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OBJECTIVE: To investigate the characteristic of circulating microparticle in patients with acute myocardial infarction (AMI) and its possible mechanism of promoting coagulation. METHODS: A prospective case-control study was conducted. The patients with coronary heart disease admitted to the second department of cardiology in Harbin First Hospital from June to November 2023 were enrolled, and they were grouped according to whether the patients occurred AMI or not. On the day of admission, disseminated intravascular coagulation (DIC) score was calculated. At the same time, fasting venous blood was collected, and the levels of D-dimer, fibrin degradation product (FDP) and the activities of major coagulation factors were detected. The level of circulating microparticle was determined by microparticle trapping method. The microparticle carrying tissue factor (TF+MP) level was detected by tissue factor (TF) dependent F Xa production assay. Spearman correlation method was used to analyze the correlation among the indicators. RESULTS: A total of 52 patients with coronary heart disease were enrolled, including 26 patients in AMI group and 26 patients in non-AMI group. There was no significant difference in gender, age, body mass index (BMI), underlying diseases, smoking history, and pre-admission treatment of patients between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the non-AMI group, the DIC score and D-dimer, FDP levels in the AMI group were significantly increased [DIC score: 3 (3, 4) vs. 3 (2, 3), D-dimer (mg/L): 8.80 (6.84, 15.66) vs. 2.13 (1.64, 3.86), FDP (mg/L): 30.13 (19.30, 52.54) vs. 20.00 (13.51, 28.37), all P < 0.01], indicating that the degree of coagulation activation in AMI patients was more severe. The consumption of major coagulation factors in the coagulation pathway in the AMI group was heavier than that in the non-AMI group [F II: 59.45% (49.65%, 71.25%) vs. 63.65% (49.98%, 73.22%), F V: 96.95% (73.50%, 112.78%) vs. 105.05% (73.48%, 131.48%), F VII: 42.30% (36.98%, 51.98%) vs. 53.40% (46.58%, 69.88%), F X: 60.90% (48.22%, 80.82%) vs. 73.50% (56.80%, 85.98%), F XI: 82.45% (62.90%, 99.10%) vs. 92.40% (73.90%, 114.25%), F XII: 29.90% (12.42%, 42.38%) vs. 34.65% (16.32%, 48.20%), all P < 0.05]. The circulating TF+MP level in the AMI group was significantly higher than that in the non-AMI group [nmol/L: 0.13 (0.06, 0.20) vs. 0.08 (0.04, 0.15), P < 0.05]. There was no significant difference in the level of circulating microparticle between AMI group and non-AMI group [nmol/L: 1.24 (0.71, 3.77) vs. 1.35 (0.73, 2.14), P > 0.05]. Correlation analysis showed that circulating TF+MP level in the patients with coronary heart disease was significantly positively correlated with coagulation indicator DIC score (r = 0.307, P = 0.027), D-dimer (r = 0.696, P < 0.001) and FDP (r = 0.582, P < 0.001), and there was a strong negative correlation with exogenous pathway factor F VII (r = -0.521, P < 0.001) and common pathway factor F X (r = -0.332, P = 0.016). CONCLUSIONS: The circulating TF+MP level in AMI patients was significantly higher than that in the non-AMI patients. TF+MP may play an important role in activating the extrinsic coagulation pathway, exacerbating coagulation factor consumption, and promoting clot formation during AMI occurrence.

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BACKGROUND: The relationship between the pregnancy modified DIC score, which is applied in obstetric conditions where the risk of disseminated intravascular coagulation is high, and underlying disease, as well as its effect on the prognosis, was investigated. METHODS: Those with a DIC score ≥ 26 from obstetric conditions, such as obstetric bleeding, placental abruption, or preeclampsia/HELLP syndrome, which are at high risk of developing DIC, were included in the study. These patients were compared in terms of laboratory results, maternal morbidity/mortality, and neonatal outcomes, according to the underlying disease. RESULTS: The DIC score was ≥ 26 in 224 of 154,233 deliveries in our center, and the incidence was 0.14%. In the preeclampsia/HELLP syndrome group, the platelet count and prothrombin time were lower, and the fibrinogen level was higher than those of the obstetric hemorrhage and placental abruption groups. In addition, the rates of blood transfusion and hysterectomy were lower in women who developed DIC due to pre-eclampsia/HELLP syndrome than in those with obstetric hemorrhage. CONCLUSIONS: Considering the underlying disease is an important factor in predicting prognosis, when using the new pregnancy modified diagnostic scores for DIC diagnosis.

