Standard Laboratory Coagulation Tests Research Articles

Hemostatic Profiles of Patients Who Underwent Transcatheter Versus Surgical Aortic Valve Replacement Versus Percutaneous Coronary Intervention

Guidelines for transcatheter aortic valve replacement (TAVR) antithrombotic prophylaxis are extrapolated predominantly from percutaneous coronary intervention (PCI) data. Here, we examined temporal coagulation changes occurring in the early perioperative period to determine the pathobiologic validity of this supposition. This was a prospective observational study of consecutive patients who underwent transfemoral TAVR (n=27), PCI (n=12), or surgical aortic valve replacement (SAVR) requiring cardiopulmonary bypass and cross-clamping (n=12). Blood samples were taken at 4 time points: T1 (baseline), after general anesthesia or sedation; T2, after heparin administration; T3, at the end of the procedure; and T4, 6 hours after the procedure. The samples were assessed concurrently using standard laboratory coagulation tests and viscoelastic tests of whole blood clotting, including the latest generation thromboelastometry (ROTEM sigma) and thromboelastometry (TEG 6s). Patients in the TAVR cohort were older and a had lower baseline hemoglobin level than patients in the PCI and SAVR cohorts. The baseline platelet function was similar between the TAVR and PCI cohorts and impaired in the SAVR cohort Figure S1. The baseline hemostatic measures were comparable among cohorts. Regarding the per-patient change from baseline, the TAVR cohort showed an overall more prothrombotic state than the other cohorts, with the most marked differences from the SAVR cohort after intraoperative heparin administration and from the PCI cohorts 6hours after the procedure. In addition, the ROTEM and TEG parameters were well correlated but not interchangeable. In conclusion, patients who underwent TAVR have a more prothrombotic hemostatic profile than PCI and SAVR patients. These findings question the current guidelines that extrapolate antithrombotic regimens from PCI to TAVR settings.

A prospective study on the correlation between thromboelastometry and standard laboratory tests – influence of type of surgery and perioperative sampling times

This prospective study aimed at investigating the influence of surgery type and perioperative sampling times on the correlations between rotational thromboelastometry (ROTEM) parameters and standard laboratory coagulation tests assessing comparable coagulation phases. Patients undergoing glioblastoma multiforme resection (GBR group, n = 60) or laparoscopic colon cancer resection (CCR group, n = 40) were prospectively included. Blood samples for ROTEM and laboratory assessments were consecutively drawn within 24-hours prior to surgery (baseline), and at 2, 24 and 48-hours after surgery. Correlations between perioperative ExTEM clotting-time (CT-exTEM) and prothrombin time (PT), and between FibTEM maximum clot firmness (MCF-fibTEM) with and plasma fibrinogen (pFB) concentration (Clauss method), were evaluated using the Spearman’s rho test. The efficiency of recommended cut-offs of CT-exTEM (>75 s) and MCF-fibTEM (<10 mm) for predicting a prolonged PT (>15 s) or a low pFB (<2 g/L), respectively, was assessed using Receiver-Operator Characteristic curves. Correlations between CT-exTEM and PT were weak in GBR (rho = 0.25 [0.12–0.38], p < .01), and very weak in CCR (rho = 0.06 [−0.12–0.27]). Those between MCF-fibTEM and pFB, were strong in both GBR (rho = 0.69 [0.61–0.76], p < .01) and CCR (rho = 0.70 [0.60–0.78], p < .01). These correlations remained largely unchanged over the studied perioperative period in both groups. Recommended CT-exTEM and MCF-fibTEM cut-offs had poor sensitivity for predicting a prolonged PT (17% [8–31]) or a low pFB (46% [32–62]), without group-related differences. Neither the type of surgery nor the perioperative sampling times had a significant influence on the correlations between ROTEM parameters and standard laboratory tests. ClinicalTrials.gov ID: NCT02652897

Congenital Cyanotic Cardiac Surgery in Children: Is Algorithm-Based Point-of-Care Testing Essential to Prevent Bleeding?

