Miroslav Durila

Early diagnostic markers of sepsis after oesophagectomy (including thromboelastography)

BackgroundEarly diagnosis of sepsis and its differentiation from the noninfective SIRS is very important in order that treatment can be initiated in a timely and appropriate way. In this study we investigated standard haematological and biochemical parameters and thromboelastography (TEG) in patients who had undergone surgical resection of the oesophagus to find out if changes in any of these parameters could help in early differentiation between SIRS and sepsis development.MethodsWe enrolled 43 patients (aged 41–74 years) of whom 38 were evaluable. Blood samples were obtained on the morning of surgery and then at 24-hour intervals for the next 6 days. Samples were analysed for procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL- 6), aspartate transaminase (AST), alanine transaminase (ALT) , lactate, white blood count (WBC), D-dimers, antithrombin (AT), international normalised ratio (INR), activated partial thromboplastin time (APTT) and parameters of TEG.ResultsSignificant differences between patients who developed sepsis during this period (9 patients) and SIRS were found in ALT on Day 1, in AST on Days 1–4, in PCT on Days 2–6; in CRP on Days 3–6; in IL-6 on Days 2–5; in leucocytes on Days 2, 3 and 6; and in D-dimers on Days 2 and 4. Significance values ranged from p < 0.0001 to p < 0.05.ConclusionsSequential measurements of ALT, AST, PCT and IL-6 during the early postoperative period can be used for early differentiation of sepsis and postoperative SIRS after oesophagectomy. Among the coagulation parameters measured, only D-dimer concentrations appeared to be helpful in this process. TEG does not seem to be a useful early predictor of sepsis development; however it can be used to differentiate sepsis and SIRS from Day 5 after surgery.

Arteriovenous differences of hematological and coagulation parameters in patients with sepsis

In critically ill patients, either arterial or venous blood is usually available for sampling and measurement of basic coagulation parameters. The aim of this study was to examine whether in these patients the values of coagulation parameters differ significantly with respect to the source of the blood samples. In a group of 44 patients with severe sepsis, we compared the values of coagulation, thromboelastography and selected hematological parameters between the arterial and venous blood. In most of the investigated parameters (international normalized ratio, activated partial thromboplastin time, fibrinogen concentration, erythrocyte count, leukocyte and platelet count, hemoglobin level and thromboelastography parameters), we did not find significant differences (P > 0.1). However, we found a significantly lower antithrombin activity and a significantly higher D-dimer concentration in venous blood compared to arterial blood (P < 0.05). This could be associated with increased consumption of antithrombin and generation of D-dimer as a consequence of microthrombi formation in the capillaries. We therefore conclude that for the purpose of assessment of coagulation status in septic patients, arterial and venous blood cannot be treated as equivalent.

Discard volume necessary for elimination of heparin flush effect on thromboelastography.

Heparin is commonly used to prevent obstruction of indwelling arterial catheters with blood clots. It is known to affect the outcomes of analysis of coagulation parameters with thromboelastography (TEG); therefore, it has been recommended to neutralize its effect with heparinase. However, heparinase may also neutralize the effect of low molecular weight heparin and endogenous heparinoids present in critically ill patients and thus yields unreliable results. The aim of this study was to evaluate the minimal discard blood volume needed to eliminate the effect of heparin flush on TEG parameters without the use of heparinase. Ten patients with indwelling arterial catheter were included in the study. Coagulation parameters were evaluated with kaolin-activated TEG. Blood samples were obtained after discarding 1, 2, 3, 4, 5 or 10 ml of blood to eliminate the effect of heparin. We investigated the influence of the discard volume on time until the first detectable clot (R), speed of clot development (α angle), maximal amplitude of the measured clot and time to maximal amplitude of the measured clot. We found an increase in coagulation (reflecting the heparin elimination) with the increasing discard volume between 1 and 4 ml. This was obvious from an increase in α angle and maximal amplitude of the measured clot and a decrease in R and time to maximal amplitude of the measured clot (P < 0.001). However, values obtained after discarding 4, 5 and 10 ml of blood did not differ markedly. To obtain valid information about TEG parameters, it is necessary to discard volume of at least 4 ml of blood (i.e., five times the volume of catheter dead space).

Rotational thromboelastometry along with thromboelastography plays a critical role in the management of traumatic bleeding.

Massive posttraumatic bleeding is the leading cause of potentially preventable death among patients with severe trauma. Immediate diagnosis and treatment of traumatic coagulopathy and its differentiation from surgical bleeding after major trauma are critical in the management of such patients. In this case report, we present a 33-year-old woman who had multiple injuries to the head and trunk in motor vehicle collision, resulting in severe bleeding and necessitating emergency surgery. We demonstrate how repeated rotational thromboelastometry and thromboelastography analyses were used to direct the choice of therapy to stabilize her circulatory system for surgery and to differentiate surgical bleed from coagulopathy. Therapy based on massive transfusion protocol and on laboratory coagulation tests would be insufficient to stop bleeding. We conclude that rotational thromboelastometry/thromboelastography analysis plays a critical role in the management of traumatic bleeding and helps us provide more aggressive and targeted therapy for coagulopathy both in the acute and later phases of treatment of severe bleeding.

