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International Journal of Molecular... Jul 2023Stroke, a complex and heterogeneous disease, is a leading cause of morbidity and mortality worldwide. The timely therapeutic intervention significantly impacts patient... (Review)
Review
Unlocking the Potential of Stroke Blood Biomarkers: Early Diagnosis, Ischemic vs. Haemorrhagic Differentiation and Haemorrhagic Transformation Risk: A Comprehensive Review.
Stroke, a complex and heterogeneous disease, is a leading cause of morbidity and mortality worldwide. The timely therapeutic intervention significantly impacts patient outcomes, but early stroke diagnosis is challenging due to the lack of specific diagnostic biomarkers. This review critically examines the literature for potential biomarkers that may aid in early diagnosis, differentiation between ischemic and hemorrhagic stroke, and prediction of hemorrhagic transformation in ischemic stroke. After a thorough analysis, four promising biomarkers were identified: Antithrombin III (ATIII), fibrinogen, and ischemia-modified albumin (IMA) for diagnostic purposes; glial fibrillary acidic protein (GFAP), micro RNA 124-3p, and a panel of 11 metabolites for distinguishing between ischemic and hemorrhagic stroke; and matrix metalloproteinase-9 (MMP-9), s100b, and interleukin 33 for predicting hemorrhagic transformation. We propose a biomarker panel integrating these markers, each reflecting different pathophysiological stages of stroke, that could significantly improve stroke patients' early detection and treatment. Despite promising results, further research and validation are needed to demonstrate the clinical utility of this proposed panel for routine stroke treatment.
Topics: Humans; Brain Ischemia; Hemorrhagic Stroke; Biomarkers; Serum Albumin; Stroke
PubMed: 37511304
DOI: 10.3390/ijms241411545 -
Journal of Medical Case Reports Jul 2023SERPINC1 is a glycoprotein that regulates blood coagulation. SERPINC1 congenital or acquired deficiencies represent a significant risk factor for thromboembolic disease....
BACKGROUND
SERPINC1 is a glycoprotein that regulates blood coagulation. SERPINC1 congenital or acquired deficiencies represent a significant risk factor for thromboembolic disease. SERPINC1 acquired defects are observed in very few cases and can occur in many clinical conditions such as treatment with L-asparaginase or oral contraceptive (particularly estrogen derivatives), but these conditions are not routinely investigated.
CASE PRESENTATION
A 50-year-old Caucasian woman who took gestodene 75 µg/ethinylestradiol 20 µg as oral contraceptive, was sent to our thrombophilia clinic because, on thrombophilia testing, a reduction of SERPINC1 (74%) and a slight increase in circulating D-dimer and homocysteine were found. We investigated triggers of such SERPINC1 reduction, and identified gestodene 75 µg/ethinylestradiol 20 µg use as the most likely candidate. Two months after the discontinuation of the oral contraceptive, SERPINC1 value returned to normal (92%) and D-dimer and homocysteine were normalized.
CONCLUSION
Each patient has a different sensitivity to contraceptive use. Genetic (or epigenetic) regulation of anticoagulant proteins might account for a different rate of consumption of anticoagulant proteins as oral contraceptives and probably determine the susceptibility to thrombotic events.
Topics: Female; Humans; Middle Aged; Contraceptives, Oral; Ethinyl Estradiol; Thrombophilia; Blood Coagulation Disorders; Anticoagulants; Antithrombins; Antithrombin III
PubMed: 37501065
DOI: 10.1186/s13256-023-04038-1 -
International Journal of Biological... Sep 2023Heparin is the most common anticoagulant used in clinical practice but shows some downsides such as short half-life (for the high molecular weight heparin) and secondary...
Heparin is the most common anticoagulant used in clinical practice but shows some downsides such as short half-life (for the high molecular weight heparin) and secondary effects. On the other hand, its low molecular weight analogue cannot be neutralized with protamine, and therefore cannot be used in some treatments. To address these issues, we conjugated polyethylene glycol (PEG) to heparin reducing end (end-on) via oxime ligation and studied the interactions of the conjugate (Hep-b-PEG) with antithrombin III (AT) and protamine. Isothermal titration calorimetry showed that Hep-b-PEG maintains the affinity to AT. Dynamic light scattering demonstrated that the Hep-b-PEG formed colloidal stable nanocomplexes with protamine instead of large multi-molecular aggregates, associated with heparin side effects. The in vitro (human plasma) and in vivo experiments (Sprague Dawley rats) evidenced an extended half-life and higher anticoagulant activity of the conjugate when compared to unmodified heparin.
Topics: Animals; Rats; Humans; Heparin; Protamines; Rats, Sprague-Dawley; Anticoagulants
PubMed: 37499705
DOI: 10.1016/j.ijbiomac.2023.125957 -
Journal of Clinical Medicine Jul 2023The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a... (Review)
Review
BACKGROUND
The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC).
OBJECTIVES
This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT.
METHODS
Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers' outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871).
