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Ann Thorac Surg 1995;59:1481-1486
© 1995 The Society of Thoracic Surgeons

Platelet Activation in Warm and Cold Heart Surgery

C. David Mazer, MD, Adriana Hornstein, MSc, John Freedman, MD

Department of Anaesthesia and Division of Hematology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada

Accepted for publication February 20, 1995.


   Abstract
Top
 Footnotes
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
Recent studies suggest that patients undergoing warm heart surgical procedures have reduced postoperative bleeding. To determine if this is due to differences in platelet activation, we measured platelet membrane glycoproteins (GPIb, GPIIb/IIIa, GMP 140), platelet fragments, and platelet counts before, during, and after normothermic (37°C) or hypothermic (28° to 30°C) cardiopulmonary bypass. Cardiopulmonary bypass was associated with a significant decrease in platelet count, platelet membrane GPIb, and platelet fragments, and an increase in GMP 140 (p < 0.05). Normothermic cardiopulmonary bypass induced an early significant increase in granulocytes, whereas this was delayed until after rewarming in the hypothermic group. Mean 24-hour postoperative blood loss was 786 ± 226 mL in the cold group versus 547 ± 56 mL in the warm group (p = not significant). We conclude that cardiopulmonary bypass affects platelet activation and integrity and that these changes are similar in direction and magnitude for hypothermic and normothermic techniques.


   Introduction
Top
 Footnotes
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
Bleeding after cardiac operations is an important cause of morbidity and mortality. Possible etiologies for postoperative hemorrhage include platelet dysfunction, enhanced fibrinolysis, and depletion of coagulation factors. Several studies [1–4] have suggested a central role for platelet abnormalities in the genesis of postoperative coagulopathy. Recent advances in flow cytometry have permitted the detection and quantitation of platelet membrane glycoproteins, which are markers for platelet activation, aggregation, and secretion. Whereas some studies of platelet activation in hypothermic cardiopulmonary bypass (CPB) have shown degranulation [1, 3, 5] and altered platelet membrane glycoproteins [2, 6], others have not [7, 8]. The effect of normothermic CPB on platelet activation is unknown.

Warm heart surgery (normothermic oxygenated blood cardioplegia with normothermic systemic perfusion) is a new approach to cardiac surgery that is gaining increasing clinical acceptance. Warm heart surgery may provide better myocardial protection with reduced incidence of postoperative myocardial infarction, low output syndrome, and death [9–13]. It has also been suggested that patients undergoing warm heart surgery have significantly reduced postoperative bleeding, possibly because of better preservation of platelets and platelet function [12, 14, 15].

The purpose of this study was to measure markers of platelet activation in patients having normothermic CPB and compare these results with those of patients undergoing hypothermic techniques. Specifically, we meaured platelet membrane glycoproteins (GPIb, GPIIb/IIIa, GMP 140), platelet fragments, and platelet counts to determine if the beneficial hemostatic effect of warm heart surgery is related to a differential effect on platelet activation.


   Material and Methods
Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
Twenty-two patients undergoing CPB for coronary artery bypass grafting or valve replacement were studied. Approval for the study was obtained from the Committee for Research on Human Subjects at St. Michael's Hospital. The choice of cardioplegic technique and systemic temperature management during CPB was determined by surgical preference or by randomization in a concurrent study of warm versus cold heart surgery for coronary artery bypass.

Intraoperative Management
The patients were anesthetized using a standard moderate-dose fentanyl and benzodiazepine technique, with supplementation with enflurane or isoflurane as indicated. After median sternotomy, the patients were anticoagulated with heparin sodium (300 IU/kg) to achieve an activated clotting time greater than 400 seconds. An aortic cannula and a two-stage atrial cannula were placed, and CPB was instituted using a membrane oxygenator (COBE-Baxter Laboratories, Irving, CA) primed with lactated Ringers solution and with an arterial line filter (40 µm). During CPB, systemic blood flow was maintained at 2.5 L • m-2 • min-1, target hematocrit was greater than 20%, and mean arterial pressure was maintained between 40 and 80 mm Hg using Neo-Synephrine (phenylephrine hydrochloride) and vasodilators as indicated.

