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Kinetics of plasma coagulation and lysis I: Basic kinetic model for time course of coagulation-lysis systems and its potential application to clinical studies.

The time courses of coagulation and coagulation-lysis were spectrophotometrically monitored after the addition of thrombin or thrombin-streptokinase to plasma, diluted 1:5 with normal saline, obtained from normal and presumably abnormal subjects. The kinetics of clotting, after an initial lag period of 0.5-1.5 min, demonstrated essentially first-order dependence on the amount of fibrinogen available to form the clot, and the asymptotic absorbance was independent of thrombin concentration. The rate of clotting was a function of added thrombin, and the ratios of the rate constants at 2.5 and 1.25 units of thrombin/ml of undiluted plasma were 1.65 +/- 0.03 SEM. At early times, the coagulation-lysis curve with thrombin-streptokinase could be superimposed on the clotting curve with thrombin alone for a given plasma with minor compensation for variable lag times. Subsequently, the curves diverged; lysis was monitored by the decrease in absorbance of the coagulation-lysis system. The rate of fibrinolysis increased with streptokinase concentration and was a function of the extent of lysis, and it permitted the description of the kinetics of lysis by a pseudoautocatalytic mechanism where the bimolecular rate constant appears proportional to streptokinase concentration. Ranges of clotting and lytic parameters for the plasma of normal subjects are given, and their potential use in diagnosing abnormalities is described.

Blood Coagulation↗

Study on coagulation property of metal-polysilicate coagulants in low turbidity water treatment.

In order to remove the low turbidity present in surface water, a novel metal-polysilicate coagulant was used to treat the raw water taken from Tanjiang River in Guangdong Province. This study on the effects of Al/Fe molar ratio on the performance of a complex compound formed by polysilicic acid, aluminium and ferric salt (PAFS) showed that PAFS with Al/Fe ratio of 10:3 seemed to have the best coagulation performance in removing turbidity and color. Experimental results showed that under the conditions of polymerization time of 15 d, sedimentation time of 12 min, and pH of 6-8, PAFS with Al/Fe molar ratio of 10:3 had the best coagulation efficiency and lowest residual Al concentration. The turbidity decreased from 23.8 NTU to 3.23 NTU and the residual Al concentration was only 0.165 mg/L in the product water. It could be speculated that colloidal impurities and particulate Al were removed by adsorption bridging and electrical neutralization of long chain inorganic polymer coagulants.

Adsorption↗

No interplay between the pathways mediating coagulation and inflammation in tissue factor-induced disseminated intravascular coagulation in rats.

OBJECTIVE: Previous reports have suggested an interplay between the pathways mediating coagulation and inflammation in endotoxemia and sepsis. The present study was designed to examine whether cross-signaling between the pathways mediating coagulation and inflammation occurs, as suggested by the pattern of cytokine production observed following tissue-factor (TF)-induced disseminated intravascular coagulation (DIC). DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Male Wistar rats, aged 6-7 wks, and weighing 160-170 g. INTERVENTIONS: Male Wistar rats were administered TF (3.75 units/kg every 4 hrs), TF, and tranexamic acid (TA; 50 mg/kg every 4.5 hrs) or lipopolysaccharide (30 mg/kg every 4 hrs) via the tail vein, and blood was sampled at 0, 4, 8 and 12 hrs. MEASUREMENTS AND MAIN RESULTS: Subsequent alterations in thrombin-antithrombin complex and fibrinogen levels, as well as platelet counts, indicated that the severity of both types of experimental DIC (TF-induced and lipopolysaccharide-induced) was similar with respect to hemostatic activation and development of consumption coagulopathy. In lipopolysaccharide-induced DIC, a sharp increase in plasma tumor necrosis factor levels was observed at 4 hrs, after which a sharp decline was noted. Plasma levels of interleukin-6 were markedly increased at 4 hrs, after which a sustained elevation was observed for the duration of the experimental period (tumor necrosis factor, 1270 +/- 280, 180 +/- 40, and 120 +/- 30 pg/mL at 4, 8 and 12 hrs, respectively; interleukin-6, 5810 +/- 1320, 4850 +/- 730, and 5230 +/- 1280 pg/mL at 4, 8 and 12 hrs, respectively). On the other hand, tumor necrosis factor and interleukin-6 were not detected following TF-induced DIC (0 +/- 0 at 4, 8, and 12 hrs for both tumor necrosis factor and interleukin-6). In the TF+TA group, significant increases in tumor necrosis factor and interleukin-6 were observed, compared with the TF group. CONCLUSIONS: There is no overt interplay between the pathways mediating coagulation and inflammation in TF-induced DIC, as observed in lipopolysaccharide-induced DIC.

