Heparin For Cardiopulmonary Bypass Research Articles

Comparison of Activated Clotting Time to Hepcon Protamine Titration for Anticoagulation Management during Cardiopulmonary Bypass Surgery in a Patient with Severe Hemophilia a on Emicizumab Prophylaxis

Background: Emicizumab is a bispecific monoclonal antibody that bridges factor IXa and X, substituting the cofactor function of FVIII, but artificially shortens aPTT and interferes with aPTT-based assays. The activated whole blood clotting time (ACT) is the preferred point-of-care test to monitor anticoagulation with high-dose heparin in cardiopulmonary bypass (CPB). While theoretically ACT may be susceptible to the effects of emicizumab as the intrinsic pathway is involved, in vitro human clinical data suggest that emicizumab does not interfere with the ACT. There has been little experience managing patients with hemophilia A on emicizumab during CPB, and in most cases it is not feasible to delay surgery to await clearance of emicizumab due its long half-life. Heparin concentration by Hepcon protamine titration is an alternative monitoring method. Case: We describe the perioperative management of a patient with severe hemophilia A on maintenance emicizumab prophylaxis who underwent CPB with high-dose heparin monitored with both ACT and Hepcon. This 54-year-old male has a complex medical profile including Child Pugh B cirrhosis (baseline INR 1.5, platelets 100), Hepatitis C (treated), HIV on antiretroviral therapy (undetectable viral load), and remote portal vein thrombosis in the context of FEIBA and tranexamic acid use for a gastrointestinal bleed. He was diagnosed with Group B Streptococcus infective endocarditis. Despite optimal medical management, he developed aortic root abscess and aortic regurgitation necessitating operative intervention. A multidisciplinary team of hematology, cardiology, and cardiac surgery/anesthesia/intensive care deemed the risk of bleeding significant but not prohibitive and created a perioperative plan with liberal FVIII replacement followed by chromogenic FVIII levels postop (Table 1) to guide dosing. A bioprosthetic valve was chosen to reduce the need for postoperative anticoagulation. Emicizumab prophylaxis was continued. Intra-operative heparin titration was performed by the Hepcon point-of-care assay, but concurrent ACT measurements were taken to investigate the effect of emicizumab. INR, fibrinogen, hemoglobin, and platelet levels were measured as per surgical protocol. Preop FVIII replacement with moroctocog alfa (Xyntha®) (60 U/kg) was administered to target a ~120% FVIII level. Tranexamic acid was administered intraoperatively as per surgical protocol. He underwent a successful aortic valve replacement, bovine patch reconstruction and aortic root repair on CPB pump for a total of 175 minutes with no excessive intraoperative bleeding. Table 1 summarises the perioperative course, point-of-care testing results, hemostatic therapy, and FVIII levels. Following administration of protamine at the end of CPB (ACT 135s, Hepcon 0 U/mL) there was persistent oozing from the sternum which lessened with surgical packing and additional Xyntha®, but ultimately the chest was closed in favour of medical management. Two hours post-op there was ~1600mL of blood loss via chest tubes despite a FVIII level of 89%, platelets 147, and INR 1.7. Fibrinogen concentrate, fresh frozen plasma, and platelets were given prior to a repeat OR for exploration. Bleeding was confirmed from the sternal bone and muscle, and hemostasis was achieved with cautery and sutures. The remainder of the post-op course was uneventful with no further bleeding on emicizumab prophylaxis and FVIII replacement for 14 days. Discussion: The ACT and Hepcon results followed a similar trajectory over the operative course (Fig 1). Baseline and post-protamine ACT results were above normal reference range for non-anticoagulated patients (90-120s), and the intraoperative values were consistently above the target of 480s for CPB even when the Hepcon results fell below target (4.1 U/mL). The ACT results weren't artificially lowered with emicizumab, in fact elevated ACT values could have led to heparin underdosing risking circuit thrombosis. ACT is influenced by multiple variables including platelet count and function, antiphospholipids, factor deficiencies, temperature, and hemodilution. Therefore, the results may reflect derangements in one or more of these variables. We need further preclinical and clinical studies to better characterize the effect of emicizumab on ACT and identify the safest intraoperative monitoring strategy for patients on emicizumab requiring CPB surgery. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Study on the Protective Effect of Platelet Autotransfusion in Cardiopulmonary Bypass

