Prothrombin Time Ratio Research Articles

Prothrombin Time ratio can predict mortality in severe pediatric trauma: Study in a French trauma center level 1

BackgroundInjury results in more deaths in children than all other causes combined, but there is little data regarding the association of early coagulopathy on outcomes in pediatric patients with traumatic injuries. The aim of this study was to determine the optimal cut-off value for the Prothrombin Time ratio (PTr) and to show the diagnostic characteristics of the PTr to predict mortality. MethodsWe retrospectively included during 4 years all patients less than 16 years old referred to our trauma center for traumatic injury with ISS ≥9. ResultsA total of 272 children were included. Mean age was 9.4 ± 4.8 years and median ISS was 17 [interquartile range, 12 to 26]. Day 28 mortality was 6.7%. The optimal cut-off value in our population for predicting day 28 mortality was 1.24. Using this value, the sensitivity of PTr was 84%, specificity was 82%, positive likelihood ratio was 4.7, and negative likelihood ratio was 0.19. Early mortality (i.e., mortality at 24 h) was also well-predicted (1.0% versus 16.4%, p < .0001), as the need for massive transfuion. Similarly, patients with PTr ≥1.24 at admission presented with a higher rate of severe thoracic and abdominal trauma, higher ISS, higher likelihood of admission to an intensive care unit, longer hospitalization, and higher rate of significant procedure (e.g., surgery or embolization). ConclusionsTrauma-induced coagulopathy defined only by a PTr ≥1.24 could be used as a severity predictive marker and as a sensitive, specific, quick, and easy to use tool for admission triage of pediatric patients.

A prospective observational study of acute traumatic coagulopathy in traumatic bleeding from the battlefield.

Acute trauma coagulopathy (ATC) after military trauma has not been comprehensively studied. ATC is defined as a prolonged prothrombin time ratio (PTr) or reduced clot amplitude (A5) in viscoelastic testing. Compared to civilian trauma, military trauma has more injuries from explosions and gunshot wounds (GSWs), potentially leading to a different pathophysiology for traumatic coagulopathy. This study aimed to characterize military ATC on admission to a military hospital in Afghanistan and to explore any differences due to the mechanism of injury. Severely injured military casualties were enrolled in the study. Blood samples were taken on admission and after routine testing, waste plasma was prepared, frozen, and transported to the United Kingdom for in-depth hemostatic analysis. Seventy-seven percent of casualties had ATC defined by a PTr greater than 1.2 and 19% when defined by rotational thromboelastometry (ROTEM) A5 less than 36 mm. Coagulation factor depletion correlated with degree of shock, particularly factor V (p < 0.01), factor X (p < 0.01), and fibrinogen levels (p < 0.01). Thrombin generation was well preserved. Fibrinolytic biomarkers were raised correlating with the degree of shock (p < 0.01), and 8% of casualties had hyperfibrinolysis on ROTEM analysis. Plasmin-antiplasmin complexes (p < 0.01) and d-dimer levels (p = 0.01) were higher and clot firmness lower (p = 0.02) in those injured by explosion compared to GSW's. ATC was present and correlated with shock, similar to civilian trauma. Thrombin generation remained adequate. Fibrinogen and factor V levels were disproportionately low but still sufficient to allow clot formation. Fibrinolysis is a key feature, probably due to a tissue plasminogen activator surge at the time of injury. Blast injuries are associated with a greater activation of fibrinolysis than GSWs.

CLIF-C Organ Failure Score and Liver Volume Predict Prognosis in Steroid-Treated Severe Acute Autoimmune Hepatitis.

Controversies and debates remain regarding the best management of severe acute‐onset autoimmune hepatitis (SA‐AIH) due to the lack of useful outcome or complication prediction systems. We conducted this clinical practice‐based observational study to clarify whether Chronic Liver Failure Consortium Organ Failure scores (CLIF‐C OFs) and the computed tomography–derived liver volume to standard liver volume (CTLV/SLV) ratio at admission to a tertiary transplant center can predict outcomes and complications due to infection. Thirty‐four consecutive corticosteroid‐treated patients with SA‐AIH from 2007 to 2018 were included. Severe hepatitis was defined as an international normalized ratio (of prothrombin time) over 1.3 any time before admission. Of the 34 corticosteroid‐treated patients with SA‐AIH inclusive of 25 (73.5%) acute liver failure cases, transplant‐free survival was observed in 24 patients (70.6%). Any infection was noticed in 10 patients (29.4%). CLIF‐C OFs, at the cutoff of 9, significantly predicted survival (P = 0.0002, log‐rank test), outperformed the Model for End‐stage Liver Disease system in predicting outcome (P = 0.0325), and significantly discriminated between liver transplant and death in a competing risk analysis. SA‐AIH was characterized as having decreased CTLV/SLV, which was also predictive of survival (P < 0.0001). Interestingly, CLIF‐C OFs, especially the subscores for respiratory dysfunction, also predicted infection (P = 0.007). Conclusion: In corticosteroid‐treated patients with SA‐AIH, CLIF‐C OFs and CTLV/SLV ratios predicted both survival outcome and complications due to infection. Further investigation is warranted to determine whether making decisions based on CLIF‐C OFs or CTLV/SLV ratios is useful.

