Pediatric systemic lupus erythematosus with lupus anticoagulant hypoprothrombinemia syndrome-A case series with review of literature.

INTRODUCTION: Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare phenomenon that leads to concomitant thrombosis and hemorrhage in children with SLE. LAHPS in pediatric SLE (pSLE) has a protracted course requiring long-term immunosuppressive therapy. Due to the rarity of this syndrome and paucity of reported cases, there is lack of standardized management. We herewith report 5 children with pSLE with LAHPS.Methodology: We retrospectively reviewed clinical features, laboratory features, treatment and outcome for 5 children with lupus anticoagulant hypoprothrombinemia syndrome with SLE and a review of literature of similar cases published. RESULTS: Mean age of presentation was 10.2 ± 2.38 years (mean ± SD) and female to male ratio was 4:1. All children presented with mild to severe bleeding manifestations like gum bleed, epistaxis, hematuria, menorrhagia and subarachnoid bleed. Coagulation profile revealed prolonged PT and aPTT, with low prothrombin levels and positive Lupus anticoagulant in all children. Mixing studies were characteristic in these children. On comparing laboratory parameters majority had low C3, C4 levels, ANA and anti-DsDNA antibody positivity and three children had anticardiolipin positivity. One child had lupus nephritis along with LAHPS at presentation. All responded well to steroids and supportive measures. CONCLUSION: High index of suspicion is needed when child with lupus presents with bleeding manifestations for early diagnosis and treatment.

Coagulation tests on admission correlate with mortality and morbidity in general ICU patients: An observational study.

BACKGROUND: It is well known that low platelet count on admission to intensive care units (ICU) is associated with increased mortality. However, it is unknown whether prothrombin time (PT-INR) and activated partial thromboplastin time (APTT) on admission correlate with mortality and organ failure. Therefore, the aim of this study was to investigate whether PT-INR and APTT at admission can predict outcome in the critically ill patient after adjusting for severity of illness measured with Simplified Acute Physiology Score 3 (SAPS 3). MATERIALS AND METHODS: Data were retrospectively collected. APTT and PT-INR taken on admission and SAPS 3 score were independent variables in all regression analyses. Survival analysis was done with Cox regression. Organ failure was reported as days alive and free (DAF) of vasopressors and invasive ventilation, need of continuous renal replacement therapy (CRRT) and Acute Kidney Injury Network creatinine score (AKIN-crea). RESULTS: A total of 3585 ICU patients were included. Prolonged APTT correlated with mortality with 95% confidence interval (CI) of hazard ratio 1.001-1.010. Prolonged APTT also correlated with DAF vasopressor, CRRT and AKIN-crea with 95% CI of odds ratio (OR) 1.009-1.034, 1.016-1.037 and 1.009-1.028, respectively. Increased PT-INR correlated with DAF vasopressor and DAF ventilator with 95% CI of OR 1.112-2.014 and 1.135-1.847, respectively. CONCLUSIONS: Activated partial thromboplastin time prolongation was associated with mortality and all morbidity outcomes except the DAF ventilator. PT-INR increase at admission was associated with DAF vasopressor and DAF ventilator. APTT and PT-INR at admission correlate with morbidity, which is not accounted for in the SAPS 3 model.

The correlation between conventional coagulation tests and thromboelastography in each phase of liver transplantation.

