Fibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion

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Chernysh, Irina N.; Nagaswami, Chandrasekaran; Purohit, Prashant K.; Weisel, John W.

2012-01-01

Fibrin polymerization is a necessary part of hemostasis but clots can obstruct blood vessels and cause heart attacks and strokes. The polymerization reactions are specific and controlled, involving strong knob-into-hole interactions to convert soluble fibrinogen into insoluble fibrin. It has long been assumed that clots and thrombi are stable structures until proteolytic digestion. On the contrary, using the technique of fluorescence recovery after photobleaching, we demonstrate here that the...

Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

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Reed, G. L.; Matsueda, G. R.; Haber, E.

1992-01-01

Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

Effect of Tranexamic Acid on Blood Loss, D-Dimer, and Fibrinogen Kinetics in Adult Spinal Deformity Surgery.

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Pong, Ryan P; Leveque, Jean-Christophe A; Edwards, Alicia; Yanamadala, Vijay; Wright, Anna K; Herodes, Megan; Sethi, Rajiv K

2018-05-02

Antifibrinolytics such as tranexamic acid reduce operative blood loss and blood product transfusion requirements in patients undergoing surgical correction of scoliosis. The factors involved in the unrelenting coagulopathy seen in scoliosis surgery are not well understood. One potential contributor is activation of the fibrinolytic system during a surgical procedure, likely related to clot dissolution and consumption of fibrinogen. The addition of tranexamic acid during a surgical procedure may mitigate the coagulopathy by impeding the derangement in D-dimer and fibrinogen kinetics. We retrospectively studied consecutive patients who had undergone surgical correction of adult spinal deformity between January 2010 and July 2016 at our institution. Intraoperative hemostatic data, surgical time, estimated blood loss, and transfusion records were analyzed for patients before and after the addition of tranexamic acid to our protocol. Each patient who received tranexamic acid and met inclusion criteria was cohort-matched with a patient who underwent a surgical procedure without tranexamic acid administration. There were 17 patients in the tranexamic acid cohort, with a mean age of 60.7 years, and 17 patients in the control cohort, with a mean age of 60.9 years. Estimated blood loss (932 ± 539 mL compared with 1,800 ± 1,029 mL; p = 0.005) and packed red blood-cell transfusions (1.5 ± 1.6 units compared with 4.0 ± 2.1 units; p = 0.001) were significantly lower in the tranexamic acid cohort. In all single-stage surgical procedures that met inclusion criteria, the rise of D-dimer was attenuated from 8.3 ± 5.0 μg/mL in the control cohort to 3.3 ± 3.2 μg/mL for the tranexamic acid cohort (p tranexamic acid cohort to 60.6 ± 35.1 mg/dL (p = 0.004). In patients undergoing spinal surgery, intravenous administration of tranexamic acid is effective at reducing intraoperative blood loss. Monitoring of D-dimer and fibrinogen during spinal surgery suggests that tranexamic acid

Examining platelet-fibrin interactions during traumatic shock in a swine model using platelet contractile force and clot elastic modulus.

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White, Nathan J; Martin, Erika J; Brophy, Donald F; Ward, Kevin R

2011-07-01

A significant proportion of severely injured patients develop early coagulopathy, characterized by abnormal clot formation, which impairs resuscitation and increases mortality. We have previously demonstrated an isolated decrease in clot strength by thrombelastography in a swine model of nonresuscitated traumatic shock. In order to more closely examine platelet-fibrin interactions in this setting, we define the observed decrease in clot strength in terms of platelet-induced clot contraction and clot elastic modulus using the Hemostasis Analysis System (HAS) (Hemodyne Inc., Richmond, Virginia, USA). Whole blood was sampled for HAS measurements, metabolic measurements, cell counts, and fibrinogen concentration at baseline prior to injury and again at a predetermined level of traumatic shock defined by oxygen debt. Male swine (N=17) received femur fracture and controlled arterial hemorrhage to achieve an oxygen debt of 80 ml/kg. Platelet counts were unchanged, but fibrinogen concentration was reduced significantly during shock (167.6 vs. 66.7 mg/dl, P=0.0007). Platelet contractile force generated during clot formation did not change during shock (11.7 vs. 10.4 kdynes, P=0.41), but clot elastic modulus was dynamically altered, resulting in a lower final value (22.9 vs. 17.3 kdynes/cm, Pshock, platelet function was preserved, whereas terminal clot elastic modulus was reduced during shock in a manner most consistent with early changes in the mechanical properties of the developing fibrin fiber network.

