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Ann Thorac Surg 1995;60:1317-1323
© 1995 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Disparity in Blood Activation by Two Different Heparin-Coated Cardiopulmonary Bypass Systems

Departments of Surgery and Anesthesiology, Institute for Experimental Research, Ullevaal Hospital, Oslo, Norway

Accepted for publication July 5, 1995.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. Several studies have indicated reduced ``blood activation'' in heparin-coated cardiopulmonary bypass systems. The present study compares the effect of two different heparin coatings on different blood activation indices.

Methods. Low-risk patients (n = 40) were randomized to coronary artery bypass grafting using cardiopulmonary bypass with surfaces coated entirely by either the Duraflo II heparin coat or the Carmeda Biological Active Surface, or with identical uncoated equipment. In all cases, a standard systemic heparin dosage was used. Complement activation (C3 activation products C3bc and C3a and formation of fluid phase terminal SC5b-9 complement complex), neutrophil activation (lactoferrin and myeloperoxidase), and lytic inhibitors (vitronectin and clusterin) were quantified during cardiopulmonary bypass and 6 hours postoperatively.

Results. Heparin coating by either method reduced the formation of terminal SC5b-9 complement complex and the release of lactoferrin and myeloperoxidase compared with uncoated systems. Lactoferrin and myeloperoxidase levels increased significantly during cardiopulmonary bypass in the Duraflo II group, whereas no significant increase was observed in the Carmeda Biological Active Surface group. The least formation of terminal SC5b-9 complement complex and neutrophil activation was observed with the Maxima Carmeda Biological Active Surface–coated equipment. The vitronectin and clusterin concentrations were significantly less reduced in the Duraflo II compared with the control group. This study underlines the importance of terminal SC5b-9 complement complex as a suitable marker in the evaluation of complement activation during cardiopulmonary bypass.

Conclusions. Both heparin coatings reduce blood activation, probably more so with Carmeda Biological Active Surface than with Duraflo II.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The postperfusional systemic inflammatory response has a multifactorial cause, although complement activation has been proposed to be of major importance [1]. Animal studies in which complement activation has been inhibited by soluble complement receptor 1 have shown improved pulmonary function, thus indicating a central role of complement in postperfusional respiratory distress [2]. An inflammatory reaction may be induced by C5a and terminal SC5b-9 complement complex (TCC), which also stimulates leukocytes and platelets to release other inflammatory mediators, with potential endothelial damage as a result. The capillary endothelial damage is essential in the development of the ``whole body inflammatory reaction'' [1]. In addition to complement activation, the other blood cascade systems are activated during cardiopulmonary bypass (CPB). This is demonstrated for instance by thrombin formation, which may induce several effects also involved in the inflammatory response.

Complement activation is mainly caused by the contact between blood and foreign surfaces in the extracorporeal circulation, and the degree of complement activation is therefore an important indicator of biocompatibility [3]. Heparin coating of the blood-exposed surfaces has been suggested to improve CPB biocompatibility [3]. Complement activation during CPB is in addition to the contact between blood and foreign surface induced by the blood-gas interaction [4] and protamine-heparin complexes [1]. Reduced complement activation has been demonstrated in oxygenators and tubing coated with end-point attached, covalently bound heparin (Carmeda Bioactive Surface, CBAS) [5]. In both CBAS and Duraflo II heparin-coated systems, reduced neutrophil activation has been shown [6, 7]. An in vitro study on a Duraflo II–coated system did not demonstrate reduced complement activation [8].

The inhibitory mechanisms against complement activation are only partly known, but the glycoproteins vitronectin and clusterin are able to inhibit complement-mediated lysis [9, 10]. If these complement lytic inhibitors are preserved during CPB, one would expect them to improve biocompatibility.

In vivo and in vitro studies have demonstrated a reduced need for systemic heparin in heparin-coated systems [11]. In the present study, all patients received equal systemic heparinization, which may be an important precondition for a reliable comparison of the two different heparin coatings.

The aim of the present study was to evaluate the CBAS and the Duraflo II heparin-coated CPB equipment based on the effect of the two coated surfaces on complement activation (assessed by C3bc, C3a, and TCC formation in plasma), on the regulatory plasma proteins clusterin and vitronectin, and on neutrophil activation (assessed by myeloperoxidase and lactoferrin increase in plasma).