Objective: To study the blood protective effect of platelet autotransfusion in cardiopulmonary bypass. Methods: In this study, 80 patients with cardiopulmonary bypass heart surgery in our hospital from January 2018 to July 2019 were divided into two groups. The control group was not given platelet separation, the study group was given platelet separation after anesthesia induction, platelet rich plasma was extracted before heparinization for cardiopulmonary bypass and heparin was recycled. The blood clotting function, postoperative recovery, blood transfusion volume and postoperative drainage volume were analyzed before operation, 1H, 24h and 48h after operation. Result: Compared with the control group, the volume of blood flow, blood plasma and platelet transfusion in the study group decreased significantly in the first hour after operation, the difference was statistically significant (P < 0.05). The recovery of the study group was slightly better than that of the control group, and the difference was not statistically significant (P > 0.05). Conclusion: Autotransfusion of platelets can alleviate the coagulation function of patients undergoing cardiopulmonary bypass, reduce the amount of postoperative bleeding and allogeneic blood transfusion, and protect the blood.

A comparative analysis of four activated clotting time measurement devices in cardiac surgery with cardiopulmonary bypass

In cardiac surgery on cardiopulmonary bypass (CPB), heparin anticoagulation is monitored by point-of-care measurement of activated clotting time (ACT). The objective of this study was to compare four ACT systems in cardiac surgery in terms of their reproducibility, agreement and potential clinical impact at relevant medical decision points. The study included 40 cardiac surgery patients. Samples were taken at five time points before (T1), after heparinization for CPB (T2, T3, T4), and after heparin reversal (T5). The reproducibility, correlation, and differences in ACT values were assessed with two devices from each of the four ACT systems: Instrumentation Laboratory Hemochron Elite (Hmch), Medtronic HMS Plus (HMS), Abbott i-STAT, and Helena Abrazo. Subrange analyses were performed for low ACT values (results from T1, T5) and high ACT values (results from T2, T3, T4). Within-system analysis showed strong linear correlation between paired measurements (R = 0.968-0.993). However, Hmch showed poorer reproducibility with highest proportion of values that exceed a difference of 10% and highest overall standard error of 74 seconds across the measurement range compared to that of the others (range 39-47 seconds, respectively). For inter-system comparison, using Hmch as reference, ACTs were strongly correlated as follows: HMS (R = 0.938), i-STAT (R = 0.911), and Abrazo (R = 0.911). Agreement analysis in the high ACT range showed HMS tended to have higher ACT values with +11% bias over Hmch, whereas i-STAT (-8% bias) and Abrazo (-13% bias) tended to underestimate. Post-protamine ACT results were dependent on device type where Hmch yielded highest post-protamine ACT (+13% higher than baseline) compared to -16% for HMS, -10% for iSTAT and 0% for Abrazo. Each device had individual reproducibility and biases, which may impact peri-operative heparin management. Careful validation must be undertaken when adopting a different method as decision limits would be affected. Clinicians should also be cautious using ACT as the only indicator for full heparin reversal.

Application of goal-directed therapy for the use of concentrated antithrombin for heparin resistance during cardiac surgery.

