Clot Lysis Index Research Articles

Factor XIII and Tranexamic Acid But Not Recombinant Factor VIIa Attenuate Tissue Plasminogen Activator–Induced Hyperfibrinolysis in Human Whole Blood

Hyperfibrinolysis is a pathological state that often results in depletion of coagulation factors and platelets and can contribute to bleeding. Factor XIII (FXIII) and thrombin activatable fibrinolysis inhibitor have key roles in protecting clots against fibrinolysis. We tested the hypotheses that FXIII concentrate, prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), and tranexamic acid (TA) inhibit fibrinolysis to different degrees, and that platelets contribute to antifibrinolysis. Hyperfibrinolysis was induced by addition of recombinant tissue plasminogen activator (r-tPA) (final concentration: 100 ng · mL(-1)) to citrated whole blood obtained from 13 healthy volunteers. To assess inhibition of fibrinolysis, we added to the assays FXIII-A(2)B(2) (0.42 U · mL(-1)), PCC (0.42 U · mL(-1)), rFVIIa (final concentration: 1.6 μg · mL(-1)), TA (final concentration: 0.33 mg · mL(-1)), or saline. Coagulation was analyzed by rotational thromboelastometry (ROTEM®) using the clot lysis index (CLI) after 45 and 60 minutes in extrinsically activated assays, with (FIBTEM®) and without (EXTEM®) inhibition of platelet function by cytochalasin D. After r-tPA-evoked fibrinolysis (CLI45: median 78%; 72/85.5, 25th/75th percentile), FXIII (90%; 82.5/96, P = 0.025), PCC (89%; 74/91, P = 0.0465), and TA (94%; 92/96, P = 0.001) but not rFVIIa (79%; 72/86.5, P = 1.0) significantly attenuated the decrease in CLI. Similarly, CLI60 increased only with FXIII (66%; 33/90.5, P = 0.017) and TA (90%; 89/92, P = 0.001) compared with r-tPA alone (21%; 7/59). After abolition of platelet function by cytochalasin D, only TA (95%; 89/97.5, P = 0.0025) and PCC (84%; 70.5/90, P = 0.0305) but not FXIII or rFVIIa significantly increased CLI45 and CLI60 (TA: 89%; 84.5/96, P = 0.01 and PCC: 55%; 29.5/60, P = 0.0405) compared with r-tPA alone (CLI45: 59%; 40.5/72.5 and CLI60: 10%; 0/30). In thromboelastometric assays using whole blood, only TA, FXIII, and PCC significantly inhibited r-tPA-evoked hyperfibrinolysis whereas rFVIIa had no effect. We also found that the effects of exogenous FXIII were dependent on the presence of functional platelets.

Comparison of porcine and human coagulation by thrombelastometry

Introduction Although the pig is a standard model for the evaluation of various diseases in humans, including coagulopathy, it is not clear whether results in animals can be extrapolated to man. Materials and methods In 75 anesthetized pigs, we assessed reagent-supported thrombelastometry (ExTEM®), platelet-blocked thrombelastometry (FibTEM®), and aprotinin thrombelastometry (ApTEM®). Results were compared to values from 13 anesthetized humans. Results (median, 95% CI) ExTEM®: While clot strength was comparable in pigs (66 mm, 65–67 mm) and in humans (64 mm, 60–68 mm; NS), clotting time in animals was longer (pigs 64 s, 62–66 s; humans 55 s, 49–71 s; P < 0.05) and clot formation time shorter (pigs 52 s, 49–54 s; humans 83 s, 67–98 s, P < 0.001). The clot lysis index at 30 minutes was lower in animals (96.9%, 95.1-97.3%) than in humans (99.5%, 98.6-99.9%; P < 0.001). ApTEM® showed no hyperfibrinolysis in animals. Modification of the anesthesia protocol in animals resulted in significant ExTEM® changes. FibTEM®: Complete platelet inhibition yielded significantly higher platelet contribution to clot strength in pigs (79%, 76-81%) than in humans (73%, 71–77%; P < 0.05), whereas fibrinogen contribution to clot strength was higher in humans (27%, 24-29%) than in animals (21%, 19-24%; P < 0.05). Conclusions Maximum clot firmness is comparable in human and porcine blood. However, clot lysis, platelet and fibrinogen contribution to clot strength, as well as initiation and propagation of clotting, are considerably different between pigs and humans. In addition, anesthesic drugs seem to influence thrombelastometry in animals. Accordingly, coagulation abnormalities in pigs subjected to diseases may not necessarily represent the coagulation profile in sick patients.

