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PubMed2006

Quantifying the effect of antiplatelet therapy: a comparison of the platelet function analyzer (PFA-100) and modified thromboelastography (mTEG) with light transmission platelet aggregometry.

BACKGROUND: Antiplatelet therapy with aspirin and clopidogrel is known to confer protection against ischemic events. Increasing numbers of patients are presenting for surgery while taking these drugs. This may lead to an increase in perioperative blood loss, particularly in those who have a heightened response to the drugs. Identifying these patients preoperatively would allow us to plan appropriate management. METHODS: The antiplatelet effect of aspirin and/or clopidogrel was measured using two point-of-care monitors: the platelet function analyzer (PFA-100; Dade, Miami, FL) and the modified thromboelastograph (mTEG; Haemoscope Corp., Niles, IL). This was compared with optical light transmission aggregometry. RESULTS: All people taking aspirin displayed a definitive aspirin effect on aggregometry (n = 20). Ninety percent of these were identified by modified thromboelastography (n = 18). Seventy percent were identified by the platelet function analyzer (n = 14). Fifty percent of people taking clopidogrel displayed a definitive response to the drug on aggregometry. Seventy percent of these were identified on modified thromboelastography (n = 7). None were identified by the platelet function analyzer. There was good agreement between the results of the aggregometry and modified thromboelastography in clopidogrel patients (kappa = 0.81). CONCLUSION: The search for a point-of-care monitor of platelet function has been the focus of much research. This study has shown that the modified thromboelastograph can be used for monitoring the effect of clopidogrel as well as aspirin. It potentially has a wide scope to be used for the monitoring of effectiveness of therapy as well as a possible predictor of perioperative bleeding.

Adult↗
PubMed2006

Effect of high- and low-molecular-weight low-substituted hydroxyethyl starch on blood coagulation during acute normovolemic hemodilution in pigs.

BACKGROUND: Hydroxyethyl starches (HES) with lower impact on blood coagulation but longer intravascular persistence are of clinical interest. The current study aimed to investigate in vivo the isolated effect of molecular weight on blood coagulation during progressive acute normovolemic hemodilution. METHODS: Twenty-four pigs were normovolemically hemodiluted up to a total exchange of 50 ml . kg . body weight of HES 650/0.42 or HES 130/0.42. Serial blood sampling was performed to measure HES plasma concentration and to assess blood coagulation. Concentration-effect relations were analyzed by linear regression, followed by the Student t test on regression parameters. RESULTS: Blood coagulation was increasingly compromised toward hypocoagulability by acute normovolemic hemodilution with both treatments (P < 0.01). Significantly greater impact on activated partial thromboplastin time (P = 0.04) and significantly stronger decrease of maximal amplitude (P = 0.04), angle alpha (P = 0.02), and coagulation index (P = 0.02) was seen after acute normovolemic hemodilution with HES 650/0.42 as compared with HES 130/0.42. Except for factor VIII (P = 0.04), no significant differences between both treatments were observed when relating antihemostatic effects to HES plasma concentrations (P > 0.05). A significantly lesser decrease of hemoglobin concentration has been found with HES 650/0.42 as compared with HES 130/0.42 (P < 0.01) in relation to HES plasma concentrations. CONCLUSION: High-molecular-weight HES (650/0.42) shows a moderately greater antihemostatic effect than low-molecular-weight HES (130/0.42) during acute normovolemic hemodilution. However, similar effects on hemostasis were observed with both treatments when observed antihemostatic effects were related to measured HES plasma concentrations. In addition, HES 650/0.42 may have a lower efficacy in immediately restoring plasma volume.

Animals↗
PubMed1987

Coagulopathy post peritoneovenous shunt.

In 1942, 53% of medically treated patients with cirrhosis were dead 6 months after the onset of ascites. Only 30% survived 1 year. This dismal outlook has improved only slightly with advances in medicine. Yet, some internists reject the peritoneovenous shunt (PVS) for this fatal condition even if they are aware that a diminished blood volume causes the abnormal sodium retention responsible for ascites. Their objections are based on life-threatening complications of PVS, especially post shunt coagulopathy (PSC). Blood shed into the peritoneal cavity becomes incoagulable. Such blood is immediately coagulated by a protocoagulant (soluble collagen) and concurrently lysed by tissue plasminogen activator (TPA) secreted by the peritoneal serosa. Wide zones of lysis surround peritoneal tissue placed on fibrin plates. Large volumes of ascitic fluid infused into circulating blood simulates the fate of blood shed into the peritoneal cavity with lysis playing the major role. Addition of ascitic fluid to normal platelet-rich plasma in vitro initiates clot lysis on thromboelastogram (TEG). Epsilon-aminocaproic acid (EACA) counteracts this lysis. EACA and clotting factors normalize the TEG and arrest PSC. Disposal of ascitic fluid at surgery prevents or ameliorates PSC. Mild PSC was encountered only twice in 150+ consecutive patients (1.3%) with only one case being clinically significant (0.6%). Severe PSC occurred seven times in 98 early shunt patients whose ascitic fluid was not discarded. Severe PSC requires shunt interruption and control of bleeding with clotting factors and EACA. Peritoneal lavage with saline prevents the recurrence of PSC on reopening the shunt. In four patients, EACA and clotting factors were adequate to arrest coagulopathy. Three earlier patients died of PSC before its cause and treatment were understood. Proper management eliminates this life-threatening complication, and PSC cannot be considered a deterrent to PVS. Disseminated intravascular coagulopathy (DIC) is produced in experimental animals only by the injection of thrombin or thromboplastin. PSC is a distinct entity differing from DIC; EACA and not heparin is the antidote for PSC.