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Sepsis is a life-threatening condition that has the potential to multiple organ dysfunction and mortality. One of its frequent complications is disseminated intravascular coagulation (DIC), characterized by hyperactive clotting mechanisms that cause widespread clot formation and tissue damage. This study aimed to investigate early diagnostic markers of sepsis-associated DIC by comparing inflammatory factor levels, 28-day survival rates, coagulation function, and markers between patients with sepsis (non-DIC group) and those with sepsis-induced DIC (DIC group). The study analyzed the diagnostic efficacy of coagulation function and markers in predicting the occurrence and prognosis of sepsis-associated DIC, presenting survival curves. Results indicated significantly increased levels of APTT, TAT, tPAIC, PIC, and sTM in the DIC group compared to the non-DIC group. Sequential Organ Failure Assessment (SOFA) scores on days 1, 3, and 7 were notably lower in the non-DIC group. Correlation analysis revealed positive associations between PT, APTT, TAT, tPAIC, PIC, sTM levels, and SOFA scores, as well as negative associations with Fib and SOFA scores. Survival curves showed substantially lower mortality rates in the non-DIC group, highlighting significant survival disparities between groups. Combining all four coagulation indicators (TAT+ tPAIC + PIC + sTM) showed promising diagnostic value in evaluating disease severity, early DIC diagnosis, and sepsis prognosis.

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A new scoring system termed sepsis-induced coagulopathy (SIC) has been proposed to diagnose early sepsis-induced disseminated intravascular coagulation (DIC). This study performed DIC-related analyses in patients with confirmed SIC. Data from the intensive care unit (ICU) departments of the three hospitals between 2020 and 2022 were retrospectively analyzed. Finally, 125 patients with confirmed SIC were enrolled in the study. The diagnostic value of three widely used DIC criteria was assessed in patients with newly diagnosed SIC. In addition, the diagnostic and prognostic value of antithrombin (AT) was analyzed in patients with SIC. The Japanese Association for Acute Medicine DIC criteria (JAAM) exhibited the highest DIC diagnostic rate, while the mortality risk of SIC patients demonstrated a proportional increase with higher International Society on Thrombosis and Haemostasis (ISTH) and Chinese DIC scoring system (CDSS) scores. Low AT activity (<70%) in septic patients upon SIC diagnosis predicted a very high 28-day mortality rate, almost twice as high as in the normal AT activity (≥70%) group. A decreasing tendency in AT activity after clinical interventions was correlated with increased mortality. The area under the ROC curve (AU-ROC) of AT in DIC diagnosis was statistically significant when CDSS and ISTH were used as diagnostic criteria, but not JAAM. Each of the three DIC diagnostic criteria showed diagnostic and prognostic advantages for SIC. AT could be an independent prognostic indicator for SIC but demonstrated a relatively limited DIC diagnostic value. Adding AT to the SIC scoring system may increase its prognostic power.

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Since July 2022, obstetrical disseminated intravascular coagulation (DIC) in Japan has been diagnosed based on the new criteria (tentative version), which assesses the main underlying disease, fibrinogen level, and fibrin/fibrinogen degradation products or D-dimer level. In June 2024, the tentative version underwent minor revision and the final version was released. The previous Japanese criteria assessed underlying disease, clinical symptoms, and various laboratory findings. This study aimed to prove the effectiveness, reliability, and validity of the new criteria (final version). We analyzed 212 women with singleton pregnancies who delivered after 22 gestational weeks and experienced blood loss ≥ 1000 mL during vaginal delivery or ≥ 2000 mL during cesarean section. Those with missing laboratory findings before receiving blood transfusion at delivery were excluded. In the obstetrical DIC group, the frequency of fibrinogen levels < 150 mg/dL was significantly higher than in the control group (90% vs. 5%, p < 0.0001), as was the frequency of scores ≥ 8 according to the previous Japanese criteria (100% vs. 10%, p < 0.0001). Cronbach alpha was 0.757 and Spearman's rank-order correlation was 0.558 between the new and previous criteria. In conclusion, we proved the effectiveness, reliability, and validity of the Japanese new criteria (final version) to diagnose obstetrical DIC.

