Prothrombin Time Ratio Research Articles

Impact of serum albumin levels on supratherapeutic PT-INR control and bleeding risk in atrial fibrillation patients on warfarin: A prospective cohort study

BackgroundSince warfarin is primarily bound to serum albumin, hypoalbuminemia is likely to increase the free fraction of warfarin and to increase the risk of bleeding. We prospectively evaluated the impact of serum albumin levels (ALB) on international normalized ratio of prothrombin time (PT-INR) control and hemorrhagic events in atrial fibrillation (AF) patients treated with warfarin. MethodsSeven hundred fifty-five non-valvular AF patients on warfarin were enrolled. PT-INR control and major bleeding events (MB, International Society on Thrombosis and Haemostasis) were prospectively followed and were related to ALB at enrollment. ResultsTwenty-seven patients developed MB during 1-year follow-up. In univariate/multivariate analyses, ALB (OR = 0.49, 95% CI 0.26–0.99, p = 0.04) and hemoglobin levels (OR = 0.78, 95% CI 0.65–0.92, p = < 0.01) were predictive for the annual risk of MB. In Spearman's rank correlation analysis, the baseline ALB was inversely correlated with the percentage of the time in PT-INR > 3.0 (ρ = −0.15, p < 0.0001), but neither 2.0 ≤ PT-INR ≤ 3.0 (ρ = 0.056, p = 0.13) nor PT-INR < 2.0 (ρ = −0.008, p = 0.82) during 1-year follow-up, suggesting that patients with low ALB had a directional tendency to be supratherapeutic control of PT-INR. The ROC curve showed that a cutoff of ALB was 3.6 g/dl to identify MB (AUC = 0.65). In Kaplan-Meier analysis, patients with ALB <3.6 g/dl (23/80, 29%) had more MB than those with ALB ≥3.6 g/dl (87/675, 13%, log-rank = 16.80, p < 0.0001) during long-term follow-up (3.8 ± 2.0 years). ConclusionsHypoalbuminemia increases the likelihood of supratherapeutic PT-INR control and the risk of MB. ALB can be a practical surrogate marker to prevent excessive warfarin control and warfarin-related MB.

Spontaneous intramural hematoma of the duodenum secondary to anticoagulant drug intoxication

Introduction. Duodenal hematomas are commonly traumatic, caused by blunt abdominal trauma. Nontraumatic spontaneous intramural hematomas of the duodenum are rare, and in most cases induced by anticoagulant therapy. The diagnosis is based on clinical and biochemical parameters, endoscopy, and radiological examinations. The objective of this report was to present a clinical and radiological presentation of an intramural duodenal hematoma caused by anticoagulant therapy. Case outline. A 43-year-old female was presented with epigastric pain, nausea, hematemesis, and melena. She had a positive medical history of deep venous thrombosis of the pelvis, which was diagnosed the previous month, for which she received oral anticoagulant therapy (coumarin). Physical examination revealed diffuse abdominal tenderness, while laboratory analyses showed markedly elevated international normalized ratio (INR) of prothrombin time (INR &gt; 7), which indicated the anticoagulant intoxication. Computed tomography (CT) showed luminal narrowing with uniform circumferential wall thickening of the descendent and horizontal part of duodenum, which was hyper dense in the native series and slight and uniform ring-formed enhancement in post-contrast phases, a typical CT presentation of intramural duodenal hematoma. Periduodenal and right sided pararenal hematomas were also visualized. After stopping the anticoagulant therapy and performing conservative treatment (vitamin K) with good therapeutic effect being monitored by physical examination, laboratory analyses and transabdominal ultrasonography, spontaneous resolution of the duodenal hematoma was revealed by follow-up CT examination two weeks after the onset. Conclusion. Ultrasonography and CT are useful diagnostic tools in recognition of the intramural duodenal hematoma and other locations of hemorrhage and in monitoring therapeutic effects.

Prognostic indicators among laboratory data on arrival to assess the severity of mamushi bites.

