The marker in question is prothrombin time activity, or PTA, a prothrombin-time result expressed as a percentage of normal activity. PTA reflects the extrinsic and common coagulation pathways rather than any single factor, and its interpretation depends on the analytical system, including the thromboplastin reagent and calibration used by each laboratory. In patients with ATAAD, preoperative coagulation abnormalities have previously been linked to disease severity and adverse outcomes. But the dissection process itself exposes tissue factor and activates coagulation and fibrinolysis before surgery, while cardiopulmonary bypass, hypothermia, circulatory arrest, operative trauma, hemorrhage, and transfusion all further perturb hemostasis. An abnormal result may reflect the presenting dissection, physiological stress, operative exposure, administered treatment, or a combination of these influences — which makes coagulation status both clinically relevant and difficult to summarize with a single measurement.

The research team, led by Hongle Yan, Xuejun Shen, Huozhen Weng, Weiping Li, and Shengli Yang, reasoned that serial PTA measurements might follow different longitudinal morphologies. Patients who begin with similar postoperative values may have arrived there from markedly different preoperative levels, and patients with comparable preoperative values may diverge after surgery. A single value cannot represent these paths. To capture them, the investigators turned to group-based trajectory modeling, a descriptive statistical framework for identifying latent groups of patients with similar within-person patterns, provided that the number and shape of groups are selected with attention to fit, classification, stability, parsimony, and clinical interpretability.

The study was a single-center retrospective cohort of consecutive adults with computed tomography angiography-confirmed ATAAD who underwent surgical repair between January 2021 and December 2023. Hospital records identified 1,002 patients with aortic dissection; 522 had Stanford type A dissection, 444 met the acute definition, and 285 surgically treated patients met clinical eligibility criteria. One was excluded because essential perioperative laboratory data were unavailable, leaving 284 patients in the final cohort. The dataset contained 4,037 PTA measurements, with a median of 12 measurements per patient. Fourteen patients died during postoperative days 0 through 7 and one was censored on postoperative day 6, leaving 269 patients observable immediately after postoperative day 7. One patient had insufficient longitudinal information for trajectory assignment, yielding a trajectory cohort of 268 patients contributing 1,895 observed values across the last-preoperative and postoperative-day-1-to-7 window.

The outcome-blind modeling identified four reproducible perioperative PTA trajectory groups. The moderate-stable group, comprising 87 patients or 32.5 percent, began with moderately reduced PTA and remained comparatively stable. The low-declining group, 50 patients or 18.7 percent, entered surgery with lower PTA and declined further. The preserved-rapidly-declining group, 61 patients or 22.8 percent, started at a relatively preserved level but showed a marked postoperative fall. The high-preserved group, 70 patients or 26.1 percent, maintained higher PTA throughout the observation window. Classification diagnostics were strong: entropy was 0.830, group-specific average posterior probabilities ranged from 0.897 to 0.922, and all 30 multistart fits reached the same optimum. Although a five-group model had marginally better information criteria, it added a level split and showed poorer bootstrap stability, with 23 unstable and three collapsed solutions among 200 successful repetitions compared with five unstable and no collapsed solutions for the four-group model. In a high-completeness subgroup of 235 patients, agreement with the primary four-group assignment was 98.7 percent.

Mortality analyses began immediately after postoperative day 7 to preserve temporal ordering between the exposure window and subsequent outcome — a landmark design that avoids immortal time bias. During follow-up, 27 deaths occurred among the 268 trajectory participants: 9 of 87 in the moderate-stable group, 11 of 50 in the low-declining group, 6 of 61 in the preserved-rapidly-declining group, and 1 of 70 in the high-preserved group. Kaplan-Meier cumulative mortality by postoperative day 365 differed globally across groups, with a log-rank P value of 0.00210. The estimated cumulative mortality was 10.5 percent in the moderate-stable group, 24.0 percent in the low-declining group, 10.0 percent in the preserved-rapidly-declining group, and just 1.4 percent in the high-preserved group. Trajectory group remained globally associated with subsequent mortality in the age- and sex-adjusted Cox model, with a global P value of 0.0322, and in a Firth-penalized sensitivity analysis designed to address sparse events, with a global P value of 0.0481.

But the story is more nuanced than a simple risk ranking. The high-preserved reference group contained only one death, making class-specific hazard ratios imprecise and unreliable. The investigators had prespecified a direct comparison between the two declining morphologies — the low-declining and preserved-rapidly-declining groups — after the trajectory solution was selected but before survival outcomes were examined. That comparison did not demonstrate a clear difference: the age- and sex-adjusted hazard ratio was 1.543 with a 95 percent confidence interval of 0.544 to 4.378, and the Firth hazard ratio was 1.503 with a confidence interval of 0.558 to 4.378. Both groups reached low PTA levels during the postoperative window, but they arrived there through different paths — one from an already reduced preoperative level and the other after a pronounced postoperative decline. This distinction illustrates how a longitudinal trajectory retains information about temporal morphology that a single postoperative measurement cannot fully represent, yet it does not establish different mortality tiers.

Perhaps the most sobering finding came from the incremental analysis. Adding the four-group trajectory classification to age, sex, and the last preoperative PTA did not meet the prespecified likelihood-ratio criterion, with a P value of 0.304 and a Firth penalized-likelihood P value of 0.380. Optimism-corrected performance differences between models with and without trajectory membership were small and uncertain: the difference in Harrell’s C statistic was 0.008 with a bootstrap interval spanning negative to positive values, and the difference in the area under the time-dependent curve at day 358 was less than 0.001. In other words, the last preoperative PTA already contained prognostic information that was not clearly augmented by trajectory-group membership in this sample. The simple PTA analyses reinforced this boundary: postoperative-day-1 PTA was associated with subsequent mortality, with a hazard ratio of 0.800 per 10 percentage points, but the preoperative-to-postoperative-day-1 change itself did not show clear incremental information beyond the preoperative value.

The clinical context of the trajectory groups was equally revealing. Aortic cross-clamp duration differed across groups, and Bentall procedures and mechanical valves were descriptively more frequent in the two declining trajectory groups than in the moderate-stable and high-preserved groups. Because mechanical-valve replacement entails a distinct postoperative antithrombotic context, the investigators refitted the trajectories after outcome-blind exclusion of mechanical-valve recipients. The broad four-pattern structure persisted among 197 patients, with high agreement with the primary assignment, although the rapid decline was attenuated. This indicates that the overall structure was not confined to mechanical-valve recipients, but it does not establish independence from postoperative antithrombotic treatment, because patient-level treatment exposure was unavailable. The trajectories are therefore best understood as composite perioperative patterns reflecting the combined influence of baseline disease state, anatomy, operative exposure, bleeding and transfusion, and postoperative treatment — not as discrete readouts of intrinsic coagulation biology.

The authors are candid about the study’s limitations. PTA was obtained during routine care rather than on a research-mandated schedule, and measurement frequency varied with early death, continuous renal replacement therapy, delayed sternal closure, and the intensity of intensive care — meaning the observation process may have been informative. A complementary flexible joint longitudinal-survival model that could have accommodated irregular measurements failed to meet predefined MCMC convergence criteria, so no association estimate from that model was reportable. Nonconvergence, the authors stress, should not be interpreted as evidence of no association. Residual confounding by baseline disease severity cannot be excluded, and external reproducibility remains to be established. The clinical implications are deliberately modest: characterizing perioperative PTA trajectories may provide a useful way to conceptualize heterogeneous longitudinal patterns and to structure postoperative reassessment or research stratification, but trajectory-group assignment requires observations through postoperative day 7 and is unavailable at surgery. The study did not evaluate a real-time classifier, treatment guidance, or PTA-guided anticoagulation. Prospective multicenter studies with standardized sampling, recoverable assay metadata, time-aligned treatment data, and sufficient events are needed before longitudinal PTA morphology can be considered for clinical implementation. Until then, the four trajectories stand as a hypothesis-generating map of the perioperative coagulation landscape — one that shows where patients travel, even if it cannot yet predict who survives the journey.

Subject of Research: Perioperative coagulation trajectories and mortality after acute type A aortic dissection repair

Article Title: Perioperative prothrombin time activity trajectories and subsequent mortality after surgical repair of acute type A aortic dissection

Article References: Yan, H., Shen, X., Weng, H., Li, W., & Yang, S. (2026). Perioperative prothrombin time activity trajectories and subsequent mortality after surgical repair of acute type A aortic dissection. Frontiers in Medicine, 13, Article 1885240. https://doi.org/10.3389/fmed.2026.1885240

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1885240

Keywords: acute type A aortic dissection, prothrombin time activity, group-based trajectory modeling, landmark analysis, cardiac surgery, coagulopathy, cardiopulmonary bypass, all-cause mortality, retrospective cohort study, Frontiers in Medicine, aortic repair, hemostasis

The analysis, led by Samuel G. J. Fodop of the Winners Foundation in Yaounde, Cameroon, and colleagues across Cameroon, Kenya, and the United States, pooled five randomized controlled trials encompassing 711 adult cardiac surgery patients. Of these, 363 patients — just over half — received prothrombin complex concentrate, or PCC, a sterile powder reconstituted into a small-volume infusion containing the four vitamin K-dependent clotting factors II, VII, IX, and X, along with regulatory proteins such as protein C and protein S in some formulations. The remaining 348 patients received fresh frozen plasma, the traditional mainstay used in more than 15 percent of cardiac surgeries in the United States. The researchers searched PubMed, Embase, and the Cochrane Central Register from inception to May 2025, registered their protocol prospectively on PROSPERO, and applied the Cochrane Risk of Bias 2 tool to every included trial.

