Prothrombin Time Values Research Articles

INVESTIGATION OF TOTAL PHENOLIC CONTENT, FLAVONOID CONTENT, AND HEMOSTATIC ACTIVITY OF BEETROOT (Beta vulgaris. L) EXTRACT IN HEPARININDUCED THROMBOCYTOPENIA RAT

The goal of the research was to find out the concentration of phenolic and flavonoid content and also to identify the hemostatic activity of the ethanolic extract of beetroot (Beta vulgaris L) in heparin-induced thrombocytopenia rats. The identification of total phenol content using Folin-Ciocalteu as reagent and flavonoid content were determined by spectrophotometer and continued to the determination of hemostatic activity using heparin as an inducer and then determined the bleeding time, platelet count, and prothrombin time. The results showed that the ethanol extract of beetroot had a total phenolic content of 312.2 mg GAE/g extract and a flavonoid content equivalent to 38.5 mg quercetin equivalent/g. The investigation of bleeding time at doses of 100 mg/kg BW, 200 mg/kg BW, and 400 mg/kg BW was significantly different (p<0.05P) compared to the negative group. The dose of 400 mg/kg BW reduced the bleeding time by 5.90±0.11 minutes, which was substantially different from the other doses (p<0.05). At a dose of 400mg/kg BW, the greatest platelet count number was seen, which was statistically different from the control group (p<0.05) The prothrombin Time (PT) values at a dose of 400 mg/kg BW likewise revealed increased activity and were significantly different (p>0.05) from the negative group. The ethanol extract of beetroot (Beta vulgaris L) possesses hemostatic action and is dose-dependent, with a total phenolic concentration of 312.2 mg GAE/g extract and a flavonoid content equivalent to 38.5 mg quercetin equivalent/g extract.

Sickle cell disease: Assessment of hemostasis parameters in steady-state patients at Tertiary Care Hospital, Indore, India

Background: The evidence from various studies showed that patients with sickle cell disease (SCD) have altered components of hemostasis such as platelet function, procoagulant, anticoagulant and fibrinolytic pathways, and modulate inflammation such as acute or chronic inflammatory state. These components may alter based on race, regions, or environment. Assessment of the hemostatic parameters in our region is imperative because the altered components so involved may give an insight as to the clinical phenotypes of Arab-Indian haplotypes we have in our setting. The objective of present study is to assess basic hemostatic and inflammatory parameters in patients with SCD during steady state at a tertiary care hospital. Methods: Blood samples of 95 patients with SCD during steady state attending M. Y. Hospital, Indore, India, during the period of November 2019 to March 2020 were screened for C-reactive protein (CRP) levels and platelet counts using latex enhanced immune-turbidimetric assay and hemotology analyzer, respectively, while prothrombin time (PT) and activated partial thromboplastin time (APTT) by automated coagulation analyzer. Results: It was observed that there is no significant difference among the mean platelet count (321.9 ± 97.63 × 109/l) of SCD patients and control groups (P = 0.69). CRP levels (6.60 ± 2.83 mg/l) were found to be significantly increased (P < 0.01) in SCD patients in comparison with their respective control. The mean PT (15.21 ± 1.58 s) and APTT values (37.69 ± 2.50 s) were found to be significantly increased (P < 0.05 for both) in SCD patient group when compared with control group. Conclusion: The study confirms that patients with SCD in steady state have significant prolonged coagulation indices. These can be an evidence of hypercoagulable state in SCD and may provide reference values appropriate for therapeutic target. We recommend that patients of SCD especially those with severe vaso-occlusive crises should have these hemostatic parameters as a basic test and during routine clinic follow-up for improved management.

Changes of plasma nitric oxide, endothelin-1, and blood coagulation following intravitreal conbercept

Intravitreal anti-VEGF (anti-vascular endothelial growth factor) biologics have revolutionized the pharmacological management of chorioretinal diseases. However, the systemic adverse events such as stroke or bleeding are the concerns for many patients and physicians. The mechanism to develop these side effects are poorly understood. Consecutive 95 patients with retinal diseases were studied for their blood activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), and concentration of fibrinogen before and after intravitreal conbercept. Additionally, plasma nitric oxide (NO) and endothelin-1 (ET-1) were investigated on 38 of the 95 patients. Compared with the pre-injection, 4-week post-injection values of APTT and PT were increased by 0.582 s (p = 0.038, paired t test) and by 0.086 s (p = 0.080, paired t test; p = 0.0475, Sign test), respectively. At the same time, fibrinogen decreased by 0.048 g/L. Plasma levels of NO or ET-1 or VEGF did not significantly change from pre-injection levels. Our findings advanced the understanding of mechanism for systemic side effects associated with intravitreal anti-VEGF and emphasized paying more attention to higher risk of possible bleedings for patients following intravitreal conbercept.

