Sepsis is a common and severe infectious disease, and its associated coagulation dysfunction can cause disseminated intravascular coagulation (DIC) and organ failure, leading to a significant increase in mortality. Pyroptosis is a form of programmed cell death mediated by caspase-1 in the classical pathway and caspase-4/caspase-5/caspase-11 in the non-classical pathway, along with the effector molecule gasdermin (GSDM) family. Recent studies have shown that pyroptosis plays an important role in the development of coagulation disorders in sepsis. Pyroptosis leads to the formation of cytoplasmic membrane pores, cell swelling and membrane rupture, as well as the release and enhanced activity of procoagulant contents, strongly promoting the development of systemic coagulation activation and DIC in sepsis. Therefore, exploring the role and molecular mechanisms of pyroptosis in sepsis-related coagulation disorders is of great significance for the prevention and treatment of sepsis. This article provides a review of the mechanisms involved in pyroptosis and coagulation disorders in sepsis, as well as the role and mechanisms of pyroptosis in sepsis-associated coagulation disorders to provide new ideas for sepsis related research.

OBJECTIVE: To analyze the laboratory phenotype and genetic variants of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein (PK) and High molecular weight kininogen (HMWK) deficiency and explore their molecular pathogenesis.
METHODS: A PK deficiency pedigree (10 individuals from 4 generations) and a HMWK deficiency pedigree (6 individuals from 3 generations) which were admitted to the First Affiliated Hospital of Wenzhou Medical University on December 3, 2021 and June 16, 2022, respectively were selected as the study subjects. Clinical data of the two pedigrees were collected, and the related coagulation indexes of the probands and their family members were determined. Genomic DNA of the two pedigrees was extracted from peripheral blood samples. All of the exons and flanking sequences of the KLKB1 and KNG1 genes of the probands were analyzed by direct sequencing. And the corresponding sites were sequenced among other family members. Bioinformatic software was used to analyze the conservation of variation sites and the effect of variant on the protein function.
RESULTS: The plasma PK activity of proband 1, a 29-year-old female, and her brother were extremely low (< 1.0%). Proband 2 was a 66-year-old male with extremely low plasma HMWK activity (< 1.0%). Genetic sequencing revealed that the proband 1 and her brother had both harbored a homozygous c.417_418insCATTCTTA (p.Arg140Hisfs*3) insertional variant in exon 5 of the KLKB1 gene. Proband 2 had harbored a homozygous c.460C>A (p.Pro154Thr) missense variant in exon 4 of the KNG1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively rated as pathogenic (PVS1+PM2_Supporting+PM4) and likely pathogenic (PS4+PM2_Supporting+PP3+PP4).
CONCLUSIONS: The c.417_418insCATTCTTA (p.Arg140Hisfs*3) variant of the KLKB1 gene and the c.460C>A (p.Pro154Thr) variant of the KNG1 gene probably underlay the decreased PK and HMWK activities in the two pedigrees, respectively.

Diesel inhalation poisoning represents a rare yet critical medical condition necessitating prompt medical attention due to its potential to induce severe respiratory distress and coagulation dysfunction. The present case study describes the distinctive clinical presentation of a male patient in his early 40s who experienced acute respiratory distress and manifested coagulation factor VII deficiency subsequent to unintentional inhalation of diesel oil during engine repair. The patient demonstrated symptoms including chest tightness and dyspnea, indicative of chemical aspiration pneumonia, alongside an unforeseen coagulation abnormality. Treatment involved rigorous intervention, comprising endotracheal intubation, mechanical ventilation, and administration of pharmacotherapy, including ambroxol, dihydroxypropylline, and methylprednisolone. Moreover, procedural measures, such as repeated bronchoscopic alveolar lavage, pathogen culture, and targeted antibiotic therapy, were employed to mitigate respiratory complications. The patient\'s clotting disorder was treated with blood transfusions, and he was discharged with improvement. The present case highlights the imperative nature of immediate medical intervention in instances of diesel inhalation to avert further clinical deterioration and unfavorable outcomes. Additionally, it underscores the necessity for expanded research endeavors aimed at elucidating the indirect repercussions of diesel inhalation on the coagulation cascade, an area that remains relatively underexplored within the medical literature.

