A randomized,controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis

Introduction

To test the hypothesis that the administration of antithrombin concentrate improves disseminated intravascular coagulation (DIC), resulting in recovery from DIC and better outcomes in patients with sepsis, we conducted a prospective, randomized controlled multicenter trial at 13 critical care centers in tertiary care hospitals.

Methods

We enrolled 60 DIC patients with sepsis and antithrombin levels of 50 to 80% in this study. The participating patients were randomly assigned to an antithrombin arm receiving antithrombin at a dose of 30 IU/kg per day for three days or a control arm treated with no intervention. The primary efficacy end point was recovery from DIC on day 3. The analysis was conducted with an intention-to-treat approach. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) scoring system. The systemic inflammatory response syndrome (SIRS) score, platelet count and global markers of coagulation and fibrinolysis were measured on day 0 and day 3.

Results

Antithrombin treatment resulted in significantly decreased DIC scores and better recovery rates from DIC compared with those observed in the control group on day 3. The incidence of minor bleeding complications did not increase, and no major bleeding related to antithrombin treatment was observed. The platelet count significantly increased; however, antithrombin did not influence the sequential organ failure assessment (SOFA) score or markers of coagulation and fibrinolysis on day 3.

Conclusions

Moderate doses of antithrombin improve DIC scores, thereby increasing the recovery rate from DIC without any risk of bleeding in DIC patients with sepsis.

Trial registration

UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000882     

Hemostasis during the early stages of trauma: comparison with disseminated intravascular coagulation

Introduction

We tested two hypotheses that disseminated intravascular coagulation (DIC) and acute coagulopathy of trauma-shock (ACOTS) in the early phase of trauma are similar disease entities and that the DIC score on admission can be used to predict the prognosis of patients with coagulopathy of trauma.

Methods

We conducted a retrospective study of 562 trauma patients, including 338 patients whose data were obtained immediately after admission to the emergency department. We collected serial data for the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) DIC scoring system, and ACOTS was defined as a prothrombin-time ratio of >1.2.

Results

The higher levels of fibrin/fibrinogen degradation products (FDP) and D-dimer and greater FDP/D-dimer ratios in the DIC patients suggested DIC with the fibrinolytic phenotype. The DIC patients with the fibrinolytic phenotype exhibited persistently lower platelet counts and fibrinogen levels, increased prothrombin time ratios, higher FDP and D-dimer levels, and lower antithrombin levels compared with the non-DIC patients on arrival to the emergency department and during the early stage of trauma. Almost all ACOTS patients met the criteria for a diagnosis of DIC; therefore, the same changes were observed in the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels as noted in the DIC patients. The JAAM DIC score obtained immediately after arrival to the emergency department was an independent predictor of massive transfusion and death due to trauma and correlated with the amount of blood transfused.

Conclusions

Patients who develop DIC with the fibrinolytic phenotype during the early stage of trauma exhibit consumption coagulopathy associated with increased fibrin(ogen)olysis and lower levels of antithrombin. The same is true in patients with ACOTS. The JAAM DIC score can be used to predict the prognosis of patients with coagulopathy of trauma.     

Anticoagulation with a synthetic thrombin inhibitor after cardiovascular surgery and for treatment of disseminated intravascular coagulation

A synthetic thrombin inhibitor, MD-805, was used to anticoagulate 15 patients after cardiovascular surgery (CVS). A mean infusion rate of 0.71 +/- 0.1 (SD) microgram/kg . min maintained an activated coagulation time of about 150 sec in all patients, and significantly prolonged both activated partial thromboplastin time and prothrombin time. MD-805 was also administered to ten patients with disseminated intravascular coagulation (DIC), eight of whom had not responded to either heparin or gabexate mesilate (FOY), and eight of whom had circulating antithrombin III levels below 20 mg/dl. MD-805 therapy was successful in nine DIC patients. These results recommend MD-805 anticoagulant therapy after CVS and for treatment of DIC, especially when circulating levels of antithrombin III are low.     

d-Dimer in patients with suspected acute mesenteric ischemia

Objectives

The aims of this study were to assess the diagnostic value of d-dimer in patients with suspected acute mesenteric ischemia (AMI) and to evaluate the correlation between d-dimer levels and the severity of bowel necrosis.

Methods

A prospective, noninterventional study of 67 patients with clinical suspicion of AMI was performed. Measurement of d-dimer levels was performed using a latex turbidimetric method.

