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PubMed2004

Optimizing donor heart outcome after prolonged storage with endothelial function analysis and continuous perfusion.

BACKGROUND: By minimizing tissue ischemia, continuous perfusion (CP) during organ transport may increase the safety of "marginal donors." My colleagues and I investigated whether an analysis of donor heart viability predicts recovery of grafts challenged with a 24-hour preservation interval. METHODS: Dog hearts underwent cold static storage (CS) for 8 hours (n = 8) or 24 hours (n = 2) or CP for 24 hours with cold asanguinous, oxygenated solution (n = 8). Myocardial systolic and diastolic function and oxygen and lactate consumption were assessed at base line, during CP, and after Langendorff blood reperfusion. Base line endothelial function was evaluated by the percentage transcoronary change ([coronary sinus - aorta]/aorta) in myeloperoxidase and by platelet function and coronary flow reserve after 20 seconds of coronary artery occlusion. During CP, the endothelium was assessed by transcoronary protein release and coronary resistance. Edema was assessed by weight gain and histology. RESULTS: Base line systolic and metabolic functions showed no relation to post-Langendorff function. Compared with CS, CP resulted in a greater recovery in systolic function (87% +/- 35% vs 65% +/- 15% of baseline; p = 0.05) and a shorter interval required for lactate consumption to exceed production (7.0 +/- 6.8 minutes vs 15.0 +/- 8.9 minutes; p = 0.06). Endothelial function was heterogeneous: coronary flow reserve, 2.7 +/- 0.7; percentage change in myeloperoxidase, -8.4% +/- 6.8%; and change in platelet function, 4.3% +/- 3.5%, as determined by thromboelastography angle at base line. Protein release during CP for 24 hours was 8.3 +/- 7.1 g. Two factors predicted more than 75% systolic pressure generation recovery: use of CP and normal endothelial function (p = 0.05; Fisher's exact test). However, CP led to edema according to histology, weight gain (72 +/- 29 g), and impaired diastolic function versus CS (end-diastolic pressure-volume relationship, 1.4 +/- 0.4 mm Hg/mL vs 0.8 +/- 0.3 mm Hg/mL; p = 0.08). CONCLUSIONS: Better systolic function despite 16 hours' more preservation than cold storage corroborates the idea that CP supports aerobic metabolism at physiologically important levels. Viability analysis focused on endothelial function and identified organs that were able to tolerate this 24-hour preservation interval.

Aerobiosis↗
PubMed2004

In vitro evidence of gender-related heparin resistance.

Coagulability varies among men, women, and pregnant women, along a spectrum where the blood of men is the least and that of pregnant women the most coagulable. The effects of differences in coagulation status on the action of heparin cannot be measured by specific laboratory tests such as aPTT or anti-Factor Xa assay. Thromboelastography which measures whole blood coagulation can assess the effect of heparin against differing backgrounds of coagulation. The aim of this in vitro study was to explore differences in heparin effect between men, women and pregnant women. Fifteen male and female staff volunteers, and 15 pregnant women approaching term, donated venous blood, which was added to four cups in two TEG 5000 analysers. In the cups of the analysers was 0.03 mL of saline control, or heparin 0.4, 0.6 or 1 unit/mL. TEG variables r and k, angle and MA were compared across the groups using two way ANOVA. All subject groups demonstrated a significant heparin effect, which was least in the control group and greatest with 1 unit/mL (P < 0.0001). Across the subject groups, from men to pregnant women, increasing coagulability was seen, with shortening of r and k (P < 0.04), and increasing angle and MA (P < 0.0001). A relationship between gender and heparin was significant for r and k (P < 0.02) but not for angle and MA. This result assists the case against a one-size-fits-all approach to policies on heparinisation.

Adolescent↗
PubMed2006

Failure of surface-modified bypass circuits to improve platelet function during pediatric cardiac surgery.

