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Cureus Jan 2024Antithrombin (AT) deficiency and antiphospholipid syndrome (APS) are distinct but potentially overlapping disorders with significant implications for thrombosis. We...
Antithrombin (AT) deficiency and antiphospholipid syndrome (APS) are distinct but potentially overlapping disorders with significant implications for thrombosis. We present a case of a 28-year-old male with hereditary AT deficiency who subsequently developed primary APS. Despite the challenges of overlapping symptoms and anticoagulation therapy, a careful diagnostic approach revealed the coexistence of these rare conditions. The patient was successfully managed with long-term anticoagulation, hydroxychloroquine, and other supportive measures. This case underscores the importance of comprehensive laboratory testing, especially when managing patients with pre-existing anticoagulation needs.
PubMed: 38314001
DOI: 10.7759/cureus.51555 -
Research and Practice in Thrombosis and... Jan 2024Several studies have examined parameters of increased thrombogenicity in COVID-19, but studies examining their association with long-term outcome and potential effects...
BACKGROUND
Several studies have examined parameters of increased thrombogenicity in COVID-19, but studies examining their association with long-term outcome and potential effects of antiviral agents in hospitalized patients with COVID-19 are scarce.
OBJECTIVES
To evaluate plasma levels of hemostatic proteins during hospitalization in relation to disease severity, treatment modalities, and persistent pulmonary pathology after 3 months.
METHODS
In 165 patients with COVID-19 recruited into the NOR-Solidarity trial (NCT04321616) and randomized to treatment with hydroxychloroquine, remdesivir, or standard of care, we analyzed plasma levels of hemostatic proteins during the first 10 days of hospitalization ( = 160) and at 3 months of follow-up ( = 100) by enzyme immunoassay.
RESULTS
Our main findings were as follows: (i) tissue plasminogen activator (tPA) and tissue factor pathway inhibitor (TFPI) were increased in patients with severe disease (ie, the combined endpoint of respiratory failure [Po-to-FiO ratio, <26.6 kPa] or need for treatment at an intensive care unit) during hospitalization. Compared to patients without severe disease, tPA levels were a median of 42% ( < .001), 29% ( = .002), and 36% ( = .015) higher at baseline, 3 to 5 days, and 7 to 10 days, respectively. For TFPI, median levels were 37% ( = .003), 25% ( < .001), and 10% ( = .13) higher in patients with severe disease at these time points, respectively. No changes in thrombin-antithrombin complex; alpha 2-antiplasmin; a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; or antithrombin were observed in relation to severe disease. (ii) Patients treated with remdesivir had lower levels of TFPI than those in patients treated with standard of care alone. (iii) TFPI levels during hospitalization, but not at 3 months of follow-up, were higher in those with persistent pathology on chest computed tomography imaging 3 months after hospital admission than in those without such pathology. No consistent changes in thrombin-antithrombin complex, alpha 2-antiplasmin, ADAMTS-13, tPA, or antithrombin were observed in relation to pulmonary pathology at 3 months of follow-up.
CONCLUSION
TFPI and tPA are associated with severe disease in hospitalized patients with COVID-19. For TFPI, high levels measured during the first 10 days of hospitalization were also associated with persistent pulmonary pathology even 3 months after hospital admittance.
PubMed: 38292350
DOI: 10.1016/j.rpth.2023.102289 -
Cureus Dec 2023Andexanet alfa (AnAl) is utilized for the urgent reversal of direct oral anticoagulants (DOACs) in cases of severe bleeding. While the guidelines from the Society of...
Andexanet alfa (AnAl) is utilized for the urgent reversal of direct oral anticoagulants (DOACs) in cases of severe bleeding. While the guidelines from the Society of Thoracic Surgeons recommend AnAl for urgent cardiac surgery in patients treated with DOACs, concerns persist regarding the potential of AnAl to induce heparin resistance. This report details the case of an 85-year-old woman diagnosed with acute type A aortic dissection, who received AnAl due to prior edoxaban use. During the emergent aortic surgery, she exhibited heparin resistance following the administration of unfractionated heparin (UFH). The administration of antithrombin III (ATIII) significantly influenced activated clotting times, facilitating successful surgery while maintaining adequate anticoagulation. This case underscores the importance of cautious management of AnAl-induced heparin resistance during critical surgeries, emphasizing the role of ATIII supplementation for effective anticoagulation.
PubMed: 38249168
DOI: 10.7759/cureus.50856 -
Journal of Cancer Research and Clinical... Jan 2024Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication following hematopoietic stem cell transplantation (HSCT) in which early diagnosis improves...
Analysis of laboratory parameters before the occurrence of hepatic sinusoidal obstruction syndrome in children, adolescents, and young adults after hematopoietic stem cell transplantation.
