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Practical Laboratory Medicine Aug 2023To evaluate whether the routine coagulation tests can be performed using platelet depleted plasma (PDP, residual platelet count <40000/μL) to achieve maximum efficiency...
OBJECTIVES
To evaluate whether the routine coagulation tests can be performed using platelet depleted plasma (PDP, residual platelet count <40000/μL) to achieve maximum efficiency of the automated workflow and compare results of these tests performed with platelet poor plasma (PPP residual platelet count <10,000/μL) prepared manually 'offline'.
DESIGN AND METHODS
The PDP was obtained first following 'on line' centrifugation at 4150 RPM (3000) for 7 min. The routine coagulation tests, Prothrombin Time (PT), Activated Partial Thromboplastin Clotting Time (aPTT), D-dimer (DD), Antithrombin III (AT3) and Fibrinogen (FBG) were performed. The PPP was obtained from an aliquot of PDP samples with additional 'manual off line' centrifugation at 7700 RPM (3314) for 3 min (total 10 min, online + offline) and the same tests were performed. The statistical analysis was carried out using EP Evaluator v11 to compare results from both methods.
RESULTS
The results from both PPP and PDP samples demonstrated strong correlation. For example, PT (R = 0.9989; N = 55, and of Bias -0.12 (-0.67%), aPTT(R = 0.9957; N = 60, Bias 0.26 (0.58%)), AT3(R = 0.9800; N = 49, Bias -2.0 (-2.2%)), FBG (R = 0.9956; N = 57, Bias -1.9 (-0.5%)) and DD (R = 0.9981; N = 38, Bias 0.005 (0.373%)) with insignificant bias.
CONCLUSIONS
The utilization of the Roche cobas® 8100 automated 'online' centrifugation helps achieve optimal workflow efficiency without impacting analytical performance of the PT, aPTT, DD, AT3 and FBG assays. The use of PDP can be superior method to PPP for routine coagulation tests.
PubMed: 37649543
DOI: 10.1016/j.plabm.2023.e00324 -
Journal of Atherosclerosis and... Mar 2024Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from...
AIMS
Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from the phase 3 trial ANNEXA-4. We aimed to assess the efficacy and safety of andexanet alfa treatment in FXa inhibitor-related acute major bleeding in patients enrolled for ANNEXA-4 in Japan.
METHODS
This prespecified analysis included patients enrolled at Japanese sites in the prospective, open-label, single-arm ANNEXA-4 trial. Eligible patients had major bleeding within 18 hours of oral FXa inhibitor administration. The coprimary efficacy endpoints were percent change in anti-FXa activity and proportion of patients achieving excellent or good hemostatic efficacy 12 hours post-treatment.
RESULTS
A total of 19 patients were enrolled, all of whom had intracranial hemorrhage; 16 patients were evaluable for efficacy. Median percent reduction in anti-FXa activity from baseline to nadir was 95.4% in patients taking apixaban, 96.1% in patients taking rivaroxaban, and 82.2% in patients taking edoxaban. Overall, 14/16 patients (88%) achieved excellent or good hemostasis (apixaban, 5/5; rivaroxaban, 6/7; edoxaban, 3/4). Within 30 days, treatment-related adverse events (AEs) and serious AEs occurred in 2 and 5 patients, respectively. One patient died during follow-up, and 2 patients experienced thrombotic events.
CONCLUSION
Treatment with andexanet alfa rapidly reduced anti-FXa activity with favorable hemostatic efficacy in Japanese patients with acute major bleeding. Serious AEs of thrombotic events during rapid reversal of anti-FXa activity arose as particular safety concerns in this population as with previous studies.
Topics: Humans; Factor Xa Inhibitors; Rivaroxaban; Factor Xa; Japan; Prospective Studies; Hemorrhage; Antithrombin III; Hemostatics; Thrombosis; Fibrinolytic Agents; Recombinant Proteins; Anticoagulants; Pyridines; Thiazoles
PubMed: 37635060
DOI: 10.5551/jat.64223 -
Biomolecules Jul 2023Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl...
Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl phosphorylcholine (p(PMβCD-co-MPC)) with various monomer ratios were formed on magnetic nanoparticles and characterized. Surface chemistry effects on protein denaturation were evaluated and indicated that unmodified magnetic nanoparticles greatly perturbed the structure of proteins compared to coated particles. Plasma clotting assays were conducted to investigate the stability of plasma in the presence of particles, where a 2:2 monomer ratio yielded the best results for a given total surface area of particles. Total protein adsorption results revealed that modified surfaces exhibited reduced protein adsorption compared to bare particles, and pure MPC showed the lowest adsorption. Immunoblot results showed that fibrinogen, α1-antitrypsin, vitronectin, prekallikrein, antithrombin, albumin, and C3 correlated with film composition. Hemocompatibility testing with whole blood illustrated that the 1:3 ratio of CD to MPC had a negative impact on platelets, as evidenced by the increased activation, reduced response to an agonist, and reduced platelet count. Other formulations had statistically significant effects on platelet activation, but no formulation yielded apparent adverse effects on hemostasis. For the first time, p(PMβCD-co-MPC)-coated MNP were synthesized and their general hemocompatibility assessed.
Topics: Phosphorylcholine; Magnetite Nanoparticles; Adsorption; Antithrombin III; Blood Coagulation
PubMed: 37627230
DOI: 10.3390/biom13081165 -
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 -
International Journal of Molecular... Jul 2023Preeclampsia (PE) is a pregnancy-specific disorder affecting 4-10% of all expectant women. It greatly increases the risk of maternal and foetal death. Although the main... (Review)
Review
Preeclampsia (PE) is a pregnancy-specific disorder affecting 4-10% of all expectant women. It greatly increases the risk of maternal and foetal death. Although the main symptoms generally appear after week 20 of gestation, scientific studies indicate that the mechanism underpinning PE is initiated at the beginning of gestation. It is known that the pathomechanism of preeclampsia is strongly related to inflammation and oxidative stress, which influence placentation and provoke endothelial dysfunction in the mother. However, as of yet, no "key players" regulating all these processes have been discovered. This might be why current therapeutic strategies intended for prevention or treatment are not fully effective, and the only effective method to stop the disease is the premature induction of delivery, mostly by caesarean section. Therefore, there is a need for further research into new pharmacological strategies for the treatment and prevention of preeclampsia. This review presents new preventive methods and therapies for PE not yet recommended by obstetrical and gynaecological societies. As many of these therapies are in preclinical studies or under evaluation in clinical trials, this paper reports the molecular targets of the tested agents or methods.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Cesarean Section; Placentation; Oxidative Stress; Vascular Endothelial Growth Factor Receptor-1
PubMed: 37569476
DOI: 10.3390/ijms241512100 -
BMC Neurology Aug 2023Cerebral venous thrombosis is a rare type of stroke, occurring more among young individuals. The presentation is highly variable, and this can delay diagnosis and...
BACKGROUND
Cerebral venous thrombosis is a rare type of stroke, occurring more among young individuals. The presentation is highly variable, and this can delay diagnosis and management, thereby affecting outcome. The aim is to study the clinical, radiological profile, risk factors for cerebral venous thrombosis (CVT) and the role of transcranial color-coded duplex (TCCD) in CVT prognosis among Egyptian patients.
METHODS
Eighty CVT patients and 80 normal healthy individuals were included. Magnetic resonance imaging, magnetic resonance venography, and genetic thrombophilia tests were done for patients. Deep cerebral venous system was evaluated using B-mode transcranial color-coded duplex (TCCD) for both groups.
RESULTS
Showed female predominance with gender specific risk factors being the most common etiology. The most common hereditary thrombophilia was homozygous factor V Leiden mutation and anti-thrombin III (AT III). Headache was the most common presentation. Forty-three patients had transverse sinus thrombosis. Regarding TCCD, there was an increase in mean blood flow velocities, peak flow velocities and end diastolic flow velocities in deep middle cerebral vein and basal veins in CVT group compared to control group. There was a positive correlation not reaching statistical significance between flow velocities in the deep venous system and modified Rankin Scale.
CONCLUSION
Clinical presentation is extremely variable. In our population, homozygous factor V Leiden mutation and AT III deficiency were the most common. Increased deep cerebral venous system flow velocities using TCCD in patients with CVT reflect their venous hemodynamic state.
Topics: Humans; Female; Male; Prognosis; Case-Control Studies; Intracranial Thrombosis; Cerebral Veins; Venous Thrombosis
PubMed: 37550633
DOI: 10.1186/s12883-023-03342-z -
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