Fibrinogen monitor

International Nuclear Information System (INIS)

1980-01-01

Apparatus is described for use in detecting the formation of blood clots in a patient who has previously been injected with a tracer quantity of radioactive fibrinogen. It consists of a scintillation detector, associated electronics for pulse processing and a digital display for the operator as well as a punched paper-tape for permanent record. The detector measures the radioactive count rate along the patient's leg over a given interval and compares this with a reference value. Higher count rate events which are deemed to be statistically significant, indicate thrombosis. Lower than average count rates usually indicate mis-alignment of the detector and patient's leg and warning of such is given to the operator. Compared to previous instruments, the present apparatus is easier to use and is also more comfortable for the patient. (UK)

Some Important Milestones in the Field of Blood Clotting.

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Doolittle, Russell F

2016-01-01

Several different kinds of 'milestone' in the field of blood coagulation are described from the middle decades of the 20th century. Although viewed from the standpoint of clotting per se, attention is also given to implications for innate immunity. The first milestone considered is the protracted saga of clotting dependence on vitamin K, an adventure that spanned more than five decades beginning in the 1920s. The second has to do with the discovery of a half-dozen 'new' clotting factors during the period immediately following World War II. A third pursues a narrower focus and examines the once mysterious transformation of fibrinogen into fibrin. Finally, the clinical treatment of classical hemophilia had a remarkable turning point in the 1960s as the result of simple but sensible measures. © 2015 S. Karger AG, Basel.

Skeletal changes in congenital fibrinogen abnormalities

Energy Technology Data Exchange (ETDEWEB)

Lagier, R.; Bouvier, C.A.; van Strijthem, N.

1980-01-01

We report anatomico-radiologic study of humerus, femur, and tibia from a case of total congenital afibrinogenemia. Juxtatrabecular hemorrhages occur mainly in metaphyses and seem to be related to normal lines of stress. They may lead to the formation of intraosseous cysts and to a remodelling of bone trabeculae. The radiologic lesions in a second case, diagnosed as congenital dysfibrinogenemia, are similar to those found in Case 1 (femoral trabeculae remodelling) but also resemble some alterations described in hemophilia (pseudotumor of the right iliac bone). Anatomic study of the lesions in Case 2 was not possible. The significance of these observations could be better defined by a more extended skeletal study (radiologic and when feasible anatomic) of patients with congenital clotting defects and especially with inherited disorders of the fibrinogen molecule. It would also be worthwhile investigating manifest or latent hemostatic disorders (particularly at the fibrinogen level) in patients with solitary or aneurysmal bone cysts, and even with bone infarct or unexplained trabecular remodelling.

The effects of Aloe vera [gel] on clotting time, prothrombin time and ...

African Journals Online (AJOL)

Background: Published reports on the effects of Aloe vera gel on blood coagulation in experimental animals are relatively scanty. Aim: To determine the effect of Aloe vera gel on clotting time, prothrombin time and plasma fibrinogen concentration in albino Wistar rats. Methods: A total of 28 adult albino Wistar rats divided ...

