Approach to thromboelastography-based transfusion in cirrhosis:An alternative perspective on coagulation disorders

Viscoelastic tests,specifically thromboelastography and rotational thromboelastometry,are increasingly being used in the management of postoperative bleeding in surgical intensive care units(ICUs).However,life-threatening bleeds may complicate the clinical course of many patients admitted to medical ICUs,especially those with underlying liver dysfunction.Patients with cirrhosis have multiple coagulation abnormalities that can lead to bleeding or thrombotic complications.Compared to conventional coagulation tests,a comprehensive depiction of the coagulation process and point-of-care availability are advantages favoring these devices,which may aid physicians in making a rapid diagnosis and instituting early interventions.These tests may help predict bleeding and rationalize the use of blood products in these patients.

Combining Serum Procalcitonin Level,Thromboelastography,and Platelet Count to Predict Short-term Development of Septic Shock in Intensive Care Unit

Objective Despite the recent advances in diagnosis and treatment,sepsis continues to lead to high morbidity and mortality.Early diagnosis and prompt treatment are essential to save lives.However,most biomarkers can only help to diagnose sepsis,but cannot predict the development of septic shock in high-risk patients.The present study determined whether the combined measurement of procalcitonin(PCT),thromboelastography(TEG)and platelet(PLT)count can predict the development of septic shock.Methods A retrospective study was conducted on 175 septic patients who were admitted to the intensive care unit between January 2017 and February 2021.These patients were divided into two groups:73 patients who developed septic shock were assigned to the septic shock group,while the remaining 102 patients were assigned to the sepsis group.Then,the demographic,clinical and laboratory data were recorded,and the predictive values of PCT,TEG and PLT count for the development of septic shock were analyzed.Results Compared to the sepsis group,the septic shock group had statistically lower PLT count and TEG measurements in the R value,K value,αangle,maximum amplitude,and coagulation index,but had longer prothrombin time(DT),longer activated partial thromboplastin time(APTT),and higher PCT levels.Furthermore,the Sequential Organ Failure Assessment(SOFA)score was higher in the septic shock group.The multivariate logistic regression analysis revealed that PCT,TEG and PLT count were associated with the development of septic shock.The area under the curve analysis revealed that the combined measurement of PCT,TEG and PLT count can be used to predict the development of septic shock with higher accuracy,when compared to individual measurements.Conclusion The combined measurement of PCT,TEG and PLT count is a novel approach to predict the development of septic shock in high-risk patients.

Intraoperative thromboelastography-guided transfusion in a patient with factor XI deficiency: A case report

BACKGROUND Factor XI(FXI)deficiency,also known as hemophilia C,is a rare bleeding disorder of unpredictable severity that correlates poorly with FXI coagulation activity.This often poses great challenges in perioperative hemostatic management.Thromboelastography(TEG)is a method for testing blood coagulation using a viscoelastic hemostatic assay of whole blood to assess the overall coagulation status.Here,we present the successful application of intraoperative TEG monitoring in an FXI-deficient patient as an individualized blood transfusion strategy.CASE SUMMARY A 21-year-old male patient with FXI deficiency was scheduled to undergo reconstructive surgery for macrodactyly of the left foot under general anesthesia.To minimize his bleeding risk,he was scheduled to receive fresh frozen plasma(FFP)as an empirical prophylactic FXI replacement at a dose of 15-20 mL/kg body weight(900-1200 mL)before surgery.Subsequent FFP transfusion was to be adjusted according to surgical need.Instead,TEG assessment was used at the beginning and toward the end of his surgery.According to intraoperative TEG results,the normalization of coagulation function was achieved with an infusion of only 800 mL FFP,and blood loss was minimal.The patient showed an uneventful postoperative course and was discharged on postoperative day 8.CONCLUSION TEG can be readily applied in the intraoperative period to individualize transfusion needs in patients with rare inherited coagulopathy.

