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The value of the thromboelastogram as means of monitoring the sub-cutaneous preventive action of calcium heparinate.

The index of the thrombodynamic potential (I.T.P.) as one of the biological means of controlling the prophylactic effect of sub-cutaneous injections of Calcium Heparinate has been studied in 34 spinal cord injuries during the acute phase. Individual tolerance variations, some of them important, have been noted as well as the necessity of adjusting the doses, according to the time after injury. A biological hypercoagulability has been noted within the first and third month after injury. The interest and the cost of such a method are discussed and further comparative biological investigations, using other methods, have started.

Female↗

The effect of ionised magnesium on coagulation using thromboelastography.

Magnesium is an ionised mineral with therapeutic uses. There is laboratory evidence that it may have an anticoagulant activity although recent research has been to the contrary. The clinical implications of the effect of a therapeutic dose of magnesium on coagulation have yet to be resolved conclusively. In our study, 10 healthy volunteers were given 4 g of magnesium sulphate intravenously. Thromboelastographs were recorded and blood analysed for haematological indices, before and after the infusion. All variables associated with coagulation remained unchanged except the alpha angle on the thromboelastograph which increased significantly. We conclude that in our in vivo study, the effect of magnesium sulphate on coagulation is not clinically significant.

Blood Coagulation↗

The effects of ropivacaine hydrochloride on coagulation and fibrinolysis. An assessment using thromboelastography.

Amide local anaesthetics impair coagulation by inhibition of platelet function and enhanced fibrinolysis. The potential therefore exists that the presence of amide local anaesthetics in the epidural space could contribute to the therapeutic failure of an epidural autologous blood patch. Ropivacaine is an aminoamide local anaesthetic increasingly used for epidural analgesia and anaesthesia, particularly in obstetric practice. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur clinically in the epidural space, alter coagulation or fibrinolysis. Thromboelastography was used to assess clotting and fibrinolysis of blood to which ropivacaine had been added. Although modest alterations in maximum amplitude, coagulation time and alpha angle were observed, the effect of ropivacaine on clotting and fibrinolysis was not clinically significant. We conclude that it is unlikely that the presence of ropivacaine in the epidural space would reduce the efficacy of an early or prophylactic epidural blood patch.

Adult↗

The effects of hypertonic saline solution (7.5%) on coagulation and fibrinolysis: an in vitro assessment using thromboelastography.

We studied the effects of hypertonic (7.5%) and normal saline on coagulation and fibrinolysis in an in vitro model using thromboelastography of human whole blood. Reaction times increased and alpha angles decreased with hypertonic saline replacement at 7.5% blood volume compared with similar dilution with normal saline. At 10% blood volume replacement with hypertonic saline, reaction and coagulation times were significantly increased and alpha angles were decreased. Clot lysis at 30 min was also significantly reduced. We conclude that 7.5% hypertonic saline solution has anticoagulant effects if it replaces 7.5% or more of blood volume.

Adult↗

Coagulation effects of in vitro serial haemodilution with a balanced electrolyte hetastarch solution compared with a saline-based hetastarch solution and lactated Ringer's solution.

The hydroxyethyl starches are a group of compounds that has been associated with impairment of coagulation when large volumes are administered. The thrombelastograph is commonly used to assess point-of-care whole blood coagulation. Little is known about the dose-response relationships of haemodilution, and it is reasonable to assume that a linear association exists. This may not be the case with altered electrolyte compositions of the fluids used for haemodilution. We have therefore conducted an in vitro study of haemodilution of human whole blood using lactated Ringer's solution and two high molecular weight hetastarches, one in a balanced salt solution, the other in a 0.9% saline solution. The thrombelastograph, commonly used for the assessment of the coagulation effects of synthetic colloids, was used as the coagulation assessment device. Serial haemodilution with hetastarch in a balanced salt solution demonstrated a biphasic response (of r-times and k-times, as well as alpha angles), with haemodilution in the 20-40% range causing enhanced coagulation, and higher degrees of dilution causing a decrease in overall coagulation performance. A similar picture was observed with lactated Ringer's solution, but only significantly so in alpha angles. Hetastarch in saline did not display this initial increased coagulability at mild to moderate dilutions. This biphasic response of lactated Ringer's solution and hetastarch in a balanced salt solution reflects the complex interaction of fluids and the coagulation system, and that these effects cannot be attributed to simple haemodilution. On the other hand, there was a linear decrease in maximum amplitude with haemodilution. Maximum amplitude was particularly affected by both starches, which is an expected finding in view of the known interaction between the hydroxyethyl starches and von Willebrand's factor.

