A practical predictive model to predict 30-day mortality in neonatal sepsis

SUMMARY OBJECTIVE: Neonatal sepsis is a serious disease that needs timely and immediate medical attention. So far, there is no specific prognostic biomarkers or model for dependable predict outcomes in neonatal sepsis. The aim of this study was to establish a predictive model based on readily available laboratory data to assess 30-day mortality in neonatal sepsis. METHODS: Neonates with sepsis were recruited between January 2019 and December 2022. The admission information was obtained from the medical record retrospectively. Univariate or multivariate analysis was utilized to identify independent risk factors. The receiver operating characteristic curve was drawn to check the performance of the predictive model. RESULTS: A total of 195 patients were recruited. There was a big difference between the two groups in the levels of hemoglobin and prothrombin time. Multivariate analysis confirmed that hemoglobin>133 g/L (hazard ratio: 0.351, p=0.042) and prothrombin time >16.6 s (hazard ratio: 4.140, p=0.005) were independent risk markers of 30-day mortality. Based on these results, a predictive model with the highest area under the curve (0.756) was built. CONCLUSION: We established a predictive model that can objectively and accurately predict individualized risk of 30-day mortality. The predictive model should help clinicians to improve individual treatment, make clinical decisions, and guide follow-up management strategies.

Comparing modified Lee and White method against 20-minute whole blood clotting test as bedside coagulation screening test in snake envenomation victims.

Background: Twenty-minute whole blood clotting test (20WBCT) and Modified Lee and White (MLW) method are the most routinely employed bedside tests for detecting coagulopathic snake envenomation. Our study compared the diagnostic utility of MLW and 20WBCT for snakebite victims at a tertiary care hospital in Central Kerala, South India. Methods: This single-center study recruited 267 patients admitted with snake bites. 20WBCT and MLW were performed simultaneously at admission along with the measurement of Prothrombin Time (PT). The diagnostic utility of 20WBCT and MLW was determined by comparing the sensitivity (Sn), specificity (Sp), positive and negative predictive values, likelihood ratios, and accuracy at admission with an INR value > 1.4. Results: Out of 267 patients, 20 (7.5%) patients had VICC. Amongst those who had venom-induced consumption coagulopathy (VICC), MLW was prolonged for 17 patients, (Sn 85% 95% confidence interval [CI]: 61.1-96.0) whereas 20WBCT was abnormal for 11 patients (Sn 55%, 95% CI: 32.04-76.17). MLW and 20WBCT were falsely positive for the same patient (Sp 99.6%, 95% CI: 97.4-99.9%). Conclusion: MLW is more sensitive than 20WBCT to detect coagulopathy at the bedside amongst snakebite victims. However, further studies are necessary for standardizing bedside coagulation tests in snakebite cases.

Evaluación preoperatoria de la hemostasia en cirugía mayor electiva / Preoperative evaluation of hemostasis in elective major surgery

Resumen: Introducción: Las pruebas de coagulación carecen de valor para determinar el riesgo de sangrado perioperatorio. Material y métodos: Se realizó un estudio observacional, descriptivo, y transversal en 2,114 pacientes en la consulta de Anestesiología del Hospital Universitario «Dr. Celestino Hernández Robau¼, los resultados se evaluaron mediante estadística descriptiva. Resultados: El tiempo de coagulación y sangrado se realizó en 100% de los casos y el conteo de plaquetas en 93.99%, mientras que el tiempo de protrombina y tiempo de tromboplastina parcial activado se efectuó en 66.27 y 55.62% de los casos respectivamente. De 8.834 exámenes realizados se encontraron 49 alterados en 0.55%. Los pacientes con exámenes alterados fueron 33 en 1.56%, los enfermos en riesgo de sangrado por exámenes de coagulación fueron 30 en 1.42% y los pacientes en riesgo sin antecedentes de sangrados detectados por exámenes de coagulación fueron tres en 0.14%. Se reportó sangrado perioperatorio en 16 pacientes en 0.76%, siete pacientes con interrogatorio positivo y exámenes normales y nueve pacientes con interrogatorio negativo y exámenes normales. Conclusiones: La historia clínica y el examen físico del paciente son las mejores herramientas para predecir el riesgo de sangrado quirúrgico y los exámenes aislados de coagulación no constituyen un buen predictor del sangrado perioperatorio.

Abstract: Introduction: Coagulation tests are no value to determine the risk of perioperative bleeding. Material and methods: An observational descriptive cross-sectional study was carried out in 2,114 patients in the anesthesiology consultation of the University Hospital «Dr. Celestino Hernández Robau¼. Results: The clotting and bleeding time was performed in 100% of cases, the platels count in 93.99%. While the prothrombin time and activated partial tromboplastin time were performed in 66.27 and 55.62% respectively. Of 8,834 tests carried out, 49 were found to be altered for 0.55%. Patients with altered tests were for 1.56%, patients at risk of bleeding from coagulation tests were 30 for 1.42% and patients at risk with no history of bleeding detected by coagulation tests were three for 0.14%. Perioperative bleeding was reported in 16 patients for 0.76%, seven patients with positive questioning and normal tests and nine patients with negative questioning and normal tests. Conclusions: The patient's medical history and physical examination are the best tools to predict the risk of surgical bleeding and isolated coagulation tests do not constitute a good predictor of perioperative bleeding.