Intraoperative thromboelastography as a tool to predict postoperative thrombosis during liver transplantation

BACKGROUND Thromboembolic complications are relatively common causes of increased morbidity and mortality in the perioperative period in liver transplant patients.Early postoperative portal vein thrombosis(PVT,incidence 2%-2.6%)and early hepatic artery thrombosis(HAT,incidence 3%-5%)have a poor prognosis in transplant patients,having impacts on graft and patient survival.In the present study,we attempted to identify the predictive factors of these complications for early detection and therefore monitor more closely the patients most at risk of thrombotic complications.AIM To investigate whether intraoperative thromboelastography(TEG)is useful in detecting the risk of early postoperative HAT and PVT in patients undergoing liver transplantation(LT).METHODS We retrospectively collected thromboelastographic traces,in addition to known risk factors(cold ischemic time,intraoperative requirement for red blood cells and fresh-frozen plasma transfusion,prolonged operating time),in 27 patients,selected among 530 patients(≥18 years old),who underwent their first LT from January 2002 to January 2015 at the Liver University Transplant Center and developed an early PVT or HAT(case group).Analyses of the TEG traces were performed before anesthesia and 120 min after reperfusion.We retrospectively compared these patients with the same number of nonconsecutive control patients who underwent LT in the same study period without developing these complications(1:1 match)(control group).The chosen matching parameters were:Patient graft and donor characteristics[age,sex,body mass index(BMI)],indication for transplantation,procedure details,United Network for Organ Sharing classification,BMI,warm ischemia time(WIT),cold ischemia time(CIT),the volume of blood products transfused,and conventional laboratory coagulation analysis.Normally distributed continuous data are reported as the mean±SD and compared using one-way Analysis of Variance(ANOVA).Nonnormally distributed continuous data are reported as the median(interquartile range)and compared using the Mann-Whitney test.Categorical variables were analyzed with Chi-square tests with Yates correction or Fisher’s exact test depending on best applicability.IBM SPSS Statistics version 24(SPSS Inc.,Chicago,IL,United States)was employed for statistical analysis.Statistical significance was set at P<0.05.RESULTS Postoperative thrombotic events were identified as early if they occurred within 21 d postoperatively.The incidence of early hepatic artery occlusion was 3.02%,whereas the incidence of PVT was 2.07%.A comparison between the case and control groups showed some differences in the duration of surgery,which was longer in the case group(P=0.032),whereas transfusion of blood products,red blood cells,fresh frozen plasma,and platelets,was similar between the two study groups.Thromboelastographic parameters did not show any statistically significant difference between the two groups,except for the G value measured at basal and 120’postreperfusion time.It was higher,although within the reference range,in the case group than in the control group(P=0.001 and P<0.001,respectively).In addition,clot lysis at 60 min(LY60)measured at 120’postreperfusion time was lower in the case group than in the control group(P=0.035).This parameter is representative of a fibrinolysis shutdown(LY60=0%-0.80%)in 85%of patients who experienced a thrombotic complication,resulting in a statistical correlation with HAT and PVT.CONCLUSION The end of surgery LY60 and G value may identify those recipients at greater risk of developing early HAT or PVT,suggesting that they may benefit from intense surveillance and eventually anticoagulation prophylaxis in order to prevent these serious complications after LT.

Thromboelastography: Current Applications, Future Directions

Analyzing coagulability often hinges on patient surveillance using prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) to monitor the extrinsic and intrinsic coagulation pathways, respectively A more complete assessment, however, can often be obtained using thromboelastography (TEG), a coagulation assay that evaluates the efficiency of clot formation, as well as the viscoelastic properties of the clot. Developed by Dr. Helmut Hartert in 1948 at the UniversityofHeidelberg, it provides information regarding hemostasis as a dynamic process [1,2]. Here, the TEG technique will be described, as well as its current applications and future directions for its use.

Clinical relevance of Chinese syndrome factors and thromboelastography levels in patients with phlegm-heat and fu-organ excess syndrome

Objective:Syndrome differentiation is a unique part of traditional Chinese medicine(TCM).Syndrome factors play an important role in the diagnosis and treatment of TCM syndromes.Thromboelastography(TEG)intuitively reflects the blood status of patients with acute ischemic stroke(AIS)and is important in the treatment and prognosis of AIS.To identify the relationship between TCM syndrome factors and TEG in AIS patients and standardize TCM syndrome differentiation and treatment objectives,we designed a prospective cohort study of 103 AIS patients.Methods:We used the diagnostic criteria for AIS in the Chinese Guideline for Diagnosis and Management of Acute Ischemic Stroke 2010.Diagnosis of phlegm-heat and fu-organ excess syndrome was based on the TCM Scale for the Syndrome of Phlegm-heat and fu-organ Excess.The ischemic Stroke TCM Syndrome Factor Diagnostic Scale was used to identify and diagnose syndrome factors.General information,scores of syndrome factors and values of TEG parameters of all enrolled patients were recorded.Results:There were significant differences in internal fire and phlegm-dampness scores between patients with and without phlegm-heat and fu-organ excess syndrome(P<.05).In patients with phlegm-heat and fu-organ excess syndrome,internal fire was negatively correlated with TEG parameters R and K(P<.05)and positively correlated with alpha Angle and coagulation index(P<.01).There were no significant correlations between the two syndrome factors and MA(P Z.058)and LY30(P>.05)or between both syndrome factors and TEG parameters in patients without phlegm-heat and fu-organ excess syndrome.Conclusion:The syndrome factor internal fire is a potential predictor of increased platelet function and fibrinogen activity in AIS patients with phlegm-heat and fu-organ excess,and a potentially important predictor of blood hypercoagulability in TCM.