Fibrinolytic shutdown diagnosed with rotational thromboelastometry represents a moderate form of coagulopathy associated with transfusion requirement and mortality: A retrospective analysis.

Viscoelastic techniques have made it possible to describe specific fibrinolytic phenotypes (physiological, hyperfibrinolysis and shutdown) and to establish a relationship of these phenotypes with outcome. However, there remains a debate as to whether shutdown is a state of hypercoagulability or rather a coagulopathy with moderate fibrinolysis and fibrinogen consumption. Our objectives were to describe the relationship between fibrinolytic phenotypes and outcomes, and to report the effects of tranexamic acid (TXA) administration. This was a retrospective analysis of prospectively acquired data from a trauma registry. An academic level 1 trauma centre in the Lyon Region, from March 2011 to December 2016. We included all injured patients who had a rotational thromboelastometry analysis at admission. Fibrinolytic phenotypes were determined according to the maximum lysis: shutdown less than 3%, physiological 3 to 15%, hyperfibrinolysis more than 15%. Mortality at 24 h and at hospital discharge. During the study period, 473 patients were included with the following phenotypes: physiological (344 patients, 73%), shutdown (107 patients, 23%) and hyperfibrinolysis (22 patients, 5%). There was an increase in injury severity, prothrombin time ratio, fibrin degradation products and transfusion requirements from the physiological to the shutdown and hyperfibrinolysis phenotypes. Prehospital TXA administration increased the rate of shutdown and decreased the maximum lysis value at admission. After adjustment, multivariate analysis showed that fibrinolytic phenotypes, but not TXA, were independently associated with an increased risk of early death and death before hospital discharge: shutdown [odds ratio (95% confidence interval)] 2.4 (1.2 to 4.8) and hyperfibrinolysis 67.9 (7.4 to 624.2). The results of the current study suggest that shutdown, which is associated with injury severity and mortality, probably reflects a moderate form of coagulopathy and fibrinolysis rather than a hypercoagulopathy. Therefore, the observation of shutdown fibrinolysis on thromboelastography/rotational thromboelastometry should not lead to withholding but rather to the administration of TXA.

RNA testing for the diagnosis of acute hepatitis A during the 2017 outbreak in France.

Diagnostic of acute hepatitis A virus (HAV) infection is based on the detection of anti-HAV IgM without testing for the pathogen itself. We evaluated the usefulness of HAV RNA testing for confirmation of acute hepatitis A and to provide indications about the level of HAV replication in HIV-positive and HIV-negative subjects during an unprecedented outbreak of HAV observed in France in 2017. HAV RNA was detected in 38 out of 41 (92.6%) subjects with a clinical diagnosis of acute hepatitis A, whereas nine cases tested positive for anti-HAV IgM in whom the diagnosis of acute hepatitis A was not retained were found negative for HAV RNA. All subjects in the control group were also tested negative for HAV RNA. HAV viremia was correlated to ALT peak (r=.64; P<.0001). HIV-infected patients have similar HAV RNA levels but were less likely to have prolonged international normalized ratio of prothrombin time when compared to the HIV-uninfected group (P=.016), suggesting a less severe course of acute hepatitis. HAV RNA was detected in the serum of most of the patients with acute hepatitis A, indicating that the direct detection of HAV can be used to confirm hepatitis A in patients tested positive for anti-HAV IgM antibodies. Nucleic acid tests should serve more broadly during the diagnosis workup of acute hepatitis A to improve the predictive values of HAV in vitro diagnostic tests and to confirm acute hepatitis A in patients tested positive with IgM with moderate or low S/CO values.

Characteristics Behaviors of Coagulation and Fibrinolysis Markers in Acquired Thrombotic Thrombocytopenic Purpura.

