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Coagulation Monitoring: Current Techniques and Clinical Use of Viscoelastic Point-of-Care Coagulation Devices

Ganter, Michael T., MD*; Hofer, Christoph K., MD

doi: 10.1213/ane.0b013e318168b367
Cardiovascular Anesthesiology: Review Article
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Chinese Language Editions

Perioperative monitoring of blood coagulation is critical to better understand causes of hemorrhage, to guide hemostatic therapies, and to predict the risk of bleeding during the consecutive anesthetic or surgical procedures. Point-of-care (POC) coagulation monitoring devices assessing the viscoelastic properties of whole blood, i.e., thrombelastography, rotation thrombelastometry, and Sonoclot® analysis, may overcome several limitations of routine coagulation tests in the perioperative setting. The advantage of these techniques is that they have the potential to measure the clotting process, starting with fibrin formation and continue through to clot retraction and fibrinolysis at the bedside, with minimal delays. Furthermore, the coagulation status of patients is assessed in whole blood, allowing the plasmatic coagulation system to interact with platelets and red cells, and thereby providing useful additional information on platelet function. Viscoelastic POC coagulation devices are increasingly being used in clinical practice, especially in the management of patients undergoing cardiac and liver surgery. Furthermore, they provide useful information in a large variety of clinical scenarios, e.g., massive hemorrhage, assessment of hypo- and hypercoagulable states, guiding pro- and anticoagulant therapies, and in diagnosing of a surgical bleeding. A surgical etiology of bleeding has to be considered when viscoelastic test results are normal. In summary, viscoelastic POC coagulation devices may help identify the cause of bleeding and guide pro- and anticoagulant therapies. To ensure optimal accuracy and performance, standardized procedures for blood sampling and handling, strict quality controls and trained personnel are required.

From the *Department of Anesthesia and Perioperative Care University of CA San Francisco, San Francisco California; and †Institute of Anesthesiology and Intensive Care Medicine, Triemli City Hospital Zurich, Switzerland.

Accepted for publication December 28, 2007.

This review was written without any financial support from manufacturers or the pharmaceutical industries. None of the authors is related to or has financial interests in any of the companies or manufacturers of products related to this study.

Address correspondence and reprint requests to Christoph K. Hofer, MD, Institute of Anesthesiology and Intensive Care Medicine, Triemli City Hospital Zurich, Birmensdorferstr. 497,8063 Zurich, Switzerland. Address e-mail to christoph.hofer@triemli.stzh.ch.

Perioperative monitoring of coagulation is important to diagnose potential causes of hemorrhage, to guide hemostatic therapies, and to predict the risk of bleeding during the consecutive surgical procedures.1 Most commonly, routine laboratory-based coagulation tests (e.g., prothrombin time/International Normalized Ratio, activated partial thromboplastin time, fibrinogen) and platelet numbers are being used to assess the patients’ current coagulation status. However, the value of these tests has been questioned in the acute perioperative setting2 because there are delays from blood sampling to obtaining results (45–60 min), coagulation tests are determined in plasma rather than whole blood, no information is available on platelet function (PF) and the assays are performed at a standard temperature of 37°C rather than the patient’s temperature.

Point-of-care (POC) coagulation monitoring devices assessing the viscoelastic properties of whole blood, i.e., thrombelastography (TEG®), rotation thrombelastometry (ROTEM®), and Sonoclot® analysis may overcome several limitations of routine coagulation tests.3,4 Blood is analyzed at the bedside and not necessarily in the central laboratory, allowing faster turnaround times. The coagulation status is assessed in whole blood, allowing in vivo coagulation system interactions with platelets and red blood cells to provide useful information on PF. Furthermore, the clot development can be visually displayed in real-time and the coagulation analysis can be done at the patient’s temperature. However, a significant difference between in vitro and in vivo coagulation has to be considered: viscoelastic coagulation tests measure the coagulation status under static conditions (no flow) in a cuvette (not an endothelialized blood vessel). Therefore, results obtained from these in vitro tests must be carefully interpreted after considering the clinical conditions (e.g., overt bleeding in the surgical site).

The aim of this article is to review the basic principles of the current viscoelastic POC coagulation analyzers, to outline their clinical use, and to evaluate their ability to monitor different pharmacological substances interacting with hemostasis in the perioperative setting. Viscoelastic POC devices have also been used for coagulation testing of certain hemostatic disorders or syndromes in the hemostasis laboratory, but will not be discussed in this review.

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Thrombelastography, Thrombelastometry

Thrombelastography was first described by Hartert in 1948 as a method to assess the global hemostatic function from a single blood sample.5 In the earlier literature, the terms “thrombelastography,” “thrombelastograph,” and “TEG®” have been used generically. However, in 1996 thrombelastograph® and TEG® became registered trademarks of the Hemoscope Corporation (Niles, IL) and from that time on these terms have been used to describe the assay performed using Hemoscope instrumentation only. Alternatively, Pentapharm GmbH (Munich, Germany) markets a modified instrumentation using the terminology rotation thrombelastometry, ROTEM®.3

The TEG/ROTEM® assess the viscoelastic properties of blood samples under low shear conditions. The TEG® (Fig. 1A) measures the clot’s physical property by using a stationary cylindrical cup that holds the blood sample and oscillates through an angle of 4°45′. Each rotation cycle lasts 10 s. A pin is suspended in the blood by a torsion wire and is monitored for motion (Fig. 2A). The torque of the rotation cup is transmitted to the immersed pin only after fibrin-platelet bonding has linked the cup and pin together. The strength of these fibrin-platelet bonds affects the magnitude of the pin motion. Thus, the output is directly related to the strength of the formed clot. As the clot retracts or lyses, these bonds are broken and the transfer of cup motion is again diminished. The rotation movement of the pin is converted by a mechanical-electrical transducer to an electrical signal, finally being displayed as the typical TEG® tracing (Fig. 3A). The ROTEM® instrument (Fig. 1B) uses a modified technology: the signal of the pin suspended in the blood sample is transmitted via an optical detector system, not a torsion wire, and the movement is initiated from the pin, not the cup (Fig. 2B).6 Furthermore, the instrument is equipped with an electronic pipette.

