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.

Evaluation of Haemostatic Effects of Petroselinum crispum(Parsley) in Wistar Rats

Petroselinum crispum(parsley or garden parsley), besides its use as an edible vegetable, is used in the treatment of various ailments with documented evidence validating some of these medicinal uses. The present study evaluates the impact of oral administration of P. crispumon blood coagulation parameters. Fresh leaves of P. crispum were locally sourced, authenticated and extracted using ethanol to obtain an ethanolic extract of P. crispum (PCE). Twenty-five (25) male Wistar rats were used for the study and were randomly assigned to five (5) animals of five (5) rats each. Group I served as the control group and was given distilled water, whereas groups II, III, and IV were treated as experimental groups and administered PCE at 200, 400, and 800mg/kg via oral gavage, respectively. Group V also received 800mg/kg of PCE with the administration terminated on the 28thday to allow for a 14-day recovery period. Platelet count (PLT) and other platelet indices were determined using an automated Haematology analyzer. Bleeding time (BT), clotting time (CT), prothrombin time (PT), activated partial thromboplastin time (aPTT) and plasma fibrinogen (FIB) were assayed following standard laboratory protocols. The results of the study show that the mean PLT were significantly reduced in the experimental animals compared to the control (p<0.05) while BT, CT, PT, aPTT and FIB significantly increased compared to the control (p<0.05). Also, BT, CT, PT, and aPTT recovered towards the control values after the 14-day withdrawal period. The present study shows ethanolic leaf extract of P. crispumprolonged blood coagulation. The current evidence suggests that P. crispumcould be a candidate for further exploration as a natural plant-based antithrombotic agent.

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.

Value of bedside high-flow continuous blood purificationcombined with Xuebijing in the treatment of severe sepsis / 中国医师进修杂志

Objective:To investigate the effect of bedside high-flow continuous blood purification (CBP) combined with Xuebijing in the treatment of severe sepsis (SS) and the influence on the patient′s coagulation-fibrinolysis index, immunity index and expression of peripheral blood Toll-like receptor 4 (TLR4).Methods:Ninety-three patients with SS who were admitted and treated in the Lianyungang First People′s Hospitalfrom January 2017 to October 2019 were selected. They were divided into the combined group (51 cases, treatment with bedside high-flow CBP and Xuebijing injection based on bundle therapy) and the control group (42 cases, treatment with Xuebijing injection based on bundle therapy). The changes in coagulation and fibrinolysis index, immunity index, biochemical index such as TLR4 before treatment and after 1 week of treatment were compared between the two groups. The incidences of complications in both groups were statistically analyzed, and the discharge time from ICU, mechanical ventilation time and 28-day mortality were recorded.Results:After 1 week of treatment, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the two groups were shortened, D-dimer (D-D) and fibrinogen (FIB) were decreased ( P<0.05); and the levels of PT and APTT in the combined group were shorter than those in the control group, the levels of DD and FIB were lower than those in the control group, there were statistical differences ( P<0.05). After 1 week of treatment, the levels of CD 4+ and CD 4+/CD 8+ ratio in both groups were increased ( P<0.05), and the levels of CD 4+ and CD 4+/CD 8+ ratio in the combined group were higher than those in the control group ( P<0.05). After 1 week of treatment, the levels of TLR4, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), blood lactate (Lac), blood urea nitrogen (BUN) and serum creatinine (Scr) in both groups were decreased ( P<0.05), meanwhile, the above indexes in the combined group were lower than those in the control group ( P<0.05). The incidence of multiple organ failure and the 28-day mortality rate in the combined group were lower than those in the control group: 3.92%(2/51) vs. 19.05%(8/42), 13.73%(7/51) vs. 30.95%(13/42), there were statistical differences ( P<0.05). The discharge time from ICU and mechanical ventilation time in the combined group were shorter than those in the control group: (12.35 ± 2.14) d vs. (14.17 ± 3.36) d, (7.12 ± 2.23) d vs. (8.51 ± 2.39) d, there were statistical differences ( P<0.05). Conclusions:Bedside high-flow CBP combined with Xuebijing injection in the treatment of SS can improve the patient′s condition, regulate the balance of coagulation and fibrinolysis, avoide the activation of coagulation, inhibite inflammatory response, reduce the expression of TLR4 in peripheral blood, improve immune function, protecte kidney function and promotethe patient′s recovery.