PURPOSE
Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication following hematopoietic stem cell transplantation (HSCT) in which early diagnosis improves patient outcome. The aim of our study was to detect laboratory parameters following HSCT that can predict the occurrence of SOS.
METHODS
This retrospective study included 182 children, adolescents, and young adults who underwent allogeneic or autologous HSCT for the first time (median age 7.2 years). The diagnosis of SOS was based on the pediatric criteria of European Society for Blood and Marrow Transplantation (EBMT). We investigated 15 laboratory parameters after HSCT before the onset of SOS.
RESULTS
The overall incidence of SOS was 14.8%. SOS developed in 24 of 126 allogeneic (19.1%) and in 3 of 56 autologous (5.4%) HSCT patients at a median time of 13 days after HSCT. We observed a low SOS mortality rate of 11.1% within 100 days after HSCT. International normalized ratio (INR) ≥ 1.3, activated partial thromboplastin time (aPTT) ≥ 40 s, reptilase time ≥ 18.3 s, factor VIII ≤ 80%, antithrombin III ≤ 75%, protein C ≤ 48%, D-dimer ≥ 315 µg/L, bilirubin ≥ 9 µmol/L, and ferritin ≥ 3100 µg/L showed significant associations with the onset of SOS in the univariate analyses. In the multivariate analysis, INR ≥ 1.3 [odds ratio (OR) = 8.104, p = 0.006], aPTT ≥ 40 s (OR = 10.174, p = 0.001), protein C ≤ 48% (OR = 5.215, p = 0.014), and ferritin ≥ 3100 µg/L (OR = 7.472, p = 0.004) could be confirmed as independent risk factors after HSCT before SOS. If three of the four significant cut-off values were present, the probability of developing SOS was more than 70%. The probability of SOS was 96%, if all four laboratory parameters were changed according to the cut-off values. The values of factor XIII, von Willebrand factor (vWF), von Willebrand factor activity (vWF activity), protein S, fibrinogen, and alanine aminotransferase (ALT) were not relevant for the occurrence of SOS.
CONCLUSION
In summary, the laboratory parameters INR, aPTT, protein C, and ferritin were very useful to predict the occurrence of SOS. In addition, this is the first report on a significant association between SOS and high values of INR and aPTT after HSCT before SOS.
Topics: Humans; Adolescent; Young Adult; Child; Hepatic Veno-Occlusive Disease; Protein C; von Willebrand Factor; Retrospective Studies; Ferritins; Hematopoietic Stem Cell Transplantation
PubMed: 38206490
DOI: 10.1007/s00432-023-05561-w -
International Journal of General... 2023Post-COVID-19 condition is thought to affect 10-20% of people at least 3 months after a diagnosis of COVID-19 and two months of symptoms. Post-COVID-19 condition...
BACKGROUND AND OBJECTIVES
Post-COVID-19 condition is thought to affect 10-20% of people at least 3 months after a diagnosis of COVID-19 and two months of symptoms. Post-COVID-19 condition presents itself with many clinical effects with varying degrees of severity ranging from a mild cough to a life-threatening coagulopathy. Our study aimed to identify a relationship between the titers of anti-SARS-CoV-2 IgG and anticoagulation parameters: antithrombin III (ATIII), protein C (PC) and thrombomodulin (TM).
MATERIALS AND METHODS
Blood plasma was collected from healthy donors aged 25-45 who had recovered from COVID-19 3-6 months ago and their titers of anti-SARS-CoV-2 IgG and ATIII, PC, and TM were measured.
RESULTS
We found that concentrations and activities of key anticoagulation parameters (ATIII, PC, and TM) measured in donor plasma during the post-COVID-19 varied in relation to the titers of anti-SARS-CoV-2 IgG.
CONCLUSION
While we identified a dysfunction of anticoagulation parameters in patients with post-COVID-19, we aim to explore the subpopulation antibody IgG fraction directly using in vivo and in vitro experiments with the possibility to contribute to the development of treatment options for post-COVID-19 conditions.
PubMed: 38156079
DOI: 10.2147/IJGM.S425496 -
Frontiers in Molecular Neuroscience 2023Currently, there is a shortage of the protein biomarkers for classifying spinal cord injury (SCI) severity. We attempted to explore the candidate biomarkers for...
PURPOSE
Currently, there is a shortage of the protein biomarkers for classifying spinal cord injury (SCI) severity. We attempted to explore the candidate biomarkers for predicting SCI severity.
