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PubMed2004

Does homeopathically potentized antimony stimulate coagulation? A summary of previous findings and results of an in vitro 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 D5 has a procoagulatory effect in vitro, although the results suggest an effect on MA and possibly CT. More research is warranted.

Adult↗

PubMed1995

Thrombelastography reveals two causes of haemorrhage in HELLP syndrome.

We describe the use of thrombelastography in HELLP syndrome (Haemolysis, Elevated Liver Enzymes, Low Platelets). It differentiated between two possible causes of significant haemorrhage and revealed an accompanying underlying fibrinolysis. This allowed specific therapy to be directed at both abnormalities and, we believe, helped prevent this patient from undergoing radical surgery to curb blood loss.

Adult↗

PubMed1996

Thrombelastography changes in pre-eclampsia and eclampsia.

We have measured platelet count, bleeding time and thrombelastography (TEG) variables and the correlation between these variables in 49 pregnant patients presenting with pre-eclampsia or eclampsia. Eighteen patients (37%) had a platelet count < or = 150 x 10(9) litre-1 and seven (14%) had a platelet count < or = 100 x 10(9) litre-1. Bleeding time was prolonged > 9.5 min in 13 (27%) patients and the TEG was abnormal in four (8%). The TEG variables, k time and maximum amplitude (MA) had a strong correlation with platelet count (k time-platelet count < or = 150 x 10(9) litre-1, r = -0.68, P = 0.003, platelet count < or = 100 x 10(9) litre-1, r = -0.84, P = 0.02; MA--platelet count < or = 150 x 10(9) litre-1, r = 0.72, P = 0.001, platelet count < or = 100 x 10(9) litre-1, r = 0.78, P = 0.04). There was no correlation between bleeding time and thrombocytopenia (platelet count < or = 150 x 10(9) litre-1, r = -0.18, ns; platelet count < or = 100 x 10(9) litre-1, r = 0.09, ns). There was no correlation between bleeding time and any measured TEG variable. Of the 10 (20%) patients with an adequate platelet count (> 100 x 10(9) litre-1) but prolonged bleeding time, the TEG was normal, suggesting adequate haemostasis. An MA of 53 mm, which is the lower limit for normal pregnancy, correlated with a platelet count of 54 x 10(9) litre-1 (95% confidence limits 40-75 x 10(9) litre-1). Although the number of patients with severe thrombocytopenia was small, a platelet count of 75 x 10(9) litre-1 should be associated with adequate haemostasis.

Anesthesia, Conduction↗

PubMed1996

Heparinase-guided thrombelastography in an anticoagulated parturient.

We describe the use of heparinase-guided thrombelastography in the assessment of a parturient who had been anticoagulated with heparin for suspected thromboembolic disease. Reversal of the heparin effect in the heparinase-treated sample facilitated administration of protamine and successful subarachnoid analgesia for delivery.

Adult↗

PubMed1998

Effects of hypothermia on thrombelastography in patients undergoing cardiopulmonary bypass.

Thrombelastography (TEG) correlates with postoperative chest drain output in patients undergoing cardiopulmonary bypass (CPB). In vitro incubation with heparinase allows TEG monitoring during CPB, despite heparin anticoagulation. Hypothermia impairs coagulation, but these effects cannot be assessed by standard coagulation tests performed at 37 degrees C. The aim of this study was to assess the effects of hypothermia on TEG. Therefore, we have compared normothermic and temperature-adapted TEG in 30 patients undergoing CPB. Our data showed significantly impaired reaction time (r), kinetic time (k), and angle alpha (alpha) in temperature-adapted compared with normothermic TEG. Maximum amplitude (MA), reflecting absolute clot strength, was not affected at temperatures of 33-37 degrees C. These findings indicate a decrease in the speed of clot formation, but not absolute deterioration in clot quality. Furthermore, heparinase-modified TEG indicated that there were nine cases in which heparin effects persisted after heparin reversal with protamine, providing a rational guide to protamine therapy.

Adult↗

PubMed2005

Effects of protamine and heparin can be detected and easily differentiated by modified thrombelastography (Rotem): an in vitro study.

