EJCTS Click here to go to Siemens website
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Gerhard Ziemer
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wendel, H. P.
Right arrow Articles by Ziemer, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wendel, H. P.
Right arrow Articles by Ziemer, G.

Eur J Cardiothorac Surg 1999;16:342-350
© 1999 Elsevier Science NL

Review article

Coating-techniques to improve the hemocompatibility of artificial devices used for extracorporeal circulation

Hans Peter Wendel, Gerhard Ziemer

Division of Thoracic, Cardiac and Vascular Surgery, Department of Surgery, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076 Tuebingen, Germany

Corresponding author. Tel.: +49-7071-298-6605; fax: +49-7071-295-369
e-mail: hp.wendel{at}uni-tuebingen.de


   Abstract
Top
 Abstract
1. Introduction
 2. Components and effects...
 3. Heparin-coating
 4. How heparin-coating works
 5. Coating techniques for...
 6. New surface coatings
 7. Possible contraindication for...
 8. Conclusion and future...
 References
 
Objective: Extracorporeal circulation procedures have been shown to induce complement and leukocyte activation, release of endotoxin and inflammatory mediators, including cytokines, nitric oxide, oxygen free radicals, and platelet activating factors. The contact between the blood and the various artificial surfaces of the extracorporeal system results in an unspecific post-perfusion syndrome. For diminishing these negative side effects several coating-techniques have been developed to create devices with improved hemocompatibility. Methods: This review deals with the current knowledge of heparin-coated and otherwise surface-modified perfusion systems. The pathway how heparin-coated surfaces work is discussed and techniques for surface-coatings, both clinically introduced as well as newly developed are presented. Results: Numerous clinical studies compared heparin-coated versus non-coated circuits. Heparin-bonded devices showed lessened humoral and cellular activation, in particular a reduced complement activation with a reduced inflammatory post-perfusion syndrome. Also platelet protection and more favorable post-operative lung function are of particular note. Recent clinical trials demonstrated shortened hospital stays, less drainage bleeding, and reduced cerebral complications using heparin-coated oxygenation systems. The diminished expression of the leukocyte adhesion molecules CD 11b/c in CBAS devices points to a decreased activation of neutrophils. In addition, one research group found a reduced production of oxygen radicals. Heparin-bonding minimizes oxygenator failure by a significant reduced pressure gradient across the oxygenator, probably caused by decreased fibrin and platelet deposition at the hollow fiber surfaces. A meta analysis examined the impact of heparin-bonded systems on clinical outcomes and resulting costs. Using heparin-bonded circuits led to total cost savings from US $ 1000 to 3000. Several authors demonstrated reduced blood loss and better clinical outcome by reduction of systemic heparinization and the employment of heparin-coated devices. Conclusion: Above and beyond the long-term applications, routine heart operations have also markedly begun to utilize heparin-coated devices. This trend will assuredly continue in the coming years and is an important step toward higher hemocompatibility of blood-contacting surfaces in the ECC device. Heparin-coatings are merely the beginning of improved hemocompatibility for all materials that come into contact with human blood or tissues. Intelligent materials with almost completely physiological surfaces will be at the surgeon's disposal within the next few years.

Key Words: Extracorporeal circulation • Hemocompatibility • Heparin-coating


   1. Introduction
Top
 Abstract
 1. Introduction
2. Components and effects...
 3. Heparin-coating
 4. How heparin-coating works
 5. Coating techniques for...
 6. New surface coatings
 7. Possible contraindication for...
 8. Conclusion and future...
 References
 
In 1996, 765 000 heart operations world-wide were performed with the assistance of extracorporeal circulation (ECC), whereby approximately half (380 000) were done in the USA [1]. With respect to the age and physical condition of patients, all surgeons have found a shift toward older, frailer adults on one hand and younger children (up to 50% infants, half of them new-borns) on the other. The results of this displacement could be altered to the benefit of the patients undergoing open heart surgery by continual improvement of the operative techniques, as well as the perioperative supervision and the mechanical circulatory support systems. For the last option, the optimization of the surfaces of the ECC devices becomes of increased importance, both during the operation (e.g. heart-lung machine, partial left heart ventricular bypass) and after (short term: external uni- or biventricular pump systems, such as the Berlin heart; long term: internal ventricular pumps, such as TCI or Novacor). Next to the technical perfection of all these systems, it is also particularly important to consider the surfaces presented to the in general extracorporeally circulating blood.

Since its first use 40 years ago, extracorporeal circulation (ECC) during open heart surgery has developed around the globe into a routine procedure. Nevertheless, the insufficient hemocompatibility of the materials used for ECC devices still remains a problem. The contact between the blood and the various artificial surfaces of the extracorporeal system leads postoperatively to the so-called post-perfusion syndrome (or post-pump syndrome), which can escalate in severe cases into the systemic inflammatory response syndrome (SIRS) [2], acute lung failure (ARDS: adult respiratory distress syndrome) [3], sepsis, or even multiorgan failure (MOF) [4]. The causes of these syndromes are multi-factorial: mechanical and chemotactic activation and membrane-damage of the corpuscular components of the blood, dysfunction of the cellular immune regulation, activation of the hemostaseologic activation cascades, connected to one another through various feedback mechanisms, i.e. the contact phase (Factor XII-kallikrein-kinin system), intrinsic and extrinsic coagulation, fibrinolysis, and complement, as well as their cell- and tissue-damaging release products, such as free oxygen radicals, proteinases, nitric oxide, cytokines, endotoxins, etc. [4].


   2. Components and effects of the extracorporeal devices
Top
 Abstract
 1. Introduction
 2. Components and effects...
3. Heparin-coating
 4. How heparin-coating works
 5. Coating techniques for...
 6. New surface coatings
 7. Possible contraindication for...
 8. Conclusion and future...
 References
 
The medical devices that find either intra- or extracorporeal application embrace a wide spectrum of synthetic materials: polyethylene, polypropylene, polyvinylchloride (PVC), polyester, polystyrene, polyurethane, silicone, polysulphone, polyamide, polytetrafluoroethylene, their derivatives, etc. Although these products possess excellent physical properties, they were nonetheless developed primarily for industrial use and only later found their way into biomedicine. Thus, all these synthetic materials display more or less the same disadvantage: an incompatibility with blood and tissues. Through contact with the blood, this incompatibility can provoke a pathophysiological response from the organism, similar to that of traumatic shock. As is well known, in adult patients undergoing a bypass grafting procedure the total blood volume comes into contact with about 3 m2 of these non-physiological surfaces for one to several hours. This extensive contact causes a massive activation of the humoral and cellular defense systems against the supposed ‘invader’, and with that, the human body boosts the various cascade reactions into motion.

Insofar a reduction of these pathophysiological defensive mechanisms induced by blood/material interactions has top priority. Two further fundamentally different approaches are reasonable in principal: (A), reduction of the surface-induced activation mechanisms by improving the hemocompatibility of the device materials or (B), pharmacological inhibition of the key enzymes responsible for the consecutive activation of the cascade reactions (e.g. aprotinin, tranexamic acid, {epsilon}-aminocapron acid, C1-esterase inhibitor, antioxidants, free radical scavengers, immuno-globulins, etc.)