Objective: This study aimed to retrospectively determine which laboratory data on arrival for patients with mamushi bites was useful to predict the severity of mamushi bites.Materials and Methods: The subjects were divided into the following two groups: the mild group included subjects with mamushi bites Grades I and II, while the severe group included subjects with mamushi bites Grades III, IV, and V. The subjects’ variables were compared between the two groups.Results: There were no significant differences between the two groups regarding the levels of hematocrit, total protein, alanine aminotransferase, aspartate aminotransferase, creatinine phosphokinase, blood urea nitrogen, creatinine, and international normalized ratio of prothrombin time on arrival. Moreover, white blood cell count and platelet count on arrival in the mild group were significantly lower than those in the severe group. Furthermore, activated partial thromboplastin time on arrival was significantly higher in the mild group than in the severe group. Multivariate analysis using white blood cell count and platelet count and level of activated partial thromboplastin time revealed the following significant prognostic indicators of severity of mamushi bites: white blood cell count (Log Worth, 2.1; p<0.01) and platelet count (Log Worth, 1.6; p<0.05).Conclusion: White blood cell count and platelet count on arrival of patients with mamushi bites are considered significant prognostic indicators in determining the severity of mamushi bites.

Effects of fasting on warfarin sensitivity index in patients undergoing cardiovascular surgery

Warfarin shows large inter- and intra-individual variabilities in its pharmacokinetics and pharmacodynamics. Sufficient understanding of factors affecting the response to warfarin is necessary to achieve improved outcomes for warfarin therapy. In this study, we evaluated effects of fasting on the anticoagulant properties of warfarin. We conducted a retrospective observational study involving a total of 58 patients, who received cardiovascular surgeries and subsequent warfarin therapy. The effect of dietary intake on the anticoagulant properties with warfarin was assessed by measurement of the international normalized ratio of prothrombin time (PT-INR): the anticoagulant activities of warfarin were expressed as the warfarin sensitivity index (WSI). Additionally, fluctuations in WSI during the study period were obtained as differences between the maximum and minimum WSI. The maximum PT-INR and WSI values were significantly higher for patients who were fasting for different reasons during the postoperative period than those in the group without reduced dietary intake. The differences between maximum and minimum WSI in the fasting group significantly increased compared with those in the groups with moderate or no reduced dietary intake. Meanwhile, effects of other markers of clinical conditions including the baseline Child-Pugh score and Charlson Comorbidity Index on WSI were not significant. Our results indicate that postoperative fasting was significantly associated with the anticoagulation activity of warfarin. In patients fasting for different reasons during the postoperative period, closer control of PT-INR values and warfarin adjustments may be required to avoid adverse effects such as bleeding in warfarin treatment.

Successful treatment of disseminated intravascular coagulation by recombinant human soluble thrombomodulin in patients with acute myeloid leukemia.

Disseminated intravascular coagulation (DIC) is a life-threatening condition that frequently occurs in patients with hematologic malignancies. Currently, recombinant human soluble thrombomodulin (rTM) is a therapeutic DIC drug that is manufactured and sold in Japan only. We evaluated the efficacy of rTM compared to that of gabexate mesilate (GM), which was previously used routinely for treating DIC in Japan, in patients with acute myeloid leukemia (AML). This retrospective study enrolled 43 AML patients, including 17 with acute promyelocytic leukemia (APL), that was complicated with DIC. DIC resolution rates in non-APL AML and rTM-treated APL patients were 68.4% and 81.8%, respectively. In non-APL AML patients, the duration of rTM administration was significantly shorter than that of GM (7 vs 11 days), suggesting that rTM could improve DIC earlier than GM, although rTM was used in patients with more severe DIC. Moreover, treatment with rTM significantly improved DIC score, fibrinogen, fibrin/fibrinogen degradation product (FDP), and prothrombin time (PT) ratio. Conversely, treatment with GM only improved the DIC score and FDP. In APL patients, the duration of rTM administration was also significantly shorter than that of GM. No severe side effects associated with the progression of bleeding were observed during rTM administration. These findings suggest that rTM is safe, and its anti-DIC effects are more prompt than GM for treating AML patients with DIC.

Are prothrombin time and clot waveform analysis useful in detecting a bleeding risk in liver cirrhosis?

