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1.
Zhonghua Yi Xue Za Zhi ; 103(0): 1-7, 2023 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-36634914

RESUMO

Heparin resistance is becoming a hot issue of clinical concern. In critically ill patients, heparin resistance can lead to failure of anticoagulation therapy or increase the risk of major bleeding. Prompt recognition of heparin resistance can help to precisely adjust heparin dosage and avoid deterioration and adverse events. Heparin resistance can be mechanistically classified into the antithrombin-mediated and the non-antithrombin-mediated. Common etiologies include heparin-induced thrombocytopenia, severe infections such as severe COVID-19, treatment with extracorporeal circulation or extracorporeal membrane oxygenation (ECMO), and use of factor Xa reversal agents; heparin resistance is now often identified by the concordance of activated partial thromboplastin time (APTT) ratio with anti-FXa. Common clinical management strategies include antithrombin supplementation and replacement of anticoagulant drugs (e.g., direct thrombin inhibitors), but their safety and efficacy still need to be further validated.


Assuntos
COVID-19 , Heparina , Humanos , Heparina/uso terapêutico , Heparina/efeitos adversos , Anticoagulantes/uso terapêutico , Antitrombinas , Tempo de Tromboplastina Parcial , Estudos Retrospectivos
2.
Blood Coagul Fibrinolysis ; 34(2): 93-98, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36719806

RESUMO

The Sysmex CN-6000 is a novel automated multiparameter coagulometer that performs clotting, chromogenic and immunological assays, and platelet aggregation tests in a single system. Here we evaluated its performance of routine coagulation assays. The precision, linearity, carryover and establishment of reference ranges of the CN-6000, as well as correlations between it and the currently used Diagnostica Stago STA-R Max were determined according to Clinical and Laboratory Standards Institute guidelines. The evaluated parameters included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), antithrombin (AT), d-dimers (DDi), and fibrin and FBG degradation products (FDP). The intra-run and inter-run precisions of the six tests were determined using normal and pathological control materials; all coefficients of variation were acceptable and within the allowable ranges. The CN-6000 showed excellent linearity for FBG, AT, DDi, and FDP (R = 0.999-1.00). Passing-Bablok regression (R2 > 0.95) demonstrated good agreement between the analyzers. In the carryover study, APTT, PT, FBG, AT, DDi, and FDP values were all acceptable. The establishing reference intervals revealed that each manufacturer's range was acceptable. Significant differences were observed in the APTT reference range because of using different detection systems and reagents. The CN-6000 analyzer showed reliable performance and good correlation with the currently used STA-R Max automated hemostatic analyzer. As CN-6000 uses an optical clot-detection method, its reference ranges for PT and APTT are lower than those of the STA-R Max; thus, the difference should be considered before its use.


Assuntos
Coagulação Sanguínea , Hemostáticos , Humanos , Testes de Coagulação Sanguínea/métodos , Tempo de Protrombina/métodos , Tempo de Tromboplastina Parcial , Hemostasia , Fibrinogênio/análise , Anticoagulantes , Antitrombinas
3.
Eur Rev Med Pharmacol Sci ; 26(23): 8990-9000, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36524518