Abstract Background Patients with cyanotic congenital heart disease (CCHD) have multifactorial hematologic abnormalities. In continuation of our previous study titled “Coagulopathies in Cyanotic Cardiac Patients: An Analysis with Three Point-of-Care Testing Devices (Thromboelastography, Rotational Thromboelastometry, and Sonoclot Analyzer),” we extended this prospective observational study to a larger cohort to reconfirmed the need to do a point-of-care (POC) test in bleeding cyanotic children. We formulated an algorithm. We conducted this study now by comparing three different POC parameters in an algorithm-based manner and deciphering the best parameter from an algorithm-based and the best parameter POC from an algorithm-based perspective. We conducted this study to compare three different viscoelastic POC tests: thromboelastography (TEG), rotational thromboelastometry (ROTEM), and Sonoclot analyzer to predict thrombocytopenia and hypofibrinogenemia in cyanotic cardiac surgery patients. Material and Methods A total of 105 patients of either sex, who were scheduled to undergo elective cardiac surgery for CCHD on cardiopulmonary bypass (CPB), were enrolled after obtaining written and informed consent. Blood samples for TEG, ROTEM, Sonoclot, and standard laboratory coagulation tests were collected after induction of anesthesia (T1) and 30 minutes after protamine reversal (T2). Results We observed significant correlations between POC parameters, platelet count, and serum fibrinogen levels. Area under the curve (AUC, 0.90) of ROTEM FIBTEM-A10 was found to be superior in detecting hypofibrinogenemia (serum fibrinogen &lt; 200 mg/dL). AUC of TEG α angle (AUC 0.79), TEG MA (AUC 0.77) and Sonoclot CR (AUC 0.73) were comparable. Sonoclot PF was found to have highest AUC (0.95) to detect thrombocytopenia (platelet count &lt; 100,000/μL). ROTEM FIBTEM-A10 at cutoff value ≤ 7.5 mm had highest sensitivity (87.2%) and specificity (80.3%) to detect hypofibrinogenemia. Sonoclot PF at cutoff value ≤ 0.95 had highest sensitivity (100%) and specificity (83.7%) to detect thrombocytopenia. We formulated a POC algorithm based on cutoff value derived from ROC curves. Conclusion In conclusion, although all three viscoelastic POC devices (TEG, ROTEM, and Sonoclot) can be used to detect hypofibrinogenemia and thrombocytopenia, it was reaffirmed on a larger subset of patients that ROTEM FIBTEM has highest diagnostic accuracy for hypofibrinogenemia, whereas Sonoclot PF has highest diagnostic value for thrombocytopenia in CCHD surgical patients.

Management of Major Obstetric Haemorrhage using ROTEM Point-of-Care Haemostasis Analysers Can Reduce Blood Product usage Without Increasing Fibrinogen Replacement Therapy

Major obstetric haemorrhage (MOH) is a leading cause of maternal death and morbidity, with the majority of deaths occurring within four hours of delivery. Therefore, prompt identification of women at risk of MOH is crucial for the rapid assessment and management of blood loss to urgently restore haemodynamic stability. Furthermore, as the rate of blood loss during MOH can increase rapidly in the time when laboratory results are awaited, the management of MOH could benefit from point-of-care coagulation testing by the ROTEM analyser which has a quicker turnaround time compared to standard laboratory coagulation tests. A number of studies indicate that ROTEM-based management of MOH has resulted in a significant reduction in massive transfusions and decreased transfusion of concentrated red cells (CRC) and fresh frozen plasma (FFP) due to a reduction in total blood loss. Several reports which have linked MOH to the depletion of fibrinogen reserves indicate that the reduction in CRC and FFP transfusions is largely due to an increase in early fibrinogen replacement therapy which corrects hypofibrinogenemia. This short report discusses preliminary findings on the impact of ROTEM point-of-care haemostasis analyser on the transfusion of various blood products to obstetric women experiencing MOH at the Royal Gwent Hospital in South wales. The number of blood products transfused following decisions based on the ROTEM analyser measurements (ROTEM group) was compared to historical transfusion data before the ROTEM analyser became available (Pre-ROTEM group). Blood product transfusion in the Pre-ROTEM group was guided by measurements of standard laboratory coagulation tests in conjunction with the established major haemorrhage protocols at the time. The findings indicate that the ROTEM analyser was effective in managing MOH at point-of-care and led to a reduction in the transfusion of CRC, FFP and platelets. However, contrary to published studies, the reduction in blood product usage was not accompanied by an increase in fibrinogen replacement transfusion therapy, suggesting that the ROTEM’s FIBTEM assay accurately quantified fibrinogen levels based on fibrin-clot firmness to enable an early diagnosis of hypofibrinogenemia. Early establishment of the absence of hypofibrinogenemia helped to prevent unnecessary transfusion of fibrinogen concentrate in this study. These findings support the adoption of routine use of ROTEM analysers at point-of-care on labour wards to manage MOH and reduce fibrinogen replacement therapy. The ease of use and rapidity of ROTEM tests could enable departure from globally directed correction of coagulopathy during MOH to a more focussed and precise target transfusion therapy, which will ultimately reduce blood product wastage (including fibrinogen concentrate) whilst minimising transfusion-associated side effects such as alloimmunisation, circulatory overload and dilutional coagulopathy.