OBJECTIVE: Surface-modified cardiopulmonary bypass circuits have been shown to improve platelet function and decrease postoperative bleeding after heart surgery in adults. Two surface-modified cardiopulmonary bypass circuits are approved and commercially available for pediatric cardiac surgery. There have been few studies demonstrating the efficacy of these modifications for children. We performed a prospective, randomized trial comparing surface-modified cardiopulmonary bypass circuits to a standard unmodified circuit in pediatric cardiac surgery. METHODS: Sixty-nine children (median 6 months old) undergoing first-time cardiac surgery were enrolled and randomized to an uncoated circuit or one of the two commercially available surface modified circuits for their operation. Blood samples were collected at baseline, on cardiopulmonary bypass, at the end of rewarming, after protamine, and at 18 to 24 postoperative hours. Platelet count, beta-thromboglobulin, and thromboelastography with and without abciximab were measured. Postoperative chest tube outputs and blood product utilization were also analyzed. RESULTS: The platelet counts, beta-thromboglobulin levels, thromboelastographic measures of platelet function, and postoperative bleeding were not significantly different between the surface-modified cardiopulmonary bypass circuit groups and the control group. CONCLUSION: Currently available surface-modified cardiopulmonary bypass circuits do not significantly improve platelet function or clinical outcomes after routine pediatric cardiac surgery.

Blood Platelets↗
PubMed2004

Evaluation of a novel kallikrein inhibitor on hemostatic activation in vitro.

BACKGROUND: DX-88 is a potent kallikrein inhibitor that is being studied for the treatment of hereditary angioedema (HAE) and represents a potential alternative to aprotinin in cardiac surgical patients. The current study was designed to evaluate in vitro effects of DX-88 on coagulation in comparison with aprotinin. METHODS: Blood samples were obtained from consented 12 healthy volunteers. DX-88 or aprotinin was added to blood at 200 and 800 kallikrein inhibitory units (KIU) per milliliter for aprotinin, and at 1.1, 2.2, or 8.8 microg/ml for DX-88. Thromboelastography (TEG) was performed using celite, kaolin, or tissue factor (TF) activation. Kaolin-based activated clotting times (ACTs) were measured at different heparin levels. The whole blood prothrombin time (PT)/PTT values were also measured. The endogenous thrombin generation was assessed with a fluorogenic assay using platelet-poor plasma (PPP). RESULTS: With celite and kaolin activation of TEG, the reaction time was prolonged with DX-88 and aprotinin. With tissue factor activation, TEG parameters were not affected. DX-88 caused dose-dependent kaolin-ACT prolongation that was augmented by increasing doses of heparin. DX-88 or aprotinin had no significant effects on the PT values, but PTT values were dose-dependently prolonged. Both agents delayed the onset of thrombin generation when PTT reagent was used as a trigger, whereas no change was observed when tissue factor was used. CONCLUSION: We found that DX-88 delayed contact activator induced coagulation without affecting tissue factor mediated coagulation. For evaluation of coagulation during DX-88 therapy, the use of PT or tissue factor-activated TEG may be preferable.

Aprotinin↗
PubMed2005

Direct-acting fibrinolytic enzymes in shark cartilage extract: potential therapeutic role in vascular disorders.

Fibrinogen and fibrin are molecules with overlapping roles in blood clotting, fibrinolysis, wound healing, inflammation, matrix and cellular interactions and neoplasia. There is currently much interest in the possible use of fibrinolytic agents in human therapeutics. In this study, we report the presence of fibrinolytic activities in shark cartilage extract (SCE). In vitro, SCE at 100 microg/ml completely degraded fibrin gel in an aprotinin-insensitive manner, suggesting a non-plasmin molecular nature. SCE was able to cleave all chains of fibrinogen and fibrin and the cleavage was completely inhibited by 1,10-phenanthroline, suggesting an essential role for metalloprotease(s) in this process. Using fibrinogen zymography, we show that SCE contains two plasmin-independent fibrinolytic activities and that these activities are correlated with the presence of 58 and 62 kDa proteases in the extract. SCE-fibrinolytic activities are inhibited by dithiothreitol, suggesting that disulfide bonds are necessary for the protease structure. Finally, using thromboelastography, SCE markedly induced retraction of human platelet-rich plasma (PRP) clot, this process being completely abolished by 1,10-phenanthroline. These data suggest the presence of novel non-plasmin fibrinolytic activities within SCE. This extract may thus represent a potential source of new therapeutic molecules to prevent and treat vaso-occlusive and thromboembolic disorders.

