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Sensors (Basel, Switzerland) Apr 2021Prothrombin time (PT) is a significant coagulation (hemostasis) biomarker used to diagnose several thromboembolic and hemorrhagic complications based on its direct... (Review)
Review
Prothrombin time (PT) is a significant coagulation (hemostasis) biomarker used to diagnose several thromboembolic and hemorrhagic complications based on its direct correlation with the physiological blood clotting time. Among the entire set of PT dependents, candidates with cardiovascular ailments are the major set of the population requiring lifelong anticoagulation therapy and supervised PT administration. Additionally, the increasing incidence of COVID affected by complications in coagulation dynamics has been strikingly evident. Prolonged PT along with sepsis-induced coagulopathy (SIC score > 3) has been found to be very common in critical COVID or CAC-affected cases. Considering the growing significance of an efficient point-of-care PT assaying platform to counter the increasing fatalities associated with cardio-compromised and coagulation aberrations propping up from CAC cases, the following review discusses the evolution of lab-based PT to point of care (PoC) PT assays. Recent advances in the field of PoC PT devices utilizing optics, acoustics, and mechanical and electrochemical methods in microsensors to detect blood coagulation are further elaborated. Thus, the following review holistically aims to motivate the future PT assay designers/researchers by detailing the relevance of PT and associated protocols for cardio compromised and COVID affected along with the intricacies of previously engineered PoC PT diagnostics.
Topics: Blood Coagulation Tests; COVID-19; Humans; International Normalized Ratio; Prothrombin Time; SARS-CoV-2
PubMed: 33918646
DOI: 10.3390/s21082636 -
Biosensors & Bioelectronics Jan 2021With an increasing number of patients relying on blood thinners to treat medical conditions, there is a rising need for rapid, low-cost, portable testing of blood...
With an increasing number of patients relying on blood thinners to treat medical conditions, there is a rising need for rapid, low-cost, portable testing of blood coagulation time or prothrombin time (PT). Current methods for measuring PT require regular visits to outpatient clinics, which is cumbersome and time-consuming, decreasing patient quality of life. In this work, we developed a handheld point-of-care test (POCT) to measure PT using electrical transduction. Low-cost PT sensors were fully printed using an aerosol jet printer and conductive inks of Ag nanoparticles, Ag nanowires, and carbon nanotubes. Using benchtop control electronics to test this impedance-based biosensor, it was found that the capacitive nature of blood obscures the clotting response at frequencies below 10 kHz, leading to an optimized operating frequency of 15 kHz. When printed on polyimide, the PT sensor exhibited no variation in the measured clotting time, even when flexed to a 35 mm bend radius. In addition, consistent PT measurements for both chicken and human blood illustrate the versatility of these printed biosensors under disparate operating conditions, where chicken blood clots within 30 min and anticoagulated human blood clots within 20-100 s. Finally, a low-cost, handheld POCT was developed to measure PT for human blood, yielding 70% lower noise compared to measurement with a commercial potentiostat. This POCT with printed PT sensors has the potential to dramatically improve the quality of life for patients on blood thinners and, in the long term, could be incorporated into a fully flexible and wearable sensing platform.
Topics: Biosensing Techniques; Humans; Metal Nanoparticles; Nanotubes, Carbon; Point-of-Care Systems; Point-of-Care Testing; Prothrombin Time; Quality of Life; Silver
PubMed: 33157410
DOI: 10.1016/j.bios.2020.112770 -
Anesthesiology Oct 2021From preoperative medications to intraoperative needs to postoperative thromboprophylaxis, anticoagulants are encountered throughout the perioperative period. This... (Review)
Review
From preoperative medications to intraoperative needs to postoperative thromboprophylaxis, anticoagulants are encountered throughout the perioperative period. This review will focus on coagulation testing clinicians utilize to monitor the effects of these medications.
Topics: Anticoagulants; Blood Coagulation; Humans; International Normalized Ratio; Monitoring, Intraoperative; Perioperative Care; Physician's Role; Physicians; Point-of-Care Testing; Prothrombin Time
PubMed: 34499103
DOI: 10.1097/ALN.0000000000003903 -
Clinical and Applied... 2022The study investigates the diagnostic and prognostic significance of the prothrombin time/international normalized ratio (PT/INR) in patients with sepsis and septic...
OBJECTIVE
The study investigates the diagnostic and prognostic significance of the prothrombin time/international normalized ratio (PT/INR) in patients with sepsis and septic shock.
BACKGROUND
Sepsis may be complicated by disseminated intravascular coagulation (DIC). While the status of coagulopathy of septic patients is represented within the sepsis-3 definition by assessing the platelet count, less data regarding the prognostic impact of the PT/INR in patients admitted with sepsis and septic shock is available.