Overuse of preoperative laboratory coagulation testing and ABO blood typing: a French national study

BackgroundFollowing publication of guidelines on routine preoperative tests, the French Society of Anaesthesiology and Intensive Care (SFAR), in association with French national public health insurance, conducted a survey to evaluate adherence to guidelines and the economic consequences. MethodsUsing the French Hospital Discharge Database and National Health Insurance Information system, tests performed during the 30 days before surgery were analysed for two situations: (1) standard laboratory coagulation tests and ABO blood typing in children able to walk and scheduled for tonsillectomy/adenoidectomy; and (2) ABO blood typing in adults before laparoscopic cholecystectomy, thyroidectomy, lumbar discectomy or breast surgery. Guidelines do not recommend any preoperative tests in these settings. ResultsBetween 2013 and 2015, a coagulation test was performed in 49% of the 241 017 children who underwent tonsillectomy and 39% of the 133 790 children who underwent adenoidectomy. A similar pattern was observed for ABO blood typing although re-operation rates for bleeding on the first postoperative day were very low (0.12–0.31% for tonsillectomy and 0.01–0.02% for adenoidectomy). Between 2012 and 2015, ABO blood typing was performed in 32–45% of the 1 114 082 patients who underwent one of the four selected procedures. The transfusion rate was very low (0.02–0.31%). The mean cost for the four procedures over the 4 yr period was €5 310 000 (sd €325 000). ConclusionsStandard laboratory coagulation tests and ABO blood typing are still routinely prescribed before surgery and anaesthesia despite current guidelines. This over-prescription represents a high and unnecessary cost, and should therefore be addressed.

Preoperative thrombelastography maximum amplitude predicts massive transfusion in liver transplantation

BackgroundMassive transfusion (MT) is frequently required during liver transplantation. Risk stratification of transplant patients at risk for MT is an appealing concept but remains poorly developed. Thrombelastography (TEG) has recently been shown to reduce mortality when used for trauma resuscitation. We hypothesize that preoperative TEG can be used to risk stratify patients for MT. Material and methodsLiver transplant patients had blood drawn before surgical incision and assayed via TEG. Preoperative TEG measurements were collected in addition to standard laboratory coagulation tests. TEG variables including R-time (reaction time), angle, maximum amplitude (MA), and LY30 (clot lysis 30 min after MA) were correlated to red blood cell units, plasma (fresh frozen plasma), cryoprecipitate, and platelets during the first 24 h after surgery and tested for their performance using a receiver-operating characteristic curve. ResultsTwenty-eight patients were included in the analysis with a median Model for End-Stage Liver Disease score of 17; 36% received a MT. The TEG variables associated with MT (defined as ≥10 red blood cell units/24 h) were a low MA (P < 0.001) and low angle (P = 0.014). A high international normalized ratio of prothrombin time (P = 0.003) and low platelet count (P = 0.007) were also associated with MT. MA had the highest area under the curve (0.861) followed by international normalized ratio of prothrombin time (0.803). An MA of less than 47 mm has a sensitivity of 90% and specificity of 72% to predict a MT. MA was the only coagulation variable that correlated strongly to all blood products transfused. ConclusionsTEG MA has a high predictability of MT during liver transplantation. The use of TEG preoperatively may help guide more cost effective blood bank preparation for this procedure as only a third of patients required a MT.