This review will not further debate point B. However, it should be noted that several other authors have suggested a combination of both procedures A and B, such as heparin-coated oxygenation systems and aprotinin application [5,6].


   3. Heparin-coating
Top
 Abstract
 1. Introduction
 2. Components and effects...
 3. Heparin-coating
4. How heparin-coating works
 5. Coating techniques for...
 6. New surface coatings
 7. Possible contraindication for...
 8. Conclusion and future...
 References
 
It was recognized relatively early that an improvement in the hemocompatibility of the materials used in biomedical applications could significantly contribute to reduce extreme reactions. The attempt to coat the artificial surfaces with heparin, an anticoagulant that imitates the antithrombogenic effects of heparansulfate at the endothelium, illustrates the first step toward attaining better hemocompatibility [7]. Through the homogeneous lining of the extracorporeal system, from canula to canula, the blood should encounter a uniform surface area. Gott and coworkers in 1963 [8] had previously reported on heparin-coating of synthetic materials, which had been pre-treated with colloidal graphite. Consequently, the following years saw work on an improved binding technique, in which the negatively-charged heparin molecules were bound to the solid, positively-charged ammonium ions. Larm and others [9] presented a heparin-coating method in 1983, which is still the most stable and most effective for long-term use. Their method involving covalent binding by the technique of end-point immobilization, did not adversely affect the heparin molecule's active sequence and thus produced an extremely bioactive surface structure (Fig. 1).



View larger version (45K):
[in this window]
[in a new window]
  		Fig. 1. Generalized schema of the construction of a heparin-coating.

 
As the first heparin-coated oxygenators become available in the last half of the 1980s, many research groups examined the oxygenators’ hemocompatibility in in-vitro systems, animal models, and later, in patient studies (see reviews from Gravlee, 1994 [10], Janvier, 1996 [11], and Hsu, 1997 [12]). The data published thus far are indeed relatively inhomogeneous; nonetheless, it can be assumed that heparin-coated oxygenators can cause a reduction of the following cascade reactions and/or symptoms: activation of the contact phase, complement system activation, alteration of granulocytes, inflammation, and pulmonary complications, activation of platelets, disturbance of homeostasis, loss of blood, and cerebral damage (literature overview see Tables 1 and 2).


View this table:
[in this window]
[in a new window]
  		Table 1. Overview of clinical studies dealing with Carmeda-coating published within the last 4 yearsa

 

View this table:
[in this window]
[in a new window]
  		Table 2. Overview of clinical studies dealing with Duraflo II-coating published within the last 4 yearsa

 
3.1. Oxygenator failure
A dreaded complication during ECC is oxygenator failure by development of an abnormal pressure gradient (APG) across the oxygenator. This phenomenon is presumably caused by increased fibrin and platelet deposition at the oxygenators’ surfaces, resulting in a diminished space for the blood flow particularly between the hollow-fibers. Wahba et al. [13] demonstrated in a study with 1959 patients that APG can be avoided by using heparin-coated devices.

3.2. Reduced anticoagulation protocol
Whether or not a reduction of systemic heparinization is possible through the employment of heparin-coated extracorporeal circulation components is still an issue of controversy [14–16]. By using a reduced heparin-dose, several authors demonstrated better homeostasis [17–21] and better clinical outcome [22–26]. Moreover, one must consider that the coagulation during ECC can occur not only on account of the non-physiological surfaces (intrinsic pathway) but also as a result of the surgical intervention (intrinsic and extrinsic (tissue-factor) pathway) [27].

3.3. Cost-benefit analysis
The industrial heparin-coating procedure of CPB-devices is still costly and therefore most companies have to compensate this by charging higher prices. Very rare data are available about cost efficiency of heparin-coated circuits. Mahoney [26] very recently published a meta-analysis to examine the impact of heparin-bonded systems on clinical outcomes and resulting costs. He found total cost savings of US$ 3231 by using covalently bonded circuits versus US$ 1068 with ionically coatings. However, this numbers differ extremely between the hospitals included in the analysis.


   4. How heparin-coating works
Top
 Abstract
 1. Introduction
 2. Components and effects...
 3. Heparin-coating
 4. How heparin-coating works
5. Coating techniques for...
 6. New surface coatings
 7. Possible contraindication for...
 8. Conclusion and future...
 References
 
Early on, many authors supported the hypothesis that the reduced thrombogenicity of the heparin-coated surfaces was attributable to the catalytic effects on antithrombin III and the accompanying formation of thrombin complexes. However, more recent knowledge shows that this hypothesis can no longer be maintained. Rather, the advantage of heparin-coats lies much more in the reduced, or selective, adhesion of plasma proteins, which in turn leads to a faster formation of a blood-friendly secondary superficial membrane on the one hand, and on the other hand prevents a further denaturation and hence activation of the adhered proteins and blood cells. Several research groups, in particular those of Vroman and Brash, were able to prove that plasma proteins on the artificial surface, such as F XII, fibrinogen, vitronektin, HMWK, and others, provide a significant criterion for further thrombogenicity [28]. Solid-phase bound fibrinogen leads to a strong adhesion of the platelets by their respective glycoprotein receptors, followed by platelet aggregation, and release of procoagulant contents like platelet factor 4. Additionally, PMN-leukocytes show an upregulation of the adhesion molecules CD 11b and CD 18 with increased sticking to the surface, release of elastase and superoxide generation; i.e. beginning of the inflammatory response [29,30]. Didisheim and Watson [31] put forth the hypothesis that the thrombogenicity of artificial surfaces depends mainly on the extent to which the activation and inhibition of platelet adhesion and aggregation – a process of permanent equilibrium reaction at the natural endothelium – can be simulated. This equilibrium reaction underlies both plasmatic as well as cellular auto-regulation and reverse feedback mechanisms. As soon as the blood comes in contact with the negatively-charged surface, factor XII, which occurs in an inactive complex with prekallikrein, F XI and HMWK, splits off into {alpha}- and ß-factor XIIa fragments. These fragments then initiate the entire contact phase activation system. ß-factor XIIa converts the zymogen prekallikrein into its active form, kallikrein, which splits the vasodilator bradykinin from HMWK [32]. Moreover, kallikrein possesses pro-fibrinolytic powers via plasminogen activation and also stimulates the chemotactic activity of neutrophilic granulocytes [32,33].

Relationships between the initial phases of classic complement activation (C1) and the contact phase system as well as the key enzyme for fibrinolysis (plasmin) have already been described in vitro and in-vivo [34]. Plasmin activation can occur through either the release of endothelial t-PA or kallikrein-activated urokinase. The plasmin thus generated can then activate the first factor in the complement cascade (C1) either directly or by the release of {alpha}-F XIIa, a product of F XII cleavage. These relations explain the lessened complement activation and the accordingly reduced inflammatory post-bypass syndrome that heparin-coated ECC devices make possible [29,35].