All cardioplegic techniques used included oxygenated blood mixed 4:1 with Fremes's solution. Patients undergoing hypothermic CPB were cooled to 28° to 30°C and rewarmed prior to weaning, whereas patients undergoing normothermic CPB were actively warmed as necessary throughout bypass to maintain core temperature at 37°C throughout CPB.

When the operation was completed, the patient was weaned from CPB and heparin was reversed with protamine sulfate. After achievement of adequate hemostasis, the chest was closed and the patient taken to the intensive care unit for postoperative management. The total chest tube drainage was measured at 6, 12, and 24 hours after admission to that unit.

A sample of blood was taken from each patient at the following periods: immediately prior to induction of anesthesia, after heparin administration but prior to CPB, 30 minutes after initiation of CPB, 60 minutes after initiation of CPB, just prior to termination of CPB, 1 hour to 2 hours after termination of CPB, and in the intensive care unit 16 to 24 hours postoperatively.

Flow Cytometric Methods:
Five-milliliter blood samples were drawn through the arterial catheter into a plastic syringe. Four milliliters immediately was added to a test tube containing 2 mL of 1% paraformaldehyde (PFA), and the remaining 1 mL was added to a tube containing EDTA (ethylenediaminetetraacetic acid) for complete blood count using an automated blood counter (Sysmex E 5000; TOA Medical Electronics, Los Alamos, NM).

MONOCLONAL ANTIBODIES.
The following monoclonal antibodies were used: CD41a-FITC (specific for platelet GPIIb/IIIa) and CD42b-FITC (platelet GPIb) were purchased from AMAC Inc (Westbrook, ME). CD62-PE (specific for GMP 140) was purchased from Becton Dickinson (San Jose, CA). Simply Cellular beads used for quantitation of binding sites were purchased from Flow Cytometry Standards Corp (Research Triangle Park, NC).

PURIFIED PLATELET PREPARATION.
After fixation in PFA for 30 minutes at room temperature to prevent platelet activation during further sample handling, platelets were isolated by centrifugation for 15 minutes at 150 g at room temperature and washed once in 0.9% saline solution containing 5 mmol/L EDTA.

WHOLE-BLOOD ANALYSIS.
For whole-blood staining, 10 µL of each monoclonal antibody was added to polystyrene tubes containing 50 µL of FACSFlow fluid (Becton Dickinson) and 10 µL of the prefixed blood samples. Dual staining with antibodies against GMP 140 and GPIb and against GMP 140 and GPIIb/IIIa was utilized. After a 15-minute incubation period at room temperature, the samples were resuspended into 2 mL of FACSFlow fluid and analyzed in a FACS can flow cytometer equipped with a 15 mW argon ion laser (Becton Dickinson). The fluorescence threshold was set to acquire only GPIb- or GPIIb/IIIa-positive events. The percentage of positive events for GMP 140 (compared with isotype controls) was then determined.

Purified fixed platelets were adjusted to a concentration of 1 x 108/mL. Fifty µL of platelet suspension was incubated with 10 µL of monoclonal antibody for 20 minutes, washed with saline solution and 0.5% bovine serum albumin, and resuspended in 1 mL of FACSFlow fluid. All monoclonal antibodies were used at saturating conditions, and isotype-matched monoclonal antibodies were used as nonspecific control. Simply Cellular beads were simultaneously incubated in separate tubes with the same antibodies and conditions as for platelets and were used to quantitate the numbers of GPIb and GPIIb/IIIa binding sites per platelet, according to the manufacturer's instructions. Simply Cellular beads are polystyrene particles with a known amount of binding sites that, when saturated with antibody, permit determination of the numbers of fluorescent molecules per antibody.

QUANTITATION OF FRAGMENTS.
Generation of platelet fragments was quantitated by whole-blood staining with monoclonal antibodies to GPIb and GPIIb/IIIa. Before sample acquisition, beads 0.5 µm, 1 µm, and 4 µm in diameter were added. The platelet fragments were expressed as a percentage of the number of positive events of 0.5 to 1 µm in size divided by the number of events in the 1- to 4-µm gate. The values obtained were analyzed both corrected and uncorrected for total platelet count.