Patients with acquired thrombotic thrombocytopenic purpura (TTP) show no severe abnormalities in coagulation or fibrinolysis. However, the exact extent of the abnormalities is unclear. This study analyzed 138 patients with acquired TTP and 46 patients with septic disseminated intravascular coagulation (DIC) who were included in a Japanese registry. Complete blood cell counts and 8 coagulation or fibrinolysis parameters were compared between the 2 groups. Platelet counts in the acquired TTP group were significantly lower than those in the septic DIC group (P < .001). The international normalized ratio of prothrombin time and the activated partial thromboplastin time in the septic DIC group were significantly higher and longer, respectively, than those in the acquired TTP group (P < .01). The antithrombin (AT) values were significantly lower in the septic DIC group than in the acquired TTP group (P < .001), the latter of which were almost normal. Although both groups revealed elevations of fibrinogen degradation product (FDP) and D-dimer, these levels were significantly higher in the septic DIC group than in the acquired TTP group (P < .001). Of 138 patients with acquired TTP, 25 (18.1%) were diagnosed with septic DIC by the diagnostic criteria of the Japanese Ministry Health, Labour and Welfare, and 78 (56.5%) by those of the Japanese Association of Acute Medicine. Receiver operating characteristic curve analysis showed that acquired TTP could be diagnosed based on severe thrombocytopenia (<20 × 109/L), normal AT level (>87%), and mildly elevated FDP (<23 µg/mL). Our results indicate that 3 routine laboratory tests could differentiate between acquired TTP and septic DIC.

Effects of CYP2C9 and VKORC1 genetic polymorphisms in Chinese Han population on maintenance dosage of warfarin

Objective To analyze CYP2C9 and VKORC1 gene polymorphisms in Chinese Han population and their correlation with the maintenance dosage of warfarin. Methods From October 2017 to April 2018, 458 Chinese Han patients (213 males and 245 females, aged from 26 to 94 years old) who underwent coagulation analysis in Peking University People′s Hospital were included in this retrospective study. PCR-Fluorescent probe method was applied to detect CYP2C9*3 and VKORC1-1639A>G gene polymorphisms in 458 patients, and among them, 130 patients who took warfarin for anticoagulant therapy and reached the international standard ratio of prothrombin time (INR) within the range of 2.0-3.0 were recorded. The basic information, dosage of warfarin and INR were also recorded. The statistical analysis data were compared with the reference table of recommended dosage of warfarin for different genotypes of patients recommended by FDA and the formula of predicted dosage of warfarin was simply verified by SPSS. Results Among the 458 patients who took anticoagulant therapy, the genotype frequencies of CYP2C9*1/*1(AA), CYP2C9*1/*3(AC) and CYP2C9*3/*3(CC) were 90.8%, 8.5%, and 0.7%; the genotype frequencies of VKORC1-1639GG and VKORC1-1639AG were 0.9% and 14.2%; the genotype frequencies of VKORC1-1639AA was 84.9%. After INR was reached, the results showed that the variant CYP2C9*1/*3 and CYP2C9*3/*3 required lower daily maintain dosage [(2.92±1.29) mg] than wild-type CYP2C9*1/*1 patients did [(3.91±1.63) mg], with statistically significant difference (P=0.018). And variant VKORC1-AA required lower daily maintain dosage [(3.68±1.64) mg] than variant VKORC1-AG patients did [(4.54±1.29) mg], with statistically significant difference (P=0.001). The application dosage of warfarin in patients with different VKORC1+CYP2C9 genotypes was consistent with the recommended dosage of the FDA reference table. The prediction accuracy of miao 2007 formula was lower than that of IWPC formula, and 94.1% of patients′ dosages of warfarin were underestimated. Conclusion Patients with CYP2C9*3 or VKORC1-AA genotype required lower warfarin dosage. The CYP2C9 and VKORC1 gene polymorphisms had a certain correlation with maintenance dosage of warfarin. Key words: Warfarin; Polymorphism, genetic; Cytochrome P-450 CYP2C9; Vitamin K epoxide reductases; Dose-respanse relationship,drug

Development of a Prognostic Score to Predict Mortality in Patients With Pediatric Acute Liver Failure.