Influencing of high sodium donor liver transplantation from the death of a citizen′s organ donation on the prognosis of recipients / 中华消化外科杂志

Objective:To investigate the influencing of high sodium donor liver transplan-tation from the death of a citizen′s organ donation (DCD) on the prognosis of recipients.Methods:The retrospective cohort study was constructed. The clinicopathological data of 125 pairs of donors and recipients who underwent DCD liver transplantation in Xijing Hospital of Air Force Military Medical University from January 2015 to June 2021 were collected. Of the 125 donors, there were 93 males and 32 females. Of the 125 recipients, there were 92 males and 33 females, aged 48(41,55)years. According to the last time of serum sodium level of donor liver in the 125 recipients, 9 donor livers with serum sodium level ≥170 mmol/L were divided into group 1 (extremely high sodium), 33 donor livers with serum sodium level ≥150 mmol/L and <170 mmol/L were divided into group 2 (moderate high sodium), and 83 donor livers with serum sodium level <150 mmol/L were divided into group 3 (normal sodium), respectively. Observation indicators: (1) postoperative recover situations; (2) follow-up and survival analysis. Measurement data with normal distribution were represented as Mean± SD. Repeated measures were analyzed by repeated measures ANOVA. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Kruskal-Wallis test. Count data were described as absolute numbers, and Pearson chi-square test or Fisher exact probability were used for data test. The Kaplan-Meier method was used to draw survival curves and Log-rank test was used for survival analysis. Results:(1) Postoperative recover situations. The changes of alanine transaminase (AlT), aspartate aminotransferases (AST), total bilirubin (TBil), alkaline phosphatase (ALP), prothrombin time (PT), international normalized ratio (INR), albumin (Alb) and creatinine (Cr) from the first day to the 14th day after operation were (736±972)IU/L to (75±46)IU/L, (1 290±1 651)IU/L to (38±20)IU/L, (102±98)μmol/L to (33±11)μmol/L, (66±34)IU/L to (104±54)IU/L, (19.9±3.3)seconds to (11.3±1.0)seconds, 1.76±0.31 to 1.00±0.08, (34±5)g/L to (38±3)g/L and (91±41)μmol/L to (76±19)μmol/L, respectively, in the recipients of group 1. The above indicators were (505±377)IU/L to (48±46)IU/L, (855±727)IU/L to (24±17)IU/L, (64±42)μmol/L to (32±22)μmol/L, (68±51)IU/L to (91±46)IU/L, (16.8±3.5)seconds to (11.9±1.2)seconds, 1.47±0.30 to 1.04±0.09, (33±4 g/L) to (40±5)g/L and (106±32)μmol/L to (97±27)μmol/L in the recipients of group 2 and (637±525)IU/L to (65±60)IU/L, (929±1 193)IU/L to (33±27)IU/L, (66±48)μmol/L to (33±36)μmol/L, (64±28)IU/L to (125±64)IU/L, (17.2±4.7)seconds to (13.3±12.8)seconds, 1.51±0.42 to 1.05±0.13, (35±6)g/L to (39±4)g/L, (105±44)μmol/L to (94±40)μmol/L in the recipients of groups. Results of overall effect showed there were significant differ-ences in the change trend of TBil (time effect, inter-group effect, interaction effect) in recipients among the three groups after liver transplantation ( Fgroup=5.42, Ftime=22.78, Finteraction=3.85, P<0.05). There were significant differences in the time effect of ALT, AST, ALP, PT, INR, Alb, Cr in recipients among the three groups after liver transplantation ( Ftime=50.17, 36.24, 19.24, 10.55, 59.61, 41.94, 10.82, P<0.05). (2) Follow-up and survival analysis. All recipients were followed up. Cases with early postoperative liver dysfunction, cases with donor liver failure 1 year after operation, cases with biliary complica-tions 1 year after operation, cases with vascular complications 1 year after operation, cases with rejection 1 year after operation were 2, 1, 0, 0, 0 in the recipients of group 1. The above indicators were 2, 1, 3, 0, 1 in the recipients of group 2 and 10, 8,20, 1, 6 in the recipients of group 3. There was no significant difference in the above indicators among the three groups ( χ2=1.58, 0.60, 5.19, 1.62, 0.97, P>0.05). The 1-year and 3-year cumulative survival rates of the donor liver were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 94.74% and 77.16% in the recipients of group 2 and 91.57% and 89.30% in the recipients of group 3. There was no significant difference in the cumulative survival rate of donor liver among the three groups ( χ2=2.69, P>0.05). The 1-year and 3-year cumulative survival rates were 100.00% and 100.00% in the recipients of group 1 after liver transplantation. The above indicators were 93.74% and 77.16% in the recipients of group 2 and 89.40% and 86.00% in the recipients of group 3. There was no significant difference in the cumulative survival rate among the three groups ( χ2=1.94, P>0.05). Conclusion:Donor livers with high serum sodium level can be used in the DCD liver transplantation.