Statistical Analysis
The technologist performing the laboratory testing was blinded to patients' bypass temperature. Data were analyzed using {chi}2 for categoric data and analysis of variance for continuous data using the SAS (Statistical Analysis System) statistical package. The SAS general linear model repeated-measures analysis of variance procedure was used to analyze data from sequential measurements. When a significant F ratio (p < 0.05) was present, multiple comparisons within groups between baseline (immediately prior to induction of anesthesia) and other measurements were made using unadjusted pairwise comparisons as printed out by LSMEANS comparison procedure with adjustment made on the probability of rejection using Bonferroni's correction. Dunnett's test was used for comparisons of group by time interactions. Data are reported as the mean ± the standard error of the mean.


   Results
Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
There was no significant difference between groups in terms of age, sex, CPB time, aortic cross-clamp time, or preoperative platelet count (Table 1Go). All patients in the cold group underwent CABG, whereas 2 patients in the warm group had another procedure (mitral valve replacement, aortic valve replacement). The lowest systemic temperature during CPB in the warm group was 35.6° ± 0.2°C compared with 28.6° ± 0.7°C in the cold group (p < 0.0001).


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  		Table 1. . Demographic and Perioperative Dataa
 
There was no significant difference between groups in perioperative blood loss at any time period, although the mean value and range were consistently greater in the cold group (see Table 1Go). Two patients in the cold group had excessive postoperative bleeding, defined as more than 1,000 mL in the first 6 hours or more than 1,500 mL in the first 24 hours, as opposed to none in the warm group.

The platelet count in both groups decreased significantly during CPB with the nadir in mean value occurring in the early postoperative period (Fig 1Go). The percent decrease from initial platelet count was similar in both groups. Although platelet counts were generally lower in the cold group, there were no significant differences in platelet counts between groups at any time period.



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  		Fig 1. . Perioperative platelet counts in patients undergoing normothermic (open triangles) and hypothermic (solid circles) cardiopulmonary bypass (CPB). Values are shown as the mean ± the standard error of the mean. (CPB x 30 min = 30 minutes after initiation of CPB; CPB x 60 min = 60 minutes after initiation of CPB; END CPB = immediately prior to termination of CPB; PRE CPB = prior to CPB [after heparinization]; PRE OP = prior to induction of anesthesia; 1–2 HR POST CPB = 1 to 2 hours after termination of CPB; 16–24 HR POST CPB = 16 to 24 hours after termination of CPB.)

 
The percentage of GMP 140-positive platelets increased during and after CPB in both groups, although significance was reached only in samples obtained just prior to the termination of CPB and late postoperatively (Fig 2Go). These values represent an increase in baseline value of more than 60%. The findings were similar for both warm and cold groups, with no significant differences between groups.



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  		Fig 2. . Percentage of GMP 140-positive platelets in perioperative period. Abbreviations are the same as in Figure 1Go.

 
The number of GPIb binding sites decreased significantly during CPB in both hypothermic and normothermic patients. The lowest value in each group was observed after 60 minutes of CPB, with recovery seen in the early and late postoperative periods (Fig 3Go). The differences between groups at each time period were not significant. The response of GPIIb/IIIa binding sites, on the other hand, was variable, with no significant differences with time or between groups observed at any measurement point (Fig 4Go). Platelet fragments, as expressed as a percentage of flow cytometry-detected platelets, also did not change significantly during the study period (Fig 5Go). When corrected for total platelet count, the number of platelet fragments fell in both groups, although significance was achieved only in the warm group (Fig 6Go). There were consistently more platelet fragments in the warm group.



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  		Fig 3. . Platelet glycoprotein Ib (GPIb) binding sites. Other abbreviations are the same as in Figure 1Go.

 


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  		Fig 4. . Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) binding sites. Other abbreviations are the same as in Figure 1Go.

 


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  		Fig 5. . Platelet fragments expressed as percentage of flow cytometry-detected platelets. Abbreviations are the same as in Figure 1Go.