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BACKGROUND: D-dimer, a specific product of cross-linked fibrin degradation, is of great clinical value in the early diagnosis of thrombotic diseases and in monitoring the efficacy of thrombolysis; therefore, the accuracy of D-dimer test results is crucial. METHODS: This article reports a case of a patient with disseminated intravascular coagulation (DIC) who experienced a false decrease in D-dimer due to the hook effect. RESULTS: The three D-dimer test results for DIC patients were 1.09 mg/L, 0.93 mg/L, and 1.43 mg/L. After sample dilution, the results were: first time (1:128) 842.24 mg/L, second time (1:128) 1,505.28 mg/L, third time (1:32) 415.68 mg/L. There was a significant difference in the three test results before and after dilution, because the D-dimer concentration was too high, exceeding the detection range and causing the hook effect, which falsely lowered the D-dimer value. CONCLUSIONS: When the D-dimer value of DIC patients does not match the clinical situation, the possibility of the hook effect should be considered, and the false decrease can be ruled out by the sample dilution method. In this way, accurate clinical results can be obtained to avoid delaying the diagnosis and treatment of DIC patients.

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ABSTRACT: Background: Histidine-rich glycoprotein (HRG), a potential prognostic factor in sepsis, lacks clarity regarding its relevance in septic-induced shock, disseminated intravascular coagulation (DIC), and acute respiratory distress syndrome (ARDS) pathogenesis. This study investigated the association between HRG concentrations and these critical conditions. Methods: Blood samples were collected from 53 critically ill patients on days 1, 3, 5, and 7 after ICU admission at the Kyushu University Hospital. Daily clinical and laboratory data were recorded, and patient survival was assessed 28 days after ICU admission. Results: Serum HRG concentrations were significantly reduced on days 3, 5, and 7 in patients with septic shock and DIC but not in those with ARDS. While initial HRG levels on day one were not correlated with survival, nonsurvivors displayed decreased HRG levels, notably on days 3, 5, and 7 post-ICU admissions. The HRG levels remained stable in survivors. A progressive decrease was associated with higher mortality rates, particularly on days 5 and 7. On day 5, an HRG level with a cutoff of 25.5 µg/mL showed a sensitivity of 0.77 and a specificity of 0.75, indicating significantly lower survival rates (log-rank test, P < 0.05). Conclusion: HRG presents a potential intervention for critically ill sepsis patients, providing a novel strategy to enhance outcomes. Further research is needed to explore the therapeutic potential of HRG in sepsis management.

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Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.

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Sepsis is a severe inflammatory disease characterized by cytokine storm, often accompanied by disseminated intravascular coagulation (DIC). PANoptosis is a novel form of cell death triggered by cytokine storms, characterized by a cascade reaction of pyroptosis, apoptosis, and necroptosis. It exists in septic platelets and is closely associated with the onset and progression of DIC. However, there remains an unmet need for drugs targeting PANoptosis. The anti-PANoptosis effect of myricetin was predicted using network pharmacology and confirmed through molecular docking. In vitro platelet activation models demonstrated that myricetin significantly attenuated platelet particle release, integrin activation, adhesion, spreading, clot retraction, and aggregation. Moreover, in a sepsis model, myricetin reduced inflammatory infiltration in lung tissue and platelet activation while improving DIC. Additionally, whole blood sequencing samples from sepsis patients and healthy individuals were analyzed to elucidate the up-regulation of the PANoptosis targets. Our findings demonstrate the inhibitory effect of myricetin on septic platelet PANoptosis, indicating its potential as a novel anti-cellular PANoptosis candidate and therapeutic agent for septic DIC. Furthermore, our study establishes a foundation for utilizing network pharmacology in the discovery of new drugs to treat various diseases.

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BACKGROUND: Disseminated intravascular coagulation (DIC) is a common complication of all leukemia subtypes, but it is an especially prominent feature of Acute Myeloid Leukemias (AML). DIC complicating AML can lead to a variety of complications, however, its association with acute cardiovascular complications has not been reported before. METHODS: National Inpatient Sample Database was used to procure individuals with AML, and baseline demographics and comorbidities were collected using ICD-10-DM codes. Patients were stratified into those with and without DIC. Greedy propensity matching using R was performed to match the two cohorts in 1:1 ratio on age, gender, and fifteen other baseline comorbidities. Univariate analysis pre and post-match along with binary logistic regression analysis post-match were used to analyze outcomes. RESULTS: Out of a total of 37,344 patients with AML, 996 had DIC. DIC patients were younger, predominantly males, and had lower prevalence of baseline cardiovascular comorbidities. DIC patients had statistically significant higher mortality (30.2 % vs 7.8 %), acute myocardial infarction (5.1 % vs 1.8 %), acute pulmonary edema (2.3 % vs 0.7 %), cardiac arrest (6.4 % vs 0.9 %), and acute DVT/PE (6.6 % vs 2.7 %). Logistic regression model after matching showed similar outcomes along with significantly higher rates of acute heart failure in DIC patients. CONCLUSION: These findings highlight the importance of close cardiovascular monitoring and prompt recognition of complications in AML patients with DIC. The underlying mechanisms involve a complex interplay of procoagulant factors, cytokine release, and endothelial dysfunction. Further studies are needed to develop targeted interventions for prevention and management of these complications.