BACKGROUND: Precise coagulation monitoring might help prevent heparin-protamine mismatch and thus decrease postoperative blood loss. We therefore measured coagulation time (CT) by modified thrombelastography (Rotem) as a possible differential monitor of the effects of heparin and protamine. METHODS: Undiluted and diluted blood samples from 26 healthy volunteers were spiked with increasing concentrations of heparin (0.1, 0.2, 0.4, 0.8 and 1 U ml(-1)). In addition, undiluted blood was spiked with protamine hydrochloride (0.1, 0.2, 0.4, 0.8 and 1.6 U ml(-1)), and we tested the effect of protamine on the reversal of heparin 0.4 U ml(-1). Heparin-containing samples were analysed using the heparin-sensitive INTEM test and the heparinase-containing HEPTEM test; protamine series were also analysed with the EXTEM test (tissue factor activation). RESULTS: CT by the INTEM test [CT-INTEM; median (min/max)] increased significantly and dose-dependently with increasing concentrations of heparin [control, 175 s (146/226); heparin, 1.0 U ml(-1) 1320 s (559/2100); P<0.001] and protamine [control, 172 s (150/255); protamine, 1.6 U ml(-1) 527 s (300/1345); P<0.0001]. Up to heparin concentrations of 0.4 U ml(-1), results were similar in undiluted and diluted blood samples. As expected, CT-HEPTEM remained within the normal range for all tested heparin concentrations (median 180-183 s), but increased similarly to CT-INTEM for increasing protamine concentrations. CONCLUSION: CT measurement using the Rotem technique appears to be a valuable tool for heparin-protamine management. For detection of heparin alone, protamine alone and the two combined, the ratio of CT-INTEM:CT-HEPTEM can be used to distinguish the effects of heparin excess (CT-INTEM:CT-HEPTEM>1) from those of protamine excess (CT-INTEM:CT-HEPTEM=1).

Adult↗

PubMed2000

Preparation for regional anaesthesia induces changes in thrombelastography.

The effects of crystalloid and colloid infusions on coagulation measured by thrombelastography (TEG) present a confused picture. The influence of environmental factors may explain the disparity between previous studies. We studied two groups of 20 women presenting at term for elective Caesarean section. In the first group, TEG analysis was performed before and after infusion of Gelofusine 500 ml over 15 min. The second group was treated in the same way except that subjects did not receive fluid. We found significant changes in r and k values in both groups, suggesting enhanced coagulation. As hypercoagulable changes were also seen in the group that did not receive fluid preload, the hypothesis that moderate haemodilution causes hypercoagulability must be questioned. The influence of environmental factors can explain differences reported between in vivo and in vitro studies.

Adult↗

PubMed1998

Compromised blood coagulation: an in vitro comparison of hydroxyethyl starch 130/0.4 and hydroxyethyl starch 200/0.5 using thrombelastography.

UNLABELLED: We compared the effects of progressive in vitro hemodilution (30% and 60%) on blood coagulation in 80 patients receiving one of two different 6% hydroxyethyl starch (HES) solutions using thrombelastography (TEG). The newly developed solution has a mean molecular weight of 130 kD and a degree of substitution, defined as the average number of hydroxyethyl groups per glucose moiety, of 0.4 (HES 130/0.4); the conventional solution has a mean molecular weight of 200 kD and a degree of substitution of 0.5 (HES 200/0.5). Both HES solutions significantly compromised blood coagulation, as seen by an increase in reaction time and coagulation time and a decrease in angle alpha, maximal amplitude, and coagulation index (all P < 0.05). There was no difference between HES 130/0.4 and HES 200/0.5 diluted blood (P > 0.05 for all TEG variables). When analyzing the intrinsic HES effect by taking hemodilution with 0.9% saline into account, progressive hemodilution with both HES solutions resulted in an increasing clot lysis (P < 0.05 after 60 min). Again, there was no difference between HES 130/0.4 and HES 200/0.5 diluted blood. We conclude that HES 130/ 0.4 and HES 200/0.5 compromise blood coagulation to the same degree. IMPLICATIONS: Progressive in vitro hemodilution using hydroxyethyl starch (HES) compromises blood coagulation. We observed similar effects of a new HES solution with a mean molecular weight of 130 kD and a degree of substitution of 0.4 (HES 130/0.4), compared with the conventional HES 200/0.5.

Blood Coagulation↗

PubMed2001

Thrombelastography.

Thrombelastography is a 'near patient' test of coagulation. It is easy to perform and can provide information on a patient's coagulation status within 30 min. Despite more than 25 years of clinical experience, however, several basic questions relating thromboelastograph (TEG) parameters to standard coagulation tests remain unanswered, and the value of the TEG is established only in the setting of orthotopic liver transplantation and cardiopulmonary bypass surgery. This review will focus on the principles and practise of the TEG(R), and data supporting the current accepted uses. Potential future uses will also be discussed including evaluation of hypercoagulable states, and investigating the mechanism of coagulopathies due to drugs or disease that standard tests have failed to unravel.

