搜索结果：Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis

In 2025, the International Society on Thrombosis and Haemostasis (ISTH) released updated definitions and diagnostic criteria for disseminated intravascular coagulation (DIC), reflecting advances in understanding its pathophysiology. DIC is now defined as an acquired, life-threatening condition involving systemic coagulation activation, impaired fibrinolysis, and endothelial injury. The revised framework emphasizes the condition's dynamic nature, progressing from preclinical abnormalities to overt clinical manifestations such as bleeding and organ dysfunction. A major innovation in the 2025 update is the phase-based classification of DIC: Pre-DIC, early-phase DIC, and overt DIC. Early-phase DIC-also referred to as subclinical or compensated DIC-is characterized by laboratory abnormalities preceding clinical symptoms. Overt DIC represents the advanced stage with clear evidence of coagulopathy and organ failure. Importantly, the new criteria are tailored to the underlying disease, such as sepsis, trauma, or malignancy. For example, the sepsis-induced coagulopathy score is now acknowledged as a tool for detecting early-phase DIC in septic patients. The overt DIC scoring system has been refined, including revised D-dimer thresholds: Levels >3× and >7 × , the upper normal limit now corresponds to 2 and 3 points, respectively. Platelet count, prothrombin time-international normalized ratio, and fibrinogen levels remain key indicators. The criteria also classify DIC into thrombotic and hemorrhagic phenotypes. Thrombotic DIC is marked by microvascular thrombosis and organ dysfunction, while hemorrhagic DIC is characterized by bleeding due to consumption of coagulation factors. By introducing clearer definitions and individualized approaches, these updates aim to enable earlier diagnosis and more effective management of DIC across clinical contexts.

Coronavirus disease 2019 (COVID-19) is, at present, one of the most relevant global health problems. In the literature hepatic alterations have been described in COVID-19 patients, and they are mainly represented by worsening of underlying chronic liver disease leading to hepatic decompensation and liver failure with higher mortality. Several potential mechanisms used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to cause liver damage have been hypothesized. COVID-19 primary liver injury is less common than secondary liver injury. Most of the available data demonstrate how liver damage in SARS-CoV-2 infection is likely due to systemic inflammation, and it is less likely mediated by a cytopathic effect directed on liver cells. Moreover, liver alterations could be caused by hypoxic injury and drugs (antibiotics and non-steroidal anti-inflammatory drugs, remdesivir, tocilizumab, tofacitinib and dexamethasone). SARS-CoV-2 infection can induce multiple vascular district atherothrombosis by affecting simultaneously cerebral, coronary and peripheral vascular beds. Data in the literature highlight how the virus triggers an exaggerated immune response, which added to the cytopathic effect of the virus can induce endothelial damage and a prothrombotic dysregulation of hemostasis. This leads to a higher incidence of symptomatic and confirmed venous thrombosis and of pulmonary embolisms, especially in central, lobar or segmental pulmonary arteries, in COVID-19. There are currently fewer data for arterial thrombosis, while myocardial injury was identified in 7%-17% of patients hospitalized with SARS-CoV-2 infection and 22%-31% in the intensive care unit setting. Available data also revealed a higher occurrence of stroke and more serious forms of peripheral arterial disease in COVID-19 patients. Hemostasis dysregulation is observed during the COVID-19 course. Lower platelet count, mildly increased prothrombin time and increased D-dimer are typical laboratory features of patients with severe SARS-CoV-2 infection, described as "COVID-19 associated coagulopathy." These alterations are correlated to poor outcomes. Moreover, patients with severe SARS-CoV-2 infection are characterized by high levels of von Willebrand factor with subsequent ADAMTS13 deficiency and impaired fibrinolysis. Platelet hyperreactivity, hypercoagulability and hypofibrinolysis during SARS-CoV-2 infection induce a pathological state named as "immuno-thromboinflammation." Finally, liver dysfunction and coagulopathy are often observed at the same time in patients with COVID-19. The hypothesis that liver dysfunction could be mediated by microvascular thrombosis has been supported by post-mortem findings and extensive vascular portal and sinusoidal thrombosis observation. Other evidence has shown a correlation between coagulation and liver damage in COVID-19, underlined by the transaminase association with coagulopathy, identified through laboratory markers such as prothrombin time, international normalized ratio, fibrinogen, D-dimer, fibrin/fibrinogen degradation products and platelet count. Other possible mechanisms like immunogenesis of COVID-19 damage or massive pericyte activation with consequent vessel wall fibrosis have been suggested.