INTRODUCTION: Thromboelastography (TEG) is gaining increasing acceptance in liver transplantation (LT) with conventional coagulation tests (CCTs) such as prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin III (ATIII), platelet count (PLT), and fibrinogen concentration. The purpose of this study was to evaluate the clinical utility of TEG in LT and investigate the correlation between TEG and CCT values during each phase of LT. MATERIALS AND METHODS: Medical records of patients who underwent deceased donor LT at a single, university hospital between October 2010 and July 2015 were retrospectively reviewed. Blood samples were obtained at each phase of LT (pre-anhepatic, anhepatic, and neo-hepatic phase) according to our institutional LT protocol and utilized for analysis of TEG and CCTs. The Spearman correlation coefficient between TEG and CCT values were obtained. RESULTS: During the pre-anhepatic phase, the reaction time (R), PT, and aPTT did not correlate with each other, but demonstrated a negative correlation with PLT. Clot formation time (K) demonstrated a similar correlation with R and a negative correlation with fibrinogen. The maximal amplitude (MA) and α-angle (α) were positively correlated with PLT and fibrinogen and inversely correlated with aPTT. During the anhepatic phase, MA was significantly correlated with PLT and inversely correlated with aPTT; other parameters had weak or indistinct correlation. During the neo-hepatic phase, R and K were significantly correlated with aPTT and inversely correlated with PLT and fibrinogen. A correlation of MA and α with PLT, aPTT, and fibrinogen was also observed. Clot lysis at 30 minutes and estimated percent lysis were inversely correlated with levels of ATIII and fibrinogen. CONCLUSIONS: Conventional coagulation tests and TEG show particularly poor comparability during the anhepatic period of liver transplantation. TEG can be most reliable in the anhepatic phase, during which dynamic hemostatic changes occur.

Thrombin generation is increased in patients with Clostridium difficile colitis - a pilot study.

Background: There are only limited data in the literature on the thrombotic risk of patients with Clostridium difficile (CD) colitis, although this disease is widespread throughout the world. Objective: The aim of this study was to explore thrombin generation in these patients - the best way to evaluate their coagulation. Methods: A prospective observational study was conducted during 15 months on hospitalized patients with CD colitis. Thrombin generation was performed in platelet-poor plasma using a Ceveron® alpha analyzer and was compared with a group of volunteer control subjects. Results: Thirty-three patients and 51 control subjects were enrolled in the study. Two biomarkers - mean velocity index and peak thrombin - were significantly higher in patient group, compared to the control subjects (p = 0.010, respectively, p = 0.0395). This pattern of thrombin generation suggests that patients with CD colitis without septic shock have a potential thrombotic risk. The mean velocity index significantly correlated with the estimated related risk of death according to the Charlson age-comorbidity index. Conclusions: The higher values of thrombin generation suggest that CD colitis increases the thromboembolic risk. The pattern of thrombin generation could identify patients with particularly higher thromboembolic risk. They are potential candidates for thromboprophylaxis strategies and monitorization.

First-in-human study to assess the safety, pharmacokinetics and pharmacodynamics of BMS-962212, a direct, reversible, small molecule factor XIa inhibitor in non-Japanese and Japanese healthy subjects.

AIMS: The aims of the present study were to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class factor XIa inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a randomized, placebo-controlled, double-blind, sequential, ascending-dose study of 2-h (part A) and 5-day (part B) intravenous (IV) infusions of BMS-962212. Part A used four doses (1.5, 4, 10 and 25 mg h-1 ) of BMS-962212 or placebo in a 6:2 ratio per dose. Part B used four doses (1, 3, 9 and 20 mg h-1 ) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese (n = 4 active, n = 1 placebo) subjects per dose. The PK, PD, safety and tolerability were assessed throughout the study. RESULTS: BMS-962212 was well tolerated; there were no signs of bleeding, and adverse events were mild. In parts A and B, BMS-962212 demonstrated dose proportionality. The mean half-life in parts A and B ranged from 2.04 to 4.94 h and 6.22 to 8.65 h, respectively. Exposure-dependent changes were observed in the PD parameters, activated partial thromboplastin time (aPTT) and factor XI clotting activity (FXI:C). The maximum mean aPTT and FXI:C change from baseline at 20 mg h-1 in part B was 92% and 90%, respectively. No difference was observed in weight-corrected steady-state concentrations, aPTT or FXI:C between Japanese and non-Japanese subjects (P > 0.05). CONCLUSION: BMS-962212 has tolerability, PK and PD properties suitable for investigational use as an acute antithrombotic agent in Japanese or non-Japanese subjects.

Bivalirudin Anticoagulation Dosing Protocol for Extracorporeal Membrane Oxygenation: A Retrospective Review.

