Increase In D-dimer Concentration Research Articles

SARS-COV-2 AND HYPERCOAGULATION IN PREGNANT WOMEN

The global pandemic caused by the SARS-CoV-2 virus has created unprecedented medical and social problems. The virus has the ability to induce a prothrombotic state, which in certain cases has led to severe thrombotic complications. Scientists all over the world were faced with the task of studying in detail the coagulation capacity of blood plasma and the procoagulant role of platelets in the development of pathogenic mechanisms of endothelial damage, major vascular thrombosis and systemic microangiopathies. These studies will be useful for clinicians to improve pathogenetic- based treatment schemes for this disease and to prevent serious complications. The aim of the study was to determine the eff ect of the SARS-CoV-2 virus on some parameters of the blood coagulation system in pregnant women with post-covid syndrome.Method and materials. From November 2020 to January 2022, we conducted a prospective cohort study of 50 pregnant women (main group) with SARS-CoV-2 confi rmed by the polymerase chain reaction method. The control group consisted of 25 women with physiological pregnancy who were undergoing inpatient treatment at the communal non-profi t enterprise «Ternopil City Communal Hospital No. 2». The conduct of this study was approved by the Ethics Committee of Ternopil National Medical University named after I. Gorbachevsky – protocol No. 61 dated November 13, 2020. Pregnant women were examined between 30 and 34 weeks of gestation. In the selected blood samples, the number of platelets, coagulogram indicators: international normalized ratio, prothrombin and thrombin time, prothrombin index, activated partial thromboplastin time, fi brinogen and D-dimer levels were studied. The studies were performed on a Coag Chrom 3003 analyzer. Microsoft Excel and Statistica-10 software were used for statistical analysis. The study was conducted within the framework of the National Development Program «Improvement of diagnosis and treatment of pregnant women with a burdened somatic history» of the Department of Obstetrics and Gynecology, Faculty of Postgraduate Education, TernopilNational Medical University named after I. Ya. Gorbachevsky, state registration number N 0121U100153, performance period 2021-2023).Results. A signifi cant decrease in the absolute platelet count to less than 100,000/μL was observed in 5 % of the pregnant women in the main group, and in 70 % of the patients in this group, the platelet count was less than 150,000/μL, and only 25 % of the pregnant women in this group had platelet counts within the normal range. In the control group, only 16 % of the platelets were in the 150-180 range, and 84 % of the pregnant women in this group had platelet counts within the normal range. Prothrombin time indicators were slightly longer in patients with COVID-19 (15.6 s; 14.4-16.3) compared with the control group (13.6 s; 13.0-14.3), (Р>0.05). In pregnant women with SARS-CoV-2, the concentration of fi brinogen was 1.63 times higher than in the control group (P<0.05). The indicators of activated partial thromboplastin time and international normalized ratio were longer in the group of patients with COVID-19 compared with the control group, although the diff erence was not statistically signifi cant (P>0.05). A signifi cant (P<0.05) acceleration of the thrombin time was observed in 82 % of the pregnant women in the main group compared to the control group. An increase in D-dimer concentration was the most signifi cant abnormality. Thus, when evaluating the indicators of laboratory studies of the main parameters of hemostasis in 26 % of patients with COVID-19, D-dimer increased fi ve times, and in 20 % it was 8-10 times more than in healthy pregnant women. Thus, the SARS-CoV-2 virus has a negative eff ect on the main indicators of both theprocoagulant and anticoagulant systems of homeostasis. And these changes are particularly dangerous for pregnant women, because micro- and macrothrombosis of the placenta and umbilical cord lead to life-threatening conditions for the fetus. The SARS-CoV-2 virus leads to hypercoagulation in the homeostatic system of pregnant women compared to control women who were not infected with the coronavirus. Conclusion: Thus, the results of our research allow us to pathogenetically justify the need for long-term use of anticoagulant therapy in pregnant women with post- CoV syndrome.

Evaluation of perioperative D-dimer concentration for predicting postoperative deep vein thrombosis following hepatobiliary-pancreatic surgery

PurposeThis study was performed to investigate the predictive value of the perioperative D-dimer concentration for the development of postoperative deep vein thrombosis (DVT) after hepatobiliary-pancreatic (HBP) surgery.MethodsThe subjects of this retrospective study were 178 patients who underwent HBP surgery in our hospital between January, 2017 and December, 2021. The D-dimer concentration was measured preoperatively and on postoperative days (POD) 1, 3, and 5. Postoperative DVT was diagnosed based on compression ultrasonography in both lower limbs on POD 6 or 7.ResultsPostoperative DVT developed in 21 (11.8%) of the 178 patients. The D-dimer concentration was significantly higher in the patients with than in those without postoperative DVT before surgery and on PODs 1, 3, and 5. The highest area under the curve of the D-dimer concentration for predicting DVT was 0.762 on POD 3. Multivariate analysis revealed that the D-dimer concentration on POD 3 was an independent predictive risk factor for postoperative DVT, along with the preoperative estimated glomerular filtration rate. Preoperative albumin and D-dimer concentrations were also identified as independent predictive factors of an increase in D-dimer concentration on POD 3.ConclusionsThe D-dimer concentration on POD 3 is a useful predictor of DVT after HBP surgery.