Thromboelastography Use in the Perioperative Transfusion Management of a Patient with Hemophilia A Undergoing Liver Transplantation

The thrombelastogram is a method used to monitor clotting dynamics. Thrombelastography (TE) has been used to guide therapy of coagulation disorders mostly in cardiac surgery but also in liver surgery. TE is a useful tool for perioperative management of patients at risk for coagulopathy. There are several reports describing the use of the thrombelastogram in patients undergoing orthotopic liver transplantation (OLT), but only few cases include patients with both liver disease and inherited bleeding disorders. We describe the use of TE in a patient with hemophilia A and advanced cirrhosis undergoing OLT.

Value of Thromboelastography in Judging Abnormal Coagulation Function in Patients with Early Hemorrhagic Shock

Objective: To detect the changes of coagulation function in patients with early hemorrhagic shock by thromboelastography (TEG). Methods: TEG was performed in 50 patients with early hemorrhagic shock and surgical indications. The TEG parameters were compared with 50 healthy people. The coagulation and fibrinolysis in patients with early hemorrhagic shock were observed. Results: In terms of coagulation parameters, the R value decreased, the α angle increased, and the K value and MA value did not change significantly in patients with early hemorrhagic shock. Fibrinolytic aspects: EPL, LY30 observations have no significant changes compared to normal values. Conclusion: The plasma coagulation factor activity is increased in patients with early hemorrhagic shock;the fibrin level is increased;the blood is in a hypercoagulable state;and the fibrinolysis function is not changed. The timely detection of TEG can be used for coagulation function monitoring and blood transfusion therapy in patients with surgical hemorrhagic shock. It provides an important basis for preventing the formation of deep vein thrombosis.

Rotation Thromboelastography for Assessment of Hypercoagulation and Thrombosis in Patients with Cardiovascular Diseases

Hypercoagulation is not detected in clinical practice with routinely performed blood coagulation tests. More advanced laboratory analyses to detect or monitor hypercoagulation have not yet been introduced into routine clinical management. Thromboelastography assesses the influence of plasma factors and platelets during all phases of haemostasis, thus permits evaluation of hypo- and hyper- coagulation status. This prospective study included assessment of 35 patients with thrombotic complications （II-nd group）, compared with 34 healthy controls （I-st group）. Haemostasis was analyzed with routine clotting tests： protrombin time （PT）, activated partial thromboplastin time （APTT）, fibrinogen, platelets and rotation thromboelastography （ROTEM~） with measuring time to 20 min. All data are presented as mean and standard deviation （SD）. Statistical comparisons of samples were performed by student＇s t-test. The sensitivity, specificity, positive and negative predictive value of the parameters was calculated by using the receiver operator characteristic （ROC） curves for two groups. There was significant difference （P 〈 0.05） observed in the parameters of ROTEM： clot formation time （CFT）, a-angle, maximum clot firmness （MCF） and thrombodynamic potential index （TPI） in the patient＇s population compared to the healthy controls. No significant difference was observed in CT （ROTEM） and routine coagulation tests when the two groups were compared. Rotation thromboelastography analysis demonstrated to be a reliable method for diagnosis of hypercoagulable state.