Finally, though, the exact reaction pathways followed when blood comes in contact with the heparin-coated surfaces have yet to be definitively elucidated.


   5. Coating techniques for extracorporeal devices
Top
 Abstract
 1. Introduction
 2. Components and effects...
 3. Heparin-coating
 4. How heparin-coating works
 5. Coating techniques for...
6. New surface coatings
 7. Possible contraindication for...
 8. Conclusion and future...
 References
 
In the following section, the currently known techniques for surface-coatings or surface-treatments will be presented without value judgments. The information about the coating procedures originates with the manufacturer, when not otherwise noted by citations.

5.1. Established heparin-coatings with years of clinical use
5.1.1. Medtronic Inc. (Carmeda Bioactive Surface®=CBAS)
At the beginning of the 1980s, Olle Larm and coworkers had developed a heparin-coating method for the Swedish company Carmeda. A short time later, Medtronic took on the license for extracorporeal circulation applications. The so-called ‘endpoint attachment ’achieved by a special covalent coupling mechanism allows a large part of the active heparin sequence to operate effectively in the bloodstream. This property attains a less thrombogenic surface on the one hand and decreases the denaturation of the adhered plasma proteins on the other hand [36]. Oxygenation systems with Carmeda heparin immobilization have been in clinical use for over a decade. Of the various coating systems, the CBAS® heparin-coating has been the best researched so far; numerous of experimental and clinical studies have been able to show the benefits of this coating (Table 2). The lessened humoral and cellular activation [37–40], in particular the reduced complement activation [37,40–43], deserve special attention. Recent clinical trials with 120 patients demonstrated shortened hospital stays, less drainage bleeding, and reduced cerebral complications with CBAS® compared to uncoated devices [44]. In addition, Bozdayi and coworkers found the production of oyxgen radicals was reduced by using this heparin-coat [45]. The diminished expression of the leukocyte adhesion molecule CD 11b/c in CBAS devices points to a decreased activation of neutrophils [46]. Comparative studies with other types of heparin-bondings have shown the high quality of this coating method [43,47–50].Taken together, the use of CBAS coatings can reduce the inflammatory post-perfusion syndrome, and all of this coating technique's advantages are of particular relevance for long-term applications (ECMO).

5.1.2. Baxter (Duraflo II®)
The key to Duraflo II® heparin-coating is an ionically-bound heparin-benzalkonium-chloride complex, which enables a relatively firm (for ionic bonds) connection with the foreign surface. Duraflo II® has been in clinical use since 1988 after numerous in vitro, animal, and clinical trials tested its effectiveness (Table 1). Platelet protection [51], reduced complement activation [29,52–54], and more favorable post-operative lung function [55] are of particular note.

The newest and most comprehensive study of this material was recently published within the framework of a European multi-center study [56] with 805 patients undergoing aortocoronary bypass operations. With regard to blood loss, transfusion needs, intubation time, morbidity, mortality, and the length of the stay in intensive care, the study found no significant differences between Duraflo II® and uncoated systems. Nonetheless, for women and patients with aortic clamping times over 60 min, the use of Duraflo II® decreased the need for blood products, intubation time, and the period of intensive care stay.

5.1.3. Jostra (BioLine Coating®)
The coating method BioLine Coating® developed by the German company Jostra brings the high molecular weight heparin Liquemin® (Hoffman La-Roche, Basel, Switzerland) onto a base layer of immobilized polypeptides. This polypeptide adsorption can occur on hydrophilic as well as hydrophobic surfaces, whereby the creation of covalent bonds and ionic interactions between the heparin and the immobilized peptide achieves the stable coupling of the heparin molecule. The specific tie between the heparin molecule and the polypeptide preserves the active sequence of the heparin. BioLine Coating®, in clinical use since 1992, can be used to coat all components of the extracorporeal device including silicone parts.

The effectiveness of this heparin-coating could be proved pre-clinically in ex-vivo models and animal experiments [57–59]. Various clinical tests were also able to show BioLine Coating®’s positive influence on the reaction mechanism triggered by contact activation. Another prospective randomized evaluation of 60 male patients who had to undergo an elective coronary operation clearly highlighted the advantages of the heparin-coated device during relatively short bypass times. In comparison to an uncoated perfusion system, the use of BioLine-Coating® demonstrated delayed contact activation and decreased alteration of leucocytes, as well as lessened coagulatory activity and improved platelet protection [60]. Moreover, studies of BioLine-Coating® perfusion devices used during surgical correction of congenital anomalies in infants and small children showed, in comparison to uncoated devices, a significantly better platelet protection and lessened activation of the cytolytic complexes of the complement system [61]. In a very interesting study, Matheis and associates further revealed that BioLine-Coating® devices could reduce cerebral alterations resulting from extracorporeal circulation [62].

In order to meet properly the demands of different application procedures and perfusion times, the Jostra Company offers two coatings: BioLine-Coating® (Extracorporeal Circulation=ECC) for short perfusion times, especially in the area of heart surgery, and BioLine-Coating® (Long Term Perfusion=LTP) for extracorporeal circulation of several days duration (ECMO, support systems, etc.)

5.2. New heparin-coatings
5.2.1. AOT (artificial organ technology) (AOThel®)
The AOT company provides a heparin-coating named AOThel, which has found itself in clinical use since 1997. The system is a universally and from the structure itself hemocompatible coating procedure for tubing and oxygenation systems. The central feature is a heparin-coat with a certified low molecular weight heparin. The AOThel procedure forsakes traditional substances for immobilizing heparin, such as polyamides and cationic tensides. Instead, the bond occurs comparable to the proteoglycan of the natural endothelium. All components of the extracorporeal device, including silicone, could be so coated, without altering their function or mechanical properties.

5.2.2. Corline Systems AB (Corline®)
The Swedish company Corline Systems AB, in cooperation with Rolf Larsson, a pioneer of heparin-coating technology, developed a new, simple, and easily reproducible technique for improving the hemocompatibility of glass, metal, and synthetic polymers [9,63]. The Corline® heparin surface is produced by means of a uniform macromolecular heparin conjugate. This conjugate consists of multiple heparin molecules, which are covalently bound by specific linkers to an inert polyamine chain. After special pre-treatment, the conjugate binds itself to those surfaces of the medical device that come into contact with the blood. The specificity of this covalent bond guarantees that the immobilized heparin's pentasaccharide sequence, important for its biological activity, is completely preserved.

The Corline® heparin-coat effects a minimal deposition and activation of both platelets and granulocytes (CB 11b), as well as a drastically reduced activation of the complement and coagulation systems. Corline®-coated internal coronary prostheses (stents) and ECC systems have now been in clinical since 1997.

5.2.3. 3M
The newly developed heparin-coating procedure from the 3M company revolves around a technique for binding heparin covalently on polymer and metal surfaces. The method displays several parallels with the Carmeda coat: water soluble polyethylamine is bound to the surface to be coated, a layer of dextran-sulfate comes next, then another layer of polyethylamine, on which the oxidized heparin is finally, covalently bound by the addition of cyanoborohydride. The surface presented to the blood therefore consists of biologically active heparin.

