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Blood Coagulation & Fibrinolysis : An... Jan 2024Preeclampsia is a worldwide contributor to maternal and fetal morbidity and mortality. Women with preeclampsia are in a hyper-coagulable state with increased risk of...
Preeclampsia is a worldwide contributor to maternal and fetal morbidity and mortality. Women with preeclampsia are in a hyper-coagulable state with increased risk of thromboembolic disease later in life compared with normal pregnant women. The contact system (CAS) in plasma can mediate thrombin generation and is an important contributor to thrombus growth, but the activation of CAS during pregnancy complicated by preeclampsia is not yet elucidated, and CAS may play a role in the pathophysiology of preeclampsia. Therefore, the aim of the study is to address thrombin generation, and in particular, the capacity of the CAS-mediated pathway in patients with preeclampsia compared with pregnant controls. One hundred and seventeen women with preeclampsia and matched controls were included. The project was registered at www.clinicaltrials.gov as NCT04825145. CAS and tissue factor induced thrombin generation, proteins C and S, antithrombin, and histidine-rich glycoprotein (HRG) were assessed. Women with preeclampsia had significantly increased CAS and tissue factor-induced endogenous thrombin potential (ETP), and HRG compared with controls, P = 0.022, P = 0.024, and P = 0.02, respectively. The concentrations of protein C and antithrombin were significantly reduced in the preeclampsia group, P = 0.024 and P < 0.0001, respectively. No significant difference in the concentration of protein S was detected, P = 0.06. This study demonstrates a significant increased CAS-induced ETP and an overall decrease of important regulators of coagulation in women with preeclampsia compared with controls. These aspects can contribute to the hyper-coagulable state characterizing preeclampsia.
Topics: Female; Humans; Pregnancy; Pregnant Women; Thrombin; Thromboplastin; Pre-Eclampsia; Anticoagulants; Protein C; Antithrombin III; Antithrombins
PubMed: 38051647
DOI: 10.1097/MBC.0000000000001269 -
Anesthesiology and Pain Medicine Jun 2023After the COVID-19 pandemic, multiple reviews have documented the success of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Patients who experience... (Review)
Review
CONTEXT
After the COVID-19 pandemic, multiple reviews have documented the success of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Patients who experience hypoxemia but have normal contractility may be switched to veno-venous-ECMO (VV-ECMO).
PURPOSE
In this review, we present three protocols for anesthesiologists. Firstly, transesophageal echocardiography (TEE) aids in cannulation and weaning off inotropes and fluids. Our main objective is to assist in patient selection for the Avalon Elite single catheter, which is inserted into the right internal jugular vein and terminates in the right atrium. Secondly, we propose appropriate anticoagulant doses. We outline day-to-day monitoring protocols to prevent heparin-induced thrombocytopenia (HIT) or resistance. Once the effects of neuromuscular paralysis subside, sedation should be reduced. Therefore, we describe techniques that may prevent delirium from progressing into permanent cognitive decline.
METHODS
We conducted a PubMed search using the keywords VV-ECMO, TEE, Avalon Elite (Maquet, Germany), and quetiapine. We combined these findings with interviews conducted with nurses and anesthesiologists from two academic ECMO centers, focusing on anticoagulation and sedation.
RESULTS
Our qualitative evidence synthesis reveals how TEE confirms cannulation while avoiding right atrial rupture or low flows. Additionally, we discovered that typically, after initial heparinization, activated partial thromboplastin time (PTT) is drawn every 1 to 2 hours or every 6 to 8 hours once stable. Daily thromboelastograms, along with platelet counts and antithrombin III levels, may detect HIT or resistance, respectively. These side effects can be prevented by discontinuing heparin on day two and initiating argatroban at a dose of 1 μg/kg/min while maintaining PTT between 61 - 80 seconds. The argatroban dose is adjusted by 10 - 20% if PTT is between 40 - 60 or 80 - 90 seconds. Perfusionists assist in establishing protocols following manufacturer guidelines. Lastly, we describe the replacement of narcotics and benzodiazepines with dexmedetomidine at a dose of 0.5 to 1 μg/kg/hour, limited by bradycardia, and the use of quetiapine starting at 25 mg per day and gradually increasing up to 200 mg twice a day, limited by prolonged QT interval.
CONCLUSIONS
The limitation of this review is that it necessarily covers a broad range of ECMO decisions faced by an anesthesiologist. However, its main advantage lies in the identification of straightforward argatroban protocols through interviews, as well as the discovery, via PubMed, of the usefulness of TEE in determining cannula position and contractility estimates for transitioning from VA-ECMO to VV-ECMO. Additionally, we emphasize the benefits in terms of morbidity and mortality of a seldom-discussed sedation supplement, quetiapine, to dexmedetomidine.
PubMed: 38021335
DOI: 10.5812/aapm-136524 -
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 -
Thrombosis Journal Nov 2023Mixed phenotype acute leukaemia (MPAL) is associated with worse overall survival, compared with other acute leukaemias in adults. Lack of clear treatment guidelines...