BACKGROUND: Trauma induced coagulopathy remains to be an important cause of high transfusion requirements and mortality and shock induced endotheliopathy (SHINE) has been implicated.
METHODS: European multicenter observational study of adult trauma patients with injury severity score ≥ 16 arriving within 2 h from injury to the trauma centers. Admission blood samples obtained were used for analysis of the SHINE biomarkers (syndecan-1, soluble thrombomodulin, adrenaline) and extensive analysis of coagulation, -and fibrinolytic factors together with collection of clinical data. Hierarchical clustering of the SHINE biomarkers was used to identify the SHINE phenotypes.
RESULTS: The 313 patients clustered into four SHINE phenotypes. Phenotype 2, having the highest glycocalyx shedding, encompassing 22% of the whole cohort, had severe coagulopathy with lower levels of prothrombin, FV, IX, X, XI and severe hyperfibrinolysis with higher plasmin - alpha 2-antiplasmin (PAP) - and tPA levels and lower alpha2 - antiplasmin levels. This phenotype had significantly higher transfusion requirements and higher mortality (39% vs. 23%, 15% and 14%) but similar injury severity score (ISS) compared to the others phenotypes.
CONCLUSIONS: Hierarchical clustering identified four SHINE phenotype in a cohort of trauma patients. Trauma induced coagulopathy was confined to only one of the SHINE phenotypes, encompassing 22% of the total cohort. This phenotype was characterized by severe hypocoagulability and hyperfibrinolysis, which translated to significantly higher transfusion requirements and higher mortality compared to the other SHINE phenotypes with similar injury severity, warranting further investigation.

BACKGROUND: Vitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent factors (VKDFs), resulting in higher factor (F)II levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents.
OBJECTIVE: To evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK.
METHODS: We retrospectively assessed consecutive cases from 2002 to 2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as international normalized ratio correction/improvement of ≥0.5 after VK.
RESULTS: Two hundred ninety-two patients (males, 58.2%; adults, 85.6%; median age, 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care, 71.6% with active liver disease, and 28% deceased at discharge) and 25% to 38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios of ≤0.84 to 0.91 and FIIE-FII differences of >0.04 U/mL had similar modest sensitivity (47.7%-69.3%) and modest to good specificity (67.1%-91.5%) for VKD. FII/FIIE ratios of <0.86, suggestive of VKD (sensitivity, 47.7%; specificity, 90.2%), were more common in patients deficient in only VKDF (P = .0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (P = .0002). Patients with and without probable VKD (based on FII/FIIE ratios of <0.86) had similar mortality, bleeding, and rates of prothrombin complex concentrate and red cell transfusions (P ≥ .78), but fewer with probable VKD received plasma and fibrinogen replacement (P ≤ .024).
CONCLUSIONS: FII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies.

Disorders of blood coagulation can lead to manifest spontaneous bleeding and an increased risk of bleeding during surgical procedures and interventions. Pathophysiologically, a distinction can be made between defects in primary haemostasis, which lead to impaired platelet adhesion and platelet aggregation, and disorders of secondary (plasmatic) haemostasis, which are characterised by impaired fibrin formation or fibrin stabilisation. Aetiologically, a distinction can be made between rare genetically-determined hereditary defects and common acquired coagulation disorders, which may be based on different pathomechanisms. This overview is intended to provide ophthalmic surgeons with a basis for the perioperative management of patients with genetically determined coagulation disorders undergoing ophthalmic surgery. As there are no specific recommendations in this regard, the recommendations are based on the procedure for other surgical interventions, taking into account the specific bleeding risk associated with ophthalmic surgery.
Störungen der Blutgerinnung können zu spontanen Blutungsmanifestationen und einem erhöhten Blutungsrisiko bei operativen Eingriffen und Interventionen führen. Pathophysiologisch lassen sich Defekte der primären Hämostase, die zu einer gestörten Thrombozytenadhäsion und Thrombozytenaggregation führen, sowie Störungen der sekundären (plasmatischen) Hämostase, die durch eine Beeinträchtigung der Fibrinbildung oder Fibrinstabilisierung charakterisiert sind, unterscheiden. Ätiologisch kann man seltene genetisch determinierte hereditäre Defekte und häufige erworbene Gerinnungsstörungen unterscheiden, denen unterschiedliche Pathomechanismen zugrunde liegen können. Mit dieser Übersicht soll Ophthalmochirurgen eine Grundlage zum perioperativen Management von Patienten mit genetisch determinierten Gerinnungsstörungen gegeben werden, die sich einem ophthalmochirurgischen Eingriff unterziehen müssen. Da diesbezüglich keine spezifischen Empfehlungen existieren, beruhen die Empfehlungen auf dem Vorgehen bei sonstigen operativen Eingriffen, wobei das spezifische Blutungsrisiko im Rahmen der Ophthalmochirurgie berücksichtigt wird.