Effects of botropase on clotting factors in healthy human volunteers

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Ashok K Shenoy

2014-01-01

Full Text Available Objective: To evaluate the effects of botropase on various clotting factors in human volunteers. Materials and Methods: It was a prospective open label study conducted on human healthy volunteers. After the baseline screening, subjects fulfilling inclusion criteria were enrolled. On the study day, 1 ml of botropase was administered intravenously and after an hour same dose of botropase (1 ml was given by intramuscular (IM route. The efficacy and safety parameters were monitored up to 72 h from the time of intravenous (IV administration. Results: A total of 15 volunteers, belonging to 24-35 years of age were included in the study. Botropase significantly reduced the plasma level of fibrinogen and fibrin degradation products after 5 min of IV administration (P < 0.05. In addition, factor X was observed to reduce constantly by botropase administration suggesting enhanced turnover between 5 and 20 min of IV administration. Although botropase reduced clotting and bleeding time in all the volunteers, the data remains to be statistically insignificant. Conclusion: Present study demonstrated the safety and efficacy of botropase in human healthy volunteers. The study has shown that it is a factor X activator and reduces effectively clotting and bleeding time.

Addition of a sequence from α2-antiplasmin transforms human serum albumin into a blood clot component that speeds clot lysis

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Gataiance Sharon

2009-03-01

Full Text Available Abstract Background The plasma protein α2-antiplasmin (α2AP is cross-linked to fibrin in blood clots by the transglutaminase factor XIIIa, and in that location retards clot lysis. Competition for this effect could be clinically useful in patients with thrombosis. We hypothesized that fusion of N-terminal portions of α2-antiplasmin to human serum albumin (HSA and production of the chimeric proteins in Pichia pastoris yeast would produce a stable and effective competitor protein. Results Fusion protein α2AP(13-42-HSA was efficiently secreted from transformed yeast and purified preparations contained within a mixed population the full-length intact form, while fusions with longer α2AP moieties were inefficiently secreted and/or degraded. The α2AP(13-42-HSA protein, but not recombinant HSA, was cross-linked to both chemical lysine donors and fibrin or fibrinogen by factor XIIIa, although with less rapid kinetics than native α2AP. Excess α2AP(13-42-HSA competed with α2AP for cross-linking to chemical lysine donors more effectively than a synthetic α2AP(13-42 peptide, and reduced the α2AP-dependent resistance to fibrinolysis of plasma clots equally effectively as the peptide. Native α2AP was found in in vivo clots in rabbits to a greater extent than α2AP(13-42, however. Conclusion In this first report of transfer of transglutamination substrate status from one plasma protein to another, fusion protein α2AP(13-42-HSA was shown to satisfy initial requirements for a long-lasting, well-tolerated competitive inhibitor of α2-antiplasmin predicted to act in a clot-localized manner.

Clot lysis time in platelet-rich plasma: method assessment, comparison with assays in platelet-free and platelet-poor plasmas, and response to tranexamic acid.

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Panes, Olga; Padilla, Oslando; Matus, Valeria; Sáez, Claudia G; Berkovits, Alejandro; Pereira, Jaime; Mezzano, Diego

2012-01-01

Fibrinolysis dysfunctions cause bleeding or predisposition to thrombosis. Platelets contain several factors of the fibrinolytic system, which could up or down regulate this process. However, the temporal relationship and relative contributions of plasma and platelet components in clot lysis are mostly unknown. We developed a clot lysis time (CLT) assay in platelet-rich plasma (PRP-CLT, with and without stimulation) and compared it to a similar one in platelet-free plasma (PFP) and to another previously reported test in platelet-poor plasma (PPP). We also studied the differential effects of a single dose of tranexamic acid (TXA) on these tests in healthy subjects. PFP- and PPP-CLT were significantly shorter than PRP-CLT, and the three assays were highly correlated (p plasma PAI-1, von Willebrand factor, fibrinogen, LDL-cholesterol, and triglycerides (p platelet aggregation/secretion, platelet counts, and pro-coagulant tests to explore factor X activation by platelets, PRP clotting time, and thrombin generation in PRP. Among all the studied variables, PFP-CLT was independently associated with plasma PAI-1, LDL-cholesterol, and triglycerides and, additionally, stimulated PRP-CLT was also independently associated with plasma fibrinogen. A single 1 g dose of TXA strikingly prolonged all three CLTs, but in contrast to the results without the drug, the lysis times were substantially shorter in non-stimulated or stimulated PRP than in PFP and PPP. This standardized PRP-CLT may become a useful tool to study the role of platelets in clot resistance and lysis. Our results suggest that initially, the platelets enmeshed in the clot slow down the fibrinolysis process. However, the increased clot resistance to lysis induced by TXA is overcome earlier in platelet-rich clots than in PFP or PPP clots. This is likely explained by the display of platelet pro-fibrinolytic effects. Focused research is needed to disclose the mechanisms for the relationship between CLT and plasma