Animals↗

[Effect of aprotinin on selected parameters of coagulation and drainage blood loss after cardiac operations in patients without coagulation disorders].

THE AIM OF THE STUDY: An estimation of influence of different doses of aprotynin on bleeding, coagulation parameters and safety of its use after coronary artery bypass grafting (CABG) in pts without coagulation disorders. MATERIAL AND METHODS: 91 patients underwent CABG, 73 men, 18 women in age 37 to 76 +/- 56.5 years. Patients were randomly assigned to 3 groups; Group I; 38 pts. 6.5 mln KIU aprotynin. Group II; placebo--30 pts. Group III; 23 pts. 2 mln. KIU. There were 4 measurements 1.--before operation, 2. after discontinuing CPB, 3.--6 h after operation, 4.--24 h after operation. We measured Hb, Ht, PLT Glucose, D-dimers, APTT, TT Fibrynogen, INR, AT3, Ca2+, factor V, VIII, GOT GPT CK, CK-MB, CRP, ACT concentration of Hb in drainage 6 h after operation. There were estimated: renal function profile, drainage loss, perioperative MI, mortality, reoperation rate due to bleeding. RESULTS: The level of blood count and coagulation parameters did not differ between the groups in any test periods. D-dimer levels were significantly higher in the placebo group than in group I and III. The decrease of fibrin degradation was not related to the dose of aprotynin. Drainage was insignificantly higher in placebo group. Renal function was impaired in neither group. Reoperation rate perioperative infarction and mortality did not differ between the groups, however was highest in group I. CONCLUSION: Aprotynin reduces blood loss after operation in CPB and decrease fibrin degradation independently to the dose of the drug. The high-dose of aprotynin may increase the risk of early graft occlusion in patients without coagulation disorders.

Adult↗

Amino sugar levels in normally coagulating and poorly coagulating human ejaculates.

Free and total amino sugar levels were determined in human prostatic fluid, vasectomized semen, presumably fertile semen, and in ejaculates having different degrees of coagulation. About 87% of the total amino sugar in seminal plasma was found in the bound form. The seminal vesicles were the richest source for seminal amino sugar, being followed by the prostate, while the epididymes contributed negligibly, if at all. Total amino sugar level of the poorly coagulating ejaculates was found to be significantly lower than those of the vasectomized, presumably fertile, and normally coagulating ejaculates. The degree of coagulation and the amino sugar level of human ejaculates were related by a correlation coefficient of .468 (n = 60; P less than .001).

Adult↗

Changes in the coagulation-fibrinolysis balance of endothelial cells and mononuclear phagocytes: role in disseminated intravascular coagulation associated with infectious diseases.

Over the last few years, evidence has accumulated that the pathogenetic mechanism of disseminated intravascular coagulation encountered in patients with infectious diseases is extraordinarily complex and involves multiple interactions between the microorganism itself and/or a number of mediators, both microorganism derived and host manufactured, and multifunctional cellular systems, namely endothelial cells and mononuclear phagocytes. In particular, infectious agents and mediators shift the coagulation-fibrinolysis equilibrium of these cells towards fibrin formation and accumulation, via enhancement of procoagulant properties and reduction of both anticoagulant and fibrinolytic capacities. New insights into the pathogenetic mechanism may have important implications for the management of infected patients with disseminated intravascular coagulation.