Prothrombin time is thought to be unreliable in cirrhotic patients to predict the risk of bleeding. We investigated whether prothrombin time ratio was an independent risk factor for bleeding alongside its clot waveform analysis. We studied 307 consecutive cirrhotic patients and 115 healthy subjects. A coagulometer was used for detecting both prothrombin time and clot waveform analysis which included velocity (1st derivative) and acceleration (2nd derivative) of clot formation, and area of parabolic segment of the 1st and 2nd derivatives of prothrombin time (entire cycle of the clot formation). Logistic regression shows that prothrombin time ratio was the only variable significantly associated with the history of bleeding. Using a hemorrhagic score, the stepwise model included prothrombin time ratio and the area of parabolic segment of the 1st derivative of Prothrombin Time. Odds ratio was used to create a new score to be challenged against the hemorrhagic score in a ROC analysis. The AUC was 0.72, 95% CI: 0.67-0.77. Prothrombin time ratio is associated to an increased bleeding risk. Its role may be further emphasized considering clot waveform analysis. The new score, if aggregated to prothrombin time ratio, could be useful to provide a single parameter immediately ready to assess the bleeding risk in the individual cirrhotic patient.

Consensus Guides on Stroke Thrombolysis for Anticoagulated Patients from Japan: Application to Other Populations.

Development of direct oral anticoagulants and their antidotes has led to the need to reconsider the eligibility of acute stroke patients who have been taking oral anticoagulants for intravenous thrombolysis. Officially authorized Japanese guidelines on this issue were revised twice at the time of approval for clinical use of direct oral anticoagulants and idarucizumab, a specific reversal agent for dabigatran. A unique recommendation in the latest Japanese clinical guides was that thrombolysis can be recommended if the time of the last dose of direct oral anticoagulants exceeds 4 hours and if commonly available anticoagulation markers are normal or subnormal, i.e., international normalized ratio of prothrombin time <1.7 and activated partial thromboplastin time <1.5 times the baseline value (≤40 seconds only as a guide). These criteria are partly supported by the findings of domestic multicenter and single-center surveys that symptomatic or asymptomatic intracranial hemorrhage following thrombolysis was rare under the conditions of the criteria. Even for dabigatran users, stroke thrombolysis can be considered without pretreatment by idarucizumab if patients meet the above criteria. If not, direct mechanical thrombectomy can be considered without pretreatment by idarucizumab or thrombolysis, and use of idarucizumab, followed immediately by thrombolysis, can be considered only when thrombectomy cannot be quickly performed. These clinical guides are practical and to some extent economical, but they have some limitations, including lack of corroborating information from sufficient numbers of relevant cases. The guides will be further modified based on the results of future research.

Time in Therapeutic Range and Disease Outcomes in Elderly Japanese Patients With Nonvalvular Atrial Fibrillation.

The relationship between warfarin treatment quality and prognosis for Japanese patients with nonvalvular atrial fibrillation (NVAF) has not been studied thoroughly. Methods and Results: Data from the J-RHYTHM Registry were used to determine the time in therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time in elderly patients (≥70 years). Target INR was 1.6-2.6. Of 7,406 patients with NVAF in the database, 3,832 elderly patients (mean [±SD] age 77.0±5.0 years) constituted the study group. Of these patients, 459 did not receive warfarin and 3,373 received warfarin. Patients on warfarin were subdivided into 4 TTR groups: <40%, 40-59.9%, 60-79.9%, and ≥80%. During the 2-year follow-up, the incidence of thromboembolism and all-cause death was lower in patients with higher TTR (Ptrend<0.001); however, the incidence of major hemorrhage was higher in patients with TTR <40%. In multivariate analysis, compared with the no-warfarin group, TTR 60-79.9% and ≥80% were associated with lower thromboembolic risk, with hazard ratios (HR) of 0.34 (95% confidence interval [CI] 0.17-0.67; P=0.002) and 0.35 (95% CI 0.18-0.68; P=0.002), respectively, and lower all-cause death (HR 0.37 [95% CI 0.22-0.65; P<0.001] and 0.43 [95% CI 0.26-0.71; P=0.001], respectively). TTR <40% was associated with major hemorrhage (HR 5.57; 95% CI 2.04-15.25; P=0.001). In elderly Japanese patients with NVAF, TTR should be maintained ≥60% to prevent thromboembolism and all-cause death. TTR <40% should be avoided to prevent major hemorrhage.