Figure 1.

Figure 1.

Figure 2.

Figure 2.

Figure 3.

Figure 3.

Table 2

Table 2

Table 3

Table 3

TEG/ROTEM® both measure and graphically display the changes in viscoelasticity at all stages of the developing and resolving clot, i.e., the time until initial fibrin formation (TEG® reaction time; ROTEM® clotting time [CT]), the kinetics of fibrin formation and clot development (TEG® kinetics, α angle [α]; ROTEM® clot formation time, α angle [α]), the ultimate strength and stability of the fibrin clot (TEG® maximum amplitude [MA]; ROTEM® maximum clot firmness [MCF]), and clot lysis (fibrinolysis) (Table 2).7,8 TEG/ROTEM® are fibrinolysis-sensitive assays and allow for diagnosis of hyperfibrinolysis in bleeding patients.3,9 In our review, the variables from the TEG/ROTEM® will be referred to as they respectively relate to each instrument, for example, R/CT or MA/MCF.

Commercially available tests for both technologies are listed in Table 1. Typically, blood samples are activated extrinsically (tissue factor) and/or intrinsically (contact activator). Furthermore, to determine fibrinogen levels, tests in the presence of a platelet inhibitor (e.g., cytochalasin D in fib-TEM) should be performed. This modified MA/MCF then represents the fibrin clot that developed in the absence of any platelets, i.e., the functional fibrinogen.6,10 It has been shown that the MA/MCF of these modified tests correlates well with the fibrinogen assessed by the Clauss method (r = 0.85 [TEG 5000 User Manual] and r = 0.7511). The traditional Clauss method, however, determines fibrinogen levels indirectly: Excess thrombin is added to diluted plasma, the time is measured until a clot develops and fibrinogen is calculated with the help of a calibration curve. Although the Clauss method is considered a standard assay, it has been shown that hemodilution with colloids may interfere with this assays, reporting falsely high levels of fibrinogen.12

Table 1

Table 1

Although TEG® and ROTEM® tracings look similar (Fig. 3), the nomenclature and reference ranges are different (Table 2).13 The differences may be explained by different cups and pins used in both systems (ROTEM® cups and pins are composed of a plastic with greater surface charge resulting in greater contact activation compared with cups and pins used in TEG®) and different proprietary formulas of the coagulation activators (composition, concentrations).13 For example, if the same blood specimen is analyzed by TEG® and ROTEM® with their proprietary intrinsic coagulation activator, i.e., kaolin and in-TEM (partial thromboplastin phospholipids), respectively, the results obtained with both systems are significantly different: A recent study by Nielsen showed that the CT was nearly three-fold shorter than the R time and that the α-angle was 7% greater in the ROTEM® compared to the TEG®. It is therefore critical that care be taken when practicing with TEG® and ROTEM® systems, especially if the clinician uses a treatment algorithm created with one system (e.g., TEG®) while analyzing patient samples with the other system (e.g., ROTEM®).13 The repeatability of measurements by both devices is acceptable (summarized in Table 3) provided they are performed exactly as outlined in the users manuals [TEG 5000 User Manual].6

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Sonoclot Analysis

The Sonoclot Analyzer (Fig. 1C, Sonoclot Coagulation & Platelet Function Analyzer, Sienco Inc., Arvada, CO) was introduced in 1975 by von Kaulla et al.14 The principle of the Sonoclot analysis has been described in detail.4 Briefly, the Sonoclot measurements are based on the detection of viscoelastic changes of a whole blood or plasma sample. To start a measurement, a hollow, open-ended disposable plastic probe is mounted on the transducer head. Then, the test sample is added to the cuvette containing different coagulation activators/inhibitors. After an automated mixing procedure, the probe is immersed into the sample and oscillates vertically in the sample. The changes in impedance to movement imposed by the developing clot are measured (Fig. 2C). Different cuvettes with different coagulation activators/inhibitors are commercially available (Table 1). Normal values for the Sonoclot Analyzer are shown in Table 4.

Table 4

Table 4

The Sonoclot Analyzer provides information on the entire hemostasis process both in a qualitative graph, known as the Sonoclot Signature (Fig. 3C) and as quantitative results: the activated clotting time (ACT), the clot rate (CR), and the PF. The ACT is the time from the activation of the sample until the beginning of a fibrin formation. This onset of clot formation is defined as an upward deflection of the Sonoclot Signature. Sonoclot’s ACT corresponds to the conventional ACT measurement, provided that cuvettes containing a high concentration of a typical activators (celite, kaolin) are being used.15–18 How can we compare R/CT of TEG/ROTEM® to the ACT determined by Sonoclot? The rotation of the pin of the TEG/ROTEM® begins to be impaired after fibrin-platelet bonding has linked the cup and pin together. Thus, the output is directly related to the strength of the formed clot. The output of Sonoclot’s oscillating plastic probe, however, is sensitive to viscosity and monitors viscosity changes that occur during initiation of coagulation and clot development. Therefore, the ACT reflects initial fibrin formation, whereas R/CT reflects a more developed, and later, stage of initial clot formation. This theoretical claim is being supported by a recent study by Tanaka et al.19: Simultaneously, ACT and R values were determined in kaolin activated whole blood samples. R values of TEG® were 1.5 fold (native blood samples), 3.9 fold (heparinized samples) or 4.2 fold (bivalirudin treated samples) higher compared with ACT values determined by Sonoclot.