Comparative studies between humans and golden Syrian hamsters via thromboelastography

Background:Thromboelastography(TEG)is a widely utilized clinical testing method for real-time monitoring of platelet function and the thrombosis process.Lipid metab-olism disorders are crucial risk factors for thrombosis.The lipid metabolism charac-teristics of hamsters resemble those of humans more closely than mice and rats,and their relatively large blood volume makes them suitable for studying the mechanisms of thrombosis related to plasma lipid mechanisms.Whole blood samples from golden Syrian hamsters and healthy humans were obtained following standard clinical pro-cedures.TEG was employed to evaluate coagulation factor function,fibrinogen(Fib)function,platelet function,and the fibrinolytic system.Methods:The whole blood from hamster or healthy human was isolated following the clinical procedure,and TEG was employed to evaluate the coagulation factor func-tion,Fib function,platelet function,and fibrinolytic system.Coagulation analysis used ACLTOP750 automatic coagulation analysis pipeline.Blood routine testing used XN-2000 automatic blood analyzer.Results:TEG parameters revealed that hamsters exhibited stronger coagulation fac-tor function than humans(reaction time[R],p=0.0117),with stronger Fib function(alpha angle,p<0.0001;K-time[K],p<0.0001).Platelet function did not differ signifi-cantly(maximum amplitude[MA],p=0.077).Hamsters displayed higher coagulation status than humans(coagulation index[CI],p=0.0023),and the rate of blood clot dissolution in hamsters differed from that in humans(percentage lysis 30 min after MA,p=0.02).Coagulation analysis parameters indicated that prothrombin time(PT)and activated partial thromboplastin time(APTT)were faster in hamsters than in hu-mans(PT,p=0.0014;APTT,p=0.03),whereas the Fib content was significantly lower in hamsters than in humans(p<0.0001).No significant difference was observed in thrombin time(p=0.1949).Conclusions:In summary,TEG could be used to evaluate thrombosis and bleeding parameters in whole blood samples from hamsters.The platelet function of hamsters closely resembled that of humans,whereas their coagulation function was signifi-cantly stronger.

Transfusion and coagulation management in liver transplantation

There is wide variation in the management of coagulation and blood transfusion practice in liver transplantation. The use of blood products intraoperatively is declining and transfusion free transplantations take place ever more frequently. Allogenic blood products have been shown to increase morbidity and mortality. Primary haemostasis, coagulation and fibrinolysis are altered by liver disease. This, combined with intraoperative disturbances of coagulation, increases the risk of bleeding. Meanwhile, the rebalancing of coagulation homeostasis can put patients at risk of hypercoagulability and thrombosis. The application of the principles of patient blood management to transplantation can reduce the risk of transfusion. This includes: preoperative recognition and treatment of anaemia, reduction of perioperative blood loss and the use of restrictive haemoglobin based transfusion triggers. The use of point of care coagulation monitoring using whole blood viscoelastic testing provides a picture of the complete coagulation process by which to guide and direct coagulation management. Pharmacological methods to reduce blood loss include the use of anti-fibrinolytic drugs to reduce fibrinolysis, and rarely, the use of recombinant factor VIIa. Factor concentrates are increasingly used; fibrinogen concentrates to improve clot strength and stability, and prothrombin complex concentrates to improve thrombin generation. Non-pharmacological methods to reduce blood loss include surgical utilisation of the piggyback technique and maintenance of a low central venous pressure. The use of intraoperative cell salvage and normovolaemic haemodilution reduces allogenic blood transfusion. Further research into methods of decreasing blood loss and alternatives to blood transfusion remains necessary to continue to improve outcomes after transplantation.

Perioperative thromboprophylaxis in liver transplant patients

Improvements in surgical and anesthetic procedures have increased patient survival after liver transplantation(LT). However, the perioperative period of LT can still be affected by several complications. Among these, thromboembolic complications(intracardiac thrombosis, pulmonary embolism, hepatic artery and portal vein thrombosis) are relatively common causes of increased morbidity and mortality. The benefit of thromboprophylaxis in general surgical patients has already been established, but it is not the standard of care in LT recipients. LT is associated with a high bleeding risk, as it is performed in a setting of already unstable hemostasis. For this reason, the role of routine perioperative prophylactic anticoagulation is usually restricted. However, recent data have shown that the bleeding tendency of cirrhotic patients is not an expression of an acquired bleeding disorder but rather of coexisting factors(portal hypertension, hypervolemia and infections). Furthermore, in cirrhotic patients, the new paradigm of ‘‘rebalanced hemostasis' ' can easily tip towards hypercoagulability because of the recently described enhanced thrombin generation, procoagulant changes in fibrin structure and platelet hyperreactivity. This new coagulation balance, along with improvements in surgical techniques and critical support, has led to a dramatic reduction in transfusion requirements, and the intraoperative thromboembolic-favoring factors(venous stasis, vessels clamping, surgical injury) have increased the awareness of thrombotic complications and led clinicians to reconsider the limited use of anticoagulants or antiplatelets in the postoperative period of LT.