Dual antiplatelet therapy of patients with acute myocardial infarction after coronary artery stenting

Objective: to study the effectiveness of dual antiplatelet therapy (DAPT) in patients with myocardial infarction (MI) after emergency percutaneous coronary intervention (PCI).Material and methods. The study involved 20 patients who underwent PCI at the Department of Interventional Cardiology in Khust district hospital, Zakarpattia region. After PCI and coronary artery stenting during 12 months in addition to the complex therapy (Metoprolol, Rosuvastatin, Ramipril, Pantoprazole) the patients received dual antiplatelet therapy (DAPT) with acetylsalicylic acid and Ticagrelor (Brilinta). A clinical course of the disease was analyzed. Prothrombin time, prothrombin index, international normalized ratio (INR), activity of the liver transaminases, and total bilirubin concentration in the blood serum were determined. Results. During the period of 12 months after PCI for acute transmural MI and coronary artery stenting, re-admissions for exacerbation of the underlying disease were not registered. One patient developed a side effect after DAPT in the form of mild gastrointestinal bleeding. 12 months after DAPT, a reliable increase of prothrombin time from 12,77±0,18 sec. to 13,45±0,34 sec. (р&lt;0,05) and international normalized ratio (INR) from 0,95±0,008 Un to 1,0±0,026 Un were registered. (р&lt;0,05). Inconsiderable but reliable increase of alanine aminotransferase (ALT) activity from 14,4±1,11 Un/L to 16,67±1,25 Un/L was found (р&lt;0,05).Conclusions1. Patients after percutaneous coronary intervention (PCI) and coronary artery stenting for acute transmural myocardial infarction (MI) are well tolerant to dual antiplatelet therapy (DAPT) with acetylsalicylic acid and Ticagrelor. For 12 months re-admissions for exacerbation of the underlying disease were not registered.2. Increase of prothrombin time values and international normalized ratio in patients with MI after PCI and DAPT is indicative of a decrease in blood coagulation activity.

Indicators of Hypoxia Tolerance as Determined by Cellular Elements of Rat Blood.

Although hypoxia tolerance is mainly determined genetically, it is important to study individual variability of animal organisms in order to identify the factors that underlie their tolerance to hypoxic exposure. We investigated blood cell counts and coagulograms in Wistar rats as predictors allowing the animal population to be split into hypoxia-tolerant and hypoxia-intolerant individuals. The validity of the specific predictors’ choice was proved by a coincidence between the population split in accordance with the detected individual parameters and the results of testing animals in a decompression chamber at a rarefaction corresponding to the “rise to an altitude” of 11500 m above sea level. Circulating blood cells were quantitatively assessed by eighteen indicators before and after hypoxic exposure. The differences between animals low-tolerant (LT), high-tolerant (HT), and medium-tolerant (MT) to hypoxia were determined by five indicators: white blood cell count (WBC), granulocyte count (Gran#), red blood cell count (RBC), reticulocyte count/percent (RTC), and mean corpuscular hemoglobin (MCH). The RBC, RTC, and MCH values in HT rats were significantly higher than in LT animals (by 1.4, 1.9, and 1.1 times, respectively). The WBC and Gran# values in HT rats were lower than in LT individuals. The hypoxia tolerance indices (HTI) were calculated using the original formula. It was established that in LT rats, the HTI ≤ 0.203, in HT rats ≥ 0.335, and in MT rats < 0.335 but > 0.203. After testing in a decompression chamber, the activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) decreased, but the fibrinogen level increased. LT rats were characterized by the lowest APTT, TT, and PT values and the highest values of the fibrinogen level. Our results indicate that one of the most important mechanisms underlying a high hypoxia tolerance in rats consists in sustaining reciprocal relationships between the complex of RBC indicators, which tend to increase under hypoxia, and Gran# indicators, which tend to decrease after hypoxic exposure.