The headline finding concerns reoperation for bleeding, one of the most dreaded complications after cardiac surgery. When operative techniques or transfusions fail to stop ongoing blood loss, surgeons must reopen the chest — a rescue maneuver that is not innocuous and adversely affects outcomes. In the pooled trials, 5.83 percent of PCC patients required reoperation compared with 8.53 percent of plasma patients, a 31 percent relative reduction with a risk ratio of 0.69 and a 95 percent confidence interval of 0.48 to 0.98. The p-value of 0.04 barely clears the conventional threshold for statistical significance, and the confidence interval narrowly excludes the null, but the estimate carries moderate certainty under the GRADE framework — the strongest rating any outcome received in the analysis. Notably, heterogeneity was zero, meaning the five trials told a consistent story on this endpoint.

Chest tube drainage, the volume of blood collected through tubes placed in the chest after surgery, also favored the concentrated clotting factors. Patients receiving PCC drained an average of 143.59 milliliters less over 24 hours than those receiving plasma, with a confidence interval ranging from 278.76 to 8.41 milliliters lower. That p-value of 0.04 again sits at the edge of significance, but the certainty rating is only low, downgraded for substantial heterogeneity — an I-squared of 69 percent — reflecting genuine differences between trials. The largest and most precise study, the FARES-II trial with 420 patients, used weight-based dosing of 15 to 25 international units per kilogram, while a smaller trial used a fixed low dose of 1,000 international units. When the researchers omitted the fixed-dose trial in a leave-one-out sensitivity analysis, the pooled estimate deepened to roughly 189 milliliters and heterogeneity fell, suggesting that insufficient dosing in larger patients may explain why that trial’s results diverged.

Red blood cell transfusion requirements, a proxy for how much blood patients actually lose, shifted by nearly one full unit in favor of PCC. The mean difference was 0.93 units lower, with a confidence interval of 1.83 to 0.02 units lower and moderate certainty. At the individual level, sparing a patient a single transfused unit may sound modest, but the researchers emphasize that cumulative savings across an institution or health system could be substantial — particularly in low- and middle-income countries where blood product availability is constrained. Every avoided transfusion also sidesteps the risks inherent to donated blood, including transfusion-related acute lung injury and transfusion-associated circulatory overload, the two adverse reactions most closely tied to plasma infusion.

Safety outcomes tell a more complicated story. Overall adverse events occurred in 87.53 percent of PCC patients versus 89.36 percent of plasma patients, a risk ratio of 0.99 with a confidence interval of 0.95 to 1.04 and zero heterogeneity — essentially no difference. All-cause mortality showed a slight numerical advantage for PCC at 3.20 percent versus 3.96 percent, but the confidence interval crossed the null and the certainty was low. Stroke or transient ischemic attack, acute kidney injury, length of intensive care unit stay, and length of hospital stay all showed no statistically significant differences, with certainty ratings ranging from low to very low. The one safety signal that raised eyebrows was thromboembolic events: PCC was associated with a 22 percent relative increase, at 9.32 percent versus 7.62 percent, though the confidence interval of 0.64 to 2.33 was wide enough to include both substantial harm and substantial benefit, and the finding was not statistically significant.

That thrombotic signal is precisely why the analysis matters beyond its pooled estimates. Concentrated clotting factors deliver a potent procoagulant payload in a small volume, and clinicians have long worried that this could tip patients toward strokes, heart attacks, or venous clots — especially those with mechanical prosthetic valves or recent coronary stents. The authors are careful to note that their GRADE-informed interpretation tempers the conclusions of an earlier meta-analysis by Viana and colleagues, which had suggested PCC could be used without increased thromboembolic risk. The new analysis argues that this conclusion overstated the certainty of the evidence, since the wide confidence interval does not rule out clinically important harm. The researchers also calculated that the current evidence base of 711 patients remains below the optimal information size of roughly 800 needed to reliably detect a 25 percent relative risk reduction in binary outcomes, underscoring that the field is still underpowered.

Methodologically, the analysis distinguishes itself from its predecessors in several ways. It restricted inclusion to randomized controlled trials only, eliminating the confounding that plagues observational comparisons. It incorporated the recently published FARES-II trial, expanding the pooled sample by 28 percent over the prior meta-analysis. It applied comprehensive GRADE certainty assessments to every outcome, performed leave-one-out sensitivity analyses with influence diagnostics, and used the contemporary Risk of Bias 2 tool rather than the older Cochrane instrument. Only one trial, by Smith and colleagues, raised some concerns — because randomization assignments were disclosed to study staff — while the remaining four were rated low risk across all five bias domains. Publication bias could not be formally assessed with fewer than ten studies, leaving open the possibility that unpublished negative trials exist.

The economics add a final layer of complexity. In a heart transplantation cohort, PCC cost a median of 4,949 dollars per patient compared with 3,677 dollars for those who did not receive it — a difference of roughly 1,272 dollars. In resource-limited settings where the concentrate may simply not be available, plasma remains the only viable option. Even in well-resourced centers, the authors conclude that the modest absolute benefits and uncertain safety profile do not support routine PCC use in every cardiac surgery patient. Instead, the evidence points toward selective deployment: patients with ongoing coagulopathic bleeding after bypass, those at risk of fluid overload from large plasma volumes, or those where the logistical advantages of a rapidly reconstituted, small-volume infusion outweigh the cost differential.

What emerges from this synthesis is a picture of cautious optimism rather than revolution. Prothrombin complex concentrate probably reduces the need to reopen the chest, likely drains less blood through chest tubes, and likely spares patients nearly a full unit of transfused red cells — all without a statistically detectable increase in death, stroke, kidney injury, or hospital stay. But the certainty behind most of these claims is low to moderate, the thrombotic question remains genuinely open, and the field needs adequately powered trials of several hundred additional patients before concentrated clotting factors can claim routine superiority over plasma. For now, the analysis offers clinicians a rigorous, nuanced map of what the randomized evidence actually shows — and a clear signal of where the next chapter of this debate must be written.

Subject of Research: Medicine

Article Title: Prothrombin complex concentrate versus fresh frozen plasma in patients undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials

Article References: Fodop, S. G. J., Bena Nnang, J. Y., Ahidjo, O. M., Nforngang, N. B. H., K. Mekontso, J. G., & Takow, S. (2026). Prothrombin complex concentrate versus fresh frozen plasma in patients undergoing cardiac surgery: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Anesthesiology, 5, Article 1843947. https://doi.org/10.3389/fanes.2026.1843947

Image Credits: AI Generated

DOI: 10.3389/fanes.2026.1843947

Keywords: cardiac surgery, prothrombin complex concentrate, fresh frozen plasma, coagulopathy, meta-analysis, transfusion medicine, cardiopulmonary bypass, bleeding, Prothrombin, complex, concentrate, versus

The collected studies span an unusually broad surgical landscape, from pediatric cardiac surgery to orthopedic and spine procedures, preoperative optimization, liver transplantation, and complex oncologic surgery. Taken together, they map the full arc of modern PBM: preserving red cell mass before surgery, limiting surgical and coagulopathic bleeding with topical and intravenous treatments, recognizing comorbidities that amplify bleeding risk, and understanding unforeseen postoperative transfusion hazards. Within established PBM programs, hemoglobin thresholds remain useful targets that can reduce transfusion practice at appropriate levels without causing adverse events. But the editorial is emphatic that thresholds alone are insufficient. They represent only a small subset of what works within the three pillars of PBM, and treating them as the whole strategy misses the point of the discipline.

One of the collection’s central reframings is temporal. Transfusion is not a single intraoperative event but the culmination of decisions made throughout the preoperative, intraoperative, and postoperative periods. Nowhere is this clearer than in pediatric cardiac surgery, where a review by Munlemvo examines the mechanisms of coagulopathy in neonates and infants undergoing cardiopulmonary bypass. In these smallest patients, bleeding and thrombosis arise from a delicate imbalance among thrombin generation, platelet activation, fibrinogen availability, antithrombin activity, and fibrinolysis. Because developmental hemostasis produces threshold values that may differ substantially from adult norms, the review argues that pediatric cardiac anesthesiologists need protocols reflecting the biology of developing hemostatic systems rather than simple adoption of adult transfusion triggers.

The same principle of mechanism-driven, patient-specific care applies to adults, where preoperative risk modification can act synergistically with transfusion triggers. A systematic review and meta-analysis by Chen and colleagues found that preoperative erythropoietin reduced both the rate of allogeneic transfusion and the average number of red cell units transfused in adult surgical patients. Critically, the analysis detected no significant differences in mortality, venous thromboembolism, infection, complications, or length of stay between treated and untreated groups. This does not circumvent the need for careful patient selection, thorough anemia evaluation, and vigilance for thrombosis, but it strengthens the case for treating correctable anemia before or during surgery whenever time and clinical context permit. The authors of the editorial note that such evidence also helps erode the lingering stigma surrounding erythropoietin and its perceived risks.