All synthetic materials of the extracorporeal device, again, inclusive silicone, can be treated with this method. At the present time, though, this procedure finds itself still under preclinical evaluation, albeit awaiting clinical introduction in the very near future.


   6. New surface coatings
Top
 Abstract
 1. Introduction
 2. Components and effects...
 3. Heparin-coating
 4. How heparin-coating works
 5. Coating techniques for...
 6. New surface coatings
7. Possible contraindication for...
 8. Conclusion and future...
 References
 
6.1. Avecor (Trilium Bio-passive Surface=TBS®)
Also just developed, this technique works with water-soluble synthetic polymers that are immobilized in two superficial layers. The first polymer layer serves as a primer and binds itself tightly to the artificial materials of the ECC device. The second layer, containing sulfonate groups, polyethylene-oxide chains, and heparin, is covalently bound to the primer and results in an insoluble surface coat. This surface in turn prevents the adhesion of blood cells and plasma proteins during contact with the blood.

The first experiments with this technique indicated that the treated synthetic materials prevented the activation of the contact phase as well as platelet and leukocyte activation. The TBS coating intervened in the initial phases of the blood-material interactions and thereby prevented further activation at a very early stage in the cascade reaction. ECC systems with this coating are available since mid-1998.

6.2. Biocompatibles
Dennis Chapman has developed a method that provides an extremely interesting alternative to coating surfaces with anticoagulants: employing phospholipids from natural membranes as a coating substance. Zwaal and coworkers [64] had already proved in 1977 that, in contrast to their exterior surfaces, the interior surfaces of erythrocyte membranes possess strong thrombogenic properties. Further examination showed an asymmetrical distribution of the phospholipids over the cell membrane, with phosphorylcholine-containing lipids dominating in the outer membrane of the bilayer [65] (Fig. 2).



View larger version (19K):
[in this window]
[in a new window]
  		Fig. 2. Structure of a biological membrane.

 
Chapman's group succeeded in coupling synthetic methacryloyl-phosphorylcholine/lauryl-methacrylate copolymers to metal and synthetic surfaces. The term ‘biomembrane mimicry’ accordingly arose for phosphorylcholine-coated foreign surfaces [66].

In vitro experiments and animal tests have shown that phosphorylcholine-coated artificial polymers possess outstanding thrombogenic resistance and display only minimal adhesion of plasma proteins and platelets [67,68]. Until now, this coating technique has only been offered for contact lenses, although it should be soon ready for the market of extracorporeal circulation devices.

6.3. Cobe (SMARxTTM)
This coating procedure, applicable to all surfaces of the ECC systems, is not a coating technique in the usual sense. Rather, it is a surface modifying additive (SMA), which is contributed to the initial synthetic materials in the device's production phase. The copolymer distributes itself in the synthetic materials during the polymerization process and due to its charge characteristics, moves to the surface of the basis material as it cools. Thus, a new surface of 100% SMA forms. The surface's microscopic structure of alternating hydrophilic and hydrophobic regions carries a net neutral charge, thereby reducing platelet and leukocyte deposition. Tsai and others [69] could prove that SMA surfaces decreased coagulation activation and significantly reduced contact phase and complement activation. Gu et al. [70] found a better platelet protection in clinical CPB by using SMA treated devices. Such SMA surfaces in extracorporeal devices have undergone evaluative testing in select centers since 1996 and have been available since mid-1997.


   7. Possible contraindication for heparin-coated devices
Top
 Abstract
 1. Introduction
 2. Components and effects...
 3. Heparin-coating
 4. How heparin-coating works
 5. Coating techniques for...
 6. New surface coatings
 7. Possible contraindication for...
8. Conclusion and future...
 References
 
Heparin-coated surfaces are, in principal, universally applicable without concern. Only one potentially troublesome area exists at this time: the ventricular assist devices (VAD). These devices are increasingly employed for therapy-refractory pump failure or as ‘bridging to transplant’ endeavors. On account of their material properties, all these assist devices reveal a more or less pronounced bioincompatibility, and thus their use can be associated with subsequently heightened bleeding complications or thromboembolic events. Most cardiac centers attempt to minimize both the thrombogenicity and systemic heparin dose by using heparin-coated VADs. Yet a reduction of their hemocompatibility cannot be completely excluded for the following reason: after the implantation of the VAD, the anticoagulant that was necessary during the ECC now needs to be neutralized, normally by its antidote protamine. However, unbound protamine could come into contact with the heparin-coating of the VAD and accordingly neutralize it, and its hemocompatible characteristics, as well [71,72].

A recently-presented study examined the influence of protamine application on the hemocompatibility of heparin-coatings in an in-vitro ‘closed loop’ model. Judging from the measured coagulation and inflammation markers, the protamine contact had significantly worsened the hemocompatibility of the heparin-coated surface. In light of these results, especial caution should be given to protamine application and the anticoagulation status during the clinical use of VADs with heparin-coatings, so as to minimize thromboembolic complications. In future it would be even better to eliminate the high systemic heparin concentrations by extracorporeal heparin removal devices [73].


   8. Conclusion and future prospects
Top
 Abstract
 1. Introduction
 2. Components and effects...
 3. Heparin-coating
 4. How heparin-coating works
 5. Coating techniques for...
 6. New surface coatings
 7. Possible contraindication for...
 8. Conclusion and future...
References
 
In spite of all the technical improvements made to improve the hemocompatibility of ECC components, a noticeable activation of plasma proteins and corpuscular blood components still transpires. The long-range goal remains the creation of an optimally hemocompatible surface (endothelium-like), which the blood would no longer recognize as unphysiological and hence would not induce humoral and cellular defenses as well as rejection mechanisms against it.

In summary, however, with the results of numerous studies on the hemocompatibility of extracorporeal circulation in hand, one can definitely work from the assumption that heparin-coated devices retard the activation of cellular and humoral mechanisms. Above all, the reduction of a general inflammatory response initiated by the extracorporeal circulation represents an important application for heparin-coated devices.

Above and beyond the long-term applications, routine heart operations have also markedly begun to utilize heparin-coated devices. This trend will assuredly continue in the coming years and is an important step toward higher hemocompatibility of blood-contacting surfaces in the ECC device.

Heparin-coatings are merely the beginning of improved hemocompatibility for all materials that come into contact with human blood or tissues. Intelligent materials with almost completely physiological surfaces will be at the surgeon's disposal within the next few years. Such materials will be able to mimic endothelial functions and respond to individual changes in the patient's status with the controlled release of adequate pharmacological substances.