Animals↗
PubMed2006

Intraoperative coagulation evaluation of ischemia-reperfusion injury in small bowel transplantation: a way to explore.

BACKGROUND AND AIM OF STUDY: The success of intestinal transplantation is affected by the extreme susceptibility of the small bowel to ischemia-reperfusion (I/R) injury. Platelet aggregation decreases after reperfusion in small intestinal ischemia and liver transplantation. Thromboelastography (TEG) is a coagulation test performed whole on blood. The aims of this study were to assess coagulation derangements during bowel transplantation to define appropriate modalities of intraoperative coagulation monitoring. A secondary endpoint was to determine whether measurements of coagulation derangements were useful to estimate small intestinal I/R injury. MATERIALS AND METHODS: We recruited 19 patients who had undergone elective small bowel transplantation for primary short-gut syndrome. We divided our patients into two groups depending on their reperfusion injury as evaluated with a biopsy after reperfusion: group A composed of eight patients who had a reperfusion injury: group B composed of 11 patients who did not experience this problem. We measured five thromboelastogram indicators (r, k, angle, MA, CL30) at defined intervals: dissection phase (T1), vascular anastomoses phase (T2) as well as 30 minutes (T3) and 120 minutes (T4) after reperfusion during the intestinal reconstruction phase. RESULTS: We did not observe any significant difference between intraoperative blood loss, core temperature, or volume of fluid fresh frozen plasma, or platelet administration. Angle and MA were decreased significantly among patients with reperfusion injury. DISCUSSION: Patients showed a hypocoagulation pattern during all the manipulations. This derangement did not depend on the ischemia time. In patients with I/R injury the angle and MA did not change during ischemia, but did change significantly upon reperfusion. Several mechanisms may cause coagulation derangements. During the ischemic period, there may be damage to the vascular bed of the ischemic organ. When arterial blood passes through the damaged vascular bed after reperfusion, platelet activation occurs to varying degrees, resulting in reduced platelet function. CONCLUSION: Further studies are needed to confirm this preliminary work, which was limited by the low number of patients, in order to elucidate relevant mechanisms and develop predictive algorithms.

Anastomosis, Surgical↗
PubMed2006

Intraoperative coagulation monitoring and small bowel transplantation: a way to explore.

BACKGROUND: The existence of coagulation disorders during intestinal transplantation is getting more important for a correct anesthetic management. Both a condition of hypocoagulation and hypercoagulation can happen during the intraoperative course. Thromboelastography (TEG), a test on whole blood coagulation, allows measurement of different phases of coagulation function. The aims of our study were to evaluate coagulation derangements during bowel transplantation using TEG. MATERIALS AND METHODS: We measured cold ischemia time in 19 patients who underwent general anesthesia for intestinal transplantation. We measured five TEG indicators (R, K, angle, MA, CL50) at defined intervals: dissection phase (T1), vascular anastomosis phase (T2), 30' (T3) and 120' (T4) after reperfusion during the intestinal reconstruction. RESULTS: We found a statistically significant difference between MA measured at T1 versus T3 and T4. There was no significant relation between MA derangements and ischemia time. CONCLUSIONS: Patients showed hypocoagulation pattern during all periods. MA indicator variation between the initial value and the value after reperfusion may relate to release of hypocoagulation factors. We observed important coagulation derangements during small bowel transplantation, particularly on platelet function after graft reperfusion. The derangements did not depend on ischemia time.

Blood Coagulation Disorders↗
PubMed2006

Study on biological variation of haemostatic parameters in clinically healthy dogs.

