Effect of six-month use of oral contraceptive pills on plasminogen activator inhibitor-1 & factor VIII among women with polycystic ovary syndrome: An observational pilot study

Background & objectives: Polycystic ovary syndrome (PCOS) is an endocrinopathy warranting lifelong individualized management by lifestyle and pharmacological agents mainly oral contraceptive pills (OCPs). This study was aimed to report the impact of six-month OCP use on plasminogen activator inhibitor-1 (PAI-1) and factor VIII (FVIII) in women with PCOS. Methods: PCOS women diagnosed on the basis of Rotterdam 2003 criteria, either treated with OCPs (ethinyl estradiol-0.03 mg, levonorgestrel-0.15 mg) for a period of six months (n=40) or drug-naïve (n=42), were enrolled in this study. Blood was drawn to estimate glucose, insulin levels and lipid profile. Chemiluminescence immunoassays were used to measure hormones (LH, FSH, PRL, T4). Plasma levels of PAI-I and FVIII were measured by commercially available kits. Results: Menstrual regularity, Ferriman-Gallwey score and serum total testosterone significantly improved in the OCP group compared to drug-naïve group (P<0.01). No significant difference was observed in PAI-1 levels of the two groups; however, significant decrease in FVIII levels was observed in OCP group as compared to drug-naïve group. PAI-1 levels of OCP group correlated positively with blood glucose two hours, triglycerides and insulin two hours, while FVIII levels of OCP group correlated negatively with fasting insulin and homoeostatic model assessment-insulin resistance. Interpretation & conclusions: OCPs use has differential effect on pro-coagulant markers among women with PCOS. Well-designed, long-term, prospective, large-scale studies are prerequisite to elucidate the efficacy and safety of OCP in the treatment of PCOS.

Analysis on detection of Hcy ,vWf and TF-PCA within 48 h of onset in patients with coronary heart disease / 国际检验医学杂志

Objective To observe the change of serum homocysteine (Hcy) ,plasma von willebrand factor (vWF) and whole blood tissue factor procoagulant activity (TF-PCA) within 48 h of onset in the patients with coronary heart disease (CHD).Meth-ods The relevant instrument was adopted to detect the level of serum Hcy ,plasma vWF and whole blood TF-PCA in 300 CHD pa-tients and 100 individuals undergoing the healthy physical examination ,and then the statistical analysis was performed.Three hundreds cases of CHD were divided into the stable angina group (SAP group ,n= 96) ,unstable angina group (UAP group ,n=100) and acute myocardial infarction group (AMI group ,n=104).Results The Hcy ,vWF and TF-PCA levels in the CHD patients were higher than those in the control group ,the difference was statistically significant (PUAP group> SAP group ,the difference was statistically significant (P<0.05).The vWF and TF-PCA levels in the AMI group and UAP group were higher than those in the SAP group with statistical difference (P<0.05).The Hcy level in SAP ,UAP and AMI patients complicated with diabetes and hypertension was significantly increased compared with the patients without complicating di-abetes and hypertension ,the difference was statistically significant (P<0.05).The vWF and TF-PCA levels had statistical differ-ence between the UAP group and AMI group(P<0.05).Conclusion Routinely detecting the levels of Hcy ,vWF and TF-PCA has an important clinical value for the diagnosis and curative effect observation in the patients with CHD.

In vivo evaluation of homeostatic effects of Echis carinatus snake venom in Iran

The venom of the family Viperidae, including the saw-scaled viper, is rich in serine proteinases and metalloproteinases, which affect the nervous system, complementary system, blood coagulation, platelet aggregation and blood pressure. One of the most prominent effects of the snake venom of Echis carinatus (Ec) is its coagulation activity, used for killing prey. Materials and methods Subfractions F1A and F1B were isolated from Ec crude venom by a combination of gel chromatography (Sephadex G-75) and ion exchange chromatography on a DEAE-Sepharose (DE-52). These subfractions were then intravenously (IV) injected into NIH male mice. Blood samples were taken before and after the administration of these subfractions. Times for prothrombin, partial thromboplastin and fibrinogen were recorded. Results and conclusions Comparison of the prothrombin time before and after F1A and F1B administrations showed that time for blood coagulation after injection is shorter than that of normal blood coagulation and also reduced coagulation time after Ec crude venom injection. This difference in coagulation time shows the intense coagulation activity of these subfractions that significantly increase the coagulation cascade rate and Causes to quick blood coagulation. The LD50 of the Ec crude venom was also determined to be 11.1 μg/mouse. Different crude venom doses were prepared with physiological serum and injected into four mice. Comparison of the prothrombin times after injection of subfractions F1A and F1B showed that the rate of mouse blood coagulation increases considerably. Comparing the partial thromboplastin times after injecting these subfractions with this normal test time showed that the activity rate of intrinsic blood coagulation system rose sharply in mice. Finally, by comparing the fibrinogen time after subfraction injections and normal test time, we can.