Anticoagulation with unfractionated heparin during extracorporeal membrane oxygenation (ECMO) is common, but alternative agents are being evaluated for safety and efficacy. The objective of this analysis was to assess if a comprehensive bivalirudin dosing and monitoring protocol effectively guides dose adjustments and monitoring of bivalirudin in patients during ECMO. Our analysis included 11 patients who received bivalirudin during ECMO therapy and had dosing managed using our hospital derived protocol. Patients treated over a 1-year period were included in this retrospective analysis. Clinical characteristics and changes in activated partial thromboplastin time (aPTT) were evaluated from medical records to determine the efficacy of the dosing protocol. ECMO was initiated for acute respiratory distress syndrome in eight (72.7%) patients and for cardiac arrest in three (27.3%) patients. A total of 178 protocol guided dose adjustments were made during the study. Among the dose adjustments, 56 (31.5%) attained the protocol predicted aPTT level change, 96 (53.9%) of the measured aPTT changes were less than predicted, and 26 (14.6%) of the measured aPTT changes were more than predicted. On average, patients were within their defined therapeutic aPTT target range 66.3% of the time. All patients reached their designated aPTT target range within the first 24 hours of therapy. Significant bleeding was documented in eight (72.7%) patients. No clinically evident thromboembolic events were identified in vivo while cannulated. This analysis suggests that bivalirudin can be managed using a dosing protocol to provide anticoagulation therapy to patients during ECMO and can provide foundational guidance for dose adjustment and monitoring for other institutions.

Utility of Sonoclot in Prediction of Postoperative Bleeding in Pediatric Patients Undergoing Cardiac Surgery for Congenital Cyanotic Heart Disease: A Prospective Observational Study.

OBJECTIVES: To assess the utility of Sonoclot in prediction of postoperative bleeding in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass for congenital cyanotic heart disease. DESIGN: Prospective, observational study. SETTING: Single university hospital. PARTICIPANTS: Eighty-seven pediatric patients undergoing cardiac surgery for congenital cyanotic heart disease. INTERVENTIONS: Laboratory coagulation parameters (prothrombin time, international normalization ratio, activated partial thromboplastin time, fibrinogen, D-dimer) as well as point-of-care Sonoclot glass bead activation time, clot rate, and platelet function (gbPF) were done before induction of anesthesia and following heparin reversal after termination of cardiopulmonary bypass (CPB) in all patients. MEASUREMENTS AND MAIN RESULTS: Postoperative blood loss was monitored by the amount of chest tube drainage. The primary outcome was to define Sonoclot parameters for prediction of postoperative bleeding. Secondary outcomes studied were amount of postoperative blood loss, transfusion requirement of various blood products, incidence of surgical re-exploration, duration of postoperative mechanical ventilation, intensive care unit and hospital stay. Among studied subjects, 37.9% (33 of 87 patients) were designated as bleeders while 62.1% (54 of 87 patients) were non-bleeders. Lower age, D-dimer, and gbPF test after termination of CPB following heparin neutralization were predictive for postoperative bleeders. Among these, post-protamine gbPF had the highest area under the curve (0.725), 95% confidence interval (0.619-0.831) for prediction of postoperative bleeders. Duration of mechanical ventilation (26.41±36.44 v 8.25±6.36 h, respectively, p = 0.001), intensive care unit stay (7.36 ± 4.05 v 4.96 ± 2.49, p = 0.001), and hospital stay (11.69±4.82 v 8.63±3.48 p = 0.001) were higher in bleeders; however, incidence of re-exploration was comparable between both groups. CONCLUSION: Postoperative bleeders may be predicted independently by post-CPB gbPF, postoperative D-dimer, and lower age of patients. Among these, post-CPB gbPF has maximum predictive value.

Indications and Effects of Plasma Transfusions in Critically Ill Children.