Mixed phenotype acute leukaemia (MPAL) is associated with worse overall survival, compared with other acute leukaemias in adults. Lack of clear treatment guidelines makes the therapy challenging. ALL-like induction and consolidation treatment followed by allo-HSCT is the preferred first-line treatment. We present a case of a 36-year-old woman diagnosed with MPAL (EGIL Myelo/B) with KMT2A rearrangement, treated with the PALG-ALL-7 (including PEG-asparaginase) protocol. On day 25 after the induction therapy initiation, numbness of limbs and dizziness were observed. Therefore, the imaging studies (CT and MRI) were performed and a diagnosis of thrombosis of superior sagittal sinus of the brain was established. Routinely performed blood coagulation tests showed prolonged APTT and PT, decreased antithrombin III activity and decreased free protein S concentration. LMWH treatment and substitutional therapy with antithrombin III were started, which resulted in a significant reduction in the thrombosis associated symptoms and improvement of the neurological status after 3 days. After induction and consolidation therapy, the patient obtained complete haematological remission and negative measurable residual disease. Six months after the diagnosis, allo-HSCT was successfully performed. During the 4 months follow-up, the patient remained MRD negative and thrombotic symptoms free. To the best of our knowledge, our communication has been the first report of such complication in an MPAL patient treated with PEG-asparaginase containing protocol in adults. We recommend increased vigilance in patients manifesting any mild neurological symptoms and early decision about the MRI study performance.
PubMed: 37974201
DOI: 10.1186/s12959-023-00561-9 -
IScience Nov 2023Repetitive sequences represent about 45% of the human genome. Some are transposable elements (TEs) with the ability to change their position in the genome, creating...
Repetitive sequences represent about 45% of the human genome. Some are transposable elements (TEs) with the ability to change their position in the genome, creating genetic variability both as insertions or deletions, with potential pathogenic consequences. We used long-read nanopore sequencing to identify TE variants in the genomes of 24 patients with antithrombin deficiency. We identified 7 344 TE insertions and 3 056 TE deletions, 2 926 were not previously described in publicly available databases. The insertions affected 3 955 genes, with 6 insertions located in exons, 3 929 in introns, and 147 in promoters. Potential functional impact was evaluated with gene annotation and enrichment analysis, which suggested a strong relationship with neuron-related functions and autism. We conclude that this study encourages the generation of a complete map of TEs in the human genome, which will be useful for identifying new TEs involved in genetic disorders.
PubMed: 37953943
DOI: 10.1016/j.isci.2023.108214 -
Nephrology, Dialysis, Transplantation :... Apr 2024The risk of diabetic kidney disease (DKD) progression is significant despite treatment with renin-angiotensin system (RAS) blocking agents. Current clinical tools cannot...
BACKGROUND
The risk of diabetic kidney disease (DKD) progression is significant despite treatment with renin-angiotensin system (RAS) blocking agents. Current clinical tools cannot predict whether or not patients will respond to treatment with RAS inhibitors (RASi). We aimed to investigate whether proteome analysis could identify urinary peptides as biomarkers that could predict the response to angiotensin-converting enzyme inhibitor and angiotensin-receptor blockers treatment to avoid DKD progression. Furthermore, we investigated the comparability of the estimated glomerular filtration rate (eGFR), calculated using four different GFR equations, for DKD progression.
METHODS
We evaluated urine samples from a discovery cohort of 199 diabetic patients treated with RASi. DKD progression was defined based on eGFR percentage slope results between visits (∼1 year) and for the entire period (∼3 years) based on the eGFR values of each GFR equation. Urine samples were analysed using capillary electrophoresis-coupled mass spectrometry. Statistical analysis was performed between the uncontrolled (patients who did not respond to RASi treatment) and controlled kidney function groups (patients who responded to the RASi treatment). Peptides were combined in a support vector machine-based model. The area under the receiver operating characteristic curve was used to evaluate the risk prediction models in two independent validation cohorts treated with RASi.
RESULTS
The classification of patients into uncontrolled and controlled kidney function varies depending on the GFR equation used, despite the same sample set. We identified 227 peptides showing nominal significant difference and consistent fold changes between uncontrolled and controlled patients in at least three methods of eGFR calculation. These included fragments of collagens, alpha-1-antitrypsin, antithrombin-III, CD99 antigen and uromodulin. A model based on 189 of 227 peptides (DKDp189) showed a significant prediction of non-response to the treatment/DKD progression in two independent cohorts.
CONCLUSIONS
The DKDp189 model demonstrates potential as a predictive tool for guiding treatment with RASi in diabetic patients.
Topics: Humans; Female; Male; Glomerular Filtration Rate; Middle Aged; Diabetic Nephropathies; Biomarkers; Peptides; Aged; Angiotensin-Converting Enzyme Inhibitors; Renin-Angiotensin System; Prognosis; Disease Progression; Follow-Up Studies; Blood Pressure; Antihypertensive Agents; Hypertension
PubMed: 37930730
DOI: 10.1093/ndt/gfad223 -
Neurology India 2023Hereditary antithrombin (AT) deficiency is a rare thrombophilia associated with cerebral vein thrombosis (CVT). We report a case study of hereditary AT deficiency...