Coagulation Management Strategies in Cardiac Surgery

Postoperative hemorrhage remains a clinically important problem after major cardiac surgery. This review focuses on the current evidence and emerging data relating to modern strategies in coagulation management in bleeding patients after cardiac surgery. The use of standard laboratory coagulation tests including prothrombin time and activated partial thromboplastin time is limited by long turn-around time, and questionable sensitivity and specificity in major bleeding. Point-of-care coagulation testing including thromboelastometry and thromboelastography has been shown to reduce allogeneic blood product usage, and potentially morbidity. Perioperative coagulation therapy includes the transfusion of platelet concentrates or plasma products and the infusion of coagulation factor concentrates. However, threshold for intervention with these procoagulants are controversial, varying widely among institutions. Coagulopathy and bleeding after cardiac surgery are often multifactorial. A timely and proper hemostatic intervention guided by point-of-care coagulation testing might reduce complications secondary to hemodynamic instability, prolonged mechanical ventilation, and transfusion of large amounts of allogeneic blood products.

Anticoagulation in cirrhosis: a new paradigm?

The liver plays a crucial role in coagulation cascade. Global hemostatic process is profoundly influenced by the presence of liver disease and its complications. Patients with cirrhosis have impaired synthesis of most of the factors involved in coagulation and fibrinolysis process due to a reduced liver function and altered platelet count secondary to portal hypertension. Altered routine tests and thrombocytopenia were considered in the past as associated with increased risk of bleeding. These concepts explain both the routine use of plasma and/or platelets transfusion in patients with liver cirrhosis, especially before invasive procedures, and why these patients were considered “auto-anticoagulated”. New recent evidences show that patients with liver cirrhosis have a more complex hemostatic alteration. Despite the presence of altered levels of factors involved in primary hemostasis, coagulation and fibrinolysis, patients with stable cirrhosis have a rebalanced hemostatic, which however can easily be altered by decompensation or infection, both in hemorrhagic or thrombotic direction. Patients with cirrhosis have an increased risk of venous thrombotic events (namely portal vein thrombosis) while bleeding seems to be related to the grade of portal hypertension rather than to a hemostatic imbalance. The use of anticoagulants both as treatment or prophylaxis is safe, reduces the rate of portal vein thrombosis and decompensation, and improves survival. Standard laboratory coagulation tests are unable to predict bleeding and are inadequate for the assessment of hemostatic status in these patients, hence more comprehensive tests are required to guide the management of thrombotic and bleeding complications.

Coagulopathies in cyanotic cardiac patients: An analysis with three point - of - care testing devices (Thromboelastography, rotational thromboelastometry, and sonoclot analyzer).

Introduction:In the last few years, viscoelastic point-of-care (POC) coagulation devices such as thromboelastography (TEG), rotational thromboelastometry (ROTEM), and Sonoclot (SON) analyzer have been increasingly used in major surgeries for timely assessment and management of coagulopathies. The aim of the present study was to evaluate coagulation profile of cyanotic cardiac patients with TEG, ROTEM, and SON analyzer. In addition, we assessed the correlation of standard laboratory coagulation tests and postoperative chest drain output (CDO) with the parameters of POC testing devices.Materials and Methods:Thirty-five patients of either gender, belonging to the American Society of Anesthesiologists Grade I–III, and undergoing elective cardiac surgery on cardiopulmonary bypass for cyanotic congenital heart disease were included in this study. To identify possible coagulation abnormalities, blood samples for TEG, ROTEM, SON, and standard laboratory coagulation were collected after induction of anesthesia. The correlations between variables were assessed using Pearson's correlation coefficient. P < 0.05 was considered statistically significant.Results and Discussion:EXTEM clot time (CT) and clot formation time (CFT) were prolonged in 87% and 45% patients whereas INTEM CT and CFT were prolonged in 36% and 73% patients, respectively. FIBTEM maximum clot firmness (MCF) was decreased in 30% patients. We observed significant correlation between fibrinogen concentration and ROTEM FIBTEM MCF (r = 0.94, P < 0.001). The SON platelet function (SON PF) showed good correlation with platelet count (r = 0.85, P < 0.001). We also found significant correlation between preoperative FIBTEM MCF and CDO in first 4 postoperative hours (r = 0.49, P = 0.004) and 24 postoperative hours (r = 0.52, P = 0.005). Receiver operating characteristic analysis demonstrated that SON PF and TEG maximum amplitude are highly predictive of thrombocytopenia below 100 × 109/L (area under the curve [AUC] - 0.97 and 0.92, respectively), while FIBTEM-MCF is highly predictive of hypofibrinogenemia (fibrinogen <150 mg/dL (AUC, 0.99).Conclusion:Cyanotic cardiac patients have preoperative coagulation abnormalities in ROTEM, TEG, and SON parameters. ROTEM FIBTEM is highly predictive of hypofibrinogenemia while SON PF is highly predictive of thrombocytopenia. ROTEM FIBTEM can be studied as a marker of increased postoperative CDO.