Besides providing information on the initiation phase of coagulation, the Sonoclot Analyzer also measures the kinetics of fibrin formation and clot development, expressed as CR (the maximum slope of the Sonoclot Signature during initial fibrin polymerization and clot development). Furthermore, the function of the platelets is being analyzed and reported as PF (derived from the timing and quality of the clot retraction). The nominal range of values for the PF goes from 0, representing no PF (no clot retraction and flat Sonoclot Signature after fibrin formation), to approximately 5, representing strong PF (clot retraction occurs sooner and is very strong, with clearly defined, sharp peaks in the Sonoclot Signature after fibrin formation) (see manufacturer’s reference).20

The Sonoclot Analyzer has been criticized because its results were influenced by age, sex, and platelet count.21 Additionally, studies showed poor reproducibility of some of the measured variables, especially CR and PF.22,23 However, others found the Sonoclot Analyzer to be valuable and reliable in patients undergoing cardiac surgical procedures24,25 and the Sonoclot Analyzer has even demonstrated a precision close to that of thrombelastography.26 In more recent studies, test variability of ACT values determined by Sonoclot were comparable to other established ACT analyzers (8%–9% on average).15–18 Furthermore, test variability for PF determined by gbACT+ and H-gbACT+ (heparinase glass-bead test) was 6%–10% in a recent study assessing PF after administration of the glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist tirofiban with or without heparin.20

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Cardiac Surgery and Postoperative Care

Coagulation management of patients undergoing cardiac surgery is complex because of a balance between anticoagulation for cardiopulmonary bypass (CPB) and hemostasis after CPB. Furthermore, an increasing number of patients have impaired platelet function at baseline due to administration of antiplatelet drugs. During CPB, optimal anticoagulation dictates that coagulation is antagonized and platelets are prevented from activation so that clots do not form. After surgery, coagulation abnormalities, platelet dysfunction, and fibrinolysis can occur, creating a situation whereby hemostatic integrity must be restored. The complex process of anticoagulation with heparin, antagonism with protamine, and postoperative hemostasis therapy can be guided by POC tests that assess hemostatic function in a timely and accurate manner.1

Although studies report that viscoelastic POC coagulation devices may predict excessive bleeding after CPB, findings are not consistent and evidence supporting its usefulness as a predictor of bleeding is minimal.27–29 Normal viscoelastic test results in a bleeding patient is unlikely due to a significant coagulopathy (high negative predictive value).30 Therefore, viscoelastic POC tests may be useful in early identification and targeted treatment of a surgical bleeding.

The institution of transfusion algorithms based on TEG/ROTEM® parameters has been demonstrated to reduce transfusion requirements in adults and children undergoing cardiac surgery.31–35 Furthermore, it has been recently shown that implementation of ROTEM®-guided coagulation management is cost-effective.33 To detect nonheparin related hemostatic problems in the presence of large amounts of heparin, tests with heparinase have been developed (Table 1) and one study showed that implementation of an algorithm based upon heparinase-modified TEG resulted in a significant reduction of transfusion blood products.36

POC coagulation analyzers measuring ACT are routinely being used in cardiac surgical patients to guide heparin-induced anticoagulation and its reversal.37–40 Besides standard ACT machines, viscoelastic POC analyzers also provide ACT results with comparable accuracy and performance. The ACT provided by the Sonoclot Analyzer is being used to guide heparin therapy, and several tests with different characteristics are commercially available (Table 1).15–17 More recently, a novel assay has also been developed to measure ACT by TEG.41

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Hepatic Surgery and Postoperative Care

Patients undergoing hepatic surgery, and particularly orthotopic liver transplantation (OLT), may have large derangement in their coagulation, making POC coagulation monitoring highly desirable. Problems associated with the defective organ (decreased synthesis and clearance of clotting factors, platelet defects) lead to impaired hemostasis and hyperfibrinolysis. Furthermore, systemic complications, such as sepsis and disseminated intravascular coagulation, further complicate a preexisting coagulopathy. Finally, marked changes in hemostasis in OLT occur during the anhepatic phase and immediately after organ reperfusion, mainly a hyperfibrinolysis resulting from accumulation of tissue plasminogen activator due to inadequate hepatic clearance and a release of exogenous heparin and endogenous heparin-like substances.