ROTEM and multiplate – a suitable tool for POC?

The early recognition of perioperative coagulation disorders is essential to identify non-surgical reasons of bleeding, to initiate appropriate haemostatic treatment and finally to reduce perioperative blood loss. Conventional laboratory coagulation tests include prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels and platelet counts. Although these parameters are frequently assessed, their value has been challenged at least in the setting of acute perioperative bleeding [1]. PT and aPTT are performed in an artificial ‘in vitro’ system, i.e. in plasma separated from whole blood, which is then warmed to 37 C and buffered to a pH of 7AE4. These standardized conditions often do not reflect the patient’s situation [2]. Plasmatic ‘in vitro’ tests merely reflect the time elapsing until the activation of thrombin, but provide only marginal information about the functional state of the coagulation system (e.g. platelet function, interaction of plasmatic coagulation factors with platelets and red blood cells, clot firmness, fibrinolysis). Routine coagulation tests are mostly performed in the central laboratory, i.e. remote from the operating theatre. As a consequence, test results are often not available in time or with a considerable delay [3]. Current devices designed for point-of-care (POC) monitoring of coagulation have been designed for the assessment of coagulation directly at the bedside, so that results could be available earlier. Moreover, POC tests are usually performed in whole blood, thereby comprising interactions between cellular components (i.e. platelets and red blood cells) and plasmatic coagulation factors. Commonly used POC devices for assessment of plasmatic coagulation and platelet function are listed in Table 1. This review focuses on rotation thrombelastography (ROTEM ) as a global coagulation test and multiple electrode aggregometry (MEA, Multiplate ) for assessment of platelet function. Rotation thrombelastometry (ROTEM )

Comparison of thromboelastometry with procalcitonin, interleukin 6, and C-reactive protein as diagnostic tests for severe sepsis in critically ill adults

IntroductionEstablished biomarkers for the diagnosis of sepsis are procalcitonin, interleukin 6, and C-reactive protein. Although sepsis evokes changes of coagulation and fibrinolysis, it is unknown whether thromboelastometry can detect these alterations. We investigated whether thromboelastometry variables are suitable as biomarkers for severe sepsis in critically ill adults.MethodsIn the observational cohort study, blood samples were obtained from patients on the day of diagnosis of severe sepsis (n = 56) and from postoperative patients (n = 52), and clotting time, clot formation time, maximum clot firmness, alpha angle, and lysis index were measured with thromboelastometry. In addition, procalcitonin, interleukin 6, and C-reactive protein levels were determined. For comparison of biomarkers, receiver operating characteristic (ROC) curves were used, and the optimal cut-offs and odds ratios were calculated.ResultsIn comparison with postoperative controls, patients with sepsis showed an increase in lysis index (97% ± 0.3 versus 92 ± 0.5; P < 0.001; mean and SEM) and procalcitonin (2.5 ng/ml ± 0.5 versus 30.6 ± 8.7; P < 0.001). Clot-formation time, alpha angle, maximum clot firmness, as well as interleukin 6 and C-reactive protein concentrations were not different between groups; clotting time was slightly prolonged. ROC analysis demonstrated an area under the curve (AUC) of 0.901 (CI 0.838 - 0.964) for the lysis index, and 0.756 (CI 0.666 - 0.846) for procalcitonin. The calculated cut-off for the lysis index was > 96.5%, resulting in a sensitivity of 84.2%, and a specificity of 94.2%, with an odds ratio of 85.3 (CI 21.7 - 334.5).ConclusionsThe thromboelastometry lysis index proved to be a more reliable biomarker of severe sepsis in critically ill adults than were procalcitonin, interleukin 6, and C-reactive protein. The results also demonstrate that early involvement of the hemostatic system is a common event in severe sepsis.