Assessment of Hemostasis after Plasma Exchange Using Rotational Thrombelastometry (ROTEM).

BackgroundTherapeutic plasma exchange (TPE)-based protocols immediately before cadaveric donor kidney transplantation have been extensively used in highly sensitized recipients. Plasma is generally preferred over human albumin as replacement fluid to avoid depletion of coagulation factors and perioperative bleeding. The aim of this study was to estimate bleeding risk after TPE replaced with albumin using rotational thromboelastography (ROTEM).MethodologyTen patients without overt coagulation abnormalities underwent TPE. Standard laboratory coagulation tests (thromboplastin time, activated partial thromboplastin time (aPTT), international normalized ratio (INR), thrombin clotting time, fibrinogen levels and antithrombin activity) were compared with thrombelastometry analysis (EXTEM and INTEM tests) before and after TPE.Principal FindingsTPE significantly reduced fibrinogen levels (482 ± 182 vs. 223 ± 122 mg/dL), antithrombin activity (103 ± 11 vs. 54 ± 11 %), and prolonged aPTT (28 ± 3 vs. 45 ± 8 s), thromboplastin time (108 ± 11 vs. 68 ± 11 %), INR (0.95 ± 0.06 vs. 1.25 ± 0.16), and thrombin clotting time (18 ± 2 vs. 20 ± 3 s). INTEM and EXTEM analyses revealed significantly prolonged clot-formation time and reduced maximum clot firmness.Conclusions/SignificanceTPE replaced with albumin induces significant changes in global hemostasis parameters thus potentially increasing bleeding risk. Therefore, pretransplant TPE should be considered carefully in indicated patients before kidney transplantation. The role of the ROTEM point-of-care test to estimate the risk of bleeding in renal transplantation needs to be evaluated in further studies.

Solvent detergent vs. fresh frozen plasma in cirrhotic patients undergoing liver transplant surgery: a prospective randomized control study

Although orthotopic liver transplantation (OLT) is nowadays considered standard practice at experienced centres, it can still be affected by a significant risk of massive bleeding and its related complications. Solvent/detergent plasma (S/D Plasma) has been proposed as an alternative to fresh frozen plasma (FFP) to curtail such complications. This study aimed at evaluating the efficacy of S/D Plasma in OLT patients by comparing it to FFP. Sixty-three OLT patients were randomized into two groups depending on whether they were transfused with FFP or S/D plasma. A thromboelastography-based protocol aimed at achieving and maintaining predetermined coagulation goals was used to guide plasma transfusions. At the beginning and the end of surgery, standard laboratory coagulation tests were performed together with the assessment of the VII, VIII, V, XII factors and S protein blood levels. The two study groups equally achieved the thromboelastography goals but with a reduced amount of transfusions in the S/D plasma group (P < 0.0001). At the end of surgery, factors V and XII and S protein blood levels were lower in the S/D plasma patients who also showed lower INR, aPTT and antithrombin III levels. In cirrhotic patients undergoing OLT, the use of S\D plasma associated with thromboelastography allows the same clinical results but with a significant reduction in the amount of plasma transfusions.