Animals↗

Progestational agents and blood coagulation. VIII. Effect of low-dose, alternate-day, estrogen-progestin combinations on blood coagulation factors in man, with a special note on the effect of freezing of blood samples.

Changes in the blood coagulation system were studied in three groups of 20 patients each. The first group received 0.5 mg. of norethindrone daily, plus 0.06 mg. of ethinyl estradiol on alternate days from cycle Day 5 through 25. The second group, all of whom had been fitted with an intrauterine contraceptive device (IUD), received no hormonal treatment and served as a control group. The third group received 0.5 mg. of norethindrone daily, combined with 0.045 mg. of ethinyl estradiol given on alternate days from cycle Day 5 through 25. Blood samples were drawn prior to the initiation of the study and after three months of treatment. Tests of the following parameters of the blood coagulation system were performed: direct platelet count; platelet adhesiveness; prothrombin time; thrombin time; fibrinogen; factor II assay; activity of factors V, VII, VIII, IX, and X; antithrombin III; and fibrin/fibrinogen degradation products. For a number of these factors, both fresh and frozen blood samples were examined. It was concluded that the two treatment regimens, with the use of alternate-day estrogen administration over a three-month period, had no clinically significant effect on the blood coagulation system.

Adolescent↗

Activation of coagulation and disseminated intravascular coagulation in the newborn.

Human newborns have certain hemostatic "deficiencies" which seem to be peculiar to this period of life, such as reduced factors II, VII, IX, X, XI, and XII, reduced antithrombin III levels, and reduced plasminogen levels. However, they are capable of activating the coagulation mechanism to elicit either the entity of disseminated intravascular coagulation or the occurrence of localized and diffuse thrombotic events. The mechanisms involved have yet to be defined. Evidence has been presented to suggest that preterm infants may manifest a variant form of disseminated intravascular coagulation in which thrombocytopenia is not present.

Adult↗

Acquired coagulation inhibitor in association with Rocky Mountain spotted fever. With a review of other acquired coagulation inhibitors.

An acutely ill 4-year-old girl with Rocky Mountain spotted fever (RMSF) was found to have a coagulation inhibitor. This child had no serious bleeding manifestations and minimal hemorrhagic skin manifestations despite severe RMSF, concurrent thrombocytopenia, as well as the coagulation inhibitor. Hemostatic abnormalities that occur with RMSF as well as other infectious illnesses associated with coagulation inhibitors are reviewed.

Autoantibodies↗

Blood coagulation and fibrinolysis of rats fed fish oil: reduced coagulation factors especially involved in intrinsic pathway and increased activity of plasminogen activator inhibitor.

Differences in the coagulation and fibrinolytic system of rats fed a fish oil based diet (fish oil diet) and fed a soybean oil based diet (control diet) were determined. Concentrations of plasma lipids were depressed in rats fed the fish oil diet. Prothrombin time (PT) and activated partial thromboplastin time (APTT) of rats fed the fish oil diet were longer than for the rats fed the control diet. Fish oil intake lowered the activities of most of the blood coagulation factors, and strongly depressed the factors involved in the intrinsic pathway. Fish oil also affected the fibrinolysis of rats. Plasminogen activator inhibitor (PAI) activity was elevated in rats fed the fish oil diet. In this study, both blood coagulation and fibrinolysis were down-regulated by feeding the fish oil diet.

Animals↗

Simultaneous determination of coagulation and fibrinolysis parameters for diagnostics of disseminated intravascular blood coagulation (DIC).

A diagnostic method is described for determining the parameters of the human blood plasma coagulation and fibrinolysis by turbidimetry. Diluted plasma with thrombin and streptokinase is mixed to initiate clot formation and subsequent clot dissolution. The resultant profile of absorbance versus time is analysed to determine six parameters: plasma coagulation time, the rate of coagulation, fibrinogen concentration, the rate of fibrinolysis, fibrin clot half-lysis and lysis time. The assay is precise, sensitive and requires 0.1 ml plasma. The method has a good correlation with generally accepted haemostatic tests and allowed us to recognize the stage of DIC syndrome for less than 10 minutes. This new approach was successfully applied for studying the haemostasis in patients with acute intestinal infection.