RESULTS
Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 μg/mL, 95% CI 0.02, 0.72; = 0.04, I = 92%; for heterogeneity < 0.00001) and with higher platelets (8.76 × 10/L, 95% CI 1.62, 15.91; = 0.02, I = 41%; for heterogeneity = 0.06).
CONCLUSIONS
High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin-antithrombin complex, and WBC were not related to the development of DVT associated with PICC.
PubMed: 37445515
DOI: 10.3390/jcm12134480 -
Northern Clinics of Istanbul 2023Literature shows evidence of the use of mean platelet volume (MPV) as a biomarker in thromboembolic conditions. It is recommended that genetic testing be performed...
OBJECTIVE
Literature shows evidence of the use of mean platelet volume (MPV) as a biomarker in thromboembolic conditions. It is recommended that genetic testing be performed selectively for hereditary thrombophilia. It might be useful to determine the priority of patients for genetic testing of hereditary thrombophilia through appropriate methods. We aimed to investigate the predictive value of MPV for high-risk patients of hereditary thrombophilia.
METHODS
The hematologic (MPV), biochemical (antithrombin III, protein S, protein C), molecular genetic test results (factor V Leiden [FVL], and prothrombin G20210A [PT]) obtained retrospectively from medical files of 263 patients categorized into high- versus low-risk for thrombophilia were statistically analyzed and the value of MPV in predicting high-risk patients was assessed by receiver operating characteristic (ROC) analysis.
RESULTS
The frequencies of high- versus low-risk patients were 45.2% and 54.8%, respectively. Significantly more high-risk patients (n=81) compared to low-risk patients had FVL (n=66) and PT mutations (n=80 vs. 34) (p<0.001). The MPV values in high-risk patients (mean=11.1 fl, range=7.8-13.6) were significantly higher than those in the low-risk patients (mean=8.6 fl, range=6-10.9) (p<0.001). The ROC curve analysis for MPV revealed a statistically significant area under the curve of 0.961 (95% confidence interval=0.931-0.981) at a cut-off point of 10.1 fl with a sensitivity of 89.1% and a specificity of 91.7% (p<0.001).
CONCLUSION
MPV might be used as an effective biomarker to screen and select patients for genetic thrombophilia testing. Large multicenter studies are needed for recommending the inclusion of MPV in future guidelines for hereditary thrombophilia.
PubMed: 37435289
DOI: 10.14744/nci.2023.92331 -
Korean Journal of Neurotrauma Jun 2023Immune reactions following traumatic brain injury (TBI) cause many complications, including intravascular dissemination. Antithrombin III (AT-III) plays an important...
OBJECTIVE
Immune reactions following traumatic brain injury (TBI) cause many complications, including intravascular dissemination. Antithrombin III (AT-III) plays an important role in suppressing abnormal clot formation and ensuring hemostasis. Therefore, we investigated the efficacy of serum AT-III in patients with severe TBI.
METHODS
This retrospective study included 224 patients with severe TBI who visited a single regional trauma center between 2018 and 2020. AT-III levels were measured immediately after the TBI diagnosis. AT-III deficiency was defined as an AT-III serum level <70%. Patient characteristics, injury severity, and procedures were also investigated. Patient outcomes included Glasgow Outcome Scale scores at discharge and mortality.
RESULTS
AT-III levels were significantly lower in the AT-III deficient group (n=89; 48.27% ± 1.91%) than in the AT-III sufficient group (n = 135, 78.90% ± 1.52%) (p < 0.001). Mortality occurred in 72 of the 224 patients (33.04%), indicating that there were significantly more patients in the AT-III-deficient group (45/89, 50.6%) than in the AT-III-sufficient group (27/135, 20%). Significant risk factors for mortality included the Glasgow Coma Scale score (P = 0.003), pupil dilatation (P = 0.031), disseminated intravascular coagulopathy (P = 0.012), serum AT-III level (P = 0.033), and procedures including barbiturate coma therapy (P = 0.010). Serum AT-III levels were significantly correlated with Glasgow Outcome Scale scores at discharge (correlation coefficient = 0.455, p < 0.001).
CONCLUSION
Patients with AT-III deficiency after severe TBI may require more intensive care during treatment, because AT-III levels reflect injury severity and correlate with mortality.
PubMed: 37431370
DOI: 10.13004/kjnt.2023.19.e29 -
European Journal of Gastroenterology &... Aug 2023Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are characterized by severe liver function impairment, coagulation disorder, and...
OBJECTIVE
Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are characterized by severe liver function impairment, coagulation disorder, and multiple organ function impairment. The aim of this study was to explore the predictive value of antithrombin Ⅲ activity to the prognosis of HBV-ACLF patients.
METHODS
A total of 186 HBV-ACLF patients were included in the analysis, and the baseline clinical data of patients were recorded to analyze the risk factors affecting the 30-day survival outcome of patients. Bacterial infection, sepsis, and hepatic encephalopathy were observed in ACLF patients. Antithrombin Ⅲ activity and serum cytokine levels were determined.