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Forty patients accepted for coronary artery bypass grafting without any additional procedures were included in the study after giving informed consent. The regional ethical committee approved the study. The criteria for excluding patients were as follows: known coagulopathy or ongoing anticoagulation therapy (warfarin, heparin, or acetylsalicylic acid); use of steroids or nonsteroidal antiinflammatory drugs within the 8 days before operation; respiratory-, liver-, or renal insufficiency; or ejection fraction less than 0.40. No patients received aprotinin in the present study. The patients were randomly assigned to CPB in one of four groups. In 10 patients, Duraflo II–coated Univox oxygenators, cardiotomy reservoirs, and tubing (Baxter Healthcare Corp, Irvine, CA) were used. In 10 patients, identical uncoated systems (Baxter Healthcare Corp.) were used. Ten patients were operated on with CBAS–coated Maxima oxygenator and cardiotomy reservoir and tubing (Medtronic, Anaheim, CA), and in 10 patients identical uncoated systems (Medtronic) were used. The extracorporeal circuit was primed with 2,000 mL Ringer's acetate (Kabi Vitrum, Norway). Anesthesia was induced with diazepam, fentanyl, and pancuronium and was maintained with fentanyl, midazolam, isoflurane, and nitrous oxide. For all operations, a nonpulsatile roller pump (Gambro, Horten, Norway) was used and adjusted to low occlusion (pressure reduction from 300 to 200 mm Hg in 10 seconds). Heparin was administered intravenously before the onset of CPB with 4 mg/kg body weight (Heparin Leo, 5,000 IE/mL; Leo, Denmark). The minimum allowed activated coagulation time was 480 seconds. The operations were performed under moderate general hypothermia (28° to 32°C) with topical cooling by crushed ice in addition to cold St. Thomas cardioplegic solution. Cardiotomy reservoirs were used in all operations. Retransfusion was started after termination of CPB. Protamine sulfate (10 mg/mL; Leo) was administered to reestablish the preoperative activated coagulation time level. The amounts of heparin and protamine, activated coagulation time values, 12-hour postoperative blood loss from the two mediastinal drains, and autotransfused volumes were recorded in all patients.

Analysis of Samples
A baseline sample was obtained immediately before the onset of CPB. Ethylenediamine tetraacetic acid samples were obtained after 30 minutes on bypass, 10 minutes after release of the aortic clamp, 10 minutes after protamine infusion, at the end of the operation, and 6 hours postoperatively for analysis of complement, vitronectin, clusterin, lactoferrin, myeloperoxidase, and routine hematology (hemoglobin). Immediately after sampling, the test tubes were kept on melting ice and centrifuged at 2,000 g within 3 hours; the plasma was stored at -70°C and analyzed in batches. The ethylenediamine tetraacetic acid test tubes for routine hematology analyses were stored at room temperature from sampling to analysis in a Technicon analyzer (Technicon Instruments Corp, Tarrytown, NY).

Complement Activation
(1) C3bc was measured in a double-antibody enzyme immunoassay (EIA) using the monoclonal antibody bH6 reacting with a neoepitope exposed in C3b, iC3b, and C3c, but not in native C3, as capture antibody [12]. The standard was a zymosan-activated human serum pool defined to contain 1,000 arbitrary units (AU)/mL. (2) C3a was quantified in a double-antibody EIA principally as described by Zilow and co-workers [13]. The monoclonal antibodies were kindly provided by PROGEN Biotechnik (Heidelberg, Germany). The standard was as described for C3bc. (3) Terminal complement complex was quantified in a similar double-antibody EIA using the monoclonal antibody aE11 specific for a C9 neoepitope expressed in TCC, but not in the native C9, as capture antibody [14]. The standard was as described for the C3bc assay.

Lytic Inhibitory Consumption
Vitronectin (S-protein) was quantified in a double-antibody EIA. The coating antibody was a monoclonal antibody to vitronectin, and the secondary antibody was a rabbit polyclonal antibody to vitronectin produced in our own laboratory [15]. Clusterin (SP-40, 40) was quantified in a single-antibody EIA in which samples were coated directly onto Maxisorp microtiter plates (NUNC, Denmark) in the presence of 0.2% Tween 20 (Sigma Chemical Co, St. Louis, MO). Bound clusterin was detected with a monoclonal antibody (Quidel, San Diego, CA) [16].