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D-dimer, a universally unique marker for fibrin degradation, is generated through the enzymatic interplay of thrombin, factor XIIIa, and plasmin. The emergence of D-dimer-containing fibrin molecules occurs in both intravascular and extravascular spaces during pivotal physiological processes like haemostasis, thrombosis, and tissue repair. Given the inherently physiological nature of fibrin formation and fibrinolysis, basal levels of D-dimer fragments are present in plasma. Beyond its role as a marker of routine physiological processes, aberrations in D-dimer levels are indicative of a spectrum of conditions, both non-pathological and pathological. The clinical utility of D-dimer has been firmly established, particularly in scenarios like venous thromboembolism (VTE), pulmonary embolism (PE), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). Additionally, recent applications have extended to assess the prognosis of COVID-19. While D-dimer is commonly associated with thrombotic conditions, its elevation is not confined to these conditions alone. Elevated D-dimer levels are observed across various diseases, where its significance extends beyond diagnostic indicators to prognostic implications.

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ABSTRACT: Microclots have been associated with various conditions, including postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. They have been postulated to be amyloid-fibrin(ogen) aggregates, but their role as a prognostic biomarker remains unclear. To examine their possible clinical utility, blood samples were collected for the first 96 hours from critically ill patients (n = 104) admitted to the intensive care unit (ICU). Detection was by staining platelet-poor plasma samples with thioflavin T and visualized by fluorescent microscopy. Image J software was trained to identify and quantify microclots, which were detected in 44 patients (42.3%) on ICU admission but not in the remaining 60 (57.7%) or the 20 healthy controls (0.0%). Microclots on admission to ICU were associated with a primary diagnosis of sepsis (microclots present in sepsis, 23/44 [52.3%] vs microclots absent in sepsis, 19/60 [31.7%]; P = .044). Multicolor immunofluorescence demonstrated that microclots consisted of amyloid-fibrinogen aggregates, which was supported by proteomic analysis. Patients with either a high number or larger-sized microclots had a higher likelihood of developing disseminated intravascular coagulation (odds ratio [OR], 51.4; 95% confidence interval [CI], 6.3-6721.1; P < .001) and had an increased probability of 28-day mortality (OR, 5.3; 95% CI, 2.0-15.6; P < .001). This study concludes that microclots, as defined by amyloid-fibrin(ogen) aggregates, are potentially useful in identifying sepsis and predicting adverse coagulopathic and clinical outcomes.

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BACKGROUND: Emicizumab (Emi) is used as haemostatic prophylaxis for patients with haemophilia A (PwHA). Disseminated intravascular coagulation (DIC) is a condition characterized by persistent systemic activation of coagulation, but there is yet no information on coagulation and fibrinolysis potentials in Emi-treated PwHA with DIC. AIM: To examine the effect of Emi on coagulation and fibrinolysis potentials in HA-model DIC plasmas. METHODS: Plasma from a patient with sepsis-DIC (seven patients) was treated with anti-factor (F)VIII monoclonal antibody (HA-model DIC plasma) and incubated with Emi (50 µg/mL). The plasma was then assessed using clot-fibrinolysis waveform analysis (CFWA). Coagulation and fibrinolysis parameters were expressed as ratios relative to normal plasma (|min1|-ratio and |FL-min1|-ratio, respectively). PATIENTS AND RESULTS: In case 1, coagulant potential was slightly high and fibrinolytic potential was extremely low, presenting a coagulant-dominant state (|min1|-ratio/|FL-min1|-ratio: 1.1/.38). In cases 2-5, fibrinolytic potential was not suppressed, but there were marked hypercoagulant potentials, indicating relative coagulant-dominant states. In case 6, coagulant and fibrinolytic potentials were increased but well balanced (|min1|-ratio/|FL-min1|-ratio: 1.38/1.28). In case 7, both potentials were severely deteriorated in not only CFWA but also the thrombin/plasmin generation assay. The addition of Emi into the HA-model DIC plasmas increased |min1|-ratio values in all cases, but the coagulant potentials did not exceed the initial ones (DIC plasma before treatment with anti-FVIII antibody). CONCLUSIONS: The presence of Emi in the HA-model DIC plasma improved coagulation potentials, but did not increase coagulation potentials beyond those of DIC plasma in non-HA states.