METHODS
Consecutive patients with sepsis and septic shock from 2019 to 2021 were included. Blood samples were retrieved from day of disease onset (ie, day 0), as well as on day 1, 2, 4, 6 and 9 thereafter. Firstly, the diagnostic value of the PT/INR in comparison to the activated partial thromboplastin time (aPTT) was tested for septic shock compared to sepsis without shock. Secondly, the prognostic value of the PT/INR for 30-day all-cause mortality was tested. Statistical analyses included univariable t-tests, Spearman's correlations, C-statistics, Kaplan-Meier analyses and Cox proportional regression analyses.
RESULTS
338 patients were included (56% sepsis without shock, 44% septic shock). The overall rate of all-cause mortality at 30 days was 52%. With an area under the curve (AUC) of 0.682 (= .001) on day 0, the PT/INR revealed moderate discrimination of septic shock and sepsis without shock. Furthermore, PT/ INR was able to discriminate non-survivors and survivors at 30 days (AUC = 0.612; = .001). Patients with a PT/INR >1.5 had higher rates of 30-day all-cause mortality than patients with lower values (mortality rate 73% vs 48%; log rank = .001; HR = 2.129; 95% CI 1.494-3.033; = .001), even after multivariable adjustment (HR = 1.793; 95% CI 1.343-2.392; = .001). Increased risk of 30-day all-cause mortality was observed irrespective of concomitant thrombocytopenia.
CONCLUSION
The PT/INR revealed moderate diagnostic accuracy for septic shock but was associated with reliable prognostic accuracy with regard to 30-day all-cause mortality in patients admitted with sepsis and septic shock.
Topics: Humans; Prothrombin Time; Shock, Septic; International Normalized Ratio; Prognosis; Sepsis; Retrospective Studies
PubMed: 36503298
DOI: 10.1177/10760296221137893 -
Journal of Veterinary Internal Medicine May 2019The chromogenic anti-Xa assay, the gold standard for monitoring the anti-Xa effect of rivaroxaban, is not available as a cage-side diagnostic test for use in a clinical...
BACKGROUND
The chromogenic anti-Xa assay, the gold standard for monitoring the anti-Xa effect of rivaroxaban, is not available as a cage-side diagnostic test for use in a clinical setting.
HYPOTHESIS/OBJECTIVES
To evaluate clinical modalities for measuring the anticoagulant effects of rivaroxaban using a point-of-care prothrombin time (PT) and thromboelastography (TEG).
ANIMALS
Six healthy Beagle dogs.
METHODS
Prospective, experimental study. Four different doses of rivaroxaban (0.5, 1, 2, and 4 mg/kg) were administered PO to dogs. Single PO and 3 consecutive dosing regimens also were assessed. Plasma rivaroxaban concentration was determined using a chromogenic anti-Xa assay, point-of-care PT, and TEG analysis with 4 activators (RapidTEG, 1 : 100 tissue factor [TF100], 1 : 3700 tissue factor [TF3700], and kaolin), and results were compared. Spearman correlation coefficients were calculated between ratios (peak to baseline PT; peak reaction time [R] of TEG to baseline [R] of TEG) and anti-Xa concentration.
RESULTS
Anti-Xa concentration had a significant correlation with point-of-care PT (R = 0.82, P < .001) and RapidTEG-TEG, TF100-TEG, and TF3700-TEG (R = 0.76, P < .001; R = 0.82, P < .001; and R = 0.83, P < .001, respectively).
CONCLUSIONS AND CLINICAL IMPORTANCE
Overall, a 1.5-1.9 × delay in PT and R values of TEG 3 hours after rivaroxaban administration is required to achieve therapeutic anti-Xa concentrations of rivaroxaban in canine plasma. The R values of TEG, specifically using tissue factors (RapidTEG, TF100, TF3700) and point-of-care PT for rivaroxaban can be used practically for therapeutic monitoring of rivaroxaban in dogs.
Topics: Animals; Dogs; Factor Xa Inhibitors; Male; Prospective Studies; Prothrombin Time; Rivaroxaban; Thrombelastography
PubMed: 30859645
DOI: 10.1111/jvim.15478 -
Annals of the Academy of Medicine,... Apr 2021Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Coronavirus disease 2019 (COVID-19)-induced coagulopathy (CIC) has been widely reported in the literature. However, the spectrum of abnormalities associated with CIC has been highly variable.
METHODS
We conducted a systematic review of the literature (until 1 June 2020) to assess CIC and disease severity during the early COVID-19 pandemic. Primary outcomes were pooled mean differences in platelet count, D-dimer level, prothrombin time, activated partial thromboplastin time (aPTT) and fibrinogen level between non-severe and severe patients, stratified by degree of hypoxaemia or those who died. The risk factors for CIC were analysed. Random-effects meta-analyses and meta-regression were performed using R version 3.6.1, and certainty of evidence was rated using the Grading of Recommendation, Assessment, Development, and Evaluation approach.