One of the first clinical applications of TEG was in the hemostatic management of OLT.42 Although the value of TEG/ROTEM® in management of patients undergoing OLT has been established in the literature,11,43,44 only one third of all OLT programs in the United States routinely used viscoelastic coagulation devices according to a national survey in 2002.45 In addition to the hemorrhagic risk associated with hepatic surgery and OLT, hypercoagulability and thrombotic complication have been described in the postoperative period and can be adequately assessed with TEG/ROTEM®.46,47 Only a few studies are available on the use of the Sonoclot Analyzer in hepatic surgery and OLT; however, this technique has also been found to be useful in the perioperative coagulation management of these patients.48,49

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Hypercoagulability, Thrombosis, and Other Clinical Situations

Recognized risk factors for thrombosis are generally related to one or more elements of Virchow’s triad (stasis, vessel injury, and hypercoagulability).50 Major surgery has been shown to induce a hypercoagulable state in the postoperative period, and this hypercoagulability has been implicated in the pathogenesis of postoperative thrombotic complications, including deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, and vascular graft thrombosis.51,52

Identifying hypercoagulability with conventional nonviscoelastic laboratory tests is difficult unless the fibrinogen concentration or platelet count is markedly increased. However, hypercoagulability is readily being diagnosed by viscoelastic POC coagulation analyzers and TEG/ROTEM® (there are only few data on the use of Sonoclot) have been increasingly used in the assessment of postoperative hypercoagulability for a variety of surgical procedures.51,53–55 Hypercoagulability is being diagnosed if the R/CT time is short and the MA/MCF is increased (exceeding 65–70 mm).7,51

Viscoelastic techniques have been used to assess blood coagulation in multiple clinical situations besides the assessment of hypercoagulability and outside the cardiac and hepatic units, but experience is limited. For example, TEG® has been successfully applied to assess the coagulation status in trauma patients.55,56 Finally, there is a long list of publications on the successful use of TEG/ROTEM® and Sonoclot in other clinical areas, summarized in several reviews.3,4,57

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Monitoring Anticoagulation

ACT measurements to guide heparin therapy and the use of modified POC coagulation tests with heparinase to assess the coagulation status in the absence of the anticoagulatory effects of heparin have been described above. However, besides the monitoring of unfractioned heparin, studies have shown that treatment with low molecular weight heparin and heparinoids (e.g., danaparoid) can also be assessed with POC viscoelastic tests.58 Both standard and heparinase-modified tests have to be performed to increase the sensitivity of TEG/ROTEM® for the effects of low molecular weight heparin and heparinoids.

Direct thrombin inhibitors are increasingly being used for prevention and treatment of venous thromboembolic events, management of patients with acute coronary syndromes and percutaneous coronary interventions and anticoagulation in patients with heparin-induced thrombocytopenia.59 POC viscoelastic techniques, especially the ecarin clotting time (ecarin directly activates thrombin), have proven helpful in assessing the hemostasis system in patients treated with direct thrombin inhibitors.60,61

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Monitoring Antiplatelet Therapy/PF

In Western countries, antiplatelet therapy is increasingly being prescribed for primary and secondary prevention of cardiovascular disease to decrease the incidence of acute cerebro- and cardiovascular events. Antiplatelet drugs typically target to inhibit cyclooxygenase 1/thromboxaneA2 receptors (e.g., aspirin), adenosine diphosphate (ADP) receptors (e.g., clopidogrel) or GPIIb/IIIa receptors (e.g., abciximab, tirofiban). Although antiplatelet drugs are thought to work primarily by decreasing platelet aggregation, they also have been shown to function as anticoagulants: Activated platelets facilitate thrombin generation by providing a catalytic cell surface on which coagulation reactions may occur and they release activated Factor V. Vice versa, anticoagulants may also alter PF.62,63 Because platelets play a key role in overall coagulation, the assessment of the PF (more than their number) is critical in the perioperative setting.64,65

Traditional assays, such as turbidimetric platelet aggregometry, are still considered a clinical standard for PF testing. However, conventional platelet aggregometry is labor-intensive, costly, time-consuming, and requires a high degree of experience and expertise to perform and interpret. Furthermore, platelets are tested under relatively low shear conditions in platelet rich plasma, conditions that do not accurately simulate primary hemostasis.65

Viscoelastic POC coagulation analyzers may provide information on PF but these tests also assess coagulation under low shear conditions. The MA/MCF from TEG/ROTEM® reflects overall PF and fibrinogen levels. It is recommended that two different tests be run simultaneously, e.g., ex-TEM (tissue factor activated test) and fib-TEM (ex-TEM plus cytochalasin D to inhibit PF): The difference between clot firmness of ex-TEM and fib-TEM then represents the platelet contribution. However, since conventional TEG/ROTEM® are not sensitive to targeted pharmacological inhibition, a more sophisticated test has recently been developed for the TEG to specifically determine PF in the presence of antiplatelet therapy (PlateletMapping™).66,67 Briefly, the maximal hemostatic activity of the blood specimen is first measured by a kaolin activated whole blood sample. Then, further measurements are performed in the presence of heparin to eliminate thrombin activity: Reptilase and Factor XIII (Activator F) generate a crosslinked fibrin clot to isolate the fibrin contribution to the clot strength. The contribution of the ADP or thromboxane A2 receptors to the clot formation is provided by the addition of the appropriate agonists, ADP or arachidonic acid. The results from these different tests are then compared with each other and the PF calculated.68

The Sonoclot Analyzer has also been shown to reliably detect pharmacological GPIIb/IIIa inhibition.20,69 To obtain reliable results for PF, cuvettes containing glass beads for specific platelet activation (gbACT+) should be used.20

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Monitoring Procoagulant Therapy

The modern practice of coagulation management is based on the concept of specific component therapy and requires rapid diagnosis and monitoring of the pro-coagulant therapy. It has been shown, for example, that platelet transfusion in the perioperative period of coronary artery bypass graft surgery is associated with increased risk for serious adverse events.70 Clinical judgment alone, or combined with conventional nonviscoelastic laboratory tests, cannot predict who will benefit from a platelet transfusion in the acute perioperative setting. Therefore, the most recent guidelines on perioperative blood transfusion and blood conservation of The Society of Thoracic Surgeons and Society of Cardiovascular Anesthesiologists clearly state that transfusion of coagulation products should be preferably guided by POC tests that assess hemostatic function in a timely and accurate manner.1