RATIONALE: Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients. OBJECTIVES: To identify patient characteristics and to characterize indications leading to plasma transfusions in critically ill children, and to assess the effect of plasma transfusions on coagulation tests. METHODS: Point-prevalence study in 101 pediatric intensive care units in 21 countries, on 6 predefined weeks. All critically ill children admitted to a participating unit were included if they received at least one plasma transfusion. MEASUREMENTS AND MAIN RESULTS: During the 6 study weeks, 13,192 children were eligible. Among these, 443 (3.4%) received at least one plasma transfusion and were included. The primary indications for plasma transfusion were critical bleeding in 22.3%, minor bleeding in 21.2%, planned surgery or procedure in 11.7%, and high risk of postoperative bleeding in 10.6%. No bleeding or planned procedures were reported in 34.1%. Before plasma transfusion, the median international normalized ratio (INR) and activated partial thromboplastin time (aPTT) values were 1.5 and 48, respectively. After plasma transfusion, the median INR and aPTT changes were -0.2 and -5, respectively. Plasma transfusion significantly improved INR only in patients with a baseline INR greater than 2.5. CONCLUSIONS: One-third of transfused patients were not bleeding and had no planned procedure. In addition, in most patients, coagulation tests are not sensitive to increases in coagulation factors resulting from plasma transfusion. Studies assessing appropriate plasma transfusion strategies are urgently needed.

[THE COMPARATIVE CHARACTERISTIC OF KAOLIN-ACTIVATED THROMBOELASTOGRAPHY IN HEALTHY NEWBORNS AND NEWBORNS WITH HEART AILMENTS].

The study was carried out to diferentiate reference values for kaolin-activated thromboelastography in newborns with congenital heart disease. The study included two groups ofpatients. The first one consisted of 62 newborns with congenital heart disease and the second one consisted of 35 healthy newborns. The results of kaolin-activated thromboelastography implemented in groups are evaluated as condition of normal coagulation. The valuable diferences of homeostasis system in healthy newborns and newborns with congenital heart disease (without severe concomitant pathology) are not established. They have similar indicators of kaolin-activated thromboelastography. The derived results can be applied as standards in full-term newborns with congenital heart disease.

Effect of unfractionated heparin on endothelial glycocalyx in a septic shock model.

BACKGROUND: The constituents of vascular endothelial glycocalyx, such as syndecan-1 and heparan sulphate (HS), can be detected in the plasma of patients and animals with septic shock. However, the dynamics of glycocalyx degradation and its association with inflammation remains largely unknown. In this study, we investigated the association between the biomarkers of acute endothelial glycocalyx degradation and inflammatory factors. We also evaluated the effect of unfractionated heparin (UFH) on glycocalyx shedding in a canine septic shock model. METHODS: Twenty adult beagle dogs were randomly allocated to one of the following four groups (n = 5): (1) a sham group; (2) a shock group [3.5 × 10(8) colony-forming unit (cfu) Escherichia coli (E. coli)/kg]; (3) a basic therapy group (sensitive antibiotics and 0.9% saline, 10 ml/kg/h); and (4) a heparin group (40 units/kg/h UFH plus basic therapy). After the onset of septic shock, systemic haemodynamic indices were measured. Endothelial glycocalyx degradation markers (i.e., syndecan-1, HS) and inflammatory factors [i.e., interleukin 6 (IL-6), tumour necrosis factor (TNF)-α], platelet count and activated partial thromboplastin time were measured at various time points. RESULTS: A lethal dose of E. coli induced a progressive septic shock model. We observed increased syndecan-1 and HS levels, which correlated with IL-6 and TNF-α in the septic shock model. The glycocalyx shedding was reduced by UFH, which might be regulated by the inhibition of inflammatory factors. CONCLUSIONS: A therapeutic dose of UFH can protect glycocalyx from shedding by inhibiting inflammation. Additional studies with larger sample sizes are needed to confirm our conclusions.

Effect of food on the pharmacokinetics and pharmacodynamics of R1663, an oral factor Xa inhibitor, in healthy male volunteers.