Deficiencia congénita de factor VII / Congenital factor VII deficiency

Resumen La deficiencia congénita de factor VII es uno de los desórdenes congénitos de la coagulación más comunes, con una prevalencia a nivel mundial de 1:300,000- 1:500,000. Se presenta el caso de un paciente masculino de 37 semanas y 5 días, nacido por cesárea intraparto y con el antecedente heredofamiliar de muerte de hermano a los 4 días de nacido por hemorragia intracraneal, quien a los 14 días de nacido es llevado a emergencias por sangrado umbilical que persistía después del desprendimiento del cordón. Su abordaje inicial incluyó la toma de tiempos de coagulación, lo que mostró alteración del tiempo de protrombina con tiempo de tromboplastina parcial y fibrinógeno normales. El sangrado, así como el tiempo de protrombina prolongado, persistió a pesar de que se administrara vitamina K en tres ocasiones y de transfundir plasma fresco congelado. Se sospechó defecto congénito de factor VII, que se confirmó con la cuantificación del factor. A los 2 meses y 10 días de edad, se le realizaron estudios moleculares basados en secuenciación masiva de nueva generación (NGS por sus siglas en inglés). El análisis determinó dos variantes heterocigotas: F7, intrón 5, c.430+1G>A y F7, intrón 8, c.805+1G>A. Actualmente, el paciente se maneja con profilaxis 5 días de la semana con factor VII recombinante 200 µg/día intravenoso (280 µg/kg) sin recurrencia de sangrados.

Abstract Factor VII congenital deficiency is one of the most common congenital deficiencies of the blood system, with a worldwide prevalence of 1:300,000- 1:500,000. Here we describe a male patient, born by C section, with the family history of death at 4 days old of a sibling caused by intracranial hemorrhage, who presented bleeding at the umbilical cord site at 14 days old, even after falling of the cord. The initial assessment included laboratory tests with coagulation times revealing prolonged prothrombin time, with normal partial thromboplastin time as well as fibrinogen. The bleeding and the prolonged prothrombin time persisted despite the administration of vitamin K in three doses as well as fresh frozen plasma. Congenital defect of factor VII was suspected and later confirmed by measuring the factor. At the age of 2 months and 10 days, molecular studies based on next-generation massive sequencing (NGS) were performed. The analysis exhibited two heterozygous variants: F7, intron 5, c.430+1G>A y F7, intron 8, c.805+1G>A. Currently the patient is receiving prophylaxis 5 days per week with recombinant factor VII 200 µg/ day intravenous (280 µg/kg) with no recurrent bleeding.

Comparing modified Lee and White method against 20-minute whole blood clotting test as bedside coagulation screening test in snake envenomation victims

Abstract Background: Twenty-minute whole blood clotting test (20WBCT) and Modified Lee and White (MLW) method are the most routinely employed bedside tests for detecting coagulopathic snake envenomation. Our study compared the diagnostic utility of MLW and 20WBCT for snakebite victims at a tertiary care hospital in Central Kerala, South India. Methods: This single-center study recruited 267 patients admitted with snake bites. 20WBCT and MLW were performed simultaneously at admission along with the measurement of Prothrombin Time (PT). The diagnostic utility of 20WBCT and MLW was determined by comparing the sensitivity (Sn), specificity (Sp), positive and negative predictive values, likelihood ratios, and accuracy at admission with an INR value > 1.4. Results: Out of 267 patients, 20 (7.5%) patients had VICC. Amongst those who had venom-induced consumption coagulopathy (VICC), MLW was prolonged for 17 patients, (Sn 85% 95% confidence interval [CI]: 61.1-96.0) whereas 20WBCT was abnormal for 11 patients (Sn 55%, 95% CI: 32.04-76.17). MLW and 20WBCT were falsely positive for the same patient (Sp 99.6%, 95% CI: 97.4-99.9%). Conclusion: MLW is more sensitive than 20WBCT to detect coagulopathy at the bedside amongst snakebite victims. However, further studies are necessary for standardizing bedside coagulation tests in snakebite cases.

Estandarización del índice internacional normalizado en pacientes pre-quirúrgicos del Hospital San Juan de Dios de Cuenca / Standarization of the Internacional Normalized Index in pre-surgical patients at Hospital San Juan de Dios of Cuenca / Padronização do Índice Normalizado Internacional em pacientes pré-cirúrgicos do Hospital San Juan de Dios em Cuenca

El índice internacional normalizado (INR, por sus siglas en inglés), es un tipo de cálculo matemático que se basa en las pruebas de tiempo de protrombina. La seguridad y eficacia de la terapia dependen del efecto anticoagulante que reciban dentro del margen terapéutico fijado por el médico en base al estudio de sus tiempos de coagulación, específicamente expresado como el intervalo de INR. Establecer los rangos de referencia del INR aplicado en resultados obtenidos en pacientes del sexo masculino y femenino en edades entre los 18 hasta 60 años de edad en el Hospital San Juan de Dios de Cuenca, durante los meses de enero a junio del año 2021. Los datos fueron recopilados de 699 pacientes que acudieron a consulta externa del Hospital San Juan de Dios de Cuenca del área de hematología, que incluyen valores de tiempo de tromboplastina y su referente INR en base al ISI establecido en el reactivo emitido por el fabricante. Se establecieron los valores normales de INR los cuales varían en referencia al sexo del paciente. Para el sexo masculino valores con límite inferior 0,82 y límite superior 1,16; para el sexo femenino con límite inferior de 0,51 y el límite superior de 1,51. Los valores de INR tienen variaciones de acuerdo al sexo siendo los valores de hombres mas altos en relación al de las mujeres en el rango inferiores, Evidentemente los factores influyentes van en relación del sexo, edad, dieta y sobretodo la genética del paciente.

The International Normalized Ratio (INR) is a type of mathematical calculation based on prothrombin time testing. The safety and efficacy of therapy depend on the anticoagulant effect they receive within the therapeutic range set by the physician based on the study of their clotting times, specifically expressed as the INR range. To establish the reference ranges of the INR applied in results obtained in male and female patients between 18 and 60 years of age at the San Juan de Dios Hospital in Cuenca, during the months of January to June 2021. The data were collected from 699 patients who attended the outpatient clinic of the Hospital San Juan de Dios de Cuenca in the hematology area, including thromboplastin time values and their INR referent based on the ISI established in the reagent issued by the manufacturer. Normal INR values were established, which vary according to the patient's sex. For the male sex values with a lower limit of 0.82 and an upper limit of 1.16; for the female sex with a lower limit of 0.51 and an upper limit of 1.51. The INR values vary according to sex, with the values for men being higher in relation to those for women in the lower range. Evidently, the influencing factors are related to sex, age, diet and above all the patient's genetics.

