D-dimer Concentration Research Articles

Risk factors for lower extremity deep vein thrombosis in acute stroke patients following endovascular thrombectomy: a retrospective cohort study.

Deep vein thrombosis (DVT) in lower extremities as a common complication of acute ischemic stroke (AIS) has long been studied. However, as the therapeutic options for AIS continue to advance, the pathogenic mechanisms behind DVT may change. Endovascular thrombectomy (EVT) has replaced intravenous thrombolysis and become the preferred treatment for AIS patients with large vessel occlusions. Therefore, it is important to update our understanding of DVT and its management. This study aimed to determine the prevalence and risk factors of DVT in AIS patients following EVT. In this retrospective study, 245 AIS patients who had received EVT were recruited between January 2020 and December 2021. Within 10 days (median 4 days) of thrombectomy, DVT was diagnosed by ultrasonography. Demographic characteristics, clinical findings, and therapeutic procedures were compared between patients with and without DVT using univariate analysis. Cutoff points were defined for EVT time and plasma D-dimer concentration. Multivariable logistic regression was then used to determine the independent risk factors for DVT and evaluate their predictive power. The prevalence of DVT in AIS patients after EVT was 27.3%. Multifactorial logistic regression analysis showed that age (OR 1.036, 95% CI 1.001-1.073; P = 0.045), female sex (OR 3.015, 95% CI 1.446-6.289; P = 0.003), lower limb muscle strength less than grade three (OR 7.015, 95% CI 1.887-26.080; P = 0.004), longer EVT time (OR 1.012, 95% CI 1.004-1.020; P = 0.003), and higher D-dimer levels (OR 1.350, 95% CI 1.150-1.585; P < 0.001) were independently associated with higher DVT risk in AIS patients following EVT. The cutoff points for operative time of EVT and plasma D-dimer were 65.5 min and 1.62 mg/L, respectively, above which the risk for DVT was dramatically increased with OR > 4 in AIS patients. AIS patients are at increased risk of developing DVT following EVT particularly if they have undergone prolonged thrombectomy procedures and exhibit high plasma levels of D-dimers. However, the results of our study need to be validated by a multicenter prospective study with a larger population of stroke patients.

Implication of myddosome complex genetic variants in outcome severity of COVID-19 patients.

During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio=1.98 (95% IC=1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG+GG vs. AA), we observed an Odd Ratio=1.70 (95% CI=1.02-2.86) with severe, Odd Ratio=1.82 (95% CI=1.04-3.21) with critical, and Odd Ratio=2.44 (95% CI=1.21-4.9) with deceased outcomes. To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

Effect of interval hypoxic therapy in the hypoxia-hyperoxia mode on the hemostatic system of patients who have suffered a new coronavirus infection COVID-19

Background. The positive effect of interval hypoxic therapy in the treatment of many diseases has become the basis for its use in rehabilitation after a new coronavirus infection to normalize disorders of the hemostatic system.&#x0D; Aim. To identify the peculiarities of the interval hypoxic therapy effect on the hemostatic system of patients who have suffered a new coronavirus infection.&#x0D; Material and methods. The work was carried out from April 2020 to May 2022. 220 men aged 4559 years (average age 48.82.4 years) were examined. The main group included 90 people who had a moderate coronavirus infection a month ago; the control group (n=70) was represented by relatively healthy people; the comparison group (n=60) suffered coronavirus infection and underwent standard rehabilitation without hypoxic therapy. The content of platelets, D-dimer, international normalized ratio, prothrombin time, activated partial thromboplastin time, antithrombin III activity, interleukin-6 level, and C-reactive protein content in the blood serum was determined. To assess statistically significant differences, a parametric method applying paired and unpaired Student's t-test was used. Differences were considered statistically significant at p 0.05.&#x0D; Results. In patients of the main group, a violation of the hemostatic system, indicating increased thrombogenicity of the blood against the background of persistent inflammatory activity, was revealed. After interval hypoxic therapy, the platelet count increased to 215.5323.57109/l (p=0.035), activated partial thromboplastin time to 26.741.84 s (p=0.035), international normalized ratio to 0.890.06 (p=0.005), antithrombin III activity in the blood up to 81.814.33% (p=0.007); the level of fibrinogen decreased to 3.861.09 g/l (p=0.035) and the content of D-dimer in the blood to 255.5817.36 ng/ml (p=0.035). There was a decrease in the level of interleukin-6 to 6.030.65 pg/ml (p=0.035) and C-reactive blood protein to 1.030.15 mg/l (p=0.035).&#x0D; Conclusion. Interval hypoxic therapy had a normalizing effect on the hemostatic system of patients who suffered a new coronavirus infection, as a result of suppressing the inflammatory process in the body.