Neutrophil Enzyme Release
The lactoferrin concentration was quantified by radioimmunoassay as described [17]. The myeloperoxidase concentration was measured by a commercial radioimmunoassay according to the instructions of the manufacturer (Pharmacia Diagnostics, Uppsala, Sweden).

The concentrations of C3bc, C3a, TCC, lactoferrin, myeloperoxidase, clusterin, and vitronectin were corrected for hemodilution during CPB by multiplying the sample concentrations with a correction factor yielded by the formula: [100/(100 - initial hemoglobin)] x [100 x (initial hemoglobin - sample hemoglobin)/sample hemoglobin] [18].

Statistical Analysis
Results are presented as median values and quartiles. Nonparametric tests were used because of the small number of patients in each group and to avoid the possibility of a skewed distribution of the data. The measurements in each patient were summed, and the sums were compared for the groups. In addition, the maximum values of C3bc, C3a, TCC, lactoferrin, and myeloperoxidase and the minimum values of clusterin and vitronectin regardless of sample point were compared using the Kruskal Wallis test. Correlation analysis was performed using the Spearman test.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Thirty-six of the 40 patients enrolled in the study were men. The proportion of male to female was equally distributed among the groups. There were nonsignificant differences in age distribution and number of distal anastomoses. The times on extracorporeal circulation, the aortic cross-clamp times, the amounts of administered heparin and protamine, the activated coagulation time values, the 12-hour postoperative mediastinal blood loss, and autotransfused volumes did not differ significantly among the groups (Table 1).

View larger version (33K): [in this window] [in a new window]   Fig 1. . Median concentrations of the C3 activation products C3bc (C3b, iC3b, and C3c) and C3a and the terminal SC5b-9 complement complex (TCC) before, during, and after aortocoronary bypass in patients operated on with Univox Duraflo II–coated, Univox-uncoated, Maxima Carmeda Biological Active Surface (CBAS)-coated, and Maxima-uncoated equipment (n = 10 in each group). There was significantly lower TCC formation in the CBAS-coated versus Duraflo II–coated groups. (ECC = extracorporeal circulation.)

The sums of C3bc and C3a concentrations were significantly correlated (r_s = 0.72, p < 0.0001), and the maximum C3bc and C3a values correlated significantly (r_s = 0.64, p = 0.00001). The median C3bc and C3a values correlated significantly (r_s = 0.96, p < 0.0005) at all sample points except for baseline and 6 hours postoperatively.

Terminal SC5b-9 Complement Complex
In all four groups, a significant increase in TCC concentration was observed during the operation; the increase was significant (p < 0.05) compared with baseline from 30 minutes on bypass in all four groups (Fig 1). The maximum TCC values (Table 2) were significantly lower in both coated groups compared with their respective control groups (p < 0.01). The total TCC formation, calculated as the sum of the generated amounts in each patient, was significantly lower in both coated groups than in their respective control groups (p < 0.01). Both the maximum value and the sum of the generated amount of TCC were significantly lower in the Maxima CBAS-coated group than in the Univox Duraflo II–coated group (p < 0.05). The difference in maximum TCC between the Univox-uncoated and the Univox Duraflo II groups was 3.1 AU/mL, and between the Maxima-uncoated and the Maxima CBAS groups was 1.3 AU/mL. In accordance with this, the sum of the generated TCC was significantly lower in the Maxima-uncoated than in the Univox Duraflo II–coated group (p < 0.05). Baseline values were not significantly different.

Lactoferrin
The lactoferrin concentration remained almost unchanged in the Maxima CBAS group, but increased from baseline to maximum values 10 minutes after release of the aortic clamp in the other three groups, followed by a decrease at the end of the operation (Fig 2). The maximum values (Table 2) were significantly higher than those at baseline (p < 0.01) in the Univox-uncoated, Univox Duraflo II–coated, and Maxima-uncoated groups, but not in the Maxima CBAS-coated group. The maximum values and the sum of released amounts in each patient were significantly lower in both the coated groups compared with their respective control groups (p < 0.05).