The orthopedic studies in the collection spotlight a problem that is often underappreciated in operating rooms: hidden blood loss. Song and colleagues demonstrated that hidden blood loss accounted for the majority of perioperative bleeding after total hip arthroplasty, and that hypertension, particularly grade 2 or grade 3 disease, was independently associated with greater loss. The implication is striking. Preoperative blood pressure control should be regarded not merely as a cardiovascular safety metric but as an active blood-conservation measure in its own right. Building on this theme, Zhao and colleagues showed that combining intravenous tranexamic acid with intra-articular fluid gelatin substantially reduced total blood loss in elderly patients with femoral neck fractures undergoing total hip arthroplasty, without an observed increase in thromboembolic or wound complications.

Spine surgery adds a complementary lesson about dosing schedules and the timing of antifibrinolytic therapy. In patients undergoing transforaminal lumbar interbody fusion, Ye and colleagues found that intravenous tranexamic acid followed by three days of oral therapy reduced total and hidden blood loss, postoperative drainage, length of stay, and transfusion rates compared with preoperative intravenous therapy alone. Extending the oral regimen to five days added no additional benefit, suggesting a plateau in effect. Together, the orthopedic and spine studies imply that blood management should be tailored not only to the operation being performed but also to the biology and timing of postoperative fibrinolysis, the natural process of clot breakdown that continues for days after tissue injury.

The two major abdominal surgery studies in the collection speak to the genuine complexity of transfusion-outcome associations. Wang and colleagues studied liver transplantation patients and found that intraoperative allogeneic transfusion was associated with acute kidney injury and in-hospital mortality before statistical matching. After propensity matching and multivariable analysis, however, transfusion was no longer an independent risk factor. This illustrates the difficulty of attributing causality to transfusion when confounders such as illness severity, anhepatic time, and the volume of surgical bleeding are in play, and it affirms that allogeneic transfusion remains a necessary measure when clinically appropriate. Li and colleagues reached a different conclusion in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, where higher intraoperative packed red blood cell volume was associated with poorer overall survival after propensity matching, plausibly reflecting the immunomodulatory effects of transfused blood.

The contrast between these two oncologic and transplant findings is instructive rather than contradictory. Transfusion should neither be reflexively blamed for every adverse outcome nor treated as a neutral exposure when cumulative red cell volume may correlate with modifiable bleeding, inflammatory burden, or surgical complexity. The editorial argues that these studies collectively demand context-aware interpretation of transfusion in high-acuity surgery, where the same unit of blood may be lifesaving in one scenario and a marker of escalating physiologic stress in another. Discerning the difference requires integrating transfusion data with the full clinical picture rather than reading it in isolation.

Across the seven papers, several priorities emerge for the next phase of PBM. First, programs should begin earlier, identifying anemia, uncontrolled hypertension, hypoalbuminemia, anticoagulant exposure, and procedure-specific bleeding risk well before the day of surgery. Second, intraoperative decisions should be guided by mechanism, with antifibrinolytic therapy, topical hemostatic strategies, coagulation testing with or without viscoelastic assays, and transfusion itself stratified according to the patient’s age, diagnosis, operation, and hemostatic phenotype. Third, postoperative surveillance should explicitly include hidden blood loss and anemia recovery. A shared clinical pathway can help multidisciplinary teams synthesize this information into timely, procedure-specific action rather than leaving each decision to individual improvisation.

The Research Topic also exposes significant evidence gaps in transfusion medicine. Many of the included studies are retrospective or single-center, and several evaluate pragmatic interventions in populations with narrow procedural or institutional contexts. Future trials, the editorial argues, should compare bundled, multimodal PBM pathways against usual care, report thrombotic, infectious, renal, functional, and patient-reported outcomes, and clarify definitive transfusion thresholds for children, older adults, patients with cardiovascular disease, patients with liver failure, and those undergoing major cancer surgery. Real-world implementation will be equally important, because a protocol that performs well under ideal clinical conditions may fail if screening, testing, blood availability, or multidisciplinary communication are unreliable. The ultimate message is one of calibrated precision rather than restriction. Optimal perioperative transfusion management is less about withholding blood and more about choosing the right intervention at the right moment. Blood products remain lifesaving when hemorrhage threatens oxygen delivery and organ perfusion, yet avoidable transfusion is itself a modifiable exposure. By connecting preoperative optimization, mechanism-based hemostasis, disciplined transfusion practice, and postoperative recovery metrics, perioperative teams can move closer to genuinely patient-centered blood management, achieving safer surgery through preservation of the patient’s own physiologic reserve.

Subject of Research: Perioperative blood transfusion management and patient blood management strategies across surgical settings

Article Title: Editorial: Perioperative blood transfusion management in the perioperative setting

Article References: Henderson, R. (2026). Editorial: Perioperative blood transfusion management in the perioperative setting. Frontiers in Anesthesiology, 5, Article 1971889. https://doi.org/10.3389/fanes.2026.1971889

Image Credits: AI Generated

DOI: 10.3389/fanes.2026.1971889

Keywords: patient blood management, blood transfusion, perioperative medicine, tranexamic acid, hidden blood loss, anemia, coagulopathy, orthopedic surgery, liver transplantation, erythropoietin, hemostasis, anesthesiology

The research team set out to answer a deceptively simple question: when the same critically ill child is assessed with different diagnostic criteria, does the label of DIC change, and does any particular scoring system do a better job of predicting which children will die? This question matters because the major diagnostic frameworks were developed in different eras, for different populations, and with different laboratory variables. The International Society on Thrombosis and Haemostasis overt DIC score, first proposed in 2001 and updated in 2021 and again in 2025, relies on routine coagulation tests such as platelet count, fibrin-related markers, prothrombin time and fibrinogen. The sepsis-induced coagulopathy score, or SIC, was designed as an earlier-warning system for the coagulopathy that precedes overt DIC in sepsis, while the Chinese DIC Scoring System emerged from multicenter studies of critically ill patients in China and incorporates a broader panel of hemostatic markers.

Using a cohort of 2,015 critically ill children, the investigators applied all five criteria to every patient and tracked how often each one flagged DIC, how well the different labels agreed with one another, and how strongly a positive diagnosis correlated with pediatric intensive care unit mortality. The results revealed a striking degree of divergence. Depending on which scoring system was used, the proportion of children classified as having DIC varied substantially, with the SIC-ISTH criteria consistently identifying the highest proportion of cases. In practical terms, this means that the same blood samples from the same children can yield dramatically different epidemiological pictures of DIC depending on the diagnostic lens applied, a finding that helps explain why published incidence rates for pediatric DIC have ranged so widely across the literature.

Agreement analysis added an important layer of nuance. The researchers found excellent agreement between the 2021 and 2025 versions of the DIC-ISTH criteria, suggesting that the recent international update did not fundamentally alter which children are classified as having overt DIC. Even more striking was the near-perfect agreement between the SIC-ISTH and SIC-China criteria, two scoring systems developed independently on different continents, and this consistency held across every clinical subgroup the team examined. For clinicians, this convergence is reassuring: it implies that the sepsis-induced coagulopathy concept is robust and that its two operational definitions are capturing essentially the same underlying physiological state, regardless of which side of the Pacific the score was calibrated on.

The prognostic performance of the criteria diverged sharply by clinical subgroup, and this is where the study delivers its most actionable message. Among children with sepsis, the SIC criteria outperformed the DIC criteria, showing both a higher area under the receiver operating characteristic curve and greater sensitivity for predicting PICU mortality. This finding fits the underlying biology: sepsis-induced coagulopathy is conceived as an early, still-compensated stage of the coagulation response to infection, and the SIC score was explicitly designed to catch this pre-overt phase before the full-blown consumptive coagulopathy of DIC takes hold. In septic children, catching the process early appears to translate directly into better discrimination between those who will survive and those who will not.

Among children with hematologic malignancies, however, the picture changed. In this subgroup, mortality rates and the sensitivity of mortality discrimination were comparable between the SIC and DIC criteria. This makes physiological sense as well, because children with leukemia and other blood cancers often have baseline abnormalities in platelet counts and coagulation parameters from their disease or its treatment, blurring the distinction between an early coagulopathy and established overt DIC. The finding suggests that for oncology patients, the traditional DIC scores retain their value and that a single sepsis-oriented screening tool cannot simply be transplanted across all critically ill populations without losing diagnostic precision.

Weaving these threads together, the authors arrived at a pragmatic recommendation: a combination of the SIC-ISTH criteria and the DIC-ISTH criteria should be used to screen for overt DIC in critically ill pediatric patients. The logic is a two-step screening strategy in which the highly sensitive SIC score serves as an early alarm for coagulopathy, particularly in septic children, while the DIC-ISTH framework confirms which of those children have progressed to overt DIC. This layered approach mirrors proposals in adult critical care, where experts have increasingly advocated sequential diagnosis of sepsis-associated coagulopathy, but the new study is among the first to validate such a strategy specifically in a large, heterogeneous pediatric cohort that includes both sepsis and hematologic malignancy subgroups.