Aminocaproic Acid↗
PubMed1995

Effects of the platelet-activating factor receptor antagonist WEB 2086 on whole blood coagulation and fibrinolysis in a thromboelastography assay.

The effects of WEB 2086 on human blood coagulation and fibrinolysis were studied in vitro using computerized thromboelastography and native whole blood. WEB 2086 (3.0, 30, 150, and 300 microM) had no apparent effect on the split point (SP), reaction time (R) and lysis of the clot. The biKoatugulierung time (K) was prolonged, the angle (alpha) and maximum amplitude (MA) were diminished, and the overall coagulation index (TEG index) was smaller. SP and R indicate onset of coagulation with the formation of fibrin strands, suggesting that WEB 2086 had no effect on the plasma factors. Since the Lysis parameter reflects fibrinolysis, WEB 2086 had no demonstrable fibrinolytic activity. K, alpha and MA involve platelet function and the integrity of fibrin; the fact that these factors were affected to the exclusion of SP and R suggests an effect largely on platelets. There was lack of a dose-response relationship at this concentration range (3.0-300 microM), probably due to saturation of PAF receptors even at the lowest effective concentration. These findings are consistent with the known effects of WEB 2086 on platelet function and suggest that thromboelastography may be a useful tool in the study of the activity of PAF receptor antagonists on coagulation profiles. Furthermore, since WEB 2086 is a highly specific PAF receptor antagonist devoid of intrinsic activity, and the samples used were not treated with exogenous PAF, these results suggest that endogenous PAF may play a significant role in the normal clotting mechanism.

Azepines↗
PubMed1996

A thromboelastography study on the in vitro effects of L-arginine and L-NG-nitro arginine methyl ester on human whole blood coagulation and fibrinolysis.

The effects of L-arginine and L-NG-nitro arginine methyl ester (L-NAME) on human blood coagulation and fibrinolysis were studied in vitro using computerized thromboelastography and native whole blood. L-Arginine (8-80 microM) prolonged the split point (SP), reaction time (R) and biKoatugulierung time (K); and diminished the angle (alpha), maximum amplitude (MA) and TEG index. L-NAME (0.5-50 microM) shortened SP, R and K and increased alpha, MA and the TEG index in a concentration-dependent manner. Neither L-arginine nor L-NAME had any effect on clot lysis. SP and R indicated the initiation of fibrin-strand formation, therefore L-arginine delayed, while L-NAME promoted the processes leading to fibrin formation. K and alpha reflect the rate of clot formation and involve fibrin build-up and platelets. Thus, L-arginine inhibited and L-NAME enhanced the rate of clot formation. MA (clot strength) involves the integrity of fibrin strands and platelet aggregation, and again L-arginine was inhibitory, while L-NAME enhanced this interaction. The TEG index indicates the coagulability of the sample; L-arginine was anticoagulant while L-NAME had procoagulant effects. These results are consistent with the inhibitory effects of NO on platelet function and of the platelet-aggregating properties of NOS inhibitors. In addition, NO may play an inhibitory role in the process leading to fibrin formation and also on the interactions between platelets and fibrin. Such effects may be important when considering the clinical use of drugs that affect the NO-cGMP pathway.

Adult↗
PubMed2001

Factor XIIIA and clot strength after cardiopulmonary bypass.

