-
Biochemistry and Biophysics Reports Sep 2023SARS-CoV-2 causes substantial extrapulmonary manifestations in addition to pulmonary disease. Some of the major organs affected are cardiovascular, hematological and...
SARS-CoV-2 causes substantial extrapulmonary manifestations in addition to pulmonary disease. Some of the major organs affected are cardiovascular, hematological and thrombotic, renal, neurological, and digestive systems. These types of muti-organ dysfunctions make it difficult and challenging for clinicians to manage and treat COVID-19 patients. The article focuses to identify potential protein biomarkers that can flag various organ systems affected in COVID-19. Publicly reposited high throughput proteomic data from human serum (HS), HEK293T/17 (HEK) and Vero E6 (VE) kidney cell culture were downloaded from ProteomeXchange consortium. The raw data was analyzed in Proteome Discoverer 2.4 to delineate the complete list of proteins in the three studies. These proteins were analyzed in Ingenuity Pathway Analysis (IPA) to associate them to various organ diseases. The shortlisted proteins were analyzed in MetaboAnalyst 5.0 to shortlist potential biomarker proteins. These were then assessed for disease-gene association in DisGeNET and validated by Protein-protein interactome (PPI) and functional enrichment studies (GO_BP, KEGG and Reactome pathways) in STRING. Protein profiling resulted in shortlisting 20 proteins in 7 organ systems. Of these 15 proteins showed at least 1.25-fold changes with a sensitivity and specificity of 70%. Association analysis further shortlisted 10 proteins with a potential association with 4 organ diseases. Validation studies established possible interacting networks and pathways affected, confirmingh the ability of 6 of these proteins to flag 4 different organ systems affected in COVID-19 disease. This study helps to establish a platform to seek protein signatures in different clinical phenotypes of COVID-19. The potential biomarker candidates that can flag organ systems involved are: (a) Vitamin K-dependent protein S and Antithrombin-III for hematological disorders; (b) Voltage-dependent anion-selective channel protein 1 for neurological disorders; (c) Filamin-A for cardiovascular disorder and, (d) Peptidyl-prolyl -trans isomerase A and Peptidyl-prolyl -trans isomerase FKBP1A for digestive disorders.
PubMed: 37304132
DOI: 10.1016/j.bbrep.2023.101493 -
Medicine Nov 2023Subchorionic hemorrhage (SCH) or hematoma is one of the abnormal ultrasonic manifestations. At present, there are few studies on the pathogenesis of SCH, and its...
Subchorionic hemorrhage (SCH) or hematoma is one of the abnormal ultrasonic manifestations. At present, there are few studies on the pathogenesis of SCH, and its underlying mechanism is still unclear. It may be related to abnormal placenta formation and implantation, autoimmune dysfunction, and coagulation dysfunction. As a unique complication of pregnancy, SCH has a controversial effect on pregnancy outcome. The aim of the present study was to explore the possible etiology of SCH, especially its association with autoimmune dysfunctions, as well as the pregnancy outcomes of SCH patients. This retrospective cohort study was conducted at the Third Affiliated Hospital of Zhengzhou University. Patients with a singleton pregnancy of ≤14 weeks gestation from June 2021 to June 2022 were included. Patients with SCH detected by ultrasound were selected as the study group, while patients without SCH during the same period were chosen as the control group. Immunological indicators and pregnancy outcomes were primarily compared between the 2 groups. The decrease in protein S activity and antithrombin-III levels, the increase in homocysteine levels, and the presence of autoantibodies (such as lupus anticoagulant, anticardiolipin antibody, and antinuclear antibody spectrum) were found to be risk factors for SCH. SCH in the first trimester was associated with higher rates of premature rupture of membranes (13.5% vs 3.8%) and miscarriage (14.4% vs 6.4%). However, there were no significant differences in the rates of placental abruption, fetal distress, cesarean section, neonatal birth weight, and gestational age. The incidence of miscarriage was also significantly higher in patients with subchorionic hematoma (SCH) who tested positive for autoantibodies (28.2% vs 7.6%). There were no significant differences in other clinical characteristics and pregnancy outcomes between patients with SCH who had positive autoantibodies and those who did not. The occurrence of SCH may be related to maternal immune abnormalities. SCH may increase the risk of premature rupture of membranes and abortion. However, there is no correlation between the presence or absence of SCH and neonatal outcomes.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Pregnancy Outcome; Abortion, Spontaneous; Pregnant Women; Retrospective Studies; Cesarean Section; Placenta; Pregnancy Complications; Hematoma; Premature Birth; Risk Factors; Autoantibodies
PubMed: 38013360
DOI: 10.1097/MD.0000000000035874 -
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 -
JBRA Assisted Reproduction May 2024Many pieces of literature have reported that inherited and acquired thrombophilia might be a risk factor for recurrent implantation failure (RIF), however, most studies...
