of CPB (after protamine administration), at the end of the operation, and on day 1 after the operation. For platelet aggregometry, 4.5 mL of whole blood was taken and stored in silicone-coated tubes with 0.5 mL sodium citrate solution. The PRP was obtained by centrifuging whole blood at 120 g for 10 minutes at room temperature and aspirating the supernatant. The PRP was incubated for 3 minutes at 37°C. The PPP was obtained by centrifuging whole PRP at 1,800 g for 10 minutes. Aggregation was induced by addition of 2.5 µmol/L adenosine diphosphate (ADP) and 2 µg/mL collagen (final concentration; Sigma Chemical Co, St. Louis, MO). The solution is constantly stirred by a magnetic bar at a rate of 1,000 rpm.

Aggregation of PRP by assessing the LS intensity was determined simultaneously with the OD method by evaluating maximal percent decrease. Platelet aggregation after stimulation by 2.5 µmol/L ADP and 2.0 µg/mL collagen was determined using both OD and LS methods. Using the LS method, small, medium, and large aggregates were counted. Aggregation curves were recorded for 8 minutes after addition of the agonist. Figure 1 shows the typical aggregation patterns of healthy volunteers measured by LS method and OD method using the Cowa AG-10 aggregometer. After stimulation, small aggregates are formed transiently in the first phase of aggregation, and larger aggregates are formed in the second phase. This fact implies that a progression from small to larger aggregates is the natural course of platelet aggregation.

View larger version (22K): [in this window] [in a new window]   Fig 1. Typical platelet aggregation patterns of blood samples from healthy volunteers using optical density (OD) and light scattering intensity (LSI) methods (agonist: 2.5 µmol/L adenosine diphosphate). Small aggregates (9 to 25 µm; S); medium aggregates (25 to 50 µm; M), and large aggregates (50 to 70 µm; L) are measured by LSI. Platelet aggregation capacity (T) is measured by OD. Small aggregates are formed in the first phase of aggregation, and larger aggregates are formed in the second phase. After stimulation, the quantity of small aggregates are increased transiently and larger aggregates are increased after that. An arrow indicates the point at which the agonist is added. Scale for LSI is on the left side, for OD on the right side.

Statistical analysis
All data are presented as mean ± standard deviation. A Wilcoxon matched-pairs signed-ranks test was used for comparisons of values from one variable between two time points. A p value less than 0.05 was considered significant.

	Results

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Platelet count
Platelet counts decreased during and after the operation, presumably because of hemodilution and consumption. The platelet count remained decreased until 1 day after the operation (Table 1).

Platelet aggregation pattern measured by light-scattering methods
Figure 2 shows a typical pattern with time in LS intensity detection of small, medium, and large aggregates after stimulation with ADP. Before the operation, small aggregates formed in the first phase of aggregation and larger aggregates formed in the second phase after stimulation. The quantity of small aggregates increased, and larger aggregates increased after that (Fig 2A). Contrary to this, in the samples taken 1 hour after initiation of CPB, LS intensity detection showed small aggregates increasing rapidly and remaining at an elevated level after stimulation with ADP, whereas medium and large aggregates did not increase and were suppressed (Fig 2B). Table 1 shows the analyzed data of each aggregate size. Although the quantification (area under the curve) of small aggregates was not significantly different between samples drawn before the operation and 1 hour after initiation of CPB (366 ± 167 versus 346 ± 142 x 10⁵ mV), large aggregate formation was significantly decreased at 1 hour after initiation of CPB (196 ± 160 versus 73 ± 96 x 10⁵ mV; p < 0.01). The samples taken after CPB showed a similar pattern (Fig 2C). The quantification of small aggregates did not show any difference between before the operation and after CPB (366 ± 167 versus 312 ± 189 x 10⁵ mV), whereas total LS intensities of large aggregates decreased after CPB (196 ± 160 versus 44 ± 85 x 10⁵ mV; p < 0.01) (see Table 1). Figures 2D and 2E showed the aggregation pattern after the operation and at day 1 after the operation, respectively. Generation of large aggregates was recovered at day 1 after the operation (Fig 2E). As shown in Table 1, quantification of large aggregates increased at day 1 after the operation (after CPB versus day 1 after the operation, 44 ± 85 versus 115 ± 103 x 10⁵ mV; p < 0.01).