Blood Coagulation↗

Dose dependent effect of aprotinin on rate of clot formation.

Forty-eight patients scheduled for elective cardiac surgery were randomly assigned to receive aprotinin in the following doses: 0.2 mg kg-1 (group A), 0.7 mg kg-1 (group B), 1 mg kg-1 (group C) and 1.4 mg kg-1 (group D). Clot formation was analysed by thromboelastography immediately after induction of anaesthesia and again 30 min after administration of aprotinin. Rate of clot formation was assessed using R (reaction time = rate of initial fibrin formation), K (clot formation time = rate of fibrin build-up and cross linking) and angle of clot formation (denoting speed at which solid clot forms). Strength of the clot was assessed by maximal amplitude of clot formation (MA) and % lysis after 30 and 60 min. Significant reduction of R and K times and increase in angle of clot formation was observed in groups A and B. This effect was not apparent in the other groups. In group D, an increase in R time was noted. These findings indicate a dose-dependent effect of aprotinin on rate of clot formation with an earlier clot formation at low doses.

Aged↗

Evaluation of the anticoagulant properties of aprotinin in vitro.

The interaction of aprotinin with normal coagulation was studied in blood samples obtained from 10 healthy subjects. Each sample was simultaneously tested in four different preparations: NaCl-treated blood: 0.03 mL 0.9% NaCl in 0.33 mL blood; aprotinin treated blood: 0.33 mL blood+aprotinin in 0.03 mL in aliquots to obtain a final blood concentration of respectively 50 KIU mL-1; 100 KIU mL-1 and 200 KIU mL-1. The coagulation process was analysed by thromboelastography. R-time, reflecting intrinsic coagulation, increased in a dose dependent manner between NaCl-treated and aprotinin-treated blood. These findings suggest a dose dependent impairment of intrinsic coagulation by aprotinin.

Anticoagulants↗

A retrospective survey of fibrinolysis as an indicator of poor outcome after cardiopulmonary bypass and a possible early sign of systemic inflammation syndrome.

A retrospective survey was undertaken of 142 adults who had undergone cardiac surgery with cardiopulmonary bypass. According to the manufacturer's instructions for thromboelastography, patients were identified as showing evidence of fibrinolysis if after coming off bypass the Ly30 index was > or =7.5%. In the 20 fibrinolytic patients, fibrinolysis was readily corrected by tranexamic acid but these patients needed more colloid and more vasopressor support than the non-fibrinolytic patients. There were three deaths, all in the fibrinolytic patients. It is possible that fibrinolysis is a marker for onset of systemic inflammation syndrome. It is recommended that, until the association between fibrinolysis and worse outcome is investigated further, patients showing fibrinolysis early after cardiopulmonary bypass should not be discharged too soon from intensive care.

Aged↗

Evaluation of the effects of levobupivacaine on clotting and fibrinolysis using thromboelastography.

Amide local anaesthetics inhibit platelet function. We hypothesized that residual anaesthetic in the epidural space could decrease efficacy of an epidural blood patch in preventing postdural puncture headache. Levobupivacaine has recently been approved for epidural anaesthesia. Its effects on coagulation have not previously been studied. The aim of this study was to determine the effects of levobupivacaine on clotting using thromboelastography. Ten ASA Class I volunteers were studied. Venous blood samples were analysed using a Haemoscope 2000D TEG analyser. Whole blood, a 50% saline control and two levobupivacaine solutions (2.5 mg mL(-1) and 2.5 microg mL(-1) in blood) were compared. The former reproduces that produced in the epidural space by blood (20 mL for an epidural blood patch) and levobupivacaine 0.5% (20 mL). The latter approximates plasma concentrations following epidural injection of levobupivacaine 0.5% (20 mL). P < 0.05 was considered significant. Maximum amplitude (MA), a measure of clot strength, is decreased by levobupivacaine 2.5 mg mL(-1). Levobupivacaine 2.5 mg mL(-1) decreases clot strength and may reduce efficacy of a prophylactic epidural blood patch.