Results

Acute mesenteric ischemia was diagnosed in 23 patients (34.3%) and non-AMI in 44 patients (65.7%). Median d-dimer levels on admission were 6.24 μg fibrinogen equivalent units (FEU)/mL (range, 0.96-53.48 μg FEU/mL) in patients with AMI and 3.45 μg FEU/mL (range, 0.50-44.69 μg FEU/mL) in non-AMI patients (P = .064). d-Dimer had poor discriminative value to differentiate the presence from the absence of AMI with an area under the receiver operating characteristic curve of 0.64 (95% confidence interval, 0.50-0.78). A serum d-dimer cutoff value of 1.0 μg FEU/mL had a sensitivity of 96%, a specificity of 18%, a positive likelihood ratio of 1.17, and a negative likelihood ratio of 0.24. Among patients with AMI verified at operation, 8 had resectable bowl necrosis and 9 had unresectable bowel necrosis. There was no difference in serum d-dimer levels between resectable and unresectable bowel necrosis (P = .665).

Conclusions

Detection of serum d-dimer could not help to differentiate patient with AMI from those with non-AMI. We did not find a correlation between serum d-dimer levels and the severity of AMI. However, measurement of d-dimer levels can be of value for a small decrease in the likelihood of AMI, when the result is low.     

Magnitude of d-dimer matters for diagnosing pulmonary embolus

Objective

The objective of this study is to determine whether the magnitude of the d-dimer correlates with a higher likelihood of pulmonary embolus (PE).

Methods

We performed an electronic chart review at our academic, tertiary care center, annual emergency department (ED) census greater than 100 000. All patients with a chest computed tomographic (CT) scan with intravenous contrast and an elevated d-dimer level obtained in the ED between January 2001 and July 2008 were identified. Specific, predetermined, predefined data elements including sex, age, d-dimer level, and final ED diagnosis were recorded by a hypothesis-blinded extractor using a preformatted data form. d-dimer level less than 0.58 μg/mL constitutes the normal laboratory reference range for our turbidometric d-dimer assay. Data were analyzed using standard statistical methods, and a linear regression analysis was performed for correlation analysis of d-dimer and diagnosis of PE.

Results

We identified 544 subjects who had both a chest CT scan performed and an elevated d-dimer level obtained in the ED. Fifty-eight subjects (10.7%; mean d-dimer, 4.9 μg/mL) were diagnosed with PE, and 486 (89.3%; mean d-dimer, 2.0) did not have a PE. The percentages of PE diagnoses for d-dimers in the ranges 0.58 to 1.0, 1.0 to 2.0, 2.0 to 5.0, 5.0 to 20.0, and greater than 20.0 (n = 11) were 3.6%, 8.0%, 16.2%, 35.3%, and 45.5%, respectively. The positive predictive value of PE for d-dimer level cutoffs of greater than 0.58, greater than 1.0, greater than 2.0, greater than 5.0, and greater than 20.0 was 10.7%, 14.6%, 22.2%, 37.8%, and 45.5%, respectively. Increasing d-dimer values were strongly correlated with the presence of PE (odds ratio, 1.1685 per stratum; P < .001).

Conclusion

Increasing magnitude of d-dimer correlates with increasing likelihood of PE diagnosed by CT angiography.     

Can d-dimer become a new diagnostic parameter for acute appendicitis?

Introduction

In this study, we investigated d-dimer serum level as a diagnostic parameter for acute appendicitis.

Materials and Methods

Forty-nine patients were enrolled in the study. Patients were classified according to age; sex; duration between the beginning of pain and referral to a hospital or clinic; Alvarado scores; and in physical examination, presence of muscular defense, the number of leukocytes, preoperative ultrasonography, and d-dimer levels of histopathologic study groups were analyzed.

Results

Of the patients enrolled in the study, 26.5% were females and 73.5% males. The average age was 21 years (range, 16-38 years) and 81.7% acute appendicitis (AA). According the duration of pain, 63.2% of the patients were referred to the hospital within the first 24 hours, 26.5% of the patients were referred to the hospital within 24 to 48 hours, and 10.3% were referred to the hospital within a period of more than 48 hours. No statistically significant difference was determined regarding d-dimer levels between the histopathologic study groups (P > .05). Alvarado scores lower than 7 were found in 36.7% and 7 or higher in 63.3% of the patients. There was no statistically significant difference related with d-dimer levels between histopathologic study groups (P > .05). The ratio of cases with a number of leukocytes below the upper limit were determined respectively as 32.7% and 67.3%, and no statistically significant difference was found regarding d-dimer levels between histopathologic study groups (P > .05).

