blood coagulation analysis is very important for resuscitation with fluid and blood components in critical situations , especially in patients injured by multiple trauma or operated on with massive bleeding , because accurate information about the hemostatic status of patients can contribute to guiding appropriate management and improving the patients outcome . ideally , real - time monitoring of hemostasis is helpful for treating coagulopathy ; however , conventional hemostatic test results are available about 60  minutes after blood sampling . rotational thromboelastometry ( rotem ; tem international gmbh , munich , germany ) , which is known as a point - of - care ( poc ) tool , can detect coagulation cascade abnormalities very rapidly and provides comprehensive assessment of the patient 's hemostatic status . , a number of articles have reported the usefulness of rotem as a poc device in numerous clinical situations such as emergency care , cardiovascular surgery , liver transplantation , trauma surgery , and septic disseminated intravascular coagulation . in critical care , patient management is performed aggressively , and numerous fluids and monitoring devices are established , such as arterial line placement . therefore , the risks of blood sampling errors ( e.g. , collection of blood from the same limb where intravenous fluid is being administered or the risk of blood sample contamination from wrong arterial line infusions such as glucose - containing fluid ) still exist . recently , lippi et al reported that contamination of blood samples with glucose could cause spurious results in conventional coagulation tests including prothrombin time ( pt ) , activated partial thromboplastin time ( aptt ) , and fibrinogen concentration . for this reason , we performed a study to investigate whether contamination of blood samples with a standard glucose solution might generate spurious results in the rotem tests : intem , extem , and fibtem . this study was approved by the institutional review board at seoul national university bundang hospital ( seongnam - si , south korea , approval on december 15 , 2015 , b-1512/326 - 301 ) , this observational study was registered in the clinical research information service ( cris , http://cris.nih.go.kr , kct0001749 ) . written informed consent was obtained from 12 healthy volunteers ( 5 males and 7 females ) who had not been taking medications known to interfere with hemostasis such as anticoagulants , antiplatelets , or nonsteroidal antiinflammatory drugs . , 12  ml of fresh venous blood was obtained from an antecubital vein and placed in citrate - containing polypropylene tubes ( vacutainer , becton dickinson , plymouth , uk ) . the 1st blood sample was discarded , and then the study blood sample was taken immediately . based on the study protocol of lippi et al , the collected specimens were pooled and then divided into 4 bottles of 2.0  ml each . to create final contamination levels of 0% , 5% , 10% , and 20% , 100 , 200 , and 400  l of a standard 5% glucose solution ( 50  g glucose monohydrate in 1000  ml water , 278  mosm / l ; jw pharmaceutical , seoul , south korea ) was added to 3 bottles , respectively , and 1 sample was used as a control ( baseline ) . we obtained the following 4 rotem parameters : clotting time ( ct ) , clot formation time ( cft ) , -angle , and maximum clot firmness ( mcf ) . intem and extem values , which offer information on the intrinsic and extrinsic pathway , respectively , were assessed using the recommended reagents ( in - tem : 0.2  m cacl2 20  l and thromboplastin - phospholipid 20  l ; ex - tem : 0.2  m cacl2 20  l and tissue factor 20  l ) . the change of fibrin polymerization was examined using a fibtem test with the fib - tem reagent ( 0.2  m cacl2 20  l with cytochalasin d and tissue factor 20  l ) . . repeated measures analysis of variance test was used to compare the baseline values with values after glucose contamination . pearson correlation coefficient was used to determine the correlation between the degree of glucose contamination and the percentage changes . data are expressed as means ( sd ) . a p - value less than 0.05 was considered to indicate statistical significance . measured plasma glucose concentrations increased with increasing glucose contamination ( table 1 ) . with increasing glucose contamination , rotem parameters showed a hypocoagulable pattern as follows ( table 1 ) : prolonged ct and cft values , and decreased -angle and mcf values . significant