Role of Coagulation Profile in Predicting Disease Severity Among Patients of COVID-19.

BackgroundCoronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), affects the coagulation cascade. In this retrospective study, we aimed to analyze the association of different coagulation parameters including that of D-dimer, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT) with severity in COVID-19 patients.MethodologyA total of 90 patients positive for SARS-CoV-2 on real-time reverse transcription-polymerase chain reaction (rRT-PCR) were included in the study. The patients were categorized as severe and non-severe, and their D-dimer, fibrinogen, PT, and aPTT values on admission were evaluated. The association of the coagulation parameters with disease severity was analyzed by independent t-test and Chi-square test. The cut-off values of these parameters were calculated to predict the disease severity by receiver operator characteristic (ROC) curve.ResultsOut of 90 patients admitted, 42 patients were categorized as severe and the rest 48 patients were categorized as non-severe. D-dimer, fibrinogen, and PT in the severe group were significantly higher than the non-severe group with p-values of <0.001, 0.005, and <0.001, respectively. Cut-off values of 0.99 mg/L for D-dimer,349.5 mg/dL for fibrinogen, and 13.05 seconds for PT were predictive of disease severity among COVID-19 patients.ConclusionSevere COVID-19 patients showed significantly higher levels of D-dimer and fibrinogen and prolongation of PT as compared to non-severe COVID-19 patients. Higher levels of D-dimer and fibrinogen, and prolonged PT are predictive of increased disease severity among COVID-19 patients.

Comparison of various principles of coagulation tests in handling hemolysed blood samples

Background: Rejection of hemolysed samples for coagulation test is the standard practice.However, when clinicians deal with extremely sick patients where repeat sampling is difficult toobtain, rejection of the sample is a lost opportunity for the lab physician to assist inpatient care.Proceeding with the test and providing a clinically helpful interpretation of the results will ensure theactive participation of the laboratory physician. Different principles of coagulation testing handle thehemolysed samples differently. It is essential to know the best principle to proceed with thehemolysed sample if need be. This study set out to estimate the predictive values of post-hemolyticsample coagulation test results with various coagulation test principles. Methods: This is aprospective experimental study where the non-hemolysed samples were processed for coagulationtests. Part of the sample was deliberately hemolysed, and the coagulation tests were repeated.Results: Two hundred and forty-eight samples were studied. A median of 11% hemolysis wasachieved experimentally. The mean difference in prothrombin time between pre and post hemolyticsamples with normal PT was 0.9 and with abnormal PT, it was 1.1 seconds. The same for APTT was4.9 and 1.1 seconds, respectively. The majority of the samples showed prolonged coagulation posthemolysis. Positive (PPV) and negative (NPV) predictive values for prothrombin time are 97.3 and73.4%, respectively. Similarly, PPV and NPV for APTT are 97.4 and 47.1%, respectively.Conclusions: Samples with normal values after hemolysis are more likely to be normal.

Preoperative Oral Administration of Yunnan Baiyao and Its Effect on Coagulation Parameters in Tick-Borne Disease and/or Heartworm Seropositive Dogs: A Pilot Study

The overall goal of this clinically focused pilot study was to investigate the preoperative benefit of oral administration of Yunnan Baiyao (YB) to Ehrlichia. canis, Anaplasma platys and/or heartworm seropositive canines. A total of 12 clinically normal dogs undergoing sterilization procedures were randomly subdivided into Control/Placebo Group (n=6) or Treatment Group (n=6). Each patient received three oral doses of YB (0.5g/5kg) or placebo every twelve hours with the last dose given the evening before surgery. Citrated blood measurements for prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen were obtained before the first YB dose and after the third dose. Intraoperative blood loss was estimated by blood-soaked gauze sponge counts. The study found the Control Group’s mean aPTT increased by 3.8% while the Treatment Group’s decreased by 0.42%. PT values were slightly decreased in both groups. Fibrinogen decreased in controls (9.7%) but had a modest increase in treated dogs (12.4%). Intraoperative blood loss was increased in controls (3%) compared to the Treatment Group (mean±SD: 6.6±6.8 vs. 6.4±3.6, respectively). Findings from the study which suggest preoperative benefits from YB administration to seropositive dogs include stabilizing aPTT and fibrinogen values along with reduced intraoperative blood loss in YB treated dogs. Although these modest findings were not statistically significant in this small study, the biological trends suggest potential benefits of preoperative administration of YB before routine elective surgeries in seropositive patients and support a clinical trial with larger sample size.