Thromboelastography (TEG) may be a valuable supplement to the coagulation assays activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT) and D-Dimer currently used in most clinical pathology laboratories. Allowable imprecision and bias reference limits for analytical tests can be calculated based on measurements of biological variation. No studies to date have examined the effect of biological variation on these haemostasis parameters in the same group of dogs. Plasma samples were collected after a set protocol once weekly for five consecutive weeks from eight healthy dogs (four males and four females) and stored at -80 degrees C until analysis. Randomized duplicate coagulation tests and TEG analyses were performed on all plasma samples within one run. The data were analyzed for outliers and subsequently subjected to nested analysis of variance to obtain the coefficient of analytical, intra-individual and inter-individual variation. From these objective analytical performance standards for imprecision, critical difference, total error and the index of individuality were calculated to assess the utility of conventional population-based reference ranges. All the clotting times (aPTT, PT and TT), fibrinogen, AT and D-Dimer showed a degree of individuality, which may make the use of population-based reference ranges alone an insensitive interpretation criterion, whereas a population-based reference interval seems to be sensitive for interpreting all TEG parameters. Analytical performance standards for imprecision were only met for one of the coagulation assays, whereas all TEG parameters except the alpha angle, alpha achieved this analytical goal.

Animals↗
PubMed1983

The transfer test: a new screening procedure for thrombotic diseases.

The transfer test (TT) measures by means of thromboelastography the capacity of a plasma to shorten the coagulation time of a control plasma. The value of the TT was compared to that of fibrin(ogen), degradation products (FDP), and ethanol gelatin test (EGT) in various diseases (group I), in confirmed deep venous thrombosis (group II), and in confirmed pulmonary embolism (group III). In 211 consecutive patients admitted for various diseases the results of the TT, FDP, and EGT were abnormal in 12.3, 11.3, and 66.6%, respectively, of the cases. In 59 consecutive patients with deep venous thrombosis confirmed by radiological phlebography the results of TT, FDP, and EGT were abnormal at admission time in 96.6, 89.8, and 44%, respectively, of the cases. In 45 consecutive patients with pulmonary embolism confirmed by lung scintigraphy the results of TT, FDP, and EGT were abnormal at admission time in 97.7, 97.6, and 88%, respectively, of the cases. Among the three parameters which were evaluated, the TT seems to be the most sensitive screening procedure for thrombotic diseases. A normal result of TT is a strong argument against a recent thrombotic venous phenomenon.

Acute Disease↗
PubMed1987

Hemostatic evaluation of patients undergoing liver transplantation.

A detailed coagulation and thromboelastographic study was done on the first 50 liver transplantation procedures performed at the Mayo Clinic between March 1985 and June 1986. Most of the patients suffered from primary sclerosing cholangitis, primary biliary cirrhosis, or chronic active hepatitis. Seven patients required a second liver transplantation, and six patients died, none intraoperatively. Most of the patients had distorted hemostatic mechanisms preoperatively, as would be expected because the liver generates most of the clotting factors. The outstanding exception was factor VIII, which was usually in the high-normal range or even more elevated. Substantial deterioration of coagulation factors occurred regularly during reperfusion of the donor liver. In some instances, this trend was corrected within 1 hour, but platelet counts continued to decrease, and some coagulation factors rebounded only partially. Because thromboelastographic tracings are quickly available to the liver transplant team and because they tend to forewarn of impending hemostatic problems, we believe that thromboelastography is a reasonably effective procedure for monitoring coagulation during liver transplantation.

Blood Coagulation Factors↗
PubMed2001

Induction of acquired factor IX inhibitors in cynomolgus monkey (Macaca fascicularis): a new primate model of hemophilia B.