RESUMO

OBJECTIVE: When using heparin anticoagulation for continuous renal replacement therapy (CRRT), the main challenge is to tailor the dosage to patient response. This study aimed to determine if the first activated thromboplastin time (aPTT) (measured after 3 hours post heparin bolus) can be a predictor for CRRT filter survival and if the first activated clotting time-low range (ACT-LR) (10 min post heparin bolus) can be predictive for subtherapeutic or therapeutic first aPTT. MATERIALS AND METHODS: An unfractionated heparin (UF) anticoagulation protocol was used in CRRT and heparin monitoring was performed by aPTT and ACT-LR. Extracorporeal therapy was analyzed and filter survival was assessed for general risk factors, especially coagulation tests. For statistical analysis, Logrank tests, ROC curve analysis, and the Kaplan-Meier chart for survival evaluations were utilized. RESULTS: Using the pLogrank test, the overall survival for the CRRT procedure was 47.8 hours (p=0.04), and no clotting events occurred during the first 12 hours for all examined therapies. Multivariate analysis for filter survival prediction to estimate 48 hours of CRRT revealed statistical relevance for Age (<60 years), BMI (<25.9), and INR (>1.3), with negative statistical significance for lipids, triglycerides, and fibrinogen. aPTT (180 min) values greater than 57 sec were shown to be predictive of 48-hour filter survival, and similar findings were obtained for aPTT measured at 6 hours. ACT-LR samples assessed 10 minutes after the initial heparin bolus was shown to be predictive of 48-hour filter survival (cutoff > 218 sec; p=0.04). When ACT prediction potential for therapeutic aPTT values was evaluated, ACT-LR 10 min (cut off > 200 sec.), ACT-LR 60 min (cut off > 186 sec.), and ACT-LR 180 min (cut off > 182 sec.) were found to be predictive. CONCLUSIONS: Based on this study and its sample size, ACT-LR can be a complimentary assessment to aPTT for monitoring anticoagulation with heparin on CRRT.


Assuntos
Terapia de Substituição Renal Contínua , Heparina , Humanos , Pessoa de Meia-Idade , Anticoagulantes/uso terapêutico , Heparina/química , Heparina/uso terapêutico , Tempo de Tromboplastina Parcial , Tromboplastina/química
4.
Clin Appl Thromb Hemost ; 28: 10760296221148162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36572963

RESUMO

Support with VV-ECMO requires anticoagulation with unfractionated heparin to prevent thrombotic complications. This must be monitored due to bleeding risk. A point-of-care (POC) method of testing aPTT and APR was evaluated for agreement with laboratory methods. In a prospective observational study, patients supported on VV-ECMO as a result of severe respiratory failure secondary to Covid-19 infection were given heparin as part of standard therapy. The aPTT was measured (i) at the bedside using the Hemochron Signature Elite device and (ii) at the hospital laboratory. Duplicate results were compared. Agreement between the POC and laboratory tests was poor, as assessed using the Bland-Altman method. The maximum difference between POC and laboratory methods was 133% and the minimum was 0%. Overall bias was 7.3% and limits of agreement were between -43.8% and 58.5%. Correlation increased when results were normalised to platelet count and creatinine. This POC test is insufficiently accurate for use as the primary method of heparin monitoring in patients requiring VV-ECMO for Covid-19. Platelets and renal function may influence the result of this whole blood POC test.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória , Humanos , Tempo de Tromboplastina Parcial , Heparina/uso terapêutico , Oxigenação por Membrana Extracorpórea/efeitos adversos , Sistemas Automatizados de Assistência Junto ao Leito , COVID-19/complicações , COVID-19/terapia , SARS-CoV-2 , Anticoagulantes/uso terapêutico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos
5.
Clin Lab ; 68(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36378004

RESUMO

BACKGROUND: International guidelines for plasma preparation are not always observed because high-speed centrifugation reduces turnaround times. This study assessed the effect of rapid centrifugation on sample quality and clotting time. METHODS: Blood samples were obtained from five healthy volunteers. Normal blood samples were spiked with unfractionated heparin to produce abnormal samples. The normal and abnormal coagulation ability samples were centrifuged at 1,500 x g for 15 minutes, 2,000 x g for 10 minutes (both according to international guidelines), or 3,500 x g for 7 minutes (rapid centrifugation). Microparticle procoagulant activity (MP activity), prothrombin time (PT), and activated partial thromboplastin time (APTT) were measured in the supernatant plasma. RESULTS: Rapid centrifugation caused a significant increase in MP activity compared to the two recommended conditions and significantly shortened clotting times, particularly APTT in the abnormal samples. CONCLUSIONS: Rapid centrifugation should not be used for routine processing of blood samples for coagulopathy screening and monitoring patients on anticoagulant therapy.