Hereditary antithrombin (AT) deficiency is a rare thrombophilia associated with cerebral vein thrombosis (CVT). We report a case study of hereditary AT deficiency causing CVT in three members of a family. A 29-year-old female presented with features of CVT. Her mother and a sister had CVT in the past and investigation for hereditary thrombophilia revealed low blood AT activity in all of them. The index patient (proband) was positive for the SERPINC1 gene mutation confirming the diagnosis of hereditary AT deficiency. She recovered well with anticoagulation and was advised to continue it lifelong. Diagnosing hereditary thrombophilia like AT deficiency is important in planning anticoagulation and proper counseling of asymptomatic family members regarding prophylaxis for venous thromboembolism (VTE) in high-risk situations.
Topics: Humans; Female; Adult; Antithrombin III Deficiency; Thrombophilia; Intracranial Thrombosis; Venous Thrombosis; Anticoagulants
PubMed: 37929439
DOI: 10.4103/0028-3886.388110 -
International Journal of Molecular... Oct 2023Antithrombin III is an important anticoagulant factor with anti-inflammatory properties. However, few studies have explored its anti-inflammatory actions in...
Antithrombin III is an important anticoagulant factor with anti-inflammatory properties. However, few studies have explored its anti-inflammatory actions in overexpressed transgenic animals. In this study, the dairy goats with mammary overexpression of were used to investigate their general health, milk quality and particularly their response to inflammatory challenge. The results showed that transgenic goats have a normal phenotype regarding their physiological and biochemical parameters, including whole blood cells, serum protein levels, total cholesterol, urea nitrogen, uric acid, and total bilirubin, compared to the WT. In addition, the quality of milk also improved in transgenic animals compared to the WT, as indicated by the increased milk fat and dry matter content and the reduced somatic cell numbers. Under the stimulation of an LPS injection, the transgenic goats had elevated contents of IGA, IGM and superoxide dismutase SOD, and had reduced proinflammatory cytokine release, including IL-6, TNF-α and IFN-β. A 16S rDNA sequencing analysis also showed that the transgenic animals had a similar compositions of gut microbiota to the WT goats under the stimulation of LPS injections. Mammary gland overexpression in dairy goats is a safe process, and it did not jeopardize the general health of the transgenic animals; moreover, the compositions of their gut microbiota also improved with the milk quality. The LPS stimulation study suggests that the increased expression may directly or indirectly suppress the inflammatory response to increase the resistance of transgenic animals to pathogen invasion. This will be explored in future studies.
Topics: Animals; Female; Lipopolysaccharides; Antithrombin III; Milk; Animals, Genetically Modified; Anticoagulants; Goats; Health Status; Mammary Glands, Animal; Lactation
PubMed: 37894983
DOI: 10.3390/ijms242015303 -
Diseases (Basel, Switzerland) Oct 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated an unprecedented challenge for healthcare systems worldwide. Currently, the...
UNLABELLED
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated an unprecedented challenge for healthcare systems worldwide. Currently, the scientific community wonders if liver injury in patients suffering from severe forms is a direct consequence of the virus or secondary manifestations of systemic inflammation. The liver plays an essential role in the development of the inflammatory storm typical of this disease, and its involvement is associated with worse clinical outcomes and a higher risk of morbidity and mortality from Coronavirus disease 2019 (COVID-19).
METHODS
Ten patients suffering from severe COVID-19 disease who died between January 2020 and December 2021 were included in the present analysis. These subjects underwent a post mortem examination with a focused evaluation of the hepatic injury. Also, several laboratory parameters have been evaluated, with a primary focus on prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers to detect coagulative changes.
RESULTS
The main cause of death was represented by pulmonary thromboembolism events (50%). The analysis of coagulation laboratory parameters and liver biomarkers revealed a statistically significant rise in aPTT and ALP, and a decrease in albumin, when comparing the blood value at admission and death. We also found high levels of D-dimers in most of the subjects at the time of hospitalization. Interestingly, the post mortem analysis of the liver showed ample morphologic variability, with several disease features. In detail, the liver histology revealed the following: the presence of a variable degree of micro- and macrovacuolar steatosis, inflammation (also, hepato-cholangitis), and variable fibrosis. Of mention, we were also able to detect organized fibrinous material.
CONCLUSIONS
Our results indicate that in subjects with a severe form of COVID-19, liver disease is related to changes in coagulative and fibrinolytic pathways. In particular, we noted low fibrinogen levels and high D-dimer levels with histological liver findings. Our data suggest that fibrinogen and D-dimers may be used as prognostic markers to detect the severity of liver disease in patients with COVID-19. Finally, we underline the crucial role of coagulation balance in subjects with severe forms of COVID-19.
PubMed: 37873785
DOI: 10.3390/diseases11040141