The study also addresses a critical gap in pediatric critical care research more broadly. Diagnostic criteria for DIC were largely developed and validated in adults, and their pediatric applicability has long been uncertain because children differ from adults in baseline platelet counts, fibrinogen levels and the etiologies of critical illness. By systematically evaluating five established frameworks in more than two thousand children and reporting results across clinical subgroups, the researchers have given the field its clearest evidence yet about which tools transfer to pediatric practice and which do not. The work was funded by the National Natural Science Foundation of China and the Jiangsu Province Science and Technology Support Program, and the authors report no competing interests.

For the practicing intensivist, the immediate implications are concrete. Measuring the components of the SIC score in every septic child admitted to the PICU could identify, at an earlier stage, the subset at highest risk of progressing to overt DIC and death, creating a window for closer monitoring and earlier hemostatic intervention. At the same time, the substantial variation in incidence across criteria serves as a caution for researchers and guideline writers: any statement about how common DIC is in critically ill children is meaningless without specifying which diagnostic definition was used. As international societies continue to refine their definitions, as they did with the 2025 ISTH update, studies like this one provide the pediatric evidence base needed to ensure that those definitions actually work for the smallest and most vulnerable patients in the intensive care unit.

Beyond the immediate clinical takeaways, the study highlights a broader trend in critical care research: the recognition that coagulopathy is not a binary state but a dynamic continuum, evolving from subtle activation through compensated coagulopathy to full-blown consumptive DIC. The near-perfect agreement between the two SIC frameworks and the strong performance of early-warning scores in sepsis reinforce the idea that the most valuable diagnostic information often lies in the earliest, most treatable phase of the process. For children, whose physiological reserves are small and whose diseases progress quickly, that shift in focus from late confirmation to early detection could ultimately matter more than any single laboratory cutoff, and the combined SIC and DIC-ISTH screening strategy proposed by this study offers a practical roadmap for putting that principle into everyday pediatric practice.

Subject of Research: Comparison of five diagnostic criteria for disseminated intravascular coagulation in critically ill children

Article Title: Comparison of diagnostic criteria for disseminated intravascular coagulation in critically ill children

Article References: Chen, J., Li, X., Sun, Y., Fu, Y., & Chen, H. (2026). Comparison of diagnostic criteria for disseminated intravascular coagulation in critically ill children. Pediatric Research. https://doi.org/10.1038/s41390-026-05394-6

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05394-6

Keywords: disseminated intravascular coagulation, pediatric intensive care, sepsis-induced coagulopathy, ISTH criteria, SIC score, hematologic malignancies, PICU mortality, diagnostic criteria, coagulopathy, critical care, pediatric research, screening strategy

The core of the argument is deceptively simple. A platelet count tells you how many platelets are circulating, but says nothing about whether they work. Platelets contribute to hemostasis through adhesion, activation, granule release, aggregation, and support of thrombin generation, and none of these functions is captured by a routine count. Multiple studies have now documented profound platelet dysfunction in patients with traumatic brain injury even when their counts sit comfortably within the normal range. The authors define this dysfunction as a measurable impairment in agonist-induced aggregation, in the responsiveness of specific receptor pathways, or in the platelet’s contribution to whole-blood clot strength, occurring disproportionately to or entirely in the absence of thrombocytopenia. In other words, a patient can have plenty of platelets and still have platelets that fail.

The biological explanation lies in the unique nature of brain injury. When neural tissue is disrupted, it releases tissue factor, damage-associated molecular patterns, microparticles, and lipid mediators into the circulation, triggering thrombin generation, platelet activation, and ultimately receptor desensitization. The result is a paradoxical hemostatic state the authors describe as activation exhaustion: early procoagulant activation coexists with downstream hyporesponsiveness. Platelet activation and platelet dysfunction, far from being mutually exclusive, appear to be overlapping temporal phases of the same post-injury response. This may explain a frustrating clinical pattern in which patients with traumatic brain injury suffer early hemorrhagic progression of their intracranial lesions and later develop thrombotic complications, two seemingly opposite outcomes arising from the same underlying biology.

The strongest mechanistic evidence comes from a study by Castellino and colleagues, who examined 70 patients with isolated head injury, carefully excluding hemorrhagic shock, hypotension, and antiplatelet medication use. In severe traumatic brain injury, they found adenosine diphosphate, or ADP, pathway inhibition of 93.1 percent, with an interquartile range of 44.8 to 98.3 percent, compared with just 15.5 percent in controls, a difference that was highly statistically significant, and the arachidonic acid pathway was involved concurrently. A parallel rat model confirmed ADP inhibition of 77.6 percent, plus or minus 6.7 percent, just 15 minutes after injury. These findings establish that brain injury alone, independent of systemic hemodynamic compromise, generates profound receptor-level platelet dysfunction, a mechanism distinct from pharmacological blockade and from inhibition driven by circulating mediators.

Current clinical guidelines recommend maintaining platelet counts above 50 billion per liter in active intracranial hemorrhage and above 100 billion per liter around surgery. Those thresholds remain essential, the authors stress, but they address only quantity. A patient whose count is well above both limits may still harbor significant dysfunction at the level of the ADP/P2Y12 or arachidonic acid/cyclooxygenase-1 receptor pathways. The authors also warn against two opposite errors: equating thrombocytopenia with platelet failure, and treating any detected dysfunction as an automatic indication for transfusion. Their framework rests on three clinical questions: which phenotype is present, is it clinically meaningful, and can correcting it actually improve outcomes?

Detecting these phenotypes requires functional testing, and here the landscape is complicated. Standard coagulation tests, including prothrombin time, international normalized ratio, and fibrinogen measurement, are essentially blind to platelet function. Viscoelastic assays such as thromboelastography and rotational thromboelastometry assess whole-blood clot kinetics and strength, and platelet mapping modules add agonist-specific response data. Other platforms, including Multiplate, VerifyNow, and light transmission aggregometry, measure different biological parameters and cannot be directly compared with one another. Cross-platform equivalence in traumatic brain injury has not been established, and the most frequently cited working thresholds, ADP or arachidonic acid inhibition greater than 60 percent on thromboelastography with platelet mapping, were never prospectively validated. They represent observational approximations, not clinical standards, and no universally accepted intervention cutoffs exist for any platform.

The therapeutic evidence is strikingly discordant, and the authors argue that the discordance follows a pattern rather than being random. On the positive side, one retrospective series found that goal-directed platelet transfusion guided by platelet mapping in severe traumatic brain injury was associated with lower mortality, and a platelet mapping algorithm reduced transfusion exposure without apparent harm in patients exposed to antiplatelet drugs. Against this, multiple studies found no benefit and potential harm from empirical platelet transfusion or desmopressin in less severely injured populations or when treatment was not guided by functional testing. The positive studies were conducted in severe injury with documented profound dysfunction and function-guided decisions; the negative studies applied empirical treatment in milder populations. The lesson, the authors conclude, is that intervention should be phenotype-guided and risk-stratified, not routine and empirical.

The risks of getting this wrong are not trivial. Platelet transfusion carries the danger of transfusion-associated circulatory overload, transfusion-related acute lung injury, alloimmunization, and prothrombotic complications, while desmopressin, typically dosed at 0.3 to 0.4 micrograms per kilogram intravenously in structured protocols, can cause hyponatremia, fluid retention, and thrombosis. The authors frame their recommendation through the lens of patient blood management: the question is not whether platelets are good or bad, but whether a clinically relevant, modifiable phenotype exists in which intervention is likely to change meaningful outcomes. They propose a five-category taxonomy matching platelet-related phenotypes to clinical context, dominant mechanism, and therapeutic implication, while candidly noting that this construct is expert-synthesized and has not been prospectively validated as a diagnostic classification system.

The practical approach they sketch is deliberately cautious. Platelet function testing is most defensible in moderate-to-severe injury, traumatic intracranial hemorrhage, radiological progression, planned neurosurgery or invasive neuromonitoring, known preinjury antiplatelet exposure, systemic polytrauma with coagulopathy, or unexplained bleeding despite a normal count. When function is preserved, empirical reversal should generally be avoided. When dysfunction is documented in high-risk patients requiring surgery or invasive monitoring, desmopressin or platelet transfusion may be considered according to phenotype, antiplatelet exposure, count, and procedural urgency, with post-intervention reassessment by clinical status, imaging, and repeat functional testing. Centers without access to viscoelastic platforms can fall back on clinical risk stratification using the Glasgow Coma Scale, lesion subtype, antiplatelet exposure, and procedural urgency, consistent with American College of Surgeons guidance. In emergent surgical scenarios, urgency simply overrides testing; in nonemergent settings, a 30-to-60-minute window permits targeted hemostatic preparation.

The authors are explicit about the limits of their case. Most clinical evidence is observational, retrospective, or single-center; interassay discordance remains a fundamental barrier; dysfunction rarely occurs in isolation and overlaps with fibrinogen abnormalities, acidosis, hypothermia, hypocalcemia, and hemodilution; the dynamic evolution of dysfunction over the first 72 hours is poorly characterized; and findings from moderate-to-severe cohorts cannot be extrapolated to mild injury. Many studies report laboratory correction without demonstrating improved patient outcomes. What they call for is a new generation of prospective, multicenter trials to determine which assay best identifies clinically meaningful dysfunction, which threshold predicts hemorrhagic progression, and whether phenotype-guided correction improves neurological outcomes rather than merely normalizing laboratory values. In neurocritical care, they write, what is hidden beyond the platelet count may be clinically decisive, and the next step is not simply to transfuse more platelets but to understand which platelet phenotype matters, when it matters, and how it can be safely corrected.