OBJECTIVE
Many pieces of literature have reported that inherited and acquired thrombophilia might be a risk factor for recurrent implantation failure (RIF), however, most studies have only focused on RIF patients and not their male partners. We studied the possible association of paternal thrombophilia with RIF risk.
METHODS
Forty-two male partners aged 20-45 suffered from RIF compared with 42 males from couples with at least one successful pregnancy. All participants were investigated for thrombophilia markers.
RESULTS
The prevalence of coagulation Factor V activity was significantly higher in the case group (42.9%) than in the control group (16.7%) (p=0.008) (OR=3.75; 95% CI, 1.38, 10.12). The prevalence of protein C and protein S deficiencies in RIF patients were 4.8% and 2.4%, respectively, and 0% in the controls. The prevalence of antithrombin III (ATIII) deficiency was significantly higher in the case group (19%) than in the control group (2.4%) (p=0.01). None of MTHFR C677T and MTHFR A1298C were statistically significant between the two groups. Combined thrombophilia was 45.2% in the men of the RIF group when compared with the control, 14.2% (p=0.001) (OR = 4.95; 95% CI, 1.75-13.86).
CONCLUSIONS
Paternal thrombophilia may be related to recurrent implantation failure, so evaluation of this factor in RIF patients could be used to identify relevant risk groups and may help in the proper management of these cases to enhance the chance of implantation.
PubMed: 38712835
DOI: 10.5935/1518-0557.20240026 -
British Journal of Clinical Pharmacology Aug 2023There remains a paucity of literature regarding best practice for antithrombin (AT) monitoring, dosing and dose-response in paediatric extracorporeal membrane...
AIMS
There remains a paucity of literature regarding best practice for antithrombin (AT) monitoring, dosing and dose-response in paediatric extracorporeal membrane oxygenation (ECMO) patients.
METHODS
We conducted a retrospective cohort study at a quaternary care paediatric intensive care unit in all patients <18 years of age supported on ECMO from 1 June 2011 to 30 April 2020. Adverse events and outcomes were characterized for all ECMO runs. AT activity and replacement were characterized and compared between two clinical protocols. AT activities measured post- vs. pre-AT replacement were compared in order to characterize a dose-response relationship.
RESULTS
The final cohort included 191 patients with 201 ECMO runs and 2028 AT activity measurements. The median AT activity was 65% (interquartile range [IQR], 51-82) and 879 (43.3%) measurements met the criteria of deficient. The overall median AT dose and increase in AT activity were 50.6 units/kg/dose (IQR, 39.5-67.2) and 23.5% (IQR, 9.8-36.0), respectively. In the protocol that restricted AT activity measurements to clinical scenarios concerning for heparin resistance, there was significantly higher dosing in conjunction with significantly fewer overall administrations. Approximately one third of AT activity remained deficient after repletion. There was no difference in mechanical complications, reasons for discontinuation of ECMO support, time on ECMO or survival between protocols.
CONCLUSIONS
There was a high prevalence of AT deficiency in paediatric ECMO patients. An AT replacement protocol based on evaluating heparin resistance is associated with fewer AT administrations, with similar circuit and patient outcomes. Further data are needed to identify optimal dosing strategies.
Topics: Humans; Child; Extracorporeal Membrane Oxygenation; Retrospective Studies; Anticoagulants; Antithrombins; Heparin; Antithrombin III
PubMed: 36850024
DOI: 10.1111/bcp.15703 -
Annals of Medicine and Surgery (2012) Mar 2024The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the...