Reduced factor XIIIA levels and decreased clot strength have been associated with increased bleeding after cardiopulmonary bypass (CPB). The purpose of this study was to evaluate the relationship between hemostatic factors, including factor XIIIA, and clot strength before, during and after CPB. Factor XIIIA antigen, platelet counts, fibrinogen, factor V activity, tissue plasminogen activator and clot strength (by thromboelastograph) were measured at baseline, after 45 min of CPB, at the end of CPB and 4 h post-operatively in 34 patients. Baseline factor XIIIA antigen was 5.2 +/- 1.4 mg/l. On average, factor XIIIA levels dropped to 64% and clot strength to 77% of baseline values after 45 min on CPB and remained below baseline during the immediate post-operative period. Clot strength was significantly correlated (r = 0.81) with platelet count and fibrinogen but not plasma factor XIIIA levels. Addition of 10 mg/l recombinant factor XIII[a2] significantly increased clot strength. Postoperative bleeding at 2 h was inversely correlated with platelet count, factor XIIIA antigen and clot strength measured at the end of CPB. Maintenance of adequate platelet counts and factor XIIIA levels at the end of CPB may play a role in maintaining clot strength and reducing blood loss.

Adult↗
PubMed2001

Thromboelastography: a reliable test?

The thromboelastograph (TEG), a measure of global haemostasis, is routinely used during cardiac and hepatic surgery to optimize blood product selection and usage. It has recently been suggested that it may also be a useful tool to screen patients with hypercoagulable states. Limited published data on performance characteristics has led to speculation regarding its consistency and, therefore, validity of the results. This study was designed to assess the effect of stability of blood samples prior to testing, repeated sampling, intra- and inter-assay variability using the native, celite, tissue factor (TF) and Reopro-modified TEG. Analysis of native and celite samples after storage over 90 min showed a period of instability up to 30 min. Thereafter, all parameters between 30 and 90 min were stable [P = not significant (NS)]. When the same sample was repeatedly assayed, both native and celite TEG parameters showed a significant change towards hypercoagulability (P < 0.01), whereas the TF and Reopro-modified TEG showed no change. Intra- and inter-assay variability on samples tested after 30 min showed excellent reproducibility for all parameters (P = NS). The data suggest that the TEG is a useful tool in haemostasis but requires a formal standard operating procedure to be adopted that takes into account the initial period of sample instability.

Blood Specimen Collection↗
PubMed2001

Disintegration and reorganization of fibrin networks during tissue-type plasminogen activator-induced clot lysis.

In this study, we investigated tissue-type plasminogen activator (tPA)-induced lysis of glutamic acid (glu)-plasminogen-containing or lysine (lys)-plasminogen-containing thrombin-induced fibrin clots. We measured clot development and plasmin-mediated clot disintegration by thromboelastography, and used scanning electron microscopy (SEM) to document the structural changes taking place during clot formation and lysis. These events occurred in three overlapping stages, which were initiated by the addition of thrombin, resulting first in fibrin polymerization and clot network organization (Stage I). Autolytic plasmin cleavage of glu-plasminogen at lys-77 generates lys-plasminogen, exposing lysine binding sites in its kringle domains. The presence of lys-plasminogen within the thrombin-induced fibrin clot enhanced network reorganization to form thicker fibers as well as globular complexes containing fibrin and lys-plasminogen having a greater level of turbidity and a higher elastic modulus (G) than occurred with thrombin alone. Lys-plasminogen or glu-plasminogen that had been incorporated into the fibrin clot was activated to plasmin by tPA admixed with the thrombin, and led directly to clot disintegration (Stage II) concomitant with fibrin network reorganization. The onset of Stage III (clot dissolution) was signaled by a sustained secondary rise in turbidity that was due to the combined effects of lys-plasminogen presence or its conversion from glu-plasminogen, plus clot network reorganization. SEM images documented dynamic structural changes in the lysing fibrin network and showed that the secondary turbidity rise was due to extensive reorganization of severed fibrils and fibers to form wide, occasionally branched fibers. These degraded structures contributed little, if anything, to the structural integrity of the residual clot, and eventually collapsed completely during the course of progressive clot dissolution. These results provide new perspectives on the major structural events that occur in the fibrin clot matrix during fibrinolysis.

Fibrin↗
PubMed2002

Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation.

Besides the conventional laboratory tests, thromboelastography (TEG) is used to monitor hemostasis during liver transplantation. A previous pilot study suggested a beneficial effect of recombinant activated factor VII (rFVIIa) on transfusion requirements in liver transplantation. In the present study, we assess the effects of rFVIIa on coagulation variables and TEG. In six study patients, the prothrombin time (PT), the activated partial thromboplastin time (aPTT) and TEG variables [reaction time (r), kinetic time (k), or clot formation time, alpha angle (alpha), and maximal amplitude (MA)] were recorded before and after the administration of a bolus of 80 microg/kg rFVIIa. These patients were compared with six controls who did not receive rFVIIa. In contrast with the control group, a significant shortening of PT (P = 0.028) and aPTT (P = 0.028), r (P = 0.046) and k (P = 0.043) values, and a significant incline of the alpha angle (P = 0.028) were noticed after injection of rFVIIa, whereas MA increased not significantly (P = 0.075). rFVIIa rapidly improved coagulation variables in liver transplant patients including PT and aPTT. Of the TEG variables, r, k and alpha angle significantly improved, and MA showed a trend to increase. These data suggest that rFVIIa not only influences the speed of clot formation, but also the physical properties of the clot, which cannot be detected by routine coagulation tests.