lengthening of intemct was observed in the 10% and 20% contamination groups compared with baseline values ( 7.7% and 9% , p  =  0.041 and p  =  0.037 , respectively ) ( fig . intemcft was significantly increased , by 20.1% , in the 20% contamination group ( p  =  0.005 ) ( fig . intem-angle and intemmcf were significantly decreased , by 3.9% and 2.7% , respectively , in the 20% contamination group ( p  =  0.010 and p  =  0.049 , respectively ) ( fig . extemcft was prolonged significantly , by 10.2% , 15.5% , and 25.6% , in the 5% , 10% , and 20% contamination groups , respectively ( p  =  0.004 , p  <  0.001 , and p  <  0.001 , respectively ) ( fig . extem-angle decreased significantly , by 1.9% , 3.2% , and 4.0% , in the 5% , 10% , and 20% contamination groups , respectively ( p  =  0.014 , p  =  0.001 , and p  =  0.005 , respectively ) ( fig . extemmcf was significantly decreased , by 3.4% , in the 20% contamination group ( p  =  0.023 ) ( fig . fibtemmcf was significantly decreased , by 9.2% and 17.5% , in the 10% and 20% contamination groups , respectively ( p  =  0.019 and p  =  0.021 , respectively ) ( fig . percentage change from preoperative values for rotem parameters : ( a ) intem , ( b ) extem , and ( c ) fibtem ; 5% ( black ) , 10% ( pale grey ) , and 20% ( dark gray ) diluted groups . =  -angle (  ) , cft  =  clot formation time ( second ) , ct  =  clotting time ( second ) , mcf  =  maximum clot firmness ( mm ) , rotem = rotational thromboelastometry . a significant correlation was observed between standard glucose solution contamination in the specimens and percentage variation of extemcft , extemmcf , and fibtemmcf ( fig . correlations between the standard glucose solution contamination in the specimens and percentage variation of rotem parameters : ( a ) extemcft ( r  =  0.9860 , p  =  0.0140 ) , ( b ) extemmcf ( r  =  0.9855 , p  =  0.0145 ) , and ( c ) fibtemmcf ( r  =  0.9705 , p  =  0.0295 ) . cft  =  clot formation time , mcf  =  maximum clot firmness , rotem  =  rotational thromboelastometry . interesting findings were observed in the present study regarding the effect of acute hyperglycemic contamination on the blood coagulation profile analyzed with rotem . all coagulation pathways , including the intrinsic , extrinsic , and fibrinolytic systems , seemed to be impaired with increasing glucose contamination . volume replacement therapy is one of the most common clinical practices , and various fluids ( e.g. , crystalloid and colloids ) and blood components ( e.g. , red blood cells , fresh frozen plasma ) are generally used . laboratory findings play an important role in establishing the plan of resuscitation , transfusion , or fluid therapy . in particular , monitoring the change of hemostatic profiles is essential to guide appropriate management of massive bleeding , disseminated intravascular coagulation , or coagulopathy of unknown origin . there are several reports related to the risk of errors during blood collection and the effect of blood sample contamination with glucose - containing solutions on the interpretation of chemistry parameters . conventional coagulation tests could also show spurious results because of iatrogenic acute hyperglycemia caused by hemodilution with a glucose - containing solution . lippi et al performed an in vitro study of the relation between glucose contamination and results of conventional coagulation testing . they reported that the value of pt was prolonged ( hypocoagulable pattern ) , and aptt ( hypercoagulable pattern ) and fibrinogen concentration were decreased with increasing glucose contamination . pt , aptt , and fibrinogen concentration represent the extrinsic , intrinsic , and fibrinolytic pathways in the coagulation cascade , respectively . on the other hand , in the present study , intem , extem , and these conflicting results in the extrinsic coagulation pathway ( pt vs extem ) might be due to the different techniques used to measure the blood coagulation state . hemostasis is modulated by various factors such as platelet function , tissue factor , and procoagulant factors . because the conventional coagulation test is performed using the patient 's plasma in contrast , rotem analyses the viscoelasticity of whole blood and interprets the interaction of various factors participating in hemostasis . another possible causal factor that may explain the difference in changes between pt and extem is the inconsistent turnaround time ( time delay from blood sampling to laboratory analysis ) . in the present study , we performed the rotem test within 10  minutes after blood sampling . nevertheless , the important point of our report , and of that by lippi el al , is that glucose contamination of blood samples could cause interpretation errors in both the conventional test and rotem . , crystalloids such as saline and lactated ringer solution could induce a hypercoagulable state in the patient . on the other hand , hemodilution with hydroxyethyl starches ( hess ) although he s and 5% glucose solution differ in composition , they might exert similar hemodilution effects on blood coagulation as fluid solutions . there are various results regarding the effect of acute hyperglycemia on the coagulation cascade . in an animal study , acute moderate hyperglycemia ( 10.013.3  mmol / l ) maintained for 6  hours did not show a detectable influence on blood coagulation as measured by rotem . in an in vivo study , platelets and endothelial cells were not activated during 6  hours of hyperglycemia with concentrations of 11.1 and 16.7 in contrast , hyperglycemia produced increases in tissue factor procoagulant and platelet activity in healthy volunteers . first , our study was conducted in the hyperacute hyperglycemic state ( i.e. , within 10  minutes ) . in contrast , other studies were performed about 6 or 24  hours after the hyperglycemic condition . therefore , there is a possibility that our study may not reflect the glucose effect on the coagulation cascade during 6 or 24  hours . however , not only hyperglycemia but also hyperinsulinemia are the hallmarks of type 2 diabetes mellitus . vaidyula et al reported that exposure to combined hyperglycemia / hyperinsulinemia caused an approximate 9-fold rise in circulating tissue factor procoagulant activity . similarly , meigs et al demonstrated that an elevated level of fasting insulin is related to impaired fibrinolysis and hypercoagulability . although , there were significant findings in relation between glucose contamination and the rotem values in the present study , further study would be needed to show more potent findings . second , the study population consisted mostly of young adults ( mean age : 32 years ) . to extent our findings to the general population , further studies will be required aimed at clarifying the role of age on the effect of glucose contamination in blood coagulation analysis . in conclusion , this study showed that hemostatic analysis could be influenced by contamination with a glucose - containing solution that resulted in hemodilution and a hyperglycemic state of a blood sample , as judged by rotem . to obtain accurate data from the rotem test regarding the hemostatic status of patients , blood samples suspected of contamination 02 - 2014 - 057 ) from the research fund of seoul national university bundang hospital , south korea for the support .
abstractwe performed a study to investigate whether contamination of hemostasis samples with a glucose - containing solution might generate spurious results in rotational thromboelastometry ( rotem ) tests.venous blood was taken from 12 healthy volunteers and divided into 4 specimen bottles , which were contaminated with different concentrations ( 0% , 5% , 10% , and 20% ) of glucose solution.significant lengthening of intemct was observed in the 10% and 20% groups compared with baseline values ( 7.7% and 9% , p  =  0.041 and p  =  0.037 , respectively ) . 
 intemcft increased by 20.1% in the 20% group ( p  =  0.005 ) . 
 intem-angle and intemmcf decreased by 3.9% and 2.7% , respectively , in the 20% group ( p  =  0.010 and p  =  0.049 , respectively ) . 
 extemcft was prolonged significantly , by 10.2% , 15.5% , and 25.6% , in the 5% , 10% , and 20% groups , respectively ( p  =  0.004 , p  <  0.001 , and p  <  0.001 , respectively ) . 
 extem-angle decreased significantly by 1.9% , 3.2% , and 4.0% in the 5% , 10% , and 20% groups , respectively ( p  =  0.014 , p  =  0.001 , and p  =  0.005 , respectively ) . 
 extemmcf decreased by 3.4% in the 20% group ( p  =  0.023 ) . 
 fibtemmcf decreased by 9.2% and 17.5% in the 10% and 20% groups , respectively ( p  =  0.019 and p  =  0.021 , respectively ) . 
 a significant correlation was observed between standard glucose solution contamination in the specimens and percentage variation of extemcft , extemmcf , and fibtemmcf.to obtain accurate data from the rotem test regarding the hemostatic status of patients , specimens with suspected or known contamination should not be analyzed .