Blood Coagulation Tests↗

PubMed1997

Usefulness of thrombelastography in assessment of trauma patient coagulation.

OBJECTIVE: Thrombelastography (TEG) is used to rapidly assess coagulation abnormalities in cardiac and transplant surgery. The purpose of this study was to investigate TEG in the initial assessment of trauma patient coagulation. METHODS: TEG was performed on 69 adult blunt trauma patients during their initial evaluation. Demographics, history of inherited coagulopathies, medications, TEG parameters, platelet count, prothrombin time/partial thromboplastin time, Revised Trauma Score (RTS), Injury Severity Score (ISS), use of blood products, and outcome were recorded. RESULTS: Mortality was 4.3%. Fifty-two patients demonstrated coagulation abnormalities by TEG; of these, 45 were hypercoagulable (mean ISS 13.1), and seven were hypocoagulable (mean ISS 28.6). Six of the seven hypocoagulable patients received blood transfusions within the first 24 hours. Mean ISS of the 17 patients with normal TEG parameters was 3.7. Logistic regression of ISS, Revised Trauma Score, prothrombin time/partial thromboplastin time, and TEG on use/nonuse of blood products within the first 24 hours demonstrates that only ISS (p < 0.001) and TEG (p < 0.05) are predictive of early transfusion. CONCLUSIONS: The majority of blunt trauma patients in this series were hypercoagulable. TEG is a rapid, simple test that can broadly determine coagulation abnormalities. TEG is an early predictor of transfusion in blunt injury patients.

Adolescent↗

PubMed2002

Differential efficacy of different platelet glycoprotein IIb/IIIa antagonists on platelet/fibrin-mediated clot dynamics under different conditions using thrombelastography: the critical need for anticoagulant.

BACKGROUND: Intravenous GpIIb/IIIa antagonists demonstrate various significant clinical benefits depending on the agent used. In contrast, oral delivery of GpIIb/IIIa antagonists failed in achieving clinical benefits. This raises the question about the differences among different GpII/IIIa antagonists. METHODS: The effect of various platelet glycoprotein (GP) IIb/IIIa antagonists on the dynamics of platelet/fibrin clot formation and strength was determined using thrombelastography under different conditions. RESULTS: GPIIb/IIIa antagonists with high affinity for resting and activated platelets and with slow rates of dissociation from GPIIb/IIIa (Class I antagonists) demonstrated potent and comparable inhibition of platelet aggregation and platelet-mediated clot strength under different conditions. In contrast to antagonists that dissociate rapidly from GPIIb/IIIa (class II antagonists). Class I antagonists such as the free acid form of roxifiban inhibited platelet-mediated clot strength, with the inhibiting concentration required for 50% effect (IC50) = 70 n mol/l, whereas the IC50 of the class II antagonists such as the free acid forms of orbofiban, sibrafiban, lotrafiban, integrilin or aggrastat ranged from 1 to 15 micromol/l. The IC50s for class II antagonists in inhibiting platelet/fibrin clot formation and strength were substantially greater (10-15 fold) than their clinically achievable concentrations. The limited efficacy for class II antagonists in inhibiting platelet-mediated clot dynamics was enhanced by the combination with heparin. CONCLUSIONS: Thus, these data indicated that there are differences in the efficacy of various GPIIb/IIIa antagonists in inhibiting platelet/fibrin clot formation and strength, which might be corrected by heparin. Data also suggest that inhibition of platelet aggregation may not be the sole determinant for the in-vivo efficacy of various GPIIb/IIIa antagonists.

Anticoagulants↗

PubMed2005

Using thrombelastography to determine the efficacy of the platelet glycoprotein IIb/IIIa antagonist, roxifiban, on platelet/fibrin-mediated clot dynamics in humans.