Paediatric COVID-19 Outcomes: Haematology Parameters, Mortality Rates, and Hospitalization Duration.

The global COVID-19 pandemic has strained healthcare systems around the globe, necessitating extensive research into the variables that affect patient outcomes. This study examines the relationships between key haematology parameters, duration of hospital stay (LOS), and mortality rates in COVID-19 cases in paediatric patients. Researchers analyse relationships between independent variables (COVID-19 status, age, sex) and dependent variables (mortality, LOS, coagulation parameters, WBC count, RBC parameters) using multivariate regression models. Although the R-square values (0.6-3.7%) indicate limited explanatory power, coefficients with statistical significance establish the impact of independent variables on outcomes. Age emerges as a crucial predictor of mortality; the mortality rate decreases by 1.768% per age group. Both COVID-19 status and age have an inverse relationship with length of stay, emphasising the milder hospitalisation of children. Platelet counts decline with age and male gender, potentially revealing the influence of COVID-19 on haematological markers. There are significant correlations between COVID-19 status, age, gender and coagulation measures. Lower prothrombin time and D-dimer concentrations in elder COVID-19 patients are indicative of distinct coagulation profiles. WBC and RBC parameters exhibit correlations with variables: COVID-19-positive patients have lower WBC counts, whereas male COVID-19-positive patients have higher RBC counts. In addition, correlations exist between independent variables and the red cell distribution width, mean corpuscular volume, and mean corpuscular haemoglobin. However, there is no correlation between mean corpuscular haemoglobin concentration and outcomes, indicating complex interactions between haematological markers and outcomes. In essence, this study underlines the importance of age in COVID-19 mortality, provides novel insights into platelet counts, and emphasises the complexity of the relationships between haematological parameters and disease outcomes.

Гемостаз у судинах пуповини в недоношених і екстремально недоношених новонароджених

According to the WHO, about 10% of children are born prematurely every year. The hemostatic system of the fetus and newborn is markedly different from the ones of adults. Physiological concentrations of coagulation proteins gradually increase during pregnancy and are expected lower in preterm infants compared to full-term infants. It’s known today that neonates have a reduction of coagulation factors I-XII (except VIII), the coagulation inhibitors antithrombin III, protein C, and heparin cofactor II at the same time. The tendency to hypocoagulation is more pronounced in premature newborns. Purpose - to compare the main parameters of hemostasis in full-term and premature newborns in different gestational periods. Materials and methods. This study has analyzed the level of fibrinogen, D-dimer, prothrombin index, and activated partial thromboplastin time in the blood of mothers and their newborns. The study included three groups of mothers and their newborns: the Group I at 37-41 weeks of gestation, the Group II - 28-34 weeks, the Group III - 22-27 weeks. Results. The studies have shown that the level of fibrinogen in umbilical cord blood is much lower than in maternal, both in fulltime delivery and in preterm cases of 28-34 weeks and 22-27 weeks. The increase of the D-dimer range comparatively to mother’s is received in all terms and more than double in 22-27 weeks (910±347.6 μg/l in newborn against maternal 487±267.0 μg/l, p&lt;0.05). A fetal prothrombin index level was one and a half more two times smaller in comparison to mothers signs in all cases: 56±9.8% in 35-41 weeks, 53±13.2% in 28-34 weeks and 60±11.7% in 22-27 weeks of gestations. And vice versa, an activated partial thromboplastin time is one and a half more two times higher than all maternal values - 49.7±7.86 sec., 59.4±19.11 sec., and 50.1±22.15 sec. in accordance with terms of gestations with a normal 28-40 sec. in adult. Conclusions. The blood of newborns in all terms is characterized by a higher level of D-dimer compared to maternal values (970±430.9 μg/l in the term 37-41 weeks, 875±226.1 μg/l in 28-34 weeks, 910±347.6 μg/l in 22-27 weeks). D-dimer concentration ranges in neonates differ from those in adults, so caution is required in their use and interpretation. A higher level of AChT (49.7±7.86 sec; 59.4±19.11 sec; 50.1±22.15 sec, according to groups) and lower fibrinogen values (1840±660.5 mg/l in term 37-41 weeks; 1734±542.6 mg/l in 28-34 weeks; 1498±1005.5 mg/l in 22-27 weeks) and PI (56±9.8%; 53±13.2%; 60±11.7%) compared to their mothers. 2. The level of fibrinogen concentration of full-term newborns (1840±660.5 mg/l) is probably higher, compared to 1498±1005.5 mg/l in the period of 22-27 weeks of gestation (p&lt;0.05), the difference in other indicators of coagulation independently from the gestational age was not statistically significant. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Імунозапальні зміни важкого перебігу COVID-19 у вагітних