Subject of Research: Platelet dysfunction as a hemostatic phenotype in traumatic brain injury coagulopathy

Article Title: Rethinking Platelet Dysfunction in Traumatic Brain Injury: From Platelet Count to Hemostatic Phenotype

Article References: Quintana Diaz, M., & Godoy, D. A. (2026). Rethinking Platelet Dysfunction in Traumatic Brain Injury: From Platelet Count to Hemostatic Phenotype. Neurocritical Care. https://doi.org/10.1007/s12028-026-02670-5

Image Credits: AI Generated

DOI: 10.1007/s12028-026-02670-5

Keywords: traumatic brain injury, platelet dysfunction, coagulopathy, hemostatic phenotype, thromboelastography, platelet mapping, platelet transfusion, desmopressin, intracranial hemorrhage, neurocritical care, patient blood management, P2Y12 pathway

The study team, led by Reza Zabihi of the Student Research Committee at Babol University of Medical Sciences together with colleagues from the university’s departments of internal medicine, social determinants of health, and infectious diseases research, designed the investigation as a matched-style comparison rather than a simple survey of liver patients. They enrolled 37 hospitalized COVID-19 patients with documented pre-existing chronic liver disease and selected 77 comparison patients who were hospitalized with confirmed COVID-19 but had neither chronic liver disease nor other documented chronic comorbidities. This deliberate selection of a relatively clean comparison group is analytically important: by stripping away diabetes, cardiovascular disease, and other common confounders, the researchers sought to isolate the contribution of liver pathology itself to COVID-19 outcomes, rather than the contribution of multimorbidity in general.

The demographic profiles of the two groups were closely aligned. The mean age in the chronic liver disease group was 57.03 years with a standard deviation of 13.85, while the comparison group averaged 55.05 years with a standard deviation of 14.42, a difference that did not reach statistical significance. This age matching matters because age is among the strongest predictors of severe COVID-19, and any meaningful gap in age distribution could have distorted the apparent effect of liver disease. Within the liver disease group, cirrhosis dominated the diagnostic landscape, accounting for 45.9 percent of cases, making advanced scarring of the liver the single most common underlying hepatic disorder among the affected patients.

The laboratory data revealed a striking biochemical signature distinguishing the liver disease cohort. Patients with chronic liver disease showed significantly higher serum levels of aspartate aminotransferase and alanine aminotransferase, the two canonical enzymes released when hepatocytes are injured, as well as elevated bilirubin, the pigment that accumulates when the liver’s processing capacity falters. Their prothrombin times were prolonged, indicating impaired synthesis of clotting factors by a struggling liver, and their blood urea nitrogen levels were elevated, a marker that can reflect dehydration, catabolic stress, or impaired renal perfusion, all common in decompensating cirrhotic patients. These differences were statistically significant at the conventional threshold of P less than 0.05, and together they paint a picture of patients whose hepatic reserve was already compromised before the viral infection added its own burden.

Clinical presentation also diverged between the groups in ways that carry practical implications for frontline physicians. Abdominal pain and confusion were reported more frequently among patients with chronic liver disease. Both symptoms are readily explicable by hepatic pathophysiology: abdominal pain can arise from portal hypertension, ascites stretching the peritoneum, or the capsular distension of an inflamed liver, while confusion in cirrhotic patients frequently signals hepatic encephalopathy, the neuropsychiatric syndrome caused when the failing liver fails to clear ammonia and other neurotoxic metabolites from the circulation. The overlap between encephalopathy and the confusion of severe COVID-19 hypoxia presents a genuine diagnostic challenge, and the study’s finding underscores that clinicians evaluating a confused COVID-19 patient with known liver disease must consider both mechanisms simultaneously.

The central result of the study concerns survival. After accounting for the comparison design, the researchers found that chronic liver disease was associated with higher odds of in-hospital mortality compared with the selected non-CLD comparison group. In other words, even against counterparts who were similar in age and free of other recorded chronic conditions, patients whose livers were chronically diseased died in the hospital at a meaningfully higher rate. This aligns with the mechanistic expectations that motivated the study in the first place. Patients with chronic liver disease are considered particularly vulnerable to COVID-19 because of immune dysregulation, chronic inflammation, and impaired metabolic function, a triad that leaves them less equipped to mount an effective antiviral response and more prone to the runaway inflammatory cascades that characterize severe disease.

The mechanistic plausibility of this vulnerability rests on well-characterized biology. The angiotensin-converting enzyme 2 receptor, which SARS-CoV-2 uses to enter cells, is expressed on cholangiocytes, the epithelial cells lining the bile ducts, providing a potential route for direct viral injury to the biliary tree and, indirectly, to hepatocytes. Beyond direct infection, the systemic inflammation of severe COVID-19, driven by elevated interleukin-6 and C-reactive protein, can precipitate decompensation in a cirrhotic liver that was already operating near its functional ceiling. The coagulopathy of COVID-19, marked by prolonged prothrombin times and elevated D-dimers in the sickest patients, compounds the baseline coagulation abnormalities of advanced liver disease, creating a convergent prothrombotic and prohemorrhagic hazard that neither condition alone would produce to the same degree.

Not every measured outcome differed between the groups, and the negative findings are themselves informative. The duration of hospitalization was statistically indistinguishable between patients with and without chronic liver disease, with a P value of 0.972, suggesting that among those who survived, the liver disease did not prolong the hospital stay in this cohort. The study also evaluated intensive care unit admission as an outcome, alongside demographic characteristics, clinical manifestations, laboratory parameters, and treatment outcomes, providing a broad clinical picture of how the two cohorts fared across the arc of their admissions. Analyses were performed using SPSS version 26, the standard statistical package for medical cohort studies of this scale.

The authors are careful to flag the boundaries of what their data can support. Because subgroup analyses according to cirrhosis status were not performed, no conclusions can be drawn from this cohort regarding the specific association between cirrhosis itself and clinical outcomes, even though cirrhosis was the most common underlying disorder among the liver disease patients. This is a meaningful limitation, since cirrhosis represents the extreme end of the chronic liver disease spectrum, and its specific contribution to COVID-19 mortality has been debated in the international literature. The single-center design at one hospital in Babol, and the modest sample size of 37 exposed patients, further counsel caution in generalizing the effect estimates to other populations and health care settings.

Nevertheless, the study’s practical message for clinicians is clear and actionable. A hospitalized COVID-19 patient with chronic liver disease should be recognized from the outset as belonging to a higher-risk category, warranting closer laboratory surveillance of transaminases, bilirubin, and coagulation parameters, a lower threshold for investigating altered mental status as possible encephalopathy, and heightened vigilance for the decompensation events, such as variceal bleeding, infection, and renal failure, that convert chronic hepatic disease into acute organ failure. The research was approved by the Ethics Committee of Babol University of Medical Sciences under code IR.MUBABOL.REC.1402.155, received no external funding, and was published open access on 6 October 2026, with the authors declaring no competing interests. As the pandemic’s legacy continues to be mapped across vulnerable populations, studies of this kind sharpen the clinical stratification tools that determine which patients need the most aggressive monitoring when SARS-CoV-2 arrives on the ward.

Subject of Research: The association between chronic liver disease and clinical outcomes, including in-hospital mortality, in patients hospitalized with COVID-19.

Article Title: Association of chronic liver disease with clinical outcomes and in-hospital mortality among hospitalized patients with COVID-19: a retrospective cohort study from Northern Iran

Article References: Zabihi, R., Abedi, S. H., Shirafkan, H., Dehpanah, A. A., Raei, A., Zebardast, A., & Yahyapour, Y. (2026). Association of chronic liver disease with clinical outcomes and in-hospital mortality among hospitalized patients with COVID-19: a retrospective cohort study from Northern Iran. Gut Pathogens. https://doi.org/10.1186/s13099-026-00888-4

Image Credits: AI Generated

DOI: 10.1186/s13099-026-00888-4

Keywords: COVID-19, chronic liver disease, cirrhosis, SARS-CoV-2, in-hospital mortality, clinical outcomes, retrospective cohort study, liver enzymes, hepatic encephalopathy, Iran, Gut Pathogens, coagulopathy

The birds in the study were not killed for research. All 24 cadavers arrived opportunistically between June 2022 and November 2023, a window that coincided with regional mouse infestations. Some were donated by the university’s Veterinary Teaching Hospital after being euthanised for medical reasons, while others were roadkill collected during unrelated fieldwork. Ten raptor species and one nightjar were represented, with Eastern Barn Owls dominating the sample at ten individuals, followed by three Australian Boobook Owls. Two Wedge-tailed Eagles, two Black-shouldered Kites, a Peregrine Falcon, a Powerful Owl, a Grey Goshawk, a Brown Goshawk, a Nankeen Kestrel, a Black Kite and a Tawny Frogmouth rounded out the list. Thirteen birds were male, ten female and one of undetermined sex; fourteen were adults and ten immature.

