Heparin-coated Cardiopulmonary Bypass Research Articles

Haemostasis at Low Heparin Dosage During Cardiopulmonary Bypass with Heparin-coated Circuits in Pigs

Cardiopulmonary bypass (CPB) causes activation of cascade systems. Although heparin coating of CPB circuits improves biocompatibility, the effects on coagulation remain controversial. Theoretically, heparin coating should permit the reduction of systemic anticoagulation during CPB. We investigated influences on haemostatic variables in animal CPB, comparing heparin-coated circuits and reduced systemic heparinization (group HC) with uncoated circuits and full heparinization (group C). Twenty pigs underwent 2-h CPB. Seven (HC, n = 4; C, n = 3) were weaned from CPB and studied for up to 4 h. Total administered heparin was 470 ± 6 IU/kg (mean ± SEM) in group C and 100 ± 0 IU/kg in group HC. Protamine dosage was significantly reduced in group HC. In group C, levels of prothrombin complex, factor VIII and adhesive platelets were reduced significantly during CPB, and postoperatively there were significantly lower values of prothrombin complex, fibrinogen, antithrombin III, factor VIII and adhesive platelets but a significantly increased concentration of von Willebrand factor and cumulative bleeding after 4 h. In conclusion, heparin-coated CPB circuits combined with lowered heparin dosage reduced coagulation factor consumption and preserved platelet function, possibly contributing to improved postoperative haemostasis.

Case 5—1996 thrombosis after the use of a heparin-coated cardiopulmonary bypass circuit in a patient with heparin-induced thrombocytopenia

A 64-year-old, 165-cm, 58-kg woman was admitted to the hospital with an inferior myocardial infarction. She underwent an emergent percutaneous transluminal coronary angioplasty (PTCA) complicated by an early reocclusion necessitating a second PTCA. The second PTCA complicated itself by the dissection of the right coronary artery (RCA), necessitating the placement of four stents in the RCA. The patient was then treated with porcine heparin (H) for 7 days. Warfarin was progressively titrated to a prothrombin time of 23% (international normalized ratio = 3.8), and heparin was then stopped. After 3 days of effectwe warfarin treatment, she suddenly developed cardiogenic shock with third-degree atrioventricular block, necessitating resuscitation maneuvers, intubation, placement of an intra-aortic balloon pump, and a pacemaker. After this resuscitation, she recovered well except for a right hemiparesis that was attributed to a prolonged hypotensive state. Coronary angiography disclosed a reocclusion of the RCA. Fibrinolytic therapy was then administered, and a continuous infusion of heparin was reintroduced. Forty-eight hours after her ischemic event, a cerebral computed tomography (CT) scan was normal, and she had no neurologic sequelae. Nine days later, despite receiving a continuous infusion of heparin, she became ischemic in the right coronary artery territory, and an emergent coronary revascularization was planned. While evaluating the patient's files, the attending anesthesiologist found that the platelet level was below 35,000/mm 3 from the beginning of the second heparin administration 10 days earlier (Fig 1), and he suspected a syndrome of heparin-induced thrombocytopenia (HIT). Because of the presence of four stents in the patient's RCA and owing to her history of the repetitive coronary occlusions, the cardiologists refused to stop the heparin infusion. This infusion was therefore stopped in the operating room. A central venous catheter was already in place, a radial arterial catheter was then placed under local anesthesia, and both were flushed with 0.9% saline without heparin. Anesthesia was induced with etomidate and sufentanil, and muscle paralysis achieved with pancuronium. Anesthesia was maintained with midazolam, and a continuous infusion of sufentanil, 2 Ixg/kg/hr. Iloprost is not available in Belgium; neither are the heparin substitutes proposed in the literature. The anesthesiologist had no experience with the use of low-molecularweight heparin (LMWH) during bypass. Therefore, he elected to use a heparin-coated cardiopulmonary bypass (CPB) circuit (HC-CPB) (Durafio II; Bentley [Englewood, CO], because of its theoretical advantages of biocompatibility and protection of platelets against activation caused by contact with the artificial surfaces. Only 50 IU/kg of porcine heparin were administered in place of the usual 300 IU/kg. Two saphenous grafts were sutured on the RCA. The procedure was performed under normothermia and intermittent antegrade warm blood cardioplegia. Aortic crossclamp time was 34 minutes, and CPB lasted 55 minutes. No pharmacologic support was needed to come off bypass. The platelet level was 34,000/mm 3 before surgery and 39,000/mm 3 after 50 IU/kg of H. It decreased to 22,000/ mm 3 after 7 minutes of CPB, possibly because of hemodilution, and returned to 39,000/mm 3 after discontinuation of CPB. Activated coagulation times with kaolin (ACT) (Hemotec; Medtronic [Uden, The Netherlands]) were 151 seconds before heparin administration, 231 seconds after 50 IU/kg of H, 445 and 443 seconds during CPB, and 295 seconds after CPB. Only 10 mg (2,000 IU) of protamine were then administered, and ACT returned to 148 seconds (Fig 2). After administration of another 1,000 IU of protamine, the ACT was 82 seconds. Despite this, the patient was still bleeding actwely. It was then judged that no more heparin was circulating at that time, and it was decided that it would