In vivo evaluation of homeostatic effects of Echis carinatus snake venom in Iran

Background: The venom of the family Viperidae, including the saw-scaled viper, is rich in serine proteinases and metalloproteinases, which affect the nervous system, complementary system, blood coagulation, platelet aggregation and blood pressure. One of the most prominent effects of the snake venom of Echis carinatus (Ec) is its coagulation activity, used for killing prey. Materials and methods: Subfractions F1A and F1B were isolated from Ec crude venom by a combination of gel chromatography (Sephadex G-75) and ion exchange chromatography on a DEAE-Sepharose (DE-52). These subfractions were then intravenously (IV) injected into NIH male mice. Blood samples were taken before and after the administration of these subfractions. Times for prothrombin, partial thromboplastin and fibrinogen were recorded. Results and conclusions: Comparison of the prothrombin time before and after F1A and F1B administrations showed that time for blood coagulation after injection is shorter than that of normal blood coagulation and also reduced coagulation time after Ec crude venom injection. This difference in coagulation time shows the intense coagulation activity of these subfractions that significantly increase the coagulation cascade rate and Causes to quick blood coagulation. The LD50 of the Ec crude venom was also determined to be 11.1 µg/mouse. Different crude venom doses were prepared with physiological serum and injected into four mice. Comparison of the prothrombin times after injection of subfractions F1A and F1B showed that the rate of mouse blood coagulation increases considerably. Comparing the partial thromboplastin times after injecting these subfractions with this normal test time showed that the activity rate of intrinsic blood coagulation system rose sharply in mice. Finally, by comparing the fibrinogen time after subfraction injections and normal test time, we can infer intense activation of coagulation cascade and fibrin production.(AU)

Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation

Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline (SG) or recombinant Lopap (rLopap) at 1 µg/kg (LG1) or 10 µg/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals (CG) were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 µg/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.

Association of protein C deficiency with heat stroke in cool environment.

Heat stroke in cool environmental conditions has been a rare occurrence. We describe a case of heat stroke occurring in cool conditions in a previously healthy male who on work up was detected to have underlying procoagulant state.

Inhibition of local effects of Indian Daboia/Vipera russelli venom by the methanolic extract of grape (Vitis vinifera L.) seeds.

Although anti-venom therapy is available for the treatment of fatal bite by snakes, it offers less or no protection against the local effects such as dermo- and myonecrosis, edema, hemorrhage and inflammation at the bitten region. The viper species are known for their violent local effects and such effects have been commonly treated with plant extracts without any scientific validation in rural India. In this investigation, the methanolic extract of grapes (Vitis vinifera L.) seed was studied against the Indian Daboia/Vipera russelli venom-induced local effects. The extract abolished the proteolytic and hyaluronidase activities and also efficiently neutralized the hemorrhage, edema-inducing and myonecrotic properties of the venom. In addition, the extract also inhibited partially the pro-coagulant activity of the venom and abolished the degradation of Aα and Bβ chains of human fibrinogen. Thus, the extract possesses potent anti-snake venom property, especially against the local effects of viper bites.

Trastornos de coagulación en trauma craneoencefálico / Coagulation disorders in cranioencephalic trauma

La comprensión del proceso de la coagulación ha progresado durante la última década, evolucionando a partir del concepto según el cual la producción del coágulo se iniciaba por acción de las plaquetas y la activación de uno de los dos sistemas separados, la vía extrínseca y la vía intrínseca, al concepto actual que hace énfasis sobre la vía común y un sistema proteolítico que da lugar a la degradación de los coágulos formados y a la prevención de la formación indeseada de coágulos. La alteración de este equilibrio cobra especial importancia en los pacientes con trauma craneoencefálico, en quienes -a la luz de los conocimientos actuales- se pueden presentar trastornos de la coagulación que van desde lesiones procoagulantes, en un extremo, hasta lesiones anticoagulantes, en el otro extremo. La meta de los autores es brindar a los clínicos de una guía de evaluación inicial, de seguimiento y, de las posibilidades terapéuticas disponibles en el momento.

The understanding of the coagulation process has progressed during last decade evolving from the concept according to which the production of the clot begins by means of the action of platelets and the activation of one of two separated systems, the extrinsic route and the intrinsic route, to the present concept that makes emphasis on the common route and a proteolytic system that give rise to the degradation of formed clots and to the undesired prevention of the formation of the clot. The alteration of this balance receives special importance in the patients with brain trauma in those who to the light of the present knowledge may present upheavals of the coagulation which can go from procoagulating injuries in one end to anticoagulating injuries in the other. The goal of the authors is to provide a clinical guide with initial evaluation, pursuit and therapeutic possibiliti.es available at the moment.