   References
Top
 Abstract
 1. Introduction
 2. Components and effects...
 3. Heparin-coating
 4. How heparin-coating works
 5. Coating techniques for...
 6. New surface coatings
 7. Possible contraindication for...
 8. Conclusion and future...
 References
 

  1. Market analysis: perfusion. In: Theta Reports, editor. Theta reports–cardiac equipment and materials markets. New York (212) 262-8230,1997:92-129.
  2. Taylor K.M. SIRS – the systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg 1996;61:1607-1608.[Free Full Text]
  3. Müller E. Adult respiratory distress syndrome (ARDS): activation of complement, coagulation and fibrinolytic systems. Biomedical Progress 1991;4:3-6.
  4. Colman R.W. Hemostatic complications of cardiopulmonary bypass. Am J Hematol 1995;48:267-272.[Medline]
  5. Bannan S., Martin P.G. Aprotinin complements heparin bonding in an in vitro model of cardiopulmonary bypass. Br J Haematol 1998;101:455-461.[Medline]
  6. Baufreton C., Jansen P.G., Le Besnerais P., te Velthuis H., Thijs C.M., Wildevuur C.R., Loisance D.Y. Heparin coating with aprotinin reduces blood activation during coronary artery operations. Ann Thorac Surg 1997;63:50-56.[Abstract/Free Full Text]
  7. Marcum J.A., Rosenberg R.D. The biochemistry, cell biology, and pathophysiology of anticoagulantly heparin-like molecules of the vessel wall. In: Lane D.A., Lindahl U, eds. Heparin: clinical and biological properties, clinical applications. Boca Raton FL: CRC Press, 1989:275-294.
  8. Gott V.L., Whiffen J.D., Dutton R.C. Heparin bonding on colloidal graphite surfaces. Science 1963;142:1297-1298.[Abstract/Free Full Text]
  9. Larm O., Larsson R., Olsson P. A new non-thrombogenic surface prepared by selective covalent binding of heparin via a modified reducing terminal residue. Biomater Med Devices Artif Organs 1983;11:161-173.[Medline]
  10. Gravlee G.P. Heparin-coated cardiopulmonary bypass circuits. J Cardiothorac Vasc Anesth 1994;8:213-222.[Medline]
  11. Janvier G., Baquey C., Roth C., Benillan N., Belisle S., Hardy J.F. Extracorporeal circulation, hemocompatibility, and biomaterials. Ann Thorac Surg 1996;62:1926-1934.[Abstract/Free Full Text]
  12. Hsu L.C. Biocompatibility in cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1997;11:376-382.[Medline]
  13. Wahba A., Philipp A., Behr R., Birnbaum D.E. Heparin-coated equipment reduces the risk of oxygenator failure. Ann Thorac Surg 1998;65:1310-1312.[Abstract/Free Full Text]
  14. Von Segesser L.K., Weiss B.M., Pasic M., Garcia E., Turina M.I. Risk and benefit of low systemic heparinization during open heart operations. Ann Thorac Surg 1994;58:391-397.[Abstract]
  15. Borowiec J., Thelin S., Bagge L., van der Linden J., Thorno E., Hansson H.E. Heparin-coated cardiopulmonary bypass circuits and 25% reduction of heparin dose in coronary artery surgery – a clinical study. Ups J Med Sci 1992;97:55-66.[Medline]
  16. Kuitunen A.H., Heikkila L.J., Salmenpera M.T. Cardiopulmonary bypass with heparin-coated circuits and reduced systemic anticoagulation. Ann Thorac Surg 1997;63:438-444.[Abstract/Free Full Text]
  17. Aldea G.S., Zhang X., Memmolo C.A., Shapira O.M., Treanor P.R., Kupferschmid J.P., Lazar H.L., Shemin R.J. Enhanced blood conservation in primary coronary artery bypass surgery using heparin-bonded circuits with lower anticoagulation. J Card Surg 1996;11:85-95.[Medline]
  18. Ovrum E., Brosstad F., Am Holen E., Tangen G., Abdelnoor M. Effects on coagulation and fibrinolysis with reduced versus full systemic heparinization and heparin-coated cardiopulmonary bypass. Circulation 1995;92:2579-2584.[Abstract/Free Full Text]
  19. Pekna M., Borowiec J.W., Fagerhol M.K., Venge P., Thelin S. Biocompatibility of heparin-coated circuits used in cardiopulmonary bypass. Scand J Thorac Cardiovasc Surg 1994;28:5-11.[Medline]
  20. Ovrum E., Mollnes T.E., Fosse E., Holen E.A., Tangen G., Ringdal M.A., Videm V. High and low heparin dose with heparin-coated cardiopulmonary bypass: activation of complement and granulocytes. Ann Thorac Surg 1995;60:1755-1761.[Abstract/Free Full Text]
  21. Von Segesser L.K., Weiss B.M., Garcia E., von Felten A., Turina M.I. Reduction and elimination of systemic heparinization during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1992;103:790-799.[Abstract]
  22. Aldea G.S., O'Gara P., Shapira O.M., Treanor P., Osman A., Patalis E., Arkin C., Diamond R., Babikian V., Lazar H.L., Shemin R.J. Effect of anticoagulation protocol on outcome in patients undergoing CABG with heparin-bonded cardiopulmonary bypass circuits. Ann Thorac Surg 1998;65:425-433.[Abstract/Free Full Text]
  23. Aldea G.S., Doursounian M., O'Gara P., Treanor P., Shapira O.M., Lazar H.L., Shemin R.J. Heparin-bonded circuits with a reduced anticoagulation protocol in primary CABG: a prospective, randomized study. Ann Thorac Surg 1996;62:410-417.[Abstract/Free Full Text]
  24. Borowiec J., Thelin S., Bagge L., Hultman J., Hansson H.E. Decreased blood loss after cardiopulmonary bypass using heparin-coated circuit and 50% reduction of heparin dose. Scand J Thorac Cardiovasc Surg 1992;26:177-185.[Medline]
  25. Bannan S., Danby A., Cowan D., Ashraf S., Martin P.G. Low heparinization with heparin-bonded bypass circuits: is it a safe strategy?. Ann Thorac Surg 1997;63:663-668.[Abstract/Free Full Text]
  26. Mahoney C.B. Heparin-bonded circuits: clinical outcomes and costs. Perfusion 1988;13:192-204.
  27. Boisclair M.D., Lane D.A., Philippou H., Esnouf M.P., Sheikh S., Hunt B., Smith K.J. Mechanisms of thrombin generation during surgery and cardiopulmonary bypass. Blood 1993;82:3350-3357.[Abstract/Free Full Text]
  28. Vroman L. The life of an artificial device in contact with blood: initial events and their effect on its final state. Bull NY Acad Med 1998;64:352-357.
  29. Moen O., Hogasen K., Fosse E., Dregelid E., Brockmeier V., Venge P., Harboe M., Mollnes T.E. Attenuation of changes in leukocyte surface markers and complement activation with heparin-coated cardiopulmonary bypass. Ann Thorac Surg 1997;63:105-111.[Abstract/Free Full Text]
  30. Wan S., LeClerc J.L., Vincent J.L. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest 1997;112:676-692.[Abstract/Free Full Text]
  31. Didisheim D., Watson J. Thromboembolic complications of cardiovascular devices and artificial surfaces. In: Kwaan H., Samama M.Y., eds. Clinical thrombosis. Boca Raton: CRC Press, 1989:275-296.
  32. Fuhrer G., Gallimore M.J., Heller W., Hoffmeister H.E. F XII (Review). Blut 1990;61:258-266.[Medline]
  33. Colman R.W., Scott C.F., Schmaier A.H., Wachtfogel Y.T., Pixley R.A., Edmunds Jr L.H. Initiation of blood coagulation at artificial surfaces. In: Leonard E.F., Turrito V.T., Vroman L., eds. Ann NY Acad Sci. 1987:253-267.
  34. Mammen E.F. Contact activation: the interaction of clotting, fibrinolytic, kinin and complement systems. Biomedical Progress 1990;2:31-34.
  35. Jansen P.G., te Velthuis H, Huybregts R.A., Paulus R., Bulder E.R., van der Spoel H.I., Bezemer P.D., Slaats E.H., Eijsman L., Wildevuur C.R.H. Reduced complement activation and improved postoperative performance after cardiopulmonary bypass with heparin-coated circuits. J Thorac Cardiovasc Surg 1995;110:829-834.[Abstract/Free Full Text]