Inherited hemophilia dog and other transient hemophilic animal models have been used for evaluation of hemostatic agents for use in treatment of hemophilia. We established the first nonhuman primate hemophilic model by immunizing cynomolgus monkeys with human FIX (hFIX) in adjuvants. FIX activities of all three hFIX-immunized monkeys decreased transiently to less than 10% in accordance with prolongation of activated partial thromboplastin time (APTT). Forty micrograms of human factor VIIa (hFVIIa) per kilogram body weight (that was reported to be clinically effective) was administered to the monkey with the highest inhibitor titer to evaluate its usefulness as a hemophilia inhibitor model. Results of thromboelastography (TEG) after the injection demonstrated that the hemostatic effect of FVIIa in this model would be similar to that in hemophiliacs with inhibitors. The antibodies purified from the monkey's plasma by hFIX-immobilized gel were composed of two types: Ca(2+)-dependent and -independent antibodies, with features of IgG(1) and IgG(4). Both types of antibodies reacted to cynomolgus FIX, and only Ca(2+)-dependent antibodies also expressed inhibitory activity against cynomolgus FIX. Immunoblotting analyses of Ca(2+)-dependent antibodies using hFIX and its derivatives suggested that they recognized the Ca(2+)-dependent conformation related to the gamma-carboxyglutamic acid (Gla) domain. Comparison of FIX cDNA from human, cynomolgus monkey, and other species, and the results of immunization of various animals (goats, beagle dogs, rabbits, and rats) with hFIX in adjuvants strongly suggested that the development of acquired FIX inhibitors in the monkeys might be due to high cross-reactivity of the antibodies to molecular mimic antigens, hFIX, and cynomolgus FIX.

Animals↗
PubMed2002

Regulation of clot retraction by glycoprotein IIb/IIIa antagonists.

Binding of fibrinogen to platelet glycoprotein (GP) IIb/IIIa induces clot retraction. Significant differences among GP IIb/IIIa antagonists were previously noted to inhibit thromboelastography in whole blood specimens. The relationship between efficacy of these agents and inhibition of clot retraction is unclear. Here, we use a plasma-free clot retraction assay to evaluate potency of GP IIb/IIIa antagonists to inhibit clot retraction and modulate platelet signaling, and to address whether these effects are realized in the clinically relevant dose range. The potencies for inhibition of clot retraction and aggregation are similar for antagonists with high affinity for resting platelets and slow off-rates, whereas lower affinity and fast off-rate antagonists are disproportionately less effective in blocking clot retraction. A positive correlation is observed between inhibition of clot retraction and inhibition of tyrosine dephosphorylation across a number of GP IIb/IIIa antagonist pharmacophores. For lower affinity and fast off-rate antagonists, the concentrations required for inhibition of clot retraction clearly exceed the clinical dose range. Site occupancy studies combined with clot retraction experiments addressed whether high affinity and slow off-rate compounds can alter clot retraction during the dosing interval. Binding studies using [3H] Roxifiban, a high affinity GP IIb/IIIa antagonist, indicate that occupancy of >95% of GP IIb/IIIa sites is required to inhibit clot retraction. This level of occupancy is not routinely achieved in the clinic and is not tolerated, at least for chronic therapy. These results suggest that inhibition of clot retraction is not necessary for efficacy of GP IIb/IIIa antagonists.

Abciximab↗
PubMed2003

Recombinant factor VIIa reduces bleeding in severely thrombocytopenic rabbits.

Severe thrombocytopenia is a common complication to intensive chemotherapeutic regimens. For bleeding episodes associated with severe thrombocytopenia, the current standard treatment is platelet transfusion. However, due to several transfusion complications such as transfusion-transmitted diseases, platelet refractoriness and immunomodulation, as well as increasing problems with sufficient supply of platelet products, it is imperative to search for alternatives to platelet transfusion. To test the efficacy of recombinant activated human coagulation factor VII (rFVIIa, NovoSeven) in thrombocytopenia, a preclinical study was conducted in thrombocytopenic rabbits. Thrombocytopenia was induced by a combination of gamma-irradiation and the use of platelet antibodies, and the effect of rFVIIa on nail cuticle bleeding was determined. Administration of rFVIIa at 2 mg/kg significantly shortened the prolonged bleeding time in thrombocytopenic animals (rFVIIa vs. control, median 23 min 41 s vs. 60 min, p=0.016) as well as significantly reducing the blood loss (rFVIIa vs. control, median: 8.8 vs. 12.2 nmol hemoglobin/ml, p=0.016). This effect was also reflected by a significant reduction of the prothrombin time, activated partial thromboplastin time, as well as improvement in clotting parameters in an in vitro thromboelastography thrombocytopenia model. Histopathological evaluation of kidney biopsies for the presence of micro thrombi did not reveal evidence of prothrombotic effects of rFVIIa in this model. These data demonstrate the haemostatic efficacy of rFVIIa in a rabbit model of severe thrombocytopenia. Clinical trials will be needed to further explore the potential of NovoSeven as a haemostatic agent in thrombocytopenic patients.