The maintenance of anticoagulation in adult patients undergoing cardiopulmonary bypass is dependent upon a number of factors, including heparin concentration and adequate antithrombin activity. Inadequate anticoagulation increases the risk of thrombosis and jeopardizes both vascular and extracorporeal circuit integrity. The purpose of this study was to evaluate a goal-directed approach for the use of antithrombin in patients who were resistant to heparin. Following institutional review board approval, data were obtained from quality improvement records. A goal-directed protocol for antithrombin was established based upon heparin dosing (400 IU kg-1 body weight) and achieving an activated clotting time of ⩾500 seconds prior to cardiopulmonary bypass. Two groups of patients were identified as those receiving antithrombin and those not receiving antithrombin. Outcome measures included activated clotting time values and transfusion rates. Consecutive patients (n = 140) were included in the study with 10 (7.1%) in the antithrombin group. The average antithrombin dose was 1,029.0 ± 164.5 IU and all patients had restoration to the activated clotting time levels. Patients in the antithrombin group were on preoperative heparin therapy (80.0% vs. 24.6%, p = 0.001). Prior to cardiopulmonary bypass the activated clotting time values were lower in the antithrombin group (417.7 ± 56.1 seconds vs. 581.1 ± 169.8 seconds, p = 0.003). Antithrombin patients had a lower heparin sensitivity index (0.55 ± 0.17 vs. 1.05 ± 0.44 seconds heparin-1 IU kg-1, p = 0.001), received more total heparin (961.3 ± 158.5 IU kg-1 vs. 677.5 ± 199.0 IU kg-1, p = 0.001), more cardiopulmonary bypass heparin (22,500 ± 10,300 IU vs. 12,100 ± 13,200 IU, p = 0.016), and more protamine (5.4 ± 1.2 vs. 4.1 ± 1.1 mg kg-1, p = 0.003). The intraoperative transfusion rate was higher in the antithrombin group (70.0% vs. 35.4%, p = 0.035), but no differences were seen postoperatively. Utilization of a goal-directed algorithm for the administration of antithrombin for the treatment of heparin resistance is effective in patients undergoing cardiac surgery.

Idarucizumab for the Reversal of Dabigatran in Patients Undergoing Heart Transplantation

Purpose Atrial fibrillation is common among patients listed for HTx. NOACs offer several advantages over VKAs. However, in case of HTx surgery an immediate normalization of coagulation is required. Idarucizumab is a monoclonal antibody fragment that was developed to neutralize the activity of the direct thrombin inhibitor dabigatran. Although RE-VERSE AD included 202 patients requiring emergent procedures, there have been only 2 reports of idarucizumab use in heart transplant surgery to date. Methods At time of listing, patients requiring anticoagulation because of non-valvular atrial fibrillation, CHA2DS2VASc 2 and without LVAD or end-stage renal failure, were started on or switched to dabigatran. Upon availability of a donor organ, dabigatran was neutralized with 5 g of intravenous idarucizumab, immediately prior to induction of anaesthesia. Results Dabigatran concentration and aPTT after idarucizumab are represented in Figure 1. During surgery, patients received on average 1.0 unit of packed cell transfusion, 4.1 units fresh frozen plasma, 0.9 pools platelets and 587 mL blood that was recovered via cell salvage. Two patients needed re-intervention because. No adverse reactions or unexpected events that could potentially be related to idarucizumab administration were noted. There were no thrombotic complications. Conclusion This is the largest report describing the use of idarucizumab to normalize coagulation in patients on dabigatran awaiting HTx. Administration of idarucizumab led to a sustained and complete biochemical reversal, without thrombotic complications, and without interfering with heparinization for cardiopulmonary bypass. In conclusion, the availability of an immediately-acting complete reversal agent makes dabigatran an attractive choice for non-VAD patients with non-valvular atrial fibrillation who are listed for heart transplantation.

Literature review of apheresis procedures performed perioperatively in cardiac surgery for ASFA category indications.

Perioperative therapeutic plasma exchange in patients with cardiovascular diseases poses several challenges, including alterations in intravascular volume, serum electrolytes, the coagulation cascade, and drug pharmacokinetics. This review article summarizes different indications of plasma exchange for patients requiring cardiac surgery based on reported case reports and case series. The most common reported indication is plasma exchange for the management of allosensitized cardiac transplant candidate patients in combination with immunosuppressive regimens, which increases the likelihood of obtaining a cross-match-negative allograft, improving post-transplant clinical outcome. The second most common indication is for patients with a history of heparin-induced thrombocytopenia syndrome that permits the use of heparin in cardiopulmonary bypass in an urgent cardiac surgery. Less common indications are restoration of clotting factors for patients with congenital bleeding disorders or removal of cold agglutinins. No severe complications were described in reported cases. Therapeutic plasma exchange is an effective and safe procedure that could be performed preoperatively and intraoperatively in urgent cardiac surgery for the management of antibody-mediated disorders including allosensitized cardiac transplant candidate patients or patients with heparin-induced thrombocytopenia syndrome.