View larger version (37K): [in this window] [in a new window]   Fig 2. . Median concentrations of lactoferrin and myeloperoxidase before, during, and after aortocoronary bypass in patients operated on with Univox Duraflo II–coated, Univox-uncoated, Maxima Carmeda Biological Active Surface (CBAS)-coated, and Maxima-uncoated equipment (n = 10 in each group). (ECC = extracorporeal circulation.)

Vitronectin
The vitronectin concentrations decreased from baseline to minimum values at 30 minutes on bypass and then increased to approximately the baseline values by 6 hours postoperatively (Fig 3). The decrease from baseline to minimum values was significant in all four groups (p < 0.05). The differences in minimum values (Table 2) among the groups were nonsignificant, but the baseline values were different among the groups. The differences between baseline and minimum values were significantly lower in the Univox Duraflo II–coated group compared with the Univox-uncoated group (p < 0.05). The sum of vitronectin concentration reductions in each patient was also significantly lower in the Univox Duraflo II–coated compared with the Univox-uncoated group (p < 0.05). The Maxima CBAS-coated and the Maxima-uncoated groups showed no significant differences with respect to vitronectin values.

View larger version (36K): [in this window] [in a new window]   Fig 3. . Median concentrations of vitronectin and clusterin before, during, and after aortocoronary bypass in patients operated on with Univox Duraflo II–coated, Univox-uncoated, Maxima Carmeda Biological Active Surface (CBAS)-coated, and Maxima-uncoated equipment (n = 10 in each group). (ECC = extracorporeal circulation.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The main issue in this study is the comparison of Duraflo II and CBAS heparin-coated CPB during coronary artery bypass grafting in low-risk patients. All patients received an equal systemic heparin dosage, which may be an important precondition for the comparisons made between the groups, as it is known that systemic heparin may interfere with complement activation [19]. Equal systemic heparin dosage also allowed an equal protamine dosage (Table 1). Activation of the terminal part of the complement cascade was significantly reduced in both the coated groups compared with the controls. As the TCC formation in the Univox Duraflo II group was significantly higher than that in the Maxima-uncoated group, it is difficult to attribute this difference only to an effect of the different heparin coatings. Probably the equipment difference in the two groups—Univox oxygenator as opposed to Maxima oxygenator—explains some of the observed differences regarding TCC formation.

On the other hand, activation of the early part of the complement cascade, assessed both as C3bc (C3b, iC3, and C3c) and C3a, was not influenced by the heparin coating in this study. In a recent report by Pekna and co-workers [20], C3a levels were not significantly reduced in Duraflo II-coated CPB compared with uncoated setups during the bypass time, but were significantly reduced 30 minutes after CPB. The most reliable assessment of C3 activation has been debated [21], and the concentrations of C3bc were compared with the concentrations of C3a in the present study. Except that maximum values were reached at the sample point 10 minutes after protamine administration for the C3a assay, and at the end of the operation for the C3bc assay, the two assays seem to give virtually identical information. The comparisons of the two methods for assessing C3 activation showed that they are equal with respect to biocompatibility analysis. The results of complement activation in this study emphasize the importance of monitoring activation of the terminal part of the complement cascade as a marker for biocompatibility.

The formation of C5a in particular is associated with the activation of neutrophils. Lactoferrin and myeloperoxidase are mediators in the inflammatory response, and increased levels of lactoferrin and myeloperoxidase have been demonstrated previously in the settings of both in vitro and in vivo CPB. Lactoferrin is stored in specific cytoplasmic granules of the neutrophils; myeloperoxidase is synthesized in early myeloid cells and stored in the azurophilic granules of the neutrophils [6, 17]. Reduced myeloperoxidase release in a CPB circuit coated with CBAS has been documented previously in vitro and in vivo. Myeloperoxidase and to some degree lactoferrin may be suitable markers for neutrophil activation in biocompatibility studies [6]. The lactoferrin and myeloperoxidase concentrations increased significantly from baseline to maximum values 10 minutes after release of the aortic clamp in all groups except the Maxima CBAS-coated group. This difference between the CBAS-coated and control groups is in accordance with earlier observations. Both coated systems had significantly reduced levels of lactoferrin and myeloperoxidase compared with their control groups. The maximum values and the sum of released amounts of both lactoferrin and myeloperoxidase were significantly lower in the Maxima CBAS-coated than in the Univox Duraflo II group. The differences in baseline values between the Univox Duraflo II and the Maxima CBAS-coated groups were not significant and do not explain this difference in summary measures. Both lactoferrin and myeloperoxidase concentrations correlated significantly with TCC concentrations (r_s = 0.86, p = 0.00001, and r_s = 0.87, p = 0.00001, respectively), but did not correlate with C3 activation products (neither C3b nor C3a). This indicates that TCC probably is a more useful index than C3 activation when complement activation and neutrophil activation are included in CPB biocompatibility studies. This is in accord with conclusions in a recent study [22].