&#x3b1;2-Antiplasmin (A2AP) deficiency is a rare and often unidentified disorder characterized by increased fibrinolysis and subsequent bleeding. Global hemostasis assays may increase insight into the altered coagulation and fibrinolysis in these patients. To explore thrombin and plasmin generation profiles in A2AP-deficient patients, corresponding A2AP activity levels and associated bleeding phenotypes. The Nijmegen hemostasis assay was used to assess thrombin and plasmin generation in 23 A2AP-deficient patients (median age, 50 years; 70% women) from the cross-sectional Rare Bleeding disorders in the Netherlands study. Analyzed parameters included thrombin peak height, thrombin potential, fibrin lysis time, plasmin peak height, plasmin velocity index, and plasmin potential. These parameters were expressed as percentages of a reference obtained from 37 healthy controls (median age, 46 years; 57% women). The Nijmegen hemostasis assay data were correlated with A2AP activity levels and International Society on Thrombosis and Hemostasis Bleeding Assessment Tool scores using Pearson correlation coefficients. Patients' A2AP activity levels ranged from 23% to 83% (reference range, 89%-122%). Plasmin generation increased, as evidenced by significantly shorter fibrin lysis times (73%; P&#xa0;< .001) and higher plasmin peak heights (203%; P&#xa0;< .001), plasmin velocity indices (302%; P&#xa0;< .001) and plasmin potentials (154%; P&#xa0;< .001) in A2AP-deficient patients than those in healthy controls. Moreover, significantly higher thrombin potentials (146%; P&#xa0;< .001) and thrombin peak heights (132%; P&#xa0;< .001) were observed. Enhanced plasmin generation parameters showed statistically significant correlations with lower A2AP activity levels and higher International Society on Thrombosis and Hemostasis Bleeding Assessment Tool scores. A2AP-deficient patients exhibited augmented plasmin generation profiles that correlated with A2AP activity level and bleeding phenotype. Interestingly, increased thrombin generation profiles were also found in these patients.

Fibrinolysis is a series of enzymatic reactions that degrade insoluble fibrin. Plasminogen activators convert the zymogen plasminogen to the active serine protease plasmin, which cleaves and solubilizes crosslinked fibrin clots into fibrin degradation products. The quantity and quality of fibrinolytic enzymes, their respective inhibitors, and clot structure determine overall fibrinolysis. The quantity of protein can be measured by antigen-based assays, and both quantity and quality can be assessed using functional assays. Furthermore, variations of commonly used assays have been reported, which are tailored to address the role(s) of specific fibrinolytic factors and cellular elements (eg, platelets, neutrophils, and red blood cells). Although the concentration and/or activity of a protein can be quantified, how these individual components contribute to the overall fibrinolysis outcome can be challenging to determine. This difficulty is due to temporal changes within and around the thrombi during the clot breakdown, particularly the fibrin matrix structure, and composition. Furthermore, terms such as "fibrinolytic activity/potential," "plasminogen activation," and "plasmin activity" are often used interchangeably despite having different definitions. The purpose of this review is to 1) summarize the assays measuring fibrinolysis activity and potential, 2) facilitate the interpretation of data generated by these assays, and 3) summarize the strengths and limitations of these assays.

