Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study.

BACKGROUND: Unfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to investigate discrepancies between APTT and anti-Xa activity during UFH monitoring in critically ill patients and explore their underlying causes. METHODS: This study analyzed 271 pairs of laboratory test results from blood samples of 99 critically ill patients receiving continuous intravenous UFH. Theoretical APTT values were calculated using fitted curve equations from spiked sample measurements with anti-Xa activity. Samples were categorized into three groups based on the measurement of the APTT/theoretical APTT ratio: the lower group (< 80%), the concordant group (80-120%), and the upper group (> 120%). RESULTS: The overall concordance rate between APTT and anti-Xa activity was 45%, with a 55% discrepancy rate. The lower group frequently showed apparent heparin overdoses, while coagulation factor activities in the lower and upper groups were higher and lower, respectively, than those in the concordant group. Particularly, the lower group exhibited higher factor VIII activity levels than the upper and concordant groups. CONCLUSIONS: Discrepancies between APTT and anti-Xa activity were frequently observed, influenced by changes in coagulation factors activity levels. The lower and upper groups were classified as pseudo-heparin-resistant and coagulopathy types, respectively. Accurate monitoring of heparin in critically ill patients is crucial, especially in cases of pseudo-heparin resistance, where APTT values may wrongly indicate inadequate heparin dosing despite sufficient anti-Xa activity. Understanding these discrepancies is important for managing heparin therapy in critically ill patients. TRIAL REGISTRATION: Not applicable.

Delayed neurologic improvement and long-term survival of patients with poor neurologic status after out-of-hospital cardiac arrest: A retrospective cohort study in Japan.

AIM: To assess survival duration and frequency of delayed neurologic improvement in patients with poor neurologic status at discharge from emergency hospitals after out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective cohort study included OHCA patients admitted to two tertiary emergency hospitals in Japan between January 2014 and December 2020. Pre-hospital, tertiary emergency hospital, and post-acute care hospital data, were retrospectively collected by reviewing medical records. Neurologic improvements were defined as an improvement of Cerebral Performance Category (CPC) scores from 3 or 4 at hospital discharge to 1 or 2. The primary outcome was neurologic improvement after discharge, while the secondary outcome was survival time after cardiac arrest. RESULTS: Of all patients (n = 1,012) admitted to tertiary emergency hospitals after OHCA during the observation period, 239 with CPC 3 or 4 at discharge were included, and all were Japanese. Median age was 75 years, 64% were male, and 31% had initially shockable rhythms. Neurologic improvements were observed in nine patients (3.6%), higher in CPC 3 (31%) than CPC 4 (1.3%) patients, but not after 6 months from cardiac arrest. The median survival time after cardiac arrest was 386 days (95% confidence interval: 303-469). CONCLUSION: Survival probability in patients with CPC 3 or 4 was 50% at 1-year and 20% at 3-year. Neurologic improvements were observed in 3.6% patients, higher in CPC 3 than in CPC 4 patients. During the first 6 months after OHCA, the neurologic status may improve in patients with CPC 3 or 4.

The impact of relative hypotension on acute kidney injury progression after cardiac surgery: a multicenter retrospective cohort study.

BACKGROUND: Cardiac surgery is performed worldwide, and acute kidney injury (AKI) following cardiac surgery is a risk factor for mortality. However, the optimal blood pressure target to prevent AKI after cardiac surgery remains unclear. We aimed to investigate whether relative hypotension and other hemodynamic parameters after cardiac surgery are associated with subsequent AKI progression. METHODS: We retrospectively enrolled adult patients admitted to 14 intensive care units after elective cardiac surgery between January and December 2018. We defined mean perfusion pressure (MPP) as the difference between mean arterial pressure (MAP) and central venous pressure (CVP). The main exposure variables were time-weighted-average MPP-deficit (i.e., the percentage difference between preoperative and postoperative MPP) and time spent with MPP-deficit > 20% within the first 24 h. We defined other pressure-related hemodynamic parameters during the initial 24 h as exploratory exposure variables. The primary outcome was AKI progression, defined as one or more AKI stages using Kidney Disease: Improving Global Outcomes' creatinine and urine output criteria between 24 and 72 h. We used multivariable logistic regression analyses to assess the association between the exposure variables and AKI progression. RESULTS: Among the 746 patients enrolled, the median time-weighted-average MPP-deficit was 20% [interquartile range (IQR): 10-27%], and the median duration with MPP-deficit > 20% was 12 h (IQR: 3-20 h). One-hundred-and-twenty patients (16.1%) experienced AKI progression. In the multivariable analyses, time-weighted-average MPP-deficit or time spent with MPP-deficit > 20% was not associated with AKI progression [odds ratio (OR): 1.01, 95% confidence interval (95% CI): 0.99-1.03]. Likewise, time spent with MPP-deficit > 20% was not associated with AKI progression (OR: 1.01, 95% CI 0.99-1.04). Among exploratory exposure variables, time-weighted-average CVP, time-weighted-average MPP, and time spent with MPP < 60 mmHg were associated with AKI progression (OR: 1.12, 95% CI 1.05-1.20; OR: 0.97, 95% CI 0.94-0.99; OR: 1.03, 95% CI 1.00-1.06, respectively). CONCLUSIONS: Although higher CVP and lower MPP were associated with AKI progression, relative hypotension was not associated with AKI progression in patients after cardiac surgery. However, these findings were based on exploratory investigation, and further studies for validating them are required. Trial Registration UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm , UMIN000037074.