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

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Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro

2016-01-01

The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma. PMID:27009516

Fibrinogen assays: a collaborative study of six different methods. C.I.S.M.E.L. Comitato Italiano per la Standardizzazione dei Metodi in Ematologia e Laboratorio.

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Palareti, G; Maccaferri, M; Manotti, C; Tripodi, A; Chantarangkul, V; Rodeghiero, F; Ruggeri, M; Mannucci, P M

1991-05-01

This collaborative study, organized by the Hemostasis Subcommittee of C.I.S.M.E.L., evaluated the accuracy, precision, and comparability of the following six widely used fibrinogen assays: total clottable fibrinogen (Blombäck and Blombäck), clotting time (Von Clauss), turbidimetry (Ellis and Stransky), Chromotime System, prothrombin time (PT)-derived, and radial immunodiffusion (RID). The same frozen samples, with normal and high contents of fibrinogen, were examined in four laboratories. The methods were calibrated with an internal standard whose fibrinogen content was determined gravimetrically. Both the Von Clauss and the RID methods were reliable, accurate, and precise, if adequate calibration was used. The PT-derived method was highly reproducible, but had some problems with accuracy. We demonstrate that an adequate calibration procedure is indispensable for reliable fibrinogen measurements whatever method is used. Because neither the calibration procedures proposed by the manufacturers nor the use of lyophilized commercial plasmas is adequate for this purpose, we urge that an international standard for fibrinogen measurement be promptly established.

Evaluation of in vivo stability of Ga-67 labeled human fibrinogen

International Nuclear Information System (INIS)

Takahashi, Keietsu; Takahashi, Jun; Okano, Sakae; Kurami, Miki; Ueda, Nobuo; Hazue, Masaaki

1987-01-01

Human fibrinogen (Fib) was conjugated with a large number of deferoxamine (DFO) through dialdehyde starch (DAS), and the conjugate (Fib-DAS-DFO) was labeled with Ga-67. Thus labeled fibrinogen (Ga-67-Fib-DAS-DFO) showed a high labeling efficiency (more than 90 %) and retained clottability (more than 80 %). For the evaluation of plasma radioactive species, blood samples were collected at various time periods after the i.v. administration of Ga-67-Fib-DAS-DFO into rats, and the plasma radioactivity was analyzed by high performance liquid chromatography (HPLC) and electrophoresis (EP). The radioactive HPLC elution profiles for the plasma samples were identical with that of the original Ga-67-Fib-DAS-DFO; the EP patterns for the plasma were also identical with the original one, and no radioactive species, except for Ga-67-Fib-DAS-DFO, was detected by HPLC or EP. Furthermore, the presence of transferrin in the labeling formulation did not affect the labeling yield of Ga-67-Fib-DAS-DFO indicating that the transchelation of Ga-67 from DFO on Fib to transferrin is negligible. These findings indicated that Ga-67 is tightly bound to Fib-DAS-DFO in blood, and the Ga-67-Fib-DAS-DFO can be efficiently trapped by clots as the result of its high retention of physiological activities as fibrinogen. (author)

Rational and timely haemostatic interventions following cardiac surgery - coagulation factor concentrates or blood bank products.