Evaluación de inhibidores fisiológicos de la coagulación en pacientes diabéticos tipo 2 / Evaluation about coagulation physiological inhibitors in type 2 diabetic patients

La diabetes mellitus está asociada a disturbios en la hemostasis que pueden contribuir al desarrollo de enfermedad vascular diabética. El objetivo de este trabajo fue estudiar la coagulación en una población diabética de Uruguay y compararla con una población de referencia normal. Se trabajó con 100 pacientes diabéticos tipo 2, de ambos sexos (49 mujeres y 51 hombres), con edades comprendidas entre 42 y 79 años, y una población control representada por 130 individuos aparentemente sanos (73 mujeres y 57 hombres) cuyas edades oscilaron entre 37 y 78 años, los que fueron tomados como referencia. Se realizaron las determinaciones de tiempo de protrombina (TP), fibrinógeno (Fib), proteína C (PC), proteína S (PS), antitrombina III (ATIII) e inhibidor del activador de plasminógeno (PAI) en plasma citratado. El TP y el Fib se realizaron por nefelometría, la PC, ATIII y PAI se midieron cromogénicamente y la PS se determinó por coagulometría. Se encontró que los inhibidores fisiológicos de la coagulación PS y ATIII son significativamente menores en la población diabética, en tanto que los factores procoagulantes Fib y PAI son significativamente mayores, comparados con la población de referencia. De los hallazgos precedentes se confirma una tendencia a un disbalance hemostático que contribuiría al estado protrombótico que acompaña a un alto porcentaje de la población diabética.

Diabetes mellitus is associated with disturbances in hemostasis, which may contribute to the development of diabetic vascular disease. Coagulation tests were performed both in diabetic patients and healthy individuals in Uruguay. The results obtained were compared. Diabetic patients were 100, with ages between 42 and 79 years, 49 females and 51 males. Reference population were 130 healthy individuals between 37 and 78 years, 73 females and 57 males. Prothrombin time (PT), fibrinogen( Fib), protein C (PC), protein S (PS), antithrombin III (ATIII) and plasminogen activator inhibitor (PAI) were measured on citrated plasma. PT and Fib were determined nephelometrically, PC, ATIII y PAI were measured cromogenically and PS was determined by coagulometry. Coagulation physiological inhibitors outcomes such as PS and ATIII showed significantly lower levels in the diabetic patient than in the healthy person, and at the same time, Fib and PAI, which are procoagulant factors, have significantly higher concentrations in the diabetic patient than in the healthy person. These findings permit to assess that an impaired haemostatic balance is present in the diabetic population, which may contribute to the hypercoagulability that accompanies a high percentage of these patients.

Plasma Level of IL-6 and Its Relationship to Procoagulant and Fibrinolytic Markers in Acute Ischemic Stroke

Procoagulant or impaired fibrinolytic states as well as inflammatory reactions mediated by cytokines are likely involved in the pathogenesis of acute ischemic stroke. We examined the potential relationship between interleukin 6 (IL-6) and hemostatic markers. The procoagulant and fibrinolytic states were assessed in 46 patients with acute stroke by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT), and plasminogen-antiplasmin complex (PAP). Circulating IL-6 levels were measured using ELISA (Quantikine, R and D systems, MN, USA). Circulating IL-6 (mean, 26.5 pg/mL) and PAI-1 (mean, 19.9 ng/mL) levels were higher in patients with acute stroke than in healthy subjects (mean, 3.0 pg/mL, 10.4 ng/mL, respectively). TAT levels were statistically different according to the etiologic subtypes of stroke (atherogenic, 2.5 ng/mL; lacunar 3.2 ng/mL; cardiogenic 9.9 ng/mL, p = 0.021). Neither procoagulant levels nor fibrinolytic markers significantly correlated with circulating IL-6 levels. Our findings suggest that elevated proinflammatory cytokines during the initial hours of ischemic stroke may be an independent pathogenic factor or a consequence of the thrombotic event with no relationship to the procoagulant or fibrinolytic states.

A simple method for quantitation of procoagulant activity of tissue factor / 中华检验医学杂志

Objective To develop a quantitative assay method for the determination of tissue factor. Methods Lyophilized prothrombin complex was used as the source of factor Ⅶ,Ⅹ. Synthetic chromogenic substrate (S2222)was hydrolyzed into p nitroaniline. The absorbency of p nitroaniline measured spectrophotometrically at 405 nm is proportional to TF quantity in logarithm ( r =0.998). Results The linear range was from 10 U to 10 5 U. Low and high coefficients of variation were 10.3%, 6.6% within day and 18.1%, 10.2% day to day. Conclusions The method is very simple, sensitive, with good linearity, and applicable to quantitation of TF activity quickly.

Procoagulant activity and thrombelastography in korean hemorrhagic fever

Twenty male patients with Korean hemorrhagic fever were evaluated with thrombelastography (TEG) to assess the changes in coagulation system, and the results were compared with those of conventional coagulation tests. Procoagulant activity in the plasma was determined by comparing the reaction time "r" of the normal plasma and that of the mixture of equal parts of the normal plasma and the patient's plasma. The TEG was found to be a useful measure of the changes in the coagulation profile, and provided instant accurate assessment of the patient's hemostatic function. Presence of the procoagulant activity was demonstrated in the plasma of the patients and indicated occurrence of active intravascular coagulation during the early stage of the disease.