Vitronectin and clusterin are multifunctional proteins that inhibit complement lysis [9, 10]. They bind to TCC during its formation and thereby inhibit the penetration of TCC into cell membranes. The vitronectin- and clusterin-containing TCC thus remains in the fluid phase as a nonlytic complex (SC5b-9). Vitronectin also binds to the thrombin-antithrombin complex and to plasminogen activation inhibitor [23]. Vitronectin is a highly adhesive serum protein and binds to various surfaces, such as plastic [16]. When bound to TCC and thrombin-antithrombin complex, vitronectin exposes a heparin-binding site which is hidden in the native protein molecule. This site may be involved in the rapid removal of such complexes from the circulation [24]. Clusterin is a more recently discovered serum protein with pronounced adhesive properties [16]. Vitronectin and clusterin would be expected to adhere to the foreign surface in CPB, and adhesion probably explains the significant decrease of vitronectin and clusterin concentrations in the present study. The effects of CPB on vitronectin and clusterin have not been studied before. In the present study, the decreases in serum concentrations of vitronectin and clusterin were significantly lower in the Univox Duraflo II–coated group than in the control, whereas CBAS coating resulted in a nonsignificant reduction compared with controls. Thus, several mechanisms may contribute to the reduced levels of vitronectin and clusterin during CPB. The decrease cannot be explained by hemodilution, as the values were corrected for this variable. The reduction of vitronectin and clusterin by as much as 50%, as seen in this in vivo study, may reduce the inhibitory activity of these proteins and thus increase the lytic ability of complement.

In conclusion, the present study demonstrates that both Duraflo II and CBAS coating reduce complement and neutrophil activation during coronary artery bypass graft surgery. The CBAS-coated Maxima system caused the least complement and neutrophil activation.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The study was funded in part by grants from the Anders Jahre Fund for the Promotion of Science and Alexander Malthe's Legacy.