Measurement of Activated Coagulation Time in Children: Evaluation of the Blood-Saving Kaolin i-STAT Activated Coagulation Time Technique in Pediatric Cardiac Anesthesia

To compare the activated coagulation times (ACTs) measured with the blood-saving kaolin i-STAT 1 ACT technique (Abbott Point of Care Inc, Princeton, NJ) with ACTs obtained from the widely used ACTR II device (Medtronic, Inc, Minneapolis, MN) in children undergoing cardiac surgery. A prospective, observational single-center study. Forty-four pediatric cardiac surgery patients. Surgery was performed with cardiopulmonary bypass (CPB) necessitating heparinization. ACTs measured on the i-STAT 1 device (2 × 95 μL) were compared with those obtained from the Medtronic ACTR II device (2 × 0.5 mL). Blood samples were drawn before, during, and after heparinization for CPB and paired for statistical analysis. The 2 techniques were compared using simple and multiregression analyses and the Bland-Altman method. In total, 179 intrarater and 142 interrater data pairs were analyzed. The intrarater reliability of the 2 devices was good, with a mean bias and limits of agreement of +2.0 and -55.5/+59.5 seconds for the Medtronic ACTR II and +0.5 and -59.9/+60.9 seconds for the i-STAT 1. An interrater reliability analysis of the mean of simultaneously measured ACT of the Medtronic ACTR II and both i-STAT 1 devices yielded a mean bias of -5.3 seconds and limits of agreement of -210.1/+199.5 seconds. A comparison of the higher of the paired ACT values from both devices showed similar results. After the removal of heparin, the i-STAT 1's ACT values became significantly lower than those measured on the Medtronic ACTR II (p < 0.001). Simple and multiregression analyses revealed that base excess independently influenced the mean bias of the ACT values from the Medtronic ACTR II (p = 0.037) and i-STAT 1 devices (p = 0.036). The kaolin i-STAT 1 ACT technique agreed well with the Medtronic ACTR II technique during the nonheparinized phase that preceded CPB. The overall agreement between the ACT obtained from the 2 devices was poor. The routine use of i-STAT 1 measured ACT values cannot be recommended as a reliable alternative to the Medtronic ACTR II.

Pharmacodynamic and Efficacy Profile of TGN 255, a Novel Direct Thrombin Inhibitor, in Canine Cardiopulmonary Bypass and Simulated Mitral Valve Repair

Heparin-induced thrombocytopenia can be a life-threatening sequel to conventional use of unfractionated heparin in cardiopulmonary bypass (CPB). This study evaluated the pharmacokinetic/pharmacodynamic (PK/PD) and efficacy profile of a novel direct thrombin inhibitor, TGN 255, during cardiac surgery in dogs. Point-of-care coagulation monitoring was also compared against the plasma concentrations of TRI 50c, the active metabolite of TGN 255. The study was conducted in three phases using 10 animals: phase 1 was a dose-ranging study in conscious animals (n = 6), phase 2 was a similar but terminal dose-ranging study in dogs undergoing CPB (n = 6), and phase 3 was with animals undergoing simulated mitral valve repair (terminal) using optimal TGN 255 dose regimens derived from phases I and II (n = 4). During the study, PD markers and drug plasma levels were determined. In addition, determinations of hematologic markers and blood loss were undertaken. Phase 1 studies showed that a high-dose regimen of a 5-mg/kg bolus and infusion of 20 mg/kg/h elevated PD markers in conscious animals, at which time there were no measured effects on platelet or red blood cell counts, and the mean plasma concentration of TRI 50C was 20.6 fg/mL. In the phase 2 CPB dose-ranging study, this dosing regimen significantly elevated all the PD markers and produced hemorrhagic and paradoxical thrombogenic effects. In the phase 3 surgical study, a lower TGN 255 dose regimen of a 2.5-mg/kg bolus plus 10 mg/kg/h produced anticoagulation, elevated PD markers, and produced minimal post-operative blood loss in the animals. Plasma levels of TRI 50C trended well with the conventional point-of-care coagulation monitoring. TGN 255 provided effective anticoagulation in a canine CPB procedure, enabling successful completion with minimal blood loss. These findings support further evaluation of TGN 255 as an anticoagulant for CPB.