Centrifugal pump and heparin coating improves cardiopulmonary bypass biocompatibility

Centrifugal pumps are being used increasingly for short-term extracorporeal circulation purposes such as during heart operations. Whether the centrifugal pump improves the cardiopulmonary bypass biocompatibility has not been fully documented. A roller pump (n = 20) was compared in vivo with a centrifugal pump (n = 20) in groups of patients in which cardiopulmonary bypass circuits that were either totally heparin coated (Carmeda BioActive Surface; n = 20) or uncoated (n = 20) were used. We expected the heparin coating to attenuate blood activation, thus possibly making the comparison of the two pumps easier with respect to their different blood activation potentials. Samples of blood plasma, obtained during cardiopulmonary bypass from low-risk coronary artery bypass grafting patients, were analyzed for hemolysis (plasma haemoglobin), complement activation (C3bc and the terminal complement complex), a complement lytic inhibitor (vitronectin), coagulation activation (fibrinopeptide A), granulocyte activation (lactoferrin), and platelet activation (beta-thromboglobulin). The concentrations of terminal complement complex, lactoferrin, and beta-thromboglobulin were significantly lower in association with heparin-coated surfaces. The concentration of plasma hemoglobin was significantly lower in association with the centrifugal pump. In uncoated circuits, the beta-thromboglobulin level was significantly higher in association with the roller pump than with the centrifugal pump, but this significant reduction in the beta-thromboglobulin level did not hold true for the heparin-coated circuit group. A heparin-coated cardiopulmonary bypass surface reduces the blood activation potential during cardiopulmonary bypass, and the centrifugal pump causes less hemolysis than the roller pump.

Biocompatibility of heparin-coated extracorporeal bypass circuits: A randomized, masked clinical trial

Cardiopulmonary bypass circuits cause morbidity during cardiac operations. Plasma proteins and cellular components are stimulated by contact with the cardiopulmonary bypass circuit and can cause bleeding and postperfusion syndrome. This is especially true in patients undergoing reoperative cardiac procedures, which carries a higher risk of postoperative bleeding and prolonged ventilation compared with primary cardiac surgical procedures. Recently, cardiopulmonary bypass circuit surfaces have been coated with antithrombotic agents to improve their biocompatibility. This study evaluated the effect of a heparin-coated cardiopulmonary bypass system (Duraflo II, Baxter Bentley Healthcare Systems, Irvine, Calif.) on thrombin formation, platelet stimulation, and leukocyte activation in patients undergoing reoperative coronary artery bypass grafting or valve operation. Fifty patients were selected and randomly assigned to a standard noncoated control system ( n = 26) or the Duraflo heparin-coated system ( n = 24). Similar heparin doses were used in both groups (3 mg/kg). The heparin-coated group used a completely heparin-coated bypass circuit including the cardiotomy reservoir; arterial filters were heparin-coated in both groups. Samples were obtained before cardiopulmonary bypass, 30 minutes into cardiopulmonary bypass, 5 minutes after crossclamp removal, and 5 minutes after protamine administration. Thrombin formation (thrombin-antithrombin III by enzyme-linked immunosorbent assays) and platelet activation (β-thromboglobulin by enzyme-linked immunosorbent assays; P-selectin expression by flow cytometry) were assayed. Leukocyte activation was determined by quantitative and qualitative analysis of arterial filters by scanning electron microscopy in six patients from each group. In both circuits, thrombin values increased markedly 30 minutes into cardiopulmonary bypass compared with baseline values ( p < 0.001) (heparin-coated, 7 ± 5 to 96 ± 115 ng/ml; noncoated, 10 ± 9 to 115 ± 125 ng/ml). Platelet activation as measured by β-thromboglobulin (heparin-coated, 104 ± 100 to 284 ± 166 IU/ml; noncoated, 81 ± 74 to 288 ± 277 IU/ml) and P-selectin expression (heparin-coated, 1.5% ± 1.5% to 6.4% ± 6.1%; noncoated, 1.4% ± 1.1% to 6.2% ± 4.3%) also significantly increased 30 minutes into cardiopulmonary bypass compared with baseline values ( p < 0.001). Platelet activation and thrombin generation did not differ between the two circuits at any time. Granulocyte activation and platelet deposition did not differ between the two circuits when arterial filters were evaluated. Both groups had similar heparin and protamine administration, blood transfusions, postoperative alveolar-arterial oxygen gradient, time to extubation, length of intensive care unit stay, and overall morbidity and mortality. Clinical outcome and blood loss did not differ between the groups. We conclude that heparin-coated cardiopulmonary bypass circuits did not improve biochemical or clinical markers of biocompatibility in a reoperative patient population. (J T horac C ardiovasc S urg 1996;112:472-83)

