Tomas Vymazal

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.

Impact of retransfusion of blood processed in cell-saver on coagulation versus cardiopulmonary bypass: a prospective observational study using thromboelastography

AIMS To compare an impact of retransfusion of blood processed in cell-saver (CS) with that of cardiopulmonary bypass (CPB) on blood coagulation in patients undergoing cardiac surgery. METHODS Prospective observational study using thromboelastography (TEG). RESULTS TEG samples from 170 patients were analyzed. Cardiopulmonary bypass was used in 100 patients while 70 patients were operated off-pump. In 20 off-pump patients collected blood was processed by cell-saver and returned. In all patients clot formation after heparin neutralization by protamine was unimpaired. However, there was a significant increase in fibrinolysis defined by the TEG parameter Lysis time 30 min after the maximum amplitude of the clot was reached (Ly30) in groups with CPB or CS but this increase still did not exceed the threshold for clinical fibrinolysis (Ly30 > 7.5%). In the group without CPB there was no significant impact on coagulation. CONCLUSION Surgery that avoids CPB and/or CS is the gentlest method for inducing blood coagulation.

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.

Stability of Non-Activated Rotational Thromboelastometry Assay in Time of Citrated Blood (Appropriate Time Interval for Analysis).

BACKGROUND Activated methods of thromboelastometry such as EXTEM and INTEM are routinely used in management of severe bleeding. However, sometimes the patient is bleeding despite the normal values of EXTEM/ INTEM. Non-activated thromboelastometry (NATEM) is the most sensitive to coagulopathy and shows pathologic results in such cases. However, it is necessary to find an appropriate time interval between blood sampling and NATEM analysis as the results are strongly influenced by time. METHODS In 18 healthy volunteers we performed NATEM analyses of citrated blood samples at 0, 5, 10, 15, 20, 30, and 60 minutes after sampling. RESULTS All NATEM parameters showed a procoagulation trend with the time elapsing from blood sample collection with coagulation time (CT) being the most sensitive parameter. After 20 minutes this parameter became relatively stable as the difference among CT at 20th, 30th, and 60th minute was not statistically significant (p > 0.05). The least differences of CT values with maximum time window were found between 30 and 60 minutes. CONCLUSIONS Citrated blood sample becomes stable after 20 minutes of storage but the time window between 30 and 60 minutes seems to be more suitable for NATEM analysis in clinical practice.

Minimally invasive approach to calcified aortic valve replacement: Anaesthetic considerations.

For symptomatic patients with severe calcified aortic valve stenosis, open heart surgery for aortic valve replacement remains the gold standard. However, elderly patients with an increased risk profile can be treated by using transcatheter approaches (transcatheter aortic valve implantation [TAVI]). The major considerations related to use of general and local anaesthesia for TAVI are discussed in this review.