This study aims to develop a new prognostic score based on changes in serial laboratory data from patients with pediatric acute liver failure (PALF). We retrospectively reviewed data on 146 patients with PALF at the Seoul National University Children Hospital (SNUCH) and the Asan Medical Center (AMC). Daily morning laboratory records were obtained for up to 7 days after diagnosis of PALF: total bilirubin (TB) (mg/dL), international normalized ratio for prothrombin time (INR) at enrolment; peak TB, peak INR, peak ammonia (μmol/L); the difference between the peak TB and TB at enrollment (ie, Δpeak TB), the difference between the peak INR and INR at enrollment (ie, Δpeak INR), the maximum change in serial TB (ie, Δdaily TB), the maximum change in serial INR level (ie, Δdaily INR). We assigned nontransplanted patients in SNUCH and AMC to derivation and validation cohorts, respectively. Δpeak TB, Δdaily TB, Δpeak INR, and Δdaily INR were significantly higher in the nonsurvival group. We developed a new score that can predict mortality in nontransplanted patients (derivation cohort n = 42, validation cohort n = 33). PALF-Delta score (PALF-Ds) = [0.232 × Δpeak TB (mg/dL)] + [2.263 × Δdaily INR] + [0.013 × peak ammonia (μmol/L)] - 4.498. The score yielded AUC 0.918 in the derivation cohort (sensitivity 81%, specificity 91%) and AUC 0.947 in the validation cohort (sensitivity 100%, specificity 89%). A prognostic scoring system using the change of TB/INR may be useful for predicting mortality in patients with PALF.

The coagulation profile as a marker for acute appendicitis in the paediatric population: Retrospective study.

Introduction:Appendicitis is the commonest and most frequently misdiagnosed acute abdominal surgical illness in the paediatric population worldwide. The aim of this study is to evaluate the role of coagulation profile in acute appendicitis (AA) in children.Materials and Methods:we retrospectively collected data of patients submitted to appendectomy from 2011 to 2017. According to histopathology, patients were divided into three groups: not histologically confirmed AA (NAA), simple AA (SAA) and complicated AA (CAA). White blood cell (WBC) count, relative neutrophilia (Neutr%), C-reactive protein (CRP), prothrombin time ratio (PTratio), activated partial thromboplastin time ratio (APTTratio) and fibrinogen (Fib) were compared among groups.Results:Three hundred and seven patients were included: 57 NAA, 184 SAA and 66 CAA. WBC was significantly different among groups: CAA (mean 16.67 × 103/ml), SAA (14.73 × 103/ml, P = 0.01) and NAA (10.85 × 103/ml, P < 0.0001). Significant differences were found for Neutr% (mean CAA 81.14 vs. SAA 77.03 P = 0.006, vs. NAA 63.86 P < 0.0001) and CRP (mean NAA 2.56, SAA 3.26, CAA 11.58, P < 0.0001). PTratio and Fib increased with the severity of AA receiver operator characteristic curves were similar for CRP (0.739), Fib (0.726), WBC (0.746) and Neutr% (0.754), while for PTratio and aPTTratio were 0.634 and 0.441, respectively.Conclusions:extrinsic coagulation pathway is altered in AA, especially in CAA. Coagulation can be useful in the diagnostic and perioperative anaesthetic management of AA in children. Fib seems to have the highest accuracy.

Impact of Anticoagulation Intensity in Korean Patients with Atrial Fibrillation: Is It Different from Western Population?

Background and ObjectivesAlthough anticoagulation with warfarin is recommended as an international normalized ratio (INR) of prothrombin time between 2.0 and 3.0 and mean time in the therapeutic range (TTR) ≥70%, little has been proven that universal criteria might be suitable in Korean atrial fibrillation (AF) patients.MethodsWe analyzed 710 patients with non-valvular AF who took warfarin. INR value and clinical outcomes were assessed during 2-year follow-up. Intensity of anticoagulation was assessed as mean INR value and TTR according to target INR range. Primary net-clinical outcome was defined as the composite of new-onset stroke and major bleeding. Secondary net-clinical outcome was defined as the composite of new-onset stroke, major bleeding and death.ResultsThromboembolism was significantly decreased when mean INR was over 1.6. Major bleeding was significantly decreased when TTR was over 70% and mean INR was less than 2.6. Mean INR 1.6–2.6 significantly reduced thromboembolism (adjusted hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.19–0.85), major bleeding (HR, 0.43; 95% CI, 0.23–0.81), primary (HR, 0.50; 95% CI, 0.29–0.84) and secondary (HR, 0.45; 95% CI, 0.28–0.74) net-clinical outcomes, whereas mean INR 2.0–3.0 did not. Simultaneous satisfaction of mean INR 1.6–2.6 and TTR ≥70% was associated with significant risk reduction of major bleeding, primary and secondary net-clinical outcomes.ConclusionsMean INR 1.6–2.6 was better than mean INR 2.0–3.0 for the prevention of thromboembolism and major bleeding. However, INR 1.6–2.6 and TTR ≥70% had similar clinical outcomes to INR 2.0–3.0 and TTR ≥70% in Korean patients with non-valvular AF.