Renal Dysfunction Affects Anticoagulation Control With Warfarin and Outcomes in Japanese Elderly Patients With Non-Valvular Atrial Fibrillation.

It is unclear whether renal dysfunction affects warfarin control in patients with non-valvular atrial fibrillation (NVAF). Methods and Results: Using a dataset from the J-RHYTHM Registry, time in therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time, and creatinine clearance (CrCl) were determined in elderly patients aged ≥70 years. Target INR values were 1.6-2.6 following Japanese guidelines. Incidences of thromboembolism, major hemorrhage, and all-cause death were determined over 2 years. Of 7,406 NVAF patients enrolled in the registry, 2,782 elderly patients (mean age, 75 years) had data for CrCl measured at baseline and TTR. TTR values were lower in the lower CrCl groups (P<0.001 for trend). CrCl <30 mL/min was independently associated with TTR <65% (odds ratio, 1.49; 95% confidence interval, 1.13-1.95; P=0.004). In the multivariate analysis, TTR <65% was independently associated with thromboembolism (hazard ratio, 2.26; 95% confidence interval, 1.37-3.72; P=0.001), but CrCl was not (CrCl <30 mL/min, 1.68, 0.41-6.85, P=0.473). However, CrCl <30 mL/min and TTR <65% were independently associated with all-cause death (5.32, 1.56-18.18, P=0.008 and 1.60, 1.07-2.38, P=0.022, respectively) and the composite event (thromboembolism, major hemorrhage and all-cause death) (2.03, 1.10-3.76, P=0.024 and 1.58, 1.22-2.04, P=0.001, respectively). Elderly NVAF patients with renal dysfunction had poor warfarin control, which was associated with higher risk of thromboembolism and all-cause death.

The significance of the levels of fibrin/fibrinogen degradation products for predicting trauma severity

Background: On initial treatment in the emergency room, trauma patients should be assessed using simple clinical indicators that can be measured quickly. Objectives: The purpose of this study is to investigate the relationship between the injury severity score and blood test parameters measured on emergency room arrival in trauma patients. Methods: Trauma patients transferred to Gunma University Hospital between May 2013 and April 2014 were evaluated in this prospective, observational study. Blood samples were collected immediately on their arrival at our emergency room and their hematocrit, platelet, international normalized ratio of prothrombin time, activated partial thromboplastin time, fibrin/fibrinogen degradation products, and D-dimer were measured. We evaluated the correlations between the injury severity score and those biomarkers, and examined whether the correlation varied according to the injury severity score value. We also evaluated the correlations between the biomarkers and the abbreviated injury scale values of six regions. Results: We analyzed 371 patients. Fibrin/fibrinogen degradation products and D-dimer showed the greatest coefficients of correlation with injury severity score (0.556 and 0.543, respectively). The area under the curve of the receiver operating characteristic was larger in patients with injury severity score ⩾ 9 than in those with injury severity score ⩾ 4; however, patients with injury severity score ⩾ 9 or ⩾16 showed no significant differences. The area under the curve of fibrin/fibrinogen degradation products was larger than that of D-dimer at all injury severity score values. The chest abbreviated injury scale had the strongest relationship with fibrin/fibrinogen degradation products. Conclusion: Fibrin/fibrinogen degradation products and D-dimer were positively correlated with injury severity score, and the relationships varied according to trauma severity. Chest trauma contributed most strongly to fibrin/fibrinogen degradation product elevation.

Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock

BackgroundAfter a person has been injured, prehospital administration of plasma in addition to the initiation of standard resuscitation procedures in the prehospital environment may reduce the risk of downstream complications from hemorrhage and shock. Data from large clinical trials are lacking to show either the efficacy or the risks associated with plasma transfusion in the prehospital setting.MethodsTo determine the efficacy and safety of prehospital administration of thawed plasma in injured patients who are at risk for hemorrhagic shock, we conducted a pragmatic, multicenter, cluster-randomized, phase 3 superiority trial that compared the administration of thawed plasma with standard-care resuscitation during air medical transport. The primary outcome was mortality at 30 days.ResultsA total of 501 patients were evaluated: 230 patients received plasma (plasma group) and 271 received standard-care resuscitation (standard-care group). Mortality at 30 days was significantly lower in the plasma group than in the standard-care group (23.2% vs. 33.0%; difference, −9.8 percentage points; 95% confidence interval, −18.6 to −1.0%; P=0.03). A similar treatment effect was observed across nine prespecified subgroups (heterogeneity chi-square test, 12.21; P=0.79). Kaplan–Meier curves showed an early separation of the two treatment groups that began 3 hours after randomization and persisted until 30 days after randomization (log-rank chi-square test, 5.70; P=0.02). The median prothrombin-time ratio was lower in the plasma group than in the standard-care group (1.2 [interquartile range, 1.1 to 1.4] vs. 1.3 [interquartile range, 1.1 to 1.6], P<0.001) after the patients’ arrival at the trauma center. No significant differences between the two groups were noted with respect to multiorgan failure, acute lung injury–acute respiratory distress syndrome, nosocomial infections, or allergic or transfusion-related reactions.ConclusionsIn injured patients at risk for hemorrhagic shock, the prehospital administration of thawed plasma was safe and resulted in lower 30-day mortality and a lower median prothrombin-time ratio than standard-care resuscitation. (Funded by the U.S. Army Medical Research and Materiel Command; PAMPer ClinicalTrials.gov number, NCT01818427.)

Predicting Pre-transplant Abstinence in Patients with Alcohol-Induced Liver Disease.

Some patients with alcohol-induced liver failure will succumb to their disease prior to demonstrating compliance with the six months abstinence rule for liver transplantation. The purpose of this study was to determine whether a patient's self-reported, longest period of abstinence predicts subsequent abstinence. Adult patients (n=63) with alcohol-induced liver disease were asked to recall their longest period of abstinence prior to their initial hepatology visit. Compliance with instructions to remain abstinent was then documented. Nineteen patients (30%) achieved abstinence and 44 (70%) relapsed within six months of seeing their hepatologist. Relapses were more common in patients who self-reported previous periods of abstinence exceeding six months (19/44, 43%) compared with 2/19 (11%) in those with periods of less than six months (p=0.01). Serum albumin levels were lower in relapsers but other tests of liver function (bilirubin level and international ratio of prothrombin time) and predictors of post-transplant recidivism did not associate with relapses. On multivariate analysis, self-reported abstinence (OR: 0.11, 95% CI: 0.02-0.57, p=0.008) and serum albumin levels (regression coefficient 0.113, p=0.02) predicted relapses. A self-reported period of abstinence in excess of six months was associated with an increased risk of subsequent relapse following a hepatologist's instructions to remain abstinent. These counter-intuitive findings should be confirmed by larger, prospective studies.

High-dose intravenous methylprednisolone therapy in patients with Graves\u2019 orbitopathy is associated with the increased activity of factor VIII

PurposeVenous thromboembolic events (VTE), with their life-threatening manifestation as pulmonary embolism, are potential adverse effects of intravenous methylprednisolone (IVMP) pulse therapy, partially due to a hypercoagulable state. The aim of the study was to analyze the influence of IVMP on selected hemostatic parameters in patients with moderate-to-severe Graves’ orbitopathy (GO).Methods26 euthyroid patients with GO were treated with 12 pulses of IVMP (6 × 0.5, 6 × 0.25 g every week). Hemostatic variables [factor (F) II, FV, FVII, FVIII, fibrinogen, antithrombin, activated partial thromboplastin time (aPTT), prothrombin time, international normalized ratio of prothrombin time, platelets and D-dimer] were analysed before, 24 and 48 h after 1st, 6th and 12th pulse.ResultsA constant, transient trend in changes of some hemostatic variables was observed after all assessed pulses. We discovered an increase in median activity of FVIII 24 and 48 h after pulses, with a shortening of aPTT 24 h after each IVMP pulse (p < 0.00005). FVII decreased 24 h after each pulse (p < 0.0005 after 1st and 12th, p < 0.00005 after 6th). Fibrinogen level decreased 48 h after each pulse (P < 0.00005). We did not observe any statistically significant changes in hemostatic parameters in the long-term evaluation. Therapy was concluded in one patient after the 9th pulse due to pulmonary embolism.ConclusionsThe increase of FVIII activity is a consequence of treatment with IVMP and occurs after each pulse. In patients with additional risk factors of VTE, anticoagulation prophylaxis should be considered.