Assuntos
Heparina , Humanos , Tempo de Tromboplastina Parcial , Testes de Coagulação Sanguínea , Tempo de Protrombina , Centrifugação
7.
Int J Mol Sci ; 23(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36232517

RESUMO

Current guidelines recommend monitoring the anticoagulant effect of unfractionated heparin (UFH) by measuring anti-Xa activity rather than activated partial thromboplastin time (aPTT) in intensive care unit (ICU) patients. The primary objective of this study was to evaluate the correlation of aPTT, anti-Xa activity, and thrombin generation in UFH-treated ICU patients. A prospective observational pilot study was conducted in adult surgical ICU patients treated with UFH. aPTT and anti-Xa activity were monitored daily. The therapeutic target was aPTT between 50 s and 84 s, and/or anti-Xa between 0.3 and 0.7 U/mL. Correlation among aPTT, anti-Xa activity, and thrombin generation was determined by measuring endogenous thrombin potential (ETP), with the inflammatory response evaluated. C-reactive protein (CRP) was used as a marker of inflammatory response. The plasma of 107 samples from 30 ICU patients was analyzed. The correlation between aPTT and anti-Xa activity was 0.66, CI95% [0.54;0.76] (p < 0.0001). Although thrombin generation, aPTT, and anti-Xa were correlated with inflammatory responses, the correlation was higher with thrombin generation and anti-Xa activity compared to aPTT. When aPTT was in a therapeutic range, a low thrombin generation was observed but was 50% inhibited when anti-Xa was in a therapeutic range. Coagulation testing with aPTT, anti-Xa correlated with thrombin generation. A 50% decrease in thrombin generation was observed when anti-Xa was within a therapeutic range. Further work is needed to evaluate coagulation biomarker responses and clinical outcomes in specific ICU populations.


Assuntos
Heparina , Trombina , Adulto , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Biomarcadores , Proteína C-Reativa , Monitoramento de Medicamentos , Inibidores do Fator Xa/farmacologia , Inibidores do Fator Xa/uso terapêutico , Heparina/farmacologia , Heparina de Baixo Peso Molecular , Humanos , Unidades de Terapia Intensiva , Tempo de Tromboplastina Parcial , Estudos Prospectivos
8.
J Thromb Haemost ; 20(12): 2953-2963, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36200348

RESUMO

BACKGROUND: The Perioperative Anticoagulation Use for Surgery Evaluation study prospectively evaluated a prespecified periprocedural interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Coagulation testing is widely available and frequently requested prior to invasive procedures. Coagulation assays display poor sensitivity to clinically relevant DOAC concentrations. OBJECTIVES: Determine the utility of routinely available coagulation testing at predicting a DOAC concentration of <30 ng/ml among patients in the preprocedural setting. METHODS: We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratio (LR+ and LR-) of a normal coagulation assay result for identifying patients with a preprocedural DOAC level < 30 ng/ml. RESULTS: We identified weak or very weak correlations between coagulation assay results and DOAC levels in the preprocedural setting, except for a moderate correlation between the thrombin time (TT) and dabigatran concentrations (ρ = 0.68; p < .001). The prothrombin time (PT) and activated partial thromboplastin time (APTT) demonstrated modest sensitivity (78.9% to 88.2%) and PPVs (76.4% to 93.1%) but poor specificity (13.2% to 53.3%) and NPVs (16.3% to 30.2%) across all three DOACs. A normal TT was associated with 100% specificity and PPV values for a dabigatran level < 30 ng/ml. A normal APTT among patients on dabigatran was associated with an LR+ of 1.671 (95% confidence interval [CI] 1.297, 2.154) and an LR- of 0.395 (95% CI 0.207, 0.751) for levels <30 ng/ml. CONCLUSIONS: The PT and APTT perform poorly at safely identifying patients with negligible DOAC levels in the preprocedural setting.


Assuntos
Dabigatrana , Rivaroxabana , Humanos , Piridonas , Pirazóis , Testes de Coagulação Sanguínea/métodos , Anticoagulantes/uso terapêutico , Tempo de Tromboplastina Parcial , Administração Oral
9.
Genes (Basel) ; 13(10)2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36292752

RESUMO

(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.