Time impact on non-activated and kaolin-activated blood samples in thromboelastography.

BackgroundThe correct methodology of thrombelastography might be influenced by elapsing time. In our study we investigated kaolin activated citrated samples together with non-activated citrated samples in relation to the elapsed times of 0, 15 and 30 minutes to compare both methods and to find out if there is an impact of time on results of thrombelastography.MethodsBlood samples obtained from 10 healthy volunteers were analyzed after 0, 15 and 30 minutes from sampling with kaolin activation and without activation. Then the results were analysed and compared between the non-activated and the kaolin-activated method.ResultsAll blood samples became more hypercoagulable with the time elapsing, both in non-activated and kaolin-activated samples and differences between both groups were found statistically and clinically significant after only 0 minutes.ConclusionsThe non-activated citrated method seems to be reliable and suitable for thrombelastography in non-emergency cases (planned surgical procedures) when we have time to wait 15–30 minutes to get results. In urgent situations a rapid thrombelastography test should be preferred. Although the kaolin-activated method can also be used, results must be interpreted with caution.

Evaluation of fibrinogen concentrates and prothrombin complex concentrates on coagulation changes in a hypothermic in vitro model using thromboelastometry and thromboelastography

Abstract Background. Hypothermic coagulopathy is very challenging in bleeding trauma patients. Therefore, we decided to evaluate the efficacy of fibrinogen and prothrombin complex in 30°C hypothermia in vitro to investigate if higher levels of fibrinogen and prothrombin complex concentrate can compensate for the hypothermic effect on coagulation as measured by thromboelastometry/thromboelastography. Methods. Blood samples were obtained from 12 healthy volunteers (six men and six women) in our study. Measurements were performed at 37°C and 30°C simultaneously, then at 30°C with adding fibrinogen and prothrombin complex and in the last step samples with added coagulation factors were warmed back to 37°C. Results. We found that 30°C hypothermic coagulopathy can be detected both by thromboelastometry and thromboelastography. Hypothermic coagulopathy can be restored by fibrinogen to the point where the results do not significantly differ from 37°C values (p > 0.05). After warming the sample with fibrinogen to 37°C, the thrombodynamic potential index was not significantly different from baseline (p > 0.05), although there was a trend to prothrombotic status. The addition of prothrombin complex concentrate to 30°C hypothermic sample was not able to correct hypothermic coagulopathy in vitro. Conclusions. Coagulopathy caused by the 30°C hypothermia in vitro model can be corrected by fibrinogen concentrate compared to prothrombin complex concentrate. In spite of a tendency to prothrombotic status, this was not significant with the use of the recommended dose of fibrinogen even after warming the blood to 37°C. However, measurement performed at 37°C seems to be safer than at 30°C.

Evaluation of Thromboelastometry in Sepsis in Correlation With Bleeding During Invasive Procedures

Prolongation of prothrombin time (PT) is often encountered in patients with sepsis. On the other hand, thromboelastometry as a global coagulation test might yield normal results. The aim of our study was to evaluate whether prolonged PT in the presence of normal thromboelastometry parameters is associated with severe bleeding in patients with sepsis undergoing invasive procedures. In patients with sepsis undergoing low-risk bleeding invasive procedures (central venous catheter placement, dialysis catheter insertion, drain insertion, and so on) or high-risk bleeding invasive procedures (surgical tracheostomy, surgical laparotomy, thoracotomy, and so on), coagulation was assessed by thromboelastometry using EXTEM test (test for evaluation of the extrinsic pathway of coagulation, contains activator of extrinsic pathway) and with PT. For period of years 2013 to 2016, we assessed occurrence of severe bleeding during those procedures and 24 hours later in patients with prolonged PT and normal thromboelastometry results. This retrospective study was performed at Department of Anaesthesiology and Intensive Care Medicine of Motol University Hospital in Prague. Data from 76 patients with sepsis were analyzed. Median value of international normalized ratio (INR) was 1.59 (min—1.3 and max—2.56), and median value of prothrombin ratio (PR) was 1.5 (min—1.23 and max—2.55) with normal thromboelastometry finding. Despite prolonged INR/PR, no severe bleeding was observed during invasive procedures. Our data show that sepsis may be accompanied by normal thromboelastometry results, despite prolonged values of PT, and invasive procedures were performed without severe bleeding. This approach to coagulation assessment in sepsis may reduce administration of fresh frozen plasma to the patients. The study was registered at Clinical Trials.gov with assigned number NCT02971111.

Nonactivated thromboelastometry able to detect fibrinolysis in contrast to activated methods (EXTEM, INTEM) in a bleeding patient.