A Relação Internacional Normalizada (INR) é um tipo de cálculo matemático baseado em testes de tempo de protrombina. A segurança e eficácia da terapia depende do efeito anticoagulante que recebem dentro da faixa terapêutica estabelecida pelo médico com base no estudo de seus tempos de coagulação, expressa especificamente como a faixa INR. Estabelecer as faixas de referência do INR aplicadas em resultados obtidos em pacientes do sexo masculino e feminino com idade entre 18 e 60 anos no Hospital San Juan de Dios em Cuenca, durante os meses de janeiro a junho de 2021. Os dados foram coletados de 699 pacientes que compareceram ao ambulatório do Hospital San Juan de Dios de Cuenca na área de hematologia, incluindo os valores de tempo de tromboplastina e sua referência INR baseada no ISI estabelecido no reagente emitido pelo fabricante. Foram estabelecidos valores normais de INR, que variam de acordo com o sexo do paciente. Para o sexo masculino, com um limite inferior de 0,82 e um limite superior de 1,16; para o sexo feminino, com um limite inferior de 0,51 e um limite superior de 1,51. Os valores de INR variam de acordo com o sexo, sendo os valores para os homens maiores em relação àqueles para as mulheres na faixa inferior. Evidentemente, os fatores de influência estão relacionados ao sexo, idade, dieta e, acima de tudo, à genética do paciente.

CoaguChek® XS versus standard laboratory prothrombin time for anticoagulant monitoring in patients with antiphospholipid syndrome.

INTRODUCTION: The standard of care for thrombotic antiphospholipid syndrome (APS) is anticoagulation with vitamin K antagonists (VKAs). Prothrombin time, and its corresponding international normalized ratio (INR), is the laboratory test routinely performed to assess anticoagulation. Self-management of VKA therapy using point-of-care (POC) devices seems to be an attractive option. PURPOSE/OBJECTIVE: To evaluate the accuracy of a POC device (CoaguChek XS) in APS patients by comparing it with venous laboratory INR. Furthermore, we analyzed whether other clinical and laboratory features could interfere with the CoaguChek XS results. PATIENTS AND METHODS: This is a single-center cross-sectional study with 94 APS patients from a tertiary rheumatology clinic performed from August 2014 to March 2015. The comparison between CoaguChek XS and venous laboratory INR results was evaluated using the coefficient of determination (r) followed by the Bland-Altman test. A paired t-test was also applied. A difference of up to ±0.5 INR unit between the two systems was considered clinically acceptable. RESULTS: The mean CoaguChek-INR was 2.94 ± 1.41 and venous laboratory INR was 2.43±0.86, with a correlation coefficient (r) of 0.95. Categorizing INR values in ranges (INR <2, INR 2-3, INR 3-4, and INR >4), we found that the INR >4 group presented a lower correlation (r = 0.64) compared to the other ranges (p < 0.05). Although both methods were highly correlated, CoaguChek XS showed higher values than the venous laboratory INR, with an increased average of 0.42 ± 0.54. Therefore, we proposed a simple linear regression model to predict the venous laboratory INR values, using results obtained from CoaguChek XS. A difference ≤0.5 INR unit between the two systems was observed in 57.4% of patients, and the aPL profile did not influence the results. CONCLUSION: Although CoaguChek XS and venous laboratory INR demonstrated a good linear correlation in the group of INR ≤4, extra caution should be taken in APS patients, since a reasonable proportion of patients can present differences in INR results that are not acceptable. We do not recommend routine POC in APS patients.

Actividad anticoagulante in vitro del extracto etanólico de las hojas de dos especies de la familia Euphorbiaceae / In vitro anticoagulant activity of the ethanolic extract of the leaves of two species of the family Euphorbiaceae

RESUMEN Las enfermedades cardiovasculares (ECV) son un conjunto de trastornos del corazón y de los vasos sanguíneos, que constituyen la principal causa de mortalidad en el mundo. En la búsqueda de alternativas para esta problemática, plantas medicinales de la familia Euphorbiaceae, han sido empeladas con fines terapéuticos, para prevenir, atenuar o curar los efectos generados por estas enfermedades. El objetivo de este trabajo fue conocer el perfil fitoquímico y evaluar la actividad anticoagulante in vitro de los extractos etanólicos de las hojas de Croton malambo y Acalypha hispida sobre plasma humano. Para ello, se obtuvo el extracto de las hojas y se le realizó el tamizaje fitoquímico, la evaluación del Tiempo de Tromboplastina Parcial activada (TTPa) y del Tiempo de Protombina (TP). En el perfil fitoquímico, se confirmó la presencia de alcaloides, taninos, flavonoides, leucoantocianidinas, fenoles, sesquiterpenlactonas, glucósidos cardiotónicos y terpenos. En la actividad anticoagulante, se evidenció la inhibición de la coagulación en la vía intrínseca, obteniendo resultados significativos para el TTPa, a diferencia que el test TP, donde los resultados obtenidos se encontraron similares al control. Esta investigación demuestra la acción anticoagulante de las plantas, ya que induce, significativamente, a una mayor prolongación del tiempo de coagulación; ambas especies presentaron una mayor actividad, a 200 mg/mL.