The effect of platelet glycoprotein IIb/IIIa antagonists on the dynamics of platelet/fibrin clot formation and strength was determined using thrombelastography (TEG) under conditions of recalcification or tissue factor addition. In the present investigation, the effect of roxifiban (class I) on ex vivo clot dynamics using recalcified blood was tested in normal, healthy volunteers (n = 7) dosed with 1 mg BID roxifiban for 9 days. Roxifiban inhibited platelet aggregation induced by 20 mumol/l adenosine diphosphate by 60-90% but did not significantly affect any of the TEG parameters either at peak, trough, or subtrough drug levels. Addition of 30 nmol/l roxifiban free acid (XV459; which is ineffective by itself to modify TEG parameters) to human blood obtained from roxifiban-treated subjects resulted in 45-60% (P < 0.01) inhibition of clot strength (maximum amplitude), 90-100% (P < 0.01) inhibition of initial kinetic of clot development (angle alpha), and 50-70% (P < 0.01) inhibition of early clot initiation (K). These data suggest that a subthreshold blood level of 40-50 nmol/l roxifiban active form was achieved in those subjects, as estimated from an in vitro calibration with XV459. These data indicate (not studied) that roxifiban, at a targeted clinical dosing regimen, failed to achieve sufficient exposure to modulate platelet-mediated clot retraction.

Amidines↗

PubMed1990

Usefulness of thrombelastography for dosage monitoring of low molecular weight heparin and unfractionated heparin during hemodialysis.

Low molecular weight heparin (LMH) acts as an anticoagulation agent mainly through its anti-activated coagulation factor X (Xa) activity. Thrombelastography (TEG) is expected to be useful to monitor the dosage of LMH during hemodialysis because reaction time on TEG (TEG-r) is considered to reflect blood thromboplastin formation time, which depends on the formation of Xa. To test this possibility, we compared the usefulness of TEG, activated coagulation time (ACT), activated partial thromboplastin time (APTT), and anti-Xa activity in 28 hemodialysis patients using both conventional unfractionated heparin (UFH) and LMH on separate dialysis procedures. Anti-Xa activity of LMH was comparable to that of UFH when it was measured using both LMH and UFH as standards. Anti-Xa activity, which theoretically depended on the heparin concentration in blood samples, did not correlate with the degree of dialyzer clotting. The APTT correlated well with anti-Xa activity in patients using LMH (r = 0.686, p less than 0.01) and UFH (r = 0.906, p less than 0.01), but not with the degree of dialyzer clotting. The TEG-r correlated well with the degree of dialyzer clotting both in patients using LMH and those using UFH (measurements of samples obtained from the venous side of the extracorporeal circuit) and weakly correlated with anti-Xa activity in patients using LMH (r = 0.402, p less than 0.05). The ACT did not correlate with the degree of dialyzer clotting or anti-Xa activity. These results suggest that TEG-r reflects the efficacy of heparin in the extra-corporeal blood circuit, whereas APTT mainly reflects heparin concentration of the blood samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Factor Xa Inhibitors↗

PubMed2004

Different effects of abciximab and cytochalasin D on clot strength in thrombelastography.

Maximum amplitude (MA) in thrombelastography (TEG) consists of a plasmatic and a platelet component. To assess the magnitude of the plasmatic component, pharmacological approaches have been proposed to eliminate the platelet component. We evaluated the individual and combined effects of abciximab and cytochalasin D on the MA of TEG. Whole blood, platelet-rich plasma (PRP) and homologous platelet-poor plasma (PPP) from 20 healthy volunteers were spiked with abciximab or cytochalasin D or a combination of both and TEGs performed. Abciximab and cytochalasin D decreased MA in all samples. MA of whole blood (18.6 +/- 3.1 mm) and PRP (33.7 +/- 3.5 mm) spiked with abciximab or cytochalasin D alone (15.0 +/- 2.9 mm and 25.0 +/- 4.0 mm) were significantly higher when compared with abciximab and cytochalasin D combined (10.4 +/- 3.0 and 20.2 +/- 3.5 mm). While MA of PRP and homologous PPP were significantly (P < 0.001) different after individual administration of abciximab and cytochalasin D, combination of both abolished this difference (20.2 +/- 3.5 mm and 20.4 +/- 3.7 mm, P = 0.372). In whole blood of critically ill patients or patients undergoing major surgery there was also a significant difference of MA between abciximab alone and in combination with cytochalasin D (16.5 +/- 11.3 mm and 11.3 +/- 7.7 mm, P < 0.001). This indicates that in contrast to individual administration of abciximab or cytochalasin D, a combination of both compounds eliminates the platelet-specific effect on MA of TEG tracings.

Abciximab↗

PubMed2006

Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography.