Thromboelastometry in patients with severe sepsis and disseminated intravascular coagulation

Severe sepsis induces coagulopathy, which may lead to disseminated intravascular coagulation (DIC). Thromboelastometry is a point-of-care whole blood coagulation monitor, which has been validated in human endotoxemia model. We assessed thromboelastometry in severe sepsis and overt DIC and investigated its applicability in differentiating sepsis-related coagulation disturbances. Thromboelastometry (EXTEM and FIBTEM tests) and traditional coagulation assays were analyzed in 28 patients with severe sepsis, 12 of who fulfilled the criteria of overt DIC on admission. Ten healthy persons served as controls. Coagulation parameters, clotting time, clot formation time (CFT), alpha angle, maximal clot firmness (MCF) and lysis index at 60 min, were registered. In patients with overt DIC, EXTEM MCF, CFT and alpha angle differed from that in both healthy controls and patients without DIC, indicating hypocoagulation (MCF 52, 63 and 68 mm; CFT 184, 88 and 73 s; and alpha angle 58, 72 and 76 degrees , respectively, P < 0.01 for all). In patients without DIC, the trend was toward hypercoagulation in EXTEM and FIBTEM MCF (68 vs. 63 mm, P = 0.042 and 23 vs. 15 mm, P = 0.034, respectively). Receiver operating characteristic curves showed that MCF, CFT and alpha angle discriminated patients with overt DIC moderately (area under curve 0.891, 0.815 and 0.828, respectively, P < 0.001 for all). Traditional coagulation assays showed progressively worsening coagulopathy from controls to septic patients without DIC and further to those with overt DIC. We conclude that thromboelastometry may be a valuable tool in assessing whole blood coagulation capacity in patients with severe sepsis with and without overt DIC.

Coagulation assessment by rotation thrombelastometry in normal pregnancy

We analysed changes in coagulation during normal pregnancy with a novel point-of-care device based on thrombelastometry (ROTEM). We compared the results obtained with those of standard coagulation tests in 104 patients: 20 non-pregnant women (controls) and 84 women in the first (T1, n = 17), second (T2, n = 9) and third (T3, n = 58) trimesters of pregnancy. We measured the clotting time (CT), the maximum clot firmness (MCF), the early clot amplitude at 5 and 15 minutes (CA(5), CA(15)) and the clot lysis index (CLI(30)) with four tests containing specific reagents. (a) The INTEM test involving ellagic acid activated the intrinsic pathway and (b) the EXTEM test using tissue factor triggered the extrinsic pathway; (c) The FIBTEM test based on a platelet inhibitor (cytochalasin D) evaluated the contribution of fibrinogen to clot formation and (d) the APTEM test was similar to the EXTEM but was based on inhibition in vitro of fibrinolysis by aprotinin. CT and CLI(30) were not significantly modified during pregnancy whereas MCF, CA(5) and CA(15) (INTEM, EXTEM, FIBTEM) increased significantly between the second and third trimesters (e.g. median [interquartile range]: MCF-FIBTEM, 13 [11-16] mm vs. 19 [17-23] mm, respectively, in controls and T3, p < 0.001). EXTEM values were not significantly different from those measured with APTEM. There were significant correlations between the results obtained with ROTEM and those from standard coagulation tests. ROTEM analysis showed a marked increase in coagulability during normal pregnancy. ROTEM values may serve as the basis for future studies in pregnant women.

Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients

BackgroundBlood loss and uncontrollable bleeding are major factors affecting survival in trauma patients. Because treatment with antifibrinolytic drugs may be effective, early detection of hyperfibrinolysis with rotation thrombelastography (ROTEM®) may be beneficial. MethodsEighty-seven trauma patients were included in this prospective observational study. Blood samples were collected at admission. After in vitro activation with tissue factor (EXTEM) and inhibition with aprotinin (APTEM), ROTEM® parameters including maximal clot firmness (MCF) and clot lysis index at 30 min (CLI30) were determined. Hyperfibrinolysis was defined as a euglobulin lysis time (ELT) <90 min. Threshold for ROTEM® parameters were determined with receiver-operating characteristic curves (ROC) analysis according to the ELT results. ResultsELT was determined in a subgroup of 23 patients. In this group of patients, ROC analysis showed that for a threshold of 18 mm (MCF-EXTEM), 71% (CLI30) and 7% (increase of MCF-APTEM), sensitivity was, respectively, 100%, 75%, and 80% with a specificity of 100%. With the application of these thresholds to the whole trauma cohort, ROTEM® analysis detected hyperfibrinolysis in five patients [6%, 95% confidence interval (CI): 2–13%]. As expected, patients with hyperfibrinolysis were more severely injured (median Injury Severity Score: 75 vs 20, P<0.05), had greater coagulation abnormalities [international normalized ratio (INR): 8.2 vs 1.3, P<0.05; fibrinogen: 0.0 vs 2.2 g litre−1, P<0.05], and a higher mortality rate (100%, CI: 48–100% vs 11% CI: 5–20%, P<0.05). ConclusionsROTEM® provided rapid and accurate detection of hyperfibrinolysis in severely injured trauma patients.