Variations of coagulation biochemical markers in normal pregnant women in early and late pregnancy

Objective To investigate the changes of coagulation indexes in normal pregnant women in early and late pregnancy. Methods The coagulation indexes in early and late pregnancy including activated partial thromboplastin time (APTT), APTT ratio, prothrombin time (PT), PT ratio, prothrombin activity, international normalized ratio, fibrinogen (Fib) and thrombin time (TT) were retrospectively collected from 196 normal pregnant women delivered in Peking University First Hospital from August 2013 to September 2014. Differences in these indexes before and after the seventh gestational week of early pregnancy and in early and late pregnancy were compared. In addition, the normal reference values were calculated. Paired t test and sum-rank test were used for statistical analysis. The reference values were presented with P2.5-P97.5. Results In early pregnancy, some coagulation indexes after the seventh weeks were shorter than those before, such as APTT [30.3 (26.1-35.5) vs 32.1 (27.9-36.8) s, Z=25.850, P<0.001] and TT [13.8 (12.2-16.0) vs 14.5 (12.3-16.4) s, Z=16.720, P<0.001], but Fib [3.3 (2.5-4.3) vs 2.9 (2.2-3.8) g/L, Z=43.180, P<0.001] became higher. APTT [(27.5±1.6) vs (31.4±2.4) s, t=24.736, P<0.001], PT [(9.7±0.5) vs (11.0±0.8) s, t=18.647, P<0.001] and TT [(13.3±0.8) vs (14.2±1.0) s, t=9.255, P<0.001] were significantly shorter, while Fib [(4.4±0.5) vs (3.1±0.4) g/L, t=-29.152, P<0.001] was higher in late pregnancy than in early pregnancy. The reference values of APTT, PT, Fib and TT in early pregnancy were 26.5-36.0 s, 9.4-12.4 s, 2.4-4.0 g/L and 12.3-16.4 s, and those in late pregnancy were 25.0-31.2 s, 8.8-10.6 s, 3.4-5.4 g/L and 12.0-14.9 s, respectively. Conclusions The coagulation indexes of pregnant women change significantly since the beginning of early pregnancy. APTT, PT and TT are shorter, while Fib is higher in late pregnancy than in early pregnancy. Key words: Partial thromboplastin time; Prothrombin time; Thrombin time; Fibrinogen; Pregnancy trimester, first; Pregnancy trimester, third

Establishing reference intervals of coagulation indices based on the ACL Top 700 system for children in Southwestern Fujian, China

BackgroundTill date, China has not issued industry standards for reference intervals (RIs) of pediatric blood coagulation indices. Here, we evaluated changes in the coagulation indices in the venous blood of healthy children aged 29 days to 12 years derived using the ACL Top 700 system and established appropriate RIs. MethodsWe analyzed venous blood from 1770 healthy children for five coagulation indices. RIs were established according to the Clinical and Laboratory Standards Institute C28-A3c guideline. ResultsThe coagulation indices were grouped by age. For prothrombin time (PT) and international normalization ratio (INR), the RIs of infants and toddlers were identical; preschool children had the same RI as school-age children. Pediatric RIs for PT and INR were slightly lower than those for adults. The RIs of activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) in childhood were divided into two groups by age (1 month to 1 year and 1–12 years). The RI of APTT in infants was the widest; the overall level of FIB in infants was the lowest; children's APTT and FIB RIs were lower than those of adults. The pattern of TT values and RI trends in childhood were similar to those of APTT. ConclusionsThere were minor changes in the RIs of coagulation indices for children. The RIs of PT, INR, APTT, TT, and FIB must be grouped by age. The RIs of coagulation indices for children were different from those for adults; therefore, establishing separate RIs for children is necessary.

Early Identification of Acute Traumatic Coagulopathy Using Clinical Prediction Tools: A Systematic Review.