Assuntos
Actinina , Estudo de Associação Genômica Ampla , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Aurora Quinase B , Administração Oral , Marcadores Genéticos , Elementos de DNA Transponíveis , Anticoagulantes , Testes de Coagulação Sanguínea , Polimorfismo Genético , Complemento C5 , Histona Desacetilases , Proteínas Cromossômicas não Histona
10.
Zhonghua Fu Chan Ke Za Zhi ; 57(10): 740-745, 2022 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-36299176

RESUMO

Objective: To explore and compare the reference ranges of four coagulation tests in normal pregnant women during early and late pregnancy and the influence of age. Methods: Values of four coagulation tests from 4 974 pregnant women, who gave single birth at Peking University First Hospital, Obstetrics and Gynecology Hospital of Fudan University, West China Second University Hospital, Peking University Third Hospital and Shengjing Hospital of China Medical University from February 2017 to July 2020, were measured and analyzed in this study, including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and thrombin time (TT). The four normal reference ranges of coagulation during early and late pregnancy phases were expressed as P2.5-P97.5. The difference of two pregnancy phases was compared by non-parametric test of two related samples. And the difference between pregnant women of advanced and non-advanced age in the same pregnancy phase was compared by independent sample non-parametric test. Chi-square test was used to compare the incidence of pregnancy complications in different coagulation reference ranges. Results: The reference ranges of PT of normal pregnant women's early and late pregnancy were 10.0-13.9 s and 9.6-12.3 s, the reference ranges of APTT were 22.6-35.3 s and 22.4-30.9 s, the reference ranges of Fib were 2.4-5.0 g/L and 3.0-5.7 g/L, the reference ranges of TT were 12.0-19.0 s and 11.5-18.4 s. Compared with early pregnancy, PT, APTT and TT shortened significantly, while the Fib significantly increased in late pregnancy (all P<0.001). PT, APTT and TT of advanced and non-advanced age pregnant women were significantly different (all P<0.01). Compared with the ranges of non-pregnant population, more pregnant women were included in the normal pregnant reference ranges of PT in early pregnancy and APTT in the early and late pregnancy, while the incidence of pregnancy complications had no significant differences (all P>0.05). The incidence of fetal distress was higher and the incidence of preterm birth was lower in the reference range of PT in late pregnancy. The incidence of gestational diabetes mellitus was higher in the early and late gestational Fib reference ranges, and the incidence of hypertensive disorders in pregnancy was higher in the late gestational Fib reference range (all P<0.05). Conclusions: The coagulation function of pregnant women increases significantly with the growth of pregnancy, and there is a significant difference between advanced significantly and non-advanced age pregnant women. The recommended ranges of normal pregnant women's early and late pregnancy PT are 10.0-13.9 s and 9.6-12.3 s, the recommended ranges of APTT are 22.6-35.3 s and 22.4-30.9 s, the recommended ranges of TT are 12.0-19.0 s and 11.5-18.4 s. The appropriate ranges of normal pregnant women's early and late pregnancy Fib still need further exploration.


Assuntos
Gestantes , Nascimento Prematuro , Recém-Nascido , Feminino , Gravidez , Humanos , Testes de Coagulação Sanguínea , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Fibrinogênio/análise
12.
Transfusion ; 62(11): 2223-2234, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36250486