 


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  		Fig 6. . Platelet fragments corrected for total platelet count. Abbreviations are the same as in Figure 1Go.

 
Figure 7Go shows the granulocyte response to warm and cold CPB. The granulocyte count rose from 4.6 ± 0.9 x 106/L to a maximum of 11.1 ± 1.7 x 106/L after 60 minutes of CPB in the normothermic group. The hypothermic group, however, did not show a rise in granulocyte count until the end of CPB, which was after rewarming. Both groups had elevated granulocyte counts in the postoperative period.



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  		Fig 7. . Perioperative granulocyte counts. Abbreviations are the same as in Figure 1Go.

 

   Comment
Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
The mechanisms of postoperative bleeding after heart surgery and the role played by cold versus warm heart surgery remain not fully defined [4, 14, 15]. Yau and associates [14] studied patients who were randomized to moderately hypothermic (25° to 29°C) or normothermic (35° to 37°C) techniques and who received tranexamic acid, {varepsilon}-aminocaproic acid, or no antifibrinolytic agents. They found that blood loss was significantly greater in patients having cold cardioplegia who received no antifibrinolytic agents compared with patients who had normothermic bypass procedures or who received antifibrinolytic agents. The findings suggested that normothermic systemic perfusion is as effective as either {varepsilon}-aminocaproic acid or tranexamic acid in reducing postoperative blood loss. Vaughn and co-workers [12] reported a 20% reduction in daily blood loss in patients who had undergone normothermic compared with 27°C systemic perfusion during CPB. Valeri and colleagues [15] observed that local skin temperature was correlated inversely with bleeding time. Michelson and associates [16] described reversible inhibition of platelet activation at 22°C. Our group [9, 11] previously found no significant difference in postoperative blood loss in patients undergoing warm or cold heart operations, although in those studies, as in this, the blood loss in the cold group was slightly higher. In the current study in which the patients did not receive antifibrinolytic agents, mean blood loss in the 24 hours after operation was 786 mL in the cold group versus 547 mL in the warm group.

In studies of platelet activation, the methods of sample preparation and analysis are important in evaluating results. Unless strict attention is given to prevention of platelet activation in vitro, after withdrawal of the blood from the patient and during sample manipulation, staining, and flow cytometric acquisition, markers of platelet activation in vivo may be artifactually altered and thus yield erroneous results. Consequently, in these studies, blood samples were fixed immediately in PFA on withdrawal from the patient. In parallel studies in which the sample was not placed in PFA for 30 to 60 minutes, expression of the platelet activation marker GMP 140 was 20% to 50% increased. We found that PFA fixation did not significantly alter the sensitivity of staining with monoclonal antibodies used in our study.

A variety of markers have been used to detect platelet activation by flow cytometry. A commonly used marker is surface expression of GMP 140 (P-selectin, PADGEM, CD62), which is released from the platelet alpha granules on activation by a number of agonists [17]. Platelet membrane GPIb (CD42b), the von Willebrand receptor, may show decreased expression with platelet activation because of redistribution of GPI-IX within the open canalicular system [18]. Platelet membrane GPIIb/IIIa (CD41a), the fibrinogen receptor, on the other hand, may be released from an internal pool in the alpha granules on platelet activation, resulting in an increased expression of GPIIb/IIIa on the platelet surface.

Recently, several studies [8, 18–21], using similar methods of sample preparation and staining have examined platelet activation in patients undergoing CPB. In contrast to the current study, only patients undergoing hypothermic CPB were examined. Results from these studies, however, have been variable. Kestin and associates [8] reported no changes in platelet membrane GPIb or IIb/IIIa or in surface expression of GMP 140 either during or after CPB. For example, GMP 140 varied from 2% to 3% during the procedure. Metzelaar and co-workers [21] reported similar findings before and after bypass for GMP 140 expression, the percentage of GMP 140-positive platelets increasing from 4.4% ± 2.3% to only 6.6% ± 3.3%; platelet membrane GPIIIa mean fluorescence intensity did, however, increase from channel 162 ± 60 to 275 ± 127. Huang and coauthors [3] found a 50% reduction in GPIb, which was prevented by pretreatment with aprotinin. Rinder and colleagues [19] observed a 28% and a 38% decrease in expression of GPIb and IIb/IIIa, respectively, and an increase in GMP 140-positive platelets from 7% to 17% during bypass; they [20] had previously reported an increase (from 7% to 30%) in GMP 140-positive platelets during CPB.