RESULTS
Of the included 5,243 adult COVID-19 patients, patients with severe COVID-19 had a significantly lower platelet count, and higher D-dimer level, prothrombin time and fibrinogen level than non-severe patients. Pooled mean differences in platelet count (-19.7×109/L, 95% confidence interval [CI] -31.7 to -7.6), D-dimer level (0.8μg/mL, 95% CI 0.5-1.1), prothrombin time (0.4 second, 95% CI 0.2-0.6) and fibrinogen level (0.6g/L, 95% CI 0.3-0.8) were significant between the groups. Platelet count and D-dimer level were significant predictors of disease severity on meta-regression analysis. Older men had higher risks of severe coagulopathic disease.
CONCLUSION
Significant variability in CIC exists between non-severe and severe patients, with platelet count and D-dimer level correlating with disease severity. Routine monitoring of all coagulation parameters may help to assess CIC and decide on the appropriate management.
Topics: Adult; Aged; Blood Coagulation Disorders; COVID-19; Humans; Male; Pandemics; Prothrombin Time; SARS-CoV-2
PubMed: 33990820
DOI: 10.47102/annals-acadmedsg.2020420 -
International Journal of Laboratory... Apr 2022The definition of the International Normalized Ratio (INR) depends on a reference measurement procedure for the prothrombin time (PT) determined with international...
INTRODUCTION
The definition of the International Normalized Ratio (INR) depends on a reference measurement procedure for the prothrombin time (PT) determined with international standards for thromboplastins. The agreed water bath temperature for PT determination in the reference measurement procedure is 37°C. The aim of the study was to assess the influence of small deviations of the agreed reaction temperature on PT and INR determined with World Health Organization international standards for thromboplastins rTF/16 (recombinant human) and RBT/16 (rabbit brain).
METHODS
Prothrombin time was determined, with a manual hook technique, in glass test tubes in a water bath at a controlled temperature. The PT reaction temperatures were varied between 28 and 40°C. Pooled normal plasma and pooled coumarin plasma (INR ≈ 2.8) were used as test plasmas. The data were fitted to a quadratic relationship between PT and temperature.
RESULTS
Prothrombin times with rTF/16 were shortened by increasing the reaction temperature up to approximately 39-40°C. PTs with RBT/16 were shortened by increasing the reaction temperature up to approximately 34-37°C, but were prolonged at higher temperatures. The apparent INR change of the coumarin plasma at 37.0°C was 0.06/°C and 0.11/°C for rTF/16 and RBT/16, respectively.
CONCLUSIONS
Reaction temperature had a significant effect on PT and the apparent INR with the International Standards. At 37.0°C, the apparent INR of coumarin plasma determined with RBT/16 was more responsive to temperature change than the apparent INR determined with rTF/16. The required accuracy of the water bath temperature should be 37.0 ± 0.1°C.
Topics: Animals; Anticoagulants; Calibration; Humans; International Normalized Ratio; Prothrombin Time; Rabbits; Reference Standards; Temperature; Thromboplastin
PubMed: 34747561
DOI: 10.1111/ijlh.13737 -
Clinical and Applied... 2020To investigate changes in coagulation during twin pregnancies. Methods: A total of 108 women with twin pregnancies and 442 women with singleton pregnancies were...
To investigate changes in coagulation during twin pregnancies. Methods: A total of 108 women with twin pregnancies and 442 women with singleton pregnancies were recruited. Coagulation tests, including fibrinogen (Fib), activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT), were performed during the course of the pregnancy. The level of fibrinogen gradually increased during singleton pregnancies, while the APTT and PT levels showed a decreasing trend with increasing gestational weeks. In twin pregnancies, the changes in PT and TT were similar, but other parameters displayed a different trend. Fibrinogen showed no significant difference between the second and third trimesters, while APTT showed an increasing trend from the second trimester to the third trimester. Compared with singleton pregnancies, the level of fibrinogen was higher in women pregnant with twins. APTT was longer in women pregnant with twins than in women with singleton pregnancies in the third trimester. PT was shorter in women pregnant with twins than in women with singleton pregnancies in the first and third trimesters. TT was shorter in women pregnant with twins than in women with singleton pregnancies in the first and second trimesters. Through this retrospective longitudinal analysis, this study presents the main coagulation parameter changes in singleton and twin pregnancies and confirms that coagulation is more enhanced in twin pregnancies than in singleton pregnancies.
Topics: Adult; Blood Coagulation; Blood Coagulation Tests; Female; Fibrinogen; Humans; Partial Thromboplastin Time; Pregnancy; Pregnancy, Twin; Prothrombin Time; Retrospective Studies
PubMed: 33372546
DOI: 10.1177/1076029620983898 -
American Journal of Veterinary Research Jul 2022To assess the safety and efficacy of the platelet-like nanoparticle (PLN), and to assess its safety in repeated administration.