RESUMO

INTRODUCTION: Preoperative coagulation screening for patients without bleeding disorders remains controversial. The combinatorial risk of INR, aPTT, and platelet count (PLT) abnormalities leading to bleeding requiring transfusion is not known in these patients. We examined the association between abnormal coagulation profile and the risk of transfusion following common elective surgery in patients without bleeding disorders. STUDY DESIGN AND METHODS: We utilized the National Surgical Quality Improvement Program (NSQIP) database from 2004 to 2018 to identify patients without a history of bleeding disorders undergoing common 23 major elective procedures across 10 specialties. Multivariable logistic regression was used to assess the association between coagulation profile and bleeding requiring packed red blood cell transfusion intra-/post-operatively. RESULTS: Of the 672,075 patients meeting inclusion criteria, 53.7% presented with normal coagulation profile preoperatively. Overall, 12.2% (n = 82,368) received transfusion. In the setting of normal aPTT/PLT, both Equivocal INR of 1.1-1.5 (aOR 1.41, 95% CI 1.38-1.44) and Abnormal INR of >1.5 (aOR 1.81, 95% CI 1.71-1.93) were significantly associated with an increased risk of transfusion. Equivocal (60-70) and Abnormal (>70) aPTT with normal INR/PLT did not demonstrate a comparable risk of transfusion. We observed a synergistic effect of combinatorial lab abnormalities on the risk of transfusion when both Abnormal INR/aPTT and Low PLT of <100,000 were present (aOR 5.18, 95% CI 3.04-8.84), compared to the effect of Abnormal INR/aPTT and normal/elevated PLT (aOR 1.90, 95% CI 1.48-2.45). DISCUSSION: The preoperative presence of abnormal findings in INR or PLT was significantly associated with the risk of bleeding requiring transfusion during intraoperative and postoperative periods.


Assuntos
Transtornos da Coagulação Sanguínea , Melhoria de Qualidade , Humanos , Transtornos da Coagulação Sanguínea/terapia , Transtornos da Coagulação Sanguínea/complicações , Transfusão de Sangue , Tempo de Tromboplastina Parcial , Hemorragia/etiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
14.
J Clin Lab Anal ; 36(10): e24695, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36099012

RESUMO

BACKGROUND: The high concentrated thrombin time (hcTT), a thrombin time modified by increasing the thrombin concentration, is a possible alternative assay to activated partial thromboplastin time (aPTT) in unfractionated heparin (UFH) monitoring. This study aimed to determine the optimal thrombin concentration used in the hcTT assay for UFH monitoring. METHODS: A total of 30 blood samples obtained from healthy volunteers were included in this study. Thrombin concentrations of 10.0, 15.0, 20.0, and 25.0 IU/ml were used in the hcTT assay. The consistency between the hcTT and anti-FXa assays was evaluated. To validate the hcTT assay, linearity, repeatability, reproducibility, and diagnostic performance of the assay were assessed. RESULTS: The hcTT assay using thrombin concentration of 15.0 IU/ml showed a strong correlation to the anti-FXa assay with R2 of 0.72 and the Spearman's correlation coefficient (rs ) of 0.97 (95% CI, 0.96-0.98). Within-run and day-to-day run variabilities of the assay were satisfactory (all coefficients of variation <10%). We found an excellent correlation between the results which were measured using different reagents with intra- or inter-laboratory instruments. Notably, as compared to the aPTT assay, the hcTT assay showed a significantly better performance in identifying the samples which contain UFH at the supratherapeutic level, with an AUC of 0.97 vs. 0.91, p = 0.049. CONCLUSION: The hcTT assay can be used as an alternative assay for UFH therapy monitoring. A further study using clinical samples is recommended to confirm the appropriateness of the hcTT assay for clinical application.


Assuntos
Heparina , Trombina , Anticoagulantes/uso terapêutico , Monitoramento de Medicamentos/métodos , Humanos , Tempo de Tromboplastina Parcial , Reprodutibilidade dos Testes , Tempo de Trombina
15.
Dis Markers ; 2022: 2918654, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36168325