Efficacy and safety of percutaneous left atrial appendage occlusion for nonvalvular atrial fibrillation / 中国基层医药

Objective:To investigate the efficacy and safety of percutaneous left atrial appendage occlusion in the treatment of nonvalvular atrial fibrillation.Methods:Eighty-eight patients with percutaneous left nonvalvular atrial fibrillation who received treatment in The Second Hospital of Anhui Medical University from January 2019 to January 2021 were included in this study. These patients were divided into three groups according to different anticoagulant methods: group A (percutaneous left atrial appendage occlusion), group B (livaraban), and group C (warfarin). The incidence of stroke, the incidence of bleeding events, the incidence of adverse cardiovascular events, and live and kidney function and coagulation function after 3 months of treatment were compared among the three groups.Results:There were no significant differences in the incidence of stroke and adverse cardiovascular events among the three groups ( P > 0.05). The incidence of bleeding events in groups A, B, and C was 9.3% (3/32), 15.0% (6/40), and 31.2% (5/16), respectively. There was a significant difference in the incidence of bleeding events among the three groups ( χ2 = 8.07, P = 0.001). After 3 months of treatment, there were no significant differences in prothrombin time, fibrinogen, prothrombin time-international normalized ratio, alanine aminotransferase, aspartate transaminase, and creatinine clearance among the three groups (all P > 0.05). Conclusion:Percutaneous left atrial appendage occlusion, warfarin, and rivaroxaban can prevent stroke in patients with nonvalvular atrial fibrillation. Percutaneous left atrial appendage occlusion is safer and more feasible than warfarin and rivaroxaban alone in the treatment of nonvalvular atrial fibrillation.

Effect of hepatic artery reconstruction techniques on prognosis of liver transplantation / 器官移植

Objective To evaluate the effect of different techniques of hepatic artery reconstruction on postoperative hepatic artery complications and clinical prognosis in liver transplantation. Methods Clinical data of 140 liver transplant recipients were retrospectively analyzed. All recipients were divided into the conventional hepatic artery reconstruction group (n=123) and special hepatic artery reconstruction group (n=17) according to hepatic artery reconstruction methods. Intraoperative and postoperative clinical indexes, the incidence of postoperative hepatic artery complications and survival rate were compared between two groups. Results The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at postoperative 1 d, total bilirubin (TB) at postoperative 7 d and prothrombin time international normalized ratio (PT-INR) at postoperative 30 d in special hepatic artery reconstruction group were higher than those in conventional hepatic artery reconstruction group, and the differences were statistically significant (all P < 0.05). There were no significant differences in the operation time, anhepatic phase, intraoperative blood loss, intraoperative transfusion volume of red blood cells, cold or warm ischemia time, the length of intensive care unit (ICU) stay, the length of hospital stay and postoperative blood flow of liver allograft between two groups (all P > 0.05). In the conventional hepatic artery reconstruction group, 5 recipients developed hepatic artery complications, whereas no hepatic artery complications occurred in the special hepatic artery reconstruction group, with no significant difference between two groups (P > 0.05). In the special hepatic artery reconstruction group, the 1-, 3- and 5-year cumulative survival rates were equally 82.4%, compared with 85.0%, 78.9% and 75.6% in the conventional hepatic artery reconstruction group, respectively. There was no significant difference between two groups (all P > 0.05). Conclusions When hepatic artery variations and (or) lesions are detected in donors and recipients, use of special hepatic artery reconstruction may effectively restore the hepatic arterial blood flow of liver allograft after liver transplantation, and will not affect the incidence of hepatic artery complications and survival rate of the recipients following liver transplantation.