Rotational thromboelastometry (ROTEM) is increasingly used in practice to monitor coagulation status of severely bleeding patients and it helps to provide aimed therapy. The main advantage of ROTEM is detection of fibrinolysis. To get fast results, the reagents for activation, either extrinsic or intrinsic pathway of coagulation, are used. Although this method gives information about whole blood coagulation, in some cases, the patient is bleeding despite normal values of ROTEM. We present a case of a bleeding patient with normal values of activated ROTEM method (EXTEM, INTEM). However, nonactivated method (NATEM) was able to detect fibrinolysis and no clot was found in the cuvette. When tranexamic acid was added to the cuvette, the trace came back to normal value and a clot was formed inside the cuvette. According to this finding, the patient was effectively treated with antifibrinolytic drugs and stopped bleeding. In this case, we want to demonstrate that NATEM, as nonactivated ROTEM, seems to be more sensitive to coagulation changes, especially in detection of fibrinolysis, than activated ROTEM methods.

Thromboelastometry as an Alternative Method for Coagulation Assessment in Pediatric Patients Undergoing Invasive Procedures: A Pilot Study

Introduction Standard coagulation tests (activated partial thromboplastin time [aPTT] and prothrombin time [PT]) are used for the assessment of coagulation profile in critically ill pediatric patients undergoing invasive interventions such as insertion of central venous catheter, tonsillectomy, laparotomy, etc. However, these tests do not reflect the profile of whole blood coagulation. Rotational thromboelastometry (ROTEM) as a point of care (POC) viscoelastic test may serve as an alternative method. Due to its ability to assess coagulation profile of the whole blood, it might yield normal results despite prolonged aPTT/PT results. The aim of this study was to find out if there was any severe bleeding during or after invasive procedures if ROTEM test was normal despite prolonged values of aPTT/PT in pediatric patients. Materials and Methods We retrospectively analyzed data for the years 2015 to 2017 for pediatric patients with prolonged values of aPTT or PT and normal ROTEM tests—internal thromboelastometry (INTEM) (assessing internal pathway of coagulation) and external thromboelastometry (EXTEM) (assessing external pathway of coagulation)—and we looked for severe bleeding during or after invasive procedures. Results In 26 pediatric patients (children from 2 months to 17 years old), we found that INTEM and EXTEM tests showed normal coagulation despite prolonged values of aPTT ratio with a median of 1.47 (minimum 1.04 and maximum 2.05), international normalized ratio with a median of 1.4 (minimum 0.99 and maximum 2.10), and PT ratio with a median of 1.30 (minimum 0.89 and maximum 2.11). In these patients, no severe bleeding was observed during interventions or postoperatively. Conclusion Our data support using thromboelastometry method as an alternative coagulation test for the assessment of coagulation profile in pediatric patients undergoing surgical or other invasive procedures, especially using it as a POC test. All invasive procedures in our study were performed without severe bleeding despite prolonged values of PT/aPTT with normal ROTEM results. It seems that ROTEM assessment of coagulation may lead to decreased administration of fresh frozen plasma and shorten time of patient preparation for intervention.

Effect of Balanced Crystalloid, Gelatin and Hydroxyethyl Starch on Coagulation Detected by Rotational Thromboelastometry In Vitro

BACKGROUND Fluid resuscitation with crystalloid and colloid solutions is a common treatment in perioperative medicine. However, a variety of unbalanced or balanced solutions are used in clinical practice and there is still vivid debate going on regarding selection of optimal fluid with minimal negative effect on coagulation to minimize bleeding and blood transfusion requirements. The aim of the study was to investigate adverse effects of balanced crystalloids and colloids on coagulation measured by thromboelastometry in vitro. METHODS Blood samples were obtained from healthy volunteers undergoing knee arthroscopy. Adverse effects of balanced crystalloid, hydroxyethyl starch, and gelatin were evaluated by thromboelastometry after 20% dilution of blood with the solution in vitro. Parameters of EXTEM and FIBTEM test were evaluated. RESULTS Clotting time of EXTEM was not significantly influenced by any of the investigated solutions (p > 0.05). However, significant impairment of clot formation time of EXTEM was detected in hydroxyethyl starch and gelatin groups in comparison with controls (p < 0.05), while crystalloid did not affect this parameter significantly (p > 0.05). Similar results were found in α angle although significant coagulopathy effect was found only in hydroxyethyl starch samples (p < 0.05). Maximum clot firmness of EXTEM and FIBTEM tests was significantly affected by both hydroxyethyl starch and gelatin (p < 0.05) but not by crystalloid. CONCLUSIONS Balanced crystalloid solution does not seem to have a negative influence on the coagulation process as measured by thromboelastometry. On the other hand, balanced colloids may impair propagation phase of coagulation, strength of coagulum, and level of functional fibrinogen. Hydroxyethyl starch seems to have a stronger anticoagulant effect compared to gelatin.