Background and objectives: Prompt identification of patients with acute traumatic coagulopathy (ATC) is necessary to expedite appropriate treatment. An early clinical prediction tool that does not require laboratory testing is a convenient way to estimate risk. Prediction models have been developed, but none are in widespread use. This systematic review aimed to identify and assess accuracy of prediction tools for ATC. Materials and Methods: A search of OVID Medline and Embase was performed for articles published between January 1998 and February 2018. We searched for prognostic and predictive studies of coagulopathy in adult trauma patients. Studies that described stand-alone predictive or associated factors were excluded. Studies describing prediction of laboratory-diagnosed ATC were extracted. Performance of these tools was described. Results: Six studies were identified describing four different ATC prediction tools. The COAST score uses five prehospital variables (blood pressure, temperature, chest decompression, vehicular entrapment and abdominal injury) and performed with 60% sensitivity and 96% specificity to identify an International Normalised Ratio (INR) of >1.5 on an Australian single centre cohort. TICCS predicted an INR of >1.3 in a small Belgian cohort with 100% sensitivity and 96% specificity based on admissions to resuscitation rooms, blood pressure and injury distribution but performed with an Area under the Receiver Operating Characteristic (AUROC) curve of 0.700 on a German trauma registry validation. Prediction of Acute Coagulopathy of Trauma (PACT) was developed in USA using six weighted variables (shock index, age, mechanism of injury, Glasgow Coma Scale, cardiopulmonary resuscitation, intubation) and predicted an INR of >1.5 with 73.1% sensitivity and 73.8% specificity. The Bayesian network model is an artificial intelligence system that predicted a prothrombin time ratio of >1.2 based on 14 clinical variables with 90% sensitivity and 92% specificity. Conclusions: The search for ATC prediction models yielded four scoring systems. While there is some potential to be implemented effectively in clinical practice, none have been sufficiently externally validated to demonstrate associations with patient outcomes. These tools remain useful for research purposes to identify populations at risk of ATC.

Fresh frozen plasma transfusion in patients with cirrhosis and coagulopathy: Effect on conventional coagulation tests and thrombomodulin-modified thrombin generation

The efficacy of fresh frozen plasma (FFP) transfusion in enhancing thrombin generation in patients with cirrhosis and impaired conventional coagulation tests has not been sufficiently explored. Thus, we aimed to assess the effect of FFP transfusion on thrombin generation in these patients. Fifty-three consecutive patients receiving a standard dose of FFP to treat bleeding and/or before invasive procedures - if international normalized ratio (INR)/prothrombin time (PT) ratio were ≥1.5 - were prospectively enrolled. The primary endpoint was the amelioration of endogenous thrombin potential (ETP) with thrombomodulin (ETP-TM) after transfusion, which corresponds to the total amount of generated thrombin. INR/PT ratio and activated partial thromboplastin time (aPTT) were also assessed before and after transfusion. FFP enhanced ETP-TM by 5.7%, from 973 (731-1,258) to 1,028 (885-1,343 nM × min; p = 0.019). Before transfusion, evidence of normal or high ETP-TM was found in 94% of patients, even in those with bacterial infections. Only 1 (1.9%) patient had ETP-TM values reverting to the normal range after transfusion. Notably, no patients with low ETP-TM had bleeding. The median decrease in ETP-TM was 8.3% and the mean was 12.8% in 18 (34%) patients after transfusion (from 1,225 [1,071-1,537] to 1,124 [812-1,370] nM × min; p ≤0.0001). Similar responses to FFP transfusion were observed in patients with compensated and acute decompensated cirrhosis, acute-on-chronic liver failure, infection or shock. FFP significantly ameliorated INR and aPTT values (p <0.0001), but in a minority of patients the values were reduced to less than the cut-off point of 1.5. FFP transfusion enhanced thrombin generation and ameliorated conventional coagulation tests to normal values in a limited number of patients, and slightly decreased thrombin generation in 34% of cases. Transfusion of fresh frozen plasma in patients with cirrhosis only slightly improves coagulation test values in a limited number of patients and even appears to worsen them in a third of cases. Transfusion for the purpose of preventing or treating bleeding events could cause inherent risks and costs without clear benefits.