Development and validation of a mobile application based on a machine learning model to aid in predicting dosage of vitamin K antagonists among Indian patients post mechanical heart valve replacement

Patients who undergo heart valve replacements with mechanical valves need to take Vitamin K Antagonists (VKA) drugs (Warfarin, Nicoumalone) which has got a very narrow therapeutic range and needs very close monitoring using PT-INR. Accessibility to physicians to titrate drugs doses is a major problem in low-middle income countries (LMIC) like India. Our work was aimed at predicting the maintenance dosage of these drugs, using the de-identified medical data collected from patients attending an INR Clinic in South India. We used artificial intelligence (AI) - machine learning to develop the algorithm. A Support Vector Machine (SVM) regression model was built to predict the maintenance dosage of warfarin, who have stable INR values between 2.0 and 4.0. We developed a simple user friendly android mobile application for patients to use the algorithm to predict the doses. The algorithm generated drug doses in 1100 patients were compared to cardiologist prescribed doses and found to have an excellent correlation.

A study of coagulation profile in preeclampsia compared to normal pregnancy

Background: Preeclampsia is a condition of unknown etiology of multiorgan disease and is distinguished by a raised blood pressure (B.P. >140/90 mmHg) and proteinuria (>300 mg per 24 h) and/or edema following 20 weeks of pregnancy. Aims and Objectives: The study was conducted to differentiate coagulation variables between normotensives and preeclamptic patients. Materials and Methods: Prior consent was obtained from Institutional Ethics Committee. Patients diagnosed with preeclampsia aged between 20 and 35 years were incorporated into the study. Patients with a previous history of hypertension, thyroid disease, and diabetes were excluded from the study. Age-matched controls were taken and analyzed. Data collection done by (i) BP measured in supine posture; (ii) bleeding time (B.T) estimation – by Duke’s method; (iii) clotting time (C.T) estimation – by Wright’s capillary tube method; (iv) platelet count (P.C) estimation – by automated hematology analyzer; and (v) prothrombin time (P.T) and activated partial thromboplastin time (APTT) – estimation by semi-automated analyzer. Results: The study revealed a significant interrelation between P.C and B.T when preeclampsia patients were correlated with normotensives patients while P.T, APTT, and C.T were insignificant statistically. Conclusion: A statistically significant change was observed proposing parameters derangement as the disease becomes more progressive.

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.

In vitroMeasurement of Anticoagulant Effect of Acacia Nilotica Aqueous Extract on Normal Human Plasma

Aims:To determine the anticoagulant effect of Acacia Nilotica aqueous extract on normal human plasma.Study Design:This is an experimental study.Place and Duration of the Study:Department of Haematology, Faculty of Medical Laboratory sciences, Alzaiem Alazhari, Khartoum –Sudan, during the period from July –August 2021. Methodology:A total of 20 human blood samples were collected for this study from apparently healthy subjects following ethical considerations. Samples were collected in tri-sodium citrate and platelets poor plasma (PPP) were immediately prepared by centrifugation. Aqueous solution of Acacia nilotica was prepared with distilled water (D.W), three concentrations of the solution (50%, 75% and 100%) were prepared. Prothrombin Time (PT) and Activated partial thromboplastin time (APTT) were tested by manual method before and after adding different concentrations of Acacia Nilotica solution. Statistical tests were performed by using SPSS version 16. Results:The results of study showed that Acacia Nilotica significantly prolonged the PT and APTT results of human plasma (Pvalues for 50%, 75% and 100% solutions were 0.000, 0.000 and 0.000 while for APTT 0.036, 0.000 and 0.000 for PT respectively). Also the study showed no significant correlation between control and A. nilotica concentrations among coagulation profile, except a significant positive correlation between control and 75% Acacia nilotica on APPT.Conclusion:Acacia Nilotica solutions had anticoagulant effect in human plasma, and could be nominated as a potential preventive agent for thromboembolic diseases

Comparison of four-coagulation-tests values in normal pregnant women during early and late pregnancy and the influence of age / 中华妇产科杂志

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

Study on the value of prothrombin time for predicting the severity and prognosis of septic patients / 中华危重病急救医学