Does Homeopathically Potentized Antimony Stimulate Coagulation? A Summary of Previous Findings and Results of an &lt;I&gt;In Vitro&lt;/I&gt; Pilot Study by Means of Thrombelastography

Background: Potentized antimony is traditionally used in anthroposophic medicine to enhance hemostasis in bleeding disorders, but evidence of its effectiveness is scarce. On the other hand, non-toxic and economic additional therapeutic options for hemostatic disorders are desirable. Objectives: We examined all available literature on the subject and performed a controlled pilot in vitro study to test the procoagulatory potency of antimony D 5. Design: Freshly drawn citrated whole blood of 12 healthy volunteers and 12 patients with bleeding disorders was equally distributed into 344 portions, after which it was mixed with antimony D 5, or its potentized vehicle (lactose D 5) as control solution and tested with thrombelastography. The paired t-test and the Wilcoxon signed rank test were used for statistical analysis. In 5 of the 12 healthy donors, a second blood sample was drawn to assess individual variability and increase the total number of replicates. Thus three separate calculations were performed: for the 12 patients, the 12 healthy donors, and the 5 later samples from the same donors. The analysis was exploratory, and no Bonferroni correction was applied. Results: In the antimony D5 samples of the 12 healthy subjects, but not the patients, there was a tendency toward a shorter clotting time (CT) (p = 0.074) and a trend for an increased clot firmness, expressed as maximal amplitude (MA) (p = 0.058). The increase of MA was significant (p = 0.011) when the later samples were included. No statistical difference was detected for the clot formation time and the clot lysis index. Conclusion: The exploratory results of this pilot study are inconclusive as to whether antimony D5has a procoagulatory effect in vitro, although the results suggest an effect on MA and possibly CT. More research is warranted.

Disseminated intravascular coagulation in liver cirrhosis: fact or fiction?

Cirrhosis is commonly associated with haemostatic dysfunction. The similarities of laboratory tests of disseminated intravascular coagulation (DIC) to those found in cirrhosis has led to the belief that DIC is a feature of the haemostatic failure of cirrhosis. The aim of this study was to determine whether DIC is part of the coagulopathy of cirrhosis by applying quantitative tests for prothrombin fragment 1 + 2, antithrombin III, thrombin-antithrombin complex, and specific fribrinogen degradation products levels (XDP), as well as the thrombelastograph for detecting the Clot Lysis Index. Fifty-two stable cirrhotic patients (33 men, 19 women; mean age, 58.8 yr; range, 24-72 yr) with differing etiologies were studied. On tests of thrombin generation: thrombin-antithrombin complexes, fibrin(ogen) degradation products, and prothrombin fragments 1 + 2 were not found to be significantly different from an age- and gender-matched control group (p = 0.18, 0.3, and 0.67, respectively), whereas albumin, Factor V, fibrinogen, antithrombin III, and alpha2-antiplasmin were all significantly low (p = 0.0004, 0.002, 0.06, 0.004, and 0.004, respectively), reflecting reduced synthetic function and correlation in ascitic and non-ascitic patients. There was no correlation between impaired synthesis (antithrombin III and alpha2-antiplasmin) and indices of DIC (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, and XDP) (p = not significant). The percentage of patients with high prothrombin fragments 1 + 2 and thrombin antithrombin levels in each Child grade group was similar. Thrombin time was significantly elevated in the cirrhotic group (a manifestation of low fibrinogen levels). The Clot Lysis Index as measured by thrombelastography was significantly abnormal, indicating mild hyperfibrinolysis. We conclude that DIC is not part of the coagulopathy in stable liver cirrhosis without recent complications.

Disseminated intravascular coagulation in liver cirrhosis: fact or fiction?