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PURPOSE: To develop a new cost-effective marker named creatinine-fibrinogen ratio (CFR) for the prediction of composite adverse outcomes (CAO) in placental abruption cases. METHODS: A total of 109 placental abruption patients (30 with adverse outcomes, 79 without adverse outcomes) were enrolled in this retrospective cohort study. Patients with at least one of the features listed below were included in the abruption with CAO group: requirement of blood product transfusion (erythrocyte suspension, fresh frozen plasma, pooled thrombocyte, thrombocyte apheresis), development of acute kidney injury or disseminated intravascular coagulation, and need for intensive care unit. Laboratory parameters and CFR values at admission to the hospital were compared between the two groups. RESULTS: Higher creatinine and lower fibrinogen levels were found in the CAO group (p = 0.007 and p < 0.001 respectively). The CFR value of the CAO group was significantly higher (p < 0.001). In the ROC curve analysis performed to investigate the value of CFR in CAO prediction, the area under the curve (AUC) was calculated as 0,802 (95% CI 0.709-0.895, 77% sensitivity, 65% specificity). CONCLUSION: CFR seems to be a practical marker for the prediction of CAOs in pregnant women with ablatio placenta.

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Hospitalized patients with COVID-19 infection frequently have coagulopathy resembling disseminated intravascular coagulation (DIC). An elevation of D-dimer level is associated with a poor prognosis; however, the role of other fibrin degradation products, such as soluble fibrin monomers (SFMC), is not known. The objective of the study was to investigate the frequency and prognostic role of elevated SFMC in patients with COVID-19. In this retrospective cohort study, patients hospitalized between April 1, 2020 and December 14, 2020 at Mayo Clinic with COVID-19 infection who underwent DIC panel testing were identified. Results of laboratory tests and outcomes (thrombosis and death) within 40 days of testing were obtained via medical record review. Of 108 patients, D-dimer was elevated in 82 (75.9%) patients. Of those with elevated D-dimer, SFMC was elevated in 19/82 (23%) patients. There were 16 thrombotic events and 16 deaths during the 40-day follow-up. The incidence of overt-DIC was 4.6%. In univariate analysis, D-dimer ≥5 x highest upper limit normal (ULN) and elevated SFMC were each associated with higher 40-day mortality. However, when used in combination with D-dimer ≥5 x highest ULN, an elevated SFMC provided no further mortality predictive value. Compared to 75.9% of patients with elevated D-dimers, of those tested, only 23% had elevated SFMC. These results support the hypothesis that elevated D-dimer in COVID-19 infection is a direct consequence of endothelial damage and not overt-DIC.

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OBJECTIVES: Coagulation dysfunction is an evident factor in the clinical diagnosis and treatment of patients with coronavirus disease 2019 (COVID-19), appearing even in COVID-19 patients with normal inflammation indices. Therefore, this study aimed to analyze the characteristics of coagulation function indices in COVID-19 patients to investigate possible mechanisms through the comparison of non-severe and severe COVID-19 patients. METHODS: We included 143 patients whose clinical characteristics, coagulation function, and other indices such as inflammatory factors were collected and compared based on disease severity. RESULTS: Activated partial thromboplastin time (APTT), D-dimer, and fibrinogen levels were evidently higher in the severe group than in the non-severe group. Among non-severe COVID-19 patients, the aforementioned indicators depicted increasing trends, but the fibrinogen level alone was higher than normal. However, in severe COVID-19 patients, values of all three indices were higher than normal. In severe COVID-19 patients, fibrinogen and D-dimer were correlated with several inflammation indices during the early stage of the disease. However, no correlation between fibrinogen and inflammatory factors was observed in non-severe COVID-19 patients at any time point. DISCUSSION: Results revealed that the hypercoagulability tendency of severe COVID-19 patients was more evident. The relationship between coagulation function and inflammatory factors showed that changes in coagulation function in severe COVID-19 patients may be related to abnormal increase in inflammatory factors at an early stage; however, in non-severe COVID-19 patients, there might be other factors leading to abnormal coagulation. CONCLUSION: Inflammatory factors were not the only cause of abnormal coagulation function in COVID-19 patients.