  36. Elgue G., Blomback M., Olsson P., Riesenfeld J. On the mechanism of coagulation inhibition on surfaces with end point immobilized heparin. Thromb Haemost 1993;70:289-293.[Medline]
  37. Moen O., Fosse E., Dregelid E., Brockmeier V., Andersson C., Hogasen K., Venge P., Mollnes T.E., Kierulf P. Centrifugal pump and heparin coating improves cardiopulmonary bypass biocompatibility. Ann Thorac Surg 1996;62:1134-1140.[Abstract/Free Full Text]
  38. Korn R.L., Fisher C.A., Livingston E.R., Stenach N., Fishman S.J., Jeevanadam V., Addonizio V.P. The effects of Carmeda Bioactive Surface on human blood components during simulated extracorporeal circulation. J Thorac Cardiovasc Surg 1996;111:1073-1084.[Abstract/Free Full Text]
  39. Wagner W.R., Johnson P.C., Thompson K.A., Marrone G.C. Heparin-coated cardiopulmonary bypass circuits: hemostatic alterations and postoperative blood loss. Ann Thorac Surg 1994;58:734-740.[Abstract]
  40. Fukutomi M., Kobayashi S., Niwaya K., Hamada Y., Kitamura S. Changes in platelet, granulocyte, and complement activation during cardiopulmonary bypass using heparin-coated equipment. Artif Organs 1996;20:767-776.[Medline]
  41. Kagisaki K., Masai T., Kadoba K., Sawa Y., Nomura F., Fukushima N., Ichikawa H., Ohata T., Suzuki K., Taketani S., Matsuda H. Biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass. Artif Organs 1997;21:836-840.[Medline]
  42. Ovrum E., Fosse E., Mollnes T.E., Am Holen E., Tangen G., Abdelnoor M., Ringdal M.A., Oystese R., Venge P. Complete heparin-coated cardiopulmonary bypass and low heparin dose reduce complement and granulocyte activation. Eur J Cardiothorac Surg 1996;10:54-60.[Abstract]
  43. Ovrum E., Mollnes T.E., Fosse E., Holen E.A., Tangen G., Abdelnoor M., Ringdal M.A., Oystese R., Venge P. Complement and granulocyte activation in two different types of heparinized extracorporeal circuits. J Thorac Cardiovasc Surg 1995;110:1623-1632.[Abstract/Free Full Text]
  44. Svenmarker S., Sandström E., Karlsson T., Jansson E., Häggmark S., Lindholm R., Appelblad M., Aberg T. Clinical effects of the heparin coated surface in cardiopulmonary bypass. Eur J Cardiothorac Surg 1997;11:957-964.[Abstract]
  45. Bozdayi M., Borowiec J., Nilsson L., Venge P., Thelin S., Hansson H.E. Effects of heparin coating of cardiopulmonary bypass circuits on in vitro oxygen free radical production during coronary bypass surgery. Artif Organs 1996;20:1008-1016.[Medline]
  46. Hogevold H.E., Moen O., Fosse E., Venge P., Braten J., Andersson C. Effects of heparin coating on the expression of CD11b. CD11c and CD62L by leucocytes in extracorporeal circulation in vitro. Perfusion 1997;12:9-20.[Abstract/Free Full Text]
  47. Moen O., Fosse E., Brockmeier V., Andersson C., Mollnes T.E., Hogasen K., Venge P. Disparity in blood activation by two different heparin-coated cardiopulmonary bypass systems. Ann Thorac Surg 1995;60:1317-1323.[Abstract/Free Full Text]
  48. Lundblad R., Moen O., Fosse E. Endothelin-1 and neutrophil activation during heparin-coated cardiopulmonary bypass. Ann Thorac Surg 1997;63:1361-1367.[Abstract/Free Full Text]
  49. Baba T., Morisita K., Sakata J., Ito T., Hachiro Y., Kazui T., Abe A., Komatu S. Experimental studies on three types of heparin-coated cardiopulmonary circuits. Artificial Organs 1997;21(7):779-781.[Medline]
  50. Akihiko U., Fumihiko M., Hideki O., Yasuhiro T., Katsuhiko Y., Michiaki H., Mitsuo K., Mitsuya M. A clinical study for the durability of oxygenators on cardiopulmonary support. Artificial Organs 1997;21(7):772-778.[Medline]
  51. Palatianos G.M., Dewanjee M.K., Smith W., Novak S., Hsu L.C., Kapadvanjwala M., Sfakianakis G.N., Kaiser G.A. Platelet preservation during cardiopulmonary bypass with iloprost and Duraflo-II heparin-coated surfaces. ASAIO Trans 1991;37:620-622.[Medline]
  52. Horimoto H., Kondo K., Asada K., Sasaki S. Heparin-coated cardiopulmonary bypass circuits in coronary bypass surgery. Artif Organs 1996;20:936-940.[Medline]
  53. te Velthuis H., Jansen P.G., Hack C.E., Eijsman L., Wildevuur C.R.H. Specific complement inhibition with heparin-coated extracorporeal circuits. Ann Thorac Surg 1996;61:1153-1157.[Abstract/Free Full Text]
  54. Yamanaka J., Takeuchi Y., Torii S., Gomi A., Nakatani H., Kohno K. The evaluation of the bio-compatibility and the clinical usefulness of heparin-coated cardiopulmonary bypass circuits. Nippon Kyobu Geka Gakkai Zasshi 1996;44:47-53.[Medline]
  55. Ranucci M., Cirri S., Conti D., Ditta A., Boncilli A., Frigiola A., Menicanti L. Beneficial effects of Duraflo II heparin-coated circuits on postperfusion lung dysfunction. Ann Thorac Surg 1996;61:76-81.[Abstract/Free Full Text]
  56. Wildevuur C.R.H., Jansen P.G., Bezemer P.D., Kuik D.J., Eijsman L., Bruins P., de Jong D., Van Hardevelt F.W.J., Biervliet J.D., Hasenkam J.M., Kure H.H., Knudsen L., Bellaiche L., Ahlburg P., Loisance D.Y., Baufreton C., Le Besnerais P., Bajan G., Matta A., Van Dyck M., Renotte M.T., Ponlot-Lois A., Baele P.L., Mcgovern E.A., McCarthy J., McCarthy A., O'Donell A., Fosse E., Moen O., Dregelid E., Brockmeier V., Anderson C., Pomar J.L., Ranucci M., Conti D., Cirri S., Conti E., Ditta A., Von Segesser L.K., Tkebuchava T., Weiss B.M., Turina M.I., Svennevig J.L., Mohr B., Videm V., Karlsen H., Pedersen T.H., Thelin S., Halden E., Hagman L., Thörnö E., Ahlvin E. Clinical evaluation of Duraflo II heparin treated extracorporeal circulation circuits (2nd version). The European working group on heparin coated extracorporeal circulation circuits. Eur J Cardiothorac Surg 1997;11:616-623.
  57. Wendel H.P., Klaffschenkel R., Heller W., Hoffmeister H.E. Kardiopulmonaler Bypass unter Verzicht von Antikoagulantien? – Ex-vivo-Modelluntersuchungen mit Verwendung eines heparinbeschichteten Membranoxygenators. In: Fraedrich G, von Segesser L.K., Hasse J, Schlosser V, eds. Besondere aspekte der extrakorporalen zirkulation. Darmstad: Steinkopff Verlag, 1992:47-52.
  58. Tkebuchava T., Von Segesser L.K., Leskosek B., Pei P., Turina M. Thrombosis-resistant heparin-coated diffusion membrane oxygenators: an experimental study. Swiss Surg Suppl 1996;1:36-40.
  59. van der Kamp K.W., Magielse C.P., Elstrodt J.M., van der Meer J., van Oeveren W., Rakhorst G. Blood interaction with a Bioline heparin coated HIA-VAD: a study on calves. Int J Artif Organs 1997;20:43-50.[Medline]
  60. Fraedrich G., Hoh A., Scheidel U., Mayer U.H., Böhler J., Beyersdorf F. A new covalent heparin bonding process of extracorporeal circuits improves the hemocompatibility of cardiopulmonary bypass (Abstract 112). CREF San Diego 1995.
  61. Knobl H.J., Kind K., Dramburg W., Weigkemper H.H., Breymann T., Thies W.R., Brinkmann T., Körfer R. Erste klinische Erfahrungen mit der Bioline Coating-Beschichtung bei Säuglingen und Kleinkindern mit kongenitalen Vitien – Beschichtung des extracorporalen Systems (Abstract). Int T Ges Kardiotech 1995:24.
