Plasma Prothrombin Time Research Articles

Are mechanical and electromechanical methods accurately interchangeable for measuring plasma prothrombin time and activated partial thromboplastin time? A comparative analysis study and potential implication to cardiovascular disease

INTRODUCTION: The DT100 offers both optical and mechanical modes, with its mechanical mode showing better homogenization than the STAGO, but comparative study is limited. OBJECTIVES: The study aimed to evaluate the diagnostic accuracy of plasma Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) measurements using the DT100 and STAGO instruments. METHODS: Designated as a cross-sectional study, this study was conducted at RSUD Dr. Soetomo from October 2022 to January 2023. Venous blood samples with plasma citrate anticoagulant 0.109 M 3.2% were consecutively collected from hospitalized patients, and all samples underwent testing using both the DT100 in mechanical mode (DT100, TCoag Ireland Limited, Ireland) and the STAGO employing an electromechanical method (Compact Max3, STAGO, France). Statistical analysis included comparison using Paired t-test, Pearson correlation, and Bland-Altman analysis to assess agreement between the results obtained from the two instruments. RESULTS: The study included 51 patients. PT levels were significantly lower with the DT100 compared to STAGO (MD: -2.0; 95%CI: (-2.30) – (-1.3); p<0.0001), and showed a strong positive correlation between methods (r:0.9535; p<0.0001). However, Bland-Altman analysis for PT showed a bias of 1.84, with limits of agreement (3.30-0.37), indicating systematic differences and variability. APTT levels were significantly higher with DT100 compared to STAGO (MD:3.60; 95%CI: 2.13–5.07; p<0.0001), with a moderate positive correlation (r:0.6690; p<0.0001). For APTT, bias of Bland-Altman analysis was -3.60, with limits ((-9.84) – (2.64)), suggesting significant discrepancies and variability between methods. CONCLUSION: The study found significant variability in PT and APTT measurements between the DT100 and STAGO methods. Keywords: Prothrombin time, activated partial thromboplastin time, mechanical method, DT100 TCoag, STAGO Compact Max 3

Identification of biomarkers for knee osteoarthritis through clinical data and machine learning models

Knee osteoarthritis (KOA) represents a progressive degenerative disorder characterized by the gradual erosion of articular cartilage. This study aimed to develop and validate biomarker-based predictive models for KOA diagnosis using machine learning techniques. Clinical data from 2594 samples were obtained and stratified into training and validation datasets in a 7:3 ratio. Key clinical features were identified through differential analysis between KOA and control groups, combined with least absolute shrinkage and selection operator (LASSO) regression. The SHapley Additive Planning (SHAP) method was employed to rank feature importance quantitatively. Based on these rankings, predictive models were constructed using Logistic Regression (LR), Random Forest (RF), eXtreme Gradient Boosting (xGBoost), Naive Bayes (NB), Support Vector Machine (SVM), and Decision Tree (DT) algorithms. Models were developed for subsets of variables, including the top 5, top 10, top 15, and all identified features. Receiver operating characteristic (ROC) curves were applied to compare diagnostic performance across models. Additionally, a risk stratification framework for KOA prediction was designed using recursive partitioning analysis (RPA). Using difference analysis and LASSO, 44 critical clinical features were identified. Among these, age, plasma prothrombin time, gender, body mass index (BMI), and prothrombin time and international normalized ratio (PTINR) emerged as the top five features, with SHAP values of 0.1990, 0.0981, 0.0471, 0.0433, and 0.0422, respectively. Machine learning analysis demonstrated that these variables provided robust diagnostic performance for KOA. In the training set, area under the curve (AUC) values for LR, RF, xGBoost, NB, SVM, and DT models were 0.947, 0.961, 0.892, 0.952, 0.885, and 0.779, respectively. Similarly, in the validation dataset, these models achieved AUC values of 0.961, 0.943, 0.789, 0.957, 0.824, and 0.76. Among them, RF consistently exhibited superior diagnostic accuracy for KOA. Additionally, RPA analysis indicated a higher prevalence of KOA among individuals aged 54 years and older. The integration of the top five clinical variables significantly enhanced the diagnostic accuracy for KOA, particularly when employing the RF model. Moreover, the RPA model offered valuable insights to assist clinicians in refining prognostic assessments and optimizing clinical decision-making processes.