Adult↗
PubMed2003

Assessment of blood coagulation in severe liver disease using thromboelastography: use of citrate storage versus native blood.

Thromboelastography evaluates the viscoelastic properties of blood coagulation. Using native blood, measurement must start soon after sampling. With normal coagulation, native and citrated blood values correlate well. No data exists from cirrhotic patients. We compared native and citrate thromboelastography parameters in 30 cirrhotic patients (20 Child-Pugh C class, two liver failure). Thromboelastography was performed within 4 min using native blood and after recalcification within 1-2 h of citrate storage. Thromboelastography variables (, alpha, ) were compared using the Mann-Whitney test, correlation investigated with the Pearson method and the degree of agreement with the Bland-Altman method. There was no significant difference between citrated and native blood for all variables. Median values for native and citrated were, respectively, 16.4 (range 2.3-22.5) and 15.1 (range 9.8-29.9); 6.3 (range 3.5-11.3) and 6.2 (range 2.8-10.9); 48.3 (range 30.7-62.9) and 46.2 (range 30.4-60.4); angle alpha 30.8 (range 18.7-46.8) and 33.2 (range 19.9-55.8). Correlation for each variable was significant ( 0.01). There was a good degree of agreement for all but two patients (both bleeding) for all variables. Citrated blood can substitute native blood using thromboelastography in cirrhotic patients, allowing more time between sampling and the thromboelastography measurement.

Adult↗
PubMed2004

Thromboelastography with citrated blood: comparability with native blood, stability of citrate storage and effect of repeated sampling.

Thromboelastography (TEG) with recalcified citrate blood is used as an alternative to native blood, but there is insufficient data regarding sample reliability and stability over time. Thus, TEG parameters of freshly drawn native blood were compared with those of recalcified citrated blood without celite in 10 healthy subjects, and the effect of repeated sampling over 240-min storage was evaluated. All TEG parameters following citrate storage remained stable between 30 min [clot formation time (k) = 7.2 +/- 0.6 min; maximum amplitude (ma) = 48.5 +/- 1.9 mm] and 2 h (k = 7.1 +/- 0.6 min; ma = 46.2 +/- 2.5 mm) after initial sampling, but were not comparable with native blood (k = 9.3 +/- 0.7 min; ma = 43.5 +/- 2.5 mm) at any time point. TEG parameters of repeatedly sampled citrated blood had a significant overall hypercoagulable trend throughout 4 h following sampling. In conclusion, in order to achieve reproducible results, citrated blood without celite may be utilized between 30 min and 2 h following sampling, but in normal subjects the TEG parameters following citrate storage are not comparable with native blood, possibly because of incomplete inhibition of the activation of the coagulation cascade. Thus, citrated blood can be used as a surrogate of native blood in assessing coagulation using TEG, but if repeated sampling is used the trend in hypercoagulability must be considered.

Anticoagulants↗
PubMed2004

Role of the Thrombelastograph as an adjunctive test in thrombophilia screening.

The Thrombelastograph (TEG) provides a global assessment of haemostatic function. We have investigated the potential role of TEG in thrombophilia testing by studying 87 consecutive patients (all with personal or family history of thrombosis). For each patient, routine thrombophilia screening tests and TEG were performed in parallel. In keeping with previous reports, at least one thrombophilic trait was identified in 34% of the patients. Among those patients with previous thrombosis, the yield from screening was higher (54% with prothrombotic trait). Overall, a hypercoaguable TEG was demonstrated in 45% of patients. However, TEG and standard thrombophilia testing did not necessarily identify the same subset of individuals. Of 39 patients with hypercoaguable TEG, only 17 had a demonstrable thrombophilic trait. Conversely, of 30 patients with proven thrombophilia, 17 also had a hypercoaguable TEG. We conclude that TEG cannot be used as a sole initial screening test in patients referred for thrombophilia testing, as it fails to identify 43% of underlying thrombophilic traits. However, TEG may be a useful adjunctive test, particularly in patients in whom the regular thrombophilia screen proves unremarkable. Prospective studies are warranted to determine whether a hypercoaguable TEG can be used to predict a subset of patients at increased risk for recurrent thrombotic events.

Adolescent↗
PubMed1996

Monitoring hemostasis.

As our understanding of the normal mechanisms of coagulation grows, so does our ability to monitor hemostasis. Evaluation of hemostasis will become more specific and accurate and instrumentation techniques will become simpler and more efficient as technology progress, facilitating the monitoring of hemostasis in the perioperative setting.

Blood Coagulation↗