The efficacy and associated bleeding complications of recombinant antithrombin supplementation among intensive care unit patients.

INTRODUCTION: The aim of this study was to evaluate the efficacy and complications of recombinant antithrombin (rAT) supplementation for adult patients with disseminated intravascular coagulation (DIC) compared with conventional plasma derived AT (pAT) treatment in the intensive care unit. MATERIALS AND METHODS: This study was performed in a single national university hospital in Japan. Adult patients from April 2015 to March 2016 with DIC were divided into two groups based on the type of AT agent used: the pAT group (n=24) and the rAT group (n=21). Patient demographics, medical history, diagnosis, blood tests, various clinical scores, AT activity, complications, and clinical outcome were collected and analyzed retrospectively. RESULTS: Significantly higher SIRS and APACHEII scores were confirmed in the rAT group than the pAT group. The initial dose of AT was significantly higher in the rAT group than in the pAT group. ATIII values before and after initial supplementation and during their ten-day clinical course were statistically similar between two groups. During the same period, 10 bleeding adverse events were found and there was no significant difference between both groups. Significantly more cases of the rAT group were administered with recombinant thrombomodulin concomitantly than those of the pAT group. Despite significantly more severe patients in rAT group, the clinical outcomes were the same in each group. CONCLUSIONS: Compared with pAT, the supplementation of rAT indicates clinical effectiveness without increasing the risk of bleeding complications in adult DIC patients with low AT activity.

Thromboelastometric analysis of the risk factors for return of spontaneous circulation in adult patients with out-of-hospital cardiac arrest.

It is well known that coagulopathy is observed in patients with out-of-hospital cardiac arrest (OHCA). Thrombolytic therapy for those patients has been controversial until now. The purpose of this study was to identify a significant predictor for return of spontaneous circulation (ROSC) of OHCA patients in the emergency department (ED) using whole blood viscoelastic testing. Adult non-trauma OHCA patients transported to our hospital that underwent thromboelastometry (ROTEM) during cardiopulmonary resuscitation between January 2013 and December 2015 were enrolled in this study. We divided patients into two groups based on the presence or absence of ROSC, and performed statistical analysis utilizing patient characteristics, prehospital data, laboratory data, and ROTEM data. Seventy-five patients were enrolled. The ROSC group and non-ROSC group included 23 and 52 patients, respectively. The logistic regression analysis, utilizing significant parameters by univariate analysis, demonstrated that lactate level [odds ratio (OR) 0.880, 95% confidence interval (CI) 0.785-0.986, p = 0.028] and A30 of EXTEM test [OR 1.039, 95% CI 1.010-1.070, p = 0.009] were independent risk factors for ROSC. The cut-off values of lactate and A30 in EXTEM were 12.0 mmol/L and A 48.0 mm, respectively. We defined a positive prediction for ROSC if the patient presented lower lactate level (<12.0 mmol/L) and higher A30 of EXTEM (≥48.0 mm) with high specificity (94.7%) and accuracy (75.0%). The present study showed that lactate level and ROTEM parameter of clot firmness were reliable predictors of ROSC in the ED for adult patients with OHCA.

Utility of Measurement of Serum Lactate in Diagnosis of Coagulopathy Associated with Peripheral Circulatory Insufficiency: Retrospective Evaluation Using Thromboelastometry from a Single Center in Japan.

Recently, serum lactate level rather than systolic blood pressure (sBP) has been widely used to diagnose peripheral circulatory insufficiency, which often leads to coagulopathy with systemic inflammation. However, most of the reported disorders were examined by plasma samples. The aim of this study was to evaluate the utility of serum lactate for detecting coagulopathy with circulatory failure by using thromboelastometry as well as standard coagulation test. 192 adult patients transported to our hospital between January 2013 and September 2014 were enrolled in this retrospective study. The sBP, serum lactate and thromboelastometry (ROTEM(®)) were measured in these patients in the emergency department. All patients were divided into three groups based on serum lactate levels: (1) the severe group (≥4 mmol/L, n=41); (2) the mild group (<4 mmol/L and ≥2 mmol/L, n=59); and (3) the normal group (<2 mmol/L, n=92). Patients in the severe group were of a significantly younger age but had lower pH and poor outcome. SBP was significantly lower and heart rates were higher in the severe group than in the other groups. Prolonged PT-INR and APTT were statistically confirmed in the severe group. ROTEM findings in the severe group revealed significantly lower alpha angle, shortened Lysis Onset Time and significantly more cases exhibited hyperfibrinolysis. The same analysis with the cut-off level of sBP at 90 mmHg showed no significant difference in ROTEM findings between the two groups. Abnormal serum lactate levels (≥4.0 mmol/L) properly reflected peripheral circulatory insufficiency and were more closely associated with coagulopathy such as hyperfibrinolysis and hypocoagulability than sBP.