The excellent technical assistance by the staffs of the participating laboratories is gratefully acknowledged.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Address reprint requests to Dr Moen, Department of Surgery, Ullevaal Hospital, University of Oslo, 0407 Oslo, Norway.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. Kirklin JK. The postperfusion syndrome: inflammation and the damaging effects of cardiopulmonary bypass. In: Tinker J, ed. Cardiopulmonary bypass. Philadelphia: WB Saunders, 1989:131–46.
2. Gillinov AM, Devaleria PA, Winkelstein JA, et al. Complement inhibition with soluble complement receptor type I in cardiopulmonary bypass. Ann Thorac Surg 1993;55:619–24.[Abstract]
3. Mollnes TE, Videm V, Riesenfeld J, et al. Complement activation and bioincompatibility. Clin Exp Immunol 1991;86(Suppl 1):21–6.[Medline]
4. Pekna M, Nilsson L, Nilsson-Ekdahl K, Nilsson UR, Nilsson B. Evidence for iC3 generation during cardiopulmonary bypass as the result of blood-gas interaction. Clin Exp Immunol 1993;91:404–9.[Medline]
5. Videm V, Svennevig JL, Fosse E, Semb G, Østerud A, Mollnes TE. Reduced complement activation with heparincoated oxygenator and tubings in coronary bypass surgery. J Thorac Cardiovasc Surg 1992;103:806–13.[Abstract]
6. Fosse E, Moen O, Johnson E, et al. Reduced complement and granulocyte activation with heparin-coated cardiopulmonary bypass. Ann Thorac Surg 1994;58:472–7.[Abstract]
7. Gu YJ, van Oeveren W, Akkerman C, Boonstra PW, Huyzen RJ, Wildevuur CRH. Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:917–22.[Abstract]
8. Svennevig JL, Geiran OR, Karlsen H, et al. Complement activation during extracorporeal circulation. J Thorac Cardiovasc Surg 1993;106:466–72.[Abstract]
9. Dahlback B, Podack ER. Characterization of human S-protein, an inhibition of the membrane attack complex of complement. Demonstration of a free thiol group. Biochemistry 1985;24:2368–74.[Medline]
10. Murphy BF, Saunders JR, O'Bryan MK, Kirszbaum L, Walker ID, d'Apice AJF. SP-40, 40 is an inhibitor of C5b-6 initiated haemolysis. Int Immunol 1989;1:551–4.[Abstract/Free Full Text]
11. Von Segesser LK, Weiss BM, Garcia E, von Felten A, Turina MI. Reduction and elimination of systemic heparinization during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1992;103:790–9.[Abstract]
12. Garred P, Mollnes TE, Lea T. Quantification in enzyme-linked immunosorbent assay of a C3 neoepitope expressed on activated human complement factor C3. Scand J Immunol 1988;27:329–35.[Medline]
13. Zilow G, Naser W, Rutz R, Burger R. Quantitation of the anaphylatoxin C3a in the presence of C3 by a novel sandwich ELISA using monoclonal antibody to a C3a neoepitope. J Immunol Methods 1989;121:261–8.[Medline]
14. Mollnes TE, Lea T, Frøland SS, Harboe M. Quantification of the terminal complement complex in human plasma by an enzyme-linked immunosorbent assay based on monoclonal antibodies against a neoantigen of the complex. Scand J Immunol 1985;22:197–202.[Medline]
15. Høgåsen K, Mollnes TE, Harboe M. Heparin-binding properties of vitronectin are linked to complex formation as illustrated by in vitro polymerization and binding to the terminal complement complex. J Biol Chem 1992;267: 23076–82.[Abstract/Free Full Text]
16. Høgåsen K, Mollnes TE, Tschopp J, Harboe M. Quantification of vitronectin and clusterin. Pitfalls and solutions in enzyme immunoassays for adhesive proteins. J Immunol Methods 1993;160:107–15.[Medline]
17. Olofsson T, Olsson I, Venge P, Elgefors B. Serum myeloperoxidase and lactoferrin in neutropenia. Scand J Haematol 1977;18:73–80.[Medline]
18. Van Beaumont W. Evaluation of hemoconcentration from hematocrit measurements. J Appl Physiol 1972;32:712–3.[Free Full Text]
19. Weiler JM, Yurt RW, Fearon DT, Austen KF. Modulation of the formation of the amplification convertase of complement, C3b, Bb, by native and commercial heparin. J Exp Med 1978;147:409–21.[Abstract/Free Full Text]
20. Pekna M, Hagman L, Halden L, Nilsson UR, Nilsson B, Thelin S. Complement activation during cardiopulmonary bypass: effects of immobilized heparin. Ann Thorac Surg 1994;58:421–4.[Abstract]
21. Mollnes TE, Lachmann PJ. Activation of the third component of complement (C3) detected by a monoclonal anti-C3 ``g'' neoantigen antibody in a one-step enzyme immunoassay. J Immunol Methods 1987;101:201–7.[Medline]
22. Videm V, Fosse E, Mollnes TE, Garred P, Svennevig JL. Time for new concepts about measurement of complement activation by cardiopulmonary bypass? Ann Thorac Surg 1992;54:725–31.[Abstract]
23. Wiman B, Almquist A, Sigurdardottir O, Lindahl T. Plasminogen activator inhibitor 1 (PAI) is bound to vitronectin in plasma. FEBS Lett 1988;242:125–8.[Medline]
24. Høgåsen K, Mollnes TE, Brandtzaeg P. Low levels of vitronectin and clusterin in acute meningococcal disease are closely associated with formation of the terminal complement complex and the vitronectin-thrombin-antithrombin complex. Infect Immun 1994;62:4874–80.[Abstract/Free Full Text]

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