Pregnant women are the most sensitive contingent to the effects of the virus and this is due to adaptive physiological changes in the woman’s bronchopulmonary system and features of the immune system. “Physiological tolerance” is formed during pregnancy and this is accompanied by a decrease in the level of T-helpers and natural killers in pregnant women and leads to a decrease in the resistance of the woman’s body to the action of altering viral and bacterial agents. Purpose - to reveal the peculiarities and clarify the nature of clinical and instrumental changes in pregnant women with a severe course of COVID-19 under dynamic observation. Materials and methods. The study included 40 pregnant women with coronavirus disease with a gestational age of 22 to 41 weeks, who formed the main group. The control group consisted of 40 women whose pregnancies were not complicated by coronavirus disease. The course of the disease and the influence of the coronavirus infection on the course of pregnancy were evaluated according to the results of: general - clinical examination, laboratory examination (general blood test, biochemical blood test, coagulogram, C-reactive protein, D-dimer, procalcitonin and interleukin 6), instrumental examination (cardiotocographic research, pulse oximetry). Results. Peculiarities of changes in clinical and laboratory indicators in pregnant women were studied depending on the stage of development of the coronavirus disease. During the study, it was established: a significant increase in the level of indicators in accordance with the control group, namely an increase in leukocytes by 38.2% to 10.07±1.59×109/l (р&lt;0.05), an increase in thrombocytes by 35% to 314.36±49.70 (р&lt;0.05), an increase in monocytes by 22.5% to 7.08±1.12 and a decrease in lymphocytes to 13.46±2.13, which is 51.2% lower than the indicators of the control group. The level of C-reactive protein in pregnant women with COVID-19 is probably higher than in all groups of examined patients. The level of D-dimer exceeded the indicators of the control group in patients of all groups with the maximum values of indicators in patients at the time of admission to department of anaesthesiology and intense therapy (DAIT) and was 4867.42 ng FEU/ml, which was 6.3 times higher than the level of the control group (p&lt;0.05). It should be noted that the amount of interleukin-6 in patients of all studied groups was statistically higher than that of the control group. Conclusions. Immune-inflammatory blood changes in pregnant women occur in the case of a severe course of COVID-19 and are accompanied by an increase in the level of interleukin-6 at all stages of the severe course of the disease. СRP is a marker of the severe course of the coronavirus disease in pregnant women. The identified changes are accompanied by coagulopathy and hypercoagulation with increased D-dimer content in patients with a severe course of the disease. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Time-dependent changes of platelet and D-dimer parameters in vaccinated &lt;i&gt;versus&lt;/i&gt; non-immunized COVID-19 patients

There are increasing data concerning changes in hematological (clinical) and biochemical blood tests in patients with COVID-19 infection, which indicate the severity of the manifestations of the infectious process. Coagulopathy often correlates with the severity of COVID-19 disease and the risk of death. In this regard, prediction of developing coagulopathy and its prevention remain quite relevant. The aim of our study was to identify differences in the content of platelets and D-dimer in patients with COVID-19. The study included cohorts of patients vaccinated against SARS-CoV-2, and those not immunized against this infection.&#x0D; A prospective, randomized, observational study of the patients’ response was performed in cohorts of 588/52.2% vaccinated (vaccinated) and 588/52.2% non-immunized (non-vaccinated) patients with diagnosed COVID-19 over the period from 23.06.2021 to 01.05.2022. The levels of blood platelets and D-dimer, as well as clinical outcomes of the disease in patients with COVID-19, were studied in dynamics on days 1-2, 5-6 and 10-12 of hospitalization.&#x0D; Upon admission, the normal value of the blood platelet counts did not differ between the compared groups, being 206.58 × 109 in vaccinated group and 204.85 × 109 in the unvaccinated group, respectively. a moderate increase in the concentration of D-dimer was noted in both groups upon admission, i.e., 2838.60 ng/mL in the group of vaccinated patients and 3242.08 ng/mL among the unvaccinated patients. In the course of the study, we have shown that the dynamics of D-dimer index in vaccinated versus non-immunized persons was similar according to the days of disease, showing an increase from the first day and a trend towards an higher values, starting from 5-6 days. At the same time, the dynamics in the vaccinated patients was somewhat less favorable than that of the non-immunized subjects. In the patients who were not immunized throughout the entire observation period, the platelet count exceeds the levels found in vaccinated subjects, thus suggesting higher risk of thrombosis and cytokine storm.&#x0D; The data obtained show that the dynamics of D-dimer and platelet counts in vaccinated and non-immunized people is similar on appropriate terms of the illness. However, the changes are more pronounced in vaccinated cohort, but it does not indicate a greater risk of adverse outcomes.