Blood Coagulation↗

Fluorogenic detection of primary amines in plant histochemistry with fluorescamine: a comparative study on the effects of coagulant and non-coagulant fixatives.

The new highly sensitive method of fluorescamine reaction for the topochemical detection of primary amino groups was studied as a substitude of ninhydrin-Schiff's reaction for the localisation of total proteins in plant tissues. The influence of various coagulant and non-coagulant fixatives on the induction of fluorescamine fluorescence was examined: ethanol, formaldehyde gas and solution, glutaraldehyde, acrolein, osmium tetroxide, Bouin, Rossman, Clarke and Zenker's fluids and FMA were employed. It was found that the use of the fluorogenic method is conditioned by the fixative ability to keep the amino groups disposable and by its capability to reduce the natural autofluorescence of plant material. A detailed account of the fixation methodology demonstrated that non-coagulant acrolein and coagulant mercuric chloride are the most promising fixatives for the use of the fluorescamine reaction in plant histochemistry.

Amines↗

Demonstration of the extrinsic coagulation pathway in teleostei: identification of zebrafish coagulation factor VII.

It is not known whether the mammalian mechanism of coagulation initiation is conserved in fish. Identification of factor VII is critical in providing evidence for such a mechanism. A cDNA was cloned from a zebrafish (teleost) library that predicted a protein with sequence similarity to human factor VII. Factor VII was shown to be present in zebrafish blood and liver by Western blot analysis and immunohistochemistry. Immunodepletion of factor VII from zebrafish plasma selectively inhibited thromboplastin-triggered thrombin generation. Heterologous expression of zebrafish factor VII demonstrated a secreted protein (50 kDa) that reconstituted thromboplastin-triggered thrombin generation in immunodepleted zebrafish plasma. These results suggest conservation of the extrinsic coagulation pathway between zebrafish and humans and add credence to the zebrafish as a model for mammalian hemostasis. The structure of zebrafish factor VIIa predicted by homology modeling was consistent with the overall three-dimensional structure of human factor VIIa. However, amino acid disparities were found in the epidermal growth factor-2/serine protease regions that are present in the human tissue factor-factor VIIa contact surface, suggesting a structural basis for the species specificity of this interaction. In addition, zebrafish factor VII demonstrates that the Gla-EGF-EGF-SP domain structure, which is common to coagulation factors VII, IX, X, and protein C, was present before the radiation of the teleosts from the tetrapods. Identification of zebrafish factor VII significantly narrows the evolutionary window for development of the vertebrate coagulation cascade and provides insight into the structural basis for species specificity in the tissue factor-factor VIIa interaction.

Amino Acid Sequence↗

Monitoring of coagulation performance and determination of coagulant dosage using a pilot in-line filter.

A rapid method using the pilot in-line filter to detect any change in coagulation performance was a proposed in this study. This method attempted to detect a change in coagulant dosage and mixing intensity by evaluating the filtrate quality of the in-line filter, which took the rapidly mixed water. Since the response time of this method was less than 10 min, it could be valuable to monitor the coagulation performance. The in-line filter was found more useful without underdrain. The in-line filter was more sensitive to a change in filtrate quality without underdrain than with underdrain. A new method, which combines a jar test with the in-line filter, was proposed to determine the coagulant dosage. This method reflected the actual plant situation more accurately than a jar test.

Aluminum Hydroxide↗

Time sequence of coagulation data in patients with decompensated liver cirrhosis and suspected disseminated intravascular coagulation.