Specifics of drug-drug interactions between rivaroxaban and a P-glycoprotein inhibitor depending on the <i>CYP3A4/A5</i> gene polymorphism in patients aged 80 years and older with non-valvular atrial fibrillation

BACKGROUND: An increased risk of bleeding during rivaroxaban administration is associated with polymorphism of genes involved in its biotransformation, as well as with the use of drugs inhibiting shared metabolic pathways. However, the data are inconsistent. AIM: To study specifics of drug-drug interactions between rivaroxaban and a P-glycoprotein inhibitor (using verapamil as an example) depending on the polymorphism of the CYP3A4 (rs35599367) and CYP3A5 (rs776746) genes in patients aged 80 years and older with non-valvular atrial fibrillation. MATERIALS AND METHODS: A total of 128 patients (median age 87.5 years [83; 90], 75% women) were examined. All patients underwent genotyping for the studied gene variants, determination of the minimum steady-state concentration of rivaroxaban (Cmin, ss), standardization of the minimum steady-state concentration of rivaroxaban per daily dose (Cmin, ss/D), determination of prothrombin time in plasma, and analysis of medical documentation for the occurrence of clinically significant minor bleeding. RESULTS: Compared to patients receiving rivaroxaban without calcium channel blockers, co-administration of rivaroxaban and verapamil in carriers of the CC variant of the CYP3A4 gene resulted in higher values of Cmin, ss (73.8 [49; 113.5] vs. 40.5 [25.6; 73.3] ng/mL), Cmin, ss/D (2.5 [1.7; 4.0] vs. 4.7 [2.9; 7.7] ng/mL/mg), prothrombin time (14.8 [13.3; 17.3] vs. 14.0 [12.6; 14.5] s) and clinically significant minor bleeding [10/30 (33.3%) vs. 6/45 (13.3%) cases], p 0.05. In carriers of the GG variant of the CYP3A5 gene, the same regimen resulted in higher values of Cmin, ss (74.7 [50.6; 108.8] vs. 40.2 [25.7; 72.3] ng/mL), Cmin, ss/D (4.6 [3.0; 7.3] vs. 2.5 [1.7; 4.0] ng/mL×mg), prothrombin time (14.6 [12.8; 15.2] vs. 14.0 [12.6; 14.5] s) and clinically significant minor bleeding [10/27 (37%) vs. 5/40 (12.5%) cases], p 0.05. Furthermore, in carriers of the GA+AA variant of the CYP3A5 gene, this regimen resulted in higher values of Cmin, ss (88.1 [5.5; 88.1] vs. 52.8 [25.0; 77.2] ng/mL), Cmin, ss/D (5.7 [0.4; 5.7] vs. 3.5 [1.7; 5.2] ng/mL×mg), p 0.05. The combined use of rivaroxaban with verapamil in carriers of the CT variant of the CYP3A4 gene was not observed in our sample. CONCLUSIONS: Carriers of the homozygous wild-type CYP3A4/A5 genotype showed high pharmacokinetic variability to the administration of verapamil (a strong P-glycoprotein inhibitor and a moderate CYP3A4 inhibitor).

Computed tomography-based multi-organ radiomics nomogram model for predicting the risk of esophagogastric variceal bleeding in cirrhosis.

Radiomics has been used in the diagnosis of cirrhosis and prediction of its associated complications. However, most current studies predict the risk of esophageal variceal bleeding (EVB) based on image features at a single level, which results in incomplete data. Few studies have explored the use of global multi-organ radiomics for non-invasive prediction of EVB secondary to cirrhosis. To develop a model based on clinical and multi-organ radiomic features to predict the risk of first-instance secondary EVB in patients with cirrhosis. In this study, 208 patients with cirrhosis were retrospectively evaluated and randomly split into training (n = 145) and validation (n = 63) cohorts. Three areas were chosen as regions of interest for extraction of multi-organ radiomic features: The whole liver, whole spleen, and lower esophagus-gastric fundus region. In the training cohort, radiomic score (Rad-score) was created by screening radiomic features using the inter-observer and intra-observer correlation coefficients and the least absolute shrinkage and selection operator method. Independent clinical risk factors were selected using multivariate logistic regression analyses. The radiomic features and clinical risk variables were combined to create a new radiomics-clinical model (RC model). The established models were validated using the validation cohort. The RC model yielded the best predictive performance and accurately predicted the EVB risk of patients with cirrhosis. Ascites, portal vein thrombosis, and plasma prothrombin time were identified as independent clinical risk factors. The area under the receiver operating characteristic curve (AUC) values for the RC model, Rad-score (liver + spleen + esophagus), Rad-score (liver), Rad-score (spleen), Rad-score (esophagus), and clinical model in the training cohort were 0.951, 0.930, 0.801, 0.831, 0.864, and 0.727, respectively. The corresponding AUC values in the validation cohort were 0.930, 0.886, 0.763, 0.792, 0.857, and 0.692. In patients with cirrhosis, combined multi-organ radiomics and clinical model can be used to non-invasively predict the probability of the first secondary EVB.