First Clinical Trial of a Newly Developed, Low Menaquinone-7, Fermented Soybean Natto in Warfarin-Dependent Patients.

Bacillus subtilis fermented soybeans (natto) contain high vitamin K2 levels, mostly as menaquinone-7 (MK-7), and must be avoided by warfarin-dependent patients. This is the first report which demonstrates the characteristics and clinical relevance of a low MK-7 natto for such patients. We generated a novel, mutant B. subtilis strain TTCC2051 with short-term fermentation and reduced MK-7 production, yielding 19-24% of the normal MK-7 content. After functional assessments and a preclinical trial, 10 warfarin-dependent patients underwent a clinical trial with a 7-day ingestion test of the low MK-7 natto. Functional assessments were satisfactory, and the preclinical trial showed no increases in plasma MK-7 levels after 7 days of ingestion. In the clinical trial, 20 g/day of the low MK-7 natto significantly increased plasma MK-7 levels while 10 g/day did not. However, neither dose of low MK-7 natto changed international normalized ratio of prothrombin time (PT-INR) values in either group. The low MK-7 natto neither changed PT-INR values nor precipitated adverse events if ingested with a once-daily maximum of 20 g (46 μg of MK-7). Thus, this novel food product has potential for consumption by warfarin-dependent patients.

Association between short-term heart rate variability and blood coagulation in patients with breast cancer

The purpose of this study was to investigate the relationship between heart rate variability (HRV), a non-invasive tool for evaluating autonomic function, and routine coagulation indices (RCIs) in patients with breast cancer (BC). Forty-six BC patients were enrolled in this study. Blood biochemistry tests were performed to extract RCIs, including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). Five-minute electrocardiograms were collected for analysis of HRV parameters (SDNN, RMSSD, LF, HF, LF n.u., HF n.u., LF/HF). Multiple linear regression models examined the relationship of HRV parameters with RCIs. RMSSD, LF n.u., HF n.u., LF/HF were significantly associated with PT. Specifically, the value of PT increased by 0.192 ± 0.091 or 0.231 ± 0.088 s, respectively for each 1 standard deviation (SD) increase in RMSSD or HF n.u.; it increased by 0.230 ± 0.088 or 0.215 ± 0.088 s, respectively for each 1 − SD decrease in LF n.u. or ln (LF/HF) (all P < 0.05). RMSSD was significantly associated with APTT, i.e., the value of APTT increased by 1.032 ± 0.470 s for each 1 − SD increase in RMSSD (P < 0.05). HRV parameters were associated with RCIs in patients with BC. These observations suggest that the autonomic nervous system and coagulation indices in BC patients are linked, potentially explaining the reason that they are both associated with the prognosis.

Comparison of STA-NeoPTimal (Stago) and STA-Neoplastine CI Plus (Stago) thromboplastin reagents using a STA Satellite Max analyzer to measure prothrombin times in dogs.

Different thromboplastins are available to measure prothrombin time (PT). Stago coagulation analyzers and reagents are currently used in veterinary laboratories and enable PT measurements to explore the coagulation cascade (extrinsic pathway). The main objective was to compare PT measurements obtained with the STA-NeoPTimal reagent with the commonly used STA-Neoplastine CI Plus reagent. The secondary objective was to compare the PT ratio with the international normalized ratio (INR) calculated from our derived clotting times. Analytical performance was evaluated with intra-assay and inter-assay precision. Seventy-two individual canine plasma samples were collected. Each sample was tested with both thromboplastins, using an STA Satellite Max analyzer. The PT, PT ratio, and INR values obtained with the two reagents were compared using Passing-Bablok regression for correlations and Bland-Altman plots for method agreements. The analytical performance of STA-NeoPTimal reagent was acceptable. Compared with the STA-Neoplastine CI Plus reagent, the STA-NeoPTimal reagent showed a positive proportional bias for PT values. Narrow range analyses showed good agreement for normal PT values (less than 9.5seconds, internal reference cutoff with STA-Neoplastine CI Plus), and clinical concordance was achieved. When PT was prolonged (more than 9.5seconds), PT increases were more marked with the STA-NeoPTimal reagent. Agreement was good for INR values across the whole range of PT results. STA-NeoPTimal can be reliably implemented in veterinary laboratories for canine PT measurements, as agreement between the PT results measured with the two reagents was clinically acceptable.