Objective:To explore the predictive efficacy of prothrombin time (PT) with regarding for the severity and prognosis of septic patients, along with comparing with other routine coagulation parameters.Methods:A retrospective analysis was conducted. The clinical data of 302 septic patients who were admitted to the intensive care unit (ICU) of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 1 to December 31 in 2019 were enrolled. Demographic and basic clinical data were collected. Laboratory data, including PT, activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer, fibrin (fibrinogen) degradation product (FDP), antithrombin (AT), platelet count (PLT) at ICU admission were recorded, and sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score within 24 hours of admission to ICU were also collected. What's more, some major clinical events, such as septic shock, disseminated intravascular coagulation (DIC), etc. during ICU stay were also monitored. A follow-up 28 days observation of prognosis was performed. The patients were divided into the septic shock group and the non-septic shock group according to the occurrence of septic shock, and they were divided into the survival group and the non-survival group according to the 28-day prognosis. The differences in terms of above parameters between each two groups were compared. Spearman correlation method was used to analyze the correlation between routine coagulation parameters and SOFA score or APACHEⅡ score. Receiver operator characteristic curve (ROC curve) was plotted to determine the predictive efficacy of each routine coagulation parameter with regarding to predict septic shock and 28-day mortality. Based on the cut-off value of PT, the septic patients were divided into two risk stratifications, and then the major clinical and end point outcome were compared. Kaplan-Meier survival curve analysis was applied to investigate the difference of the 28-day cumulated survival rate based on the different risk stratifications of PT level. Finally, multivariate Logistic regression analysis was used to explore whether prolonged PT level was an independent risk factor for septic shock and 28-day mortality.Results:The 302 patients were all enrolled, including 120 patients with septic shock and 182 patients without. Seventy-five patients died within 28 days, while 227 survived. Comparing with the non-septic shock group or the survival group, the septic shock group or the non-survival group patients both had longer PT, APTT and TT, higher D-dimer, FDP and lower PLT, FIB and AT. Correlation analysis revealed that PT and PLT were better correlated with SOFA score ( r values were 0.503 and -0.524, both P < 0.01), and PT was better correlated with APACHEⅡ score ( r = 0.407, P < 0.01). ROC curve analysis showed that PT had the most powerful predictive efficacy for septic shock and 28-day mortality. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) were 0.831 (0.783-0.879) and 0.739 (0.674-0.805), respectively. The cut-off value were 16.8 s and 16.3 s, respectively, with the sensitivity of 64.2%, 72.0% and the specificity of 89.0%, 70.9%, respectively. Risk stratification based on PT level revealed that the patients with PT > 16.5 s ( n = 103) had higher rate of 28-day mortality, incidence of septic shock and DIC, and score of SOFA and APACHEⅡ comparing to those with PT ≤ 16.5 s ( n = 199). Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate was significantly lower in the patients with PT > 16.5 s than those with PT ≤ 16.5 s (52.43% vs. 86.93%; Log-Rank test: χ 2 = 49.428, P < 0.001). Multivariate Logistic regression analysis revealed that PT > 16.5 s was an independent risk factor both for septic shock and 28-day mortality [model 1 (enrolled SOFA score): odds ratio ( OR) and 95% CI were 6.003 (3.040-11.855), 4.842 (2.114-11.089); model 2 (enrolled APACHEⅡ score): OR and 95% CI were 7.675 (4.007-14.702), 5.160 (2.258-11.793)]. Conclusions:Compared with other routine coagulation parameters, PT has the potential best predictive value for evaluating the severity of sepsis and the prognosis. When a patient is diagnosed with sepsis and has a result of PT longer than 16.5 s at ICU admission, the patient may have a higher risk of progression to septic shock and short-term death.

Clinical characteristics and risk factors of chronic hepatitis C complicated by fatty liver / 中国基层医药

