In a randomized trial, patients with severe Covid-19 were assigned to receive either therapeutic-dose anticoagulation or usual-care pharmacologic thromboprophylaxis. At 21 days, therapeutic-dose ...anticoagulation did not improve hospital survival or the number of days free of cardiovascular or respiratory organ support.
In a randomized trial, patients with moderately severe Covid-19 were assigned to receive either therapeutic-dose anticoagulation or usual-care thromboprophylaxis. At 21 days, therapeutic-dose ...anticoagulation resulted in a higher probability of survival until hospital discharge without organ support.
Tranexamic acid (TXA) is used as a hemostatic adjunct for hemorrhage control in the injured patient and reduces early preventable death. However, the risk of venous thromboembolism (VTE) has been ...incompletely explored. Previous studies investigating the effect of TXA on VTE vary in their findings. We performed a propensity matched analysis to investigate the association between TXA and VTE following trauma, hypothesizing that TXA is an independent risk factor for VTE.
This retrospective study queried trauma patients presenting to a single Level I trauma center from 2012 to 2016. Our primary outcome was composite pulmonary embolism or deep vein thrombosis. Mortality, transfusion, intensive care unit and hospital lengths of stay were secondary outcomes. Propensity matched mixed effects multivariate logistic regression was used to determine adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) of TXA on outcomes of interest, adjusting for prespecified confounders. Competing risks regression assessed subdistribution hazard ratio of VTE after accounting for mortality.
Of 21,931 patients, 189 pairs were well matched across propensity score variables (standardized differences <0.2). Median Injury Severity Score was 19 (interquartile range, 12-27) and 14 (interquartile range, 8-22) in TXA and non-TXA groups, respectively (p = 0.19). Tranexamic acid was associated with more than threefold increase in the odds of VTE (aOR, 3.3; 95% CI, 1.3-9.1; p = 0.02). Tranexamic acid was not significantly associated with survival (aOR, 0.86; 95% CI, 0.23-3.25; p = 0.83). Risk of VTE remained elevated in the TXA cohort despite accounting for mortality (subdistribution hazard ratio, 2.42; 95% CI, 1.11-5.29; p = 0.03).
Tranexamic acid may be an independent risk factor for VTE. Future investigation is needed to identify which patients benefit most from TXA, especially given the risks of this intervention to allow a more individualized treatment approach that maximizes benefits and mitigates potential harms.
Therapeutic, level III.
Platelets are damage sentinels of the intravascular compartment, initiating and coordinating the primary response to tissue injury. Severe trauma and hemorrhage induce profound alterations in ...platelet behavior. During the acute post-injury phase, platelets develop a state of impaired ex vivo agonist responsiveness independent of platelet count, associated with systemic coagulopathy and mortality risk. In patients surviving the initial insult, platelets become hyper-responsive, associated with increased risk of thrombotic events. Beyond coagulation, platelets constitute part of a sterile inflammatory response to injury: both directly through release of immunomodulatory molecules, and indirectly through modifying behavior of innate leukocytes. Both procoagulant and proinflammatory aspects have implications for secondary organ injury and multiple-organ dysfunction syndromes. This review details our current understanding of adaptive and maladaptive alterations in platelet biology induced by severe trauma, mechanisms underlying these alterations, potential platelet-focused therapies, and existing knowledge gaps and their research implications.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In a randomized trial comparing antibiotic therapy with appendectomy in patients with appendicitis, antibiotics were noninferior on the basis of EQ-5D scores. In the antibiotics group, nearly 3 in 10 ...participants had undergone appendectomy by 90 days, and complications were more common, especially in those with an appendicolith.
Interpersonal violence (IPV) is highly prevalent in the United States and is a major public health problem. The emergence and/or worsening of chronic pain are known sequelae of IPV; however, not all ...those who experience IPV develop chronic pain. To mitigate its development, it is critical to identify the factors that are associated with increased risk of pain after IPV. This proof-of-concept study used machine-learning strategies to predict pain severity and interference in 47 young women, ages 18 to 30, who experienced an incident of IPV (i.e., physical and/or sexual assault) within three months of their baseline assessment. Young women are more likely than men to experience IPV and to subsequently develop posttraumatic stress disorder (PTSD) and chronic pain. Women completed a comprehensive assessment of theory-driven cognitive and neurobiological predictors of pain severity and pain-related interference (e.g., pain, coping, disability, psychiatric diagnosis/symptoms, PTSD/trauma, executive function, neuroendocrine, and physiological stress response). Gradient boosting machine models were used to predict symptoms of pain severity and pain-related interference across time (Baseline, 1-,3-,6- follow-up assessments). Models showed excellent predictive performance for pain severity and adequate predictive performance for pain-related interference. This proof-of-concept study suggests that machine-learning approaches are a useful tool for identifying predictors of pain development in survivors of recent IPV. Baseline measures of pain, family life impairment, neuropsychological function, and trauma history were of greatest importance in predicting pain and pain-related interference across a 6-month follow-up period. Present findings support the use of machine-learning techniques in larger studies of post-IPV pain development and highlight theory-driven predictors that could