ABSTRACT Cardiovascular diseases (CVD) are a group of disorders of the heart and blood vessels, which correspond to the principal causes of death in the world. In the search for alternatives to this problem, medicinal plants of the Euphorbiaceae family have been investigated for therapeutic purposes to prevent, attenuate or cure the effects generated for these illnesses. The objective of this work was to know the phytochemical profile and evaluate the anticoagulant activity in vitro of the ethanolic extracts of the leaves of Croton malambo and Acalypha hispida on human plasma. For this, extract of their leaves was obtained, and phytochemical screening was performed, as well as the evaluation of the Activated Partial Thromboplastin Time (aPTT) and the Prothrombin Time (TP). The phytochemical profile confirmed the presence of alkaloids, tannins, flavonoids, leucoanthocyanidins, phenols, sesquiterpene lactones, cardiotonic glycosides, and terpenes. In the anticoagulant activity, the inhibition of coagulation in the intrinsic pathway was evidenced, obtaining significant results for aPTT, unlike the TP test where the results obtained were like the control. This research demonstrates the effectiveness of the plant with anticoagulant action since they significantly induce a longer prolongation of the clotting time, both species showed higher activity at 200 mg/mL.

Hemorragia digestiva en el contexto de una deficiencia aislada del factor VII: reporte de caso / Gastrointestinal bleeding in the context of isolated factor VII deficiency: case report

Introducción: Se conoce poco de la forma adquirida del déficit del factor VII y son pocos los casos reportados en la literatura. Objetivo: Presentar el caso de una paciente con déficit aislado del factor VII, en el contexto de una hemorragia digestiva baja. Presentación del caso: Mujer peruana de 82 años que acude a emergencia por presentar hemorragia digestiva baja. Durante los exámenes de rutina se le detecta tiempo de protrombina prolongado y déficit aislado de factor VII. No se evidencia mecanismos patológicos de deficiencia de vitamina K o malabsorción, terapia anticoagulante con antagonistas de la vitamina K, hiperfibrinolisis o coagulación intravascular diseminada. Respondió al tratamiento con plasma fresco congelado y los resultados normales de la prueba hematológica realizada a la hermana, alejan la posible etiología hereditaria. Conclusión: Este caso peruano de déficit aislado del factor VII, en el contexto de una hemorragia digestiva baja, permite sumar información a la escasa evidencia Latinoamericana(AU)

Introduction: Little is known about the acquired form of factor VII deficiency and few cases are reported in the literature. Objective: To present a case of a patient with an isolated deficit of factor VII, in the context of low gastrointestinal bleeding. Presentation of the case: 82-year-old Peruvian woman who comes to the emergency room for presenting with lower GI bleeding. Prolonged prothrombin time and isolated factor VII deficiency are detected during routine examinations. There were no evidence of pathological mechanisms of vitamin K deficiency or malabsorption, anticoagulant therapy with vitamin K antagonists, hyperfibrinolysis, or disseminated intravascular coagulation. She responded to the treatment with fresh frozen plasma and the normal results of the hematological test carried out on the sister remove the possible hereditary etiology. Conclusion: This Peruvian case of isolated factor VII deficit, in the context of low gastrointestinal bleeding, allows adding information to the limited Latin American evidence(AU)

Efecto de las diferentes drogas anticoagulantes sobre el ensayo de fibrinógeno derivado del tiempo de protrombina / Effect of different anticoagulant drugs on the prothrombin time-derived fibrinogen assay

Resumen El objetivo de este trabajo fue comparar los niveles de fibrinógeno (FBG) obtenidos por el método de Clauss con los obtenidos por el método de fibrinógeno derivado del tiempo de protrombina (FBG PT-d), con dos tromboplastinas, en pacientes anticoagulados con distintas drogas. Se estudiaron pacientes anticoagulados consecutivos: 105 con antagonistas de la vitamina K (AVK), 55 con heparina no fraccionada (HNF), 58 con heparina de bajo peso molecular (HBPM), 60 con rivaroxabán, 45 con apixabán, 60 con dabigatrán y 100 controles normales (CN). El FBG se determinó por el método de Clauss y FBG PT-d utilizando tromboplastina de cerebro de conejo o recombinante humana; los niveles de heparina, rivaroxabán y apixabán por método cromogénico anti Xa; el dabigatrán con el ensayo de tiempo de trombina diluido. Existió un sesgo positivo (p<0,001) al comparar el FBG PT-d vs. FBG por Clauss: CN: 13,7%, AVK: 31,8%, rivaroxabán: 34,8% y apixabán: 20,0% cuando se utilizó tromboplastina de conejo. En el caso de las muestras que contenían HBPM se observó este desvío con ambas tromboplastinas. El sesgo porcentual en presencia de dabigatrán y heparina no fraccionada no fue estadísticamente distinto del obtenido en el grupo control. El ensayo de FBG PT-d no debe utilizarse en pacientes anticoagulados con rivaroxabán, apixabán, HBPM o AVK, ya que sobreestima los niveles de FBG. El porcentaje de sesgo depende del tipo de tromboplastina utilizado y fue mayor con la de cerebro de conejo en el sistema de detección utilizado.

Abstract The aim of this study was to compare fibrinogen (FBG) results obtained by Clauss method (FBG-C) and by the prothrombin time-derived fibrinogen assay (FBG PT-d) with two thromboplastins in patients under anticoagulation. Consecutive anticoagulated patients were studied: 105 vitamin-K antagonist (VKA), 55 unfractioned heparin, 58 LMWH, 60 rivaroxaban, 45 apixaban and 60 dabigatran, and 100 healthy controls (NC). FBG-C was performed by Clauss and FIB PT-d with rabbit brain and human recombinant thromboplastins, respectively. Heparins, rivaroxaban and apixaban levels were measured by antiXa; dabigatran by thrombin diluted assay. A positive bias of FBG PT-d vs. FBG-C with both thromboplastins were seen in NC (13.7 and 19.0 % for HS and RP, respectively), but bias with HS in rivaroxaban, apixaban and VKA patients were significantly higher compared to NC: 34.8%, 20.0 % and 31.8 %, respectively. LMWH presented higher BIAS compared to NC with both thromboplastins. Samples with unfraction heparin and dabigatran presented similar bias to NC. FBG PT-d should not be used in patients under anticoagulant treatment because of an important overestimation of FBG could be obtained in these patients. The percentage of bias depends on the type of thromboplastin used; it was higher with rabbit brain thromboplastin in the detection system used.