Disseminated intravascular coagulation (DIC) is not a disease criterion but a pathomechanistic process that accompanies various underlying diseases. According to the International Society on Thrombosis and Haemostasis definition, endothelial injury is an essential component in addition to systemic coagulation activation. Despite this definition, current diagnostic criteria for DIC do not include biomarkers for vascular endothelial injury. Endothelial cells are critical for hemostatic regulation because they produce various antithrombotic substances and express anticoagulant factors at the same time as facilitating coagulation, inflammatory reactions, platelet aggregation, and fibrinolysis with acute injury. Endothelial cells also exhibit various receptors, adhesion molecules, and the critical role of glycocalyx that regulates cellular interactions in thromboinflammation. For clinicians, biomarkers suitable for assessing endothelial injury are not readily available. Although we still do not have ideal biomarkers, antithrombin activity and von Willebrand factor can be candidates for the endothelium-related markers because those reflect the severity and are available in most clinical settings. Further, the dysfunction of endothelial cell in DIC arising from various underlying diseases is likely highly variable. For example, the involvement of endothelial dysfunction is significant in sepsis-induced coagulopathy, while moderate in trauma-induced coagulopathy, and variable in hematologic malignancy-associated coagulopathy. Because of the complexity of disease status associated with DIC, further research searching clinically available endothelium-related biomarkers is expected to establish individualized diagnostic criteria and potential therapeutic approaches.

A state of "re-balanced haemostasis" describes complex coagulation changes that arise in patients with liver disease. Changes include alterations in procoagulant and anticoagulant proteins, platelets and von Willebrand factor, as well as the fibrinolytic system. Various circumstances including infection, trauma, or surgery may disrupt this balance and predispose an individual to bleeding or thrombosis. The prothrombin time, international normalised ratio, and activated partial thromboplastin time are conventional coagulation screening tests that are routinely employed by clinicians to investigate unexplained bleeding, monitor anticoagulation, and inform preoperative assessments of bleeding risk. These standard coagulation tests assess quantitative defects in procoagulant clotting factors and are insensitive to levels of natural anticoagulants, which together with procoagulant factors, are often perturbed in liver disease. Therefore, the prolongation of clotting times measured by these tests often does not reflect the multifaceted alterations of haemostasis in these patients. Viscoelastic testing (VET) provides a more encompassing assessment of clotting function by recording real-time viscoelastic changes in whole blood and includes parameters that provide information on coagulation factor function, platelet contribution to clot formation, as well as fibrinolysis. To date, VET has been employed to predict and inform transfusion support in obstetric, trauma, and cardiac surgical fields, and its use in patients undergoing liver transplantation is well established. The ability of VET to accurately predict bleeding risk and precisely guide transfusion algorithms for patients with liver disease undergoing other invasive procedures or experiencing bleeding complications has been the topic of research over the last decade. This review is a critical summary of this data and provides a detailed snapshot of the position of VET as a clinical tool in patients with liver disease.

Venous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality, with pregnancy increasing the risk of VTE four- to five-fold compared with the non-pregnant state and up to 60-fold in the postpartum period. The incidence of pregnancy-related VTE ranges from 0.5 to 2.0 per 1000 pregnancies, with deep vein thrombosis (DVT) and pulmonary embolism (PE) accounting for most cases. The heightened thrombotic risk during pregnancy and postpartum stems from physiological adaptations in hemostasis, creating a hypercoagulable state to mitigate hemorrhage risk at delivery. These changes involve increased coagulation activation, reduced fibrinolysis, and venous stasis, fulfilling Virchow's triad. The risk rises as pregnancy progresses, peaking in the third trimester and postpartum period, with both hormonal fluctuations and mechanical factors playing key roles. Estrogen and progesterone contribute to early pregnancy risk by enhancing clotting factor synthesis, while later stages involve uterine compression of venous structures, impairing venous return. The postpartum period presents the highest risk, driven by endothelial injury during delivery, inflammatory responses, and hemodynamic shifts. Evolving obstetric practices, such as early ambulation and compression therapy, may have influenced the temporal distribution of VTE events. This review aims to clarify how pregnancy-specific hemostatic adaptations influence thrombotic risk and to identify strategies for improved, individualized prevention. Despite updated international guidelines, major discrepancies persist in risk scoring and prophylaxis thresholds, underscoring the limitations of current empirical approaches. Functional biomarkers such as thrombin generation and the Endogenous thrombin potential (ETP)-based activated protein C (APC) resistance assay, could represent promising tools to bridge the gap between mechanistic understanding and clinical application.