OBJECTIVE: Cirrhosis is commonly associated with haemostatic dysfunction. The similarities of laboratory tests of disseminated intravascular coagulation (DIC) to those found in cirrhosis has led to the belief that DIC is a feature of the haemostatic failure of cirrhosis. METHODS: The aim of this study was to determine whether DIC is part of the coagulopathy of cirrhosis by applying quantitative tests for prothrombin fragment 1 + 2, antithrombin III, thrombin-antithrombin complex, and specific fribrinogen degradation products levels (XDP), as well as the thrombelastograph for detecting the Clot Lysis Index. RESULTS: Fifty-two stable cirrhotic patients (33 men, 19 women; mean age, 58.8 yr; range, 24–72 yr) with differing etiologies were studied. On tests of thrombin generation: thrombin-antithrombin complexes, fibrin(ogen) degradation products, and prothrombin fragments 1 + 2 were not found to be significantly different from an age- and gender-matched control group ( p = 0.18, 0.3, and 0.67, respectively), whereas albumin, Factor V, fibrinogen, antithrombin III, and α2-antiplasmin were all significantly low ( p = 0.0004, 0.002, 0.06, 0.004, and 0.004, respectively), reflecting reduced synthetic function and correlation in ascitic and nonascitic patients. There was no correlation between impaired synthesis (antithrombin III and α2-antiplasmin) and indices of DIC (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, and XDP) ( p = not significant). The percentage of patients with high prothrombin fragments 1 + 2 and thrombin antithrombin levels in each Child grade group was similar. Thrombin time was significantly elevated in the cirrhotic group (a manifestation of low fibrinogen levels). The Clot Lysis Index as measured by thrombelastography was significantly abnormal, indicating mild hyperfibrinolysis. CONCLUSION: We conclude that DIC is not part of the coagulopathy in stable liver cirrhosis without recent complications.

Efficacy of ϵ-aminocaproic acid in children undergoing cardiac surgery

Objective: To compare coagulation test results, blood loss, and blood product transfusions between patients receiving prophylactic ϵ-aminocaproic acid (EACA) and a control group matched for age, resternotomy, and surgery in children undergoing cardiac surgery. Design: Nested case-control study. Setting: University-affiliated, pediatric medical center. Participants: Same study period; 70 patients in EACA group and 70 patients in control group. Interventions: Prophylactic EACA administered intravenously (load, 150 mg/kg, infusion; 30 mg/kg/h) to 70 patients at increased risk for bleeding (reoperation or Ross procedure). Measurements and Main Results: Coagulation test values were measured before, during, and after cardiopulmonary bypass (CPB). Intraoperative blood loss, postoperative chest tube output, and allogenic blood product transfusions were recorded. Comparison of demographic and surgical data indicated close matching of the EACA and control groups. The EACA group ((median, 25th to 75th quartile] 15.6 mL/kg; 9.2 to 26.3 mL/kg) had less intraoperative blood loss than the control group (22.2 mL/kg; 14.3 to 36.3 mL/kg; p = 0.02). Postoperative chest tube output at 6 hours ( p = 0.08), 12 hours ( p = 0.07), and 24 hours ( p = 0.08) was not significantly different between groups. Fewer EACA group patients required reexploration for bleeding ( p < 0.05). There was no difference between groups in blood products transfused (in milliliters per kilogram or allogenic exposure per patient). Thromboelastography values (maximum amplitude [ma], whole blood clot lysis index at 30 minutes after MA) during CPB were better preserved in the EACA group. Conclusion: EACA reduced intraoperative blood loss but did not significantly decrease blood product transfusions. Lack of efficacy may be related to relative underdosing and should be further studied.

Evaluation of laboratory coagulation and lytic parameters resulting from autologous whole blood transfusion during primary aortocoronary artery bypass grafting