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Tang, Mariann; Fenger-Eriksen, Christian; Wierup, Per; Greisen, Jacob; Ingerslev, Jørgen; Hjortdal, Vibeke; Sørensen, Benny

2017-06-01

Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery. 30 adults were prospectively enrolled (mean age=63.9, females=27%). Ex vivo haemostatic interventions (monotherapy or combinations) were performed in whole blood taken immediately after surgery and two hours postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa (rFVIIa) were investigated. The haemostatic effect was evaluated using whole blood thromboelastometry parameters, as well as by thrombin generation. Immediately after surgery the compromised maximum clot firmness was corrected by monotherapy with fibrinogen or platelets or combination therapy with fibrinogen. At two hours postoperatively the coagulation profile was further deranged as illustrated by a prolonged clotting time, a reduced maximum velocity and further diminished maximum clot firmness. The thrombin lagtime was progressively prolonged and both peak thrombin and endogenous thrombin potential were compromised. No monotherapy effectively corrected all haemostatic abnormalities. The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood bank products were not as effective in the correction of the coagulopathy. Coagulation factor concentrates appear to provide a more optimal haemostasis profile following cardiac surgery compared to blood bank products. Copyright © 2017

Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy

OpenAIRE

Davenport, Ross; Brohi, Karim

2013-01-01

Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen con...

Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

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Geoffrey K Isbister

Full Text Available Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming.In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT, activated partial thromboplastin time (aPTT, coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13, associated with low fibrinogen [median,3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02 and aPTT (r = 0.19, p = 0.03 were correlated (non-parametric Spearman analysis.Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

Fibrinogen in trauma, an evaluation of thrombelastography and rotational thromboelastometry fibrinogen assays

DEFF Research Database (Denmark)

Meyer, Martin A S; Ostrowski, Sisse R; Sørensen, Anne Marie

2015-01-01

BACKGROUND: Identifying hypofibrinogenemia in trauma is important. The optimal method of fibrinogen determination is unknown. We therefore evaluated fibrinogen levels determined by two whole blood viscoelastic hemostatic assays, thrombelastography functional fibrinogen (FF) and rotational thrombo...

Increased Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes

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Anna Lados-Krupa

2015-01-01

Full Text Available Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes. Methods. We assessed plasma fibrin clot permeation (Ks, a measure of the pore size in fibrin networks and clot lysis time induced by recombinant tissue plasminogen activator (CLT in 163 consecutive type 2 diabetic patients (92 men and 71 women aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE, 8-iso-prostaglandin F2α (8-iso-PGF2α, oxidized low-density lipoprotein (oxLDL, and advanced glycation end products (AGE. Results. There were inverse correlations between Ks and nitrotyrosine, sRAGE, 8-iso-PGF2α, and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant for Ks after adjustment for fibrinogen, disease duration, and HbA1c (all P<0.05, while oxLDL was the only independent predictor of CLT. Conclusions. Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control.

Fibrinogen depletion in trauma: early, easy to estimate and central to trauma-induced coagulopathy.

Science.gov (United States)

Davenport, Ross; Brohi, Karim

2013-09-24

Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage, although levels are not routinely measured in the acute bleeding episode. Prompt identification of critically low levels of fibrinogen and early supplementation has the potential to correct trauma-induced coagulation and improve outcomes. Early estimation of hypofibrinogenemia is possible using surrogate markers of shock and hemorrhage; for example, hemoglobin and base excess. Rapid replacement with fibrinogen concentrate or cryoprecipitate should be considered a clinical priority in major trauma hemorrhage.

Fiber-based optic sensor for detecting human blood clot: present and future revival

Science.gov (United States)