The thromboelastometric discrepancy between septic and trauma induced disseminated intravascular coagulation diagnosed by the scoring system from the Japanese association for acute medicine.

The aim of this study is to evaluate the hematological differences between septic and traumatic disseminated intravascular coagulation (DIC) using the rotational thromboelastometry (ROTEM).This retrospective study includes all sepsis or severe trauma patients transported to our emergency department who underwent ROTEM from 2013 to 2014. All patients were divided into 2 groups based on the presence of DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We statistically analyzed the demographics, clinical characteristics, laboratory data, ROTEM findings (EXTEM and FIBTEM), and outcome.Fifty-seven patients (30 sepsis and 27 severe trauma) were included in primary analysis. Sepsis cases were significantly older and had higher systemic inflammatory response syndrome (SIRS) scores, whereas there were no significant differences in other parameters including Acute Physiology and Chronic Health Evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score. Twenty-six patients (14 sepsis and 12 severe trauma) were diagnosed with DIC. The Septic DIC (S-DIC) group was significantly older and had higher DIC scores than the traumatic DIC (T-DIC) group. Hematologic examination revealed significantly higher CRP, fibrinogen, lower FDP, DD, and higher FDP/DD ratio were found in the S-DIC group in comparison with the T-DIC group. ROTEM findings showed that the A10, A20, and MCF in the FIBTEM test were significantly higher in the S-DIC group. However, no statistical differences were confirmed in the LI30, LI45, and ML in EXTEM test.The plasma fibrinogen level and fibrinogen based clot firmness in whole-blood test revealed statistical significance between septic and traumatic DIC patients.

Effects of hyperbaric exposure on thrombus formation.

BACKGROUND: Hyperbaric oxygen (HBO2) therapy has a long history of use. However, its effect on thrombus formation is unclear. Many reports have indicated that it accelerates platelet aggregation, which suggests that it may increase thrombotic events. However, clinical trial results are inconsistent, and no previous reports have demonstrated that HBO2therapy does in fact increase thrombotic events. Here, we used a total thrombus formation analysis system (T-TAS) to analyze changes in thrombus formation in a specimen group exposed to constant hyperbaric pressure in vitro, and a control group. METHODS: Blood samples were collected from two sets of 10 healthy volunteers (mean age, 28.8 years) with no underlying disease. In the pressurized group, a constant pressure was applied to specimens in temperature-controlled test tubes; the non-pressurized group served as the control. Thrombus formation in samples from both the pressurized and control groups were measured using the T-TAS immediately, 20 minutes, and 40 minutes after pressurization. RESULTS: In the pressurized group, the onset of thrombus formation was significantly delayed, confirming a reduction in thrombus formation ability. However, the reduced ability for thrombus formation in the pressurized group recovered to the level of the control group. That is, the change in thrombus formation ability caused by pressure was proven to be reversible. CONCLUSIONS: We are the first to ascertain a decrease in the thrombus formation ability in specimens exposed to hyperbaric pressure using a T-TAS, which is capable of measuring thrombus formation in an environment similar to that in vivo.

[Anti DIC therapy].

A variety of disorders erratically activate coagulation cascades. The disseminated intravascular coagulation (DIC) is caused by unbalanced activation between coagulation and fibrinolysis. Some of auxiliary treatments for DIC on top of main therapy against causative disease are beneficial in terms of better outcome. The anticoagulation therapy is indicated when an activation of coagulation dominates in DIC caused by sepsis. Whereas in DIC associated with trauma, since balance between coagulation and fibrinolysis collapses drastically in a short period, both anticoagulantion therapy and antifibrinolytic therapy can be utilized depending on clinical conditions. There are quite a few of anti DIC agents in Japan. It is imperative to choose appropriate agents to treat DIC taking their pharmacological properties into account.

Can rotational thromboelastometry predict septic disseminated intravascular coagulation?