Fibrinolytic system activation immediately following trauma was quickly and intensely suppressed in a rat model of severe blunt trauma.

In severe trauma, excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate. However, in the first several hours after a blunt trauma, changes in fibrinolytic activation, suppression, and activation-suppression balance have not yet been elucidated, which the present study aimed to clarify. Anesthetized 9-week-old male Wistar S/T rats experienced severe blunt trauma while being placed inside the Noble-Collip drum. Rats were randomly divided into four groups of seven. The no-trauma group was not exposed to any trauma; the remaining groups were analysed 0, 60, and 180 min after trauma. Immediately following trauma, total tissue-plasminogen activator (tPA) levels significantly increased in the plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) significantly tipped toward fibrinolytic activation. After trauma, both tPA and PAI-1 levels increased gradually in various organs and active and total PAI-1 levels increased exponentially in the plasma. Total plasma tPA levels 60 min after trauma returned quickly to levels comparable to those in the no-trauma group. In conclusion, fibrinolytic activation was observed only immediately following trauma. Therefore, immediately after trauma, the fibrinolytic system was activated; however, its activation was quickly and intensely suppressed.

Simultaneous external validation of various cardiac arrest prognostic scores: a single-center retrospective study.

BACKGROUND: This study aimed to compare and validate the out-of-hospital cardiac arrest (OHCA); cardiac arrest hospital prognosis (CAHP); non-shockable rhythm, unwitnessed arrest, long no-flow or long low-flow period, blood pH < 7.2, lactate > 7.0 mmol/L, end-stage chronic kidney disease, age ≥ 85 years, still resuscitation, and extracardiac cause (NULL-PLEASE) clinical; post-cardiac arrest syndrome for therapeutic hypothermia (CAST); and revised CAST (rCAST) scores in OHCA patients treated with recent cardiopulmonary resuscitation strategies. METHODS: We retrospectively collected data on adult OHCA patients admitted to our emergency department between February 2015 and July 2018. OHCA, CAHP, NULL-PLEASE clinical, CAST, and rCAST scores were calculated based on the data collected. The predictive abilities of each score were tested using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: We identified 236 OHCA patients from computer-based medical records and analyzed 189 without missing data. In OHCA patients without bystander witnesses, CAHP and OHCA scores were not calculated. Although the predictive abilities of the scores were not significantly different, the NULL-PLEASE score had a large AUC of ROC curve in various OHCA patients. Furthermore, in patients with bystander-witnessed OHCA, the NULL-PLEASE score had large partial AUCs of ROC from sensitivity 0.8-1.0 and specificity 0.8-1.0. CONCLUSIONS: The NULL-PLEASE score had a high, comprehensive predictive ability in various OHCA patients. Furthermore, the NULL-PLEASE score had a high predictive ability for good and poor neurological outcomes in patients with bystander-witnessed OHCA.

Microparticles and Nucleosomes Are Released From Parenchymal Cells Destroyed After Injury in a Rat Model of Blunt Trauma.

We investigated the relationships between circulating procoagulants and trauma severity, including cellular destruction, and the effects of thrombin generation on procoagulants in a rat blunt trauma model. The rats were subjected to tumbling blunt trauma, where they were tumbled for 0, 250, 500, or 1000 revolutions. Creatine kinase, nucleosome, and microparticle plasma levels increased gradually with trauma severity. Strong interrelationships were observed among creatine kinase, nucleosome, and microparticle levels. Time to initiation of thrombin generation shortened with increasing trauma severity. In accordance with trauma severity, prothrombin activity decreased, but the thrombin generation ratio increased. Time to initiation of thrombin generation and the thrombin generation ratio correlated with creatine kinase levels. In an in vitro study, a homogenized muscle solution, which included massive nucleosomes and microparticles, showed accelerated thrombin generation of plasma from healthy subjects. Procoagulants, such as microparticles and nucleosomes, are released from destroyed parenchymal cells immediately after external traumatic force, activating the coagulation cascade. The procoagulants shorten the time to initiation of thrombin generation. Furthermore, although coagulation factors are consumed, the thrombin generation ratio increases.

Relationship Between Severity of Fibrinolysis Based on Rotational Thromboelastometry and Conventional Fibrinolysis Markers.