A clinical-radiomics nomogram for the prediction of the risk of upper gastrointestinal bleeding in patients with decompensated cirrhosis.

To develop a model that integrates radiomics features and clinical factors to predict upper gastrointestinal bleeding (UGIB) in patients with decompensated cirrhosis. 104 decompensated cirrhosis patients with UGIB and 104 decompensated cirrhosis patients without UGIB were randomized according to a 7:3 ratio into a training cohort (n = 145) and a validation cohort (n = 63). Radiomics features of the abdominal skeletal muscle area (SMA) were extracted from the cross-sectional image at the largest level of the third lumbar vertebrae (L3) on the abdominal unenhanced multi-detector computer tomography (MDCT) images. Clinical-radiomics nomogram were constructed by combining a radiomics signature (Rad score) with clinical independent risk factors associated with UGIB. Nomogram performance was evaluated in calibration, discrimination, and clinical utility. The radiomics signature was built using 11 features. Plasma prothrombin time (PT), sarcopenia, and Rad score were independent predictors of the risk of UGIB in patients with decompensated cirrhosis. The clinical-radiomics nomogram performed well in both the training cohort (AUC, 0.902; 95% CI, 0.850-0.954) and the validation cohort (AUC, 0.858; 95% CI, 0.762-0.953) compared with the clinical factor model and the radiomics model and displayed excellent calibration in the training cohort. Decision curve analysis (DCA) demonstrated that the predictive efficacy of the clinical-radiomics nomogram model was superior to that of the clinical and radiomics model. Clinical-radiomics nomogram that combines clinical factors and radiomics features has demonstrated favorable predictive effects in predicting the occurrence of UGIB in patients with decompensated cirrhosis. This helps in early diagnosis and treatment of the disease, warranting further exploration and research.

Spatiotemporally Controlled Release of Etamsylate from Bioinspired Peptide-Functionalized Nanoparticles Arrests Bleeding Rapidly and Improves Clot Stability in a Rabbit Internal Hemorrhage Model.

Achieving rapid clotting and clot stability are important unmet goals of clinical management of noncompressible hemorrhage. This study reports the development of a spatiotemporally controlled release system of an antihemorrhagic drug, etamsylate, in the management of internal hemorrhage. Gly-Arg-Gly-Asp-Ser (GRGDS) peptide-functionalized chitosan nanoparticles, with high affinity to bind with the GPIIa/IIIb receptor of activated platelets, were loaded with the drug etamsylate (etamsylate-loaded GRGDS peptide-functionalized chitosan nanoparticles; EGCSNP). Peptide conjugation was confirmed by LCMS, and the delivery system was characterized by DLS, SEM, XRD, and FTIR. In vitro study exhibited 90% drug release till 48 h fitting into the Weibull model. Plasma recalcification time and prothrombin time tests of GRGDS-functionalized nanoparticles proved that clot formation was 1.5 times faster than nonfunctionalized chitosan nanoparticles. The whole blood clotting time was increased by 2.5 times over clot formed under nonfunctionalized chitosan nanoparticles. Furthermore, the application of rheometric analysis revealed a 1.2 times stiffer clot over chitosan nanoparticles. In an in vivo liver laceration rabbit model, EGCSNP spatially localized at the internal injury site within 5 min of intravenous administration, and no rebleeding was recorded up to 3 h. The animals survived for 3 weeks after the injury, indicating the strong potential of the system for the management of noncompressible hemorrhage.

Predictive modeling of deep vein thrombosis risk in hospitalized patients: A Q-learning enhanced feature selection model

Deep vein thrombosis (DVT) represents a critical health concern due to its potential to lead to pulmonary embolism, a life-threatening complication. Early identification and prediction of DVT are crucial to prevent thromboembolic events and implement timely prophylactic measures in high-risk individuals. This study aims to examine the risk determinants associated with acute lower extremity DVT in hospitalized individuals. Additionally, it introduces an innovative approach by integrating Q-learning augmented colony predation search ant colony optimizer (QL-CPSACO) into the analysis. This algorithm, then combined with support vector machines (SVM), forms a bQL-CPSACO-SVM feature selection model dedicated to crafting a clinical risk prognostication model for DVT. The effectiveness of the proposed algorithm's optimization and the model's accuracy are assessed through experiments utilizing the CEC 2017 benchmark functions and predictive analyses on the DVT dataset. The experimental results reveal that the proposed model achieves an outstanding accuracy of 95.90% in predicting DVT. Key parameters such as D-dimer, normal plasma prothrombin time, prothrombin percentage activity, age, previously documented DVT, leukocyte count, and thrombocyte count demonstrate significant value in the prognostication of DVT. The proposed method provides a basis for risk assessment at the time of patient admission and offers substantial guidance to physicians in making therapeutic decisions.