The incidence and effect of coagulopathy on short-term outcomes in patients undergoing craniotomy following traumatic brain injury

Background: Coagulopathy in isolated traumatic brain injury (TBI) is well-known, and studies have found an association between coagulopathy and unfavourable outcomes. This study was conducted to determine the incidence and causes of coagulopathy in patients with TBI undergoing craniotomy and its effect on post-operative outcome. Materials and Methods: The data collected was demographics, computed tomography diagnosis, post-resuscitation Glasgow Coma Scale (GCS) score, pre- and post-operative platelet count, liver function tests, intraoperative blood loss and transfusion, fluids infused and incidence of redo surgery. Point of care (Coaguchek XS) monitor was used to obtain prothrombin time and international normalised ratio (INR) at 24 h and 72 h of injury. Coagulopathy was defined as INR ≥1.3 and thrombocytopenia as platelet count ≤100,000/mcL. Outcome measures assessed were the length of hospital stay, GCS at discharge and in-hospital mortality. Results: In 166 patients, the average pre-operative GCS was 8.8 ± 3.6. The incidence of coagulopathy was 42.8% and increased to 55.6% on the 3 rd day, and thrombocytopenia from 3.5% in the first 24 h increased to 14.7% at 72 h. Patients with coagulopathy had lower pre-operative admission GCS (median 7 vs. 9, P = 0.03), greater intraoperative blood loss and received more intravenous fluids. There was no difference in the incidence of post-operative haematomas, length of hospital stay and GCS at discharge or mortality. Conclusion: In patients with TBI, the incidence of coagulopathy increased at the end of 72 h. In this study, there was no difference in outcomes in patients who underwent craniotomy with deranged coagulation.

Clinical bleeding and thrombin generation in admissions to critical care with prolonged prothrombin time: an exploratory study.

Prolongation of prothrombin time (PT) is often recorded in critical illness, but has limited ability to predict risk of bleeding. This exploratory study was aimed at assessing a role for thrombin generation (TG) to predict bleeding. TG was measured by calibrated automated thrombography in admissions to intensive care with prolonged PT. Bleeding events were recorded up to Day 5 after enrollment and correlated with results of PT ratio (PTR) and variables of TG. A total of 306 patients were recruited. A total of 101 bleeding events developed in 46 patients during the period of observation. Many patients with prolonged PT had endogenous thrombin potential (ETP), which was within the normal range (120/251 patients, 47.8%) or even elevated (8%). Although some patients had a reduction in ETP or peak thrombin, these were present over a wide range of PTR. There was no suggestion by receiver operating characteristic analysis that variables of conventional TG were sensitive at predicting bleeding. No bleeding events were documented in patients defined as ETP high, despite elevated PTR. Future studies need to explore a role for alternatives tests of coagulation in critical illness. Development of TG assays is required to positively identify more patients at increased bleeding risk or to exclude a larger number at low risk and how this relates to subgroups, such as patients with liver disease, and the need for prophylactic plasma transfusion.

The significance of perioperative coagulation and fibrinolysis related parameters after lung surgery for predicting venous thromboembolism: a prospective, single center study.