RESULTS
The antithrombin Ⅲ activity of ACLF patients in the death group was significantly lower than that in the survival group, and antithrombin Ⅲ activity was independent factors affecting the 30-day outcome. The areas under the receiver operation characteristic (ROC) curve of antithrombin Ⅲ activity to predict the 30-day mortality of ACLF was 0.799. Survival analysis showed that the mortality of patients with antithrombin Ⅲ activity less than 13% was significantly increased. Patients with bacterial infection and sepsis had lower antithrombin Ⅲ activity than those without infection. Antithrombin Ⅲ activity was positively correlated with platelet count, fibrinogen, interferon (IFN)-γ, interleukin (IL)-13, IL-1β, IL-4, IL-6, tumor necrosis factor-α, IL-23, IL-27, and IFN-α, but negatively correlated with C-reactive protein, D dimer, total bilirubin, and creatinine levels.
CONCLUSION
As a natural anticoagulant, antithrombin Ⅲ can be regarded as a marker of inflammation and infection in patients with HBV-ACLF, and as a predictor of survival outcome in patients with ACLF.
Topics: Humans; Hepatitis B virus; Antithrombin III; Acute-On-Chronic Liver Failure; Prognosis; Inflammation; Anticoagulants; Sepsis; Hepatitis B, Chronic; Hepatitis B; Retrospective Studies
PubMed: 37395245
DOI: 10.1097/MEG.0000000000002571 -
BMC Musculoskeletal Disorders Jul 2023Spontaneous intramuscular hemorrhage (SIH) is a rare but life-threatening complication of dermatomyositis (DM). The pathogenetic mechanism and management of... (Review)
Review
BACKGROUND
Spontaneous intramuscular hemorrhage (SIH) is a rare but life-threatening complication of dermatomyositis (DM). The pathogenetic mechanism and management of intramuscular hematoma in these patients remains unclear. Here we discuss a case of recurrent hemorrhage in a patient with cancer-associated DM, and review the relevant literature for timely diagnosis and treatment.
CASE PRESENTATION
A 53-year-old male patient presented with rashes, muscle weakness, and dysphagia and was diagnosed with DM. During treatment, he developed SIH of the arm and right psoas major muscle successively. MRI showed extensive edema of the right shoulder girdle muscle and muscle groups of the upper arm. During the second SIH, a CT scan showed new-onset hematoma formation in the right psoas major muscle. The detection of D-dimer, thrombin-antithrombin III complex (TAT), plasmin-α2-plasmininhibitor complex (PIC) and tissue plasminogen activator-inhibitor complex (t-PAIC) indicated predominant hyperfibrinolysis over thrombosis. Blood transfusion and supportive treatment were immediately performed, and the hematoma did not expand. However, his abdominal distension was not relieved after active treatment. Further electronic gastroscopy discovered gastric sinus ulcers, and histopathology of the biopsy confirmed signet-ring cell carcinoma.
CONCLUSIONS
Although patients with cancer-associated DM have an increased risk of thrombosis, prophylactic anticoagulation therapy needs deliberate consideration. It is important to monitor the coagulation parameters dynamically during anticoagulation therapy. Especially when the level of D-dimer is high, and it is uncertain whether the patient is in a state of thrombosis or hyperfibrinolysis, the detection of TAT, PIC, t-PAIC can help to determine whether to initiate anticoagulation therapy.
Topics: Male; Humans; Middle Aged; Tissue Plasminogen Activator; Dermatomyositis; Hemorrhage; Hematoma; Neoplasms; Anticoagulants
PubMed: 37393235
DOI: 10.1186/s12891-023-06651-z -
Lipids in Health and Disease Jun 2023Population-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to...
BACKGROUND
Population-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.
METHODS
After 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.
RESULTS
In 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.
CONCLUSION
In 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.
Topics: Male; Humans; Female; Factor VIII; Antithrombin III; Protein S; Protein C; Blood Coagulation; Hemostatics; Anticoagulants; Fibrinogen
PubMed: 37386502
DOI: 10.1186/s12944-023-01854-8 -
Stem Cell Research Sep 2023Mutation of SERPINC1 is related to the incidence of Inherited antithrombin (AT) deficiency. In this study, we generated a human induced pluripotent stem cell (iPSC) line...
Mutation of SERPINC1 is related to the incidence of Inherited antithrombin (AT) deficiency. In this study, we generated a human induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a patient with a mutation of SERPINC1 c.236G>A (p.R79H). The generated iPSCs express pluripotent cell markers with no mycoplasma contamination. Besides, it has a normal female karyotype and could differentiate into all three germ layers in vitro.
Topics: Humans; Female; Induced Pluripotent Stem Cells; Leukocytes, Mononuclear; Mutation; Mycoplasma; Cell Differentiation; Antithrombin III
PubMed: 37385134
DOI: 10.1016/j.scr.2023.103150