Clinical utility of viscoelastic testing in chronic liver disease: A systematic review

BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion.This is despite the fact that conventional tests do not reliably separate those with a clinically significant coagulopathy from those who do not.Viscoelastic testing such as thromboelastography(TEG)correlate with bleeding risk and are more accurate in identifying those who will benefit from blood product transfusion.Despite this,viscoelastic tests have not been widely used in patients with chronic liver disease outside the transplant setting.AIM To assess the utility of Viscoelastic Testing guided transfusion in chronic liver disease patients presenting with bleeding or who require an invasive procedure.METHODS PubMed and Google Scholar searches were performed using the key words“thromboelastography”,“TEG”or“viscoelastic”and“liver transplantation”,“cirrhosis”or“liver disease”and“transfusion”,“haemostasis”,“blood management”or“haemorrhage”.A full text review was undertaken and data was extracted from randomised control trials that evaluated the outcomes of viscoelastic test guided transfusion in those with liver disease.The study subjects,inclusion and exclusion criteria,methods,outcomes and length of follow up were examined.Data was extracted by two independent individuals using a standardized collection form.The risk of bias was assessed in the included studies.RESULTS A total of five randomised control trials included in the analysis examined the use of TEG guided blood product transfusion in cirrhosis prior to invasive procedures(n=118),non-variceal haemorrhage(n=96),variceal haemorrhage(n=60)and liver transplantation(n=28).TEG guided transfusion was effective in all five studies with a statistically significant reduction in overall blood product transfusion compared to standard of care.Four of the five studies reported a significant reduction in transfusion of fresh frozen plasma and platelets.Two studies showed a significant reduction in cryoprecipitate transfusion.No increased risk of bleeding was reported in the three trials where TEG was used perioperatively or prior to an invasive procedure.Two trials in the setting of cirrhotic variceal and non-variceal bleeding showed no difference in control of initial bleeding.In those with variceal bleeding,there was a statistically significant reduction in rate of re-bleeding at 42 d in the TEG arm 10%(vs 26.7%in the standard of care arm P=0.012).Mortality data reported at various time points for all five trials from 6 wk up to 3 years was not statistically different between each arm.One trial in the setting of non-variceal bleeding demonstrated a significant reduction in adverse transfusion events in the TEG arm 30.6%(vs 74.5%in the control arm P<0.01).In this study there was no significant difference in total hospital stay although length of stay in intensive care unit was reduced by an average of 2 d in the TEG arm(P=0.012).CONCLUSION Viscoelastic testing has been shown to reduce blood product usage in chronic liver disease without compromising safety and may enable guidelines to be developed to ensure patients with liver disease are optimally managed.

Thromboelastographic reference ranges for a cirrhotic patient population undergoing liver transplantation

AIM To describe the thromboelastography(TEG) "reference" values within a population of liver transplant(LT) candidates that underline the differences from healthy patients.METHODS Between 2000 and 2013, 261 liver transplant patients with a model for end-stage liver disease(MELD) score between 15 and 40 were studied. In particular the adult patients(aged 18-70 years) underwent to a first LT with a MELD score between 15 and 40 were included, while all patients with acute liver failure, congenital bleeding disorders, and anticoagulant and/or antiplatelet drug use were excluded. In this population of cirrhotic patients, preoperative haematological and coagulation laboratory tests were collected, and the pretransplant thromboelastographic parameters were studied and compared with the parameters measured in a previously studied population of 40 healthy subjects. The basal TEG parameters analysed in the cirrhotic population of liver candidates were as follows: Reaction time(r), coagulation time(k), Angle-Rate of polymerization of clot(α Angle), Maximum strenght of clot(MA), Amplitudes of the TEG tracing at 30 min and 60 min after MA is measured(A30 and A60), and Fibrinolysis at 30 and 60 min after MA(Ly30 and Ly60). The possible correlation between the distribution of the reference range and the gender, age, MELD score(higher or lower than 20) and indications for transplantation(liver pathology) were also investigated. In particular, a MELD cut-off value of 20 was chosen to verify the possible correlation between the thromboelastographic reference range and MELD score. RESULTS Most of the TEG reference values from patients with end-stage liver disease were significantly different from those measured in the healthy population and were outside the suggested normal ranges in up to 79.3% of subjects. Wide differences were found among all TEG variables, including r(41.5% of the values), k(48.6%), α(43.7%), MA(79.3%), A30(74.4%) and A60(80.9%), indicating a prevailing trend to hypocoagulability. The differences between the mean TEG values obtained from healthy subjects and the cirrhotic population were statistically significant for r(P = 0.039), k(P < 0.001), MA(P < 0.001), A30(P < 0.001), A60(P < 0.001) and Ly60(P = 0.038), indicating slower and less stable clot formation in the cirrhotic patients. In the cirrhotic population, 9.5% of patients had an r value shorter than normal, indicating a tendency for faster clot formation. Within the cirrhotic patient population, gender, age and the presence of hepatocellular carcinoma or alcoholic cirrhosis were not significantly associated with greater clot firmness or enhanced whole blood clot formation, whereas greater clot strength was associated with a MELD score < 20, hepatitis C virus and cholestaticrelated cirrhosis(P < 0.001; P = 0.013; P < 0.001).CONCLUSION The range and distribution of TEG values in cirrhotic patients differ from those of healthy subjects, suggesting that a specific thromboelastographic reference range is required for liver transplant candidates.