Elshikeri, Nada; Bakhtiar, Hazri

2018-05-01

Sustaining human’s life-frame away from being impeded by the clot - ghost term, we attempt to approach a mobile fiber-based optical sensor (f-s) for detecting blood clot in a blood vessel (intra-arteries/veins). Blood vessels are the part of the circulatory system that transport blood throughout the human body, thus their significance of being protected arise to the monograph focus. MRI (magnetic resonance imaging), X-rays and other medical instruments are diagnostic immobility techniques with a slackest interval. The corer causation of fiber-based optical sensor is to detect a clump of blood in the bloodstream by providing a prompt mobile diagnostic intervals preserving last-minutes-breath of human’s life. The detector (f-s) has been etched by diluting sulphuric acid ~10% at certain zone to sensate its function. The in-vitro monograph peaks its maximal monitoring when the sensor is attached to Raman Spectroscopy (RS) setup. RS quantifies the relative intensities of fibrinogen bond, which is the first type of blood coagulation elements of blood plasma. Blood coagulation parameters are the major concern of the monograph investigation, such as total haemoglobin (tHb), clotting reaction time (t), clot progression time (t2), maximum clot amplitude (ma) and mean refractive index (r). A blood sample will be drawn from the patient and after centrifugation to separate blood plasma from its constituents, then an immediate sloshing of blood plasma in the (f-s) packet which has its plug-in to RS. Estimating the quantitative analysis of blood sample concentration, RS will determine the presence of coagulation in terms of intensity and medical procedures will dominate the treatment process. Thus, the suggestive monograph provides a definite instrument for investigating blood coagulation intra-arteries/veins promptly.

Competitions between fibrinogen with its degradation products for interactions with the platelet-fibrinogen receptor

International Nuclear Information System (INIS)

Thorsen, L.I.; Brosstad, F.; Gogstad, G.; Sletten, K.; Solum, N.O.

1986-01-01

Direct binding of 125 -I-labelled plasmic and CNBr-derived fibrin (ogen) fragments (pre-X, X, Y, D, Degta, Efg, E1, N-DSK, N-dsk) to gel-filtered platelets was compared to their ability to support or inhibit ADP-induced aggregation, and to compete with fibrinogen for binding to ADP-stimulated platelets. Pre-X was the only fragment that supported aggregation. All fragments tested except for E derived from fibrinogen (Efg) and Degta bound specifically to the platelets and inhibited ADP-induced aggregation in the presence of fibrinogen. Competitive binding studies with fibrinogen and fragments labelled with different isotopes of iodine, or inhibition of binding of labelled fibrinogen with unlabelled fragments showed that all of the fragments except Efg and Degta were able to compete with fibrinogen for binding. When simultaneous binding of N-dsk and fibrinogen was studied, an increased binding of both ligands was observed probably due to complex formation. The results fully agree with previous findings of binding to immunoprecipitated glycoprotein IIb-IIIa after crossed immunoelectrophoresis. We conclude that the fibrinogen molecule contains at least six sequences responsible for platelet interaction, two in the E domain and two in each of the C-terminal parts of the fibrinogen molecule

Carotid intima-media thickness and plasma fibrinogen among subjects with metabolic syndrome: Isfahan cohort study

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Zahra Bayanfar

2014-09-01

Full Text Available BACKGROUND: The role of plasma fibrinogen, a key regulator of inflammation processes and increased carotid intima-media thickness (cIMT to predict metabolic syndrome (MetS is currently under investigation. We assessed differences in the indicators of cIMT and also plasma fibrinogen level between MetS and non-MetS subjects. We also assessed the role of these two parameters for independently relationship with MetS state. METHODS: The subjects in this cross-sectional survey were population-based samples of 93 men and women aged ≥ 35 years and over who were selected from the Isfahan cohort study, Isfahan, Iran. Fibrinogen was measured by the clotting assay of Clauss. Ultrasound studies of the carotid artery were performed to measure cIMT. MetS defined based on the National Cholesterol Education Program’s Adult Treatment Panel III. RESULTS: The mean level of plasma fibrinogen was not different in the two groups with and without MetS (240.10 ± 27.80 vs. 242.56 ± 35.82, P = 0.714, but the mean of cIMT was considerably higher in MetS group than in non-MetS group (0.85 ± 0.06 mm vs. 0.66 ± 0.09 mm, P < 0.001. Using a multivariable logistic regression model, high cIMT could effectively predict MetS state with the presence of different components of MetS (odds ratio = 17.544, 95% confidence interval: 2.151-142.860, P = 0.008. The optimal cutoff point of cIMT for discriminating these two clinical states was 0.6 mm yielding a sensitivity of 61.5% and a specificity of 59.6%. CONCLUSION: Individuals with MetS demonstrated increased cIMT values compared with those without MetS. However, high plasma fibrinogen level may not be associated with MetS state.   Keywords: Metabolic Syndrome, Carotid Intima-Media Thickness, Fibrinogen, Prediction 

Blood Clotting and Pregnancy

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Full Text Available ... Blood Basics Blood Disorders Anemia Bleeding Disorders Blood Cancers Blood Clots Blood Clotting and Pregnancy Clots and ... Increased maternal age Other medical illness (e.g., cancer, infection) back to top How are Blood Clots ...