View larger version (84K): [in this window] [in a new window]   Fig 2. Typical pattern of platelet aggregation in blood samples obtained before the operation (A), 1 hour after initiation of cardiopulmonary bypass (B), at the end of cardiopulmonary bypass (C), at the end of the operation (D), and on day 1 after the operation (E); platelets were stimulated by 2.5 µmol/L adenosine diphosphate. An arrow indicates the point at which the agonist is added. Scale for LSI is on the left side, for OD on the right side. Abbreviations are same as in Figure 1.

	Comment

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Cardiopulmonary bypass is a nonphysiologic procedure, and many associated factors can affect platelet function. The contact activation with extracorporeal circuits, shear forces [7], activation of the complement system [19], fibrinolysis [13], and extrinsic factors such as ingested drugs [8–10] all contribute to platelet dysfunction, which may result in postoperative bleeding. However, the detailed pattern of the platelet functional change and its potential effect has been unclear. Many researchers report that platelets are unable to aggregate normally in response to weak agonists such as ADP and epinephrine and that they show a decreased response to lower doses of strong agonists such as collagen during CPB [1, 20]. As with the previous reports, the results of conventional OD method in our study showed a decreased response during and after CPB. However, the LS method showed a different pattern of platelet aggregation. Normally, small aggregates are formed in the first phase of aggregation, and larger aggregates are formed in the second phase. After stimulation, the quantity of small aggregates are increased transiently and larger aggregates are increased after that. In this study, however, small aggregates did not transform into larger aggregates during and after CPB. The quantification of medium and large aggregates was suppressed during and after CPB, whereas the number of small aggregates was maintained at the elevated level.

Hemodilution is one of the extrinsic factors that affect platelet aggregation. As shown in Table 1, the platelet count at 1 hour after initiation of CPB was significantly reduced because of hemodilution, and hemodilution continued until 1 day after the operation. However, LS total intensity of large aggregates significantly increased in day 1 after the operation in both ADP and collagen groups compared with after CPB in spite of low platelet concentration (ADP: after CPB versus day 1 after the operation, 44 ± 85 versus 115 ± 103 x 10⁵ mV; collagen: 33 ± 44 versus 133 ± 96 x 10⁵ mV; p < 0.01). These results suggested that platelet activity to form large aggregates was a reflection of their intrinsic factors. Although hemodilution is one of the important extrinsic factors of platelet aggregation, the generation of small aggregates was not suppressed by CPB. These results suggest that reduced activity of platelets to form larger aggregates does not reflect the hemodilution but the intrinsic factors. Also, CPB does not affect the first phase of aggregation, but rather inhibits the development of small aggregates into large aggregates.

As to the mechanisms of platelet aggregation loss with CPB, recent reports have emphasized that CPB induces defects in the platelet surface glycoprotein Ib/IX complex and glycoprotein IIb/IIIa complex [5, 21] in the initial phase of platelet aggregation. However, these findings are still controversial. As our results suggested that the first phase of platelet aggregation was not inhibited, the platelet surface integrin-mediated aggregation activity may not be completely shut down; aggregation potential may be maintained. As Kestin and associates [8] mentioned in their report, other extrinsic factors such as suppressed thrombin activity by high circulating concentrations of heparin, hypothermia, or fibrinolytic activity may partially contribute to the platelet dysfunction, especially to inhibition of the development of small aggregates into larger aggregates.