AIMS: To explore the effect of food intake on the relative bioavailability of R1663 and on its pharmacodynamic effects (prothrombin time (PT) and activated partial thromboplastin time (aPTT)) after a single oral dose of 200 mg. METHODS: This was a prospective, open-label, randomized, two-way crossover study. Eight healthy male volunteers received R1663 on two occasions, after a high fat/high calorie breakfast and after an overnight fast of 10 h, with a 7-day washout between doses. Blood was sampled up to 48 h for the pharmacokinetic and pharmacodynamic evaluation of R1663. Pharmacokinetic parameters (area under the plasma concentration-time curve from Time 0 extrapolated to infinity (AUC(0-∞)) and maximal concentration (C(max)) as well as pharmacodynamic parameters (area under the effect curve over 48 h (AUE(0-48)) and maximal effect (E(max)) were determined on both occasions. Geometric mean ratios fed/ fasted (GMR) and 90% confidence intervals (CI) were calculated for AUC(0-∞) and C(max) of R1663 and AUE(0-48) and E(max) of PT and aPTT. RESULTS: Following food intake, C(max) was reduced by 10% with CI extended outside the bioequivalence range (GMR, 0.90; CI 0.72 - 1.13). R1663 t(max) was delayed in the fed state (4 h) as compared to the fasted state (1 h). There was no significant food effect on R1663 AUC(0-∞) (GMR, 1.09; CI 0.97 - 1.24). Although the Emax of PT showed statistically significant reduction with food, the 90% CIs for Emax and AUE(0-48) of PT and aPTT were all contained within the bioequivalence range (0.80 - 1.25). CONCLUSIONS: These findings will allow the administration of R1663 without regard to food in the upcoming trials.

Verifying reference intervals for coagulation tests by using stored data.

OBJECTIVE: The purpose of the study was to verify the reference intervals for prothrombin time (PT) and activated partial thromboplastin time (APTT), using stored data of ambulatory pre-op subjects with exclusion of certain clinics, according to age and sex. MATERIALS AND METHODS: Results of test requests (13,600 PT and 14,083 APTT) of subjects aged 15?80 made from outpatient clinics of surgical departments before surgical interventions in 2008 were retrieved from the electronic medical record. Thromborel S and Actin (Dade Behring, Germany) were used on the Sysmex® CA-1500 coagulation analyzer. Extreme values were determined by using Horn's algorithm after Box-Cox transformation, and the upper and lower reference limits were determined as the 2.5th and 97.5th percentiles of the cleaned data. RESULTS: The values outside the interval of PT data 10.5-17.0 seconds and the interval of APTT data 20.6-35.8 seconds were excluded from the analysis. There were significant differences among age subsets of PT measurements ( p < 0.0001) and of APTT measurements ( p < 0.0001). Accordingly, the data were tested for gender differences and a significant difference was found in PT ( p = 0.002). APPT results did not differ statistically between men and women. CONCLUSION: Although we found values different from the limits stated in the kit insert, it would be better to confirm our findings with the direct method, especially in APTT for patients under the age of 40 and over the age of 59, and also for sex differences in PT.

Coagulation activation and fibrinolysis impairment are reduced in patients with anxiety and depression when medicated with serotonergic antidepressants.

AIMS: Anxiety disorders have been shown to be correlated with an activation of coagulation and impairment of fibrinolysis. The aim of the study was to assess whether medication with a serotonergic antidepressant, which has been associated with abnormal bleeding, may modify this effect. METHODS: Thirty-one anxiety patients, mostly with comorbid depression, and 31 healthy controls were included in the study. Group differences between anxiety patients medicated with a serotonergic antidepressant, patients without serotonergic antidepressant and controls were assessed for activated partial thromboplastin time, fibrinogen, factor VII, factor VIII, von Willebrand factor, von Willebrand ristocetin cofactor activity, prothrombin fragment 1 + 2, thrombin-antithrombin complex, d-dimer, α2-antiplasmin, plasmin-α2-antiplasmin complex (PAP), tissue plasminogen activator and plasminogen activator inhibitor. Intervening variables, such as age, sex, body mass index and smoking, were accounted for. RESULTS: We found lower coagulation measures for fibrinogen (P = 0.03) and plasminogen activator inhibitor (P = 0.01), and higher levels of PAP (P = 0.046) in patients with serotonergic antidepressant than in patients without serotonergic antidepressant. When controlling for smoking and body mass index, differences between the two groups were significant for PAP (P = 0.02), von Willebrand ristocetin cofactor activity (P = 0.02) and activated partial thromboplastin time (P = 0.046). Coagulation scores were similar in patients with serotonergic antidepressant to those of healthy controls. CONCLUSIONS: Serotonergic antidepressants may counteract a procoagulant effect of anxiety and/or depression in anxiety patients.