Animals↗
PubMed1998

Species specificity of the anticoagulant activity of human urinary soluble thrombomodulin.

The anticoagulant activities of human urinary soluble thrombomodulin (UTM) in blood taken from various species using several anticoagulant assay systems were compared; it was examined which coagulant assay system is appropriate for evaluation of the antithrombotic effects of UTM and how the species specificity of UTM is involved in the mechanisms of action of UTM. When anticoagulant activities were compared using activated partial thromboplastin time (APTT), thromboelastography (TEG), and thrombin generation test (TGT), the effect of UTM was found to be the strongest in humans among various species tested. Among the anticoagulant assays tested, TGT reflecting protein C (PC) activation by UTM, appeared to be more sensitive than APTT and TEG in detection of thrombomodulin activity. In the study of the mechanisms of action of UTM, UTM exhibited nearly the same antithrombin activity against human and rat thrombin; the rate of activation of human PC by thrombin/UTM complex was much higher than that of rat PC. Therefore, the species specificity of the anticoagulant activity of UTM may be attributable to thrombin/UTM-PC interaction, but not to UTM-thrombin interaction. From these results, we concluded that TGT reflecting PC activation by UTM will be a more useful assay than APTT and TEG for estimating the antithrombotic effects of UTM in humans. Furthermore, our findings suggest that UTM will exhibit more potent antithrombotic effects in humans than those in rats by strongly enhancing thrombin-catalyzed PC activation.

Animals↗
PubMed1999

Correction of both prothrombin time and primary haemostasis by recombinant factor VII during therapeutic alcohol injection of hepatocellular cancer in liver cirrhosis.

We evaluated the efficacy of recombinant factor VII to correct impaired haemostasis in a patient with liver cirrhosis requiring an invasive procedure. A test intravenous bolus of 80 microg/kg of recombinant factor VII was given to a Jehovah's Witness, with a solitary 4.4-cm hepatocellular carcinoma and underlying hepatitis C virus cirrhosis, in an attempt to correct his haemostatic disorders and safely inject the tumour with alcohol. An extensive portal block had precluded consideration of liver transplantation. Haemostasis was evaluated by clotting assays, bleeding time and thromboelastography 10 min before and 10 min and 1, 2, 4, 8 and 24 h after factor VII infusion. Parameters of both coagulation (prothrombin time) and platelet function (bleeding time and the alpha and ma parameters of thrombelastography) were improved 10 min after factor VII infusion; improvements lasted 4 to 8 h or more. Platelet count did not change and there was no evidence of disseminated intravascular coagulation. The improvements in haemostatic parameters correlated significantly with the increases in factor VII plasma concentrations (p<0.04). Factor VII clearance was 25.1 U/h/kg and its half-life was 5.8 h. The same dose of recombinant factor VII was given to the patient 1 week later, just before the alcohol injections. The patient had no subsequent bleeding or other complication, with no change in haemoglobin levels over 24 h. Thus, recombinant factor VII represents a therapeutic advance, as it can correct fully both coagulation and platelet function defects in cirrhosis and allow invasive procedures to be performed safely.

Carcinoma, Hepatocellular↗
PubMed2003

The management of perioperative bleeding.

Excess perioperative bleeding remains a major complication following surgery, resulting in increased morbidity and mortality. The principal causes of non-surgical haemostatic perioperative bleeding are a pre-existing undetected bleeding disorder, related to the nature of the operation itself or from coagulation abnormalities arising from massive blood loss. Very often, it is a combination and coexistence of various pathologies. Identifying patients at risk remains a major component of preventing excessive blood loss. Understanding the haemostatic changes occurring in the perioperative period, especially in complex procedures like cardiopulmonary bypass and orthotopic liver transplantation is crucial in developing new strategies for the management of perioperative bleeding. Pharmacological interventions, especially aprotinin, tranexamic acid, desmopressin and increasingly, recombinant VIIa are being used both in prophylaxis and therapeutically to stop bleeding. The use of near patient testing like thromboelastography and platelet function analyser has allowed for more detailed assessment of the various steps of haemostasis. One of the main goals is to reduce the usage of allogeneic blood transfusion and its attendant risks.