In general, our results were consistent with those of Rinder's group [19, 20]. In agreement with some [8] but in contrast with others [19, 21], we found a slight, although not significant, increase in platelet GPIIb/IIIa expression during and after warm CPB. Differences from the reports of others may be due to the strict attention to prevention of in vitro platelet activation in the current study. Alternatively, they may be the consequence of the quantitative approach using standardized beads applied in the current studies; this allows for correction of day-to-day variance caused by differences in machine settings, staining procedures, or both. Differences between this and other studies may also be accounted for by differences in epitope specificity of monoclonal antibodies employed; the anti-GPIb/IX monoclonal antibody used in the current study is not directed to the glycocalicin portion of GPIb in contrast to the 6D1 monoclonal antibody employed by Kestin and co-authors [8]. Further, differences in platelet activation may be the result of the different CPB oxygenators and other equipment used.

In addition, we examined the number of platelet fragments detected during CPB; fragmentation of platelets, or platelet microparticles, may be detected in increased amount in platelet activation [2, 7, 22]. The pattern observed of platelet microparticle generation differed according to the method of analysis applied. When expressed as a percentage of platelets, as is often done [7, 22], the number of platelet fragments did not change significantly throughout the procedure. Abrams and associates [7] suggested that platelet fragment quantitation should be corrected for the platelet count at the time; when this was done, the number of platelet fragments fell in both groups, particularly toward the end of and after bypass, although this was significant only for the normothermic group. It is unclear why the level of platelet fragments was high prior to the procedure. If the fragmentation was due to platelet activation, the decrease is in contrast to the increase in platelet activation detected by the other markers mentioned already; the decrease may be due to clearance of microparticles in the CPB apparatus.

We observed a significant and potentially clinically important difference in the granulocyte response to normothermic and hypothermic CPB. Normothermic CPB produced an early and significant increase in granulocytes, whereas this was delayed until rewarming in the hypothermic group. Granulocytes may contribute to reperfusion injury either by occluding the microvasculature or by producing oxygen free radicals [23]. Given the increasing use of blood cardioplegia, it will be important in future studies to determine the clinical significance of the observed difference in granulocyte response [24].

In summary, this study has documented the effect of normothermic CPB on select markers of platelet activation. In addition to a significant decrease in platelet count, normothermic bypass was associated with reduction in platelet membrane GPIb and increase in the percentage of GMP 140-positive platelets. The changes were similar in magnitude and direction to those observed in patients undergoing hypothermic bypass. Although differences between cold and warm bypass patients were small and not generally significant, they do indicate a general effect of CPB on platelet activation and integrity. Whether this relates to the reduced bleeding in normothermic patients remains to be determined.


   Footnotes
Top
 Footnotes
Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
Address reprint requests to Dr Mazer, Department of Anaesthesia, St. Michael's Hospital, 30 Bond St, Toronto, Ont, Canada M5B 1W8.