Associations of D-Dimer with Computed Tomographic Lung Abnormalities, Serum Biomarkers of Lung Injury, and Forced Vital Capacity: MESA Lung Study.

Rationale: The coagulation cascade may play a role in the pathogenesis of interstitial lung disease through increased production of thrombin and fibrin deposition. Whether circulating coagulation cascade factors are linked to lung inflammation and scarring among community-dwelling adults is unknown. Objectives: To test the hypothesis that higher baseline D-dimer concentrations are associated with markers of early lung injury and scarring. Methods: Using the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (n = 6,814), we examined associations of baseline D-dimer concentrations with high attenuation areas from examination 1 (2000-2002; n = 6,184) and interstitial lung abnormalities from examination 5 computed tomographic (CT) scans (2010-2012; n = 2,227), and serum MMP-7 (matrix metalloproteinase-7) and SP-A (surfactant protein-A) from examination 1 (n = 1,098). We examined longitudinal change in forced vital capacity (FVC) from examinations 3-6 (2004-2018, n = 3,562). We used linear logistic regression and linear mixed models to examine associations and adjust for potential confounders. Results: The mean (standard deviation) age of the cohort was 62 (10) years, and the D-dimer concentration was 0.35 (0.69) ug/ml. For every 10% increase in D-dimer concentration, there was an increase in high attenuation area percentage of 0.27 (95% confidence interval (CI), 0.08-0.47) after adjustment for covariates. Associations were stronger among those older than 65 years (P values for interaction < 0.001). A 10% increase in D-dimer concentration was associated with an odds ratio of 1.05 for interstitial lung abnormalities (95% CI, 0.99-1.11). Higher D-dimer concentrations were associated with higher serum MMP-7 and a faster decline in FVC. D-dimer was not associated with SP-A. Conclusions: Higher D-dimer concentrations were associated with a greater burden of lung parenchymal abnormalities detected on CT scan, MMP-7, and FVC decline among community-dwelling adults.

Plasma fibrin clot properties and cardiovascular mortality in patients with type 2 diabetes: a long\u2010term follow\u2010up study

BackgroundPatients with type 2 diabetes mellitus (T2DM) are at high risk of cardiovascular mortality, but the mechanisms behind this remain unclear. Prothrombotic fibrin clot properties have been shown in T2DM and cardiovascular disease. We hypothesized that formation of denser clots, which are resistant to fibrinolysis, has a negative impact on cardiovascular mortality in T2DM.MethodsWe studied 133 T2DM patients aged 43–83 years. Plasma fibrin clot turbidity, permeation, compaction, and efficiency of clot lysis using 3 assays including the determination of maximum concentration (D-Dmax) and rate of increase in D-dimer concentration (D-Drate) released during tissue plasminogen activator-induced degradation, were evaluated at the time of enrollment, along with thrombin generation and fibrinolytic proteins. During a median follow-up period of 72 months, cardiovascular mortality was recorded.ResultsCardiovascular deaths (n = 16, 12%) occurred more frequently in patients with increased D-Dmax (> 4.26 mg/l, hazard ratio [HR] 5.43, 95% confidence interval [CI] 1.99–14.79), or decreased D-Drate (< 0.07 mg/l/min, HR 2.97, 95% CI 1.07–8.23), or increased peak thrombin (> 283.5 nM, HR 5.65, 95% CI 2.07–15.51). These predictors had an even more potent impact on cardiovascular mortality in patients with prior cardiovascular disease (64.7%) and with corresponding risks as follows: HR 6.18, 95% CI 2.02–18.96; HR 8.98, 95% CI 2.99–26.96; and HR 5.35, 95% CI 1.62–17.72, respectively. Other investigated fibrin variables and fibrinolytic proteins did not associate with cardiovascular mortality. In multivariable analysis, cardiovascular mortality was predicted by D-Dmax > 4.26 mg/l, age > 65 years, prior cardiovascular disease, and C-reactive protein > 3 mg/l.ConclusionsThis study is the first to show that formation of denser fibrin clots resistant to fibrinolysis could be a risk factor for long-term cardiovascular mortality in T2DM.

Variations of plasma D-dimer level at various points of normal pregnancy and its trends in complicated pregnancies: A retrospective observational cohort study.