Objective:To analyze the clinical characteristics and risk factors of chronic hepatitis C (CHC) complicated by fatty liver.Methods:The clinical data of 258 patients with chronic hepatitis C who received treatment in The First People's Hospital of Huzhou from March 2017 to March 2021 were included in this study. They were divided into simple CHC group and CHC complicated by fatty liver group according to whether they had fatty liver. General data, liver function, coagulation function and blood lipid indexes were compared between the two groups.Results:Among 258 patients with CHC infection, 81 cases had fatty liver, accounting for 31.40%; 177 cases did not have fatty liver, accounting for 69.14%. There were no significant differences in age, sex, and history of smoking and alcohol use between the two groups (both P > 0.05). Body mass index (BMI) differed significantly between the two groups ( χ2 = 29.81, P < 0.001). BMI in the CHC complicated by fatty liver group was slightly higher than that in the simple CHC group. There were no significant differences in history of hypertension and coronary heart disease between the two groups (both P > 0.05). There were significant differences in the presence of hypertriglyceridemia and the increase of low-density lipoprotein between the two groups ( χ2 = 8.53, 6.99, P = 0.004, 0.008). There were no significant differences in the presence of hypercholesterolemia and the reduction of high-density lipoprotein (both P > 0.05). There were no significant differences in liver function indexes such as alanine aminotransferase and aspartate aminotransferase between the two groups (both P > 0.05). The level of γ-glutamyltransferase (γ-GGT) was significantly different between the two groups ( t =-8.71, P < 0.001). There was no significant difference in activated partial thromboplastin time between the two groups ( P > 0.05). There were significant differences in prothrombin time (PT) and international normalized ratio (INR) between the two groups [PT: (10.10 ± 0.67) seconds vs. (11.99 ± 1.33) seconds; INR: 0.91 ± 0.07 vs. 0.98 ± 0.11; t = 9.74, 4.46, both P < 0.001]. There were no significant differences in fasting blood glucose and blood uric acid levels between the two groups (both P > 0.05). Fasting insulin (FINS) differed significantly between CHC complicated by fatty liver and simple CHC groups [(16.82 ± 1.15) mlU/L vs. (12.52 ± 1.06) mlU/L, t = -24.33, P < 0.001]. The general data and clinical data were compared between the two groups. BMI, hypertriglyceridemia, high- and low-density lipoprotein, γ-GGT, PT, INR and FINS differed significantly between the two groups. Multivariate logistic regression results showed that BMI ≥ 24 kg/m 2, hypertriglyceridemia, γ-GGT, PT, INR and FINS were independent risk factors for CHC complicated by fatty liver ( P = 0.017, 0.003, 0.021, 0.034, 0.004, 0.001). After 6 months of treatment, CHC RNA negative conversion rate in the simple CHC group was significantly higher than that in the CHC complicated by fatty liver group ( χ2 = 7.32, P = 0.010). Conclusion:The related risk factors of CHC complicated by fatty liver include BMI, hypertriglyceridemia, elevated low-density lipoprotein, γ-GGT, PT, INR and FINS, among which, BMI, hypertriglyceridemia, γ-GGT, PT, INR and FINS are independent risk factors. In addition, CHC complicated by fatty liver may affect the efficacy of antiviral therapy.

Efficacy of intermittent pneumatic compression combined with drugs in the prevention of lower extremity deep venous thrombosis after joint replacement and its risk factors / 中国基层医药

Objective:To investigate the efficacy of intermittent pneumatic compression (IPC) combined with drugs in the prevention of lower extremity deep venous thrombosis (DVT) after joint replacement and its risk factors.Methods:A total of 80 patients receiving joint replacement surgery in Jinhua People's Hospital from January 2019 to December 2020 were included in this study. They were randomly divided into observation and control groups, with 40 patients in each group. To prevent lower extremity deep venous thrombosis, the control group was given low molecular weight heparin, and the observation group was given IPC in addition to DVT. The incidence of DVT post-surgery and coagulation function pre- and post-surgery were compared between the two groups. The incidence of adverse reactions was recorded in each group. In addition, 40 patients who developed DVT after joint replacement surgery from January 2019 to December 2020 (DVT group) and 40 patients who did not develop DVT (no DVT group) were included. The factors influencing the occurrence of DVT were analyzed by binary logistic regression.Results:The incidence of DVT in the observation group was significantly lower than that in the control group (5.00% vs. 20.00%, χ2 = 4.11, P < 0.05). At 7 days after surgery, prothrombin time, activated partial thromboplastin time, fibrinogen in the observation group were (11.73 ± 0.51) seconds, (27.05 ± 1.17) seconds, (3.89 ± 0.52) g/L, respectively, which were significantly lower than (12.03 ± 0.43) seconds, (27.65 ± 1.30) seconds, and (4.18 ± 0.59) g/L in the control group ( t = 2.84, 2.33, 2.17, all P < 0.05). There was no significant difference in the incidence of adverse reactions between observation and control groups (5.00% vs. 2.50%, χ2 = 0.00, P > 0.05). There were significant differences in age, body mass index, history of hypertension, and operative time between patients with DVT and those without DVT ( χ2 = 4.11, 5.16, 4.71, 8.65, all P < 0.05). Logistic regression analysis showed that age ( OR = 1.57, 95% CI = 1.239 - 2.014), body mass index ( OR = 6.71, 95% CI = 1.298 - 34.794), history of hypertension ( OR = 3.23, 95% CI = 1.980 - 5.296), operative time ( OR = 6.29, 95% CI = 2.058 - 19.225) were independent risk factors for DVT after joint replacement surgery (all P < 0.05). Conclusion:There are many factors that influence the occurrence of DVT after joint replacement surgery. Intermittent pneumatic compression combined with drugs for prevention of lower extremity DVT is safe and effective.