Changes in Platelet, Granulocyte, and Complement Activation During Cardiopulmonary Bypass Using Heparin‐coated Equipment

The effects of heparin-coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin-coated (Carmeda Bio-Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin-coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 +/- 632 ng/ml) and C4a (1088 +/- 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 +/- 1045 ng/ml and 1494 +/- 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 +/- 177 micrograms/L) and 10 min after the administration of protamine (676 +/- 314 micrograms/L) were significantly (p < 0.05) lower than in the other 2 groups (820 +/- 341 and 893 +/- 303 micrograms/L and 1365 +/- 595 and 1,258 +/- 622 micrograms/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma beta-thromboglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin-coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin-coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.

Perioperative course and recovery after heparin-coated cardiopulmonary bypass: Low-dose versus high-dose heparin management

Objective: To compare two heparin managements for a cardiopulmonary bypass (CPB) procedure with heparin-coated equipment. The hypothesis was that a lower heparin dose may reduce blood loss and homologous transfusion requirements and influence the speed of postoperative recovery. Design: Prospective, randomized, and open study. Setting: Operating room and intensive care unit in a university hospital. Participants: Twenty-four patients undergoing first-time elective coronary artery surgery. Interventions: Heparin-coated CPB equipment (Duraflo II; Baxter-Bentley) was used in all patients. The study group ( n = 12) received low-dose (100 IU/kg IV and 0 to 1,000 IU/L priming; target level of activated coagulation time [ACT] over 180 seconds during CPB; suction in a red cell washing device); and the control group ( n = 12) received high-dose (300 IU/kg IV and 5,000 IU/L priming; ACT over 480 seconds; standard cardiotomy suction) heparin management. Measurements and Main Results: ACT remained above 200 seconds after the initial heparin dose in the study group for the CPB duration up to 99 minutes. In 11 of 12 patients in the control group, additional heparin was required during CPB. Total doses of heparin and protamine (mean 8,017 v 50,508 IU and 83 v 325 mg, respectively; p < 0.0001), volume of homologous blood transfusion (median 600 v 1450 mL; p < 0.025), and blood products exposure (median 0.5 v 5.0 units/patient; p < 0.05) were significantly lower in the study group. Postoperative chest drainage showed a trend to lower volume loss (median 705 v 930 mL; p < 0.08) in patients managed with low-dose heparin. Oxygenator resistance during CPB, perioperative laboratory analyses (oxygen and metabolic data, hematocrit, platelet count, prothrombin, thrombin, activated partial thromboplastin time, fibrinogen, D-dimers, creatine kinase, and myocardial band of creatine kinase concentration), fluid balance, and the time periods required for extubation, stay in the intensive care unit, and hospital discharge were not different between the groups. There were no evidences of myocardial infarction in any of 24 patients, and all recovered after the procedure. Conclusion: Low-dose heparin management enabled uneventful procedures with heparin-coated CPB equipment, significantly decreased protamine and homologous blood requirements, but did not reduce chest drainage or influence the postoperative course and recovery in patients after coronary artery surgery.