Conclusion

Increased d-dimer levels should not be considered as a diagnostic parameter in diagnosis of acute appendicitis.     

A decision analysis to determine a testing threshold for computed tomographic angiography and d-dimer in the evaluation of aortic dissection

Objective

The objective of this study is to determine at what probability of thoracic aortic dissection (TAD) to use a computed tomographic angiography (CTA) or a d-dimer test.

Methods

We used decision analysis software to determine the testing threshold (TT) for 3 hypothetical decisions when evaluating for TAD: (1) no testing vs CTA, (2) no testing vs d-dimer, and (3) CTA vs d-dimer. One- and 2-way sensitivity analyses were performed to determine which variables were drivers of the TTs.

Results

We found TTs of 0.03%, 0.013%, and 0.6% for decisions 1, 2, and 3, respectively. For all 3 decisions, patient age and the annual rate of cancer were major drivers of the TT. In decisions 1 and 2, the probability of acute renal failure requiring renal replacement therapy was a major driver, whereas d-dimer sensitivity was a major driver for decision 3.

Conclusion

The TTs for TAD are low and reflect the large mortality benefit from diagnosis and treatment when compared with the small risks of CTA. However, given the low prevalence of TAD (~ 0.05% among emergency department patients presenting with symptoms previously attributed to TAD), our results suggest that without high-risk features, clinicians should not order a CTA test for TAD. Depending on age, CTA should be considered for those patients with a disease probability greater than 0.3% to 2.1%, whereas d-dimer testing is appropriate in the range of pretest probabilities from 0.01% to 0.6%. Future studies should focus on clinical decision rules that place disease probabilities below, between, and above the calculated TTs.     

Computed tomography angiography in patients with suspected pulmonary embolism-too often considered?

Background

Pulmonary embolism (PE) is a major cause of morbidity and mortality associated with surgery and medical illnesses. In recent years, pulmonary computed tomography angiography (CTA) has become the diagnostic method of choice. However, it remains unclear when to perform CTA and how often a decision based on clinical judgment results in positive or negative findings.

Methods

In a retrospective study, 261 patients admitted for suspected PE were evaluated with pulmonary CTA. Decisions to order CTA were based on clinical judgment and optionally quantitative d-dimer assays. Clinical, radiologic, and laboratory data were revisited and compared in patients with and without proven PE.

Results

The patients' mean age was 63 ± 1 years; almost 30% of all participants had at least a moderately reduced renal function. Pulmonary CTA demonstrated PE in only 14.9%; both age and sex distribution was comparable in the PE and non-PE group. Proximal deep vein thrombosis or pathologic chest x-rays were significantly more likely in patients with PE (P < .001 and P < .05), whereas echocardiography results were comparable. d-dimer values were noticeably higher in the PE group (P < .001); however, C-reactive protein and troponin T levels were not helpful.

Conclusions

Pulmonary CTA confirmed PE in only a minority of patients and may be overused. Clinical judgment in conjunction with d-dimer evaluation was of limited help to predict positive results but surprisingly comparable with previous results using pretest probability scoring systems. Using present and previous data, a simplified enhanced algorithm is proposed to reduce use of CTA.     

Is protease inhibitor a choice for the treatment of pre- or mild disseminated intravascular coagulation?

OBJECTIVE: To investigate the effect of a protease inhibitor, gabexate mesylate, on patients with pre- or mild disseminated intravascular coagulation (DIC) in comparison with a control group receiving no anticoagulation therapy. DESIGN: Prospective, randomized, controlled study. SETTING: General intensive care unit at a general hospital. PATIENTS: Adult patients (40) with a DIC score between 6 and 8 (pre- or mild DIC). INTERVENTIONS: In 20 patients, gabexate mesylate (2 mg/kg/hr) was administered as 2 mL/hr in saline (treated group) and in another 20 patients, saline (2 mL/hr; control group) was administered during the study (7 days). MEASUREMENTS AND MAIN RESULTS: The following variables were determined at the time of admission to the intensive care unit before treatment and 1, 3, 5, and 7 days thereafter: platelet count, antithrombin III activity, serum or plasma concentrations of fibrinogen, fibrin degradation product, D-dimer, fibrin monomer, thrombin-antithrombin III complex, and plasmin-plasmin inhibitor complex, prothrombin time ratio, and DIC score. Two patients in the treated group and four in the control group were excluded from the study because they died during the study; therefore, 34 patients were analyzed. The measured variables of coagulation and fibrinolysis were not significantly different between the two groups, except for the D-dimer on day 3 (the treated group showed a higher concentration). D-dimer concentration and DIC score went down more quickly in the control group than the treated group, but not significantly. The mortality rate at 1 month was 40% (8 of 20) in the treated group and 35% (7 of 20) in the control group, without any differences between the two groups. CONCLUSIONS: In a limited number of patients (n = 34), gabexate mesylate (2 mg/kg/hr) could not inhibit coagulation or fibrinolysis and gabexate mesylate could not improve the DIC score or mortality rate in pre- or mild DIC.     

