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Genes Oct 2022(1) Background: The purpose of this study was to evaluate the effect of gene polymorphisms on prothrombin time (PT) and activated partial thromboplastin time (APTT) in a...
(1) Background: The purpose of this study was to evaluate the effect of gene polymorphisms on prothrombin time (PT) and activated partial thromboplastin time (APTT) in a healthy Chinese population. (2) Methods: A total of 403 healthy volunteers from a series of novel oral anticoagulants (NOACs) bioequivalence trials in China were included. Coagulation tests for PT and APTT were performed in the central lab at Peking University First Hospital. Whole-exome sequencing (WES) and genome-wide association analysis were performed. (3) Results: In the correlation analysis of PT, 105 SNPs from 84 genes reached the genome-wide significance threshold (p < 1 × 10−5). Zinc Finger Protein 594 (ZNF594) rs184838268 (p = 4.50 × 10−19) was most significantly related to PT, and Actinin Alpha 1 (ACTN1) was found to interact most with other candidate genes. Significant associations with previously reported candidate genes Aurora Kinase B (AURKB), Complement C5(C5), Clock Circadian Regulator (CLOCK), and Histone Deacetylase 9(HDAC9) were detected in our dataset (p < 1 × 10−5). PiggyBac Transposable Element Derived 2(PGBD2) rs75935520 (p = 4.49 × 10−6), Bromodomain Adjacent To Zinc Finger Domain 2A(BAZ2A) rs199970765 (p = 5.69 × 10−6) and Protogenin (PRTG) rs80064850 (p = 8.69 × 10−6) were significantly correlated with APTT (p < 1 × 10−5). The heritability values of PT and APTT were 0.83 and 0.64, respectively; (4) Conclusion: The PT and APTT of healthy populations are affected by genetic polymorphisms. ZNF594 and ACTN1 variants could be novel genetic markers of PT, while PRTG polymorphisms might be associated with APTT levels. The findings could be attributed to ethnic differences, and need further investigation.
Topics: Humans; Partial Thromboplastin Time; Prothrombin Time; Actinin; Aurora Kinase B; Genome-Wide Association Study; Administration, Oral; Genetic Markers; DNA Transposable Elements; Anticoagulants; Blood Coagulation Tests; Polymorphism, Genetic; Complement C5; Histone Deacetylases; Chromosomal Proteins, Non-Histone
PubMed: 36292752
DOI: 10.3390/genes13101867 -
Annals of Laboratory Medicine Nov 2023Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT),... (Review)
Review
Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Evidence indicates that not only an abnormal waveform but also peak times and heights in derivative curves of CWA are useful for the evaluation of hemostatic abnormalities. Modified CWA, including the PT with APTT reagent, dilute PT (small amount of tissue factor [TF]-induced clotting factor IX [FIX] activation; sTF/FIXa), and dilute TT, has been proposed to evaluate physiological or pathological hemostasis. We review routine and modified CWA and their clinical applications. In CWA-sTF/FIXa, elevated peak heights indicate hypercoagulability in patients with cancer or thrombosis, whereas prolonged peak times indicate hypocoagulability in several conditions, including clotting factor deficiency and thrombocytopenia. CWA-dilute TT reflects the thrombin burst, whereas clot-fibrinolysis waveform analysis reflects both hemostasis and fibrinolysis. The relevance and usefulness of CWA-APTT and modified CWA should be further investigated in various diseases.
Topics: Humans; Hemostatics; Thrombosis; Thrombin; Prothrombin Time; Hemostasis
PubMed: 37387486
DOI: 10.3343/alm.2023.43.6.531 -
Frontiers in Public Health 2023Cardiac arrest (CA) can activate blood coagulation. This study aimed to explore the potential prognostic value of prothrombin time-international normalized ratio (INR)...
BACKGROUND
Cardiac arrest (CA) can activate blood coagulation. This study aimed to explore the potential prognostic value of prothrombin time-international normalized ratio (INR) in post-CA patients.
METHODS
The clinical data of eligible subjects diagnosed with CA was extracted from the MIMIC-IV database as the training cohort. Restricted cubic spline (RCS), Kaplan-Meier (K-M) survival curve, and Cox regression analyses were conducted to elucidate the association between the INR and all-cause mortality of post-CA patients. Subgroup analysis, propensity score matching (PSM), and inverse probability of treatment (IPTW) were also conducted to improve stability and reliability. Data of the validation cohort were collected from the eICU database, and logistic-regression analyses were performed to verify the findings of the training cohort.