A proof-of-concept study using thrombolysis with catheter-directed tissue plasminogen activator (tPA) and pulmonary angiography imaging was performed to visualize perfusion deficits and reperfusion/therapeutic effects of tPA. A prospective, open-label, compassionate study. Descriptive statistics were presented for categorical variables and as means with sds for continuous variables. The Wilcoxon test was used to determine the differences between the two-related samples and a t test for continuous variables. Statistical significance was set at p value of less than 0.05. Agreement between observations was evaluated using the Kappa Cohen index and overall agreement using the Fleiss Kappa coefficient. A single COVID-19 ICU of Mexico&#xb4;s General Hospital Dr Eduardo Liceaga. Fifteen patients with severe Delta variant severe acute respiratory syndrome coronavirus 2 infection, 18-75 years old, requiring mechanical ventilation with a persistent Fio2 requirement of 70% or higher and Pao2/Fio2 ratio (or imputed ratio) less than 150 for more than 4 hours. The coagulation inclusion criteria were International Society on Thrombosis and Haemostasis score greater than 5, and presence of a d-dimer greater than 1,200, with viscoelastic testing using rotational thromboelastometry (Instrumentation Laboratories, Mexico City, Mexico) showing both hypercoagulability (EXTEM amplitude at 5&#x2009;min > 65 FIBTEM > 30) and hypofibrinolysis (EXTEM maximum lysis < 8%). Catheter-directed tPA angiography and iFlow system analysis to assess pre-tPA baseline pulmonary perfusion and changes in response to thrombolysis. Nine patients had microvascular filling defects demonstrated by angiography, and good agreement was found with iFlow analysis (&#x199; = 0.714). Statistically significant differences were identified in the area under the curve (AUC) region of interest/AUC reference tissue with and without filling defects in phase 2 DM -0.09206 (sd &#xb1; 0.16684) (p = 0.003). The Pao2/Fio2 values measured immediately and 48 hours after the procedure were significantly higher (p = 0.001 and p = 0.005, respectively). Statistically significant differences were found in d-dimer values (p = 0.007), Fio2 (p = 0.002), and oxygen saturation in arterial blood/Fio2 (p = 0.045), as well as in the number of patients who required prone positioning before, immediately after the procedure, and at 48 hours after the procedure (p = 0.002). Thrombolysis with catheter-directed tPA resulted in imaging evidence via pulmonary angiography and iFlow technology of improved lung perfusion in COVID-19 patients with severe respiratory failure.

For patients with end-stage renal disease on hemodialysis, the durability of vascular access (VA) is still far from optimal, and access survival after intervention for access failure is an important aspect. Procoagulant status is a leading cause of access failure. Coagulation-fibrinolysis imbalance can occur in hemodialyzed patients, but the influence of the imbalance has not been fully elucidated. We prospectively examined coagulation-fibrinolysis balance to assess the risk of access failure after the intervention of revascularization in a cohort of 462 hemodialysis patients. Thrombin-antithrombin complex (TAT) and plasmin-&#x3b1;2-plasmin inhibitor complex (PIC) are markers for coagulation and fibrinolysis. Median follow-up was 243&#xa0;days. The end point was clinical access failure: revascularization or access revision. The survival curve for VA patency was assessed using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression models that allowed adjustment for baseline differences in age, sex, dialysis vintage, diabetes mellitus, and various factors (quantity of blood flow, prothrombin time-international normalized ratio, fibrin degradation products, C-reactive protein, interleukin-6, tumor necrosis factor-&#x3b1;, and pentraxin-3) were used. The 162 patients who reached an end point had smaller access flow volume and smaller percentage of arteriovenous fistula and higher TAT/PIC ratio. Kaplan-Meier analysis indicated that the patients with elevated TAT/PIC ratio showed poorer outcome (P&#xa0;< .001). On Cox regression modeling, elevated TAT/PIC was an independent risk factor for access failure (hazard ratio, 1.58; P&#xa0;= .03). Our results suggest that coagulation-fibrinolysis imbalance is a significant risk factor for access failure and may predict VA failure in hemodialyzed patients after access intervention.