Adult↗

Potential role of the dynamic properties of whole blood coagulation in assessment of dosage requirements in haemophilia.

In the clinical setting, patients suffering from haemophilia are classified according to the residual level of the deficient coagulation factor. Patients suffering from the severe form of haemophilia (critical factor level <0.01 IU mL-1) display some heterogeneity in their tendency to bleeding despite the uniform factor level. Utilizing a new thrombelastographic method in which coagulation is activated by very small amounts of tissue factor and where resulting data are processed with new software, we studied the whole blood coagulation profile in 11 patients with severe haemophilia A and 11 patients with moderate haemophilia. In both groups of patients, we found a considerable degree of heterogeneity in the coagulation signal. In moderate haemophilia with factor VIII (FVIII):C levels between 0.01 and 0.05 IU mL-1, variance was expected, whereas a quite substantial diversity had not been forecasted in patterns of the whole blood coagulation profiles in patients with the severe form of haemophilia A. Ex vivo substitution to patient's blood to reach various theoretical levels of recombinant factor VIII (rFVIII) revealed that the coagulation response to FVIII supplementation varied substantially. In some severely affected patients levels of FVIII:C close to 0.05 IU mL-1 was sufficient to normalize the coagulation profile, while others required a dose giving >0.50 IU mL-1 of FVIII to achieve a normal whole blood clotting profile. In conclusion, our study revealed that severe haemophilia A seems not to be a single entity, but rather several different clinical and biochemical phenotypes, and that the response to added FVIII varies amongst patients.

Blood Coagulation↗

The kaolin-activated Thrombelastograph predicts bleeding after cardiac surgery.

OBJECTIVE: The objective of this study was to determine the relationship of the kaolin-activated Thrombelastograph (TEG) with postoperative bleeding and laboratory tests of coagulation in the setting of cardiac surgery with the routine use of -aminocaproic acid. DESIGN: Prospective observational study. SETTING: An adult heart center at a tertiary referral, university hospital. PARTICIPANTS: Thirty adult cardiac surgical patients. INTERVENTIONS: The kaolin-activated TEG, platelet counts, prothrombin times, activated partial thromboplastin times, and fibrinogen levels were measured before induction of anesthesia, during cardiopulmonary bypass, and on arrival in the intensive care unit. Mediastinal and thoracostomy drainage were measured every hour for 4 hours after arrival in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Correlation and multivariate linear regression modeling were used to describe relationships among coagulation tests, TEG parameters, and early postoperative bleeding. The TEG maximum amplitude (MA) parameter correlated well with postoperative bleeding (r = -0.6, p = 0.0018), more so than platelet count (r = -0.45, p = 0.02), fibrinogen level (r = -0.40, p = 0.06), or prothrombin time (r = 0.43, p = 0.02). The receiver operating characteristic curve c-index describing MA as a predictor for postoperative bleeding is 0.78. Abnormalities in all the laboratory test results were associated with an abnormal MA. CONCLUSIONS: In conclusion, the kaolin-activated TEG is associated with early coagulopathic bleeding. It may reflect the severity of a global coagulopathy affecting both platelets and coagulation factors and be a guide to incremental prohemostatic therapy in this setting.

Aged↗

Transfusion triggers in orthotopic liver transplantation: a comparison of the thromboelastometry analyzer, the thromboelastogram, and conventional coagulation tests.