BACKGROUND: Preoperative identification of patients with haemostasis abnormalities leading to an increased bleeding risk was based on routine haemostasis tests: prothrombin time (PT), activated prothrombin time (aPTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population.
OBJECTIVE: To assess the diagnostic accuracy of 3 strategies, performed at the pre-anaesthesia visit before scheduled interventions, to identify patients with haemostasis abnormalities leading to an increased bleeding risk PATIENTS AND METHODS: Multicenter study in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, aPTT, and platelet count ordered in selected patients; 3-systematic PT, aPTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factors VIII, IX, and XI, platelet-function analyser, and, when required, FII, FV, FX, and FVII and haemostasis consultation.
RESULTS: Eighteen (1.2%) of 1484 patients had a haemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95%CI, 26-74; specificity 87% (95%CI, 85-88); sensitivity was 0 (95%CI, 0-41) in men vs 82% (95%CI, 48- 98) in women. For selective routine tests, sensitivity was 33% (95%CI, 13-59) and specificity 97% (95% CI, 96-98). Corresponding values for systematic routine tests were 44% (95%CI, 22-69) and 93% (95%CI, 91-94).
CONCLUSIONS: Sensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women.

Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = -0.72, FDP: r = -0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin.

Patients with liver cirrhosis often exhibit complex alterations in their hemostatic system that can be associated with both bleeding and thrombotic complications. While prophylactic correction of abnormal coagulation parameters should be avoided, an individualized approach is recommended prior to invasive procedures, whereby specific preventive measures to stabilize hemostasis should be based on the periprocedural bleeding risk. While the haemostatic system of patients with compensated cirrhosis is often in a rebalanced haemostatic state due to a parallel decline in both pro- and anti-haemostatic factors, a decompensation of liver cirrhosis can lead to destabilization of this fragile equilibrium. Since conventional coagulation tests do not adequately capture the complex changes in the hemostatic system in cirrhosis, functional analysis methods such as viscoelastic tests or thrombin generation assays can be used for evaluating the coagulation status. This review describes the underlying pathophysiological changes in the hemostatic system in liver cirrhosis, provides an overview of diagnostic methods and discusses therapeutic measures in case of bleeding and thrombotic complications.
Patienten mit Leberzirrhose weisen komplexe Veränderungen des hämostatischen Systems auf, die sowohl mit Blutungs- als auch mit thrombotischen Komplikationen einhergehen können und im Rahmen des klinischen Managements berücksichtigt werden sollten.Während eine prophylaktische Korrektur abnormaler Gerinnungsparameter vermieden werden sollte, ist vor invasiven Prozeduren ein individualisiertes Vorgehen zu empfehlen, wobei sich spezifische Präventionsmaßnahmen zur Stabilisierung der Gerinnung am periprozeduralen Blutungsrisiko orientieren sollten.Weiterhin gilt zu beachten, dass sich die hämostatischen Veränderungen in Abhängigkeit des Stadiums der Erkrankung unterscheiden. Während sich das hämostatische System bei kompensierter Zirrhose oftmals in einem Gleichgewicht befindet, kann das Auftreten einer akuten Dekompensation zu einer Destabilisierung dieses Zustands führen.Da konventionelle Gerinnungstests die komplexen Veränderungen des hämostatischen Systems bei Zirrhose nicht adäquat erfassen, können funktionelle Analysemethoden, wie viskoelastische Testverfahren oder Thrombingenerierungstests bei der Evaluation des Gerinnungsstatus hilfreich sein.Die vorliegende Übersichtsarbeit beschreibt die zugrunde liegenden pathophysiologischen Veränderungen des hämostatischen Systems bei Leberzirrhose, liefert einen Überblick über geeignete Diagnostikmethoden und thematisiert Therapiemaßnahmen im Falle von Blutungs- und thrombotischen Komplikationen.

BACKGROUND: Blood transfusion is one of the most common medical practices worldwide. However, current scientific literature has shown that the immunomodulatory effects of blood transfusion are associated with an increased likelihood of infection, prolonged hospitalization, and morbimortality. Also, it means high costs for healthcare systems.
METHODS: In this context, acknowledging that blood transfusions are essentially heterologous cell transplantations, the use of therapeutic options has gained strength and is collectively known as the patient blood management (PBM) program. PBM is an approach based on three main pillars: (1) treating anemias and coagulopathies in an optimized manner, especially in the preoperative period; (2) optimizing perioperative hemostasis and the use of blood recovery systems to avoid the loss of the patient\'s blood; (3) anemia tolerance, with improved oxygen delivery and reduced oxygen demand, particularly in the postoperative period.
RESULTS: Current scientific evidence supports the effectiveness of PBM by reducing the need for blood transfusions, decreasing associated complications, and promoting more efficient and safer blood management. Thus, PBM not only improves clinical outcomes for patients but also contributes to the economic sustainability of healthcare systems.
CONCLUSIONS: The aim of this review was to summarize PBM strategies in a comprehensive, evidence-based approach through a systematic and structured model for PBM implementation in tertiary hospitals. The recommendations proposed herein are from researchers and experts of a high-complexity university hospital in the network of the Sistema Único de Saúde, presenting itself as a strategy that can be followed as a guideline for PBM implementation in other settings.