A significant number of patients with prosthetic valve thrombosis have a prothrombin time international normalised ratio in the therapeutic range at presentation. Surgery may not be possible in many patients and traditionally a high international normalised ratio is considered a relative contraindication for fibrinolysis. We conducted an observational study in patients with left-sided obstructive prosthetic valve thrombosis with international normalised ratio at or above the therapeutic range at presentation who received fibrinolysis. The fibrinolytic regimens, timing of initiation, success of fibrinolysis, risk of major and minor bleeding and ischaemic stroke were evaluated in the study. Of 30 patients included in the study 70% received immediate fibrinolysis and in 30% it was delayed. The majority of patients (90%) presented with New York Heart Association class III/IV symptoms. The mean international normalised ratio at fibrinolysis was 3.04 &#xb1; 0.70 in the immediate group and 2.42 &#xb1; 0.89 in the delayed group. Haemodynamically stable patients who had delayed initiation of fibrinolysis had a trend towards less bleeding without an increase in mortality. The rates of intracranial haemorrhage (0% vs. 7.7%), minor bleeding (12.5% vs. 25.1%) and ischaemic stroke (0% vs. 30.7%) were lower in patients who received low dose infusion compared to a conventional dose. Fibrinolysis can be considered in patients with prosthetic valve thrombosis with high international normalised ratio at presentation. For haemodynamically stable patients, delayed initiation of fibrinolysis is associated with a marginally lower bleeding risk without an increase in mortality. Low dose infusion may be considered over a conventional dose as it is associated with a lower incidence of ischaemic stroke and a good rate of valve function restoration with a trend towards less bleeding.

Sepsis is associated with dysregulation of procoagulant, anticoagulant, and fibrinolytic pathways. To compare the measurements of coagulation activation, clot formation, stabilization, and lysis between rotational thromboelastometry (ROTEM) and standard coagulation tests (SCTs) on patients with early sepsis (SP) and healthy controls (HC). This observational study included 30 SP and 30 HC. At study inclusion, SCTs and ROTEM analyses were conducted. A modified ROTEM with exogenous tPA was used to investigate fibrinolysis resistance. SP had longer prothrombin time, higher fibrinogen levels and lower platelet count compared to HC. On ROTEM, clotting initiation was longer in SP than in HC but median clotting time maintained within reference ranges. SP had higher maximum velocity of clot formation, clot firmness, elasticity, and platelet component than HC. Clot lysis indices (CLI) were higher in EXTEM and APTEM (without and with added tPA) in SP compared to HC. The difference in CLI between APTEM and EXTEM was lower for both native and tPA-spiked samples in SP compared with HC. While SCTs suggest SP are hypocoagulable, VET revealed normal coagulation initiation in more than 80&#x202f;% of SP. Compared to HC, SP had increased clot propagation, firmness and elasticity, and decreased platelet-mediated clot retraction and lysis. In sepsis, VET provide more comprehensive information about hemostatic changes than SCTs.