[Activated partial thromboplastin time prolongation in paediatrics. Retrospective monocentric study at the Nice University Hospital]. / Allongement isolé du temps de céphaline activé en pédiatrie. Étude rétrospective monocentrique au CHU de Nice.

UNLABELLED: The study of hemostasis often arises in paediatrics. Evidence of activated partial thromboplastin time (aPTT) prolongation sometime due to the presence of a circulating anticoagulant (antiphospholipid syndrome [APS]) may be embarrassing for the physician. AIM OF THE STUDY: To evaluate the prevalence of this situation, to identify the leading indicators and assess their impact. PATIENTS AND METHOD: All children aged 1 to 18 years old undergoing blood sample whatever was the reason, at the Nice University Hospital with existing isolated aPTT prolongation, were included. The assessment was completed by a mixing test, calculation of Rosner's index as well as the study of an APS and the measurement of factor VIII, IX, XI, XII. RESULTS: Between July 2006 and March 2008, 27 of 1845 children observed (1.5%) were selected for further study. Mean age was 6.17 years old. For 16 of the patients, aPTT prolongation was fortuitously discovered. Symptomatic subjects were older (9.8 vs. 5.2 years of age; P = 0.03). A significantly higher aPTT was indicative of an APS and predicted a positive Rosner Test outcome. A prolongated kaolin clotting time, observed among the younger subjects (3.45 vs. 8.88 years of age; P = 0.0011), was associated with a high aPTT prolongation (57.3 vs. 42.6s; P = 0.0009). CONCLUSION: In our study, the discovery of a prolongated aPTT is most often incidental and tends to occur during winter. The presence of a highly prolongated aPTT, abnormal kaolin clotting time and positive Rosner Test are strong predictors of the existence of an APS, especially in very young children. These antibodies are nonpathogenic and transitional.

Vitamin K2 (Menaquinone-7) supplementation does not affect vitamin K-dependent coagulation factors activity in healthy individuals.

BACKGROUND: Vitamin K has long been regarded as a procoagulant drug by physicians, and concerns have been raised with regard to its effects on hemostasis. Although many studies have shown that vitamin K supplementation is safe for thrombotic events, the effect of vitamin K supplementation on the activities of vitamin K dependent procoagulation factors in healthy individuals is not available. OBJECTIVES: This study aimed to investigate whether vitamin K2 supplementation at recommended doses affects the activity of vitamin K dependent procoagulation factors in healthy individuals without any anticoagulation treatment. DESIGN: Forty healthy volunteers between 25 and 40 years of age were recruited. Menaquinone-7 (MK-7) was administrated at 90 µg for 30 days. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and blood coagulation factors II, VII, IX, and X activities and Protein induced by vitamin K absence or antagonist-II (PIVKA-II) were measured on days 0 and 30 after MK-7 administration. RESULTS: PT, APTT, and TT showed no significant differences on day 30 when compared with baseline. The activities of coagulation factors II, VII, IX, and X on day 30 showed no significant differences with those at baseline. PIVKA-II levels were unchanged after 30 days of MK-7 supplementation. CONCLUSIONS: MK-7 supplementation at recommended dosage does not affect vitamin K-dependent coagulation factors' coagulation activity, and does not enhance the carboxylation of prothrombin in healthy individuals. This indicated that MK-7 administration does not alter hemostatic balance in healthy populations without anticoagulation treatment.

Analysis of Partial Thromboplastin Times in Patients With Pulmonary Embolism During the First 48 Hours of Anticoagulation With Unfractionated Heparin.