Correlation of activated clotting times and standard laboratory coagulation tests in paediatric non-cardiac surgery

The activated clotting time (ACT) was invented as a whole blood test to detect coagulopathy, but nowadays is almost exclusively used to guide heparin anticoagulation. Although the ACT provides a fairly reliable and fast bedside test of the coagulation status, only a few studies have focused on its use to monitor pre- or intraoperative coagulation status as an early marker of impaired haemostasis or increased bleeding tendency. The aim of this study was to compare intraoperative i-STAT® ACT values with commonly used thresholds of standard coagulation tests for the diagnosis of coagulopathy during paediatric non-cardiac surgery. We performed a prospective, observational study in a University Children's hospital and included 50 paediatric patients who underwent major elective, non-cardiac, surgery. The i-STAT® kaolin ACT test was obtained intraoperatively and compared to the commonly used threshold of standard coagulation tests (PT/INR, aPTT, and plasma fibrinogen level). A total of 181 blood samples were taken from 50 pediatric patients. Moderate correlation was found between ACT and aPTT (r = 0.694; p < 0.001), and all other coagulation tests. The median ACT values remained within the normal range throughout the entire surgical phase, while standard coagulation tests were mostly abnormal during surgery. Intraoperative measurement of ACT did not provide comparable thresholds of normal haemostasis as compared to standard coagulation testing.

The FIB-PPH trial: fibrinogen concentrate as initial treatment for postpartum haemorrhage: study protocol for a randomised controlled trial

BackgroundPostpartum haemorrhage (PPH) remains a leading cause of maternal mortality worldwide. In Denmark 2% of parturients receive blood transfusion. During the course of bleeding fibrinogen (coagulation factor I) may be depleted and fall to critically low levels, impairing haemostasis and thus worsening the ongoing bleeding. A plasma level of fibrinogen below 2 g/L in the early phase of postpartum haemorrhage is associated with subsequent development of severe haemorrhage. Use of fibrinogen concentrate allows high-dose substitution without the need for blood type crossmatch. So far no publications of randomised controlled trials involving acutely bleeding patients in the obstetrical setting have been published. This trial aims to investigate if early treatment with fibrinogen concentrate reduces the need for blood transfusion in women suffering severe PPH.Methods/DesignIn this randomised placebo-controlled double-blind multicentre trial, parturients with primary PPH are eligible following vaginal delivery in case of: manual removal of placenta (blood loss ≥ 500 ml) or manual exploration of the uterus after the birth of placenta (blood loss ≥ 1000 ml). Caesarean sections are also eligible in case of perioperative blood loss ≥ 1000 ml. The exclusion criteria are known inherited haemostatic deficiencies, prepartum treatment with antithrombotics, pre-pregnancy weight <45 kg or refusal to receive blood transfusion. Following informed consent, patients are randomly allocated to either early treatment with 2 g fibrinogen concentrate or 100 ml isotonic saline (placebo). Haemostatic monitoring with standard laboratory coagulation tests and thromboelastography (TEG, functional fibrinogen and Rapid TEG) is performed during the initial 24 hours.Primary outcome is the need for blood transfusion. To investigate a 33% reduction in the need for blood transfusion, a total of 245 patients will be included. Four university-affiliated public tertiary care hospitals will include patients during a two-year period. Adverse events including thrombosis are assessed in accordance with International Conference on Harmonisation (ICH) good clinical practice (GCP).DiscussionA widespread belief in the benefits of early fibrinogen substitution in cases of PPH has led to increased off-label use. The FIB-PPH trial is investigator-initiated and aims to provide an evidence-based platform for the recommendations of the early use of fibrinogen concentrate in PPH.Trial registrationClincialTrials.gov NCT01359878.

Reference ranges for thromboelastography (TEG®) and traditional coagulation tests in term parturients undergoing caesarean section under spinal anaesthesia*

There has been little published work defining 'normal' thromboelastography (TEG(®) ) values in healthy parturients, and few large studies defining reference ranges for traditional coagulation tests in this patient group. Our aim was to establish peri-operative reference ranges for TEG and for standard laboratory coagulation tests in our pregnant population. Fifty healthy term parturients presenting for elective caesarean section under spinal anaesthesia had blood samples taken pre-operatively, on arrival in the recovery room and, in a subset of 33 women, 4 h after routine thromboprophylaxis with enoxaparin 40 mg. All three samples had TEG analysis, the first and second having standard laboratory coagulation tests in addition. Reference ranges for our pregnant population were established, demonstrating a hypercoagulable state in term parturients and a significant effect of enoxaparin. The standard coagulation reference ranges were within 98% of the local non-pregnant ranges. These reference ranges provide a useful comparator for peri-operative TEG and routine coagulation analysis in term parturients.