Fungi Fibrinolytic Compound 1 Plays a Core Role in Modulating Fibrinolysis, Altering Plasma Clot Structure, and Promoting Susceptibility to Lysis.

Fibrin clot structure and function are major determinants of venous and arterial thromboembolic diseases, as well as the key determinants of the efficiency of clot lysis. Studies have revealed that fungi fibrinolytic compound 1 (FGFC1) is a novel marine pyranisoindolone natural product with fibrinolytic activity. Here, we explore the impacts of FGFC1 on clot structure, lysis, and plasminogen activation in vitro using turbidimetric, enzyme-linked immunosorbent assay, confocal and electron microscopy, urokinase, or plasmin chromogenic substrate. Clots formed in the presence of FGFC1 expressed reduced fibrin polymerization rate and maximum turbidity; however, they did not influence the lag phase of fibrin polymerization. In the absence of scu-PA (single-chain urokinase plasminogen activator), microscopy revealed that FGFC1 increased the number of protofibrils within fibrin fiber and the pore diameter between protofibrils, inducing clots to form a region of thinner and looser networks separated by large pores. The effects of FGFC1 on scu-PA-mediated plasma clot structure were similar to those in the absence of scu-PA. In addition, FGFC1 promoted the lysis of clots and increased the D-dimer concentration in lysate. FGFC1 increased the generation rate of p-nitroaniline in plasma. These results show that FGFC1 has fibrinolytic activity in plasma, leading to interference with the release of fibrinopeptide B to affect lateral aggregation of protofibrils and increase clot susceptibility to fibrinolysis by altering its structure.

New-onset atrial fibrillation in patients with SARS-CoV-2 pneumonia as a manifestation of acute myocardial injury

BACKGROUND: Over the past 3 years, the prevalence of atrial fibrillation (AF) has increased significantly worldwide, which was associated with the pandemic caused by SARS-CoV-2. It is accompanied by an increase in the cases of ischemic stroke, myocardial infarction, and development of heart failure due to acute myocardial injury. Given the high lethality of SARS-CoV-2 infection (COVID-19), studying the characteristics of new-onset AF is essential.&#x0D; AIM: The study aims at determining the predictors of new-onset AF in patients with COVID-19 pneumonia and at analyzing the clinical and pathophysiological characteristics of acute myocardial injury.&#x0D; MATERIALS AND METHODS: In 36 patients aged 4482 years (average 68.0) with COVID-19 pneumonia, AF paroxysms were recorded for the first time. All of them underwent computed tomography of the chest, electrocardiography, and echocardiography. The left ventricular ejection fraction was calculated using the Simpson method. Oxygen saturation was determined as blood oxygen saturation. Clinical blood tests were performed, C-reactive protein (CRP), ferritin, D-dimer, fibrinogen, and troponin I levels were measured.&#x0D; RESULTS: Along with the well-known predictors of AF development (arterial hypertension, coronary heart disease, left ventricular myocardial hypertrophy, and left atrial dilatation), with COVID-19 pneumonia, new-onset AF paroxysms were recorded in patients of the middle, elderly, and late-life age. In 44.4% of patients with AF, cardiomegaly occurred with dilatation of both atria and ventricles. With decreased left ventricular ejection fraction, the incidence of AF paroxysms reached 61.5%. With preserved ejection fraction, AF paroxysms occurred much less frequently (27%). In patients with AF, the extent of lung damage is on average 62.5% (2080%) with oxygen support saturation of 93% (7697%). Serum troponin I levels of 2000 ng/L indicated acute myocardial injury. CRP and blood ferritin values confirmed the presence of a pronounced inflammatory component in myocardial injury. High concentrations of blood fibrinogen and D-dimer, reaching 16,301 ng/mL, were associated with a tendency to hypercoagulation in patients with AF and COVID-19 pneumonia.&#x0D; CONCLUSIONS: COVID-19 has a direct damaging effect on the myocardium and probably persists for a long time, which may induce AF in patients with acute pneumonia.