METHODS
SCI rat models with mild, moderate, and severe injury were constructed with an electro-mechanic impactor. The behavior assessment and pathological examinations were conducted before and after SCI. Then, quantitative liquid chromatography-mass spectrometry (LC-MS/MS) was performed in spinal cord tissues with different extents of injury. The differentially expressed proteins (DEPs) in SCI relative to controls were identified, followed by Mfuzz clustering, function enrichment analysis, and protein-protein interaction (PPI) network construction. The differential changes of candidate proteins were validated by using a parallel reaction monitoring (PRM) assay.
RESULTS
After SCI modeling, the motor function and mechanical pain sensitivity of SCI rats were impaired, dependent on the severity of the injury. A total of 154 DEPs overlapped in the mild, moderate, and severe SCI groups, among which 82 proteins were classified in clusters 1, 2, 3, 5, and 6 with similar expression patterns at different extents of injury. DEPs were closely related to inflammatory response and significantly enriched in the IL-17 signaling pathway. PPI network showed that Fgg (Fibrinogen gamma chain), Fga (Fibrinogen alpha chain), Serpinc1 (Antithrombin-III), and Fgb (Fibrinogen beta chain) in cluster 1 were significant nodes with the largest degrees. The upregulation of the significant nodes in SCI samples was validated by PRM.
CONCLUSION
Fgg, Fga, and Fgb may be the putative biomarkers for assessing the extent of SCI.
PubMed: 38155913
DOI: 10.3389/fnmol.2023.1153230 -
Scientific Reports Dec 2023Disseminated intravascular coagulation (DIC) is a frequent complication in patients with sepsis and is associated with increased mortality. Anticoagulant therapy may be...
Risk stratification utilizing sequential organ failure assessment (SOFA) score, antithrombin activity, and demographic data in sepsis-associated disseminated intravascular coagulation (DIC).
Disseminated intravascular coagulation (DIC) is a frequent complication in patients with sepsis and is associated with increased mortality. Anticoagulant therapy may be appropriate for certain patients with DIC, particularly those with increased disease severity and deficiency in the physiologic anticoagulant antithrombin. We retrospectively analyzed post-marketing survey data from 1562 patients with sepsis-associated DIC and antithrombin activity of 70% or less. All the patients were treated with antithrombin concentrates. Baseline sequential organ failure assessment (SOFA) score, DIC score, and antithrombin activity were assessed. Cox multivariate regression analysis, Kaplan-Meier curve analysis, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the performance of variables used to assess mortality. Furthermore, a decision tree was constructed to classify the risk of 28-day mortality. COX multivariate regression analysis demonstrated a significant association of age, sex, baseline SOFA score, baseline antithrombin activity, and the presence of pneumonia or skin/soft tissue infection with increased mortality. The area under the curve of SOFA score or antithrombin activity for mortality was 0.700 and 0.614, respectively. Kaplan-Meier analysis demonstrated that mortality was significantly higher in patients with SOFA score ≥ 12 and antithrombin activity < 47%. The decision tree analysis accurately classified the risk of death into high (> 40%), medium (40%-20%), and low (< 20%) categories in 86.1% of the cohort. Twenty eight-day mortality can be strongly predicted using baseline SOFA score, antithrombin activity, infection site, age, and sex as variables in the clinical decision tree for patients with sepsis-associated disseminated intravascular coagulation (DIC).
Topics: Humans; Antithrombins; Organ Dysfunction Scores; Disseminated Intravascular Coagulation; Retrospective Studies; Anticoagulants; Antithrombin III; Sepsis; Risk Assessment; Demography
PubMed: 38110515
DOI: 10.1038/s41598-023-49855-y -
Clinical and Applied... 2023To investigate the relationship between antithrombin (AT) activity level and prognosis in patients requiring intensive care. Patients whose AT activity was measured...
To investigate the relationship between antithrombin (AT) activity level and prognosis in patients requiring intensive care. Patients whose AT activity was measured within 24 h of intensive care unit (ICU) admission were enrolled for analysis. The primary endpoint was mortality at discharge. Prognostic accuracy was examined using receiver operating characteristic (ROC) curves and cox hazard regression analysis. Patients were divided into 6 groups based on predicted mortality, and a χ independence test was performed on the prognostic value of AT activity for each predicted mortality; < .05 was considered significant. A total of 281 cases were analyzed. AT activity was associated with mortality at discharge (AT% [interquartile range, IQR]): survivor group, 69 (56-86) versus nonsurvivor group, 56 (44-73), = .0003). We found an increasing risk for mortality in both the lowest level of AT activity (<50%; hazard ratio [HR] 2.43, 95% confidence interval [CI] 1.20-4.89, = .01) and the middle-low level of AT activity (≥ 50% and < 70%; HR 2.06, 95% CI 1.06-4.02, = .03), compared with the normal AT activity level (≥ 70%). ROC curve analysis showed that the prediction accuracy of AT was an area under the curve (AUC) of 0.66 (cutoff 58%, sensitivity 61.4%, specificity 68.2%, = .0003). AT activity was significantly prognostic in the group with 20% to 50% predicted mortality (AUC 0.74, sensitivity: 24.0%-55.5%, specificity: 83.3%-93.0%). An early decrease in AT activity level in ICU patients may be a predictor of mortality at discharge.