D-Dimer (DD) is the smallest fragment of plasmin-mediated cleavage of fibrin. There is a progressive increase in DD concentration with advancing gestation in normal pregnancies, making the upper limit of 0.5 μg/ml used in non-pregnant population an unfavorable marker during pregnancy. Coagulation and fibrinolysis parameters are also markedly disturbed in pregnancies complicated by various pathologies.We designed this retrospective observational cohort study to investigate the trimester specific reference range for DD throughout normal pregnancy, and to compare the distribution of DD in third trimester healthy pregnancies and those complicated by preeclampsia (PE), severe preeclampsia (SPE), gestational diabetes mellitus (GDM), premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM). In addition, we aimed to determine the diagnostic value of DD in PE and SPE.In this retrospective observational cohort study, 250 normal and 178 complicated pregnancies were included. Normal pregnancies included 88-first trimester, 101-second trimester and 61-third trimester pregnancies. Complicated pregnancy included 34 PE, 44 SPE, 32 GDM, 33 PROM, and 35 PPROM cases during the third trimester. Predefined exclusion criteria were used.The period of gestation (POG) accounted for 41.9% of the variance in DD, with strong correlation between the POG and DD. The trimester specific reference intervals were computed. The distribution for severe preeclampsia was statistically different compared to other categories in the third trimester. This exceptional distribution led to the generation of a receiver operating characteristic (ROC) curve with an area under curve of 0.828, attesting its possible role in predicting severe preeclampsia.We determined trimester specific reference intervals of DD. The role of DD has been explored, and it may be of diagnostic value in severe preeclampsia.

Association of D-dimer Levels with Clinical Event Rates and the Efficacy of Betrixaban versus Enoxaparin in the APEX Trial.

Background Elevated D-dimer concentrations are associated with an increased risk of venous thromboembolism (VTE). However, they may also provide prognostic value. The present analysis sought to study the association of D-dimer levels with VTE event rates and the efficacy of betrixaban versus enoxaparin in the APEX trial. Methods Hospitalized acutely medically ill subjects ( n = 7,513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35–42 days) or standard dose subcutaneous enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis. D-dimer was assessed using a central core laboratory measurement. Results For every 0.25 µg/mL increase in D-dimer concentration, there was a 2% increase in the relative risk of experiencing the primary efficacy endpoint (asymptomatic deep vein thrombosis [DVT], symptomatic DVT, nonfatal pulmonary embolism, or VTE-related death) in both the betrixaban ( p < 0.001) and enoxaparin ( p < 0.001) treatment arms. Among D-dimer-positive (≥ 2 × upper limit of normal; corresponding to ≥ 1.00 µg/mL) subjects, extended-duration betrixaban reduced the risk of experiencing the primary efficacy outcome (5.4% [ n = 124] vs. 7.6% [ n = 170]; odds ratio = 0.69; 95% confidence interval: 0.55–0.88; absolute risk reduction = 2.2%, number needed to treat = 46, p = 0.003). There was no interaction between D-dimer and the treatment effect ( p int = 0.53). Conclusion Extended-duration betrixaban was superior to standard-duration enoxaparin, irrespective of D-dimer level at baseline. To prevent one VTE event, 46 D-dimer-positive patients would need to be treated with betrixaban.

Interpretation of Coagulation Tendency Contributing to Thrombosis in Vector-Borne Diseases (Ehrlichiosis, Anaplasmosis, Leishmaniosis, and Dirofilariasis) among Dogs