Heparin-bonded surfaces in extracorporeal membrane oxygenation for cardiac support

Development of increasingly complex perfusion devices with bonded heparin allowed for significant improvement of thromboresistance of most basic components required for cardiopulmonary bypass. In his recent review of heparin-coated cardiopulmonary bypass circuits, Gravlee cited 91 references dealing with heparin-coated surfaces, and far more can be found if the search includes material technology or heparin-coated devices not designed for cardiopulmonary bypass (eg, ventricular assist devices, hemofilters, catheters). The present review is focused on long-term application of heparin-coated equipment in conjunction with basic work on heparin bonding relevant for extracorporeal membrane oxygenation. Experimental open chest cardiopulmonary bypass using heparin-coated equipment without systemic heparinization up to 36 hours has shown improved thromboresistance, and better platelet preservation was demonstrated for perfusion with heparin-coated cardiopulmonary bypass equipment up to 5 days in the experimental set-up. Similar findings were reported for roller pump perfusion with heparin-coated tubing and centrifugal pump perfusion with heparin-coated pump heads. More recently, heparin bonding was also made available for oxygenators with true membranes that preclude plasma leakage. The available knowledge on clinical applications of heparin-coated perfusion equipment is mainly based on short-term applications like ours, which now includes more than 300 patients. Reduced postoperative blood loss and as a result fewer transfusions were the main benefits of heparin-coated equipment allowing for perfusion with low systemic heparinization. There are only a few reports on long-term use of heparin-coated equipment for prolonged circulatory support. However, the longest clinical application of a single device is that of an intravascular gas exchanger that remained fully functional during a 29-day implantation period. Finally, it appears, that circulating protamine interacts with surface-bound heparin. Protamine administration should therefore be avoided during perfusion with heparin-bonded equipment to maintain the improved thromboresistance.

The evaluation of the clinical usefulness of heparin-coated cardiopulmonary bypass circuits

The evaluation of the clinical usefulness of heparin-coated cardiopulmonary bypass circuits

左心膜破裂を伴った外傷性大動脈解離の１例

We report the case of a 64-year-old housewife with a diagnosis of acute traumatic aortic dissection associated with left pericardial rupture. The patient suffered multiple left rib fractures, a right wrist fracture, fracture of the right ankle and open fracture of the left ankle. She was transferred to our hospital complaining of severe back pain and increasing blueness of the right leg, which suggested cyanosis due to advancing dissection of the aorta. Enhanced CT and intra-arterial DSA confirmed dissection of the descending aorta from the distal portion of the left subclavian artery to the right iliac artery. Standard left thoracotomy revealed pulsatile patent ductus arteriosus (PDA) and traumatic rupture of the left pericardium. The PDA was divided first. Because of the multiple injuries, a heparin-coated cardiopulmonary bypass system was used to reduce the dose of heparin. Dissection was noted around the proximal descending aorta, with the point of entry observed above and below the PDA. This finding supports the observation that traumatic rupture of the thoracic aorta occurs most frequently in the area of the ligamentum arteriosum, because the aorta is fixed at that point. The descending aorta was successfully replaced with an artificial vascular graft. Three traumatic dissections have been reported, including our case, in Japan. In our patient surgery was performed 10 hours after the injury. This may represent the earliest operative treatment of traumatic aortic dissection in Japan thus far.