Blood Clotting and Pregnancy

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Full Text Available ... For Patients Blood Disorders Blood Clots Blood Clotting & Pregnancy If you are pregnant, or you have just ... The risk of developing a blood clot during pregnancy is increased by the following: Previous blood clots ...

Changes to the structure of blood clots formed in the presence of fine particulate matter

International Nuclear Information System (INIS)

Metassan, Sofian; Routledge, Michael N; Ariens, Robert A S; Scott, D Julian

2009-01-01

Both long-term and short-term exposure (one to two hours) to particulate matter are associated with morbidity and mortality caused by cardiovascular diseases. The underlying mechanisms leading to cardiovascular events are unclear, however, changes to blood coagulability upon exposure to ultrafine particulate matter (UFPM, the smallest of which can enter the circulation) is a plausible mechanism. Objectives: This study aims to investigate the direct effects of particulate matter on fibrin polymerization, lateral aggregation and the formation of fibrin network structure. Methods: Standard Urban Particulate Matter (PM) was suspended in Tris buffer centrifuged and filtered with <200nm filter to obtain ultrafine PM or their water-soluble components. Purified normal fibrinogen was made to clot by adding thrombin and calcium chloride in the presence of varying concentrations of PM. Permeation properties (Darcy constant [Ks]) and turbidity of clots were measured to investigate the effects on flow-rate, pore size, and fibrin polymerization. In addition, confocal microscopy was performed to study detailed clot structure. Results: Total PM increased the Ks of clots in a dose dependant manner (Ks = 4.4, 6.9 and 13.2 x 10-9 cm2 for 0, 50 and 100 |ag/ml total PM concentrations, respectively). Filtered PM also produced a significant increase in Ks at PM concentration of 17 |ag/ml. Final turbidity measurements at 20min were obtained for varying concentrations of PM. Maximum optical density (OD) for 1 mg/ml fibrinogen at 0, 50, 100 and 200 |ag/ml total PM concentrations were 0.39, 0.42, 0.45 and 0.46, respectively. The maximum OD for 0, 17, 34 and 68 |ag/ml filtered PM concentrations were 0.39, 0.42 0.47 and 0.51, respectively, suggesting an increase in fibre diameter with increasing particulate concentration. The lag phase was significantly shorter and the rate of polymerisation was significantly faster in the presence of 68 |ag/ml filtered PM. Confocal microscopy results showed

Effect of fibrinogen on blood coagulation detected by optical coherence tomography

International Nuclear Information System (INIS)

Xu, Xiangqun; Teng, Xiangshuai

2015-01-01

Our previous work demonstrated that an optical coherence tomography (OCT) technique and the parameter 1/e light penetration depth (d 1/e ) were able to characterize the whole blood coagulation process in contrast to existing optical tests that are performed on plasma samples. To evaluate the feasibility of the technique for quantifying the effect of fibrinogen (Fbg) on blood coagulation, a dynamic study of d 1/e of blood in various Fbg concentrations was performed in static state. Two groups of blood samples of hematocrit (HCT) in 35, 45, and 55% were reconstituted of red blood cells with: 1) treated plasma with its intrinsic Fbg removed and commercial Fbg added (0–8 g L −1 ); and 2) native plasma with commercial Fbg added (0–8 g L −1 ). The results revealed a typical behavior due to coagulation induced by calcium ions and the clotting time is Fbg concentration-dependent. The clotting time was decreased by the increasing amount of Fbg in both groups. Besides, the blood of lower HCT with various levels of Fbg took shorter time to coagulate than that of higher HCT. Consequently, the OCT method is a useful and promising tool for the detection of blood-coagulation processes induced with different Fbg levels. (paper)

Influence of Interleukin-1 Beta on Platelet-Poor Plasma Clot Formation: A Potential Impact on Early Bone Healing.