Effects of different types of Ringer’s solution on patients with traumatic haemorrhagic shock: a prospective cohort study

ObjectiveTo compare the fluid resuscitation effect of sodium acetate Ringer’s solution and sodium bicarbonate Ringer’s solution on patients with traumatic haemorrhagic shock.MethodWe conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer’s solution group and sodium acetate Ringer’s solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients’ vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3−), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation.ResultsThe post-resuscitation heart rate of the sodium bicarbonate Ringer’s solution group was significantly lower than that of the sodium acetate Ringer’s solution group (p < 0.05), and the MAP was also significantly lower (p < 0.05). The patients in the sodium bicarbonate Ringer’s solution group had significantly higher pH, cHCO3− and PaO2 values and lower pCO2 and CLac values (p < 0.05) than those in the sodium acetate Ringer’s solution group, and the post-resuscitation peripheral platelet counts and fibrinogen levels were significantly higher, with shorter plasma prothrombin times and smaller shock indices (p < 0.001).ConclusionSodium bicarbonate Ringer’s solution is beneficial for maintaining MAP at a low level after resuscitation. The use of sodium bicarbonate Ringer’s solution in limited fluid resuscitation has positive results and is of high clinical value.

Phenotypic and genetic analysis of a Chinese pedigree affected with Hereditary antithrombin deficiency due to a novel variant of SERPINC1 gene

To analyze the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Hereditary antithrombin deficiency. A pedigree diagnosed at the the Second Affiliated Hospital of Wenzhou Medical University, Yuying Children's Hospital in June, 2020 was selected as the study subject. Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT) of the probands and their pedigree members were determined using a STA-R automatic coagulation analyzer. Antithrombin activity (AT: A) and antithrombin antigen (AT: Ag) in plasma were determined with chromogenic substrate and immunonephelometry assays. All exons and flanking sequences of the anticoagulant protein gene SERPINC1 were amplified by PCR and subjected to Sanger sequencing. Candidate variants were verified with bioinformatic tools (PolyPhen-2, SIFT, Mutation Taster and PYMOL) to explore their effect on the function and structural conformation of the protein. The probands (II-2, II-10), their brother (II-5) and sons (III-1, III-8) had shown normal PT, APTT, FIB, and TT, but significantly decreased AT: A and AT: Ag, with their levels being 34%, 57%, 56%, 48%, 53% and 13.51 mg/dL, 13.44 mg/dL, 18.39 mg/dL, 17.36 mg/dL, 17.71 mg/dL, respectively. The remaining pedigree members had normal values. Sanger sequencing revealed that the probands and all affected pedigree members had harbored a heterozygous c.851T>C (p.Met284Thr) missense variant in exon 5 of the SERPINC1 gene. Bioinformatic analysis and simulation suggested that the variant has resulted in alteration of hydrogen bonds at the c.851 position, which may affect the structure of the protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS1+PM1+PM5+PP1+PP4). The probands and other affected members were all diagnosed with type I hereditary AT deficiency, for which the c.851T>C (p.Met284Thr) variant of the SERPINC1 gene may be accountable.

Pharmacokinetics and coagulation biomarkers in children and adults with hemophilia A receiving emicizumab prophylaxis every 1, 2, or 4 weeks

BackgroundEmicizumab is a bispecific antibody that bridges activated factor (F)IX and FX, mimicking the function of missing activated FVIII and thus improving hemostasis in people with hemophilia A. The efficacy and safety of emicizumab were demonstrated in 4 phase III clinical trials (HAVEN 1-4). ObjectivesHere, we describe pharmacokinetics (PKs), pharmacodynamics (PDs), and exploratory safety biomarkers in HAVEN 1 to 4. MethodsParticipants received emicizumab at a loading dose of 3 mg/kg weekly for 4 weeks, followed by maintenance doses of 1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks. PKs, PDs, and safety biomarkers were assessed in samples collected at regular intervals during the trials. ResultsEmicizumab plasma trough concentrations increased during the loading dose period, reaching a mean of 52.9 μg/mL (SD, 13.6 μg/mL) at week 5, and were sustained at 42.1 to 52.3 μg/mL thereafter with maintenance dosing. Activated partial thromboplastin time shortened following the first emicizumab dose. Mean FVIII-like activity and thrombin generation peak height increased to 25.2 IU/dL (SD, 6.9 IU/dL) and 115.2 nM (SD, 42.5 nM) at week 5, with levels sustained at 17 to 23 IU/dL and >116 nM thereafter, respectively. Emicizumab did not notably affect FIX or FX plasma antigen levels, prothrombin time, or concentrations of exploratory safety markers of coagulation activation (D-dimer, prothrombin fragment 1 + 2, and fibrinogen). ConclusionIn HAVEN 1 to 4, emicizumab demonstrated sustained PKs and PDs and improved coagulation parameters without affecting safety biomarkers.