High and low heparin dose with heparin-coated cardiopulmonary bypass: Activation of complement and granulocytes

Cardiopulmonary bypass with heparin-coated circuits allows reduced amounts of systemic heparin. Heparin inhibits activation of the complement cascade experimentally, but the effects of different levels of systemic heparin on activation of complement and granulocytes in patients have remained unknown. Fifty-two patients undergoing coronary artery bypass procedures were studied. Cardiopulmonary bypass circuits completely coated with surface-bound heparin were used for one group given low-dose heparin (n = 17) (activated clotting time > 250 seconds), and was compared with a second group having normal high-dose heparin (activated clotting time > 480 seconds) (n = 18). A third control group was perfused with ordinary uncoated circuits and a full heparin dose (n = 17). During cardiopulmonary bypass, the C3 activation products C3b, iC3b, and C3c increased markedly in all three groups compared with baseline, but significantly less in the two heparin-coated groups (high dose, median maximal increase 58 arbitrary units (AU)/mL; low dose, 48 AU/mL) compared with the uncoated control group (74 AU/mL) (p < 0.01). The difference between the two coated groups was not significant. Similarly, the maximal increase in terminal SC5b-9 complement complex was considerably lower in the heparin-coated groups (high dose, 2.5 AU/mL; low dose, 2.6 AU/mL) compared with the level observed in the uncoated control group (5.3 AU/mL) (p < 0.01). The release of the granulocyte activation enzymes myeloperoxidase and lactoferrin increased from the beginning of the operation, with peak levels at the end of cardiopulmonary bypass (p < 0.01). The concentration of lactoferrin was significantly (p < 0.01) reduced in the low heparin dose group compared with the two other groups receiving normal high heparin doses, indicating that circulating heparin is an important granulocyte agonist, acting independently of the presence or absence of heparin-coated surfaces. Also for myeloperoxidase a higher level was observed in the high heparin dose group. Complement activation was significantly reduced in both heparin-coated groups and was independent of the level of systemic heparinization, whereas granulocyte activation was reduced only in patients who received low doses of systemically administered heparin. The results indicate that a moderate reduction of the systemic heparin dose may be an advantage with regard to improved biocompatibility when using heparin-coated cardiopulmonary bypass circuits.

Effects on Coagulation and Fibrinolysis With Reduced Versus Full Systemic Heparinization and Heparin-Coated Cardiopulmonary Bypass

Extracorporeal circulation with circuits coated with surface-bound heparin has allowed reduced levels of systemic heparinization. Clinical benefits have included reduced postoperative bleeding and less homologous blood usage. However, the effects on the hemostatic and fibrinolytic systems have remained in part unknown. Indications of thrombin generation, platelet activation, and fibrinolytic activity were investigated in patients undergoing coronary artery bypass surgery. Two groups were perfused with cardiopulmonary bypass (CPB) circuits completely coated with surface-bound heparin: one group with low systemic heparin dose (activated clotting time [ACT] > 250 seconds; n = 17) and a second group having a full heparin dose (ACT > 480 seconds; n = 18). A third control group was perfused with ordinary uncoated circuits and full heparin dose (n = 17). The plasma level of thrombin-antithrombin complex and prothrombin fragment 1.2 increased in all groups during bypass, and somewhat more in both the heparin-coated groups toward the end of CPB, compared with the control group (P < .01). However, the increase during CPB was minimal compared with the major elevation observed 2 hours after surgery in all groups. Platelet release of beta-thromboglobulin increased in all groups (P < .01) during CPB and significantly more in the high-dose group compared with the other two groups (P = .03). Fibrinolytic activities were similar in all groups, and there were no indications of major consumption of coagulation factors. Reduced systemic heparinization (ACT > 250 seconds) in patients having extracorporeal circulation with completely heparin-coated circuits did not lead to increased thrombogenicity. Thrombin formation remained within low ranges during CPB compared with patients receiving a full heparin dose and with the major elevations observed after surgery.

Disparity in blood activation by two different heparin-coated cardiopulmonary bypass systems

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

Reduction of the inflammatory response and renal tubular injury by heparin-coated cardiopulmonary bypass circuits

Different platelet preparation techniques have not previously been compared directly and simultaneously with respect to in vivo platelet viability. Using a dual-label technique with 111In and 114mIn, platelet apheresis was compared with the platelet-rich plasma (PRP) procedure with respect to platelet recovery and survival (n=4). Furthermore, a continuous flow cell separator (Cobe 2997) and an intermittent apheresis system (Haemonetics V50) were compared with each other (n=4). No differences in platelet viability were found between the PRP-platelets and the apheresis-platelets. Also no differences were found between the two apheresis systems. Although different platelet preparation methods result in a varying degree of platelet activation, no difference in platelet viability has been observed.