Thromboelastometric (ROTEM) Findings in Patients Suffering from Isolated Severe Traumatic Brain Injury

Severe traumatic brain injury (sTBI) is often accompanied by coagulopathy and an increased risk of bleeding. To identify and successfully treat bleeding disorders associated with sTBI, rapid assessment of coagulation status is crucial. This retrospective study was designed to assess the potential role of whole-blood thromboelastometry (ROTEM(®), Tem International, Munich, Germany) in patients with isolated sTBI (abbreviated injury scale [AIS](head) ≥3 and AIS(extracranial) <3). Blood samples were obtained immediately following admission to the emergency room of the Trauma Centre Salzburg in Austria. ROTEM analysis (EXTEM, INTEM, and FIBTEM tests) and standard laboratory coagulation tests (prothrombin time index [PTI, percentage of normal prothrombin time], activated partial thromboplastin time [aPTT], fibrinogen concentration, and platelet count) were compared between survivors and non-survivors. Out of 88 patients with sTBI enrolled in the study, 66 survived and 22 died. PTI, fibrinogen, and platelet count were significantly higher in survivors (p<0.005). Accordingly, aPTT was shorter in this group (p<0.0001). ROTEM analysis revealed shorter clotting times in extrinsically activated thromboelastometric test (EXTEM) and intrinsically activated thromboelastometric test (INTEM) (p<0.001), shorter clot formation times in EXTEM and INTEM (p<0.0001), and higher maximum clot firmness in EXTEM, INTEM, and FIBTEM (p<0.01) in survivors compared with non-survivors. Logistic regression analysis revealed extrinsically activated thromboelastometric test with cytochalasin D (FIBTEM) MCF and aPTT to have the best predictive value for mortality. According to the degree of coagulopathy, non-survivors received more RBC (p=0.016), fibrinogen concentrate (p=0.01), and prothrombin complex concentrate (p<0.001) within 24 h of arrival in the emergency room. ROTEM testing appeared to offer an early signal of severe life-threatening sTBI. Further studies are warranted to confirm these results and to investigate the role of ROTEM in guiding coagulation therapy.

Influence of direct thrombin inhibitor argatroban on coagulation assays in healthy individuals, patients under oral anticoagulation therapy and patients with liver dysfunction

We assumed that argatroban, a direct thrombin inhibitor, has a strong influence on different coagulation tests which is even more pronounced in patients with an established reduced factor activity like those under oral anticoagulation therapy or with liver dysfunction. To validate this influence we spiked plasma samples from healthy individuals, patients under oral anticoagulation therapy or with liver dysfunction with increasing argatroban concentrations (0-2000 ng/ml) and performed routine laboratory coagulation tests. Consequently, prothrombin time, activated partial thromboplastin time, thrombin time, batroxobin time, coagulation factor activity (FII-FXIII), protein S (activity), protein C (chromogen) and fibrinogen (derived and Clauss fibrinogen method) were measured. Furthermore, the influence of argatroban on the induced platelet aggregation was evaluated. Argatroban interference on standard coagulation assays differed markedly depending on the different subgroups of patients investigated. Prolongation of prothrombin time by argatroban (at 2000 ng/ml 2.7-fold in healthy persons) was significantly higher in oral anticoagulation therapy (3.9-fold) and even more pronounced in liver dysfunction (6.0-fold). The fibrinogen concentration was determined falsely even at low-argatroban concentrations using functional methods in healthy persons and all patient subgroups. The influence of argatroban on standard laboratory coagulation tests is significantly increased by a preexisting factor deficiency. Functional fibrinogen measurement may be helpful to assess in-vivo fibrinogen function but should be avoided to evaluate fibrinogen concentration in argatroban treated patients. Argatroban had no influence on chromogenic protein C measurement, batroxobin time and induced platelet aggregation. Knowledge of argatroban interference is a prerequisite for the reliable interpretation of coagulation assays.