Study Objective: To determine if autologous blood reinfusion influences overall hemostatic function following aortocoronary artery bypass graft (CABG) surgery, and if so, where the predominant area of this influence lies. Design: Prospective, with control values on each patient. Setting: Cardiac operating room of a major university-affiliated county hospital. Patients: 20 patients undergoing elective CABG surgery. Interventions: Following heparinization, and prior to cardiopulmonary bypass (CPB), venous blood (average 4.9 ml/kg) was removed via an indwelling internal jugular catheter into a preservative-free plastic transfer pack unit and stored without agitation at room temperature. This autologous whole blood was reinfused after systemic protamine reversal of heparin. Blood samples for analysis were drawn immediately before and 5 minutes after completion of the reinfusion. Measurements and Main Results: Autologous blood reinfusion appears to be significantly related to increased hemoglobin, hematocrit, platelet count, fibrinogen, plasminogen, and antiplasmin levels. The prothrombin time and activated partial thromboplastin times decreased significantly, whereas activated clotting times and D-dimer levels were unchanged. Significant increases occurred in the following thromboelastography parameters: maximum amplitude, amplitude 60 minutes after the maximum amplitude, and whole blood clot lysis index. Reaction time and coagulation time were not statistically different from control values. Conclusions: Significant improvements in coagulation and lytic parameters occur following CPB after the infusion of autologous blood. These improvements in coagulation indices may be the result of the infused blood or hemoconcentration, which is also known to occur during this period. Additional control studies are needed to differentiate these effects.

Surveillance de l'hémostase au cours de la transplantation hépatique : apport du thromboélastogramme

Monitoring of coagulation is mandatory during liver transplantation (LT). Standard coagulation tests may be routinely used. However, they give static information and may be inadequate in case of severe coagulation defect. Interest has been recently focused on thromboelastography (TEG) which could give more suitable and rapid information in these cases. Few studies have evaluated the clinical interest of TEG compared to conventionnal tests. This comparison was the aim of the present study, performed in 89 patients scheduled for LT. The anaesthetic management as well as procedure of transfusion were similar in all patients. Before unclamping, 5000 KUI · kg −1 of aprotinin were injected. Routine tests and TEG were performed at the beginning and end of both preanhepatic and anhepatic phases, and 5, 30, 60, and 120 min after the revascularisation of the new liver. A phase of hypocoagulability was observed after unclamping. Biological signs included an increase in activated thromboplastin time, a reduction of α angle and maximum amplitude on TEG with a lengthening of its r + k component. A strong correlation existed between maximum amplitude and platelets, maximum amplitude and fibrinogen, α and fibrinogen at each time of the surgical procedure. Euglobulin lysis time decreased significantly after clamping, whereas fibrin degradation products increased at the same time. However, typical fibrinolysis with a clot lysis index (CLI) below 55 % was only observed in 15 patients. Twelve of them had a CLI value reaching 0 %, associated with severe generalized oozing. Aprotinin (200 000 to 600 000 KIU) corrected these abnormalities. These results show that TEG may not be very helpful to determine whether platelets or fibrinogen are involved in the phase of hypocoagulability detected after unclamping. However, TEG allows the actual diagnosis of fibrinolysis and guides therapy. Moreover, it may have a predictive value in some limited cases.

The use of high dose aprotinin in liver transplantation: The influence on fibrinolysis and blood loss

Orthotopic liver transplantation (OLT) is frequently associated with systemic fibrinogenolysis and diffuse bleeding. At present antifibrinolytic treatment has not been initiated routinely in OLT. Therefore the influence of high dose aprotinin in OLT (2 million kallikrein inactivator units (KIU) given after induction of anesthesia followed by a 500,000 KIU/h infusion throughout the operation) on intraoperative blood loss and fibrinolysis was studied in 25 patients compared to 25 patients without aprotinin. The incidence of fibrinolysis shown in thrombelastography was 72 % in the control group versus 16 % in the aprotinin group. Oozing after reperfusion of the graft caused by severe fibrinolysis defined as a clot lysis index below 15 % was only observed in the control group (42.8%). In contrast no significant difference was found between the groups in the course of fibrin and fibrinogen degradation product levels (FbDP, FgDP) although the mean concentrations of both parameters were evidently lower in the aprotinin treated patients. Levels of tissue-type plasminogen activator (tPA) activity were initially high in both groups and peaked during and after the anhepatic period. After aprotinin there was a trend of lower t-PA levels which reached significance at the time of reperfusion (p <0.02). In both groups the course of thrombin antithrombin complex was in line with the variations of FbDP and FgDP. No correlation between thrombin formation and t-PA activity was found. Mean homologous blood requirement was reduced by 50 % (5.6 ±4.0 vs. 11.2 ±8.6 units, p <0.005) The blood saving effect was more pronounced in the postanhepatic period (p <0.000001). In conclusion high dose aprotinin inhibits hyperfibrinolysis and reduces intraoperative homologous blood requirement. Therefore its routine use in OLT is recommended.