A Retrospective Evaluation of the Impact of Multi-disciplinary Approach for Improving the Quality of Anticoagulation Therapy in Ambulatory Patients with Non-valvular Atrial Fibrillation Receiving Warfarin

While percent time within therapeutic range (%TTR) of international normalized ratio of prothrombin time (PT-INR) represents the quality of anticoagulation therapy with warfarin, it is often maintained less than 50% in patients with non-valvular atrial fibrillation (NVAF). We aimed to study if implementation of a multi-disciplinary ambulatory anticoagulation service (MAAS) may improve %TTR. Collaborating with cardiologists at Kanto Rosai Hospital, we conducted a MAAS for NVAF patients receiving warfarin from April 2013 to December 2015. Patients who agreed to utilize the service in addition to their appointments with cardiologists visited pharmacists to have counseling about diet, concomitant medications, and lifestyle. According to a protocol, pharmacists made dose adjustment proposals to cardiologists, if necessary. Upon approval by cardiologists, dose modifications were made. We retrospectively reviewed medical records of the patients who participated in the MAAS before and during the service. The study protocol was approved by the institutional review board. We identified 78 eligible patients (44 males and 34 females, aged 51 to 91 years). Their median %TTR increased significantly (p<0.05) from 57% during the pre-MAAS period to 77% during the MAAS period. In addition, the median percent time below therapeutic range (%TBTR) decreased significantly (p<0.05) from 35% during the baseline period to 11% during the MAAS period. The present study indicates that MAAS improves the quality of anticoagulation therapy with warfarin in ambulatory patients with NVAF. Further prospective, randomized studies with a greater number of patients are required to confirm the results of the present study.

Expression and Clinical Significance of Decoy Receptor 3 in Acute-on-Chronic Liver Failure.

Aims To explore the expression level and clinical significance of decoy receptor 3 (DcR3) in patients with acute-on-chronic liver failure (ACLF). Methods Serum DcR3 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 76 patients with ACLF and 41 non-ACLF patients with chronic liver disease. Blood routine and liver functions were accessed for their correlations with DcR3. Results Serum DcR3 in ACLF patients was significantly higher than that in non-ACLF patients. It was positively correlated with neutrophilic granulocyte, aspartate aminotransferase, prothrombin time, and international standardized ratio, but negatively correlated with platelet and serum albumin. At the early stage, the level of DcR3 was not significantly different between the survival and nonsurvival group of ACLF. However, at the late stage, DcR3 increased in nonsurvival and gradually decreased in survivals. The baseline DcR3 could not sufficiently predict the outcome of ACLF, while the change of DcR3 within the first week displayed a better predictive value than model for end-stage liver disease (MELD) score. Conclusions DcR3 was highly expressed in patients with ACLF and correlated with several clinical indices. Dynamic change of DcR3 might predict the prognosis of ACLF.

Efficacy of a strict surveillance policy towards inappropriateness of plasma transfusion

BackgroundPlasma transfusion is not without risks. Despite a limited spectrum of indications, plasma is frequently used as prophylaxis in non-bleeding patients, to correct altered coagulation tests. A high rate of inappropriate use of plasma transfusion is frequently reported, as well as underdosage. Study design and methodsSince 2010 we started an education program that occurred in several phases to disseminate the knowledge of plasma transfusion guidelines. Since 2014 a ‘zero tolerance’ policy was applied: except for massive bleedings, plasma requests were prospectively evaluated, rejecting those without an appropriate indication. When indicated, at least 10 mL/Kg b.w.were issued. The previous five year period (2005–2009) served as control. ResultsThe number of patients transfused/year decreased by 67.6% vs the control period (149 vs 460), and the liters of plasma issued/year decreased by 70.4% (233 vs 795).The deepest fall was observed in acute care wards (-70.8%). The mean volume transfused per episode raised from 731 mL ± 70 to 879 mL ± 154. The Prothrombin Time ratio at the moment of transfusion request increased from a mean of 1.35 (Interquartile range 1.20–2.64) in the control period to 1.62 (Interquartile range 1.43–1.98) in the last period (p < 0.001). ConclusionWith a proactive educational approach a remarkable reduction of plasma order and administration has been obtained, without any consequence on morbidity and mortality and with an estimated saving since 2014 of 750,000 €. A ‘zero tolerance’ policy can be effectively implemented only with a thorough workup with the local physicians, including repeated rounds of information and refreshing of the updated transfusion practice and knowledge of the established guidelines over the time.

Diagnostic performance of thromboelastometry in trauma-induced coagulopathy: a comparison between two level I trauma centres using two different devices.