inform the development of targeted early intervention programs. However, these results should be replicated in a larger dataset with lower levels of missing data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUNDClotting factor abnormalities underlying acute traumatic coagulopathy are poorly understood, with application of traditional regression techniques confounded by colinearity. We hypothesized ...that principal components analysis (PCA), a pattern-finding and data reduction technique, would identify clinically predictive patterns in the complex clotting factor milieu after trauma. METHODSPlasma was prospectively collected from 163 critically injured trauma patients. Prothrombin; factors V, VII, VIII, IX, X; D-dimer; activated and native protein C; and antithrombin III levels were assayed and subjected to nonlinear PCA to identify principal components (PCs). RESULTSOf 163 patients, 19.0% were coagulopathic on admission. PCA identified 3 significant PCs, accounting for 67.5% of overall variance. PC1 identified global clotting factor depletion; PC2 the activation of protein C and fibrinolysis; and PC3 factor VII elevation and VIII depletion. PC1 score correlated with penetrating injury and injury severity, predicting coagulopathy (odds ratio OR, 4.67; p < 0.001) and mortality (OR, 1.47; p = 0.032). PC2 score correlated with injury severity, acidosis, and shock, and significantly predicted ventilator-associated pneumonia (OR, 1.59; p = 0.008), acute lung injury (OR, 2.24; p < 0.001), multiorgan failure (OR, 1.83; p = 0.002), and mortality (OR, 1.62; p = 0.006) but was not associated with international normalized ratio (INR)-based or partial thromboplastin time (PTT)-based coagulopathy (p > 0.200). PC3 did not significantly predict outcomes. CONCLUSIONPCA identifies distinct patterns of coagulopathy: depletion coagulopathy predicts mortality and INR/PTT elevation, while fibrinolytic coagulopathy predicts infection, end-organ failure, and mortality, without detectable differences in INR or PTT. While depletion coagulopathy is intuitive, fibrinolytic coagulopathy may be a distinct but often overlapping entity with differential effects on outcomes.
The vascular system – through its development, response to injury, and remodeling during disease – constitutes one of the key organ systems sustaining normal human physiology; conversely, its ...dysregulation also underlies multiple pathophysiologic processes. Regulation of vascular endothelial cell function requires the integration of complex signals via multiple cell types, including arterial smooth muscle, capillary and post-capillary pericytes, and other perivascular cells such as glial and immune cells. Here, we focus on the pericyte and its roles in microvascular remodeling, reviewing current concepts in microvascular pathophysiology and offering new insights into the specific roles that pericyte-dependent signaling pathways may play in modulating endothelial growth and microvascular tone during pathologic angiogenesis and essential hypertension.
Coagulopathy After Traumatic Brain Injury Laroche, Mathieu; Kutcher, Matthew E.; Huang, Michael C. ...
Neurosurgery,
06/2012, Letnik:
70, Številka:
6
Journal Article
Recenzirano
Abstract
Traumatic brain injury has long been associated with abnormal coagulation parameters, but the exact mechanisms underlying this phenomenon are poorly understood. Coagulopathy after traumatic ...brain injury includes hypercoagulable and hypocoagulable states that can lead to secondary injury by either the induction of microthrombosis or the progression of hemorrhagic brain lesions. Multiple hypotheses have been proposed to explain this phenomenon, including the release of tissue factor, disseminated intravascular coagulation, hyperfibrinolysis, hypoperfusion with protein C activation, and platelet dysfunction. The diagnosis and management of these complex patients are difficult given the lack of understanding of the underlying mechanisms. The goal of this review is to summarize the current knowledge regarding the mechanisms of coagulopathy after blunt traumatic brain injury. The current and emerging diagnostic tools, radiological findings, treatment options, and prognosis are discussed.
Extracorporeal membrane oxygenation (ECMO), a rescue therapy for pulmonary failure, has traditionally been limited by anticoagulation requirements. Recent practice has challenged the absolute need ...for anticoagulation, expanding the role of ECMO to patients with higher bleeding risk. We hypothesize that mortality, bleeding, thrombotic events, and transfusions do not differ between heparin-sparing and full therapeutic anticoagulation strategies in veno-venous (VV) ECMO management.
Adult VV ECMO patients between October 2011 and May 2018 at a single center were reviewed. A heparin-sparing strategy was implemented in October 2014; we compared outcomes in an as-treated fashion. The primary end point was survival. Secondary end points included bleeding, thrombotic complications, and transfusion requirements.
Forty VV ECMO patients were included: 17 (147 circuit-days) before and 23 (214 circuit-days) after implementation of a heparin-sparing protocol. Patients treated with heparin-sparing anticoagulation had a lower body mass index (28.5 ± 7.1 versus 38.1 ± 12.4, P = 0.01), more often required inotropic support before ECMO (82 versus 50%, P = 0.05), and had a lower mean activated clotting time (167 ± 15 versus 189 ± 15 s, P < 0.01). There were no significant differences in survival to decannulation (59 versus 83%, P = 0.16) or discharge (50 versus 72%, P = 0.20), bleeding (32 versus 33%, P = 1.0), thromboembolic events (18 versus 39%, P = 0.17), or transfusion requirements (median 1.1 versus 0.9 unit per circuit-day, P = 0.48).
Survival, bleeding, thrombotic complications, and transfusion requirements did not differ between heparin-sparing and full therapeutic heparin strategies for management of VV ECMO. VV ECMO can be a safe option in patients with traditional contraindications to anticoagulation.
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