The analytical centrepiece of the study was liquid chromatography mass spectrometry, or LC-MS, performed at the CSIRO Ecosciences Precinct in Brisbane. Because decay alters the water content of tissue, the researchers homogenised and freeze-dried liver samples before extraction, then used a multi-step process involving formic acid, cold acetonitrile and lipid-removal cartridges to isolate the rodenticide residues. The instrument, an Agilent 6546 liquid chromatography quadrupole time-of-flight mass spectrometer, ran in a data-independent mode called quadrupole-resolved all-ions analysis, screening for eight rodenticides including warfarin, brodifacoum, difethialone, flocoumafen, bromadiolone, difenacoum, coumatetralyl and pindone. Calibration curves spanning 0.01 to 1,000 parts per billion achieved correlation coefficients between 0.9683 and 0.9971, and quality-control samples spiked with known concentrations of the compounds verified the method’s accuracy across low, mid and high ranges.

The results were striking. Thirteen of the 24 birds, just over half, tested positive for rodenticides registered for use in Australia. The most frequently detected compound was warfarin, a first-generation anticoagulant, found in eleven birds. Second-generation anticoagulants, which are far more toxic and persistent, also appeared: brodifacoum in three samples, difethialone in one and flocoumafen in one. Three birds carried warfarin alongside a second-generation compound, meaning they had been exposed to multiple poisons. Perhaps most telling, only six of the thirteen rodenticide-positive birds had rodent remains in their digestive tracts at the time of death. The researchers interpret this as evidence that the poisons can bioaccumulate in liver tissue over time, lingering from past meals of poisoned prey rather than reflecting a single recent exposure.

None of the detected concentrations reached the lethal dose thresholds established for other bird species. Brodifacoum levels in the Barn Owls and a Wedge-tailed Eagle fell below the reported oral LD50 range for owls of 0.15 to 9.68 milligrams per kilogram, and the difethialone concentration in the Tawny Frogmouth, 0.1 milligrams per kilogram, sat below the LD50 values of 0.26 to 23.4 milligrams per kilogram documented for Bobwhite, Japanese Quail and Mallard. Warfarin concentrations were similarly far below the 525 to 2,150 milligrams per kilogram lethal range reported for those same test species. But sublethal does not mean harmless. Second-generation anticoagulants are highly lipid-soluble and resist metabolic breakdown, and brodifacoum has been shown to cause persistent coagulopathy in birds for up to eleven days even at doses below the lethal threshold.

The clinical consequences of such exposure can be subtle but deadly. Birds suffering sublethal anticoagulant toxicosis have been documented to show lethargy, reduced agility and wing droop, impairments that degrade hunting performance and spatial navigation. For a fast-flying owl hunting at night, a momentary lapse in coordination can be fatal in a different way: collision with a vehicle. Twelve of the fifteen birds in the study showing traumatic injuries were found on roadsides, and the authors suggest that some of these roadkill birds may have been compromised by sublethal poisoning before they ever met a car. Peak coagulopathy after a single lethal ingestion typically occurs one to four days later, and after sublethal ingestion the effects may take even longer to manifest, widening the window of vulnerability.

Disentangling poisoning from trauma is one of the study’s central methodological challenges. Internal bleeding looks much the same whether it stems from a blunt impact or a drug-induced failure of the clotting cascade, and decomposition or scavenging can destroy clots that would otherwise distinguish the two. Ten birds showed haemocoelom, a coelomic cavity filled with uncoagulated blood, and in six of those there were no grossly obvious external signs of trauma such as fractures or lacerations. Yet only four of the ten haemocoelom cases were rodenticide-positive, and the statistical association between anticoagulant presence and postmortem evidence of coagulopathy was not significant. Alternative causes of bleeding disorders complicate the picture further: three birds carried low-burden apicomplexan parasites consistent with avian malaria, two had chronic enteritis with coccidian oocysts possibly of the genus Goussia, and heavy metal toxicity and bacterial infections such as salmonellosis can produce similar pathology in wild raptors.

One statistically significant pattern did emerge, and it concerned age. Immature birds were significantly more likely to carry higher brodifacoum concentrations than adults, a correlation with an f-value of 5.15 and a p-value of 0.03. The authors offer several non-exclusive explanations: inexperienced young hunters may target weakened, poisoned prey more readily; older birds may metabolise or eliminate the compound more efficiently or simply have longer intervals between exposures; or heavily affected juveniles may never survive to adulthood at all. The researchers caution, however, that the small sample size and a confidence interval hovering near zero mean the finding should be treated as a hypothesis generator rather than a settled conclusion. Species-level dietary differences add another layer of complexity, since rodent specialists such as Barn Owls and Black-shouldered Kites face theoretically higher exposure risk than bird-eating specialists like goshawks.

The conservation stakes extend beyond the species examined, all of which are currently listed as Least Concern by the International Union for Conservation of Nature. The Powerful Owl, despite its global status, numbers only an estimated 2,200 to 2,800 mature individuals, and the Grey Goshawk is estimated at fewer than 10,000 birds with a declining trend and Endangered classification in several Australian states. Sublethal poisoning that reduces foraging success, body condition and reproductive output, effects documented in vulture studies in the Pacific Northwest, could push such populations toward localised declines long before outright poisoning deaths register. Australian raptor populations remain poorly studied overall, making it difficult to assess how much hidden damage rodenticides are doing.

The study’s most policy-relevant finding may be its challenge to current Australian guidelines, which favour first-generation rodenticides such as warfarin over second-generation products on the assumption that they break down faster in rodents and pose less secondary risk. Warfarin was, after all, the most common residue in these Queensland birds. The authors point instead to coumatetralyl, another first-generation anticoagulant regarded as safer for predatory birds: mammals are generally more sensitive to it than birds, allowing lower effective doses, and while warfarin resistance has been documented in Australian rodents, no coumatetralyl resistance has yet been recorded there. The team calls for physiological studies of exposed raptors, rodent toxicity testing to track resistance, and surveys of rodenticide users to map what, how much and how often is being deployed. Until then, the poisons meant for mice appear to be quietly accumulating in the livers of the owls, eagles and falcons that share those fields, a debt the ecosystem may only now be beginning to itemise.

Subject of Research: Sublethal anticoagulant rodenticide exposure in deceased predatory birds in south-east Queensland, Australia

Article Title: Evaluating sublethal anticoagulant rodenticide exposure in deceased predatory birds of South-East Queensland, Australia

Article References: Low, Z., Murray, P. J., Naseem, N., McGilp, D., Doneley, B., Beale, D. J., Biggs, L., & Gonzalez-Astudillo, V. (2024). Evaluating sublethal anticoagulant rodenticide exposure in deceased predatory birds of South-East Queensland, Australia. Discover Toxicology, 1(1), Article 13. https://doi.org/10.1007/s44339-024-00016-4

Image Credits: AI Generated

DOI: 10.1007/s44339-024-00016-4

Keywords: anticoagulant rodenticides, raptors, owls, warfarin, brodifacoum, secondary poisoning, wildlife toxicology, LC-MS, Australia, Queensland, coagulopathy, conservation

The story began on 31 May 2023, when the girl’s grandmother brought her to a local health center with cough, runny nose, and fever. She was discharged with amoxicillin dispersible tablets, cetirizine syrup, and paracetamol tablets. What followed was a cascade of miscommunication. The prescription itself was barely legible and omitted critical details — the patient’s name, her age, and even the prescriber’s identity — making it impossible to tell whether the medication was intended for the child or the grandmother. The dispensing envelope the grandmother received simply abbreviated the drug as PCM, and she administered the tablets exactly as she understood the label: 1000 milligrams on the first day, 3000 milligrams on the second, and another 1000 milligrams on the third. The correct total for a child her age would have been roughly 1800 milligrams across the entire period.

Within days, the child’s condition deteriorated dramatically. A private facility diagnosed gastroenteritis and prescribed cotrimoxazole and promethazine, missing the true cause entirely. By 4 June, she arrived at Malindi Sub County Hospital with severe dehydration — sunken eyes, skin pinch lasting more than two seconds, reduced skin turgor — along with pneumonia, evidenced by crepitations and rapid breathing. She received aggressive rehydration with Ringer’s lactate, multiple antibiotics, and zinc supplementation. Then, at 5:30 in the evening, she began to convulse, requiring an intramuscular loading dose of phenobarbital. Even at this point, paracetamol poisoning was not on the diagnostic radar.

The turning point came the next morning, when clinicians took a more detailed history and asked the grandmother to present every medication given before admission. Medication reconciliation — the systematic process of comparing what a patient actually took against what was prescribed — revealed the overdose immediately. Liver function tests confirmed the suspicion with striking clarity: alanine aminotransferase peaked at 1566.2 IU/L, far above the 1000 IU/L threshold conventionally used to define hepatotoxicity, while aspartate aminotransferase reached 302.3 IU/L. Gamma-glutamyl transferase climbed steadily and albumin fell, painting a biochemical picture of an injured liver. The ALT-predominant pattern, with the two transaminases rising in near 1:1 proportion, is characteristic of paracetamol-induced liver injury and helped distinguish it from other causes of hepatic damage.

Then the resource limitations of the setting began to bite. Malindi Sub County Hospital did not stock N-acetylcysteine, the antidote that replenishes glutathione and neutralizes the toxic metabolite NAPQI responsible for paracetamol’s liver damage. Serum paracetamol levels, prothrombin time, and international normalized ratio — the standard laboratory tools for assessing poisoning severity and coagulation status — were simply unavailable. When clinicians attempted to place a nasogastric tube, the child’s nose began to bleed; oozing also appeared at her intravenous cannula site. These clinical signs of coagulopathy, combined with hypoalbuminemia, forced the team to act empirically, administering vitamin K and fresh frozen plasma without laboratory confirmation, a pragmatic departure from guidelines that caution against routine plasma use in pediatric liver failure.