Background: Vector-borne infectious and zoonotic diseases are an important health problem that directly affects human and animal health negatively. Results through evaluation of coagulation disorders among vector-borne diseases should be of beneficial for both human and dogs studies. According to the present author’s knowledge reports regarding changes in platelet (PLT) count, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-dimer levels in dogs naturally infected with one or more vector-borne pathogens are lacking. Therefore, the present study was aimed to detecting those parameters for relation between diagnosis and prognosis of vector-borne diseases among dogs.Materials, Methods &amp; Results: The material of this study was 46 dogs (36 were naturally infected with vector-borne diseases and 10 were healthy) from different breed, age and of both sexes. Venous blood samples were obtained to detect PLT counts, antibodies of ehrlichiosis, anaplasmosis, borreliosis, leishmaniosis and antigens of Dirofilaria immitis. The diagnosis of vector-borne diseases was performed by using a commercial ELISA assay kits. PLT count was performed with an automated blood cell counter analyser. In addition, PT, APTT and FIB concentrations were measured using a microcoagulometer. D-dimer concentrations were determined using fluorescence immunoassay rapid quantitave test analyser. Subgroups were formed according to the number of cases and the distribution of vector-borne agent. Statistically significant decreased PLT count was found in dogs mono infected with ehrlichiosis compared to healthy dogs (P &lt; 0.001). Changes in mean PT value in the studied animals did not show statistically significant differences among the groups (P &gt; 0.05). APTT values in the ehrlichiosis mono infection group were significantly higher than that of the healthy control (P &lt; 0.01). A significant increase in FIB levels were detected for ehrlichiosis mono infection and ehrlichiosis - leishmaniosis co infection versus healthy control (P &lt; 0.001). Plasma D-dimer concentrations were found to be higher in all groups infected with vector borne diseases compared to healthy group (P &lt; 0.001) and the differences between infected groups were not statistically significant.Discussion: Bleeding disorders such as epistaxis, haematuria and haemorrhagic diarrhoea has been reported in dogs with vector-borne diseases. These disorders represent the main cause of death in dogs. In the present study, thrombocytopenia was observed in dogs mono infected with ehrlichiosis compared to healthy. This finding is in agreement with those reported in dogs with ehrlichiosis. Plasma FIB is one of the most important factors in the coagulation cascade. In the present study, a significant difference between dogs with ehrlichiosis mono infection and ehrlichiosis - leishmaniosis co infection versus healthy controls group was observed. PT and APTT are commonly used in evaluating dogs with bleeding tendencies. In the present study, a significant difference between dogs with ehrlichiosis and with healthy control was observed in APTT values, however, differences in PT values compared to healthy dogs were insignificant. No statistical difference in PT values might be related to the lower sensitivity of the commercial PT assays. In dogs, D-dimer concentrations can be elevated due to disseminated intravascular coagulopathy, infections, metabolic disorders, neoplasia and post-surgically. In the present study, a significant increase in D-dimer concentration was observed in all dogs with vector-borne diseases. This finding points to the activation of the fibrinolysis system in consequence of thrombophilia. In conclusion, elevations presented in coagulation biomarkers such as APTT, FIB and D-dimer in the present study were interpreted as with the effects of vector-borne diseases. It may be briefly suggested that D-dimer levels as a marker of pro-coagulatory activity, as well as fibrinolysis, indicates the highly active and excessive coagulation, and all through are risk factors for thromboembolic disorders. Therefore, these findings should be considered in the diagnosis, treatment and prognosis of the vector-borne diseases in dogs.

Development of anin vitrofibrin clot model to evaluate fibrinolytic agents for wound care application

To describe an in vitro fibrin clot model that could reliably assess the fibrinolytic activity of enzymatic debriding agents for wound care application. A model of a fibrin clot was reconstructed in vitro by mixture of human fibrinogen and (alpha)-thrombin supplemented with factor XIII. These clots were then treated with enzymatic ointments. Fibrinolytic activity was investigated by measuring D-dimer levels, using an automated immunoturbidimetric Liatest D-dimer assay. Collagenase and papain-urea ointments demonstrated fibrinolytic activity which was macroscopically visible. Their effect was identical on the in vitro reconstructed fibrin clot and ex vivo collected wound fibrin clot; collagenase and papain-urea both induced a complete degradation and dissolution of both fibrin clots after 24 hours of treatment. This was associated with an increase in D-dimer concentration. This reconstructed fibrin clot in vitro model has the potential to predict the efficacy of fibrinolytic agents and therefore appears to be a suitable model for in vitro assays. This study was supported by a grant from URGO Laboratory.

Impairment of early fibrinolytic activation after PTCA: a mechanism for restenosis-related clinical recurrence?

Objective: This study was aimed to investigate the acute effect of PTCA on clotting activation and fibrinolytic system and the possible role of modifications of haemostasis in relation to restenosis-related clinical recurrence after PTCA. Setting: Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy. Material and methods: In 83 unselected patients (70 men and 13 women) undergoing PTCA, blood clotting (fibrinogen, F1+2 TAT) and fibrinolytic activation (D-dimer, ELT, PAI-1, t-PA) were assayed before and immediately after PTCA. Results: At the end of the procedure there was a significant decrease in plasma levels of fibrinogen ( P < 0.0001), F1+2 ( P < 0.0001), TAT ( P < 0.0001), PAI-1 ( P < 0.0001) and t-PA ( P < 0.001), a shortening of ELT ( P < 0.0001) and a significant increase in D-dimer concentration ( P < 0.0005). Post-procedyral PAI-1 activity levels were significantly higher in patients with subsequent clinical recurrence owing to restenosis than in those without ( P < 0.0005); similarly, patients with restenosis showed lower t-PA levels ( P < 0.0005) and longer ELT ( P < 0.05) after PTCA than those without. An earlier occurrence of clinical recurrence owing to restenosis was observed in patients with an increase or no variation of PAI-1 levels at the end of the procedure. Conclusion: These results suggest that the early fibrinolytic response to balloon injury is a relevant determinant of the risk of clinical recurrence owing to restenosis after PTCA, possibly by determining ‘per se’ a longer local persistence of thrombus and by triggering a release of mediators involved in the proliferation of smooth muscle cells.