Completely heparinized cardiopulmonary bypass and reduced systemic heparin: Clinical and hemostatic effects

When heparinized circuits are used for cardiopulmonary bypass, the amounts of heparin and protamine administered systemically can be reduced. However, it is not entirely known what effects this reduction in systemic anticoagulation has on clinical performance and on the coagulation and fibrinolytic systems. Two hundred three patients undergoing first-time elective myocardial revascularization were prospectively randomized either to a group in which a completely heparin-coated circuit was used for perfusion (group H; n = 101 patients) and in which a reduced heparin dose was given (activated clotting time, > 250 seconds) or to a control group (group C; n = 102 patients) in which an uncoated, but otherwise identical, circuit was used and in which full systemic heparinization was induced (activated clotting time, > 480 seconds). Indicators of thrombin generation, platelet activation, and fibrinolytic activity were studied in a subset of 34 patients. The total amount of postoperative mediastinal drainage was significantly reduced in group H (median, 575 mL) compared with that in group C (median, 635 mL; p = 0.002). Two patients in group C but none in group H received homologous red blood cell transfusions (p = not significant). The loss of hemoglobin in group H was a median of 21 g/L, and this was significantly lower than the 25 g/L noted in the control group (p = 0.006). During cardiopulmonary bypass, the plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 increased in both groups. At the end of cardiopulmonary bypass the plasma levels of these markers of thrombin formation were significantly higher in group H, although the increase was modest compared with the major increase observed 2 hours after operation in both groups. There were no significant intergroup differences in the platelet counts, the concentration of beta-thromboglobulin, or the plasma levels of fibrinogen and D-dimer. No differences in perioperative morbidity, the postoperative kidney function, or the intubation time were observed, and there were no hospital deaths. The combination of complete heparin-coated cardiopulmonary bypass circuits and low systemic heparinization is safe for patients undergoing elective coronary artery bypass procedures and reduces the perioperative blood loss. There was no evidence of increased thrombogenicity, fibrinolytic activity, or consumption of coagulation factors. No clinical or technical side effects were observed.

Haemocompatibility of a Heparin-Coated Cardiopulmonary Bypass Circuit: A Prospective Randomised Trial

Haemocompatibility of a Heparin-Coated Cardiopulmonary Bypass Circuit: A Prospective Randomised Trial

Perfusion Techniques for Heparin-Bonded Circuits

Recent advances in cardiopulmonary bypass techniques include the development of durable, covalently bonded heparin coated surfaces using end-point attachment techniques. Advantages of heparin-coated cardiopulmonary bypass include reduced systemic heparin, avoidance of protamine sulfate at the completion of the procedure, enhanced biocompatibility of the circuit, successful application of cardiopulmonary bypass in cases where bleeding may become a problem, and in application of assist devices. Our experience with this technology has led to the development of guidelines and management strategies. We generally consider application fortwo categories: 1) pharmacotoxicity, i.e., allergic reaction to heparin or protamine; and 2) progression of problems, such as prolonged bleeding tendencies (aspirin) or hemorrhage from cerebral vascular accident. Applications of this technology require tip to tip heparin-bonding, "streamlining" the circuit, meticulous attention to fluid mechanics, crystalloid cardioplegia, precise heparin management, and reversed Trendelenburg position for post-cardiopulmonary bypass volume.

Eosinophil granule proteins in cardiopulmonary bypass with and without heparin coating

Extracorporeal circulation with exposure of blood to foreign surfaces causes activation of different defense systems, eg, white cells. Several potent mediators are released into plasma, capable of causing harmful effects to different organs, contributing to postoperative morbidity after operations using cardiopulmonary bypass. The eosinophil granulocyte has not previously been investigated in this respect. We studied two of its activation products, eosinophil cationic protein and eosinophil protein X in coronary bypass patients. In 17 control patients, plasma levels of eosinophil cationic protein and eosinophil protein X increased considerably during cardiopulmonary bypass. In 19 patients with heparin-coated cardiopulmonary bypass equipment the levels were significantly reduced, indicating improved biocompatibility of the cardiopulmonary bypass circuit. The heparin-coated surface causes less activation of eosinophils; also released eosinophil cationic protein is bound to the heparinized surface.