Comparative Study of Thromboelastography with Routine Coagulation Tests for Hemostasis in Cardiopulmonary Bypass

Postoperative hemorrhage after eardiopulmonary bypass(CPB) is one of the major causes of morbidity and mortality. Approximately 3% of patients have undergone surgical reexploration after open heart surgery. Coagulopathies after CPB are due to multiple hemostatic defects caused by hemodilution of procoagulants, firbrinogen, platelet, drugs and mechanical destruction by CPB machine. Thromboelastography(TEG) is the measures of viscoelastic properties of blood coagulation by providing information on the interaction of all the coagulation precursors and gives more clinically useful information on coagulation than that available from routine coagulation tests (RCT) or activated coagulation time(ACT). TEG is simple to use and can be performed within 30 minutes of blood sampling. Thirty-five patients of open heart surgery(12 were cyanotic and 23 were noncyanotic patients) were studied for the coagulation with TEG, ACT and RCT before and after CPB. Reaction time(R time), Coagulation time(R+K time), Maximum amplitude(MA), A60(Amplitude 60 min after MA), A60/MA index(Whole blood clot lysis index) and alpha angle were mea- sured in TEG, and at the same time RCT and ACT were also measured. Statistical analysis were performed by Student-t test for, significance, and 6 of TEG and 5 of RCT measurements were evaluated by multiple regression analytic methods(stepwise methods) for the correlation. The results were as follows: 1) TEG measurements before CPB were R time; 9.5±2.0min., R+K time; 14.6±2.7 min., MA; 52.4±3.6mm., A60; 45.1±4.5mm, Alpha; 46.2±5.50 and after CPB R time, 12.3±3.6min., R+K time, 24.3±16.4min., MA; 41.7±5.8min, A60; 36.4±4.4mm, Alpha, 32.0±8.90, respectively. There were significant differences between the measurements before and after CPB(P<0.005). 2) Before and after CPB, There was no significant difference between cyanotic and noncyanotic group in TEG 3) There was no fibrinolysis after CPB on TEG 4) There was significant correlation at the level of 95% significance after CPB following as; (1) R time vs aPTT and fivrinogen (2) R+K time vs PT, platelet and fibrinogen (3) MA vs platelet and PT (4) A60 vs platelet and fibrinogen (5) Alpha angle vs PT, aPTT, fibrinogen and Platelet 5) As the result of Multiple Regression Analytic Methods, R+K time, MA and Alpha angles after CPB could predict aPTT of RCT at the level of 99.5% signficance, In summary, thromboelastography is simple and easy to use in operating room for the diagnosis of coagulopathies compared with RCT.

Epsilon-aminocaproic Acid for Treatment of Fibrinolysis during Liver Transplantation

In 97 adult patients receiving liver transplants, the coagulation system was monitored by thrombelastography and by coagulation profile including PT; aPTT; platelet count; level of factors I, II, V, VII, VIII, IX, X, XI, and XII; fibrin degradation products; ethanol gel test; protamine gel test; and euglobulin lysis time. Preoperatively, fibrinolysis defined as a whole blood clot lysis index of less than 80% was present in 29 patients (29.9%), and a euglobulin lysis time of less than 1 h was present in 13 patients. Fibrinolysis increased progressively during surgery in 80 patients (82.5%) and was most severe on reperfusion of the graft liver in 33 patients (34%). When whole blood clot lysis (F less than 180 min) was observed during reperfusion of the graft liver, blood coagulability was tested by thrombelastography using both a blood sample treated in vitro with epsilon-aminocaproic acid (0.09%) and an untreated sample. Blood treated with epsilon-aminocaproic acid showed improved coagulation without fibrinolytic activity in all 74 tests. When whole blood clot lysis time was less than 120 min, generalized oozing occurred, and the effectiveness of epsilon-aminocaproic acid was demonstrated in vitro during the pre-anhepatic and post-anhepatic stages, epsilon-aminocaproic acid (1 g, single intravenous dose) was administered. In all 20 patients treated with epsilon-aminocaproic acid, fibrinolytic activity disappeared; whole blood clot lysis was not seen on thrombelastography during a 5-h observation period, and whole blood clot lysis index improved from 28.5 +/- 29.5% to 94.8 +/- 7.4% (mean +/- SD, P less than 0.001). None of the treated patients had hemorrhagic or thrombotic complications.(ABSTRACT TRUNCATED AT 250 WORDS)