Lower dose of heparin for cardiopulmonary bypass is not necessarily associated with lower drainage loss

Lower dose of heparin for cardiopulmonary bypass is not necessarily associated with lower drainage loss

Heparinless cardiopulmonary bypass with argatroban in dogs.

Systemic heparinization is usually required for cardiopulmonary bypass (CPB). However, problems such as heparin-induced thrombocytopenia, protamine shock, and antithrombin III deficiency exist related to CPB with heparinization. The aim of this study was to evaluate argatroban (ARG) as a substitute for heparin during CPB. In the pilot study, blood samples were sequentially obtained from dogs with continuous infusion of ARG at a dose of 10 (n = 6), 20 (n = 6), or 30 (n = 6) microg/kg per min for 2 h without CPB. In the main study, dogs underwent CPB for 2 h with 10 (n = 6) or 30 (n = 6) microg/kg per min of ARG or with heparin with blood samples obtained sequentially. Thrombogenicity in each group was evaluated by observation of the blood-contacting surfaces of the CPB circuits with scanning electron microscopy (SEM). Evidence of thromboembolism in the dogs was also investigated in histological specimens of the kidney and spleen in addition to microscopic observation at autopsy. In the pilot study, the activated coagulation time (ACT) reached a maximum level dose-dependently after continuous infusion of ARG for 30 min. ACT returned to the baseline value within 60 min after the termination of continuous infusion. In the main study, CPB with 30 microg/kg per min of ARG achieved thrombin-antithrombin III complex (TAT) level similar to that achieved by CPB with heparin. Platelet count with 30 microg/kg per min of ARG tended to be higher than that with heparin or 10 microg/kg per min of ARG. The SEM appearance of blood-contacting surfaces of the CPB circuits after infusion with 30 microg/kg per min of ARG appeared to be similar to that after infusion with heparin. Depositions on the blood-contacting surfaces of the CPB circuits were also frequently observed with 10 microg/kg per min of ARG. Coagulability related to CPB was controlled by the appropriate ARG dosage without the use of heparin in dogs. ARG may be a substitute for heparin in CPB.

Monitoring the Hematologic Complications of Cardiopulmonary Bypass

Patients undergoing cardiopulmonary bypass (CPB) procedures have a variety of hemostatic defects that lead to bleeding and the frequent need for transfusion of allogeneic blood products. Dilution of the patient's blood volume by the extracorporeal circuit priming so lution causes depletion of platelets and coagulation factor levels. Contact of blood with the extracorporeal circuit induces a hemorrhagic diathesis through a vari ety of mechanisms. Contact activation causes the for mation of kallikrein, bradykinin, and complement acti vation, leading to a whole-body inflammatory reaction. Intrinsic coagulation is stimulated, leading to subse quent activation of the fibrinolytic system. Platelet dys function caused by the effects of the extracorporeal circuit on platelet membrane integrity and the effects of circulating platelet inhibitors have also been described. The use of high-dose heparin for CPB mitigates these effects but does not completely eliminate them. Prota mine, administered to antagonize heparin's effects, has antiplatelet properties and anticoagulant effects when given in excess. Because of the numerous hemostatic insults incurred during and after CPB, complex moni toring techniques are necessary to ensure adequate anticoagulation, adequate heparin neutralization, and normal platelet function. Coagulation monitoring has allowed more specific identification of particular distur bances of hemostasis and has been linked with a reduc tion in hemorrhagic complications after CPB. Copyright © 2001 by W.B. Saunders Company.