Sourcing the antidote became an ordeal in itself. The nearest supply of N-acetylcysteine was 232 kilometers away in Mombasa, and the pharmacy there would only sell an entire pack of ten ampoules when the child needed just two or three. The family lacked coverage from the National Hospital Insurance Fund, Kenya’s universal health insurance scheme at the time, and the cost was beyond their means. Only when a well-wisher stepped in to pay was the antidote secured. The first infusion began at 9:00 pm on 6 June — roughly 80 hours after the last paracetamol dose, far beyond the traditional window in which the antidote is considered most effective.

What happened next surprised the clinical team. Despite the delay of more than 84 hours from initial exposure, the child’s liver enzymes began to fall rapidly after N-acetylcysteine therapy, with ALT dropping to 431.1 IU/L and AST to 105.6 IU/L within days. Several hours into the third infusion, she regained consciousness, fully oriented, with a Glasgow Coma Scale score of 15/15 and stable vital signs. She received fresh frozen plasma on alternate days to guard against hemorrhagic complications, along with supportive care including dextrose infusions, vitamins, and lactulose. By 14 June 2023, just ten days after the overdose began, she was discharged having made a full recovery.

The case, the authors argue, is less a story of individual negligence than of compounding system failures. Incomplete prescriptions and careless dispensing practices are well-documented drivers of medication errors, particularly when drugs are handed over without patient-specific information. Caregiver misunderstanding and poor communication compound the risk, especially when health literacy is low and the dispensed formulation — adult tablets, in this case — is inherently unsuitable for a toddler. Research has suggested that standardized dosing instruments, metric-unit labeling, and picture-based dosing instructions could substantially reduce these administration errors. The diagnostic delay also reflects a broader pattern: early paracetamol poisoning mimics common childhood illnesses like gastroenteritis, with vomiting and lethargy masking the underlying toxicity until the liver begins to fail.

The authors also emphasize a lesson that may resonate far beyond Kenya: even when N-acetylcysteine is given very late — more than 24 hours after exposure — it can still abrogate severe hepatotoxicity in children. This finding challenges the rigid therapeutic windows that dominate high-resource guidelines and offers hope for clinicians working where delayed presentation is the norm rather than the exception. At the same time, the case exposes uncomfortable truths about access to essential medicines in low- and middle-income countries, where antidote stockouts, bureaucratic procurement barriers, and absent insurance coverage can force families to depend on charity for life-saving treatment. The authors call on prescribers to write complete, legible prescriptions; on pharmacists to communicate clearly with caregivers of all literacy levels; and on hospital administrators to encourage enrollment in government-subsidized health coverage.

As a single-center case report, the account cannot be generalized to every setting, and the authors acknowledge this limitation candidly. Yet its value lies precisely in the detail: a near-legible prescription, a dispensing envelope, a grandmother doing her best with the information she was given, a hospital pharmacy without the antidote, and a 232-kilometer journey that stood between a child and survival. Paracetamol was first synthesized in 1878 and marketed in 1955, and its overdose potential was recognized soon after it reached the market. Half a century of research — from the glutathione-dependent mechanism of toxicity elucidated in the 1970s to the Rumack-Matthew nomogram and the Prescott protocol — has made paracetamol poisoning one of the most treatable toxicological emergencies in medicine. This Kenyan case is a reminder that the science is settled; what remains unfinished is the harder work of ensuring that the systems around the medicine, from the prescription pad to the pharmacy shelf, are built to protect the children who depend on them.

Subject of Research: Pediatric paracetamol poisoning caused by medication error and managed in a resource-limited Kenyan hospital

Article Title: A cautionary tale of pediatric paracetamol poisoning in a low-resource setting in Kenya: a case report and review of the literature

Article References: Mongi, A., Naji, S., Rasheed, Y., Mang’ong’o, D., & Okumu, M. (2026). A cautionary tale of pediatric paracetamol poisoning in a low-resource setting in Kenya: a case report and review of the literature. Discover Toxicology, 3(1), Article 6. https://doi.org/10.1007/s44339-026-00047-z

Image Credits: AI Generated

DOI: 10.1007/s44339-026-00047-z

Keywords: paracetamol, acetaminophen overdose, N-acetylcysteine, hepatotoxicity, pediatric poisoning, medication error, Kenya, resource-limited setting, liver function tests, coagulopathy, medication reconciliation, case report

The liver has long been considered the most difficult organ to transplant across species. Unlike the heart or kidney, whose failures can be bridged by dialysis or mechanical support, the liver performs hundreds of interlocking tasks: synthesising clotting factors and albumin, clearing toxins and ammonia, producing bile, and orchestrating immune surveillance through its unique sinusoidal vasculature. Previous pig-to-human attempts relied on auxiliary transplantation, in which the pig liver was added alongside the recipient’s own liver rather than replacing it, providing partial metabolic support without fully testing the xenograft’s capacity. Earlier work, including a 2024 case in which a gene-edited pig liver supported a patient for ten days, and a 2025 report of gene-modified pig-to-human liver xenotransplantation by the same Chinese group, demonstrated feasibility but left open the question of whether an orthotopic graft, placed where the human liver once sat, could sustain life-sustaining function on its own.

Central to the new study was the donor animal itself. The team used a pig engineered with six genetic modifications, or 6-GE, designed to blunt the three-pronged human immune attack on pig tissue. Three genes were knocked out: GGTA1, CMAH and B4GALNT2, which encode enzymes that decorate pig cell surfaces with carbohydrate antigens, including the galactose-alpha-1,3-galactose epitope, N-glycolylneuraminic acid and the Sd(a)-like antigen, against which humans carry preformed natural antibodies. Three human genes were added: CD46 and CD55, which regulate complement activation at the cell surface, and thrombomodulin (THBD), an anticoagulant protein that helps convert protein C to its activated form and dampens the inflammatory coagulation cascade. Polymerase chain reaction and Sanger sequencing confirmed the edits at the genomic level, and screening found no evidence of porcine endogenous retrovirus transmission or microchimerism in the recipient’s tissues during the observation window.

The recipient was a brain-dead individual, a model that allows researchers to evaluate xenograft function under genuine human physiology while respecting the ethical framework of organ donation. Brain death, however, is a double-edged sword: the dying brain triggers a storm of systemic inflammation and endothelial injury that can itself destabilise haemodynamics and complicate interpretation of graft outcomes. The surgical team performed the orthotopic transplant, removing the native liver and connecting the pig organ to the recipient’s portal vein, hepatic artery, hepatic veins and biliary system. Preoperative ultrasound confirmed that the diameters of the donor and recipient portal veins and hepatic arteries were compatible, a practical prerequisite that is far from trivial given the size and anatomical variability of both human and porcine vasculature.

Over 11 days of continuous monitoring, the xenograft demonstrated that a pig liver can execute core hepatic functions in a human host. The graft produced albumin continuously and generated bile with normal composition, findings that indicate functioning hepatocytes and an intact biliary epithelium, even though the absolute quantities remained below what a healthy human liver would deliver. Metabolomic analyses, deposited in a public database under accession OMIX017282, tracked the biochemical interplay between graft and host. Systemic haemodynamic stability was maintained throughout, meaning the recipient did not require escalating vasopressor support attributable to graft failure, and the pig liver did not provoke the catastrophic collapse that has historically accompanied cross-species organ transplants.

Yet the study is equally notable for what went wrong, and the authors are candid about it. Imaging and functional assessment revealed suboptimal hepatic perfusion arising from microthrombosis, the formation of microscopic clots within the graft’s sinusoidal vessels, which the researchers believe contributed substantially to the late-phase decline in hepatic function. Coagulation abnormalities emerged as progressive thrombocytopenia, a falling platelet count, alongside reduced activity of clotting factors. This pattern echoes the thrombocytopenia and coagulation dysregulation seen in pig-to-baboon liver transplants and in the landmark pig-to-human heart transplants, and it points to a fundamental incompatibility between pig endothelium and the human coagulation system that current genetic engineering has only partially resolved. The liver’s consumption of platelets and clotting factors, combined with impaired thrombomodulin-mediated protein C activation in the face of endothelial stress, appears to drive a vicious cycle of microvascular clotting and bleeding risk.

The immunological portrait drawn from histopathology was in some respects encouraging. Examination of biopsy and autopsy tissue found scant infiltration by T cells and B cells and minimal deposition of immunoglobulin G, suggesting that the adaptive immune response, the arm of immunity responsible for chronic cellular rejection, was largely held in check by the genetic modifications and the targeted immunosuppressive regimen. Instead, the dominant pathology was innate: prominent activation of innate immune cells and evidence of immunoglobulin M-mediated complement activation, the rapid, antibody-triggered cascade that has historically destroyed unmodified pig organs within minutes. That the classical hyperacute rejection was avoided, while a slower innate-driven injury emerged, marks a shift in the nature of the problem rather than its elimination.