As to the potential activity of platelets, Zilla and coworkers [22] reported that circulating platelet morphology recovered from initial activation despite the maintenance of CPB in a scanning and transmission electron microscopic analysis, and the initial platelet consumption in CPB is caused by reversible primary rather than irreversible secondary aggregation phenomena. This suggests that platelets may keep their potential activity, and platelet function is not completely shut down. These primed platelets may be activated by other stimulants such as a high shear stress [6, 7], activated leukocytes [19, 23], activated complement system [19], and so on, resulting in aggregation and subsequent blood coagulation. If so, the increased number of small aggregates may partially explain the occurrence of vascular events such as ischemic cerebrovascular accidents after cardiac operations.

As Tohgi and colleagues [17] mentioned in their article, the clinical significance of aggregate size in in vitro aggregation tests is unknown. Whether a similar phenomenon occurs in the in vivo microenvironment of the vascular endothelium is not known. However, the possibility must be considered that circulating platelets during CPB may maintain aggregation activity, which has been shown not to suppress in quantity by the in vitro LS method during CPB in spite of using heparin. Small aggregates may act as very small emboli in vivo by stimulation, or activated platelet particles may play an important role in thromboembolic accidents. It is necessary to consider that platelet function is suppressed, but not completely impaired, during CPB. Furthermore, whether the in vitro aggregate size impacts the in vivo hemostatic platelet function of patients undergoing CPB is unknown. To clarify the relationship between the in vitro aggregation size and in vivo hemostatic platelet function, measurements of thromboxane B₂, which is a metabolite shed at the site of bleeding time determination, and granule packing proteins may be useful. These correlation may explain the clinical hemostatic significance and the aggregation size of platelets in vitro.

The assumption that platelet aggregation per se is reflective of in vivo hemostatic function is controversial [3, 13, 14]. Some researchers reported that aggregation defects predicted postoperative bleeding [3, 13], and others showed a discordance between platelet aggregation using OD method and in vivo hemostatic function of platelets in patients undergoing CPB [14]. As the LS method can determine size and number of aggregates simultaneously at a sensitivity 100 times greater than that of conventional OD method [16], this new methodology may have the potential of shedding new light on these controversies. However, the duration of CPB is known to be one of the important determinants of CPB-induced hemostatic dysfunction in patients undergoing cardiac operations. Although we did not evaluate the impact of the duration of CPB on platelet aggregation assessed by the LS method, measurements obtained immediately before weaning from CPB (before protamine administration) would have allowed for a better assessment of the significance of these in vitro platelet aggregation studies.

In summary, although the generation of medium and large aggregates estimated by LS was significantly decreased with CPB, there was no significant change in the number of small aggregates. Platelet aggregation dysfunction associated with CPB may be caused mainly by an inhibition in the development of small aggregates into larger aggregates.

	References

Top Abstract Introduction Material and methods Results Comment References

 