Topics: Humans; Prognosis; Antithrombins; Retrospective Studies; Critical Care; Intensive Care Units; Antithrombin III; ROC Curve; Anticoagulants; Sepsis
PubMed: 38099709
DOI: 10.1177/10760296231218711 -
Scientific Reports Dec 2023The human sulfatase HSulf-2 is one of only two known endosulfatases that play a decisive role in modulating the binding properties of heparan sulfate proteoglycans on...
The human sulfatase HSulf-2 is one of only two known endosulfatases that play a decisive role in modulating the binding properties of heparan sulfate proteoglycans on the cell surface and in the extracellular matrix. Recently, HSulf-2 was shown to exhibit an unusual post-translational modification consisting of a sulfated glycosaminoglycan chain. This study describes the structural characterization of this glycosaminoglycan (GAG) and provides new data on its impact on the catalytic properties of HSulf-2. The unrevealed nature of this GAG chain is identified as a chondroitin/dermatan sulfate (CS/DS) mixed chain, as shown by mass spectrometry combined with NMR analysis. It consists primarily of 6-O and 4-O monosulfated disaccharide units, with a slight predominance of the 4-O-sulfation. Using atomic force microscopy, we show that this unique post-translational modification dramatically impacts the enzyme hydrodynamic volume. We identified human hyaluronidase-4 as a secreted hydrolase that can digest HSulf-2 GAG chain. We also showed that HSulf-2 is able to efficiently 6-O-desulfate antithrombin III binding pentasaccharide motif, and that this activity was enhanced upon removal of the GAG chain. Finally, we identified five N-glycosylation sites on the protein and showed that, although required, reduced N-glycosylation profiles were sufficient to sustain HSulf-2 integrity.
Topics: Humans; Microscopy, Atomic Force; Glycosaminoglycans; Sulfatases; Heparan Sulfate Proteoglycans; Chondroitin Sulfates; Mass Spectrometry
PubMed: 38097644
DOI: 10.1038/s41598-023-49147-5 -
Cureus Nov 2023Introduction Budd-Chiari syndrome (BCS) is a rare cause of ascites in children, and its clinical manifestation depends upon the extent and rapidity of the occlusion of...
Introduction Budd-Chiari syndrome (BCS) is a rare cause of ascites in children, and its clinical manifestation depends upon the extent and rapidity of the occlusion of hepatic veins. This study aimed to identify the clinical manifestations, causes, treatment options, and outcomes of BCS in children. Materials and methods A retrospective descriptive study of BCS in children under 15 years of age was conducted. This study was approved by the Pakistan Kidney and Liver Institute and Research Centre on June 23, 2023, with approval number 0128. The patients' medical records from December 2020 to July 2023 were obtained from Sisoft Healthcare Information System. In this study, we employ a set of predetermined questions to retrieve relevant data retrospectively and then organise it in Excel spreadsheets. SPSS version 26 (Armonk, NY: IBM Corp.) was used to analyse the data. Categorical variables are shown as frequencies (%), while continuous variables are reported as mean±SD. Results Of 37 (n) patients diagnosed with BCS, 19 (51.35%) were male and 18 (48.65%) were female. The mean age of presentation was 9.8±4.1 years. Ascites are the predominant clinical manifestation (100%), followed by hepatomegaly (37.8%). A total of 45.9% of patients had deranged liver function tests. Chronic BCS is the predominant mode of presentation. Protein C deficiency was present in nine patients (24.3%), two patients (5.4%) had protein S deficiency and two patients (5.4%) had antithrombin III deficiency. Hepatic veins exhibited the highest incidence of obstruction (73.0%). Liver biopsies were done in 15 (40.54%) patients to determine the staging of fibrosis. Eight patients (21.62%) had undergone radiological interventions, two patients had liver transplants and the rest were treated with medications, including anticoagulants. Conclusion BCS can present in acute, subacute or chronic forms. Ascites and hepatomegaly should raise the suspicion of BCS in children. Common radiological findings are non-visualisation of the hepatic veins. BCS has a wide range of aetiologies and treatment options. Protein C deficiency is the most predominant procoagulant disorder. Radiological interventions during the acute and subacute forms of BCS usually have excellent results. Liver transplant remains the definite treatment.
PubMed: 38073981
DOI: 10.7759/cureus.48418