  62. Matheis G., Wimmer-Greinecker G., Beholz S., Skupin M., Baum R.P., Meisel M., Oremek G., Beyersdorf F., Moritz A. Heparin-coated cardiopulmonary bypass is associated with reduced pulmonary and cerebral injury (Abstract 185). Thorac Cardiovasc Surg 1996:44.
  63. Larsson R., Larm O., Olsson P. The search for thromboresistance using immobilized heparin. Ann NY Acad Sci 1987;516:102-107.[Medline]
  64. Zwaal R.F.A., Comfurius P., van Deenen L.L.M. Membrane assymmetry and blood coagulation. Nature 1977;268:358-360.[Medline]
  65. Chapman D., Lee D.C. Dynamics and structure of biomembranes. Biochem Soc Trans 1987;15:475-545.
  66. Yianni Y.P Biocompatible surfaces based upon biomembrane mimicry. In: Quinn P.J., Cherry R.J., eds. Structural and Dynamic Properties of Lipids and Membranes. London: Portland Press Ltd, 1992:187-216.
  67. Von Segesser L.K., Tonz M., Leskosek B., Turina M. Evaluation of phospholipidic surface coatings ex-vivo. Int J Artif Organs 1994;17:294.[Medline]
  68. Campbell E.J., O'Byrne V., Stratford P.W., Quirk I., Vick T.A., Wiles M.C., Yianni Y.P. Biocompatible surfaces using methacryloylphosphorylcholine laurylmethacrylate copolymer. ASAIO J 1994;40:853-857.
  69. Tsai C.C., Deppisch R.M., Forrestal L.J., Ritzau G.H., Oram A.D., Göhl H.J., Voorhees M.E. Surface modifying additives for improved device-blood compatibility. ASAIO J 1994;40:M619-M624.[Medline]
  70. Gu Y.J., Boonstra P.W., Rijnsburger A.A., Haan J., van Oeveren W. Cardiopulmonary bypass circuit treated with surface-modifying additives: a clinical evaluation of blood compatibility. Ann Thorac Surg 1998;65:1342-1347.[Abstract/Free Full Text]
  71. Von Segesser L.K., Gyurech D.D., Schilling J.J., Marquardt K., Turina M.I. Can protamine be used during perfusion with heparin surface coated equipment?. ASAIO J 1993;39:M190-M194.[Medline]
  72. Muehrcke D.D., McCarthy P.M., Stewart R.W., Seshagiri S., Ogella D.A., Foster R.C., Cosgrove D.M. Complications of extracorporeal life support systems using heparin-bound surfaces. The risk of intracardiac clot formation. J Thorac Cardiovasc Surg 1995;110:843-851.
  73. Hendrikx M., Leunens V., Vandezande E., Wallyn A., Flameng W. The use of a heparin removal device: a valid alternative to protamine. Int J Artif Organs 1997;20:166-174.[Medline]
  74. Belboul A., Al-Khaja N. Does heparin coating improve biocompatibility? A study on complement, blood cells and postoperative morbidity during cardiac surgery. Perfusion 1997;12:385-391.[Abstract/Free Full Text]
  75. Borowiec J., Bagge L., Saldeen T., Thelin S. Biocompatibility reflected by haemostasis variables during cardiopulmonary bypass using heparin-coated circuits. Thorac Cardiovasc Surg 1997;45:163-167.[Medline]
  76. Gorman R.C., Ziats N., Rao A.K., Gikakis N., Sun L., Khan M.M., Stenach N., Sapatnekar S., Chouhan V., Gorman J.H. 3rd., Niewiarowski S., Colman R.W., Anderson J.M., Edmunds L.H. Jr Surface-bound heparin fails to reduce thrombin formation during clinical cardiopulmonary bypass. J Thorac Cardiovasc Surg 1996;111:1-11.[Abstract/Free Full Text]
  77. Borowiec J.W., Hagman L., Totterman T.H., Pekna M., Venge P., Thelin S. Circulating cytokines and granulocyte-derived enzymes during complex heart surgery. A clinical study with special reference to heparin-coating of cardiopulmonary bypass circuits. Scand J Thorac Cardiovasc Surg 1995 1995;29:167-174.
  78. Steinberg B.M., Grossi E.A., Schwartz D.S., McLoughlin D.E., Aguinaga M., Bizekis C., Greenwald J., Flisser A., Spencer F.C., Colvin S.B., Galloway A.C. Heparin bonding of bypass circuits reduces cytokine release during cardiopulmonary bypass. Ann Thorac Surg 1995;60:525-529.[Abstract/Free Full Text]
  79. Weiss B.M., Von Segesser L.K., Turina M.I., Seifert B., Pasch T. Perioperative course and recovery after heparin-coated cardiopulmonary bypass: low-dose versus high-dose heparin management. J Cardiothorac Vasc Anesth 1996;10:464-470.[Medline]
  80. Ovrum E., Brosstad F., Am Holen E., Tangen G., Abdelnoor M., Oystese R. Complete heparin-coated (CBAS) cardiopulmonary bypass and reduced systemic heparin dose; effects on coagulation and fibrinolysis. Eur J Cardiothorac Surg 1996;10:449-455.[Abstract]
  81. Ernofsson M., Thelin S., Siegbahn A. Thrombin generation during cardiopulmonary bypass using heparin-coated or standard circuits. Scand J Thorac Cardiovasc Surg 1995;29:157-165.[Medline]
  82. Spiess B.D., Vocelka C., Cochran R.P., Soltow L., Chandler W.L. Heparin-coated bypass circuits (Carmeda) suppress the release of tissue plasminogen activator during normothermic coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 1998;12:299-304.[Medline]
  83. Saenz A., Larranaga G., Alvarez L., Greco E., Marrero A., Lunar M., Elosegui C., Ubago J.L., Gallo I. Heparin-coated circuit in coronary surgery. A clinical study. Eur J Cardiothorac Surg 1996;10:48-53.
  84. Yamada H., Kudoh I., Hirose Y., Toyoshima M., Abe H., Kurahashi K. Heparin-coated circuits reduce the formation of TNF alpha during cardiopulmonary bypass. Acta Anaesthesiol Scand 1996;40:311-317.[Medline]
  85. Fosse E., Thelin S., Svennevig J.L., Jansen P., Mollnes T.E., Hack E., Venge P., Moen O., Brockmeier V., Dregelid E., Halden E., Hagman L., Videm V., Pedersen T., Mohr B. Duraflo II coating of cardiopulmonary bypass circuits reduces complement activation, but does not affect the release of granulocyte enzymes: a European multicentre study. Eur J Cardiothorac Surg 1997;11:320-327.[Abstract]
  86. Ernofsson M., Thelin S., Siegbahn A. Monocyte tissue factor expression, cell activation, and thrombin formation during cardiopulmonary bypass: a clinical study. J Thorac Cardiovasc Surg 1997;113:576-584.[Abstract/Free Full Text]
  87. Hamulu A., Discigil B., Ozbaran M., Calkavur T., Kara E., Kokuludag A., Buket S., Bilkay O. Complement consumption during cardiopulmonary bypass: comparison of Duraflo II heparin-coated and uncoated circuits in fully heparinized patients. Perfusion 1996;11:333-337.[Medline]
  88. te Velthuis H., Baufreton C., Jansen P.G., Thijs C.M., Hack C.E., Sturk A., Wildevuur C.R., Loisance D.Y. Heparin coating of extracorporeal circuits inhibits contact activation during cardiac operations. J Thorac Cardiovasc Surg 1997;114:117-122.[Abstract/Free Full Text]
  89. Barstad R.M., Ovrum E., Ringdal M.A., Oystese R., Hamers M.J., Veiby O.P., Rolfsen T., Stephens R.W., Sakariassen K.S. Induction of monocyte tissue factor procoagulant activity during coronary artery bypass surgery is reduced with heparin-coated extracorporeal circuit. Br J Haematol 1996;94:517-525.[Medline]
  90. Muehrcke D.D., McCarthy P.M., Kottke Merchant K., Harasaki H., Pierre Yared J., Borsh J.A., Ogella D.A., Cosgrove D.M. Biocompatibility of heparin-coated extracorporeal bypass circuits: a randomized, masked clinical trial. J Thorac Cardiovasc Surg 1996;112:472-483.[Abstract/Free Full Text]
  91. Ovrum E., Holen E.A., Tangen G., Brosstad F., Abdelnoor M., Ringdal M.A., Oystese R., Istad R. Completely heparinized cardiopulmonary bypass and reduced systemic heparin: clinical and hemostatic effects. Ann Thorac Surg 1995;60:365-371.[Abstract/Free Full Text]
Received January 30, 1999; received in revised form May 24, 1999; accepted May 26, 1999.