In patients with liver cirrhosis, especially in the advanced stage, the coexistence of low clotting factor levels, hypofibrinogenemia, thrombocytopenia and elevated fibrin(ogen) degradation product (FDP) and D-dimer levels may suggest the presence of disseminated intravascular coagulation (DIC). In this study we evaluated, in 21 patients with decompensated liver cirrhosis and elevated FDP and D-dimer levels, the time sequence of their coagulation data during a follow-up period of 15 days after the first observation; our aim was to clarify if these patients tend to develop during this time interval a severe consumption coagulopathy as an expression of overt DIC. We evaluated serum fibrinogen, platelet count, prothrombin activity, serum FDP and plasma D-dimer levels at days 1, 3, 6, 10 and 15. The coagulation data were fairly stable during the study period in all patients, even in the two patients who had upper digestive tract bleeding during the study time. Only two patients affected by infectious diseases showed a decrease of D-dimer and FDP levels after healing. Our data suggest that in decompensated liver cirrhosis the detection of elevated FDP and D-dimer levels is seldom related to the occurrence of an overt DIC, at least during a short time interval; in this condition heparin therapy seems therefore not advisable and even potentially dangerous.

Aged↗

Changes in coagulation and fibrinolysis during pregnancy: evidence of activation of coagulation preceding spontaneous abortion.

In order to monitor physiological changes in coagulation and fibrinolysis that occur during normal pregnancy, blood samples were collected in each trimester of pregnancy from 17 volunteers. Control samples were collected from 12 non-pregnant female volunteers. As pregnancy advanced there was a rise in the basal levels of fibrinopeptide A, cross linked D-dimer fragment and the B beta 15-42 fragment and an increase in the in vitro rate of fibrinopeptide A generation. These results were consistent with an increased activation of coagulation during normal pregnancy, compensated for by a concomitant rise in fibrinolytic activity. In two patients who spontaneously aborted, evidence of uncompensated activation of coagulation could be detected before the manifestation of any clinical signs. In a second pregnancy in one of these patients similar changes were observed, but were reversed by heparin treatment and the pregnancy progressed to full-term delivery of a normal infant.

Abortion, Spontaneous↗

Stability, sterility, coagulation, and immunologic studies of salmon coagulation proteins with potential use for mammalian wound healing and cell engineering.

Fibrin sealants made by polymerization of fibrinogen activated by the protease thrombin have many applications in hemostasis and wound healing. In treatments of acute injury or surgical wounds, concentrated fibrin preparations mimic the initial matrix that normally prevents bleeding and acts as a scaffold for cells that initiate tissue repair. However risks of infectious disease, immunogenic reaction, and the high cost of purified human or other mammalian blood proteins limit widespread use of these materials. Purified coagulation proteins from Atlantic salmon represent a potentially safer, equally effective, and less costly alternative in part because of the low ambient temperature of these farmed animals and the absence of endogenous agents known to be infectious in mammalian hosts. This study reports rheologic measurements of lyophilized salmon fibrinogen and thrombin that demonstrate stability to prolonged storage and gamma irradiation sufficient to reduce viral loads by over five orders of magnitude. Coagulation and immunologic studies in rats and rabbits treated intraperitoneally with salmon fibrin show no deleterious effects on coagulation profiles and no cross reactivity with host fibrinogen or thrombin. The results support the potential of salmon fibrin as an alternative to mammalian proteins in clinical applications.

Animals↗

Study of the balance between coagulation and fibrinolysis in disseminated intravascular coagulation using molecular markers.

Plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC) and active plasminogen activator inhibitor (PAI) were assayed in 66 cases of disseminated intravascular coagulation (DIC). Significant elevation of both TAT and PIC was observed in all cases of DIC. Most elevated levels of TAT were seen in DIC with acute promyelocytic leukaemia (APL) and sepsis. The highest levels of PIC were seen in DIC with APL but were much lower in sepsis. A significant elevation in active PAI was observed in DIC due to acute leukaemia (apart from APL), chronic myeloid leukaemia and sepsis, but not in APL, non-Hodgkin lymphoma and cancer. Active PAI was higher in patients with multiple organ failure (MOF) than in those without MOF while PIC was lower in patients with this complication. Thus, the balance of coagulation and fibrinolysis varied according to the underlying cause of DIC; APL had more dominant activation of fibrinolysis, while sepsis had greater activation of coagulation. It is suggested that the inhibition of secondary fibrinolytic activation plays an important role in the progression of MOF by the disturbance of the microcirculation.

Antifibrinolytic Agents↗