Heparin-coated cardiopulmonary bypass circuits: Hemostatic alterations and postoperative blood loss

This prospective, randomized study involving patients undergoing isolated coronary artery bypass grafting investigated whether the use of heparin-coated bypass circuits with an uncoated cardiotomy reservoir (n = 10) compared with standard uncoated bypass circuits (n = 10) resulted in differences in patient outcome and hemostatic alterations. There were no differences in postoperative blood loss, transfusion requirements, and routine coagulation test results between groups. Immunoassays for platelet alpha-granule constituents platelet factor 4 and beta-thromboglobulin, thrombin generation byproduct F1.2, fibrinopeptide A, thrombin-antithrombin complex, and fibrinolysis by-product d-dimer also demonstrated no significant differences between groups, although trends for lower platelet secretion with heparin coating were noted. Increases were found in betathromboglobulin and platelet factor 4 concentrations at 10 ( p < 0.03) and 30 minutes ( p < 0.001) of CPB, respec tively, and continuing throughout CPB ( p < 0.001) for both groups versus values measured before incision. No significant differences were seen between levels 5 minutes prior to aortic cross-clamp release and those obtained 8 and 45 minutes after cross-clamp release. Conversely, no significant increases in F1.2, thrombin-antithrombin complex, and d-dimer were seen prior to release of the aortic cross-clamp, but afterward increases occurred that were highly significant ( p < 0.001). The temporal data suggest that platelet activation occurs primarily as a result of contact with the cardiopulmonary bypass circuitry, whereas thrombin generation and fibrinolytic activity are not significant until reperfusion of the heart and lungs. This latter effect may be due to reperfusion injury, humoral mediators generated by blood—biomaterial contact, or rewarming and increased use of cardiotomy suction and return of shed mediastinal blood.

Reduced complement and granulocyte activation with heparin-coated cardiopulmonary bypass

Plasma concentrations of the complement activation products C3b, iC3b, and C3c; the terminal C5b-9 complement complex; and the granulocyte proteins calprotectin, myeloperoxidase, and lactoferrin were assessed in two groups of patients undergoing aortocoronary bypass procedures. In 10 patients operated on, the bypass circuits were coated by the Canneda Bio-Active Surface and systemic heparinization was reduced to 1.5 mg/kg; in another 10, the systems were uncoated and the dosage of systemic heparinization was 4 mg/kg. In both groups, significant complement activation was observed after the onset of cardiopulmonary bypass, but the maximum levels of C3b, iC3b, and C3c and the terminal C5b-9 complement complex were significantly lower in the heparin-coated group. In both groups, a significant increase in calprotectin, myeloperoxidase, and lactoferrin release was observed by the end of operation. The maximum myelopeioxidase levels were significantly lower in the heparin-coated group than those in the uncoated group ( p = 0.03). There was a correlation of borderline significance between the formation of terminal C5b-9 complement complex and lactoferrin release, as well as between the formation of terminal C5b-9 complement complex and myelopeioxidase release ( p = 0.05). The postoperative blood loss did not differ significantly between the two groups. We conclude that coating by end point-attached and functionally active heparin allows a significant reduction in the amount of systemic heparinization, and significantly reduces complement and granulocyte activation.

Safe use of heparin-coated bypass circuits incorporating a pump-oxygenator

Durable, covalently bonded, heparin-coated cardiopulmonary bypass (CPB) circuits with oxygenators have been developed. Proposed advantages of heparin-coated CPB circuits include improved biocompatibility and thromboresistance. The purpose of this study was to evaluate our experience with heparin-coated CPB circuits in 20 patients. Heparin was given to maintain an activated clotting time equal to or greater than 200 seconds, while flow rates were kept equal to or greater than 2 L/min. Indications for use of this circuit included recent stroke, posttraumatic injuries, recent gastrointestinal bleeding, protamine allergies, combined cardiac and noncardiac procedures, and ventricular assist. Mean heparin dosage was 0.50 ± 0.18 mg/kg and protamine dosage was 57.14 ± 39.36 mg. Postoperative blood loss and transfusion requirements were minimal. Postoperative complement levels of C3a and C5a were normal, suggesting excellent biocompatibility. There were no deaths or perioperative complications. Heparin-coated CPB circuits using a pump oxygenator can be used safely with low-dose heparin administration in select patients requiring CPB.