Combination of thrombin-antithrombin complex,plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study

Introduction

Current criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption of platelet and coagulation factors. To determine early diagnostic markers for severe coagulopathy, we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis.

Methods

A single-center, prospective observational study was conducted in an adult ICU at a university hospital. Plasma samples were obtained from patients with sepsis at ICU admission. Fourteen biomarkers including global markers (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrin degradation product (FDP)); markers of thrombin generation (thrombin-antithrombin complex (TAT) and soluble fibrin); markers of anticoagulants (protein C (PC) and antithrombin); markers of fibrinolysis (plasminogen, α₂-plasmin inhibitor (PI), plasmin-α₂-PI complex, and plasminogen activator inhibitor (PAI)-1); and a marker of endothelial activation (soluble E-selectin) were assayed. Patients who had overt DIC at baseline were excluded, and the remaining patients were followed for development of overt DIC in 5 days, and for mortality in 28 days.

Results

A total of 77 patients were enrolled, and 37 developed overt DIC within the following 5 days. Most patients demonstrated hemostatic abnormalities at baseline with 98.7% TAT, 97.4% FDP and 88.3% PC. Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC. Notably, TAT, PAI-1 and PC discriminated well between patients with and without developing overt DIC (area under the receiver operating characteristic curve (AUROC), 0.77 (95% confidence interval, 0.64 to 0.86); 0.87 (0.78 to 0.92); 0.85 (0.76 to 0.91), respectively), and using the three together, significantly improved the AUROC up to 0.95 (vs. TAT, PAI-1, and PC). Among the significant diagnostic markers for overt DIC, TAT and PAI-1 were also good predictors of 28-day mortality (AUROC, 0.77 and 0.81, respectively).

Conclusions

Severe coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC. A single measurement of TAT, PAI-1, and PC activity could identify patients with ongoing severe coagulopathy, early in the course of sepsis.     

Antithrombin III (AT) and recombinant tissue plasminogen activator (R-TPA) used singly and in combination versus supportive care for treatment of endotoxin-induced disseminated intravascular coagulation (DIC) in the neonatal pig

Background

Disseminated intravascular coagulation (DIC) is a pathological disturbance of the complex balance between coagulation and anticoagulation that is precipitated by vascular injury, acidosis, endotoxin release and/or sepsis and characterized by severe bleeding and excessive clotting. The innately low levels of coagulation factors found in newborn infants place them at extremely high risk for DIC. Anecdotal reports suggest that either anticoagulant or fibrinolytic therapy may alleviate some of the manifestations of DIC. To test the hypothesis that replacement of both anticoagulants and fibrinolytics may improve survival and outcome better than either single agent or supportive care alone, we utilized a neonatal piglet model of endotoxin-induced DIC.

Methods

DIC was induced in twenty-seven neonatal pigs (7 to 14 days of age) by intravenous administration of E. coli endotoxin (800 μg/kg over 30 min). The piglets were divided into 4 groups on the basis of treatment protocol [A: supportive care alone; B: Antithrombin III (AT, 50 μg/kg bolus, 25 μg/kg per hr continuous infusion) and supportive care; C: Recombinant Tissue Plasminogen Activator (R-TPA, 25 μg/kg per hr continuous infusion) and supportive care; D: AT, R-TPA and supportive care] and monitored for 3 primary outcome parameters (survival time, macroscopic and microscopic organ involvement) and 4 secondary outcome parameters (hematocrit; platelet count; fibrinogen level; and antithrombin III level).

Results

Compared with supportive care alone, combination therapy with AT and R-TPA resulted in a significant improvement of survival time, hematocrit, AT level, macroscopic and microscopic organ involvement, p < 0.05. Compared with supportive care alone, R-TPA alone significantly reduced macroscopic organ involvement and AT alone increased AT levels.

Conclusion

The findings suggest that combining AT, R-TPA and supportive care may prove more advantageous in treating the clinical manifestations of DIC in this neonatal pig model than either single modality or supportive care alone.     