RESUMO

Background: To evaluate the prognostic value of preoperative activated partial thromboplastin time (APTT) in patients who underwent coronary artery bypass grafting (CABG). Methods: All data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The study population was divided to two groups according to the optimal cut-off value of APTT calculated by X-tile software, and Cox proportional hazard model was used to define independent effect of APTT on 4-year mortality. Survival curves were estimated by the Kaplan-Meier method, and the area under the receiver-operating characteristic curve (AUC) was calculated to compare APTT with other severity scores. Propensity score matching (PSM) analysis were applied to ensure the robustness of this study. Results: A total of 2,706 patients were included. The optimal cut-off value of APTT for 4-year mortality was 44 seconds. The Cox proportional hazard model showed that patients with APTT ≥ 44 had a significantly higher risk of all-cause death than those with APTT < 44 both before (HR (95% CI), 1.42 (1.16-1.74), P < 0.001) and after PSM (HR (95% CI), 1.47 (1.14-1.89), P = 0.003). The survival curves showed that patients with longer APTT had a significantly lower 1-year and 4-year cumulative survival probability. The ROC of APTT combined with other severity scores significantly increased predictive ability for 1-year and 4-year mortality. Conclusions: A longer APTT (≥44) was associated with a higher risk of mortality and can serve as a prognostic predictor in CABG patients.


Assuntos
Ponte de Artéria Coronária , Ponte de Artéria Coronária/métodos , Humanos , Tempo de Tromboplastina Parcial , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos
16.
PLoS One ; 17(8): e0272216, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35951632

RESUMO

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.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , COVID-19/diagnóstico , Seguimentos , Humanos , Tempo de Tromboplastina Parcial , Prognóstico , Tempo de Protrombina , Estudos Retrospectivos , Medição de Risco
17.
Rinsho Ketsueki ; 63(7): 733-739, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35922940

RESUMO

Acquired factor V deficiency is a rare disease that presents with various bleeding symptoms because of the acquired production of factor V inhibitors and decrease in factor V activity. We have experienced five cases of acquired factor V deficiency diagnosed on the basis of abnormalities in coagulation tests in the last 10 years. All five patients were older men, of whom one had no bleeding symptoms, and three had a history of renal failure and malignant tumors. In the cross-mixing test, two of three cases demonstrated an inhibitor pattern, but one case showed a deficient pattern. In all cases, steroid treatment improved factor V activity as well as prothrombin time and activated partial thromboplastin time. However, patients with intracranial hemorrhage had a poor prognosis. Although this disease is rare, careful management is necessary, especially in the absence of bleeding symptoms and where cross-mixing test does not show an inhibitor pattern.


Assuntos
Deficiência do Fator V , Idoso , Testes de Coagulação Sanguínea/efeitos adversos , Fator V/genética , Deficiência do Fator V/complicações , Deficiência do Fator V/diagnóstico , Hemorragia/etiologia , Humanos , Masculino , Tempo de Tromboplastina Parcial , Tempo de Protrombina
18.
Thromb Haemost ; 122(9): 1573-1583, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35909257

RESUMO

BACKGROUND: Dabigatran etexilate, a direct oral thrombin inhibitor, is approved to treat venous thromboembolism (VTE) in both adults and children. OBJECTIVES: This population analysis characterized relationships between dabigatran total plasma concentrations and coagulation laboratory parameters (activated partial thromboplastin time [aPTT]; diluted thrombin time [dTT]; ecarin clotting time [ECT]). METHODS: Data from three phase 2a and one single-arm and one randomized, comparative phase 2b/3 pediatric studies (measurements: aPTT 2,925 [N = 358]; dTT 2,348 [N = 324]; ECT 2,929 [N = 357]) were compared with adult data (5,740 aPTT, 3,472 dTT, 3,817 ECT measurements; N = 1,978). Population models were fitted using nonlinear mixed-effects modeling. Covariates (e.g., sex, age) were assessed on baseline and drug-effect parameters, using a stepwise covariate model-building procedure. RESULTS: Overall, relationships between dabigatran, aPTT, dTT, and ECT were similar in children and adults. For children aged <6 months, a higher proportion of baseline samples were outside or close to the upper aPTT and ECT adult ranges. No age-related differences were detected for dTT. With increasing dabigatran concentration, aPTT rose nonlinearly (half the maximum effect at 368 ng/mL dabigatran) while dTT and ECT increased linearly (0.37 and 0.73% change per ng/mL dabigatran, respectively). Mean baseline aPTT (45 vs. 36 seconds) and ECT (40 vs. 36 seconds) were slightly increased for those aged <6 months versus older children. CONCLUSION: The similar relationships of laboratory parameters observed across pediatric age groups suggests that developmental changes in the hemostatic system may have little effect on response to dabigatran.