The International Society on Thrombosis and Haemostasis (ISTH) released overt disseminated intravascular coagulation (DIC) diagnostic criteria in 2001. Since then, DIC has been understood as the end-stage consumptive coagulopathy and not the therapeutic target. However, DIC is not merely a decompensated coagulation disorder, but also includes early stages with systemic activation in coagulation. Thus, the ISTH has recently released sepsis-induced coagulopathy (SIC) criteria that can diagnose compensated-phase of coagulopathy with readily available biomarkers. DIC is a laboratory-based diagnosis due to various critical conditions, although sepsis is the most common underlying disease. The pathophysiology of sepsis-associated DIC is multifactorial, and in addition to coagulation activation with suppressed fibrinolysis, multiple inflammatory responses are initiated by activated leukocytes, platelets, and vascular endothelial cells as part of thromboinflammation. Although overt DIC diagnostic criteria were established by ISTH to diagnose the advanced stage of DIC, additional criteria that can detect an earlier stage of DIC were needed for potential therapeutic considerations. Accordingly, the ISTH introduced SIC criteria in 2019 that are easy to use and require only platelet count, prothrombin time-international normalized ratio, and Sequential Organ Failure Assessment Score. SIC score can be used to evaluate disease severity and determine the timing of potential therapeutic interventions. One of the major disadvantages in treating sepsis-associated DIC is the lack of availability of specific therapeutic approaches beyond treating the underlying infection. Clinical trials to date have failed because included patients who were not coagulopathic. Nevertheless, in addition to infection control, anticoagulant therapy will be the choice for sepsis-associated DIC. Therefore, the efficacy of heparin, antithrombin, and recombinant thrombomodulin has to be proven in future clinical studies. It is necessary to develop a novel therapeutic strategy against sepsis-associated DIC and improve the outcomes. Consequently, we recommend screening and monitoring DIC using SIC scoring system.

Cardiac amyloidosis represents a spectrum of conditions characterized by the accumulation of insoluble fibrils, resulting in progressive deposition and myocardial dysfunction. The exact mechanisms contributing to the heightened risk of thromboembolic events and bleeding tendencies in cardiac amyloidosis remain unclear. Proteins such as transthyretin in transthyretin amyloidosis and light chains in light-chain amyloidosis, along with acute phase proteins in amyloid A (AA) amyloidosis, play complex roles in the coagulation cascade, affecting both coagulation initiation and fibrinolysis regulation. The increased occurrence of atrial fibrillation, systolic and diastolic left ventricular dysfunction, and atrial myopathy in patients with cardiac amyloidosis may predispose them to thrombus formation. This predisposition can occur regardless of sinus rhythm status or even with proper anticoagulant management. Bleeding events are often linked to amyloid deposits around blood vessels, which may increase capillary fragility and cause coagulation disturbances, leading to unstable international normalized ratio levels during anticoagulant therapy. Thus, comprehensive risk assessment for both thrombotic and hemorrhagic complications, especially before commencing anticoagulant therapy, is imperative. This review will explore the essential pathophysiological, epidemiologic, and clinical aspects of thromboembolic and bleeding risk in cardiac amyloidosis, evaluating the existing evidence and uncertainties regarding thrombotic and bleeding risk assessment and antithrombotic treatment.

Hypomagnesemia reportedly has significant associations with poor clinical outcomes such as increased mortality and septic shock in patients with sepsis. Although the mechanism underlying these outcomes mostly remains unclear, some experimental data suggest that magnesium deficiency could potentiate coagulation activation in sepsis. However, in sepsis, the association between serum magnesium levels and coagulopathy, including disseminated intravascular coagulation (DIC), remains unknown. Thus, we aimed to investigate the relationship between serum magnesium levels and coagulation status and the association between hypomagnesemia and DIC in patients with sepsis. This retrospective observational study was conducted at the intensive care unit (ICU) of a university hospital from June 2011 to December 2017. Patients older than 19 years who met the Sepsis-3 definition were included. We categorized patients into three groups according to their serum magnesium levels: hypomagnesemia (< 1.6 mg/dL), normal serum magnesium level (1.6-2.4 mg/dL), and hypermagnesemia (> 2.4 mg/dL). We investigated the association between serum magnesium levels and overt DIC at the time of ICU admission according to the criteria of the International Society on Thrombosis and Haemostasis. Among 753 patients included in this study, 181 had DIC, 105 had hypomagnesemia, 552 had normal serum magnesium levels, and 96 had hypermagnesemia. Patients with hypomagnesemia had a more activated coagulation status indicated by lower platelet counts, lower fibrinogen levels, higher prothrombin time-international normalized ratios, higher thrombin-antithrombin complex, and more frequent DIC than those with normal serum magnesium levels and hypermagnesemia (DIC: 41.9% vs. 20.6% vs. 24.0%, P < 0.001). The coagulation status in patients with hypomagnesemia was more augmented toward suppressed fibrinolysis than that in patients with normal serum magnesium levels and hypermagnesemia. Multivariate logistic regression revealed that hypomagnesemia was independently associated with DIC (odds ratio, 1.69; 95% confidence interval, 1.00-2.84; P = 0.048) after adjusting for several confounding variables. Patients with hypomagnesemia had a significantly activated coagulation status and suppressed fibrinolysis. Hypomagnesemia was independently associated with DIC in patients with sepsis. Therefore, the treatment of hypomagnesemia may be a potential therapeutic strategy for the treatment of coagulopathy in sepsis.