Predictors of an unfavorable course of COVID-19

The aim of the study was to identify the features of the unfavorable clinical course of a new coronavirus infection.Material and methods. The analysis of clinical data, laboratory results and comorbidity of 168 patients with a confirmed diagnosis of a new coronavirus infection aged 65,0 [57,0; 74,0] years was carried out. Two groups of patients were distinguished – 126 persons with a moderate course and with clinical recovery in the outcome of the disease and 42 persons with a severe course and a fatal outcome of the disease. Transnosological polymorbidity was assessed by the average number of nosologies corresponding to the three-digit ICD-10 rubricification, transsystemic – by the number of affected systems. Hemogram parameters, blood content of C-reactive protein, creatinine, urea, glucose, prothrombin index, international normalized ratio, activated partial thromboplastin time, platelet count, D-dimer concentration were estimated.Results. In the group of patients with fatal outcomes, compared to patients with recovery, there were statistically significantly higher indices of transnosological and transsystemic polymorbidity (1.5 and 2 times, respectively), they were more likely to have ischaemic heart disease, myocardial infarction, transient ischemic attack in anamnesis, atrial fibrillation, chronic heart failure; blood concentration of C-reactive protein, fasting glucose, urea, D-dimer in the blood serum was higher, the number of thrombocytes was less.Conclusions. A high degree of transnosological and transsystemic polymorbidity, a history of myocardial infarction and transient ischemic attack, comorbid chronic heart failure, atrial fibrillation, an increase in D-dimer, CRP content, and a decrease in platelet number are predictors of severe course and the lethal outcome of COVID-19.

Pulmonary embolism in COVID-19 pneumonia patients admitted to temporary hospital - The follow-up study

PurposeCoronavirus disease 2019 (COVID-19) is linked with major coagulation disorders, especially higher risk of developing pulmonary embolism (PE). Our study summarizes COVID-19 patients’ management with concomitant PE during the first weeks of pandemic and underlines the importance of D-dimer concentration assessment at admission in terms of prognosis. Material and methodsStudy group consisted of 107 outpatients (mean age 68.91 ​± ​12.83 years) admitted to the Temporary COVID-19 Hospital in Bialystok, Poland with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and suspicion of PE based on elevated D-dimer concentration (>500 ​μg/l) and/or low saturation rate (<90%). The clinical follow-up lasted 6 months. Death or re-hospitalization were used as composite clinical endpoint (CEP). ResultsCumulative incidence of PE was 62.3% (73/107 patients). Most of the patients were in the intermediate PE risk group according to the pulmonary embolism severity index (PESI) score. The mean total computed tomography (CT) lung involvement of COVID-19 findings was 48.42 ​± ​27.71%. Neither D-dimers nor NT-proBNP concentrations correlated significantly with the percentage of lung abnormalities in CT. Patients with baseline D-dimer concentration higher than 1429 ​μg/l had worse prognosis in 6-months observation, log-rank test, p ​= ​0.009. ConclusionsOngoing SARS-CoV-2 infection along with massive involvement of lung tissue and concomitant thrombi in pulmonary arteries are challenging for physicians. It seems that simple D-dimer concentration assessment at admission may be a helpful tool not only to predict PE but also to estimate the long-term prognosis.

A prospective evaluation of the prevalence of thromboemboli and associated hemostatic dysfunction in dogs with carcinoma or sarcoma.