   References
Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Harker LA, Malpass TW, Branson HE, Hessel EA II, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: acquired transient platelet dysfunction associated with selective alpha-granule release. Blood 1980;56:824–34.[Free Full Text]
  2. Geroge JN, Pickett EB, Saucerman S, et al. 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.[Medline]
  3. Huang H, Ding W, Su Z, Zgang W. Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery. J Thorac Cardiovasc Surg 1993;106:11–8.[Abstract]
  4. Khuri SF, Wolfe JA, Josa M, et al. Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and nonsurgical blood loss. J Thorac Cardiovasc Surg 1992;104:94–107.[Abstract]
  5. Nieuwenhuis HK, van Oosterhout JJ, Rozemuller E, van Iwaarden F, Sixma JJ. Studies with a monoclonal antibody against activated platelets: evidence that a secreted 53,000-molecular weight lysosome-like granule protein is exposed on the surface of activated platelets in the circulation. Blood 1987;70:838–45.[Abstract/Free Full Text]
  6. Wenger RK, Lukasiewicz H, Mikuta BS, Niewiarowski S, Edmunds LH Jr. Loss of platelet fibrinogen receptors during clinical cardiopulmonary bypass. J Thorac Cardiovasc Surg 1989;97:235–9.[Abstract]
  7. Abrams CS, Ellison N, Budzynski AZ, Shattil SJ. Direct detection of activated platelets and platelet-derived microparticles in humans. Blood 1990;75:128–38.[Abstract/Free Full Text]
  8. Kestin AS, Valeri CR, Khuri SF, et al. The platelet function defect of cardiopulmonary bypass. Blood 1993;82:107–17.[Abstract/Free Full Text]
  9. The Warm Heart Investigators. Randomised trial of normothermic versus hypothermic coronary artery bypass surgery. Lancet 1994;343:559–63.[Medline]
  10. Lichtenstein SV, Ashe KA, El Dalati H, Cusimano RJ, Panos A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg 1991;101:269–74.[Abstract]
  11. Kavanagh BP, Mazer CD, Panos A, Lichtenstein SV. Effect of warm heart surgery on perioperative management of patients undergoing urgent cardiac surgery. J Cardiothorac Anesth 1992;6:127–31.
  12. Vaughn CC, Opie JC, Florendo FT, Lowell PA, Austin J. Warm blood cardioplegia. Ann Thorac Surg 1993;55:1227–32.[Abstract]
  13. Flack JE, Hafer J, Engelman RM, Rousou JA, Deaton DW, Pekow P. Effect of normothermic blood cardioplegia on postoperative conduction abnormalities and supraventricular arrhythmias. Circulation 1992;86(Suppl 2):385–92.
  14. Yau TM, Carson S, Weisel RD, et al. The effect of warm heart surgery on postoperative bleeding. J Thorac Cardiovasc Surg 1992;103:1155–63.[Abstract]
  15. Valeri CR, Khabbaz K, Khuri SF, et al. Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass. J Thorac Cardiovasc Surg 1992;104:108–16.[Abstract]
  16. Michelson AD, MacGregor H, Barnard MR, Kestin AS, Rohrer MJ, Valeri CR. Reversible inhibition of human platelet activation by hypothermia in vivo and in vitro. Thromb Haemost 1994;71:633–40.[Medline]
  17. McEver RP, Martin MN. A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem 1984;259:9799–804.[Abstract/Free Full Text]
  18. Hourdille P. Thrombin induces a rapid redistribution of glycoprotein Ib-IX complexes within the membrane systems of activated human platelets. Blood 1990;76:1503–13.[Abstract/Free Full Text]
  19. Rinder CS, Bohnert J, Rinder HM, Mitchell J, Ault K, Hillman R. Platelet activation and aggregation during cardiopulmonary bypass. Anesthesiology 1991;75:388–93.[Medline]
  20. 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.[Medline]
  21. Metzelaar MJ, Korteweg J, Sixma JJ, Nieuwenhuis HK. Comparison of platelet membrane markers for the detection of platelet activation in vitro and during platelet storage and cardiopulmonary bypass surgery. J Lab Clin Med 1993;121:579–87.[Medline]
  22. Gemmell CH, Sefton MV, Yeo EL. Platelet-derived microparticle formation involves glycoprotein IIb-IIIa. J Biol Chem 1993;268:14586–9.[Abstract/Free Full Text]
  23. Faymonville ME, Pincemail J, Duchateau J, et al. Myeloperoxidase and elastase as markers of leukocyte activation during cardiopulmonary bypass in humans. J Thorac Cardiovasc Surg 1991;102:309–17.[Abstract]
  24. Wachtfogel YT, Kucich U, Hack CE, et al. Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion. J Thorac Cardiovasc Surg 1993;106:1–10.[Abstract]



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