Anticoagulation in simultaneous pancreas kidney transplantation - On what basis?

BACKGROUND Despite technical refinements,early pancreas graft loss due to thrombosis continues to occur.Conventional coagulation tests(CCT)do not detect hypercoagulability and hence the hypercoagulable state due to diabetes is left untreated.Thromboelastogram(TEG)is an in-vitro diagnostic test which is used in liver transplantation,and in various intensive care settings to guide anticoagulation.TEG is better than CCT because it is dynamic and provides a global hemostatic profile including fibrinolysis.AIM To compare the outcomes between TEG and CCT(prothrombin time,activated partial thromboplastin time and international normalized ratio)directed anticoagulation in simultaneous pancreas and kidney(SPK)transplant recipients.METHODS A single center retrospective analysis comparing the outcomes between TEG and CCT-directed anticoagulation in SPK recipients,who were matched for donor age and graft type(donors after brainstem death and donors after circulatory death).Anticoagulation consisted of intravenous(IV)heparin titrated up to a maximum of 500 IU/h based on CCT in conjunction with various clinical parameters or directed by TEG results.Graft loss due to thrombosis,anticoagulation related bleeding,radiological incidence of partial thrombi in the pancreas graft,thrombus resolution rate after anticoagulation dose escalation,length of the hospital stays and,1-year pancreas and kidney graft survival between the two groups were compared.RESULTS Seventeen patients who received TEG-directed anticoagulation were compared against 51 contemporaneous SPK recipients(ratio of 1:3)who were anticoagulated based on CCT.No graft losses occurred in the TEG group,whereas 11 grafts(7 pancreases and 4 kidneys)were lost due to thrombosis in the CCT group(P=0.06,Fisher’s exact test).The overall incidence of anticoagulation related bleeding(hematoma/gastrointestinal bleeding/hematuria/nose bleeding/re-exploration for bleeding/post-operative blood transfusion)was 17.65%in the TEG group and 45.10%in the CCT group(P=0.05,Fisher’s exact test).The incidence of radiologically confirmed partial thrombus in pancreas allograft was 41.18%in the TEG and 25.50%in the CCT group(P=0.23,Fisher’s exact test).All recipients with partial thrombi detected in computed tomography(CT)scan had an anticoagulation dose escalation.The thrombus resolution rates in subsequent scan were 85.71%and 63.64%in the TEG group vs the CCT group(P=0.59,Fisher’s exact test).The TEG group had reduced blood product usage{10 packed red blood cell(PRBC)and 2 fresh frozen plasma(FFP)}compared to the CCT group(71 PRBC/10 FFP/2 cryoprecipitate and 2 platelets).The proportion of patients requiring transfusion in the TEG group was 17.65%vs 39.25%in the CCT group(P=0.14,Fisher’s exact test).The median length of hospital stay was 18 days in the TEG group vs 31 days in the CCT group(P=0.03,Mann Whitney test).The 1-year pancreas graft survival was 100%in the TEG group vs 82.35%in the CCT group(P=0.07,log rank test)and,the 1-year kidney graft survival was 100%in the TEG group vs 92.15%in the CCT group(P=0.23,log tank test).CONCLUSION TEG is a promising tool in guiding judicious use of anticoagulation with concomitant prevention of graft loss due to thrombosis,and reduces the length of hospital stay.