Blood coagulation and fibrinolytic factors and their inhibitors in critically ill patients

In a search for new variables, for the diagnosis of disseminated intravascular coagulation (DIC) and for guidelines of therapy in such conditions, 22 severely ill patients were studied. The diagnosis of DIC was based on determinations of platelet counts, prothrombin complex (Normotest), antithrombin (AT), fibrinogen degradation products and fibrinogen. Nine patients were diagnosed as having DIC, eight patients were referred to a suspected DIC group and five to a group of no DIC. The laboratory findings were found to agree with the clinical status. In addition several new parameters were investigated: factor XII, prekallikrein, Simplastin A — another prothrombin complex factor method, factor X, plasminogen (PLG), antiplasmin (AP) and kallikrein inhibitors (KI). Platelet counts, prothrombin complex and antithrombin were mostly pathological in DIC-patients. Of the alternative tests prothrombin complex, fibrinopeptide A and the kallikrein inhibitor as well as the two tests for fibrinolysis (PLG and AP) were significantly altered in DIC-patients. The inhibitor capacity (AT, APV and KI) was lower in patients who died than in survivors and decreased still further in those of the non-survivors who had DIC. Thus the inhibitors can be used as predictors of outcome and hopefully for guiding therapy. To establish the diagnosis of DIC we suggest measurement of platelet count, prothrombin complex, plasminogen as well as of the inhibitors.     

Steps Per Day Among Persons With Multiple Sclerosis: Variation by Demographic,Clinical, and Device Characteristics

Objectives

To identify steps per day in a large sample of persons with multiple sclerosis (MS) and to describe variation by demographic and clinical characteristics and device type.

Design

Cross-sectional design.

Setting

General community.

Participants

Convenience sample of persons with multiple sclerosis (N=645) recruited from the general community who were ambulatory and relapse free for 30 days. Mean age ± SD of the participants was 46.3±10.6 years old. Participants were mostly women (85%), white (93%), and employed (64%).

Interventions

Not applicable.

Main Outcome Measure

Step counts measured by a motion sensor during a 7-day period.

Results

The average value for the entire sample was 5903±3185 steps per day. This value varied by demographic and clinical characteristics, but not device type, and indicated that men, participants who were unemployed, had a high school education or less, progressive MS, a longer disease duration, and higher disability were less physically active based on the metric of steps per day.

Conclusions

This study provides an expected value for average steps per day among persons with MS. Such an expected value for this population is an important first step to help researchers and clinicians interested in improving the overall health of persons with MS through physical activity promotion.     

Prognostic implication of initial coagulopathy in out-of-hospital cardiac arrest

Objective

We sought to investigate the prognostic implication of early coagulopathy represented by initial DIC score in out-of-hospital cardiac arrest (OHCA).

Methods

OHCA registry was analyzed to identify patients with ROSC without recent use of anticoagulant between 2008 and 2011. Patients were assessed for prehosptial factors, initial laboratory results and therapeutic hypothermia. Outcome variables were survival discharge, 6-month CPC and survival duration within the first week after ROSC. Logistic regression and Cox proportional hazards models were used for both univariable and multivariable analysis.

Results

Among 273 eligible patients, initial DIC score was available in 252 (92.3%). Higher DIC score was associated with increased inhospital death (odds ratio [OR], 1.89 per unit; 95% confidence interval [CI], 1.48–2.41) and unfavorable long-term outcome (6-month CPC 3–5; OR, 2.21 per unit; 95% CI, 1.60–3.05). The adjusted ORs for both outcomes were 1.61 (95% CI, 1.17–2.22) and 1.84 (95% CI, 1.26–2.67), respectively. We categorized DIC score in five groups as <3, 3, 4, 5 and >5 and analyzed differential mortality risk using Cox proportional hazards model. Compared with reference group (DIC score < 3), the adjusted HR for early mortality in each remaining group was 1.96 (95% CI, 1.13–3.40), 2.26 (95% CI, 1.27–4.02), 2.77 (95% CI, 1.58–4.85) and 4.29 (95% CI, 2.22–8.30), respectively (p-trend < 0.001). The area under the receiver operating characteristic of DIC score for prediction of unfavorable long-term outcome was 0.79 (95% CI, 0.69–0.88).

Conclusion

Increased initial DIC score in OHCA was an independent predictor for poor outcomes and early mortality risk.     