Covid-19 ile ilişkili pnömoni şiddeti ile koagulopati ve mortalite arasındaki ilişki

Purpose: In the present study, the possibility of predicting mortality with the change in coagulation parameters depending on the severity of Covid-19-associated pneumonia was investigated. &#x0D; Materials and Methods: A total of 137 patients with Covid-19-associated pneumonia were included in the study. The patients were divided into three groups according to the severity of pneumonia as mild, moderate and severe. According to the severity of pneumonia, the parameters of complete blood count and the levels of biochemical parameters were compared between the groups. By examining blood parameters according to mortality, ROC analysis and regression analysis were performed to determine the net effect of these parameters on mortality. &#x0D; Results: As the severity of pneumonia increased, Prothrombin time (PT), International normalized ratio (INR) and Activated partial thromboplastin time (aPTT) values were also increased, and a statistically significant difference was found between the groups in PT and INR values. PT, INR and aPTT levels were higher in cases with mortality. Mortality can be predicted with 93.5% sensitivity and 97.5% specificity. according to the &gt;45.1 seconds(sec) cut-off value of the coagulation parameter (aPTT+PT.&#x0D; Conclusion: The coagulation parameter (aPTT + PT), whose level increases secondarily to the increase in Covid-19-associated pneumonia severity, provides successful results in predicting mortality, and may be a parameter that we can recommend in clinical use.

Abstracts of the 30th Annual Pediatric Pharmacy Association (PPA) Meeting April 21 to 25, 2021

Abstracts of the 30th Annual Pediatric Pharmacy Association (PPA) Meeting April 21 to 25, 2021

The Effect of Rivaroxaban Exposure and Clinical Risk Factors on Efficacy and Safety Outcomes in Patients with Nonvalvular Atrial Fibrillation