Resumo O objetivo deste trabalho foi comparar os níveis de fibrinogênio (FBG) obtidos pelo método de Clauss com aqueles obtidos pelo método do fibrinogênio derivado do tempo de protrombina (FBG PT-d), com duas tromboplastinas, em pacientes anticoagulados com diferentes drogas. Pacientes anticoagulados consecutivos foram estudados: 105 com antagonista da vitamina K (AVK); 55 com heparina não fracionada (UFH); 58 com heparina de baixo peso molecular (HBPM), 60 com rivaroxabana, 45 com apixabana, 60 com dabigatrana e 100 controles normais (CN). FBG foi determinado pelo método de Clauss e FBG PT-d usando tromboplastina de cérebro de coelho ou tromboplastina humana recombinante; níveis de heparina, rivaroxabana e apixabana pelo método cromogênico anti-Xa; dabigatrana com ensaio de tempo de trombina diluída. Há um viés positivo (p<0,001) ao comparar o FBG PT-d vs FBG de Clauss: CN: 13,7%; AVK: 31,8%, rivaroxabana: 34,8% e apixabana 20,0% quando foi utilizada tromboplastina de coelho. No caso das amostras contendo HBPM, esse desvio foi observado com ambas as tromboplastinas. O viés percentual na presença de dabigatrana e heparina não fracionada não foi estatisticamente diferente daquela obtida no grupo controle. O ensaio de FBG PT-d não deve ser usado em pacientes anticoagulados com rivaroxabana, apixabana, LMWH ou VKA, pois superestima os níveis de FBG. A porcentagem de viés depende do tipo de tromboplastina utilizado e foi maior com a de cérebro de coelho, no sistema de detecção utilizado.

Evaluation of coagulation parameters: Coronavirus disease 2019 (COVID-19) between survivors and nonsurvivors

SUMMARY OBJECTIVE: This study aims to investigate and compare the coagulation parameters of coronavirus disease 2019 (COVID-19) patients with mortal and nonmortal conditions. METHODS: In this study, 511 patients diagnosed with COVID-19 were included. Information about 31 deceased and 480 recovered COVID-19 patients was obtained from the hospital information management system and analyzed retrospectively. Whether there was a correlation between coagulation parameters between the mortal and nonmortal patients was analyzed. Descriptive analyses on general characteristics of the study population were performed. Visual (probability plots and histograms) and analytical methods (Kolmogorov-Smirnov and Shapiro-Wilk test) were used to test the normal distribution. Analyses were performed using the SPSS statistical software package. RESULTS: Out of 511 patients, 219 (42.9%) were females and 292 (57.1%) were males. There was no statistically significant difference between males and females in terms of mortality (p=0.521). In total, the median age was 67 (22). The median age was 74 (13) in the nonsurvivor group and 67 (22) in the survivor group, and the difference was statistically significant (p=0.007). The D-dimer, prothrombin time, international normalized ratio, neutrophil, and lymphocyte median age values with p-values, in the recovered and deceased patient groups were: 1070 (2129), 1990 (7513) μg FEU/L, p=0.005; 12.6 (2.10), 13.3 (2.1), p=0.014; 1.17 (0.21), 1.22 (0.19), p=0.028; 5.51 (6.15), 8.54 (7.05), p=0.001; and 0.99 (0.96), 0.64 (0.84), p=0.037, respectively, with statistically significant differences. CONCLUSIONS: As a result of this study, D-dimer, prothrombin time, and international normalized ratio increase were found to be associated with mortality. These parameters need to be closely monitored during the patient follow-up.

Effect of anticoagulant adjustment on prothrombin time test using two different PT reagents in patients with elevated hematocrit.

The recommendations for adjustment of citrate volume in sample tubes with high hematocrit (Ht) are based on indirect studies of underfilled tubes or artificially constructed Ht values. The aim of this study was to evaluate the effect of citrate volume adjustment in sample tubes from patients with hematocrit >55% using two different prothrombin time (PT) tests. METHODS: Paired citrate-adjusted and unadjusted blood specimens were obtained from 181 patients from the pulmonary hypertension ambulatory with high Ht values and on warfarin therapy. The samples were tested using recombinant human tissue factor (RTF) and reagents extracted from rabbit brain (HS Plus). The results are expressed as the international normalized ratio (INR). The correlation and percent change (% change) between sample pairs were calculated. RESULTS: INR-RTF results from adjusted and unadjusted citrate blood specimens showed a strong correlation (R2 â€‹= â€‹0.8226, p â€‹< â€‹0.0001). The INR median was 2.25 (95% CI 2.10 to 2.41) for citrate-adjusted samples and was 2.22 (95% CI 2.06 to 2.38) for citrate-unadjusted samples. For samples with Ht >62%, the % change between sample pairs was >10%. Results using HS Plus showed a moderate correlation between citrate-adjusted and unadjusted samples (R2 â€‹= â€‹0.4267, p â€‹< â€‹0.0001). The INR median was 2.51 (95% CI 2.35 to 2.68) for citrate-adjusted samples and 3.45 (95% CI 3.11 to 3.80) for citrate-unadjusted samples. For samples with Ht>55%, the % change between sample pairs was higher than 10%. CONCLUSION: Our data demonstrate that in patients with polycythemia on warfarin therapy, INR-RTF does not require anticoagulant adjustment for assessment of samples with Ht <62%.