RESULTS
A total of 1,324 subjects were included in the training cohort. A linear correlation existed between INR and the risk of all-cause death of post-CA patients, as shown in RCS analysis, with a hazard ratio (HR) >1 when INR exceeded 1.2. K-M survival curve preliminarily indicated that subjects with INR ≥ 1.2 presented lower survival rate and shorter survival time, and the high level of INR was independently associated with 30-day, 90-day, 1-year, and in-hospital mortalities, with multivariate-adjusted HR of 1.44 (1.20, 1.73), 1.46 (1.23, 1.74), 1.44 (1.23, 1.69), and 1.37 (1.14, 1.64), respectively. These findings were consistent and robust across the subgroup analysis, PSM and IPTW analyses, and validation cohort.
CONCLUSIONS
We systematically and comprehensively demonstrated that elevated INR was associated with increased short- and long-term all-cause mortality of post-CA patients. Therefore, elevated INR may be a promising biomarker with prognosis significance.
Topics: Humans; International Normalized Ratio; Prothrombin Time; Retrospective Studies; Reproducibility of Results; Prognosis
PubMed: 36741950
DOI: 10.3389/fpubh.2023.1112623 -
Data mining for prothrombin time and international normalized ratio reference intervals in children.PloS One 2022Reference intervals (RIs) help physicians in differentiating healthy from sick individuals. The prothrombin time (PT) and International normalized ratio (INR) fluctuate...
Reference intervals (RIs) help physicians in differentiating healthy from sick individuals. The prothrombin time (PT) and International normalized ratio (INR) fluctuate in coagulation pathway defects and have interlaboratory variability due to the instrument/reagent used. As direct method is difficult in children, we chose an indirect data mining method for the determining PT/INR RIs. The indirect method overcomes the substantial financial and logistic challenges, and ethical restrictions in children, moreover, allows partitioning in more fine-grained age groups. Prothrombin Time/INR measurements performed in patients aged birth-18 years between January 2013 and December 2020, were retrieved from laboratory management system of the Aga Khan Hospital. Reference intervals were computed using an indirect KOSMIC algorithm. The KOSMIC package function on the assumption that the non-pathologic samples follow a Gaussian distribution (after Box-Cox transformation of the data), following an elaborate statistical process to isolate distribution of physiological samples from mixed dataset. A total of 56,712 and 52,245 values were retrieved for PT and INR respectively. After the exclusion of patients with multiple specimens obtained during the study period, RIs were calculated for 37,356 (PT) and 37,192 (INR) children with stratification into 9 age groups. A comparison of 2.5th and 97.5th percentile results with those of established RIs from SickKids Handbook of Pediatric Thrombosis and Hemostasis demonstrated good agreement in between different age groups. This study supports data mining as an alternate approach for establishing PT/INR RIs, specifically in resource-limited settings. The results obtained are specific to studied population and instrument/reagent used. The study also allows understanding of fluctuations in coagulation pathways with increasing age and hence better clinical decision-making based on PT and INR results.
Topics: Humans; Child; Aged; Prothrombin Time; International Normalized Ratio; Blood Coagulation Tests; Reference Values; Indicators and Reagents; Data Mining
PubMed: 36302050
DOI: 10.1371/journal.pone.0276884 -
Clinical and Applied... 2023Legg-Calvé-Perthes disease (LCPD) is a pediatric disorder that occurs due to the avascular necrosis of the femoral head and affects the range of motion of the hip in...
BACKGROUND
Legg-Calvé-Perthes disease (LCPD) is a pediatric disorder that occurs due to the avascular necrosis of the femoral head and affects the range of motion of the hip in various degrees. Its etiology is still unknown, although it has been associated with coagulation abnormalities, however, the lack of reproducibility in the results in various studies has created a controversy as to whether hemostasis disorders are related to LCPD. On the other hand, there is little information on laboratory studies that could facilitate the diagnosis and treatment of LCPD.
METHODS
Blood and plasma samples were tested from 25 patients with LCPD and 50 healthy controls, matched by sex and age. Cellular markers were evaluated through complete blood count, as well as coagulation times, coagulation factors activity, antithrombotic proteins, and homocysteine concentration.
RESULTS
After assessing activity value frequencies in each group, the results showed more significant activity in some of the biological risk markers of thrombophilia, presenting a substantial difference in prothrombin time↘, FV↗, FVIII↗, FIX↗, and Hcy↗. These values imply that there may be hypercoagulable states in patients, which can cause thrombotic events.
CONCLUSIONS
Diminished prothrombin time and increase in FV activity, FVIII, FIX, and Hcy concentration support the hypothesis that microthrombi formation in small-caliber vessels could be causing avascularity and femoral necrosis, which are traits of LCPD. In addition, based on our results, we believe that the laboratory studies carried out are very useful in the diagnosis and treatment of LCPD.