Knowledge of the prevalence of thromboemboli and the associated hemostatic status in dogs with carcinoma or sarcoma is unknown and might allow earlier intervention. Estimate prevalence of thromboemboli and their association with hemostatic changes in dogs with carcinomas or sarcomas; estimate predictive values of hemostatic variables for thromboembolic disease in tumor-bearing dogs. Thirty-two dogs with sarcoma, 30 with carcinoma, 20 healthy age-controlled dogs. Prospective cross-sectional study. A hemostasis panel (platelet concentration, thromboelastography, fibrinogen and D-dimer concentration, factor X, VII and antithrombin activity) was performed in all dogs. Tumor-bearing dogs underwent complete post mortem and histopathological evaluation. Comparisons between healthy dogs and tumor-bearing dogs with and without intracavitary hemorrhage; and tumor-bearing dogs with and without microthrombi were analyzed. Thromboembolic disease was identified in 32/62 (52%, 95% CI: 39%-65%) tumor-bearing dogs. Microthrombi were identified in 31/62 (50%, 95% CI: 37%-63%) dogs, 21/31 (68%, 95% CI: 49%-83%) had exclusively intra-tumoral microthrombi, 10/31 (32%, 95% CI: 17%-51%) had distant microthrombi. Macrothrombi were identified in 3 tumor-bearing dogs. Hemostatic changes potentially consistent with overt and non-overt disseminated intravascular coagulation were identified in some tumor-bearing dogs. D-dimer concentrations were significantly higher (P = .02) and platelet concentration significantly lower (P = .03) in tumor-bearing dogs with microthrombi compared to tumor-bearing dogs without microthrombi. D-dimer concentration above 500 ng/mL was 80% sensitive and 41% specific for the prediction of microthrombi presence. The high microthrombi prevalence and concomitant hemostatic dysfunction in dogs with carcinomas or sarcomas has not previously been reported, though the clinical importance is unknown. Increased D-dimer concentration might increase suspicion of microthrombi.

Association of D-Dimer, C-Reactive Protein, and Ferritin with COVID-19 Severity in Pregnant Women: Important Findings of a Cross-Sectional Study in Northern Brazil.

The COVID-19 pandemic has had a great impact on pregnant women due to the broad clinical spectrum of the disease. The present study investigated the profile of three biomarkers during hospital admission of pregnant women-D-dimer, C-reactive protein (CRP), and ferritin-and their correlation with the severity and outcome of COVID-19. The cross-sectional study included 226 pregnant women hospitalized in the city of Belém, Pará, Northern Brazil, from April 2020 to July 2021. Epidemiological and laboratory data were obtained from medical records, and all pregnant women underwent RT-PCR molecular testing for the detection of SARS-CoV-2. In total, 121 (53.5%) were positive and 105 (46.5%) were negative for SARS-CoV-2 using RT-PCR. Most pregnant women (49.5%) with COVID-19 were between 26 and 34 years old, were residing in the interior of the state of Pará (51.2%), and were in the third gestational trimester (71.9%). In addition, 71.1% of them were admitted to the ward and 28.9% were admitted to the intensive care unit (ICU), with 90.9% surviving COVID-19. The concentrations of D-dimer (p = 0.0122) and ferritin (p ≤ 0.0001) were significantly higher among pregnant women with COVID-19, especially among those hospitalized in the ICU. Ferritin and D-dimer seem to serve as important biomarkers for the prognosis of COVID-19 in pregnant women, which was not observed for CRP.

Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis.

Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. PROSPERO ID 89366.

Impact of Alteplase on Mortality in Critically Ill Patients with COVID-19 and Pulmonary Embolism.

COVID-19 is an independent risk factor for pulmonary embolism (PE). Little is known about alteplase therapy in this patient group. A retrospective study analyzed 74 patients with PE and acute respiratory distress syndrome (ARDS) due to COVID-19 who were hospitalized in the intensive care unit in 2021. Patients with or without confirmed right heart thrombi (RHT) were treated with unfractionated heparin or alteplase. The mortality rate in patients with RHT treated with heparin was 100% compared to 37.9% and 55.2% in those treated with alteplase without RHT and alteplase with RHT, respectively. The risk of death in the alteplase group increased with delayed thrombolysis (p = 0.009, odds ratio (OR) = 1.73 95% CI (confidence interval) 1.14-2.62), increased D-dimer concentration (p = 0.02, OR = 1.43 95% CI 1.06-1.93), and decreased PaO2/FiO2 ratio (p = 0.001, OR = 0.56 95% CI 0.41-0.78). The receiver operating characteristic method determined that a 1-day delay in thrombolytic treatment, D-dimer concentration >5.844 mg/L, and PaO2/FiO2 <144 mmHg predicted a fatal outcome. The risk of death in patients with severe COVID-19 with ARDS and PE increases with higher D-dimer levels, decreased PaO2/FiO2, and delayed thrombolytic treatment. Thrombolysis seems to be treatment of choice in severe COVID-19 with PE and RHT. It should be carried out as soon as possible after the diagnosis is established.

Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial.

Thrombo-inflammation is central to COVID-19-associated coagulopathy. TF (tissue factor), a driver of disordered coagulation and inflammation in viral infections, may be a therapeutic target in COVID-19. The safety and efficacy of the novel TF inhibitor rNAPc2 (recombinant nematode anticoagulation protein c2) in COVID-19 are unknown. ASPEN-COVID-19 was an international, randomized, open-label, active comparator clinical trial with blinded end point adjudication. Hospitalized patients with COVID-19 and elevated D-dimer levels were randomized 1:1:2 to lower or higher dose rNAPc2 on days 1, 3, and 5 followed by heparin on day 8 or to heparin per local standard of care. In comparisons of the pooled rNAPc2 versus heparin groups, the primary safety end point was major or nonmajor clinically relevant International Society of Thrombosis and Haemostasis bleeding through day 8. The primary efficacy end point was proportional change in D-dimer concentration from baseline to day 8, or discharge if before day 8. Patients were followed for 30 days. Among 160 randomized patients, median age was 54 years, 43.1% were female, and 38.8% had severe baseline COVID-19. There were no significant differences between rNAPc2 and heparin in bleeding or other safety events. Overall, median change in D-dimer was -16.8% (interquartile range, -45.7 to 36.8; P=0.41) with rNAPc2 treatment and -11.2% (-36.0 to 34.4; P=0.91) with heparin (Pintergroup=0.47). In prespecified analyses, in severely ill patients, D-dimer levels tended to increase more within the heparin (median, 29.0% [-14.9 to 145.2]; P=0.02) than the rNAPc2 group (median, 25.9% [-49.1 to 136.4]; P=0.14; Pintergroup=0.96); in mildly ill patients, D-dimer levels were reduced within each group with a numerically greater reduction with rNAPc2 versus heparin (rNAPc2 median, -32.7% [-44.7 to 4.3]; P=0.007 and heparin median, -16.8% [-36.0 to 0.5]; P=0.008, Pintergroup=0.34). rNAPc2 treatment in hospitalized patients with COVID-19 was well tolerated without excess bleeding or serious adverse events but did not significantly reduce D-dimer more than heparin at day 8. URL: https://www. gov; Unique identifier: NCT04655586.

Association between fatty liver index and blood coagulation markers: a population-based study

BackgroundPopulation-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population.MethodsAfter the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54–74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status.ResultsIn the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients.ConclusionIn this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.

Comparative study on albumin, C-Reactive Protein (CRP) and D-dimer in chronic hemodialysis patients with COVID-19

Link of Video Abstract: https://youtu.be/-i3vr4qpQUU Background: Chronic kidney disease (CKD) patients on hemodialysis are more susceptible to COVID-19 infections. Mortality and morbidity rate are higher in this population. Thus, it is critical to understand which parameters are associated with mortality in this population. C-reactive protein (CRP), albumin, and d-dimer were shown in several studies to be associated with mortality in COVID-19-infected hemodialysis patients. Methods: This study was a comparative observational, retrospective study from the medical records of Dr. Soetomo General Hospital in Surabaya, Indonesia. Chronic kidney disease patients on maintenance hemodialysis who tested positive for COVID-19 from June 2020 to January 2021 and underwent treatment in the isolation ward were included in this study. Data were analyzed using SPSS version 21.0 for Windows. Results: The non-survivor groups have statistically significant lower albumin (2.78 (2.21-3.40) g/dL vs. 3.20 (2.45-3.80) g/dL; p=0.040) and higher CRP (10.40 (4.10-28.6) mg/L vs. 3.20 (0.10-80.0) mg/L; p=0.020) compared to the survivor group (Table 2). D-dimer value has no significant difference between the non-survivor and survivor groups (4,290 (190-18,310) ng/mL vs. 2,630 (190-19,430) ng/mL; p=0.140) Conclusion: Non-survivor CKD patients with COVID-19 infections have significantly lower serum albumin and higher CRP concentrations. There is no significant difference in D-dimer concentrations in the survivor and non-survivor groups.