1. Mohr R., Golan M., Martinowitz U., Rosner E., Goor D.A., Ramot B. Effect of cardiac operation on platelets. J Thorac Cardiovasc Surg 1986;92:434-441.[Abstract]
2. Mammen E.F., Koets M.H., Washington B.C., et al. Hemostasis changes during cardiopulmonary bypass surgery. Semin Thromb Haemost 1985;11:281-292.[Medline]
3. Ray M.J., Hawson G.A.T., Just S.J.E., McLachlan G., O’Brien M. Relationship of platelet aggregation to bleeding after cardiopulmonary bypass. Ann Thorac Surg 1994;57:981-986.[Abstract]
4. Edmunds L.H., Jr, Ellison N., Colman R.W., et al. Platelet function during cardiac operation. Comparison of membrane and bubble oxygenators. J Thorac Cardiovasc Surg 1982;83:805-812.[Abstract]
5. Van Oeveren W., Harder M.P., Roozendaal K.J., Eijsman L., Wildevuur C.R.H. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;99:788-797.[Abstract]
6. O’Brien J.R. Shear-induced platelet aggregation. Lancet 1990;335:711-713.[Medline]
7. Tabuchi N., Gallandat Huet R.C.G., Sturk A., Eijsman L., Wildevuur C.R.H. Hemostatic function of aspirin-treated platelets vulnerable to cardiopulmonary bypass. Altered shear-induced pathway. J Thorac Cardiovasc Surg 1995;110:813-818.[Abstract/Free Full Text]
8. Kestin A.S., Valeri C.R., Khuri S.F., et al. The platelet function defect of cardiopulmonary bypass. Blood 1993;82:107-117.[Abstract/Free Full Text]
9. Khuri S.F., Valeri C.R., Loscalzo J., et al. Heparin causes platelet dysfunction and induces fibrinolysis before cardiopulmonary bypass. Ann Thorac Surg 1995;60:1008-1014.[Abstract/Free Full Text]
10. Lindblad B., Wakefield T.W., Whitehouse W.M., Jr, Stanley J.C. The effect of protamine sulfate on platelet function. Scand J Thorac Cardiovasc Surg 1988;22:55-59.[Medline]
11. Born G.V.R. Observation on the change in shape of blood platelets brought about by adenosine diphosphate. J Physiol 1970;209:487-511.[Abstract/Free Full Text]
12. Cardinal D.C., Flower R.J. The electronic aggregometer: a novel device for assessing platelet behavior in blood. J Pharmacol Methods 1980;3:135-158.[Medline]
13. Huang H., Ding W., Su Z., Zhang W. Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery. J Thorac Cardiovasc Surg 1993;106:11-18.[Abstract]
14. Rinder C.S., Bohnert J., Rinder H.M., Mitchell J., Ault K., Hillman R. Platelet activation and aggregation during cardiopulmonary bypass. Anesthesiology 1991;75:388-393.[Medline]
15. Ozaki Y., Satoh K., Yatomi Y., Yamamoto T., Shirasawa Y., Kume S. Detection of platelet aggregates with a particle counting method using light scattering. Anal Biochem 1994;218:284-294.[Medline]
16. Yamamoto T., Egawa Y., Shirasawa Y., et al. A laser light scattering in situ system for counting aggregates in blood platelet aggregation. Meas Sci Technol 1995;6:174-180.
17. Tohgi H., Takahashi H., Watanabe K., Kuki H., Shirasawa Y. Development of large platelet aggregates from small aggregates as determined by laser-light scattering: effects of aggregant concentration and antiplatelet medication. Thromb Haemost 1996;75:838-843.[Medline]
18. Lentz W.J. Generating Bessel function in Mie scattering calculation using continued fractions. Appl Opt 1976;15:668-671.
19. Wachtfogel Y.T., Kucich U., Hack C.E., et al. Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion. J Thorac Cardiovasc Surg 1993;106:1-10.[Abstract]
20. Friedenberg W.R., Myers W.O., Plotka E.D., et al. Platelet dysfunction associated with cardiopulmonary bypass. Ann Thorac Surg 1978;25:298-305.[Abstract]
21. Rinder C.S., Mathew J.P., Rinder H.M., Bonan J., Ault K.A., Smith B.R. Modulation of platelet surface adhesion receptors during cardiopulmonary bypass. Anesthesiology 1991;75:563-570.[Medline]
22. Zilla P., Fasol R., Groscurth P., Klepetko W., Reichenspurner H., Wolner E. Blood platelets in cardiopulmonary bypass operations. Recovery occurs after initial stimulation, rather than continual activation. J Thorac Cardiovasc Surg 1989;97:379-388.[Abstract]
23. Primack C., Walenga J.M., Koza M.J., Shankey T.V., Pifarré R. Aprotinin modulation of platelet activation in patients undergoing cardiopulmonary bypass operations. Ann Thorac Surg 1996;61:1188-1193.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Yoshio Misawa Katsuo Fuse Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kawahito, K. Articles by Fuse, K. Search for Related Content PubMed PubMed Citation Articles by Kawahito, K. Articles by Fuse, K.