The high incidence of venous thromboembolism (VTE) has been perceived in post thoracic surgery patients. However, the significance of perioperative coagulation and fibrinolysis related parameters after lung surgery for VTE predicting is not clear. To investigate that, we conducted a prospective single center study. A total of 111 patients undergoing lung surgery were enrolled in this study, included 52 primary lung cancer patients and 59 benign lung disease patients from July 2016 to March 2017. Preoperative and postoperative days 1, 3, and 5 coagulation and fibrinolysis related parameters were tested, including antithrombin (AT), fibrinogen degradation product (FDP), prothrombin time (PT), prothrombin time activity (PA), prothrombin time ratio (PR), international normalized ratio (INR), activated partial thromboplastin time (APTT), plasma fibrinogen (FBG), thrombin time (TT) and D-Dimer. The Doppler ultrasonography was performed before and after surgery for deep venous thrombosis (DVT) confirmation. Patients with new postoperative DVT, unexplained dyspnea, hemoptysis, chest pain, or high Caprini score (≥9) were received further computer tomography pulmonary angiography (CTPA) for pulmonary embolism (PE). We used the area under receiver-operating-characteristic (ROC) curve to discriminate patients between those who developed VTE and those who did not. Single factor analysis was utilized to define risk factors associated with VTE. The overall incidence of VTE was 16.2% (18/111). The incidence of VTE in primary lung cancer patients was 23.1% (12/52), much higher than that in benign lung diseases 10.2% (6/59), but did not reach statistical significance (P=0.066). Among 18 VTE patients, 83.3% was DVT, 16.7% was DVT + PE and 72.2% was muscular veins of the calf thrombosis. D-Dimer was much higher in VTE group than that in non-VTE group preoperatively and at postoperative days 1, 3 (0.64±0.24 vs. 0.33±0.06, P=0.007; 3.14±0.75 vs. 1.51±0.09, P=0.005, and 1.88±0.53 vs. 0.76±0.05, P=0.001, respectively). And the ROC curve areas of preoperative and postoperative days 1, 3 of D-Dimer were 0.70, 0.71 and 0.74, respectively. And FDP was much higher in VTE group than that in non-VTE group at postoperative day 3 (6.78±1.43 vs. 3.79±0.15, P=0.004). But AT, PT, PA, PR, INR, APTT, FBG and TT there were no significantly difference. The overall incidence of VTE after lung surgery was 16.2%. The patients with preoperative high D-Dimer should receive VTE prophylaxis.

Development and validation of a scoring system to predict progression to acute-on-chronic liver failure in patients with acute exacerbation of chronic hepatitis B.

The aim of this study was to develop and validate a scoring system to predict the progression to acute-on-chronic liver failure (ACLF) in patients with acute exacerbation (AE) of chronic hepatitis B (CHB). The baseline characteristics of 474 patients with AE of CHB were retrospectively reviewed; 280 and 194 patients were randomly assigned to the derivation and validation cohorts, respectively. Univariate risk factors associated with ACLF development were entered into a multivariate logistic regression. The score model was established, and its predictive value was evaluated by the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUROC). Hepatitis B virus (HBV) DNA, international normalized ratio (INR) of prothrombin time, and patient age were identified as independent risk factors associated with progressing to ACLF. The prediction model was established as R = -13.323 + 0.553 × log HBV-DNA (copies/mL) + 3.631× INR + 0.053 × age. The AUROCs of our prediction model were higher than those of the Model for End-stage Liver Disease (MELD) and MELD-sodium (Na) for both cohorts. At the cut-off value of -2.43, our prediction model had higher sensitivity (87.5%), specificity (73.6%), positive predictive value (23.0%), positive likelihood ratio (3.30), and lower negative likelihood ratio (0.17) in the validation cohort than those of MELD and MELD-Na. The independent risk factors associated with progressing to ACLF in patients with AE of CHB are HBV-DNA, INR, and age. Our risk prediction model is useful for predicting the development of ACLF.