In bleeding patients with trauma-induced coagulopathy (TIC), factor (F)V becomes depleted, which may not be corrected with existing treatment strategies. It is currently unknown whether supplementing FV or FVa improves TIC. To explore the relationship between FV activity and mortality in trauma patients, and to investigate the effect of FV(a) supplementation in addition to other treatment strategies in an in vitro model of TIC. The association between FV activity and mortality was studied using an international prospective cohort study of trauma patients. In an in vitro whole blood and plasma model of TIC, the effect of FV(a) on rotational thromboelastometry and fibrin formation was studied. Effects of FV(a) were evaluated either as a standalone therapy or as adjunctive therapy in combination with tranexamic acid, fibrinogen concentrate, and/or prothrombin complex concentrate. A total of 1285 patients were included, with a median injury severity score of 16 (interquartile range: 8-26). Decreased FV activity was associated with increased mortality. In the whole blood TIC model, FVa increased maximum clot firmness and reduced fibrinolysis, both as a single and combination therapy. In the plasma TIC model, with lower tissue factor concentrations than in the whole blood model, FV(a) prolonged clotting times, both as a single treatment and in combination with other treatments. FV depletion after trauma is associated with increased mortality. In an in vitro model of TIC, FV(a) results in procoagulant, antifibrinolytic, and anticoagulant effects. Further research is highly warranted.

Septic shock patients are prone to altered fibrinolysis, which contributes to microthrombus formation, organ failure and mortality. However, characterisation of the individual patient's fibrinolytic capacity remains a challenge due to a lack of global fibrinolysis biomarkers. We aimed to assess fibrinolysis in septic shock patients using a plasma-based fibrin clot formation and lysis (clot-lysis) assay and investigate the association between clot-lysis parameters and other haemostatic markers, organ dysfunction and mortality. This was a prospective cohort study including adult septic shock patients (n = 34). Clot-lysis was assessed using our plasma-based in-house assay. Platelet count, activated partial thromboplastin time (aPTT), international normalised ratio (INR), fibrinogen, fibrin D-dimer, antithrombin, thrombin generation, circulating fibrinolysis markers and organ dysfunction markers were analysed. Disseminated intravascular coagulation score, Sequential Organ Failure Assessment (SOFA) score and 30-day mortality were registered. Three distinct clot-lysis profiles emerged in the patients: (1) severely decreased fibrin formation (flat clot-lysis curve), (2) normal fibrin formation and lysis and (3) pronounced lysis resistance. Patients with abnormal curves had lower platelet counts (p = 0.05), more prolonged aPTT (p = 0.04), higher lactate (p < 0.01) and a tendency towards higher SOFA scores (p = 0.09) than patients with normal clot-lysis curves. Fibrinogen and fibrin D-dimer were not associated with clot-lysis profile (p &#x2265; 0.37). Septic shock patients showed distinct and abnormal clot-lysis profiles that were associated with markers of coagulation and organ dysfunction. Our results provide important new insights into sepsis-related fibrinolysis disturbances and support the importance of assessing fibrinolytic capacity in septic shock.