Aprotinin↗
PubMed1995

Changes in transfusion therapy and reexploration rate after institution of a blood management program in cardiac surgical patients.

A retrospective study was performed to determine the impact of a coagulation and transfusion management program on blood utilization in 1,079 sequential patients for myocardial revascularization and open ventricle or combined procedures. Four hundred and eighty-eight patients (group 1) before, and 591 patients (group 2) after institution of thromboelastography (TEG)-guided coagulation were studied and compared for transfusion requirements, donor exposure, and the incidence of reoperation for hemorrhage. Group 2 patients had a significantly lower incidence of overall transfusion (78.5% v 86.3%) during hospitalization and in total transfusion in the operating room (57.9% v 66.4%). The incidence of each transfusion subtype was also significantly lower in group 2 patients. Actual total median donor exposure was 8 in group 1 patients and 6 exposures in group 2 patients. Mediastinal reexploration for hemorrhage was 5.7% before institution of TEG-based coagulation monitoring and 1.5% in TEG-monitored patients. Use of TEG monitoring before reexploration has decreased the cost and potential risk for patients undergoing CABG surgery.

Blood Coagulation↗
PubMed1997

Heparin detection by the activated coagulation time: a comparison of the sensitivity of coagulation tests and heparin assays.

OBJECTIVE: Laboratory and point-of-care coagulation tests are frequently obtained to determine the presence of heparin after surgical procedures. The objective of this study was (1) to compare the sensitivity of the activated coagulation time (ACT), activated partial thromboplastin time (aPTT), protamine titration (Hepcon; HMS Medtronic, Hemotec, Englewood, CO), and thromboelastography (TEG) with heparin anticoagulation and (2) to determine how frequently residual heparin is present in the 24-hour period after heparin neutralization in cardiopulmonary bypass (CPB) patients. DESIGN: A prospective study. SETTING: A tertiary care university teaching center that performs more than 15,000 surgical procedures per year. PARTICIPANTS: Vascular surgical (n = 17) and CPB (n = 29). INTERVENTIONS: In vascular surgical patients, coagulation tests (ACT, protamine titration [Hepcon], and TEG) were obtained before and 90 minutes after heparin (50 to 60 U/kg IV) and compared with heparin concentration determined by factor Xa inhibition assay. In cardiac surgical patients, ACT and heparin concentrations were measured after anesthesia induction, during CPB, after protamine neutralization, and 3 as well as 6 hours after CPB. In addition to heparin concentrations and ACT measures, platelet counts, fibrinogen levels, and bleeding times were determined before and 3 and 24 hours after CPB. MEASUREMENTS AND MAIN RESULTS: Ninety minutes after heparin, significant heparin concentrations were present in all vascular surgical patients, but ACT was elevated in only 4 of 17 patients. Protamine titration (Hepcon) correlated with the factor Xa inhibitory assay for heparin (r2 = 0.76). All 17 patients had an abnormal TEG (mean "R" time = 81 +/- 39 minutes) and a marked elevation of aPTT (135 +/- 35 sec [normal 22 to 33 seconds]) 90 minutes after heparin. In CPB patients, ACT did not correlate with heparin assays. After protamine neutralization of heparin in CPB patients, ACT returned to baseline despite the presence of heparin in 3 of 29 patients (0.22, 0.18, and 0.33 U/mL). CONCLUSIONS: ACT was less sensitive to residual heparin anticoagulation than aPTT, TEG, and whole blood heparin assay. The whole blood heparin assay (Hepcon) provided sensitive and specific data about the presence of residual heparin. Despite the limitation of ACT in detecting heparin, the investigators found that residual heparin was not common in the period after uncomplicated CPB.

Aged↗