The relationship between coagulation disorders and the risk of bleeding in cirrhotic patients.

INTRODUCTION AND OBJECTIVES: For long, bleeding in cirrhotic patients has been associated with acquired coagulation disorders. The aim of our study was to investigate the impact of acquired coagulation disorders on bleeding risk in cirrhotic patients. MATERIALS AND METHODS: Blood samples were collected from 51 cirrhotic patients with (H+) or without (H-) bleeding events and 50 controls matched by age and sex. Thrombin generation was assessed as endogenous thrombin potential (ETP). Hemostatic balance was assessed by means of ratios of pro- to anticoagulant factors and by ETP ratio with/without protein C (PC) activator (ETP ratio). RESULTS: Bleeding events occurred in 9 patients (17.6%). Compared with controls, VIII/anticoagulant factors, VII/PC and XII/PC were significantly higher in (H+) patients. No significant difference as regards all ratios across patient groups was detected. ETP ratio was significantly higher in (H+) patients than in controls (p=0.017). However, there was no significant difference between patient groups as regards ETP ratio. CONCLUSION: Hemostatic balance is shifted toward a hypercoagulability state even in cirrhotic patients who experienced bleeding. These findings provide evidence against traditional concept of hemostasis-related bleeding tendency in cirrhotic patients.

Secondary hemostasis studies of crude venom and isolated proteins from the snake Crotalus durissus terrificus.

Among the activities triggered by Crotalus durissus terrificus snake venom, coagulation is intriguing and contradictory since the venom contains both coagulant and anticoagulant precursor proteins. This work describes the in vitro effects of crude venom and purified proteins from snake Crotalus durissus terrificus as they affect coagulation factors of clotting pathways. Coagulant and/or anticoagulant activities of crude venom, and purified proteins were all analyzed directly in human plasma. Clots formed by crude venom and Gyroxin presented as flexible hyaline masses in punctiform distribution. Clot formation time evaluation of isolated proteins with PT and APTT assays made it possible to infer that these proteins interfere in all coagulation pathways. However, regarding ophidism by C. d. terrificus, Gyroxin acts directly, breaking down fibrinogen to fibrin and increasing the amount plasminogen activator, which results in the formation of thrombi. Crotoxin complex, Crotoxin A and Crotoxin B proteins can act in prothrombinase complex formation; Crotoxin B can inhibit prothrombinase complex formation by direct interaction with Factor Xa. Crotamine interacts with negatively charged regions of differing coagulation factors in all coagulation pathways, and possesses a whole set of activities causing dysfunction, activation and/or inhibition of natural anticoagulants and disturbing hemostasis.

Hemostatic profile in patients with and without postpartum hemorrhage / Perfil hemostático en pacientes con y sin hemorragia obstétrica posparto

Background: The association between coagulation profile and postpartum hemorrhage (PH) is still debated. Objective: To determine the association between hemostatic profile and PH in women with cesarean operation (CO). Methods: We included 92 patients with PH (cases) and 184 without (controls), patients were attended during 2014, at one hospital of the Instituto Mexicano del Seguro Social in Mérida, Yucatán. Demographic, clinical and laboratory data including prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count (PLC), and fibrinogen concentration were compared among cases and controls using a binary logistic regression model (LRM), from which odd ratios (OR), and 95% confidence intervals (95% CI), were obtained. Results: According to the bivariate comparison, in the LRM categorical data such as parity, any type of hypertensive comorbidity, type of anesthesia, and categorized aPTT (< 38 vs. ≥ 38 seconds), and one continuous variable (gestational age) were included. Having some hypertensive comorbidity (OR 3.55, 95% CI: 1.95-6.47), type of anesthesia (regional anesthesia, OR 0.27, 95% CI: 0.13-0.55) and aPTT (< 38 seconds, OR 0.26, 95% CI: 0.10-0.66) were all statistically significant. Categorized PT, platelet count and fibrinogen concentration, were not statistically significant. Conclusions: In this sample, having some hypertensive comorbidity increased risk of PH more than three times, while regional anesthesia and aPTT < 38 seconds reduced risk in 73% and 74%, respectively. Neither platelet count, nor fibrinogen concentration, or the PT categories modified risk of PH.

Introducción: la asociación entre el perfil hemostático y la hemorragia obstétrica posparto (HO) es controversial. Objetivo: determinar la asociación entre el perfil hemostático y la HO en pacientes con operación cesárea (OC). Métodos: se incluyeron 92 pacientes con HO (casos) y 184 sin HO (controles), atendidas durante 2014 en un hospital del Instituto Mexicano del Seguro Social de Mérida, Yucatán. Diversas variables, incluyendo la cuenta plaquetaria, el tiempo de protrombina (TP), el tiempo de tromboplastina parcial activado (TTPa) y el fibrinógeno plasmático, fueron comparadas entre casos y controles, mediante un modelo de regresión logística del que se obtuvieron razones de momios (RM) e intervalos de confianza de 95% (IC 95%). Resultados: con base en el análisis univariado se incluyeron en el modelo la paridad, comorbilidad hipertensiva (hipertensión crónica, preeclampsia, eclampsia), tipo de anestesia y el TTPa categorizado (< 38 frente a ≥ 38 segundos) y la edad gestacional (como dato continuo), resultando significativamente diferentes la presencia de comorbilidad hipertensiva (RM 3.55, IC 95%: 1.95-6.47), el tipo de anestesia (regional, RM 0.27, IC 95%: 0.13-0.55) y el TTPa (< 38 segundos, RM 0.26, IC 95%: 0.10-0.66). Conclusiones: en esta muestra, tener comorbilidad hipertensiva incrementó más de tres veces el riesgo de HO, la anestesia regional lo redujo en 73% y el TTPa < 38 segundos lo redujo en 74%. Ni el TP, ni la cuenta plaquetaria modificaron el riesgo.