This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
J. Chanard, S. Lavaud, H. Maheut, I. Kazes, F. Vitry, and P. Rieu
The clinical evaluation of low-dose heparin in haemodialysis: a prospective study using the heparin-coated AN69 ST membrane
Nephrol. Dial. Transplant., June 1, 2008; 23(6): 2003 - 2009.
[Abstract] [Full Text] [PDF]

Home page
 PerfusionHome page
R Miraziz, L Hines, M Brouwer, R Steel, and P Klineberg
Bridging circuit for the resection of retroperitoneal sarcoma involving the aorta and the IVC - veno-venous to veno-arterial perfusion
Perfusion, January 1, 2008; 23(1): 65 - 69.
[Abstract] [PDF]

Home page
 Card Surg AdultHome page
J. W. Hammon
Extracorporeal Circulation: The Response of Humoral and Cellular Elements of Blood to Extracorporeal Circulation
Card. Surg. Adult, January 1, 2008; 3(2008): 370 - 389.
[Full Text]

Home page
 PerfusionHome page
S. Gunaydin, K. Ayrancioglu, E. Dikmen, K. Mccusker, V. Vijay, T. Sari, T. Tezcaner, and Y. Zorlutuna
Clinical effects of leukofiltration and surface modification on post-cardiopulmonary bypass atrial fibrillation in different risk cohorts
Perfusion, July 1, 2007; 22(4): 279 - 288.
[Abstract] [PDF]

Home page
 Nephrol Dial TransplantHome page
J. Chanard, S. Lavaud, and P. Rieu
Anticoagulation in haemodialysis.
Nephrol. Dial. Transplant., December 1, 2006; 21(12): 3600 - 3601.
[Full Text] [PDF]

Home page
 CirculationHome page
J. Seeburger, J. Hoffmann, H. P. Wendel, G. Ziemer, and H. Aebert
Gene Expression Changes in Leukocytes During Cardiopulmonary Bypass Are Dependent on Circuit Coating
Circulation, August 30, 2005; 112(9_suppl): I-224 - I-228.
[Abstract] [Full Text] [PDF]

Home page
 Journal of Bioactive and Compatible PolymersHome page
X. Yu, A. Bichtelen, X. Wang, Y. Yan, F. Lin, Z. Xiong, R. Wu, R. Zhang, and Q. Lu
Collagen/Chitosan/Heparin Complex with Improved Biocompatibility for Hepatic Tissue Engineering
Journal of Bioactive and Compatible Polymers, January 1, 2005; 20(1): 15 - 28.
[Abstract] [PDF]