In many patients referred with significant bleeding phenotype, laboratory testing fails to define any hemostatic abnormalities. Clinical practice with respect to diagnosis and management of this patient cohort poses significant clinical challenges. We recommend that bleeding history in these patients should be objectively assessed using the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool. Patients with increased bleeding assessment tool scores should progress to hemostasis laboratory testing. To diagnose bleeding disorder of unknown cause (BDUC), normal complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, von Willebrand factor antigen, von Willebrand factor function, coagulation factors VIII, IX, and XI, and platelet light transmission aggregometry should be the minimum laboratory assessment. In some laboratories, additional specialized hemostasis testing may be performed to identify other rare causes of bleeding. We recommend that patients with a significant bleeding phenotype but normal laboratory investigations should be registered with a diagnosis of BDUC in preference to other terminology. Global hemostatic tests and markers of fibrinolysis demonstrate variable abnormalities, and their clinical significance remains uncertain. Targeted genomic sequencing examining candidate hemostatic genes has a low diagnostic yield. Underlying BDUC should be considered in patients with heavy menstrual bleeding since delays in diagnosis often extend to many years and negatively impact quality of life. Treatment options for&#xa0;BDUC patients include tranexamic acid, desmopressin, and platelet transfusions.

During pregnancy, the maternal hemostatic system undergoes significant changes to support placental angiogenesis, maintain fetal blood flow, and ensure safe delivery. This study investigates the dysregulation of hemostasis in placental insufficiency and explores potential markers for diagnosing and managing this gestational complication. Thromboelastography, coagulation and fibrinolysis functional assays, ELISA, and immunoblotting were employed to assess hemostasis dysregulation in placental dysfunction of two cohorts of pregnant women with placental dysfunction and healthy controls. Thromboelastographic analysis revealed no significant differences in clot lysis indices between the control and placental dysfunction groups, with values remaining within normal ranges, suggesting this method's limitations for assessing fibrinolysis in pregnancy. The placental dysfunction group demonstrated moderately increased fibrinogen levels and platelet sensitivity to ADP, indicating hemostasis reactiveness. Significantly lower D-dimer levels, decreased plasminogen activator inhibitor activity (total PAI-1 + PAI-2), and increased plasminogen activator activity, driven primarily by uPA in the placental dysfunction group, indicated abnormal fibrinolysis. Immunoblotting confirmed elevated uPA/uPA-PAI complexes and reduced tPA/tPA-PAI complexes, indicating that shutdown of tPA-mediated fibrinolysis and induction of uPA-driven vessel-wall-associated proteolysis are linked to placental dysfunction. Placental dysfunction involves fibrinolytic system dysregulation, marked by decreased PAI and tPA, uPA overproduction, and hypofibrinolysis, contributing to thrombotic risks, impaired placental flow, and complications like fetal growth retardation. PAI/PA ratio and D-dimer levels have diagnostic potential for placental-dysfunction-associated complications.

Compelling evidence supports the need to update the 2001 definition and diagnosis of disseminated intravascular coagulation (DIC) to reflect our current understanding of disease pathophysiology. DIC has been long considered a critical and untreatable sequela of various underlying causes, with resolution only after treatment of the eliciting etiology. Recent views have evolved to appreciate that DIC-associated mortality may be reduced by detection and treatment at an early stage. The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on DIC proposes an updated definition of DIC: "an acquired, life-threatening intravascular disorder characterized by systemic coagulation activation, dysregulated fibrinolysis, and endothelial injury, resulting in microthrombosis. DIC arises from various underlying etiologies and progresses from a potentially asymptomatic early phase to an advanced phase with hemorrhage and/or organ dysfunction." In accordance with this more comprehensive definition, we propose to establish more tailored diagnostic criteria that detect early-phase DIC based on the underlying disease. We also propose a modification to overt DIC diagnostic criteria and scoring for late-phase DIC. These consensus-driven modifications reflect knowledge obtained since the original 2001 definition, which advanced clinical practice and research on DIC. This revised framework is anticipated to foster more precise and earlier diagnoses, improve patient stratification in clinical studies, and facilitate the development of targeted therapies dependent on pathophysiological context.