CYTOPATHOLOGIC DIAGNOSIS OF LIVER MASS LESION

Objective: The objective of the study is to categorize and establish the various cytological patterns of liver lesions. Methods: The present study was a hospital-based both retrospective and prospective study, on 504 patients with liver space-occupying lesions (SOLs) as USG/CT-guided fine needle aspiration cytology or biopsy was done and the smears or tissue was sent to the Department of Pathology, for 5 years between January 2018 and December 2022. Investigations done before the procedure was platelet count and plasma prothrombin time to know patients with bleeding tendencies. Under ultrasonography guidance, fine needle aspiration was performed on patients diagnosed for nodular or diffuse lesions of the liver. Results: Mean age of the study population was 58.53±12.62 years, 60.32% were male, 87.30% were Hindu, and 68.45% were rural. The most common complaint was pain abdomen 384 (76.19%) followed by jaundice 70 (13.89%). About 95.44% were neoplastic nature out of which 98.96% were malignant, out of which 83.61% were secondary. Out of 64 primary neoplastic lesions, maximum 98.44% were hepatocellular carcinoma. Out of 398 secondary neoplastic lesions, maximum 87.69% were metastatic carcinoma. Conclusion: We concluded that in any SOL, the screening of the liver is essential for early detection and long survival of cases.

Optimal processing technology of Zhangbang vinegar-processed Olibanum with multi-indicator-response surface methodology and anticoagulant effect evaluation

This study first optimized the processing technology for Zhangbang vinegar-processed Olibanum and investigated its in vitro anticoagulant activity. A multi-index-response surface methodology was used, with yield, powder yield, and the relative percentage of the content of six non-volatile components [11-keto-boswellic acid(KBA), 3-acetyl-11-keto-boswellic acid(AKBA), β-elemonic acid, α-boswellic acid(α-BA), β-boswellic acid(β-BA), and α-acetyl-boswellic acid(α-BA)] and three volatile components(octyl acetate, incensole, and incensole acetate) as evaluation indicators. Analytical hierarchy process(AHP) combined with coefficient of variation method was used to calculate the weight of each indicator and calculate the comprehensive score(OD). Furthermore, response surface methodology was used to investigate the effects of frying temperature(A), burning time(B), rice vinegar dosage(C), and steaming time(D) on the processing technology of vinegar-processed Olibanum. Vinegar-steamed Olibanum was prepared according to the optimal processing technology for in vitro anticoagulant experiments. The results showed that the weights of octyl acetate, incensole, incensole acetate, KBA, AKBA, β-elemonic acid, α-BA, β-BA, α-ABA, yield, and powder yield were 0.358 2, 0.104 5, 0.146 4, 0.032 9, 0.123 7, 0.044 4, 0.022 1, 0.042 2, 0.110 1, 0.012 2, and 0.0032, respectively. The optimal processing technology for Zhangbang vinegar-processed Olibanum was as follows. Olibanum(50 g) with a particle size of 1-5 mm was continuously stir-fried at a low heat of 150-180 ℃ until in a gel-like state, ignited for burning for 15 s, sprayed with 7.5 g of rice vinegar(15%), and steamed for 3 min without fire. Subsequently, the cover was removed, and the product was continuously stir-fried at 150-180 ℃ until in a soft lump shape, removed, cooled, and crushed. The results of the in vitro anticoagulant experiments showed that compared with the blank group, both Olibanum and vinegar-processed Olibanum significantly prolonged the activated partial thromboplastin time(APTT), thrombin time(TT), and prothrombin time(PT) of rat platelet-poor plasma(PPP), and the effect of vinegar-processed Olibanum was significantly better than that of Olibanum(P&lt;0.05). The optimized processing technology for Zhangbang vinegar-processed Olibanum is stable, feasible, and beneficial for the further development and utilization of Olibanum slices. At the same time, using the content of volatile and non-volatile components, yield, and powder yield as indicators, and verifying through pharmacological experiments, the obtained results are more reasonable and credible, and have positive guiding significance for the clinical application of characteristic processed Olibanum products.