#5401 REAL-WORLD STUDY BETWEEN NEPHROTIC SYNDROME AND VENOUS THROMBOEMBOLISM

Abstract Background and Aims Nephrotic syndrome (NS) is a recognized risk factor of venous thromboembolism (VTE), however, there have been limited comprehensive epidemiologic data on VTE among NS patients. Therefore, we designed our study to assess the epidemiology and clinical correlates of VTE among hospitalized adults with NS in China. Method In this nationwide real-world study of 78,797 hospitalized patients with NS from 18 medical centers across China, VTE was identified by International Classification of Diseases, 10th revision (ICD-10) codes or imagological examinations during hospitalization. Multivariable logistic regression analysis was used to investigate the association between clinical variables and VTE through the R Programming software. Results A total of 1227 VTE cases were identified in the hospitalized NS population and the detection rate was 1.56%. Detection rate of VTE varied significantly in patients with different pathologic types of NS. Patients with membranous nephropathy (MN) had a significantly increased risk of VTE {Odds ratio [OR] 2.11 [95% confidence interval (CI) 1.12–4.36]}. While patients with focal segmental glomerulosclerosis (FSGS) did not show a significant high risk [OR 0.93 (95% CI 0.29–2.60)] compared with minimal change disease. We also found that male [OR 1.44 (95% CI 1.15–1.80)], age [OR 1.09 (95% CI 1.02–1.17)], anemia [OR 1.50 (95% CI 1.15–1.95)], cerebral bleeding [OR 3.23 (95% CI 1.69–6.16)], respiratory tract infection [OR 2.05 (95% CI 1.60–2.63)], respiratory failure [OR 2.24 (95% CI 1.42–3.53)], use of proton pump inhibitors (PPIs) [OR 2.19 (95% CI 1.54–3.12)], use of glucocorticoids [OR 1.46 (95% CI 1.03–2.09)] and immunosuppressants [OR 1.48 (95% CI 1.14–1.93), orthopedic operations [OR 1.97 (95% CI 1.22–3.18)], high-level D-dimer (&amp;gt;0.55 mg/L) [OR 2.62 (95% CI 1.87–3.65)] were associated with increased risk of VTE detection. While 24-hour urine protein quantification &amp;gt;10 g/d [OR 1.24 (95% CI 0.90–1.70)] showed little significant correlation with VTE. Hypertension [OR 0.74 (95% CI 0.58–0.95)] and the use of diuretics [OR 0.72 (95% CI 0.53–0.97)] were found to have a negative correlation with VTE detection. Conclusion The detection rate of VTE among patients with NS during hospitalization was 1.56%. Male, age, MN, anemia, cerebral bleeding, respiratory tract infection, respiratory failure, and use of PPIs, glucocorticoids and immunosuppressants, high D-dimer concentration were associated with VTE detection in NS. While 24-hour proteinuria did not show a significant association with VTE identification.

Construction of a nomogram risk prediction model for PICC-related venous thrombosis and its application

ObjectiveTo explore the risk factors of the peripherally inserted central catheter (PICC)-related venous thrombosis and correspondingly construct a nomogram risk prediction model. MethodsThe clinical data of 401 patients receiving PICC catheterization in our hospital from June 2019 to June 2022 were retrospectively analyzed. The independent influencing factors for venous thrombosis were predicted using logistic regression analysis, and significant indicators were screened to construct a nomogram for predicting PICC-related venous thrombosis. The difference in predictive efficacy between simple clinical data and nomogram was analyzed using a receiver operating characteristic (ROC) curve, and the nomogram was internally validated. ResultsSingle-factor analysis showed that catheter tip position, plasma D-dimer concentration, venous compression, malignant tumor, diabetes, history of thrombosis, history of chemotherapy, and history of PICC/CVC catheterization were correlated with PICC-related venous thrombosis. Further multi-factor analysis revealed that catheter tip position, plasma D-dimer elevation, venous compression, history of thrombosis and history of PICC/CVC catheterization were the risk factors for PICC-related venous thrombosis. Based on binary logistic regression analysis, a nomogram prediction model for PICC-related venous thrombosis was constructed. The area under the curve (AUC) was 0.876 (95%CI: 0.818–0.925), with a statistically significant difference (P < 0.01). ConclusionThe independent risk factors for PICC-related venous thrombosis are screened out, including catheter tip position, plasma D-dimer elevation, venous compression, history of thrombosis and history of PICC/CVC catheterization, and a nomogram prediction model with good effect is constructed to predict the risk of PICC-related venous thrombosis.