The authors argue that these findings define the research agenda for the next phase of clinical translation. Endothelial damage, microthrombosis and coagulopathy now stand out as the critical challenges, and addressing them will likely require additional genetic modifications, such as further human anticoagulant and complement-regulatory transgenes, together with refined immunosuppressive protocols tailored to the liver’s distinctive immunology. The study also underscores the value of the brain-dead recipient model, which generates clinically relevant data without exposing a living patient to an unproven therapy, even as it cautions that the inflammatory milieu of brain death may exaggerate some forms of injury. Metabolomics, serial histology and comprehensive coagulation profiling of the kind reported here give transplant teams a granular, time-resolved picture of how a xenograft fails, information that no animal model can fully replicate.

For the field at large, the experiment represents a careful step forward rather than a breakthrough cure. Global shortages of donor livers leave millions of patients with end-stage liver disease facing limited options, and pig organs, which can be gene-edited, pathogen-screened and produced on demand, remain the most credible long-term solution. The demonstration that a six-gene-edited pig liver can sustain albumin and bile production and haemodynamic stability for 11 days in a human body, while the precise mechanisms of its gradual functional decline are documented at molecular resolution, converts xenogeneic liver transplantation from a speculative concept into an engineering problem with identifiable targets. Whether the next iteration of gene-edited donors and immunosuppressive strategies can extend graft survival from days to months, and ultimately to the years a clinical therapy would demand, will be decided by the coagulation and innate immune pathways this study has now brought into sharp focus.

Subject of Research: Orthotopic xenotransplantation of a six-gene-edited pig liver into a brain-dead human recipient

Article Title: Orthotopic liver xenotransplantation from gene-modified pig to decedent human

Article References: Tao, K., Yang, Z., Zhang, X., Zhang, H., Lin, Z., Yue, S., Yang, Y., Song, W., Wang, D., Liu, Z., Li, H., Chen, Y., Zhou, J., Ding, R., Sun, S., Yu, M., Li, J., Duan, W., Wang, Z., … Dou, K. (2026). Orthotopic liver xenotransplantation from gene-modified pig to decedent human. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-026-01797-2

Image Credits: AI Generated

DOI: 10.1038/s41551-026-01797-2

Keywords: xenotransplantation, pig liver transplant, gene-edited pigs, orthotopic liver transplantation, brain-dead recipient, microthrombosis, coagulopathy, complement activation, thrombocytopenia, albumin production, bile production, organ shortage

The review, led by Ali Msheik of Hamad Medical Corporation in Doha, Qatar, together with colleagues in trauma surgery, neurocritical care, and medical ethics, synthesized all available systematic reviews of viscoelastic hemostatic assays in neurocritical illness. These assays, which include thromboelastography known as TEG, TEG Platelet Mapping, and rotational thromboelastometry known as ROTEM, differ fundamentally from standard coagulation tests. Instead of isolating plasma and timing a single clotting reaction, they measure the actual physical behavior of clot formation in whole blood: how quickly the clot initiates, how strongly it propagates, how firm the final clot becomes, and how readily fibrinolysis breaks it down. In principle, this gives clinicians a real-time picture of hemostasis that standard tests cannot capture.

To assess the accumulated evidence, the researchers followed PRISMA 2020 reporting guidelines, the Joanna Briggs Institute manual for umbrella reviews, and MOOSE recommendations, searching PubMed, Embase, Scopus, the Cochrane Library, and Web of Science from database inception to January 2026. Two physician reviewers with experience in neurocritical care independently screened records, extracted data, and appraised methodological quality. The screening funnel was dramatic: of 272 records identified, 199 were screened after duplicate removal, and only four systematic reviews survived full-text assessment. The authors emphasized that this narrowing reflects the strict restriction to review-level evidence with reproducible methods and extractable neuro-specific data, not a post hoc reshaping of the question.

Those four reviews encompassed 73 study occurrences representing 63 unique primary studies, spanning traumatic brain injury, subarachnoid hemorrhage, and mixed populations with ischemic stroke and coronary artery disease. A corrected covered area analysis quantified how much the underlying evidence overlapped, finding only slight overall redundancy at 5.3 percent. Within traumatic brain injury, however, the two dedicated reviews shared 12 primary studies, a corrected covered area of 29.4 percent, while the subarachnoid hemorrhage and antiplatelet therapy reviews shared no studies with other clusters. This low overall overlap means the field is not merely recycling the same small trials, an encouraging sign for the maturity of the evidence base even as quality concerns remain.

The methodological appraisal revealed uneven rigor. Using AMSTAR-2, a validated tool for assessing systematic reviews, only one review, a 2021 meta-analysis of thromboelastography in traumatic brain injury by Cannon and colleagues, achieved moderate confidence, supported by a registered protocol, a comprehensive search, duplicate screening, and structured bias assessment. The remaining reviews earned low or critically low confidence ratings owing to absent protocols, incomplete reporting of excluded studies, and limited transparency. When the authors then applied GRADE criteria to rate certainty in individual outcomes, most estimates in traumatic brain injury and subarachnoid hemorrhage fell to low or very low certainty, a consequence of predominantly observational designs, inconsistent definitions, and imprecise effects.

Within those constraints, the prognostic signal was remarkably consistent. Across two reviews covering 32 unique studies in traumatic brain injury, viscoelastic assays repeatedly identified clinically relevant coagulation disturbances. Abnormal clot strength and disturbed fibrinolytic activity were associated with mortality across 18 observational studies, with radiographic hemorrhage progression in 14 studies, and with the need for neurosurgical intervention in nine, though confounding and heterogeneous outcome definitions limited those latter findings. In subarachnoid hemorrhage, a single review of 19 primary studies found that hypercoagulable profiles, particularly increased clot firmness, were consistently linked to delayed cerebral ischemia in six studies and to early brain injury severity in four. These associations make biological sense: dysregulated clot formation and breakdown plausibly contribute to secondary brain injury, hemorrhage expansion, and delayed ischemia after aneurysm rupture.

The therapeutic story was different. No review provided convincing evidence that viscoelastic-guided interventions improved outcomes in traumatic brain injury or subarachnoid hemorrhage, meaning the assays currently function as crystal balls rather than steering wheels in these conditions. The one bright spot came from mixed ischemic populations: moderate-certainty evidence from a meta-analysis of ten studies, including randomized trials, suggested that TEG-guided antiplatelet therapy in patients with ischemic stroke and coronary artery disease was associated with fewer composite ischemic and bleeding events than standard care. Mortality effects, however, remained uncertain because reporting was sparse and inconsistent, and because the population blended cardiac and cerebrovascular patients, the finding cannot be directly transferred to pure stroke care without further validation.

The authors are explicit about what this means for practice. Viscoelastic assays, they conclude, may be most appropriately used as adjunctive diagnostic and prognostic tools in neurocritical care rather than as standalone guides for transfusion or hemostatic treatment decisions in brain trauma and aneurysmal hemorrhage. The finding challenges a seductive assumption, one that has driven adoption in trauma and cardiac surgery, that simply identifying a coagulation disturbance and acting on it automatically improves outcomes. In the neurocritical setting, the leap from detection to benefit has not yet been demonstrated in rigorous trials, and current clinical guidelines accordingly do not recommend routine viscoelastic testing in these populations.

Several structural obstacles help explain the gap between prognostic promise and therapeutic proof. Included studies frequently came from single centers using institution-specific protocols, with inconsistent assay platforms, variable clinical cutoffs, and differing transfusion and antiplatelet practices. Without harmonized thresholds and standardized definitions of what counts as an actionable abnormality, clinicians cannot translate an abnormal tracing into a uniform treatment decision, and trialists cannot pool results meaningfully. These limitations reduce generalizability and complicate the interpretation of every association reported to date.

The research agenda that follows is clear. The authors call for large prospective neuro-specific cohorts using standardized viscoelastic thresholds, randomized trials testing VHA-guided transfusion or reversal strategies specifically in traumatic brain injury and subarachnoid hemorrhage, harmonization of assay parameters and clinical definitions, mechanistic studies linking viscoelastic abnormalities to neurovascular pathophysiology, and targeted evaluation of TEG-guided antiplatelet therapy in stroke populations alone. Until that work is done, the review suggests, clinicians and policymakers should read abnormal viscoelastic findings as important prognostic information, valuable for risk stratification and communication, while resisting the temptation to build treatment algorithms on evidence that has yet to bear their weight. For a technology that has already transformed hemostasis management in trauma and cardiac surgery, neurocritical care remains the unfinished frontier.

Subject of Research: Viscoelastic hemostatic assays for prognosis and treatment guidance in neurocritical illness

Article Title: The utility of viscoelastic hemostatic assays in neurocritical illness

Article References: Msheik, A., Peralta, R., Al-Rumaihi, G., Rizoli, S., Al Mokdad, Z., de Oliveira Manoel, A. L., & Al-Thani, H. (2026). The utility of viscoelastic hemostatic assays in neurocritical illness. Journal of Emergency and Disaster Medicine, 2(1), Article 10. https://doi.org/10.1007/s44467-026-00012-1

Image Credits: AI Generated

DOI: 10.1007/s44467-026-00012-1

Keywords: viscoelastic hemostatic assays, thromboelastography, ROTEM, traumatic brain injury, subarachnoid hemorrhage, ischemic stroke, coagulopathy, neurocritical care, umbrella review, antiplatelet therapy, delayed cerebral ischemia, GRADE evidence