Use of four-factor prothrombin complex concentrate (4F-PCC) for management of bleeding not associated with therapeutic anticoagulant use

IntroductionFour-factor prothrombin complex concentrate (4F-PCC) may be an option for patients with bleeding unrelated to therapeutic anticoagulation to help with bleeding cessation and reduce blood component requirements. Materials and methodsRetrospective, observational study of adult patients who received 4F-PCC for bleeding not associated with therapeutic anticoagulation between June 2019 and July 2021. Primary outcome was to describe off-label 4F-PCC use in patients not on therapeutic anticoagulation for bleeding management in surgical and non-surgical patients. Additional outcomes evaluated were blood product use, chest tube and drainage output, and coagulation studies before and after 4F-PCC administration as well as other hemostatic agent use and thromboembolic events. ResultsSeventy-six patients were included; median age 64 years (IQR 50–69), 66% of bleeding events were associated with surgery, and the majority of 4F-PCC doses ordered by cardiac surgery (68.4%). A total of 110 4F-PCC doses were administered; median 1 dose/patient (IQR 1–2), median total dose 1000 units (IQR 500–1484). Other hemostatic agents commonly administered were protamine (59%), desmopressin (43%), and tranexamic acid (42%). Packed red blood cells, fresh frozen plasma, platelet, and cell saver blood administration and prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (aPTT) were significantly reduced following 4F-PCC administration. Eight patients (11%) experienced thromboembolic complications. ConclusionRelatively low doses of 4F-PCC (median total dose 1000 units) were associated with decreased blood component requirements and improved PT, INR, and aPTT values in patients with bleeding unrelated to therapeutic anticoagulation. Other hemostatic agent use was common and thromboembolic complications occurred.

Bombyx Batryticatus extract promotes microglia polarization to improve neuron injury and behaviors of cerebral ischemia/reperfusion rats

This study aims to investigate the effect of Bombyx Batryticatus extract(BBE) on behaviors of rats with global cerebral ischemia reperfusion(I/R) and the underlying mechanism. The automatic coagulometer was used to detect the four indices of human plasma coagulation after BBE intervention for quality control of the extract. Sixty 4-week-old male SD rats were randomized into sham operation group(equivalent volume of normal saline, ip), model group(equivalent volume of normal saline, ip), positive drug group(900 IU·kg~(-1) heparin, ip), and low-, medium-, and high-dose BBE groups(0.45, 0.9, and 1.8 mg·g~(-1)·d~(-1) BBE, ip). Except the sham operation group, rats were subjected to bilateral common carotid artery occlusion followed by reperfusion(BCCAO/R) to induce I/R. The administration lasted 7 days for all the groups. The behaviors of rats were examined by beam balance test(BBT). Morphological changes of brain tissue were observed based on hematoxylin-eosin(HE) staining. Immunofluorescence method was used to detect common leukocyte antigen(CD45), leukocyte differentiation antigen(CD11b), and arginase-1(Arg-1) in cerebral cortex(CC). The protein expression of interleukin-1β(IL-1β), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) was detected by enzyme-linked immunosorbent assay(ELISA). The non-targeted metabonomics was employed to detect the levels of metabolites in plasma and CC of rats after BBE intervention. The results of quality control showed that the BBE prolonged the activated partial thromboplastin time(APTT), prothrombin time(PT), and thrombin time(TT) of human plasma, which was similar to the anticoagulation effect of BBE obtained previously. The results of behavioral test showed that the BBT score of the model group increased compared with that of the sham operation group. Compared with the model group, BBE reduced the BBT score. As for the histomorphological examination, compared with the sham operation group, the model group showed morphological changes of a lot of nerve cells in CC. The nerve cells with abnormal morphology in CC decreased after the intervention of BBE compared with those in the model group. Compared with the sham operation group, the model group had high average fluorescence intensity of CD45 and CD11b in the CC. The average fluorescence intensity of CD11b decreased and the average fluorescence intensity of Arg-1 increased in CC in the low-dose BBE group compared with those in the model group. The average fluorescence intensity of CD45 and CD11b decreased and the average fluorescence intensity of Arg-1 increased in medium-and high-dose BBE groups compared with those in the model group. The expression of IL-1β and IL-6 was higher and the expression of IL-4 and IL-10 was lower in the model group than in the sham operation group. The expression of IL-1β and IL-6 was lower and the expression of IL-4 and IL-10 was higher in the low-dose, medium-dose, and high-dose BBE groups than in the model group. The results of non-targeted metabonomics showed that 809 metabolites of BBE were identified, and 57 new metabolites in rat plasma and 45 new metabolites in rat CC were found. BBE with anticoagulant effect can improve the behaviors of I/R rats, and the mechanism is that it promotes the polarization of microglia to M2 type, enhances its anti-inflammatory and phagocytic functions, and thus alleviates the damage of nerve cells in CC.