OBJECTIVE: The objective was to determine the proportion of patients with pulmonary embolism (PE) treated with unfractionated heparin (UFH) who achieved therapeutic activated partial thromboplastin time (aPTT) values within 48 hours of treatment. METHODS: Retrospective analysis of a PE response team (PERT) database was performed at a large, urban, academic teaching hospital. Inclusion criteria were adult patients with acute PE for whom the PERT was consulted and who received anticoagulation (AC) with UFH according to guideline standard dosing. aPTT values during 6-hour time periods during the first 48 hours of AC were collected and analyzed. RESULTS: A total of 505 patients met inclusion criteria. For patients receiving a bolus and infusion of UFH, the proportions (95% confidence interval [CI]) of patients in the therapeutic range were 19.0% (14.2% to 25.0%) at 12 hours, 26.3% (26.3% to 33.1%) at 24 hours, 28.3% (22.0% to 35.4%) at 36 hours, and 28.4% (20.8% to 37.5%) at 48 hours. For titrated infusion only, the proportions (95% CIs) of patients were 23.3% (16.2% to 32.3%) at 12 hours, 41.4% (31.6% to 51.9%) at 24 hours, 37.0% (26.8% to 48.5%) at 36 hours, and 42.1% (30.2% to 55.0%) at 48 hours. No patient had all therapeutic aPTT values. CONCLUSIONS: The majority of patients with acute PE spend most of their first 48 hours outside of the therapeutic range of AC when treated with guideline standard dosing of UFH. Over half of the patients fail to achieve any therapeutic PTT level within 24 hours of UFH initiation, and no patient had all therapeutic aPTTs. Future research should focus on identifying factors associated with achieving therapeutic AC with UFH.

Induction of hemodialysis with an arteriovenous fistula in a patient with hemophilia A.

An 88-year-old man with congenital hemophilia A developed end-stage renal disease due to microscopic polyangiitis. He was at risk for catheter-related infection because he was taking immunosuppressive agents for the treatment of polyangiitis. He was also unable to manipulate the peritoneal dialysis device. Therefore, hemodialysis using an arteriovenous fistula was induced for renal replacement therapy. Recombinant coagulation factor VIII (1000 IU) was administered via the venous chamber of the hemodialysis circuit 10 min before the end of each hemodialysis session, and nafamostat mesylate (25 mg/h) was employed as an anticoagulant during hemodialysis. His clotting factor VIII activity level increased to > 50% and activated partial thromboplastin time decreased to 50 s at the end of each hemodialysis session. This method allowed him to achieve hemostasis at the puncture site of the arteriovenous fistula and undergo stable hemodialysis with no complications, including bleeding. This case suggests that hemodialysis using an arteriovenous fistula with coagulation factor replacement and nafamostat mesylate in each hemodialysis session is a therapeutic option for end-stage renal disease in patients of advanced age with hemophilia at high risk of bleeding.

The abnormalities of coagulation and fibrinolysis in acute lung injury caused by gas explosion.

Acute lung injury (ALI) caused by gas explosion is common, and warrants research on the underlying mechanisms. Specifically, the role of abnormalities of coagulation and fibrinolysis in this process has not been defined. It was hypothesized that the abnormal coagulation and fibrinolysis promoted ALI caused by gas explosion. Based on the presence of ALI, 74 cases of gas explosion injury were divided into the ALI and non-ALI groups. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and platelet count (PLT) were collected within 24 hours and compared between the groups. ALI models caused by gas explosion were established in Sprague Dawley rats, and injuries were evaluated using hematoxylin and eosin (HE) staining and histopathological scoring. Moreover, the bronchoalveolar lavage fluid (BALF) was collected to examine thrombin-antithrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 (PAI-1) levels by enzyme-linked immunosorbent assay (ELISA). The patients in ALI group had shorter PT and longer APTT, raised concentration of FIB and decreased number of PLT, as compared to the non-ALI group. In ALI rats, the HE staining revealed red blood cells in alveoli and interstitial thickening within 2 hours which peaked at 72 hours. The levels of TAT/TF in the BALF increased continually until the seventh day, while the PAI-1 was raised after 24 hours and 7 days. The TFPI was elevated after 2 hours and 24 hours, and then decreased after 72 hours. Abnormalities in coagulation and fibrinolysis in lung tissues play a role in ALI caused by gas explosion.