French lyophilized plasma versus fresh frozen plasma for the initial management of trauma‐induced coagulopathy: a randomized open‐label trial

Background Guidelines recommend beginning hemostatic resuscitation immediately in trauma patients. We aimed to investigate if French lyophilized plasma (FLyP) was more effective than fresh frozen plasma (FFP) for the initial management of trauma-induced coagulopathy. Methods In an open-label, phase 3, randomized trial (NCT02750150), we enrolled adult trauma patients requiring an emergency pack of 4 plasma units within 6h of injury. We randomly assigned patients to receive 4-FLyP units or 4-FFP units. The primary endpoint was fibrinogen concentration at 45min after randomization. Secondary outcomes included time to transfusion, changes in hemostatic parameters at different time-points, blood product requirements and 30-day in-hospital mortality. Results Forty-eight patients were randomized (FLyP, n=24; FFP, n=24). FLyP reduced the time from randomization to transfusion of first plasma unit compared with FFP (median[IQR],14[5-30] vs. 77[64-90]min). FLyP achieved a higher fibrinogen concentration 45min after randomization compared with FFP (baseline-adjusted mean difference, 0.29gL-1 ; 95% confidence interval [CI], 0.08-0.49) and a greater improvement in prothrombin time ratio, factor V and factor II. The between-group differences in coagulation parameters remained significant at 6h. FLyP reduced fibrinogen concentrate requirements. Thirty-day in-hospital mortality rate was 22% with FLyP and 29% with FFP. Conclusion FLyP led to a more rapid, pronounced and extended increase in fibrinogen concentrations and coagulopathy improvement compared with FFP in the initial management of trauma patients. FLyP represents an attractive option for trauma management, especially when facing logistical issues such as combat casualties or mass casualties related to terror attacks or disasters.

Histone-Complexed DNA Fragments Levels are Associated with Coagulopathy, Endothelial Cell Damage, and Increased Mortality after Severe Pediatric Trauma.

The release of damage-associated molecular pattern molecules in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. We conducted a prospective observational study of 149 pediatric trauma patients and 62 control patients at two level 1 pediatric trauma centers from 2013 to 2016. Blood samples were collected upon arrival and at 24 h, analyzed for hcDNA, coagulation abnormalities, endothelial damage, and clinical outcome. Platelet aggregation was assessed with impedance aggregometry (Multiplate) and coagulation parameters were assessed by measuring prothrombin time ratio in plasma and the use of viscoelastic techniques (Rotational Thromboelastometry) in whole blood. The median age was 8.3 years, the median injury severity score (ISS) was 20, and overall mortality was 10%. Significantly higher levels of hcDNA were found on admission in patients with severe injury (ISS > 25), coagulopathy, and/or abnormal platelet aggregation. Patients with high hcDNA levels also had significant elevations in plasma levels of syndecan-1, suggesting damage to the endothelial glycocalyx. Finally, significantly higher hcDNA levels were found in non-survivors. hcDNA is released following injury and correlates with coagulopathy, endothelial glycocalyx damage, and poor clinical outcome early after severe pediatric trauma. These results indicate that hcDNA may play an important role in development of coagulation abnormalities and endothelial glycocalyx damage in children following trauma.

Predictive formula of coma onset and prothrombin time to distinguish patients who recover from acute liver injury.

Acute liver failure (ALF) is defined as acute liver injury (ALI) associated with coagulopathy. A follow-up strategy for ALI and characterization of ALI patients with a risk of progressing to ALF have never been established. To establish predictive markers for progression from ALI to ALF, this study compared the clinical characteristics and laboratory data on the day of registration to data from a regional referral system of patients with ALI. This prospective, observational study enrolled 365 consecutive patients with ALI/ALF between 2007 and 2016. We evaluated 109 ALI patients, 27 of whom satisfied the ALF criteria during observation and another 82 patients who recovered without progression to ALF. Four patients died; all were in the ALF group. The variables of age, incidence of autoimmune hepatitis, model of end-stage liver disease score, values for total bilirubin and prothrombin time (PT)-international ratio, and Japan Hepatic Encephalopathy Prediction Model (JHEPM) probability at registration were significantly higher in ALF patients than in ALI patients. In multivariate analysis, PT and JHEPM were identified as risk factors for progression to ALF. The cut-off values of 13%, 4.9%, 65%, and 1.32% for the model of end-stage liver disease score, JHEPM probability, PT, and PT-international ratio values, respectively, had high negative predictive values. Furthermore, among patients whose JHEPM was underestimated, none died due to ALF. The JHEPM probability is a predictive parameter that can be used to decide a follow-up treatment strategy for ALI patients.