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SARS-CoV-2 attaches to the angiotensin-converting enzyme 2 (ACE-2) receptor on human cells. The virus causes hypercytokinemia, capillary leak, pulmonary edema, acute respiratory distress syndrome, acute cardiac injury, and leads to death. Mesenchymal stem cells (MSCs) are ACE-2 negative cells; therefore, can escape from SARS-CoV-2. MSCs prevent hypercytokinemia and help the resolution of the pulmonary edema and other damages occurred during the course of COVID-19. In addition, MSCs enhance the regeneration of the lung and other tissues affected by SARS-CoV-2. The case series reported beneficial effect of MSCs in COVID-19 treatment. However, there are some concerns about the safety of MSCs, particularly referring to the increased risk of disseminated intravascular coagulation, and thromboembolism due to the expression of TF/CD142. Prospective, randomized, large scale studies are needed to reveal the optimum dose, administration way, time, efficacy, and safety of MSCs in the COVID-19 treatment.

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OBJECTIVE: The factor VIIa-Antithrombin (VIIa-AT) complex is a relatively new biomarker associated with the activation of the extrinsic coagulation pathway. Since disseminated intravascular coagulation (DIC) is primarily driven by issue factor (TF)-induced extrinsic coagulation activation, the plasma level of factor VIIa-AT, via its role as an activation marker of the extrinsic pathway, could be a potential marker for DIC. The clinical significance of extrinsic coagulation markers, including factor VIIa-AT, in DIC was investigated. METHODS: The extrinsic coagulation markers, including factor VIIa-AT, TF, factor VII, and antithrombin (AT), were measured in 148 patients clinically suspicious for DIC. Multiple linear regression and Cox proportional-hazard analysis were conducted to evaluate both contributing factors and the prognostic power of the markers. RESULTS: The factor VIIa-AT complex, factor VII, and AT levels were significantly lower in the overt-DIC group and gradually decreased according to the severity of DIC based on the DIC scores. On the contrary, TF was significantly higher in the overt-DIC group. The factor VII level was revealed as a significant independent contributor to the factor VIIa-AT level. Upon multivariable Cox proportional-hazard analysis, the factor VIIa-AT complex showed the highest hazard ratio (3.41; 95% confidence interval 1.11-10.44). CONCLUSION: The factor VIIa-AT complex reflects the severity of DIC and is an independent prognostic factor of DIC. Our findings hint at the potential of the factor VIIa-AT complex to be used as a complementary marker to well-established biomarkers such as AT.

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Early descriptions of COVID-19 associated coagulopathy identified it as a disseminated intravascular coagulation (DIC). However, recent studies have highlighted the potential role of endothelial cell injury in its pathogenesis, and other possible underlying mechanisms are being explored. This study aimed to analyse the coagulation parameters of critically and noncritically ill patients with COVID-19 bilateral pneumonia, determine if coagulation factors consumption occurs and explore other potential mechanisms of COVID-19 coagulopathy. Critically and noncritically ill patients with a diagnosis of COVID-19 bilateral pneumonia were recruited. For each patient, we performed basic coagulation tests, quantification of coagulation factors and physiological inhibitor proteins, an evaluation of the fibrinolytic system and determination of von Willebrand Factor (vWF) and ADAMTS13. Laboratory data were compared with clinical data and outcomes. The study involved 62 patients (31 ICU, 31 non-ICU). The coagulation parameters assessment demonstrated normal median prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) in our cohort and all coagulation factors were within normal range. PAI-1 median levels were elevated (median 52.6 ng/ml; IQR 37.2-85.7), as well as vWF activity (median 216%; IQR 196-439) and antigen (median 174%; IQR 153.5-174.1). A mild reduction of ADAMTS13 was observed in critically ill patients and nonsurvivors. We demonstrated an inverse correlation between ADAMTS13 levels and inflammatory markers, D-dimer and SOFA score in our cohort. Elevated vWF and PAI-1 levels, and a mild reduction of ADAMTS13 in the most severe patients, suggest that COVID-19 coagulopathy is an endotheliopathy that has shared features with thrombotic microangiopathy.

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