Prothrombin time and activated partial thromboplastin time in women with gestational diabetes mellitus

Impact of gestational diabetes mellitus (GDM) on the coagulation system still remains unclear and there is limited data available regarding haemostatic changes in GDM in Bangladesh. This study was aimed at determining plasmaprothrombin time (PT), activated partial thromboplastin time (APTT) in women with GDM. This cross sectional study encompassed 44 GDM (age: 28.5±3.8 years, BMI: 27.2±4.0kg/m2; mean±SD) and equal number of pregnant women with normal glucose tolerance (NGT) diagnosed on the basis of WHO criterion 2013 at or after 24 weeks of gestation to see PT and APTT. Plasma glucose was measured by glucose oxidase method, PT and APTT by automated coagulation analyzer. There was no statistically significant difference between the GDM and NGT groups for PT (12.3±0.5 vs. 12.2±0.4 sec, mean±SD; P=0.40) or APTT (30.53±1.01 vs. 30.9±4.5 sec, mean±SD; P=0.56). In conclusion, PT and APTT do not differ between women with or without GDM. BSMMU J 2022; 15(3): 146-150

Meta-Analysis of the Efficacy of Low Molecular Weight Heparin and Aspirin in the Treatment of Thrombosis During Pregnancy and Effects on Coagulation Function.

At present, there is no comprehensive evaluation of the efficacy and safety of low molecular weight heparin (LMWH) for the treatment of thrombophilia during pregnancy in clinical practice. This study aimed to systematically evaluate the efficacy of LMWH in the treatment of patients and its effects on coagulation function, thereby providing a reference for the clinical treatment and prognosis evaluation of thrombophilia during pregnancy. Database PubMed, Web of Science and Embase as well as China National Knowledge Infrastructure and Wanfang Database were applied for the search of data. A comparative study on the efficacy of LMWH in the treatment of gestational thrombophilia was enrolled. Stata 16.0 software (Stata, College Station, TX, USA) was utilized to conduct the meta-analysis. A total of 487 relevant articles were retrieved and 14 studies were finally included. Patients in the LMWH combined with the low-dose aspirin group had a significantly higher live birth rate than those in the aspirin or LMWH treat group (OR (odds ratio) = 4.54, 95% CI (confidence interval): 2.76, 7.45). The adverse effects rate was lower in the LMWH combined with the low-dose aspirin group than in the aspirin or LMWH treatment group (OR = 0.40, 95% CI: 0.29, 0.56). After treatment, patients in the LMWH combined with the low-dose aspirin group had significantly lower D-dimer (SMD (standardized mean differences) = -1.50, 95% CI: -2.19, 0.80) and platelet count (PLT; SMD = -0.13, 95% CI: -0.35, 0.09) than those in the aspirin or LMWH treatment group. However, activated partial thromboplastin time (APTT; SMD = 0.16, 95% CI: -0.10, 0.42), thrombin time (TT; SMD = 0.60, 95% CI: -0.14, 1.34), plasma prothrombin time (PT; SMD = 0.42, 95% CI: -0.71, 1.56), and fibrin values (FIB; SMD = -0.92, 95% CI: -2.12, 0.28) were significantly higher in the LMWH combined with low-dose aspirin group than those in the aspirin or LMWH treatment group. LMWH heparin combined with low-dose aspirin can effectively correct coagulation function in pregnant women, improve prothrombotic state and increase the live birth rate, which has high clinical value.

Corelations Between the Value of Serum Cholinesterase and Child-Pugh and MELD-NA Scores in Cirrhotic Patients

Abstract A variety of laboratory tests are used in the evaluation of the hepatic patients. Serum cholinesterase is reduced in liver disfunction in contrast with other enzymes. The aim of this study was to assess the value of serum cholinesterase in evaluation of the liver reserve function in cirrhotic patients. A total of 70 patients were divided into 3 groups according to the Child-Pugh Score. Using corelation analysis, the correlation between serum cholinesterase and albumin and serum plasma prothrombin time was analysed. Cirrhotic patients were grouped into A, B and C grades as per Child-Pugh score. The results showed that cholinesterase levels tend to decrease according to the Child-Pugh score. The cholinesterase correlated with the albumin serum levels, value of Child-Pugh score and MELD-Na score and didn’t corelate to INR. In conclusion, correlated with the damage severity of the liver cells cholinesterase may respond to liver reserve function.