OBJECTIVES: The Thromboelastogram (TEG; Haemoscope Corporation, Niles, IL) and the ROTEM thromboelastometry analyzer (Pentapharm GmbH, Munich, Germany) are coagulation monitors that measure the viscoelastic changes accompanying whole-blood coagulation generation and lysis. It is not clear whether TEG and ROTEM transfusion algorithms suggest similar blood component intervention. This study aims to report the extent to which administration of platelets, fresh frozen plasma, and cryoprecipitate would be indicated using protocol-dictated interventions by the Rotem, TEG, and conventional coagulation screens during orthotopic liver transplantation (OLT). DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: Twenty patients undergoing orthotopic liver transplantation. INTERVENTIONS: Coagulation was managed with native TEG protocols. Additional samples for kaolin TEG, kaolin heparinase TEG, Rotem in-TEM, Rotem hep-TEM, Rotem fib-TEM, full blood count, prothrombin time, and Clauss fibrinogen assays were taken at 5 fixed operative stages. MEASUREMENTS AND MAIN RESULTS: Results were reviewed and protocol-indicated interventions recorded. There was moderate agreement between Clauss fibrinogen and Rotem fib-TEM assays about fulfilling fibrinogen transfusion criteria (kappa = 0.42, p < or = 0.05). Agreement between TEG and Rotem to transfuse platelets was fair (Rotem in-TEM/native heparinase TEG, kappa = 0.33, Rotem in-TEM/kaolin heparinase TEG, kappa = 0.28). There was moderate agreement between Rotem in-TEM and prothrombin time (kappa = 0.42), and poor agreement between other tests about the point to administer fresh frozen plasma. CONCLUSIONS: Transfusion practice is likely to differ according to the method of coagulation monitoring used. A prospective case-matched study using the viscoelastic tests used in this study would be beneficial in determining the optimal therapy. Rotem fib-TEM monitoring may improve hemostasis management.

Blood Coagulation Tests↗

Calcium supplementation of saline-based colloids does not produce equivalent coagulation profiles to similarly balanced salt preparations.

OBJECTIVES: The primary objective of this study was to test the hypothesis that calcium alone does not account for the observed coagulation differences between saline-based and balanced electrolyte IV fluid preparations. DESIGN: Controlled, nonblinded, in vitro observational study. SETTING: University-based anesthesia research laboratory. PARTICIPANTS: Ten healthy volunteers. INTERVENTIONS: The volunteers donated fresh blood for in vitro 40% and 60% dilution with 6 intravenous fluid preparations (lactated Ringer's solution, human albumin solution, and 4 hydroxyethyl starch preparations). All saline-based fluids were supplemented with calcium chloride to obtain ionized concentrations >or=1.0 mmol/L. MEASUREMENTS AND MAIN RESULTS: After dilution of the fresh blood with the study fluids, samples were analyzed by using the Thrombelastograph. Three colloid preparations produced minimal coagulation derangement, even at 60% dilution (human albumin solution, tetrastarch in saline, and pentastarch in balanced electrolyte solution), whereas pentastarch in saline and hetastarch in balanced electrolyte produced a mildly hypocoagulable state at 60% dilution. CONCLUSIONS: The different coagulation profiles between the 2 pentastarch preparations, as well as similar profiles of pentastarch in saline and hetastarch in balanced electrolyte solution, suggest that calcium is not solely responsible for previously observed effects.

Albumins↗

Views on methods for monitoring recombinant factor VIIa in inhibitor patients.

The development of recombinant factor VIIa (rFVIIa) has greatly augmented the range of treatment options available for hemophilia patients with inhibitors. However, there still remains a lack of consensus regarding several aspects of treatment with bypassing agents such as rFVIIa, prothrombin complex concentrates (PCC), and activated PCC (aPCC). Such unresolved issues may be clarified by the identification of a suitable laboratory monitoring method with which to correlate clinical outcomes. This paper will review the need for an effective and informative monitoring strategy, and will discuss several candidate methods that have been employed for the measurement of hemostatic efficacy following therapy with bypassing agents. To date, however, no assay endpoint has been developed that can correlate accurately with clinical outcomes in a sufficiently large patient sample.

Blood Coagulation Factor Inhibitors↗

Thromboelastography and recombinant factor VIIa-hemophilia and beyond.

Thromboelastography (TEG), which records the continuous profiles of whole blood (WB) coagulation, can be used to evaluate the effects of hemostatic agents, such as recombinant factor VII (rFVIIa). Our group has developed a revised TEG model, involving activation with minute amounts of tissue factor and subsequent signal processing, and has used this method to evaluate the effects of rFVIIa both in patients with hemophilia and in those receiving vitamin K antagonist (VKA) thromboprophylaxis. We review the early results of our investigations, which suggest that, in clinical situations where rFVIIa has shown benefit, the changes in the profiles obtained by TEG recording appear to correlate with the clinical outcome.

Adult↗