Fibrinogen is a key coagulation factor (substrate to form a clot) and isolated fibrinogen substitution in severe models of dilutional coagulopathy has been shown to improve clot strength and reduce blood loss.71 Supplementary administration of prothrombin complex (concentrate of factor II, VII, IX, X, antithrombin III, protein C) additionally improved initiation of coagulation and reversed the dilutional coagulopathy.72 As mentioned earlier in this review, fibrinogen levels can be assessed by measuring clot strength (MCF/MA) in the presence of platelet inhibition (e.g., fib-TEM)11 or by assessing Sonoclot’s CR.73

Recombinant activated factor VII (rVIIa) treatment is currently approved for patients with congenital or acquired hemophilia with antibodies to factor VIII or IX (United States and Europe), factor VII deficiency, and Glanzmanns thrombasthenia (Europe). However, rVIIa is increasingly used in off-label indications to control severe bleeding (e.g., major trauma, surgical interventions, intracerebral hemorrhage) in theory, by locally activating hemostasis at sites of vascular injury. The resulting thrombin burst then leads to the formation of a fibrin clot, provided that fibrinogen levels are sufficient. Consensus guidelines have been published for these off-label indications, but it is still unclear how to reliably monitor patients receiving rVIIa.74,75 To better study the result of thrombin generation (i.e., fibrin polymerization, factor XIII activation, factor XIIIa crosslinking of fibrin polymers, and platelet activation), modified TEG/ROTEM® parameters based on the first derivative of original TEG/ROTEM® tracing have been introduced recently: maximum velocity of clot formation (maximum rate of thrombus generation, MaxVel), time to reach MaxVel (time to maximum thrombus generation, tMaxVel) and total thrombus generation (area under the curve).76–78 These parameters are supposed to be more sensitive to rVIIa than standard TEG/ROTEM® parameters, and dilute tissue factor should be used as coagulation activator for best sensitivity.57 In a preliminary study, we were able to monitor the effects of rVIIa in vitro after severe hemodilution using the new diluted tissue factor activated tests from ROTEM (tif-TEM) and Sonoclot (microPT).73,79

Factor XIII is needed for cross-linking fibrin, thereby stabilizing the clot, increasing clot strength, and resistance to fibrinolysis. There are case reports on patients with unexplained intraoperative bleeding due to decreased factor XIII and subsequent stabilization after substitution. Impaired clot strength and increased lysis have been observed.80

Antifibrinolytic drugs (aprotinin, tranexamic, and ε aminocaproic acid) are used mostly in cardiac surgery to reduce bleeding and transfusion requirements. Aprotinin may interact with POC coagulation assays, prolonging for example celite activated ACT tests. Therefore, kaolin or aprotinin-insensitive ACT should be used to guide heparin therapy in these patients.16,17 Antifibrinolytic therapy may be predicted in vitro in TEG/ROTEM with certain tests already containing an antifibrinolytic drug (e.g., ap-TEM). Ap-TEM predictive for a good patient response would then show a significantly improved initiation/propagation phase compared with ex-TEM and or disappearance of signs of hyperfibrinolysis. There are no conclusive studies on monitoring desmopressin therapy.

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Critiques of POC Coagulation Monitoring

Several concerns have been raised using viscoelastic POC coagulation tests because these tests are hard to standardize. The blood collection site, processing of the sample (native vs citrated samples, time delay between collection and measurement—-for citrated samples a minimum rest time of 30 min is required), patient age, and gender may significantly affect the results of these tests.3 Furthermore, equipment, activators and other modifications will alter the assay specificity. All these factors have to be considered when interpreting results in the literature and have to be known and standardized when running tests in a single center.

As with all POC devices, there is a concern that the devices are not adequately maintained, supervised, and that quality controls are not done on a regular basis. Furthermore, nonlaboratory personnel are running these POC tests, which may lead to further errors if they are not adequately trained (TEG and Sonoclot have been listed as moderate complexity tests by the Clinical Laboratory Improvement Amendment). Alternatively, to minimize these problems and release the operating room/intensive care unit personnel, the so-called POC coagulation analyzers have been recently moved into the central laboratory in some hospitals, thereby no longer being located at the bedside. A trained person runs the viscoelastic coagulation test and the results (evolving signatures) are submitted real-time to the patient’s site.

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CONCLUSIONS

Viscoelastic POC coagulation analyzers are being used in certain clinical situations known for their inherent risk of coagulation disorders, especially in the management of patients undergoing cardiac and liver surgery. Furthermore, they provide useful information in a large variety of clinical scenarios, e.g., massive hemorrhage, assessment of hypo- and hypercoagulable states and monitoring of pharmacological treatment with anti- and procoagulant drugs. The advantage of these techniques is that they have the potential to measure the entire clotting process, starting with fibrin formation and continue through to clot retraction and lysis at the bedside, with minimal time delays. Although physiological clot development is better depicted as a result of whole blood analysis of the coagulation status, these techniques measure hemostasis under static conditions in vitro, and the results of these tests must be carefully interpreted correlating them to clinical conditions. Finally, to bring viscoelastic POC coagulation analyzers to the next level in the future, several improvements, such as easier handling of blood samples, full automation, simultaneous testing with multiple activators, integrated analyzing software, and high robustness of the devices, would be highly desirable.