Analysis of risk factors of extrapulmonary organ dysfunction in children with severe refractory mycoplasma pneumoniae pneumonia / 中华急诊医学杂志

Objective:To analyze the clinical features of severe refractory mycoplasma pneumoniae pneumonia (SRMPP) in children, and explore its risk factors complicated with extrapulmonary organ dysfunction.Methods:The clinical data of children with SRMPP who were admitted to the Department of Critical Care Medicine of Shanghai Children's Hospital from July 2017 to June 2019 were retrospectively summarized. The patients were divided into two groups according to the occurrence of extrapulmonary organ dysfunction: the extrapulmonary organ dysfunction group and the respiratory dysfunction group. The differences of clinical features and laboratory indexes between the two groups were compared, and the risk factors of extrapulmonary organ dysfunction were screened out by logistic regression analysis.Results:A total of 107 cases with SRMPP were admitted to the Pediatric Intensive Care Unit during the past two years, and there were 44 cases (41.1%) complicated with pleural effusion, 17 cases (15.9%) with plastic bronchitis, 104 cases (97.2%) with positive results for macrolide resistance genes (2063, 2064), with an in-hospital mortality rate of 2.8% (3/107). Among 107 children with SRMPP, there were 51 cases (47.7%) with extrapulmonary organ dysfunction, 43 cases (40.2%) with cardiovascular dysfunction, 13 cases (12.1%) with coagulation dysfunction, 11 cases (10.3%) with gastrointestinal dysfunction, 4 cases (3.7%) with renal dysfunction, 4 cases (3.7%) with brain dysfunction, 3 cases (2.8%) with liver dysfunction, and 16 cases (15.0%) with multiple organ dysfunction. Compared with the respiratory dysfunction group, the incidence of capillary leak syndrome was higher (52.9% vs. 17.9%, P < 0.001), the capillary leak index was increased [11.71 (4.63, 27.07) vs. 5.78 (2.07, 15.71), P =0.019], serum albumin was decreased [(32.2 ± 5.6)g/L vs. (34.7 ± 6.7)g/L, P=0. 041], and prothrombin time was prolonged significantly [12.7 (11.7, 13.8)s vs. 12.0 (11.4, 13.0)s, P=0. 009]. Logistic regression analysis showed that capillary leak syndrome ( OR=0. 278, 95% CI 0.102-0.759, P=0. 013) and prolonged prothrombin time ( OR=1. 443, 95% CI 1.018-2.046, P=0. 039) were independent risk factors for SRMPP complicated with extrapulmonary organ dysfunction. Conclusions:Approximately 50% of children with SRMPP have dysfunction of extrapulmonary organs, such as circulation, coagulation and gastrointestinal disorders. Capillary leak syndrome and prolonged prothrombin time are independent risk factors for SRMPP complicated with extrapulmonary organ dysfunction.