Diverse coagulopathies in a rabbit model with different abdominal injuries

BACKGROUND: Although coagulopathy can be very common in severe traumatic shock patients, the exact incidence and mechanism remain unclear. In this study, a traumatic shock rabbit model with special abdomen injuries was developed and evaluated by examining indicators of clotting and fi brinolysis.METHODS: Forty New Zealand white rabbits were randomly divided into four groups: group 1(sham), group 2(hemorrhage), group 3(hemorrhage-liver injury), and group 4(hemorrhage-liver injury/intestinal injury-peritonitis). Coagulation was detected by thromboelastography before trauma(T0), at 1 hour(T1) and 4 hours(T2) after trauma.RESULTS: Rabbits that suffered from hemorrhage alone did not differ in coagulation capacity compared with the sham group. The clot initiations(R times) of group 3 at T1 and T2 were both shorter than those of groups 1, 2, and 4(P<0.05). In group 4, clot strength was decreased at T1 and T2 compared with those in groups 1, 2, and 3(P<0.05), whereas the R time and clot polymerization were increased at T2(P<0.05). The clotting angle signifi cantly decreased in group 4 compared with groups 2 and 3 at T2(P<0.05).CONCLUSION: This study suggests that different abdominal traumatic shock show diverse coagulopathy in the early phase. Isolated hemorrhagic shock shows no obvious effect on coagulation. In contrast, blunt hepatic injury with hemorrhage shows hypercoagulability, whereas blunt hepatic injury with hemorrhage coupled with peritonitis caused by a ruptured intestine shows a tendency toward hypocoagulability.

Perioperative effects of high doses of intraoperative thymoglobulin induction in liver transplantation

AIM:To describe our single-centre experience in liver transplantation(LT)with the infusion of high perioperative thymoglobulin doses.The optimal dosage and timing of thymoglobulin[antithymocyte globulin(ATG)]administration during LT remains controversial.Cytokine release syndrome,haemolytic anaemia,thrombocytopenia,neutropenia,fever and serum sickness are potential adverse effects associated with ATG infusion.METHODS:Between December 2009 and December 2010,16 adult non-randomized patients(ATG group),receiving a liver graft from a deceased donor,received an intraoperative infusion(4-6 h infusion)of thymoglobulin(3 mg/kg,ATG:Thymoglobuline).These patients were compared(case control approach)with 16 patients who had a liver transplant without ATG treatment(control group)to evaluate the possible effects of intraoperative ATG infusion.The matching parameters were:Sex,recipient age(±5 years),LT indication including viral status,MELD score(±5 points),international normalized ratio and platelet count(as close as possible).The exclusion criteria for both groups included the following:Multi-organ or living donor transplant,immunosuppressive therapy before transplantation,contraindications to the administration of any thymocyte globulin,human immunodeficiency virus seropositivity,thrombocytopenia[platelet<50000/μL]or leukopenia[white blood cells<1000/μL].The perioperative side effects(haemodynamic alterations,core temperature variations,colloids and crystalloids requirements,and surgical time)possibly related to ATG infusion and the thromboelastographic(TEG)evaluation of the ATG effects on coagulation,blood loss and blood product transfusion were analysed during the operation and the first three postoperative days.RESULTS:Intraoperative ATG administration was associated with longer surgical procedures[560±88 min vs 480±83 min(control group),P=0.013],an intraoperative core temperature more than 37℃(50%of ATG patients vs 6.2%of control patients,P=0.015),major intraoperative blood loss[3953±3126 mL vs 1419±940 mL(control group),P=0.05],higher red blood cell[2092±1856 mL ATG group vs 472±632 mL(control group),P=0.02],fresh frozen plasma[671±1125 mL vs 143±349 mL(control group),P=0.015],and platelet[374±537 mL vs 15.6±62.5 mL(control group),P=0.017]transfusion,and a higher requirement for catecholamines(0.08±0.07μg/kg per minutes vs 0.01±0.38μg/kg per minutes,respectively,in the ATG and control groups)for haemodynamic support.The TEG tracings changed to a straight line during ATG infusion(preanhepatic and anhepatic phases)in 81%of the patients from the ATG group compared to 6.25%from the control group(P<0.001).Patients from the ATG group compared to controls had higher post-op core temperatures(38℃±1.0℃vs 37.3℃±0.5℃;P=0.02),an increased need of noradrenaline(43.7%vs 6.25%,P=0.037),received more platelet transfusions(31.5%vs 0%,P=0.04)and required continuous renal replacement therapy(4 ATG patients vs none in the control group;P=0.10).ATG infusion was considered the cause of a fatal anaphylactic shock and of a suspected adverse reaction that led to intravascular haemolysis and acute renal failure.CONCLUSION:The side effects and the coagulation imbalance observed in patients receiving a high dosage of ATG suggest caution in the use of thymoglobulin during LT.