OBJECTIVE
To assess the safety and efficacy of the platelet-like nanoparticle (PLN), and to assess its safety in repeated administration.
ANIMALS
6 purpose-bred dogs.
PROCEDURES
The PLN was administered IV at 3 different doses using a randomized crossover design. Each dog received a full dose of 8 X 1010 particles/10 kg, half dose, and 10 times the dose, with a 14-day washout period between doses. Biochemical, prothrombin time, partial thromboplastin time, and fibrinogen analyses were performed at baseline and 96 hours postinfusion. A CBC, kaolin-activated thromboelastography, platelet function assay closure time, and buccal mucosal bleeding time were performed at baseline and 1, 6, 24, 48, 72, and 96 hours postinfusion.
RESULTS
No significant changes were observed over time in the thromboelastography parameters, closure time, and buccal mucosal bleeding time. After the administration of the half dose, hematocrit levels decreased significantly at 1, 6, 24, 48, and 96 hours, with all values within the reference range. The platelet count was decreased significantly at hours 1, 6, 24, 48, and 72 after administration of the half dose, with values less than the reference range at all hours but hour 72. No significant changes in serum biochemistry, coagulation panel, and fibrinogen were observed for all doses. No adverse events were noted during the first infusion. Three dogs experienced transient sedation and nausea after repeat infusion.
CLINICAL RELEVANCE
The PLN resulted in a dilution of hematocrit and platelets, and did not significantly alter hemostasis negatively. The safety of repeated doses should be investigated further in dogs.
Topics: Animals; Dogs; Fibrinogen; Hemostasis; Nanoparticles; Partial Thromboplastin Time; Prothrombin Time; Thrombelastography
PubMed: 35895758
DOI: 10.2460/ajvr.22.04.0069 -
Scandinavian Journal of Trauma,... Mar 2017Fibrinogen and prothrombin have been suggested to become rate limiting in trauma associated coagulopathy. Administration of fibrinogen is now recommended, however, the... (Observational Study)
Observational Study
Prothrombin time is predictive of low plasma prothrombin concentration and clinical outcome in patients with trauma hemorrhage: analyses of prospective observational cohort studies.
BACKGROUND
Fibrinogen and prothrombin have been suggested to become rate limiting in trauma associated coagulopathy. Administration of fibrinogen is now recommended, however, the importance of prothrombin to patient outcome is unknown.
METHODS
We have utilized two trauma patient databases (database 1 n = 358 and database 2 n = 331) to investigate the relationship of plasma prothrombin concentration on clinical outcome and coagulation status. Database 1 has been used to assess the relationship of plasma prothrombin to administered packed red blood cells (PRBC), clinical outcome and coagulation biomarkers (Prothrombin Time (PT), ROTEM EXTEM Coagulation Time (CT) and Maximum Clot Firmness (MCF)). ROC analyses have been performed to investigate the ability of admission coagulation biomarkers to predict low prothrombin concentration (database 1), massive transfusion and 24 h mortality (database 1 and 2). The importance of prothrombin was further investigated in vitro by PT and ROTEM assays in the presence of a prothrombin neutralizing monoclonal antibody and following step-wise dilution.
RESULTS
Patients who survived the first 24 h had higher admission prothrombin levels compared to those who died (94 vs.67 IU/dL). Patients with lower transfusion requirements within the first 24 h (≤10 units of PRBCs) also had higher admission prothrombin levels compared to patients with massive transfusion demands (>10 units of PRBCs) (95 vs.62 IU/dL). Admission PT, in comparison to admission ROTEM EXTEM CT and MCF, was found to be a better predictor of prothrombin concentration <60 IU/dL (AUC 0.94 in database 1), of massive transfusion (AUC 0.92 and 0.81 in database 1 and 2 respectively) and 24 h mortality (AUC 0.90 and 0.78 in database 1 and 2, respectively). In vitro experiments supported a critical role for prothrombin in coagulation and demonstrated that PT and ROTEM EXTEM CT are sensitive methods to measure low prothrombin concentration.
DISCUSSION
Our analyses suggest that prothrombin concentration at admission is predictive of mortality and transfusion and indicates that prothrombin and fibrinogen are rate limiting in coagulopathy.
CONCLUSIONS
Admission PT is predictive of low prothrombin concentration and clinical outcome. PT could therefore be used as a surrogate for prothrombin concentration and further evaluation of point-of-care devices for faster PT analysis is warranted.
Topics: Adult; Female; Hemorrhage; Humans; Hypoprothrombinemias; Male; Middle Aged; Plasma; Predictive Value of Tests; Prospective Studies; Prothrombin Time; Treatment Outcome; Young Adult
PubMed: 28292321
DOI: 10.1186/s13049-016-0332-2