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REFERENCES

1. Ferraris VA, Ferraris SP, Saha SP, Hessel EA, Haan CK, Royston BD, Bridges CR, Higgins RS, Despotis G, Brown JR, Spiess BD, Shore-Lesserson L, Stafford-Smith M, Mazer CD, nett-Guerrero E, Hill SE, Body S. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg 2007;83:S27–S86
2. Kozek-Langenecker S. Management of massive operative blood loss. Minerva Anestesiol 2007;73:401–15
3. Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol 2005;27:81–90
4. Hett DA, Walker D, Pilkington SN, Smith DC. Sonoclot analysis. Br J Anaesth 1995;75:771–6
5. Hartert H. Blutgerinnungstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren. Klin Wochenschrift 1948;26:557–83
6. Lang T, Bauters A, Braun SL, Potzsch B, von Pape KW, Kolde HJ, Lakner M. Multi-centre investigation on reference ranges for ROTEM thromboelastometry. Blood Coagul Fibrinolysis 2005;16: 301–10
7. Mallett SV, Cox DJ. Thrombelastography. Br J Anaesth 1992; 69:307–13
8. Di Benedetto P, Baciarello M, Cabetti L, Martucci M, Chiaschi A, Bertini L. Thrombelastography. Present and future perspectives in clinical practice. Minerva Anestesiol 2003;69:501–9
9. Spiel AO, Mayr FB, Firbas C, Quehenberger P, Jilma B. Validation of rotation thrombelastography in a model of systemic activation of fibrinolysis and coagulation in humans. J Thromb Haemost 2006;4:411–6
10. Kettner SC, Panzer OP, Kozek SA, Seibt FA, Stoiser B, Kofler J, Locker GJ, Zimpfer M. Use of abciximab-modified thrombelastography in patients undergoing cardiac surgery. Anesth Analg 1999;89:580–4
11. Coakley M, Reddy K, Mackie I, Mallett S. Transfusion triggers in orthotopic liver transplantation: a comparison of the thromboelastometry analyzer, the thromboelastogram, and conventional coagulation tests. J Cardiothorac Vasc Anesth 2006; 20:548–53
12. Hiippala ST. Dextran and hydroxyethyl starch interfere with fibrinogen assays. Blood Coagul Fibrinolysis 1995;6:743–6
13. Nielsen VG. A comparison of the thrombelastograph and the ROTEM. Blood Coagul Fibrinolysis 2007;18:247–52
14. von Kaulla KN, Ostendorf P, von KE. The impedance machine: a new bedside coagulation recording device. J Med 1975;6:73–88
15. Dalbert S, Ganter MT, Furrer L, Klaghofer R, Zollinger A, Hofer CK. Effects of heparin, haemodilution and aprotinin on kaolin-based activated clotting time: in vitro comparison of two different point of care devices. Acta Anaesthesiol Scand 2006;50:461–8
16. Ganter MT, Dalbert S, Graves K, Klaghofer R, Zollinger A, Hofer CK. Monitoring activated clotting time for combined heparin and aprotinin application: an in vitro evaluation of a new aprotinin-insensitive test using SONOCLOT. Anesth Analg 2005;101:308–14
17. Ganter MT, Monn A, Tavakoli R, Genoni M, Klaghofer R, Furrer L, Honegger H, Hofer CK. Monitoring activated clotting time for combined heparin and aprotinin application: in vivo evaluation of a new aprotinin-insensitive test using Sonoclot. Eur J Cardiothorac Surg 2006;30:278–84
18. Ganter MT, Monn A, Tavakoli R, Klaghofer R, Zollinger A, Hofer CK. Kaolin-based activated coagulation time measured by sonoclot in patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2007;21:524–8
19. Tanaka KA, Szlam F, Sun HY, Taketomi T, Levy JH. Thrombin generation assay and viscoelastic coagulation monitors demonstrate differences in the mode of thrombin inhibition between unfractionated heparin and bivalirudin. Anesth Analg 2007; 105:933–9
20. Tucci MA, Ganter MT, Hamiel CR, Klaghofer R, Zollinger A, Hofer CK. Platelet function monitoring with the Sonoclot analyzer after in vitro tirofiban and heparin administration. J Thorac Cardiovasc Surg 2006;131:1314–22
21. Horlocker TT, Schroeder DR. Effect of age, gender, and platelet count on Sonoclot coagulation analysis in patients undergoing orthopedic operations. Mayo Clin Proc 1997;72:214–9
22. McKenzie ME, Gurbel PA, Levine DJ, Serebruany VL. Clinical utility of available methods for determining platelet function. Cardiology 1999;92:240–7
23. Ekback G, Carlsson O, Schott U. Sonoclot coagulation analysis: a study of test variability. J Cardiothorac Vasc Anesth 1999;13:393–7
24. Miyashita T, Kuro M. Evaluation of platelet function by Sonoclot analysis compared with other hemostatic variables in cardiac surgery. Anesth Analg 1998;87:1228–33
25. Saleem A, Blifeld C, Saleh SA, Yawn DH, Mace ML, Schwartz M, Crawford ES. Viscoelastic measurement of clot formation: a new test of platelet function. Ann Clin Lab Sci 1983;13:115–24
26. Forestier F, Belisle S, Contant C, Harel F, Janvier G, Hardy JF. [Reproducibility and interchangeability of the Thromboelastograph, Sonoclot and Hemochron activated coagulation time in cardiac surgery]. Can J Anaesth 2001;48:902–10
27. Tuman KJ, Spiess BD, McCarthy RJ, Ivankovich AD. Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass. Anesth Analg 1989;69:69–75