BACKGROUND: Reagent-supported thromboelastometry with the rotation thrombelastography (e.g. ROTEM) is a whole blood assay that evaluates the visco-elastic properties during blood clot formation and clot lysis. A hemostatic monitor capable of rapid and accurate detection of clinical coagulopathy within the resuscitation room could improve management of bleeding after trauma. OBJECTIVES: The goals of this study were to establish whether ROTEM correlated with standard coagulation parameters to rapidly detect bleeding disorders and whether it can help to guide transfusion. METHODS: Ninety trauma patients were included in the study. At admission, standard coagulation assays were performed and ROTEM parameters such as clot formation time (CFT) and clot amplitude (CA) were obtained at 15 min (CA(15)) with two activated tests (INTEM, EXTEM) and at 10 min (CA(10)) with a test analyzing specifically the fibrin component of coagulation (FIBTEM). RESULTS: Trauma induced significant modifications of coagulation as assessed by standard assays and ROTEM. A significant correlation was found between prothrombin time (PT) and CA(15)-EXTEM (r = 0.66, P < 0.0001), between activated partial thromboplastin time and CFT-INTEM (r = 0.91, P < 0.0001), between fibrinogen level and CA(10)-FIBTEM (r = 0.85, P < 0.0001), and between platelet count and CA(15)-INTEM (r = 0.57, P < 0.0001). A cutoff value of CA(15)-EXTEM at 32 mm and CA(10)-FIBTEM at 5 mm presented a good sensitivity (87% and 91%) and specificity (100% and 85%) to detect a PT > 1.5 of control value and a fibrinogen less than 1 g L(-1), respectively. CONCLUSIONS: ROTEM is a point-of-care device that rapidly detects systemic changes of in vivo coagulation in trauma patients, and it might be a helpful device in guiding transfusion.

Blood Coagulation Disorders↗

PubMed1996

The development of hypercoagulability state, as measured by thrombelastography, associated with intraoperative surgical blood loss.

Thrombelastographic evidence of hypercoagulability, including shortening of r-time (P < 0.01); shortening of k-time (P < 0.01); and widening of trace angle (P < 0.01) were observed in a group of 21 Chinese surgical patients when (a) the amount of blood loss was at an estimated 10% of total blood volume and (b) the amount of blood loss was at an estimated 15% of blood volume. The amount of blood loss was documented by haemoglobin measurements. No evidence of hypercoagulability was observed at around one hour into the operation in the absence of bleeding. We conclude that a mild to moderate degree of surgical blood loss with haemodilution is associated with the development of hypercoagulability as measured by thrombelastography. Further studies looking at the thrombebolic outcome in such groups of patients is warranted. It is also suggested that caution should be exercised in the use of intraoperative isovolaemic haemodilution until the phenomenon is further investigated.

Adult↗

PubMed1996

The effect of aprotinin on thrombelastography in vitro.

The effect of low dose (50 KIU/ml) and high dose (200 KIU/ml) aprotinin on standard thrombelastographic variables (r, K, alpha, MA) was examined in vitro using blood from forty ASA Class 1 patients. Both concentrations of aprotinin resulted in minor increases in r time above the normal range (P < 0.05). Aprotinin did not alter other thrombelastographic variables. The results indicate that aprotinin is a mild direct anticoagulant in vitro as assessed by thrombelastography.

Adolescent↗

PubMed2004

Electron microscopic evaluations of clot morphology during thrombelastography.

In this study, we characterized clot morphology with a scanning electron microscope (SEM) at time points corresponding to the commonly used thrombelastography (TEG) variables, illustrating the correlation of the physical clot formation with TEG(R) tracings. The first channel of the TEG analyzer was used to obtain the tracings of clot formation, while the sub-samples for the SEM were obtained from the second TEG channel. Different types of samples were examined, including whole blood, abciximab-treated whole blood, platelet-rich plasma (PRP), and abciximab-treated PRP. The SEM images were obtained at reaction time, different amplitudes (5-30 mm), maximum amplitude (MA), and at amplitude 60 min after MA. In the whole blood, coarse fibrin and activated platelets were observed at reaction time and fibrin strands progressively became more solid and intertwined at amplitude 10 mm and thereafter. Red blood cells were surrounded with fibrin strands at amplitude 30 mm and were tightly packed by fibrin strands at MA. In abciximab-treated whole blood, red blood cell shape was maintained at MA. The process of fibrin formation and platelet activation was also examined in PRP. Abciximab did not block platelet shape change, although the blockage of fibrin binding to platelets was shown on the TEG analyzer. In summary, we have shown structural changes of the forming clot in relation to TEG variables.

Abciximab↗