Safety and efficacy of extended thrombophilia screening directed venous thromboembolic events (VTE) prophylaxis in live liver donors: do we really need extended thrombophilia screening routinely?
BACKGROUND AND AIMS
The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the safety and efficacy of thrombophilia profile testing directed venous thromboembolic events (VTE) prophylaxis while balancing bleeding risk and the need for routine thrombophilia testing before live liver donation among living donor candidates.
MATERIALS AND METHODS
Protein S (PS), protein C (PC), anti-thrombin (AT) III, and anti-phospholipid antibody panel (APLA) levels were measured in 567 potential donor candidates. Donors were divided into normal, borderline and high-risk groups based on Caprini score. The safety endpoints were VTE occurrence, bleeding complications or mortality.
RESULTS
Among 567 donors, 21 (3.7%) were deficient in protein C, and 14 (2.5%) were deficient in anti-thrombin-III. IgM and IgG. Anti-phospholipids antibodies were positive in 2/567 (0.4%) and 2/567 (0.4%), respectively. IgM and IgG lupus anticoagulant antibodies were positive in 3/567 (0.5%) and 3/567 (0.5%), respectively. VTE events, bleeding complications and postoperative living donors liver transplantation-related complications were comparable among the three donor groups (>0.05). One donor in the normal donor group developed pulmonary embolism, but none of the donors in either borderline or high-risk group developed VTE. The mean length of ICU and total hospital stay were comparable. No donor mortality was observed in all donor groups.
CONCLUSIONS
Due to thrombophilia testing directed VTE prophylaxis, VTE events were comparable in normal, borderline and high-risk thrombophilia donor groups, but more evaluations are required to determine the lower safe levels for various thrombophilia parameters including PC, PS and AT-III before surgery among living donor candidates.
PubMed: 38463105
DOI: 10.1097/MS9.0000000000001772 -
Blood Coagulation & Fibrinolysis : An... Dec 2023Although the contribution of antiphospholipid antibodies (aPL) to thrombolembolism in systemic lupus erythematosus (SLE) is well known, there is not enough data on the...
Although the contribution of antiphospholipid antibodies (aPL) to thrombolembolism in systemic lupus erythematosus (SLE) is well known, there is not enough data on the contribution of various hereditary thrombophilic factors. In this study, we aimed to determine acquired and hereditary thrombophilic factors in adult patients with SLE. A total of 93 SLE patients (87 women and 6 men) were included. Data on clinical, demographic and laboratory characteristics, and disease activity scores (SLEDAI) of the patients were evaluated. The patients were analyzed with a screen, including lupus anticoagulant, anticardiolipin antibodies (aCL), antithrombin III, protein C, protein S, and homocysteine levels; factor V Leiden ( FVL ), methylenetetrahydrofolate reductase ( MTHFR ) and prothrombin G20210A gene mutations. A total of 23 thromboembolic events were reported in 17 (18.3%) of the patients. The frequency of pregnancy complications and SLEDAI scores were significantly higher in SLE patients who had a thromboembolism event ( P < 0.05). Thromboembolism was detected in 12 (32.4%) of 37 patients with positive aPL antibody and 5 (8.9%) of 56 patients with negative aPL antibody ( P = 0.006). In addition, thromboembolism developed in 11 (32.3%) of 34 lupus anticoagulant-positive patients and 6 (10.1%) of 59 lupus anticoagulant-negative patients ( P = 0.012). Moreover, protein C levels were significantly lower in patients who developed thromboembolism ( P < 0.05). Patients with and without thromboembolism were similar in terms of genetic thrombophilia factors ( MTHFR A1298C, MTHFR C677T, FVL and Prothrombin G20210A ) ( P > 0.05). In conclusion, in the current study, some acquired (aPL, lupus anticoagulant and cCL IGG) and hereditary (protein C deficiency) thrombophilic factors were shown to be associated with the development of thrombosis in SLE patients. However, the effect of other hereditary factors on the development of thromboembolism could not be demonstrated. According to the data of this study, genetic screening seems inappropriate in terms of the risk of thromboembolism in patients with SLE.