The facile method developed for preparing polyvinylidene fluoride plasma separation membrane via macromolecular interaction

The design of membrane pore is critical for membrane preparation. Polyvinylidene fluoride (PVDF) membrane exhibits outstanding properties in the water-treatment field. However, it is a huge challenge to prepare PVDF macro-pore plasma separation membrane by non-solvent induced phase separation (NIPS). Herein, a facile strategy is proposed to prepare PVDF macro-pore plasma separation membrane via macromolecular interaction. ATR-FTIR and 1 H NMR showed that the intermolecular interaction existed between polyethylene oxide (PEO) and polyvinylpyrrolidone (PVP). It could significantly affect the PVDF macro-pore membrane structure. The maximum pore of the PVDF membrane could be effectively adjusted from small-pore/medium-pore to macro-pore by changing the molecular weight of PEO. The PVDF macro-pore membrane was obtained successfully when PEO-200 k existed with PVP. It exhibited higher plasma separation properties than the currently used plasma separation membrane. Moreover, it had excellent hemocompatibility due to the similar plasma effect, hemolysis, prothrombin time, blood effect and complement C 3a effect with the current utilized plasma separation membrane, implying its great potential application. The proposed facile strategy in this work provides a new method to prepare PVDF macro-pore plasma separation membrane by NIPS.

Anemia-Associated Platelets and Plasma Prothrombin Time Increase in Patients with Adenomyosis.

Patients with adenomyosis are hypercoagulable and often accompanied by anemia, but the specific changes in anemia-related coagulation parameters are still unclear. This study investigated the changes in and influencing factors of coagulation parameters related to anemia in patients with adenomyosis (AM). The coagulation parameters, including platelet count (PC), plasma prothrombin time (PT), activated partial prothrombin time (APTT), thrombin time (TT) and fibrinogen (FB), and hemoglobin (Hb), were measured in patients with adenomyosis (229 cases in AM group), uterine leiomyoma (265 cases in LM group), and undergoing tubal anastomosis (142 cases in the control group). The age of the control group was younger than that of the AM group and the LM group. Compared with the AM and LM groups, the uterus size of the control group was smaller; the AM group was larger than the LM group. The Hb concentration of the AM group was lower than that of the LM and control groups. Compared with the LM and control groups, PC increased and TT shortened in the AM group. APTT in the AM group was shorter than in the control group, and PT was longer than in the LM group. After adjustment using multiple logistic regression analysis, adenomyosis was correlated with Hb concentration (or = 0.971, 95% CI 0.954–0.988, p < 0.001), PC (or = 1.006, 95% CI 1.002–1.011, p = 0.004), PT (or = 3.878, 95% CI 2.347–6.409, p < 0.001), age (or = 1.062, 95% CI 1.013–1.114, p = 0.013), and uterine size (or = 1.103, 95% CI 1.011–1.203, p = 0.028). Correlation analysis showed that PC (r = −0.309) and PT (r = −0.252) were negatively correlated with anemia. The increase in Hb-related PC and PT in patients with adenomyosis indicates that the timely and early detection of coagulation parameters is needed for patients with severe anemia, older age, and larger uterine volume.

Analysis of Coagulation Abnormality in Patients with Multiple Myeloma and Its Clinical Significance.

Objective To analyze the abnormal changes of coagulation indexes in patients with multiple myeloma (MM) and their clinical significance on prognosis. Methods Among 80 patients with MM, there were 24 patients of light chain type, 36 patients of IgG type, and 20 patients of IgA type. In the same period, 30 healthy people were in the control group. The laboratory indexes such as plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thromboplastin time (TT), D-dimer (D-D), and platelet (PLT) were detected and compared. The prognosis of MM patients was followed up, and the effects of various coagulation indexes on the prognosis of MM were analyzed by single-factor and multifactor analyses. Results The PT and APTT of IgG and IgA groups were longer than those of the control group and the light chain group (P < 0.05), but there was no significant difference between the IgG group and the IgA group, the control group, and the light chain group. There was no significant difference in FIB values among the four groups (P > 0.05). The D-D content in the light chain group was higher than that in the control group, the IgG group, and the IgA group (P < 0.05). During the follow-up period, of 80 MM patients, 61 patients survived and 19 patients died. Univariate analysis showed that APTT, PT, and D-D were the factors affecting the prognosis of MM patients, and the differences were statistically significant (P < 0.05). Multivariate analysis showed that PT was an independent factor affecting the prognosis of MM patients (P < 0.05). Discussion. Patients with MM have clotting abnormalities. Patients with IgA and IgG type MM have a longer clotting time than patients with other types of MM, and patients with light-chain type MM have higher D-D content and are more prone to thrombosis. PT is an independent factor affecting the prognosis of MM patients, and analysis of coagulation abnormalities is important for evaluating the prognosis of patients.