28. Nuttall GA, Oliver WC, Ereth MH, Santrach PJ. Coagulation tests predict bleeding after cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1997;11:815–23
29. Wang JS, Lin CY, Hung WT, O’Connor MF, Thisted RA, Lee BK, Karp RB, Yang MW. Thromboelastogram fails to predict postoperative hemorrhage in cardiac patients. Ann Thorac Surg 1992;53:435–9
30. Cammerer U, Dietrich W, Rampf T, Braun SL, Richter JA. The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery. Anesth Analg 2003;96:51–7
31. Shore-Lesserson L, Manspeizer HE, DePerio M, Francis S, Vela-Cantos F, Ergin MA. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg 1999;88:312–9
32. Anderson L, Quasim I, Soutar R, Steven M, Macfie A, Korte W. An audit of red cell and blood product use after the institution of thromboelastometry in a cardiac intensive care unit. Transfus Med 2006;16:31–9
33. Spalding GJ, Hartrumpf M, Sierig T, Oesberg N, Kirschke CG, Albes JM. Cost reduction of perioperative coagulation management in cardiac surgery: value of ‘bedside’ thrombelastography (ROTEM). Eur J Cardiothorac Surg 2007;31:1052–7
34. Avidan MS, Alcock EL, Da FJ, Ponte J, Desai JB, Despotis GJ, Hunt BJ. Comparison of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery. Br J Anaesth 2004;92:178–86
35. Miller BE, Guzzetta NA, Tosone SR, Levy JH. Rapid evaluation of coagulopathies after cardiopulmonary bypass in children using modified thromboelastography. Anesth Analg 2000;90:1324–30
36. Royston D, von Kier S. Reduced haemostatic factor transfusion using heparinase-modified thrombelastography during cardiopulmonary bypass. Br J Anaesth 2001;86:575–8
37. Bull MH, Huse WM, Bull BS. Evaluation of tests used to monitor heparin therapy during extracorporeal circulation. Anesthesiology 1975;43:346–53
38. Despotis GJ, Gravlee G, Filos K, Levy J. Anticoagulation monitoring during cardiac surgery: a review of current and emerging techniques. Anesthesiology 1999;91:1122–51
39. Prisco D, Paniccia R. Point-of-Care Testing of Hemostasis in Cardiac Surgery. Thromb J 2003;1:1
40. Shore-Lesserson L. Monitoring anticoagulation and hemostasis in cardiac surgery. Anesthesiol Clin North Am 2003;21:511–26
41. Chavez JJ, Foley DE, Snider CC, Howell JC, Cohen E, Muenchen RA, Carroll RC. A novel thrombelastograph tissue factor/kaolin assay of activated clotting times for monitoring heparin anticoagulation during cardiopulmonary bypass. Anesth Analg 2004;99:1290–4
42. Kang YG, Martin DJ, Marquez J, Lewis JH, Bontempo FA, Shaw BW Jr, Starzl TE, Winter PM. Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg 1985;64:888–96
43. Gillies BS. Thromboelastography and liver transplantation. Semin Thromb Hemost 1995;21 Suppl 4:45–9
44. Kang Y. Coagulation and liver transplantation. Transplant Proc 1993;25:2001–5
45. Schumann R. Intraoperative resource utilization in anesthesia for liver transplantation in the United States: a survey. Anesth Analg 2003;97:21–8
46. Stahl RL, Duncan A, Hooks MA, Henderson JM, Millikan WJ, Warren WD. A hypercoagulable state follows orthotopic liver transplantation. Hepatology 1990;12:553–8
47. Cerutti E, Stratta C, Romagnoli R, Schellino MM, Skurzak S, Rizzetto M, Tamponi G, Salizzoni M. Thromboelastogram monitoring in the perioperative period of hepatectomy for adult living liver donation. Liver Transpl 2004;10:289–94
48. Chapin JW, Becker GL, Hulbert BJ, Newland MC, Cuka DJ, Wood RP, Shaw BW Jr. Comparison of Thromboelastograph and Sonoclot coagulation analyzer for assessing coagulation status during orthotopic liver transplantation. Transplant Proc 1989;21:3539
49. Bindi ML, Biancofiore GD, Consani G, Cellai F, Cecconi N, Romanelli A, Filipponi F, Mosca F, Amorese G, Vagelli A. Blood coagulation monitoring during liver transplantation: Sonoclot analysis and laboratory tests. Minerva Anestesiol 2001;67:359–69
50. Cayley WE Jr. Preventing deep vein thrombosis in hospital inpatients. BMJ 2007;335:147–51
51. McCrath DJ, Cerboni E, Frumento RJ, Hirsh AL, nett-Guerrero E. Thromboelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction. Anesth Analg 2005;100:1576–83
52. Irish A. Hypercoagulability in renal transplant recipients. Identifying patients at risk of renal allograft thrombosis and evaluating strategies for prevention. Am J Cardiovasc Drugs 2004;4:139–49
53. Arcelus JI, Traverso CI, Caprini JA. Thromboelastography for the assessment of hypercoagulability during general surgery. Semin Thromb Hemost 1995;21(suppl 4):21–6
54. Mahla E, Lang T, Vicenzi MN, Werkgartner G, Maier R, Probst C, Metzler H. Thromboelastography for monitoring prolonged hypercoagulability after major abdominal surgery. Anesth Analg 2001;92:572–7
55. Schreiber MA, Differding J, Thorborg P, Mayberry JC, Mullins RJ. Hypercoagulability is most prevalent early after injury and in female patients. J Trauma 2005;58:475–80