Topics: Adult; Male; Pregnancy; Humans; Female; Lupus Coagulation Inhibitor; Protein C; Prothrombin; Lupus Erythematosus, Systemic; Thromboembolism; Antiphospholipid Syndrome; Risk Factors
PubMed: 37756208
DOI: 10.1097/MBC.0000000000001253 -
Chemistry & Biodiversity Jun 2024Thromboembolism is the culprit of cardiovascular diseases, leading to the highest global mortality rate. Anticoagulation emerges as the primary approach for managing... (Review)
Review
Thromboembolism is the culprit of cardiovascular diseases, leading to the highest global mortality rate. Anticoagulation emerges as the primary approach for managing thrombotic conditions. Notably, sulfated polysaccharides exhibit favorable anticoagulant efficacy with reduced side effects. This review focuses on the structure-anticoagulant activity relationship of sulfated polysaccharides and the underlying action mechanisms. It is concluded that chlorosulfonicacid-pyridine method serves as the preferred technique to synthesize sulfated polysaccharides. The anticoagulant activity of sulfated polysaccharides is linked to the substitution site of sulfate groups, degree of substitution, molecular weight, main side chain structure, and glycosidic bond conformation. Moreover, sulfated polysaccharides exert anticoagulant activity via various pathways, including the inhibition of blood coagulation factors, activation of antithrombin III and heparin cofactor II, antiplatelet aggregation, and promotion of the fibrinolytic system.
Topics: Anticoagulants; Polysaccharides; Structure-Activity Relationship; Humans; Sulfates; Animals
PubMed: 38600639
DOI: 10.1002/cbdv.202400152 -
The Homozygous Type II Antithrombin Deficient Pregnant Woman Monitored by Thrombin Generation Assay.Clinical Laboratory Oct 2023We present the case study of a 28-year-old pregnant woman with antithrombin deficiency who was treated with low-molecular-weight heparin (LMWH).
BACKGROUND
We present the case study of a 28-year-old pregnant woman with antithrombin deficiency who was treated with low-molecular-weight heparin (LMWH).
METHODS
Due to severe homozygous type II antithrombin heparin binding site (HBS) deficiency, the thrombin generation (TG) was monitored in this woman via the Thrombin Generation Assay (TGA). We used Siemens diagnostic kits Berichrom® Antithrombin III (IIa) and INNOVANCE® Antithrombin (Xa) to determine antithrombin activity. We used a chromogenic method for determination of factor Xa (FXa) inhibition.
RESULTS
There were no thrombotic complications during the whole pregnancy of the observed woman. Antithrombin was administered before and after delivery, which was significantly reflected in the decrease in thrombin generation.
CONCLUSIONS
Consistent monitoring of thrombin generation with LMWH anticoagulant therapy administration during pregnancy together with antithrombin administration before and after delivery can improve the overall condition of pregnant women and the quality of their care.
Topics: Female; Humans; Pregnancy; Adult; Antithrombins; Antithrombin III; Thrombin; Pregnant Women; Heparin, Low-Molecular-Weight; Anticoagulants; Heparin; Antithrombin III Deficiency
PubMed: 37844053
DOI: 10.7754/Clin.Lab.2023.230435 -
World Journal of Clinical Cases Jul 2023Antithrombin III (AT3) deficiency, an autosomal dominant disease, increases the likelihood of an individual developing venous thromboembolism (VTE). Long-term...
BACKGROUND
Antithrombin III (AT3) deficiency, an autosomal dominant disease, increases the likelihood of an individual developing venous thromboembolism (VTE). Long-term anticoagulation treatment is required for those suffering from AT3 deficiency.
CASE SUMMARY
A man aged 23, who had a history of deep venous thrombosis (DVT), experienced recurrent pain and swelling in his right lower extremity for three days following withdrawal of Rivaroxaban. He was diagnosed with DVT and antithrombin III deficiency as genetic testing revealed a single nucleotide variant in (c.667T>C, p.S223P). The patient was advised to accept long-term anticoagulant therapy.
CONCLUSION
Inherited AT3 deficiency due to mutations results in recurrent VTE. Patients may benefit from long-term anticoagulant therapy.
PubMed: 37583989
DOI: 10.12998/wjcc.v11.i20.4956