Gabexate mesilate and antithrombin III for intraoperative anticoagulation in heparin pretreated patients.

Thirty patients scheduled for elective myocardial revascularization and having undergone preoperative heparin treatment have been admitted to this prospective, randomized study. The aim of the study was to test two different strategies for preserving circulating antithrombin III (AT-III) during cardiopulmonary bypass. Patients in the control group (group C, n = 10) were treated with a standard heparinization (300 IU/kg). Patients in group A (n = 10) received the same management plus two doses of purified antithrombin III (1000 IU each). Patients in group GA received 200 IU/kg heparin and a continuous infusion of heparin (100 IU/kg/h) and gabexate mesilate (2 mg/kg/h) plus the same dose of antithrombin III as group A. Both group A and group GA demonstrated a preservation of circulating AT-III when compared to group C; this effect was more pronounced in group GA. The total heparin dosage was less in group GA than in groups A and C. Purified AT-III administration is recommended in heparin pretreated patients; the addition of gabexate mesilate to this protocol decreases the heparin requirement and increases the AT-III preservation.     

Recombinant human thrombopoietin improves platelet counts and reduces platelet transfusion possibility among patients with severe sepsis and thrombocytopenia: A prospective study

Introduction

Thrombocytopenia is prevalent in patients with severe sepsis, and it is associated with mortalities. Effectively adjunctive treatment might be needed to reverse low platelet counts (PCs). With a growing understanding of thrombocytopenia, recombinant human thrombopoietin (rhTPO) is considered a promising beneficial drug. The present study was dedicated to evaluate the efficiency of rhTPO in improving PCs in patients with severe sepsis.

Materials and Methods

We performed a prospective study in patients with severe sepsis between March 2012 and February 2013. All enrolled patients were divided into rhTPO group and control group, depending on whether rhTPO was prescribed or not. Platelet counts and other parameters were measured initially and in the following 15 days.

Results

Totally, 72 patients (38 in the rhTPO group and 34 in the control group) were included. All enrolled parameters exhibited no significant differences between groups at the baseline. Platelet counts showed a significant increase over time in both groups. Faster improvement of PCs in the rhTPO group was observed with a significant difference. Less platelet transfusion occurred in patients who received rhTPO in our study, as well. No drug-related adverse event during the rhTPO therapy was recorded.

Conclusion

The use of rhTPO in combination with conventional medical therapies could significantly improve the PCs in patients with severe sepsis and thrombocytopenia and effectively reduce the platelet transfusion possibility.     

Thrombin generation and fibrin clot formation under hypothermic conditions: An in vitro evaluation of tissue factor initiated whole blood coagulation

Background

Despite trauma-induced hypothermic coagulopathy being familiar in the clinical setting, empirical experimentation concerning this phenomenon is lacking. In this study, we investigated the effects of hypothermia on thrombin generation, clot formation, and global hemostatic functions in an in vitro environment using a whole blood model and thromboelastography, which can recapitulate hypothermia.

Methods

Blood was collected from healthy individuals through venipuncture and treated with corn trypsin inhibitor, to block the contact pathway. Coagulation was initiated with 5pM tissue factor at temperatures 37°C, 32°C, and 27°C. Reactions were quenched over time, with soluble and insoluble components analyzed for thrombin generation, fibrinogen consumption, factor (f)XIII activation, and fibrin deposition. Global coagulation potential was evaluated through thromboelastography.

Results

Data showed that thrombin generation in samples at 37°C and 32°C had comparable rates, whereas 27°C had a much lower rate (39.2 ± 1.1 and 43 ± 2.4 nM/min vs 28.6 ± 4.4 nM/min, respectively). Fibrinogen consumption and fXIII activation were highest at 37°C, followed by 32°C and 27°C. Fibrin formation as seen through clot weights also followed this trend. Thromboelastography data showed that clot formation was fastest in samples at 37°C and lowest at 27°C. Maximum clot strength was similar for each temperature. Also, percent lysis of clots was highest at 37°C followed by 32°C and then 27°C.

Conclusions

Induced hypothermic conditions directly affect the rate of thrombin generation and clot formation, whereas global clot stability remains intact.     

Disseminated intravascular coagulation is associated with the neurologic outcome of cardiac arrest survivors

Purpose

We aimed to examine the serial changes in coagulofibrinolytic markers that occurred after the restoration of spontaneous circulation (ROSC) in cardiac arrest patients, who were treated with targeted temperature management (TTM). We also evaluated the association between the disseminated intravascular coagulation (DIC) score and clinical outcomes.