Routine Coagulation Tests in Patients With Nonvalvular Atrial Fibrillation Under Dabigatran and Rivaroxaban Therapy: An Affordable and Reliable Strategy?

Dabigatran and rivaroxaban, direct oral anticoagulants (DOACs), affect coagulation tests, and knowledge of their effects is important for therapeutic monitoring. Our aim was to examine the association between DOAC levels and routine coagulation tests in patients with nonvalvular atrial fibrillation. Samples from patients receiving dabigatran (150 mg) and patients receiving rivaroxaban (20 mg) were collected 2 hours after drug intake. Direct oral anticoagulant concentrations were determined using direct Hemoclot thrombin inhibitor (HTI) assay (HTI test) and a direct Xa inhibitor (Anti Xa-Riva). The routine coagulation measured included activated partial thromboplastin time (aPTT) and prothrombin time (PT). The median plasmatic dabigatran was 128.3 ng/mL (95% confidence interval [CI]: 93.7-222.6 ng/mL). The HTI exhibited a good correlation with aPTT ( R2 = 0.74; P < .0001). The median plasmatic rivaroxaban was 223.9 ng/mL (95% CI: 212.3-238.9 ng/mL). Anti-Xa-Riva correlated with PT ( R2 = 0.69, P< .0001) and aPTT (R2 = 0.36, P < .001), but prolonged PT results were obtained, even below the rivaroxaban therapeutic range (20%). The routine coagulation tests were able to identify out of therapeutic range concentrations for dabigatran and rivaroxaban. We suggest the use of these screening tests to better understand and monitor the subtherapeutic concentrations of these DOACs.

Influência do tempo de centrifugação em testes de coagulação: tempo de protrombina e tempo de tromboplastina parcial / Influence of the centrifuge time in coagulation tests: prothrombin time and partial thromboplastin time

Objetivo: Analisar os testes de coagulação: tempo de protrombina (TP) e tempo de tromboplastina parcial (TTP) em diferentes tempos de centrifugação da amostra da biológica, com relação ao protocolo padrão do Clinical Laboratory Standards Institute (CLSI). Métodos: As amostras foram divididas em cinco alíquotas de 1 mL. Foi realizada a centrifugação em 15, 10, 5, 2 e 1 minuto, com velocidade de 1500 g. O TP e TTP foram imediatamente analisados em aparelho automatizado. Os plasmas foram analisados para presença de elementos residuais: eritrócitos, leucócitos e plaquetas. Resultados: Observou-se alteração dos valores do TP nos tempos de centrifugação 10, 5, 2 e 1 minuto e do TTP em 5, 2 e 1 minuto, com relação ao protocolo padrão. Na interpretação de Bland Altman, observou-se um viés significativo do limite clínico aceitável para o TP e para o TTP em todos os tempos de centrifugação, com relação ao protocolo padrão. Apenas no tempo de centrifugação de 15 minutos não foram encontradas células residuais nas amostras analisadas. Conclusão: O tempo de centrifugação de 15 minutos é o ideal para remoção completa das células sanguíneas residuais e para garantia da confiabilidade dos resultados dos testes de coagulação TP e TTP.

Objective: To analyze the coagulation tests: prothrombin test (PT) and partial thromboplastin time (PTT) in different centrifugation times of the sample, in relation to the standard protocol of the Clinical Laboratory Standards Institute (CLSI). Methods: The selected samples were splitted up into five aliquots of 1 mL. Centrifugation of these aliquots was carried out at 15, 10, 5, 2 and 1 minute at 1500 g. The PT and PTT were analyzed in an automated apparatus. The plasmas were analyzed for presence of residual elements: erythrocytes, leukocytes and platelets. Results: The results showed a change in the values of PT at the 10, 5, 2 and 1 minute centrifugation times and the PTT at 5, 2 and 1 minutes, relative to the standard protocol. In the interpretation of Bland Altman, a significant bias of the acceptable clinical limit for TP and TTP at all centrifugation times was observed, relative to the standard protocol. Only in the 15 minute centrifugation time no residual cells were found in the analyzed samples. Conclusion: The present study demonstrated that the 15-minute centrifugation time is ideal for complete removal of residual blood cells and to ensure the reliability of the results of the PT and PTT coagulation

Determination of reference ranges for coagulation tests in Mexican-mestizo population / Determinación de límites de referencia de pruebas de coagulación en población mestizo-mexicana

Background: It is necessary to establish biological parameters for each population. Objective: To establish reference values for prothrombin time (PT), activated partial thromboplastin time (PTT) and fibrinogen in healthy population and to determine intra- and inter-assay concordance. Methods: Cross-sectional study that included 204 women and 202 men from the Blood Donor service. Coagulation tests were carried out in order to obtain reference ranges. All procedures were made according to the Clinical & Laboratory Standards Institute guidelines. Results: Mean PT, PTT and fibrinogen were 14.1 s, 28.8 s and 381 mg/dL in men, and 15.1 s, 29.0 s and 381 mg/dL in women. The proposed PT, PTT and fibrinogen reference ranges for men were 12.7 to 16.3 s, 24.2 to 36.3 s and 239 to 276 mg/dL, respectively; for women, 12.7 to 16.6 s, 23.5 to 35.4 s and 276 to 598 mg/dL. The latter was statistically significant (p ≤ 0.001). Conclusions: Reference values for blood coagulation tests were determined. This is of great importance for fast medical diagnosis and treatment. The results from this study can be adopted by other clinic laboratories after appropriate validation procedures.