Heparin-induced platelet dysfunction and cardiopulmonary bypass

Background. Cardiopulmonary bypass is associated with impaired platelet macroaggregation. Heparin contributes to platelet dysfunction before extracorporeal circulation. In vitro heparinization of whole blood does not impair macroaggregation. Heparin releases several endothelial proteins; thus heparin may inhibit macroaggregation indirectly. Methods. Patients undergoing operations using cardiopulmonary bypass and ABO blood group compatible volunteers were studied. Whole blood impedance aggregometry assessed macroaggregation in response to collagen (0.6 μg ml −1) in blood diluted either with normal saline or with platelet poor plasma, obtained from patients at different stages of cardiopulmonary bypass. Results. Before heparinization, blood diluted with its own platelet poor plasma recorded an impedance change of 13.0 (4.7 to 15.6) Ohms. Platelet poor plasma obtained after heparinization or during extracorporeal circulation reduced this response to 3.7 (1.1 to 8.4) and 2.0 (1.1 to 3.3) Ohms, respectively (both p < 0.0001 versus pre-heparin; n = 13). Macroaggregation in blood from volunteers was similarly inhibited by patients’ platelet poor plasma (n = 30). The macroaggregatory response in blood sampled after heparinization for cardiopulmonary bypass, decreased gradually from 11.4 (8.2 to 15.9) Ohms immediately after sampling to 1.7 (1.4 to 4.1) Ohms 2 hours later ( p < 0.0001; n = 11). Conclusions. In vivo heparinization induces plasma changes that inhibit platelet macroaggregation. This is an indirect, delayed inhibition that is transferable in vitro to normal platelets.

Uncomplicated heparinization for cardiopulmonary bypass in a patient with antiheparin antibodies

THE SYNDROME of heparin-induced thrombocytopenia (HIT) is now recognized to consist of two distinct clinical entities.1-3 HIT type I is characterized by a mild thrombocytopenia (.100 3 109/L) usually occurring within 48 hours of initiating heparin, which is not associated with thrombotic or bleeding complications and which resolves spontaneously even with continued heparin administration. HIT type II is associated with a more profound thrombocytopenia (,100 3 109/L or ,50% of preheparin count) beginning 5 to 8 days after initiating heparin and follows a more malignant course. Patients with a diagnosis of HIT type II are at high risk for proximal vein or arterial thrombosis, pulmonary embolism, amputation, and death. HIT type I is believed to represent a direct aggregating effect of heparin resulting in increased clearance of platelets from the circulation. HIT type II is a result of antibody production to the complex formed by heparin and platelet factor 4 (PF 4). The pathogenic antibody is of the IgG class and can bind with Fc receptor sites on platelets and endothelial cells, resulting in activation and production of a prothrombotic state. Reaching a diagnosis of HIT type II has been assisted by the development of several laboratory assays for antiheparin antibodies. Although the assay techniques vary considerably, they can all be described generally as either physiologic or immunologic. The physiologic assays involve the detection of platelet activation when heparin is added to the patient’s serum. The 14C-serotonin release assay (SRA) is the archetypic physiologic assay and is considered the gold standard by many authors for the laboratory diagnosis of HIT type II. The cost, technical expertise, and requirement for radioactive materials, however, have limited the access to this test to large reference laboratories. The immunologic assays involve direct detection of antibodies in the patient’s serum to the heparin-PF 4 complex, most often by an enzyme-linked immunosorbent assay (ELISA). The commercial availability of an ELISA kit now provides wider access to serologic testing for HIT type II. Traditionally, a diagnosis of HIT type II was thought to be an absolute contraindication to heparin exposure. More recently, the safe conduct of cardiopulmonary bypass (CPB) with anticoagulation with single-dose heparin was reported for heart transplant patients with a diagnosis of HIT type II when antiheparin antibodies were no longer detectable by SRA.4 Although alternative anticoagulation techniques are available for CPB, the abandonment of well-established heparin protocols carries considerable risk and should be undertaken only when this approach clearly provides the safest course. A case is presented that shows the uncertainties in diagnosing HIT type II and the factors that must be considered before CPB.