56. Rugeri L, Levrat A, David JS, Delecroix E, Floccard B, Gros A, Allaouchiche B, Negrier C. Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography. J Thromb Haemost 2007;5:289–95
57. Sorensen B, Ingerslev J. Tailoring haemostatic treatment to patient requirements—-an update on monitoring haemostatic response using thrombelastography. Haemophilia 2005;11 (suppl 1):1–6
58. Coppell JA, Thalheimer U, Zambruni A, Triantos CK, Riddell AF, Burroughs AK, Perry DJ. The effects of unfractionated heparin, low molecular weight heparin and danaparoid on the thromboelastogram (TEG): an in-vitro comparison of standard and heparinase-modified TEGs with conventional coagulation assays. Blood Coagul Fibrinolysis 2006;17:97–104
59. Di NM, Middeldorp S, Buller HR. Direct thrombin inhibitors. N Engl J Med 2005;353:1028–40
60. Nielsen VG, Steenwyk BL, Gurley WQ, Pereira SJ, Lell WA, Kirklin JK. Argatroban, bivalirudin, and lepirudin do not decrease clot propagation and strength as effectively as heparin-activated antithrombin in vitro. J Heart Lung Transplant 2006;25:653–63
61. Carroll RC, Chavez JJ, Simmons JW, Snider CC, Wortham DC, Bresee SJ, Cohen E. Measurement of patients’ bivalirudin plasma levels by a thrombelastograph ecarin clotting time assay: a comparison to a standard activated clotting time. Anesth Analg 2006;102:1316–9
62. Reverter JC, Beguin S, Kessels H, Kumar R, Hemker HC, Coller BS. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and “clinical restenosis.” J Clin Invest 1996;98:863–74
63. Tanaka KA, Katori N, Szlam F, Sato N, Kelly AB, Levy JH. Effects of tirofiban on haemostatic activation in vitro. Br J Anaesth 2004;93:263–9
64. Rand ML, Leung R, Packham MA. Platelet function assays. Transfus Apheresis Sci 2003;28:307–17
65. Harrison P. Platelet function analysis. Blood Rev 2005;19:111–23
66. Craft RM, Chavez JJ, Bresee SJ, Wortham DC, Cohen E, Carroll RC. A novel modification of the Thrombelastograph assay, isolating platelet function, correlates with optical platelet aggregation. J Lab Clin Med 2004;143:301–9
67. Carroll RC, Chavez JJ, Snider CC, Meyer DS, Muenchen RA. Correlation of perioperative platelet function and coagulation tests with bleeding after cardiopulmonary bypass surgery. J Lab Clin Med 2006;147:197–204
68. Bochsen L, Wiinberg B, Kjelgaard-Hansen M, Steinbruchel DA, Johansson PI. Evaluation of the TEG platelet mapping assay in blood donors. Thromb J 2007;5:3
69. Waters JH, Anthony DG, Gottlieb A, Sprung J. Bleeding in a patient receiving platelet aggregation inhibitors. Anesth Analg 2001;93:878–82
70. Spiess BD, Royston D, Levy JH, Fitch J, Dietrich W, Body S, Murkin J, Nadel A. Platelet transfusions during coronary artery bypass graft surgery are associated with serious adverse outcomes. Transfusion 2004;44:1143–8
71. Fries D, Krismer A, Klingler A, Streif W, Klima G, Wenzel V, Haas T, Innerhofer P. Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model. Br J Anaesth 2005; 95:172–7
72. Fries D, Haas T, Klingler A, Streif W, Klima G, Martini J, Wagner-Berger H, Innerhofer P. Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy–a porcine model. Br J Anaesth 2006;97:460–7
73. Ganter MT, Schmuck S, Hamiel CR, Zollinger A, Hofer CK. Monitoring the effects of factor VIIa treatment in-vitro after severe hemodilution (part I - Sonoclot). Anesthesiology 2006;105(suppl):A1005
74. Shander A, Goodnough LT, Ratko T, Matuszewski KA, Cohn S, Diringer M, Edmunds H, Lawson J, MacLaren R, Ness P, Shere-Wolfe R, Dubois R. Consensus recommendations for the off-label use of recombinant human factor VIIa (NovoSeven) therapy. Pharmacy & Therapeutics 2005;30:644–58
75. Vincent JL, Rossaint R, Riou B, Ozier Y, Zideman D, Spahn DR. Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding—a Eur perspective. Crit Care 2006;10:R120
76. Sorensen B, Johansen P, Christiansen K, Woelke M, Ingerslev J. Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation. J Thromb Haemost 2003;1:551–8
77. Nielsen VG, Lyerly RT III, Gurley WQ. The effect of dilution on plasma coagulation kinetics determined by thrombelastography is dependent on antithrombin activity and mode of activation. Anesth Analg 2004;99:1587–92
78. Rivard GE, Brummel-Ziedins KE, Mann KG, Fan L, Hofer A, Cohen E. Evaluation of the profile of thrombin generation during the process of whole blood clotting as assessed by thrombelastography. J Thromb Haemost 2005;3:2039–43
79. Schmuck S, Ganter MT, Hamiel CR, Zollinger A, Hofer CK. Monitoring the effects of factor VIIa treatment in-vitro after severe hemodilution (part II - ROTEM). Anesthesiology 2006;105(suppl):A1001
80. Wettstein P, Haeberli A, Stutz M, Rohner M, Corbetta C, Gabi K, Schnider T, Korte W. Decreased factor XIII availability for thrombin and early loss of clot firmness in patients with unexplained intraoperative bleeding. Anesth Analg 2004; 99:1564–9
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