Topics: Child; Humans; Legg-Calve-Perthes Disease; Factor IX; Prothrombin Time; Hemostatics; Reproducibility of Results; Thrombophilia; Blood Coagulation Disorders; Hemostasis
PubMed: 36650707
DOI: 10.1177/10760296221151166 -
Nature Communications Feb 2022Frequent prothrombin time (PT) and international normalized ratio (INR) testing is critical for millions of people on lifelong anticoagulation with warfarin. Currently,...
Frequent prothrombin time (PT) and international normalized ratio (INR) testing is critical for millions of people on lifelong anticoagulation with warfarin. Currently, testing is performed in hospital laboratories or with expensive point-of-care devices limiting the ability to test frequently and affordably. We report a proof-of-concept PT/INR testing system that uses the vibration motor and camera on smartphones to track micro-mechanical movements of a copper particle. The smartphone system computed the PT/INR with inter-class correlation coefficients of 0.963 and 0.966, compared to a clinical-grade coagulation analyzer for 140 plasma samples and demonstrated similar results for 80 whole blood samples using a single drop of blood (10 μl). When tested with 79 blood samples with coagulopathic conditions, the smartphone system demonstrated a correlation of 0.974 for both PT/INR. Given the ubiquity of smartphones in the global setting, this proof-of-concept technology may provide affordable and effective PT and INR testing in low-resource environments.
Topics: Algorithms; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Hemorrhage; Humans; International Normalized Ratio; Point-of-Care Systems; Prothrombin Time; Smartphone; Thrombosis; Warfarin
PubMed: 35149711
DOI: 10.1038/s41467-022-28499-y -
The Israel Medical Association Journal... Jun 2023Factor VII (FVII) deficiency is characterized by normal activated partial thromboplastin time (aPTT) and prolonged prothrombin time (PT) values. It is diagnosed by...
BACKGROUND
Factor VII (FVII) deficiency is characterized by normal activated partial thromboplastin time (aPTT) and prolonged prothrombin time (PT) values. It is diagnosed by determining protein level and coagulation activity (FVII:C). FVII:C measurements are expensive and time consuming.
OBJECTIVES
To analyze correlations between PT, international normalized ratio (INR), and FVII:C in pediatric patients before otolaryngology surgery and to establish alternative methods for identifying FVII deficiency.
METHODS
FVII:C data were collected from 96 patients with normal aPTT and prolonged PT values during preoperative otolaryngology surgery coagulation workup between 2016 and 2020. We compared demographic and clinical parameters using Spearman correlation coefficient and receiver operating characteristic (ROC) curve analysis to determine the accuracy of PT and INR values to predict FVII deficiency.
RESULTS
The median values of PT, INR and FVII:C were 13.5 seconds, 1.14, and 67.5%, respectively. In total, 65 participants (67.7%) displayed normal FVII:C compared to 31 (32.3%) with decreased FVII:C. A statistically significant negative correlation was observed between FVII:C and PT values and between FVII:C and INR. Despite statistically significant ROC of 0.653 for PT (P-value = 0.017, 95% confidence interval [95%CI] 0.529-0.776) and 0.669 for INR (P-value = 0.08, 95%CI 0.551-0.788), we were unable to determine an optimal cutoff point to predict FVII:C deficiency with high sensitivity and high specificity.
CONCLUSIONS
We could not identify a PT or INR threshold to best predict clinically relevant FVII:C levels. When PT is abnormal, determining FVII:C protein levels is needed for diagnosing FVII deficiency and considering surgical prophylactic treatment.
Topics: Humans; Child; Prothrombin Time; International Normalized Ratio; Factor VII; Blood Coagulation Tests; Factor VII Deficiency
PubMed: 37381933
DOI: No ID Found -
Marine Drugs Nov 2023Alginate-based materials have gained significant attention in the medical industry due to their biochemical properties. In this article, we aimed to synthesize...
Alginate-based materials have gained significant attention in the medical industry due to their biochemical properties. In this article, we aimed to synthesize Cotton-Alginate-Copper Composite Materials (COT-AlgCu). The main purpose of this study was to assess the biochemical properties of new composites in the area of blood plasma coagulation processes, including activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT). This study also involved in vitro antimicrobial activity evaluation of materials against representative colonies of Gram-positive and Gram-negative bacteria and antifungal susceptibility tests. The materials were prepared by immersing cotton fibers in an aqueous solution of sodium alginate, followed by ionic cross-linking of alginate chains within the fibers with Cu(II) ions to yield antimicrobial activity. The results showed that the obtained cotton-alginate-copper composites were promising materials to be used in biomedical applications, e.g., wound dressing.