Introducción: Es necesario establecer valores de referencia biológicos para cada población. Objetivo: Establecer los límites de referencia de tiempo de protrombina (TP), tiempo parcial de tromboplastina (TTP) y fibrinógeno en población mestizo-mexicana sana, así como la correlación y la concordancia en la determinación de estas pruebas con los dos equipos utilizados. Métodos: Estudio transversal en 204 mujeres y 202 hombres que acudieron al servicio de donadores y se les determinó TP, TTP y fibrinógeno para obtener los límites de referencia. Los procedimientos se realizaron de acuerdo con las guías del Instituto de Estándares de Laboratorio y Clínicos (CLSI C28-A3). Resultados: La media de TP, TTP y fibrinógeno en hombres fue de 14.1 s, 28.8 s y 381 mg/dL, y en mujeres de 15.1 s, 29.0 s y 381 mg/dL, respectivamente. Los límites de referencia para hombres en TP, TTP y fibrinógeno fueron de 12.7 a 16.3 s, de 24.2 a 36.3 s y de 239 a 276 mg/dL; para mujeres de 12.7 a 16.6 s, de 23.5 a 35.4 s y de 276 a 598 mg/dL, respectivamente. Este último fue estadísticamente significativo (p ≤ 0.001). Conclusiones: Se determinaron los límites de referencia para las pruebas de coagulación. Los resultados obtenidos en este estudio pueden ser adoptados por otros laboratorios clínicos, después de su apropiada validación.

Eficacia de la vitamina K en los trastornos de coagulación en los pacientes con enfermedad hepática crónica / Efficacy of vitamin K in coagulation disorders in patients with chronic liver disease

La coagulopatía es el denominador común en la amplia gama de procesos hepático crónicos, efecto principal de la deficiencia de vitamina K. A pesar de la falta de evidencia que sostiene su eficacia, su administración representa una parte del manejo de muchos pacientes con coagulopatía. Por tanto, el objetivo primario de este estudio fue comparar los tiempos de coagulación tras la administración de vitamina K en pacientes con enfermedad hepática crónica y trastornos de coagulación. Se postularon como secundarios la caracterización del paciente hepatópata según grupo nosológico por edad y sexo, así como las diferencias existentes entre las pruebas de coagulación basales con respecto a cada grupo. 72 pacientes fueron reclutados en 4 grupos, grupo 1: hepatitis B inactiva (n=6), grupo 2: hepatitis B crónica-hepatitis C (n=14), grupo 3: cirrosis (n=35) y grupo 4: hepatocarcinoma (n=17), se administraron 3 dosis de vitamina K de 10 mg cada una a intervalos de 24 horas, se midieron tiempo de protrombina (TP), radio normalizado internacional (INR) y tiempo de tromboplastina parcial activado (TPT) basales y cada 24 horas después de cada dosis. Se logró establecer una diferencia estadísticamente significativa en la corrección del tiempo de protrombina (31.04±9.62 a 21.69±8.48 P˂0.0001) así como del INR (2.81±1.013 a 1.92±0.81, P˂0.0001), hubo diferencia en cuanto a grupo diagnóstico y edad de presentación, así como en cuanto a tiempos de coagulación basales según diagnóstico. Por tanto, se demostró la efectividad de la vitamina K en la corrección del TP e INR.(AU)

Coagulopathy is the common denominator in the wide range of chronic liver processes, the main effect of vitamin K deficiency. Despite the lack of evidence supporting its efficacy, its administration represents a part of the management of many patients with coagulopathy. Therefore, the primary objective of this study was to compare clotting times after vitamin K administration in patients with chronic liver disease and coagulation disorders. The characterization of the liver disease patient according to nosological group by age and sex, as well as the differences between the baseline coagulation tests with respect to each group, were postulated as secondary. 72 patients were recruited into 4 groups, group 1: inactive hepatitis B (n = 6), group 2: chronic hepatitis B-hepatitis C (n = 14), group 3: cirrhosis (n = 35) and group 4: hepatocarcinoma ( n = 17), 3 doses of vitamin K of 10 mg each were administered at 24-hour intervals, prothrombin time (TP), international normalized radius (INR) and baseline activated partial thromboplastin time (TPT) were measured and each 24 hours after each dose. It was possible to establish a statistically significant difference in the correction of prothrombin time (31.04 ± 9.62 to 21.69 ± 8.48 P˂0.0001) as well as the INR (2.81 ± 1.013 to 1.92 ± 0.81, P˂0.0001), there was a difference in terms of group Diagnosis and age of presentation, as well as baseline clotting times according to diagnosis. Therefore, the effectiveness of vitamin K in the correction of TP and INR was demonstrated

Comparison of different laboratory tests in the evaluation of hemorrhagic risk of patients using rivaroxaban in the critical care setting: diagnostic accuracy study.

BACKGROUND: Rivaroxaban is a direct oral anticoagulant designed to dispense with the necessity of laboratory monitoring. However, monitoring rivaroxaban levels is necessary in certain clinical conditions, especially in the critical care setting. METHODS: This is a diagnostic accuracy study evaluating sensitivity and specificity of prothrombin time (PT), activated partial thromboplastin time (aPTT), and Dilute Russell viper venom time (dRVVT), to evaluate the hemorrhagic risk in patients taking rivaroxaban. The study used a convenience sample of 40 clinically stable patients using rivaroxaban to treat deep vein thrombosis or atrial fibrillation admitted in a private hospital in Brazil, compared to a group of 60 healthy controls. The samples from patients were collected two hours after the use of the medication (peak) and two hours before the next dose (trough). RESULTS: The correlation with the plasmatic concentration measured by anti-FXa assay was higher for PT and dRVVTS. The PT and aPTT tests presented higher specificity, while dRVVT was 100% sensible. CONCLUSIONS: There was a strong correlation between the tests and the plasma concentration of the drug. Additionally, our results demonstrated the potential use of dRVVT as a screening test in the emergency room and the need of a second test to improve specificity.