The association between severity of fibrinolysis, ascertained by rotational thromboelastometry to diagnose hyperfibrinolysis in patients with out-of-hospital cardiac arrest (OHCA), and conventional fibrinolysis markers (ie, tissue-plasminogen activator [t-PA], plasminogen, α2-plasmin inhibitor [α2-PI], and plasminogen activator inhibitor [PAI]) with key roles in the fibrinolytic system was investigated. This prospective observational study included 5 healthy volunteers and 35 patients with OHCA from the Hokkaido University Hospital. Blood samples were drawn immediately upon admission to the emergency department. Assessments of the extrinsic pathway using tissue factor activation (EXTEM) and of fibrinolysis by comparison with EXTEM after aprotinin addition (APTEM) were undertaken. Conventional coagulation and fibrinolysis markers were measured in the stored plasma samples. Significant hyperfibrinolysis observed in EXTEM disappeared in APTEM. Patients exhibited significantly higher levels of fibrinogen/fibrin degradation products, plasmin-α2-PI complex, and t-PA but lower levels of fibrinogen, plasminogen, and α2-PI than healthy controls. The PAI level was unchanged. Fibrinolytic parameters of EXTEM correlated with levels of lactate and conventional fibrinolysis markers, especially t-PA. Increased t-PA activity and decreased plasminogen and α2-PI significantly correlated with increased severity of fibrinolysis (hyperfibrinolysis).

Early administration of fibrinogen concentrate is associated with improved survival among severe trauma patients: a single-centre propensity score-matched analysis.

Background: Fibrinogen plays an important role in haemostasis during the early phase of trauma, and low fibrinogen levels after severe trauma are associated with haemostatic impairment, massive bleeding, and poor outcomes. Aggressive fibrinogen supplementation may improve haemostatic function, as fibrinogen levels deteriorate before other routine coagulation parameters in this setting. Therefore, we evaluated whether early administration of fibrinogen concentrate (FC) was associated with improved survival in severe trauma patients. Methods: This single-centre retrospective study evaluated patients with severe trauma (injury severity score ≥ 16) who were admitted to our emergency department between January 2010 and July 2018. The exclusion criteria included age < 18 years, cardiac arrest before emergency department arrival, cervical spinal cord injury not caused by a high-energy accident, and severe burn injuries. The FC and control groups included trauma patients who received and did not receive FC within 1 h after emergency department arrival, respectively. Propensity scores were used to balance the two groups based on the trauma and injury severity score (TRISS), heart rate at emergency department admission, and age. The primary outcome was the in-hospital survival rate. Results: The propensity scoring model had a c-statistic of 0.734, the Hosmer-Lemeshow chi-squared value was 7.036 (degrees of freedom = 8), and the non-significant p value of 0.533 indicated a good model fit. The propensity score matching created 31 matched pairs of patients, who had appropriately balanced characteristics. The FC group had a significantly higher in-hospital survival rate than the control group (log-rank p = 0.013). The FC group also used significantly higher amounts of red blood cells and fresh frozen plasma within 6 h after emergency department admission. However, the two groups had similar transfusion amounts between 6 and 24 h after emergency department admission. Conclusions: The present study revealed that early FC administration was associated with a favourable survival rate among severe trauma patients. Therefore, FC may be useful for the early management of trauma-induced coagulopathy and may improve outcomes in this setting.

Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients.

OBJECTIVE: This study aimed to test the hypothesis that coagulation, fibrinolytic markers and disseminated intravascular coagulation (DIC) score (International Society on Thrombosis and Haemostasis) at hospital admission of out-of-hospital cardiac arrest (OHCA) patients can predict neurological outcomes 1 month after cardiac arrest. METHODS: In this retrospective, observational analysis, data were collected from the Sapporo Utstein Registry and medical records at Hokkaido University Hospital. We included patients who experienced OHCA with successful return of spontaneous circulation (ROSC) between 2006 and 2012 and were transferred to Hokkaido University Hospital. From medical records, we collected information about the following coagulation and fibrinolytic factors at hospital admission: platelet count; prothrombin time; activated partial thromboplastin time; plasma levels of fibrinogen, D-dimer, fibrin/fibrinogen degradation products (FDP), and antithrombin; and calculated DIC score. Favorable neurological outcomes were defined as a cerebral performance category 1-2. RESULTS: We analyzed data for 315 patients. Except for fibrinogen level, all coagulation variables, fibrinolytic variables, and DIC score were associated with favorable neurological outcomes. In the receiver operating characteristic curve analysis, FDP level had the largest area under the curve (AUC; 0.795). In addition, the AUC of FDP level was larger than that of lactate level. CONCLUSIONS: All of the coagulation and fibrinolytic markers, except for fibrinogen level, and DIC score at hospital admission, were associated with favorable neurological outcomes. Of all of the variables, FDP level was most closely associated with favorable neurological outcomes in OHCA patients who successfully achieved ROSC.