Impact of high dose vitamin C on platelet function

AIM To examine the effect of high doses of vitamin C(VitC) on ex vivo human platelets(PLTs).METHODS Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to:(1) normal saline(control);(2) 0.3 mmol/L VitC(Lo VitC); or(3) 3 mmol/L VitC(Hi VitC, final concentrations) and stored appropriately. The Vit C additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of Vit C used here correspond to plasma Vit C levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography(TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate(ATP) secretion in response to collagen or adenosine diphosphate(ADP); and flow cytometry, for changes in expression of CD-31, CD41 a, CD62 p and CD63. In addition, PLT intracellular Vit C content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time(PT), partial thrombplastin time(PTT), functional fibrinogen] and Lipidomics analysis(UPLC ESI-MS/MS).RESULTS VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L(Lo VitC) and 15.7 mmol/L(Hi VitC, P < 0.05). VitC supplementation did not significantly change PT and PTT values, or functional fibrinogen levels over the 8 d exposure period(P > 0.05). PLT function assayed by TEG, aggregometry and flow cytometry was not significantly altered by Lo or Hi VitC for up to 5 d. However, PLTs exposed to 3 mmol/L VitC for 8 d demonstrated significantly increased R and K times by TEG and a decrease in the α-angle(P < 0.05). There was also a fall of 20 mm in maximum amplitude associated with the Hi VitC compared to both baseline and day 8 saline controls. Platelet aggregation studies, showed uniform declines in collagen and ADP-induced platelet aggregations over the 8-d study period in all three groups(P > 0.05). Collagen and ADP-induced ATP secretion was also not different between the three groups(P > 0.05). Finally, VitC at the higher dose(3 mmol/L) also induced the release of several eicosanoids including thromboxane B2 and prostaglandin E2, as well as products of arachidonic acid metabolism via the lipoxygenases pathway such as 11-/12-/15-hydroxyicosatetraenoic acid(P < 0.05).CONCLUSION Alterations in PLT function by exposure to 3 mmol/L VitC for 8 d suggest that caution should be exerted with prolonged use of intravenous high dose VitC.

Utility and correlation of known anticoagulation parameters in the management of pediatric ventricular assist devices

AIM To assess utility and correlation of known anticoagulation parameters in the management of pediatric ventricular assist device(VAD). METHODS Retrospective study of pediatric patients supported with a Berlin EXCOR VAD at a single pediatric tertiary care center during a single year.RESULTS We demonstrated associations between activated thro-mboplastin time(a PTT) and R-thromboelastography(R-TEG) values(rs = 0.65, P < 0.001) and between anti-Xa assay and R-TEG values(rs = 0.54, P < 0.001). The strongest correlation was seen between a PTT and anti-Xa assays(rs = 0.71, P < 0.001). There was also a statistically significant correlation between platelet counts and the maximum amplitude of TEG(rs = 0.71, P < 0.001). Importantly, there was no association between dose of unfractionated heparin and either measure of anticoagulation(a PTT, anti-Xa or R-TEG value). CONCLUSION This study suggests that while there is strong correlation between a PTT, anti-Xa assay and R-TEG values for patients requiring VAD support, there is a lack of relevant correlation between heparin dose and degree of effect. This raises concern as various guidelines continue to recommend using these parameters to titrate heparin therapy.

Thromboelastographic Profile of Patients with Hyperparathyroidism Secondary to Chronic Kidney Failure Submitted to Total Parathyroidectomy

Coagulopathy in surgical patients can cause perioperative complications, as both bleeding and thromboembolic events increase surgical morbimortality. The recognition of preexisting disorders and the understanding of the dynamic changes in hemostasis during surgery are prerequisites of safe patient management. The perioperative management of patients with chronic kidney failure is a huge challenge due to both the hypercoagulable state and increased risk of bleeding. Classic laboratory exams performed for the evaluation of blood clotting seem insufficient regarding the determination of the risk of bleeding and thrombosis in surgical patients. As patients with chronic kidney failure develop secondary hyperparathyroidism, the aim of the present study was to describe a case series and correlate the perioperative thromboelastographic profile of patients with chronic kidney failure submitted to parathyroidectomy with their secondary hyperparathyroidism.