Topics: Copper; Alginates; Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Blood Coagulation; Prothrombin Time; Partial Thromboplastin Time; Ions
PubMed: 38132946
DOI: 10.3390/md21120625 -
Medicina (Kaunas, Lithuania) Dec 2020Prolonged tourniquet stasis induced by venepuncture can lead to the release of the plasma of cell lysis products, as well as tissue factor (TF), impairing the quality of...
Prolonged tourniquet stasis induced by venepuncture can lead to the release of the plasma of cell lysis products, as well as tissue factor (TF), impairing the quality of coagulation test results. The accidental presence of TF in vitro can trigger the coagulation mechanism, generating a false decrease in prothrombin time (PT). Identification of short PT tests below the normal reference value that could suggest a situation of hypercoagulability. The study aimed to compare the results of the shortened PT tests at their first determination with the eventual correction following duplication of the analysis from the same sample. Identification of the shortened PT tests has been carried out for a period of 4 months, upon 544 coagulation samples referred to the Hematology department of Sf. Spiridon County Clinical Emergency Hospital from Iasi, Romania. Out of the 544 samples of which the results indicated a state of hypercoagulability, by repeating the determination from the same sample, for 200 (36.76%) PT tests ( = 0.001) the value was corrected, falling within the normal reference range. For 344 (63.24%) tests, the results suggested a situation of hypercoagulability. In order to guarantee the highest quality of the laboratory services, a proper interpretation and report of the patients' results must be congruent and harmoniously associated to the actual clinical condition of the patient. Duplication of the PT determination from the same sample would exclude situations of false hypercoagulability and would provide significant improvement for the patient's safety.
Topics: Blood Coagulation; Blood Coagulation Tests; Humans; Prothrombin Time; Romania; Thrombophilia
PubMed: 33379139
DOI: 10.3390/medicina57010013 -
PloS One 2022COVID-19 is a viral disease caused by a new strain of corona virus. Currently, prognosis and risk stratification of COVID-19 patients is done by the disease's clinical...
BACKGROUND
COVID-19 is a viral disease caused by a new strain of corona virus. Currently, prognosis and risk stratification of COVID-19 patients is done by the disease's clinical presentation. Therefore, identifying laboratory biomarkers for disease prognosis and risk stratification of COVID-19 patients is critical for prompt treatment. Therefore, the main objective of this study was to assess the risk stratification and prognostic value of basic coagulation parameters and factors associated with disease severity among COVID-19 patients at the Tibebe Ghion Specialized Hospital, COVID-19 treatment center, Northwest Ethiopia.
METHODS
A follow-up study was conducted among conveniently recruited COVID-19 patients attended from March to June 2021. Socio-demographic and clinical data were collected using a structured questionnaire and checklist, respectively. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were analyzed by the HUMACLOT DUE PLUS® machine. Descriptive statistics were used to summarize the socio-demographic and clinical characteristics of study participants. Kruskal Wallis tests were used to compare the difference between parametric and non-parametric continuous variables, respectively. The area under the receiver operating characteristic curve (AUC) was used to evaluate the value of PT and APTT in the risk stratification and disease prognosis of COVID-19 patients. Ordinal logistic regression was used to identify the factors associated with disease severity and prognosis. A P-value < 0.05 was defined as statistically significant for all results.
RESULT
Baseline PT at a cut-off value ≥ 16.25 seconds differentiated severe COVID-19 patients from mild and moderate patients (AUC: 0.89, 95% CI: 0.83-0.95). PT also differentiated mild COVID-19 patients from moderate and severe patients at a cut-off value ≤ 15.35 seconds (AUC: 0.90, 95% CI: 0.84-0.96). Moreover, alcohol drinkers were a 3.52 times more likely chance of having severe disease than non-drinkers (95% CI: 1.41-8.81). A one-year increment in age also increased the odds of disease severity by 6% (95% CI: 3-9%). An increment of ≥ 0.65 seconds from the baseline PT predicted poor prognosis (AUC: 0.93, 0.87-0.99).
CONCLUSIONS AND RECOMMENDATIONS
Prolonged baseline PT was observed in severe COVID-19 patients. Prolonged baseline PT was also predicted to worsen prognosis. An increase from the baseline PT was associated with worsen prognosis. Therefore, PT can be used as a risk stratification and prognostic marker in COVID-19 patients.
Topics: Blood Coagulation Disorders; COVID-19; Follow-Up Studies; Humans; Partial Thromboplastin Time; Prognosis; Prothrombin Time; Retrospective Studies; Risk Assessment; COVID-19 Drug Treatment
PubMed: 35951632
DOI: 10.1371/journal.pone.0272216