Rotational thromboelastometry (ROTEM), known as point-of-care testing, has been incorporated into various kinds of postsurgical management. However, the utility of ROTEM for rapid diagnosis of sepsis-induced disseminated intravascular coagulation (DIC) has not been investigated. This retrospective study includes 13 sepsis patients who underwent ROTEM in our emergency department in 2013. All patients were divided into two groups on the basis of the presence of DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We evaluated the demographics, clinical characteristics, laboratory data, ROTEM test and outcomes for each patient. The correlations between JAAM DIC score and significantly different parameters by univariate analysis and receiver operating characteristic (ROC) analysis were performed to assess the accuracy of the variables. There were seven and six patients in the DIC group and non-DIC group, respectively. The DIC group showed significantly longer prothrombin times, international normalized ratio of prothrombin time and clotting times (CTs) in the EXTEM test, and higher fibrinogen and fibrin degradation products and D-dimer. The CT in EXTEM test was correlated more with JAAM DIC score (r = 0.798), than the standard coagulation test. These parameters were accurate predictors in the diagnosis of septic DIC, with an AUC of 0.952, and a cut-off value of more than 46.0 s, resulting in a sensitivity of 100.0% and a specificity of 83.3%. CT in the EXTEM test was a single reliable indicator of sepsis-induced DIC diagnosed by the JAAM DIC score, and strongly associated with severity of DIC.

Usefulness of the endotoxin activity assay to evaluate the degree of lung injury.

PURPOSE: It has been reported that the Pulse Contour Cardiac Output (PiCCO) is very useful mainly in the field of intensive care and treatment to grasp the pathophysiological conditions of pulmonary edema because of its capability of obtaining data such as Pulmonary Vascular Permeability Index (PVPI) and Extra Vascular Lung Water (EVLW). Furthermore, a high degree of usability of various markers has been reported for better understanding of the pathological conditions in cases with septicemia. MATERIALS AND METHODS: The correlation between the cardiorespiratory status based upon the PiCCO monitor (EVLW and PVPI) and inflammatory markers including C reactive protein, procalcitonin (PC), and Endotoxin Activity Assay (EAA) were evaluated in 11 severe cases that required treatment with a respirator in an intensive care unit. RESULTS: The EAA values were significantly higher in patients with abnormal EVLW at 0.46±0.20 compared to the normal EVLW group at 0.21±0.19 (p=0.0064). In a similar fashion, patients with abnormal PVPI values tended to have higher PC levels at 18.9±21.8 compared to normal PVPI cases at 2.4±2.2 (p=0.0676). On the other hand, PVPI was significantly higher in the abnormal EAA group at 3.55±0.48 in comparison with the normal EAA group at 1.99±0.68 (p=0.0029). The abnormal EAA group tended to have higher PVPI values than the normal EAA group. CONCLUSION: The EAA is a measurement method designed to estimate the activity of endotoxins in the whole blood. Our results suggest that the EAA value, which had the greatest correlation with lung disorders diagnosed by the PiCCO monitoring, reflects inflammatory reactions predominantly in the lungs.

An Utstein-style examination of out-of-hospital cardiac arrest patients in Saga Prefecture, Japan.

INTRODUCTION: The Utstein-style guidelines have been used in various countries around the world, because they are suitable for evaluating regional emergency medical systems (EMSs) for patients who have an out-of-hospital cardiac arrest (OHCA). This report examined the present status of treating OHCA in Saga Prefecture and examined policies that can contribute to improving the rate of the return of spontaneous circulation (ROSC). METHODS: This study examined 800 cases of OHCA by means of the Utstein-style guidelines submitted for medical control verification by firefighting organizations in Saga Prefecture from July 1, 2010, to June 30, 2011. The firefighting organizations were divided into 5 areas (A-E) according to each medical classification. The 5 areas were compared in terms of the ROSC rate and background factors (patient age and sex, cardiac arrest cause, place, witnesses, initial electrocardiogram [ECG], hospital ECG, prehospital medical treatment, transfer time, oral instruction, and bystander cardiopulmonary resuscitation [CPR]). RESULTS: The ROSC rate was significantly lower in areas D (24.2%) and E (26.8%). Age, sex, cardiac arrest cause, place, witnesses, initial ECG, hospital ECG, shock, and adrenaline administration did not differ significantly among the 5 areas. The response time was significantly shorter in areas A (8: 25), D (8: 07), and E (8: 12). There were significantly fewer examples of oral CPR instruction in area E (42.1%), and there were fewer examples of CPR in areas A (44.0%), D (41.9%), and E (37.9%). CPR was performed by lay person in approximately 70% of the cases in which oral instructions were provided, but it was not performed in 90% of cases in which no oral instructions were provided. CONCLUSIONS: The Utstein-style guidelines were used to clarify differences in the ROSC rate in Saga Prefecture, thus making improvements in regional EMSs possible. Improvements in the quality of oral instruction and a reexamination of the oral instruction manual are expected to improve the ROSC rate, in parallel with education in basic life support for lay person and in advanced cardiac life support for medical personnel. In addition, it is important to reaffirm the effectiveness of CPR and encourage the participation of lay person by providing instructions by telephone from an ambulance that is en route to the scene.