Assuntos
Anticoagulantes , Dabigatrana , Adolescente , Antitrombinas , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Criança , Pré-Escolar , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Lactente , Masculino , Tempo de Tromboplastina Parcial , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Eur Rev Med Pharmacol Sci ; 26(15): 5485-5488, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35993644

RESUMO

OBJECTIVE: Coagulation parameters are used to diagnose hematological diseases. The correlation between the coagulation parameters and Apgar score at 5 min is yet to be elucidated. The present study aimed at describing the neonatal coagulation parameters in preterm infants with a low Apgar score at 5 min. PATIENTS AND METHODS: In this case-control study, 32 serious preterm infants were compared with 20 preterm infants, according to the Apgar score at 5 min. The prothrombin time (PT), thrombin time (TT), fibrinogen (Fbg), activated partial thromboplastin time (APTT), calculated international normalized ratio (INR), D-dimer (D2), fructose diphosphate sodium (FDP), and procalcitonin (PCT) values were recorded. The linear correlation between coagulation parameters and Apgar score at 5 min was analyzed by linear regression. The two groups were compared using GraphPad Prism 8 (LaJolla, CA, USA). RESULTS: In the study, the mean coagulation parameters were significantly higher in the serious preterm infants with low the Apgar score at 5 min compared to the preterm infants with normal Agar scores at 5 min (p<0.05). The correlation between coagulation parameters and Apgar score at 5 min was recorded (PT: R=0.3984; APTT: R=0.3165; INR: R=0.4139). CONCLUSIONS: The coagulation parameters were significantly higher in serious preterm infants with a low Apgar score at 5 min. Also, the coagulation parameters and Apgar score at 5 min are associated with severity in preterm infants.


Assuntos
Coagulação Sanguínea , Recém-Nascido Prematuro , Índice de Apgar , Estudos de Casos e Controles , Humanos , Lactente , Recém-Nascido , Tempo de Tromboplastina Parcial
20.
Sci Rep ; 12(1): 13155, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915103

RESUMO

There has been growing attention toward the predictive value of the coagulation parameters abnormalities in COVID-19. The aim of the study was to investigate the role of coagulation parameters namely Prothrombin concentration (PC), activated Partial thromboplastin Time (aPTT), D-Dimer (DD), Anti Thrombin III (ATIII) and fibrinogen (Fg) together with hematological, and biochemical parameters in predicting the severity of COVID-19 patients and estimating their relation to clinical outcomes in hospitalized and severe COVID-19 Patients. In a prospective study, a total of 267 newly diagnosed COVID-19 patients were enrolled. They were divided into two groups; hospitalized group which included 144 patients and non-hospitalized group that included 123 patients. According to severity, the patients were divided into severe group which included 71 patients and non-severe group that included 196 patients who were admitted to ward or not hospitalized. Clinical evaluation, measurement of coagulation parameters, biochemical indices, outcome and survival data were recorded. Hospitalized and severe patients were older and commonly presented with dyspnea (P ≤ 0.001). Differences in coagulation parameters were highly significant in hospitalized and severe groups in almost all parameters, same for inflammatory markers. D-dimer, AT-III and LDH showed excellent independently prediction of severity risk. With a cut-off of > 2.0 ng/L, the sensitivity and specificity of D dimer in predicting severity were 76% and 93%, respectively. Patients with coagulation abnormalities showed worse survival than those without (p = 0.002). Early assessment and dynamic monitoring of coagulation parameters may be a benchmark in the prediction of COVID-19 severity and death.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Coagulação Sanguínea , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Tempo de Tromboplastina Parcial , Estudos Prospectivos
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