Introduction: Rivaroxaban, an oral factor Xa inhibitor, reduces the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) when given in fixed doses without routine coagulation monitoring. An exposure-response analysis was conducted to evaluate the impact of rivaroxaban exposure and clinical risk factors on efficacy and safety outcomes in patients with NVAF to assess whether concentration-based dose adjustment would improve the benefit-risk profile of rivaroxaban in this patient population.Methods: Efficacy/safety outcome data were taken from the rivaroxaban-treated group enrolled in the ROCKET AF trial (NCT00403767) in which 14 264 patients with NVAF were randomized to receive either rivaroxaban 20 mg once daily (15 mg in patients with moderate renal impairment) or dose-adjusted warfarin. Individual rivaroxaban exposure metrics (peak concentration, trough concentration [Ctrough], and daily area under the curve at steady-state) were derived based on an integrated population pharmacokinetic (PK) model (which was previously developed using pooled data from 4918 patients in seven clinical trials across all approved rivaroxaban indications) that incorporated PK-related individual covariates and prothrombin time values measured in a central laboratory. Composite efficacy outcomes were 1) ischemic stroke and non-CNS systemic embolism (ISNSM), and 2) ischemic stroke and non-CNS systemic embolism and death from all causes (ISNSMD). Safety outcomes were 1) major plus non-major clinically relevant (NMCR) bleeding, and 2) major bleeding (MB). Kaplan-Meier analyses stratified by quartiles of exposures were performed with efficacy and safety outcomes. A multivariable Cox model was applied to link individual exposures and clinical risk factors related to efficacy/safety with the time-to-event outcomes.Results: For efficacy outcomes, the event rates were 2.2% and 5.1% (154 and 357 out of 7061 patients) for ISNSM and ISNSMD. Kaplan-Meier analyses showed no apparent trend among the quartiles of exposure metrics and the efficacy event rates. Cox regression analyses revealed no association between exposures and the two efficacy outcomes (e.g., p=0.733 and p=0.82 for the association of Ctrough with ISNSM and ISNSMD, respectively). For safety outcomes, the event rates were 20.7% and 5.6% (1475 and 375 out of 7111 patients) for major plus NMCR bleeding and MB, respectively. Kaplan-Meier analyses showed that cumulative major plus NMCR bleeding and MB event rates increased when rivaroxaban exposure levels increased. Cox regression revealed that the hazard ratio (HR) for these two safety outcomes increased with rivaroxaban exposure. The impact of increasing from the median Ctrough to the 95th percentile was a HR of 1.26 (p=0.00002) for major plus NMCR bleeding (Figure 1) and a HR of 1.25 (p=0.021) for MB (Figure 2). However, as shown in Figures 1 and 2, these HRs appeared to be of lower magnitude when compared with several clinical risk factors (e.g., HR 1.47, p=0.00089 and HR 2.55, p<0.0001 for history of gastrointestinal bleeding vs no history; HR 1.35, p<0.0001 and HR 1.41, p=0.0045 for age > 75 years vs age 65-75 years; HR 1.27, p=0.006 and HR 1.93 p<0.0001 for low baseline hemoglobin values [hemoglobin <13 g/dL for males and <12 g/dL for females] vs normal).Conclusions: The relatively small impact of exposure on the HR for safety outcomes and lack of relationship for efficacy outcomes suggest that for the approved dosing regimen, rivaroxaban exposure is not an important risk factor for the occurrence of either bleeding or ischemic events. Several clinical risk factors are more impactful than rivaroxaban exposure on these efficacy and safety outcomes. Therefore, it is unlikely that concentration-based dose adjustment would further enhance the benefit-risk profile of rivaroxaban in patients with NVAF. [Display omitted] DisclosuresYan:Janssen Research & Development: Employment. Peters:Janssen Research & Development: Employment. Sharma:Janssen Research & Development: Employment. Nandy:Janssen Research & Development: Employment. Nessel:Janssen Research & Development: Employment. Garmann:Bayer AG: Employment. Willmann:Bayer AG: Employment. Hermanowski-Vosatka:Janssen Research & Development: Employment. Solms:Bayer AG: Employment. Berkowitz:Bayer US: Employment. Spiro:Bayer US: Employment. Fox:Bayer HealthCare Pharmaceuticals: Consultancy, Honoraria; Janssen Biotech, Inc.: Consultancy, Honoraria; AstraZeneca: Research Funding. Weitz:Novartis Pharmaceuticals: Consultancy, Honoraria; Janssen Biotech, Inc.: Consultancy, Honoraria; Merck & Co., Inc.: Consultancy, Honoraria; Ionis Pharmaceuticals: Consultancy, Honoraria; Bayer HealthCare Pharmaceuticals: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Daiichi-Sankyo: Consultancy, Honoraria; Pfizer, Inc.: Consultancy, Honoraria; Portola Pharmaceuticals: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Schmidt:Bayer HealthCare Pharmaceuticals: Consultancy. Piccini:GlaxoSmithKlein: Consultancy; Johnson & Johnson: Consultancy; Abbott Medical: Research Funding; Gilead: Research Funding; Spectranetics: Consultancy, Research Funding; Janssen Pharmaceuticals: Research Funding; ARCA biopharma: Research Funding; Boston Scientific: Research Funding; Allergan: Consultancy; Medtronic: Consultancy. Patel:Astra Zeneca: Other: Attended advisory board, Research Funding; Bayer US: Other: Attended advisory board; Janssen Research & Development: Other: Attended advisory board. Becker:IONIS pharmaceuticals: Other: Safety Committee for new compound that lowers LPa; Portola Pharmaceutics: Other: DSMB for clinical trial of anticoagulant reversal compound. Zhang:Janssen Research & Development: Employment.

Role of thromboelastography in the evaluation of septic shock patients with normal prothrombin time and activated partial thromboplastin time