Changes of coagulation function in patients with adenomyosis / 中华妇产科杂志

Objective:To explore the different coagulation state in patients with adenomyosis and its clinical significance.Methods:Clinical data of the patients admitted to the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2021 were retrospectively analyzed. (1) Differential coagulation state between 25 healthy women and 25 patients with adenomyosis were compared during menstrual and non-menstrual periods. (2) The coagulation indexes of 145 patients with adenomyosis (observation group 1) and 129 patients with cervical intraepithelial neoplasia grade Ⅲ (control group 1) who underwent hysterectomy in non-menstrual period were compared. (3) The coagulation indexes of 154 patients with adenomyosis (observation group 2) and 147 women without myometrial lesions (control group 2) who underwent endometrial curettage during uterine bleeding period were compared. (4) Correlations of coagulation index with cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9) and uterine volume in patients with adenomyosis were analyzed. Results:(1) The coagulation state of each health women during the menstrual and non-menstrual period showed no significant differences (all P>0.05). For the 25 patients with adenomyosis, fibrinogen [FIB; 2.61 g/L(2.50-3.10 g/L)] and D-dimer [0.60 mg/L (0.40-1.00 mg/L)] in the menstrual period were significantly higher than those in the non-menstrual period [2.25 g/L (1.90-2.70 g/L) and 0.27 mg/L (0.20-0.40 mg/L), respectively; both P<0.01], while thrombin time [TT; 16.70 s (16.10-17.40 s)] in the menstrual period was significantly lower than that in the non-menstrual period [17.95 s (17.20-18.40 s); P<0.01]. (2) In the non-bleeding period, D-dimer [0.26 mg/L (0.20-0.40 mg/L)] and platelet count [257.0×10 9/L (212.0×10 9/L-308.5×10 9/L)] of observation group 1 were significantly higher than those of control group 1 (all P<0.01). Besides, FIB ( r=0.237, P=0.004) and D-dimer ( r=0.373, P<0.001) were positively correlated with CA 125, while prothrombin time (PT; r=-0.208, P=0.012) and internationalized normalized ratio of plasma prothrombin time (PT-INR; r=-0.201, P=0.015) were negatively correlated with CA 19-9. (3) In the bleeding period, PT [10.70 s (10.10-11.20 s)] and PT-INR [0.93 (0.90-1.00)] of observation group 2 were significantly lower than those of control group 2 (all P<0.01), while D-dimer [0.41 mg/L (0.20-0.80 mg/L)] was significantly higher than that in the control group 2 ( P<0.001). Furthermore, FIB ( r=0.252, P=0.038) and D-dimer ( r=0.321, P=0.008) were positively correlated with uterine volume, while activated partial thromboplastin time (APTT; r=-0.190, P=0.018) and TT ( r=-0.304, P=0.012) were negatively correlated with uterine volume. (4) During non-menstrual period and uterine bleeding period, APTT and TT in patients of observation group 1 and 2 combined with anemia were significantly lower than those of non-anemia patients (all P<0.05). Conclusion:Patients with adenomyosis have a tendency to hypercoagulability in both the uterine bleeding and non-bleeding periods, which may be related to enlarged uterine volume, increased serum CA 125 and anemia.

Risk factors analysis and early warning evaluation model construction of disease severity in patients with dangerous upper gastrointestinal bleeding / 中华急诊医学杂志

Objective:To explore the influencing factors of severity of upper gastrointestinal bleeding (UGIB) and to establish the early warning evaluation model in the form of line chart, so as to provide a feasible basis for emergency nurses' triage.Methods:A total of 680 UGIB patients admitted to the Emergency Department of the First Affiliated Hospital of Wenzhou Medical University from January 2019 to January 2020 were retrospectively analyzed. They were divided into a modeling group ( n=510) and a validation group ( n=170) by random number table method, and were divided into a high-risk group and a low-risk group according to the expert Consensus on Emergency Diagnosis and Treatment Procedures for Acute Upper Gastrointestinal Bleeding in 2020. The differences of various indicators between groups were compared, the factors affecting the severity of the disease were analyzed by Logistic regression, and the nomogram was drawn and validated. Results:Multivariate logistic regression analysis showed that hematemesis ( OR=3.875, 95% CI: 2.212-6.79), diabetes ( OR=2.64, 95% CI: 1.184-5.883), syncope ( OR=10.57, 95% CI: 3.675-30.403), heart rate ( OR=3.262, 95% CI: 1.753-6.068), red blood cell distribution width ( OR=3.904, 95% CI: 2.176-7.007), prothrombin time ( OR=3.665, 95% CI: 1.625-8.269), lactic acid ( OR=3.498, 95% CI: 1.926-6.354) and hemoglobin ( OR=4.984, 95% CI: 2.78-8.938) were the influencing factors of the severity of UGIB patients ( P < 0.05). The nomogram model showed good consistency and differentiation (C-index=0.903, 95% CI: 0.875-0.931), and was verified internally (C-index=0.895) and Hosmer-Lemeshow goodness-of-fit test ( P=0.7936). Externally verified C-index was 0.899 (95% CI: 0.846-0.952). The calibration curve prompt warning evaluation model had good stability and the prediction efficiency was better than the modified early warning score ( P < 0.05). Conclusions:The early warning evaluation model has a reliable predictive value, which can provide a reference for emergency medical staff to screen high-risk patients and formulate targeted nursing interventions.

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)

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.