Uncomplicated heparinization for cardiopulmonary bypass in a patient with antiheparin antibodies

Uncomplicated heparinization for cardiopulmonary bypass in a patient with antiheparin antibodies

Biomembrane Mimicry Provides Improved Thromboresistance for Total Artificial Hearts

Thromboembolic events remain a significant issue in mechanical circulatory support. The aim of this study was to evaluate the potential benefit of surface modification in total artificial hearts (TAHs) using polymeric phospholipids (biomembrane mimicry). For this purpose, pneumatic TAHs (vacuum formed pellethane housing, hard double flap hinged inflow valves, soft trileaflet polyurethane outflow valves) had their blood-exposed surfaces either modified with polymeric phospholipids or unmodified before evaluation in bovine experiments. Orthotopic implantation of the TAHs was performed with cardiopulmonary bypass (CPB) using tip-to-tip heparin surface coated perfusion equipment and very low systemic heparinization (50 IU/kg bodyweight). After weaning from CPB and stabilizing hemodynamics, circulating heparin was neutralized with protamine (1:1). All animals were totally supported for 24 hours before elective sacrifice. No heparin was added at any time during support. Mean activated coagulation time (ACT) was 167+/-24 s at baseline before heparinization for CPB, 330+/-45 s at the end of CPB, 181+/-25 s after 1 hour of support, 180+/-31 s after 6 hours, and 185+/-28 s after 18 hours. After explantation, the TAHs perfused without anticoagulation were carefully analyzed. Atrial cuff coverage with red clot was 30+/-21% for artificial surfaces modified by biomembrane mimicry versus 100+/-0% for standard control surfaces (p<0.01). The number of macroscopic deposits found on the inflow valves was 1.33+/-0.47 for surfaces modified by biomembrane mimicry versus 3.83+/-1.86 for standard control surfaces (p<0.05). Likewise, on the outflow valves the number of macroscopic deposits was 0.00+/-0.00 for surfaces modified by biomembrane mimicry versus 1.00+/-0.81 for standard control surfaces (p<0.05). We conclude that presence and distribution of red clots and other macroscopic deposits are significantly different for artificial surfaces with biomembrane mimicry versus standard control surfaces. Application of the biomembrane mimicry concept has the potential to provide improved TAHs.

Cardiac bypass haemostasis: putting blood through the mill.

Cardiac bypass haemostasis: putting blood through the mill.

Antithrombin Concentrates in Heparin-Resistant Cardiopulmonary Bypass Patients

Antithrombin, a serine protease inhibitor, plays an important role in the regulation of the coagula tion cascade. It inhibits thrombin as well as factors Xa, IXa, XIa, and XIIa. Heparin markedly accelerates the rate at which antithrombin inhibits these enzymes. To prevent the formation of clots in the extracorporeal cir cuit, heparin is used during cardiopulmonary bypass sur gery (CPB). However, in a small proportion of patients, adequate anticoagulation, defined as an activated clotting time (ACT) of &gt;400 s after an intravenous bolus of hep arin in a dose of 300 U/kg, is not achieved. Conventional treatment of heparin resistance includes fresh frozen plasma or large doses of heparin. Antithrombin concen trates were given to 12 patients who were considered to be heparin resistant at our institution. All patients had received &gt;300 U/kg of heparin before antithrombin con centrates were infused. In all patients, the ACT pro longed to &gt;400 s after concentrates were infused, and in nine of 12 cases to &gt;600 s. Of these nine patients, six (67%) did not receive any allogeneic transfusions, whereas three (33%) required allogeneic blood transfu sions. In nine of 12 patients, no more heparin was given after infusing antithrombin concentrate. It appears that antithrombin concentrate, which is a fractionated, pas teurized plasma product, is a possible safer alternative to excessive heparin doses or fresh frozen plasma for CPB patients who are heparin resistant. Key Words: An tithrombin—Cardiopulmonary bypass—Heparin resis tance.