Coagulopathy is frequent in septic shock and plays a key role in multiple organ dysfunction. The aim of this study is to investigate application values of thromboelastography (TEG) for outcome in septic shock patients with a normal value of prothrombin time (PT) and active partial thromboplastin time (aPTT). Prospective observational study using 1298 consecutive septic shock patients with TEG at admission was conducted at the emergency department (ED) of a tertiary care hospital in South Korea between 2016 and 2019. After excluding overt-disseminated intravascular coagulation (DIC) defined by scoring system, we included patients with a normal value of international normalized ratio ≤ 1.3 and aPTT ≤ 34 s. The primary outcome was 28-day mortality. 893 patients were included and 129 patients with overt DIC were excluded. Of the 764 remaining patients, 414 (54.2%) patients showed normal PT and aPTT (28-day mortality rate, 11.4%). TEG values such as reaction time, kinetic time (K), alpha angle (α), maximum amplitude (MA) and lysis index (LY 30) showed no significant mean difference between the survivor and non-survivor groups. However, hypocoagulable TEG values such as α < 53° (12.0% vs. 23.4%; p = 0.039), and MA < 50 mm (6.3% vs. 21.3%; p = 0.002) were significantly higher in the non-survived group. In multivariate analysis, hypocoagulable state (defined as K > 3 and α < 53 and MA < 50) was independent factors associated with increased risk of death (OR 4.882 [95% CI, 1.698–14.035]; p = 0.003). In conclusion, septic shock patients with normal PT and aPTT can be associated with impaired TEG profile, such as hypocoagulability, associated with increased mortality.

Effect of polymorphisms in CYP3A4*22 (rs35599367) C&gt;T, CYP3A5*3 (rs776746) A&gt;G, ABCB1 (rs4148738) C&gt;T and ABCB1 (rs1045642) C&gt;T genes on apixaban anticoagulation: pilot study results

Introduction. Apixaban is a direct oral anticoagulant prescribed for treatment and prevention of venous thromboembolism (VTE) and for prevention of stroke in patients with nonvalvular atrial fibrillation. Direct oral anticoagulants (DOACs) such as apixaban are rapidly replacing warfarin therapy due to improved efficacy and safety profile shown in clinical trials. However, anticoagulants can cause serious and adverse drug reactions (ADRs).Aim. Study of the effect of carriage of polymorphisms in CYP3A4*22 (rs35599367) C&gt;T, CYP3A5*3 (rs776746) A&gt;G, ABCB1 (rs4148738) C&gt;T and ABCB1 (rs1045642) C&gt;T genes on the change in prothrombin time (PT) and activated partial thromboplastin time (aPTT) in patients using apixaban.Materials and methods. A total of 36 patients were enrolled onto this prospective observational study. All patients received apixaban at doses in accordance with instructions on how to administer the drug. Atrial fibrillation was diagnosed in 26 patients, and secondary thrombotic complications in 23 patients. To perform pharmacogenetic tests and measure aPTT and PT parameters, venous blood samples from each patient were drawn on Days 4-5 after prescription of apixaban. The PharmGKB database was used to select candidate genes for the study. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: data were analyzed by using IBM SPSS Statistics program, Version 23.0.Results. In our study, we assessed the effect of polymorphisms in ABCB1 (rs1045738) C&gt;T, ABCB1 (rs4148642) C&gt;T genes on the aPTT and PT parameters. No statistically significant associations were found.Conclusion. The differences between PT and APTT values in patients using apixaban in the groups with different polymorphisms in ABCB1 (rs1045738) C&gt;T, ABCB1 (rs4148642) C&gt;T gene were not statistically significant. Further studies are necessary to assess the effect of pharmacogenetics on the safety and efficacy profile of apixaban.

The Effect of Sugammadex on Prothrombin and Activated Partial Thromboplastin Time.

Sugammadex is routinely used as an effective neuromuscular blockade reversal agent. Several studies have indicated that it may prolong the prothrombin time (PT) and the activated partial thromboplastin time (aPTT). This review gathers the relevant in vivo studies to accumulate knowledge on the subject. Nine studies were included. According to the results, sugammadex seems to lead to a transient increase in aPTT and PT values, compared to standard care. However, the clinical impact seems to be trivial. Nevertheless, the trials’ findings reveal great heterogeneity, preventing a meta-analysis. Therefore, more well-designed studies are needed to lead to prudent conclusions.