The implementation of a ROTEM®-based algorithm requires reliable thresholds to mirror a prothrombin time (PT) ratio > 1.2 and/or a fibrinogen concentration < 1.5gl-1. Our goal was to compare the diagnostic performances of two devices (ROTEM® Sigma and Delta, IL Werfen, Munich, Germany) in two level-I trauma centres for the diagnostic of post-traumatic coagulopathy. We conducted a retrospective analysis of two registries across two periods of time: from September 2014 to December 2015 in Lyon-Sud university trauma centre and from April 2016 to January 2018 in the Grenoble Alps Trauma Centre. Accuracies of EXTEM and FIBTEM assays to detect patients with coagulation disorders were tested for each device using receiver operating characteristic (ROC) analyses. Within the study period, 74 trauma patients in the Grenoble cohort and 75 trauma patients in the Lyon cohort had concomitant ROTEM® and standard coagulation testing on admission. No statistically significant difference was found between the two ROC curves for FIBTEM amplitude at 5min (A5), FIBTEM maximum clot firmness, EXTEM clotting time (CT) and EXTEM A5 for ROTEM® Sigma and Delta to diagnose post-traumatic coagulation disorders. The best threshold for FIBTEM A5 to predict low fibrinogen concentration was 7mm for each device. EXTEM CT thresholds to diagnose PT ratio > 1.2 were 78s and 74s for ROTEM® Sigma and Delta, respectively. These results suggest that ROTEM®-based algorithms may be transposed from one trauma centre to another independently of the setting and the ROTEM® device in use.

A Comparison of Hemostatic Properties between Monopolar and Bipolar Hysteroscopic Surgery using Rotational Thromboelastometry: A Randomized Trial

Objective: Systemic absorption of irrigation fluid can lead to a disturbed coagulation cascade. We compared the changes in hemostatic properties on using nonelectrolyte solution in monopolar hysteroscopic surgery (HS) with that on using isotonic saline in bipolar HS via rotational thromboelastometry (ROTEM) analysis. Methods: A total of 54 patients were randomized into 2 groups: 1 group underwent monopolar HS using a mixture of 2.7% sorbitol and 0.54% mannitol (the HS_MP group), whereas the other group underwent bipolar HS using 0.9% isotonic saline (the HS_BP group). The effects of these 2 methods on coagulation were assessed via pre and postoperative laboratory tests, including estimation of the international normalized ratio of prothrombin time and activated partial thromboplastin time and ROTEM analysis. In addition, the hemoglobin, hematocrit, and electrolyte levels and the platelet count were analyzed. Results: Patient characteristics, volume of irrigation fluid absorbed, and type of procedure were comparable between the 2 groups. There were no significant differences in the pre and postoperative values of ROTEM parameters between the 2 groups. Most postoperative ROTEM parameters, as compared with preoperative values, changed in both groups; clot formation time was prolonged, and the α-angle and maximum clot firmness were decreased. All ROTEM parameters were maintained within the normal range. Hematological parameters, including hemoglobin and hematocrit levels and platelet count, were significantly decreased postoperatively in both groups compared to the preoperative values. No pre and postoperative hematological and hemostatic parameters were significantly different between the 2 groups. Conclusion: Irrigation fluid absorbed in healthy women during HS caused hypocoagulable changes in the blood, irrespective of the irrigant type, and no significant differences between HS using monopolar and bipolar electrodes were demonstrated.

Correlation between interleukin-6 single nucleotide polymorphism and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure

Objective: To investigate the correlation between interleukin-6 (IL-6) single nucleotide polymorphism (SNP) and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group. SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) was determined by the improved multi-temperature ligase detection reaction (imLDRTM) technique. Simultaneously, case data were reviewed with the 3-months followed up survival condition of the ACLF group. Normally distributed data were expressed as arithmetic means and SDs, and t-test was adopted. Data with skewed distribution were expressed as medians with interquartile range, and were measured by non-parametric test. Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF. Results: Four hundred patients were included in the study, with 122 (30.5%) in the HBV-ACLF and 278 (69.5%) in the non-ACLF group. There were significant differences in total bilirubin, albumin, and white blood cell count, percentage of neutrophils, platelet count, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international standardized ratio, creatinine and the model for end-stage liver disease score between the two groups (P < 0.001). The genotype of IL-6 genes (rs1800795, rs1800797, rs2069827, and rs2069830) of all subjects showed no mutation or the mutation rate under 1%. There was no significant difference in the genotype of IL-6 (rs1524107, rs2069837, rs2069840 and rs2069845) between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk, nor had significant correlation with the 3-months prognosis. Conclusion: The SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) is unrelated to the occurrence and short-term prognosis of HBV-ACLF.