Potential use of recombinant hirudin as an anticoagulant in a cardiopulmonary bypass model

Recombinant (r) hirudin is a potent thrombin-specific inhibitor derived from the natural hirudin of the leech ( Hirudo medicinalis). We have studied the efficacy of r-hirudin compared with heparin in a canine model of cardiopulmonary bypass operations. Two administration regimens were used for r-hirudin: group 1, 1.0 mg/kg intracardiac bolus then intravenous bolus at 30 minutes (n = 10); and group 2, 1.0 mg/kg intracardiac bolus with 1.25 ± 0.04 mg · kg −1 · h −1 intravenous infusion (n = 8). Group 3 was given an intracardiac bolus of heparin, 1.66 mg/kg (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups ( p = 0.02). Decreases in platelets, fibrinogen, and hematocrit due primarily to hemodilution were the same in each group. The bleeding time assay showed less prolongation for r-hirudin than for heparin ( p < 0.001). No antagonist for r-hirudin was used; however, due to its short half-life all coagulation variables returned to base-line within 30 minutes after cardiopulmonary bypass. Because r-hirudin lacks effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in cardiopulmonary bypass. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.

Comparison of recombinant hirudin and heparin as an anticoagulant in a cardiopulmonary bypass model

Recombinant (r) hirudin is a potent thrombin-specific inhibitor originally derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared to heparin in a dog model of cardiopulmonary bypass (CPB) surgery. Two administration regimens were used for r-hirudin: Group I received 1.0 mg/kg intracardiac (i.c.) bolus then intravenous (i.v.) bolus at 30 min (n = 10); Group II received 1.0 mg/kg (i.c.) bolus with 1.25 +/- 0.04 mg/kg/h (i.v.) infusion (n = 8). Group III was given heparin 1.66 mg/kg (i.c.) bolus (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (P = 0.02). Decreases in platelets, fibrinogen and haematocrit due primarily to haemodilution were the same in each group. The bleeding time was less prolonged for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life, all coagulation parameters returned to baseline within 30 min after CPB. Since r-hirudin has no effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in CPB. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.

Heparin resistance during cardiopulmonary bypass: The role of heparin pretreatment

Resistance to heparin therapy during cardiopulmonary bypass (CPB) is an infrequent yet potentially catastrophic occurrence. Although the exact mechanism of heparin resistance remains unknown, prior exposure to heparin has been implicated as a possible etiologic factor. Of 46 patients undergoing CPB, a subgroup of eight patients requiring heparin treatment preoperatively were retrospectively identified to be at high risk for the development of heparin resistance. Seven of these patients were therapeutically given heparin preoperatively for complications of mitral valve disease. The remaining 38 patients served as a control, 12 patients requiring valvular procedures and 26 patients undergoing myocardial revascularization. Heparinization for CPB was achieved by giving serial heparin doses of 2 mg/kg until the activated clotting time (ACT) exceeded 400 seconds. The patients receiving heparin preoperatively exhibited a significantly lower ACT response (315.4 ± 58.1 seconds) after a heparin dose of 4 mg/kg than either the control valve (458.4 ± 106.7 seconds) or control coronary (442.2 ± 151.2 seconds) patients. Heparin sensitivity, which was determined by deriving the ACT response per unit of plasma heparin, was also significantly diminished in those patients who were pretreated with heparin. Upon further analysis, heparin resistance was not attributed to a difference in the plasma heparin levels, antithrombin III activity, clotting factors, fibrinogen concentration, or platelet count. The only predictive parameter for the development of heparin resistance in patients pretreated with heparin was a significantly lower baseline ACT. If a fixed heparinization protocol were used, patients receiving heparin in the preoperative interval would be at high risk for inadequate anticoagulation during CPB and would be prone to potentially lethal hemorrhagic and thrombotic sequelae. Therefore, those patients receiving heparin preoperatively require a detailed assessment of the clinical heparin effect prior to the safe institution of CPB.