Noninvasive evaluation of ovarian endometriosis: a single-center experience

To investigate the relationships of cancer antigen (CA) 125, CA 19-9, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen (FIB), and D-dimer values with ovarian endometriosis (OEM), and to explore the validation of biomarkers for noninvasive preoperative evaluation of patients with severe OEM. This retrospective case-control study included 413 women with OEM (of whom 143 cases were stage I to II, 139 cases were stage III, and 131 cases were stage IV, respectively) and 158 women without OEM as controls. Subjects' serum CA-125 and CA19-9 levels, and coagulation test results (serum PT, aPTT, and D-dimer values) were evaluated. The serum CA-125, aPTT, FIB and D-dimer levels were statistically different between OEM patients in the stages I to (and) II group and those in the stages III and IV group (P<0.05). However, a statistical difference in CA 19-9 levels and TT was only found between patients with stages III and IV OEM. In receiver operating characteristic (ROC) curve analysis of single indexes, the area under the ROC curve values for CA-125, CA19-9, aPTT, TT, FIB, and D-dimer were 0.953, 0.512, 0.66, 0.576, 0.573, and 0.624, respectively, for diagnosing stage III and stage IV OEM. In ROC curve analysis of combined indexes, the AUC values for aPTT + D-dimer, CA-125 + D-dimer, CA-125 + aPTT and CA-125 + D-dimer + aPTT were 0.672, 0.954, 0.958, and 0.961, respectively. The combined index of CA-125, aPTT, and D-dimer is a valid noninvasive preoperative method for the evaluation of moderate and severe OEM, and may help to decrease the interval between the first complaint and a definitive diagnosis.

Impact of Haemodialysis on Coagulation Profile in Chronic Kidney Disease

Background&#x0D; Chronic kidney disease (CKD) with its high prevalence, morbidity and mortality is an important public health problem. Considering the nature of the haemodialysis process, it has a considerable impact on the coagulation profile. To find out the variations in Platelet count, Prothrombin time (PT), International Normalised Ratio (INR) and Activated Partial Thromboplastin Time (aPTT) before and after haemodialysis patients.&#x0D; Materials and Methods: &#x0D; This prospective observational study of Coagulation profile and platelet count in pre and post hemodialysis patients with chronic renal failure was conducted on 150 CKD patients in the Department of Pathology, SRM Medical College Hospital &amp; Research Centre. p value &lt;0.05 was considered to be statistically significant.&#x0D; Results&#x0D; In this study, there was significant reduction in platelet count from mean 2.29 cells/cu.mm in pre dialysis to 2.03 cell/cu.mm in post dialysis. There was a significant prolongation in both PT and aPTT values in post dialysis&#x0D; Conclusion&#x0D; These findings expose CKD patients to higher risk of bleeding disorders, which may have a role in increasing the rate of patient mortality and morbidity. In the light of this study, there is a need for nephrologist to monitor the coagulation profile and platelet count of CKD patients on dialysis, and treat any derangements in the same, so as to improve outcome for these patients.

Investigation of the Value of Coagulation Parameters in Thromboembolic Events Among Patients Not Receiving Anticoagulant Therapy

Objective: The main causes of thromboembolic events are atherosclerosis, vascular endothelial injury, and hypercoagulability. Coagulation is activated through two basic mechanisms, including intrinsic and extrinsic pathways, leading to thrombin production as a result of a series of enzymatic reactions. The intrinsic pathway is evaluated with activated partial thromboplastin time (aPTT) and extrinsic pathway with prothrombin time (PT). This study aimed to investigate the relationship between thromboembolic diseases and coagulation parameters.&#x0D; Material and Methods: Patients diagnosed with acute ischemic stroke (AIS) (n=216), acute coronary syndrome (ACS) (n=25), pulmonary thromboembolism (PTE) (n=15), and patients without an emergency pathology (n=71) (Control Group) in the emergency department were retrospectively reviewed in the period from 01 November 2016 to 31 March 2019.&#x0D; Results: The aPTT (25.61±5.93 sec), PT (12.05±2.26 sec), and INR (1.04±0.19) values of the AIS group were statistically significantly lower compared to values of the control group (p = ˂0.001, ˂0.001 and ˂0.001 respectively). Similarly, the aPTT (27.15±8.97 sec), PT (12.26±2.75 sec), and INR (1.03±0.25) values of the ACS group were statistically significantly lower compared to those of the control group (p=0.012, 0.030, and 0.001, respectively). There was no statistically significant difference between the PTE group and control group in terms of aPTT, PT, and INR values (p= 0.133, 0.758, and 0.711, respectively).&#x0D; Conclusion: Shortened aPTT levels in cases without a history of anticoagulant use at the time of admission can be considered to be a predictive and effective tool for clinicians in arterial embolic events (AIS and ACS).