Directory of Open Access Journals (Sweden)

Xin Wang

Full Text Available Hematoma quality (especially the fibrin matrix plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β on fibrin clot formation from platelet-poor plasma (PPP.Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG, blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10 min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM, confocal microscopy (CM, turbidity, and clot lysis assays.The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β compared to the control group without IL-1β (543.8 ± 205.8. Maximal turbidity was observed in the control group. IL-1β (500 pg/mL treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05. The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers.IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

Clot retraction is mediated by factor XIII-dependent fibrin-αIIbβ3-myosin axis in platelet sphingomyelin-rich membrane rafts.

Science.gov (United States)

Kasahara, Kohji; Kaneda, Mizuho; Miki, Toshiaki; Iida, Kazuko; Sekino-Suzuki, Naoko; Kawashima, Ikuo; Suzuki, Hidenori; Shimonaka, Motoyuki; Arai, Morio; Ohno-Iwashita, Yoshiko; Kojima, Soichi; Abe, Mitsuhiro; Kobayashi, Toshihide; Okazaki, Toshiro; Souri, Masayoshi; Ichinose, Akitada; Yamamoto, Naomasa

2013-11-07

Membrane rafts are spatially and functionally heterogenous in the cell membrane. We observed that lysenin-positive sphingomyelin (SM)-rich rafts are identified histochemically in the central region of adhered platelets where fibrin and myosin are colocalized on activation by thrombin. The clot retraction of SM-depleted platelets from SM synthase knockout mouse was delayed significantly, suggesting that platelet SM-rich rafts are involved in clot retraction. We found that fibrin converted by thrombin translocated immediately in platelet detergent-resistant membrane (DRM) rafts but that from Glanzmann's thrombasthenic platelets failed. The fibrinogen γ-chain C-terminal (residues 144-411) fusion protein translocated to platelet DRM rafts on thrombin activation, but its mutant that was replaced by A398A399 at factor XIII crosslinking sites (Q398Q399) was inhibited. Furthermore, fibrin translocation to DRM rafts was impaired in factor XIII A subunit-deficient mouse platelets, which show impaired clot retraction. In the cytoplasm, myosin translocated concomitantly with fibrin translocation into the DRM raft of thrombin-stimulated platelets. Furthermore, the disruption of SM-rich rafts by methyl-β-cyclodextrin impaired myosin activation and clot retraction. Thus, we propose that clot retraction takes place in SM-rich rafts where a fibrin-αIIbβ3-myosin complex is formed as a primary axis to promote platelet contraction.

Fibrinogen and ceruloplasmin in plasma and milk from dairy cows with subclinical and clinical mastitis.

Science.gov (United States)

Tabrizi, A Davasaz; Batavani, R A; Rezaei, S Asri; Ahmadi, M

2008-02-15

The potential using of Acute Phase Proteins (APPs) in the assessment of mammary gland health was studied by examining the levels of Fibrinogen (Fb) and Ceruloplasmin (Cp) in plasma and milk from dairy cows with different grades of mastitis. Plasma samples were taken from jugular vein and milk samples were collected from quarters of cows with subclinical and clinical mastitis, as well as healthy controls. California Mastitis Test (CMT) were performed on each udder quarter of cows for detection of CMT2+ and CMT3+ quarters. CMT (0) and culture negative cases were considered healthy cows. Clinical mastitis, was graded as mild (clots in milk) or moderate (clots in milk and visible signs of inflammation in the mammary gland/s). The concentrations of Fb in the plasma of the cows with subclinical and clinical mastitis were higher than in the plasma of the healthy cows (p0.05), but differences between clinical and healthy groups were significant (pmastitis were higher than in the milk of the healthy cows (pmastitis in dairy cows.

Unfavorably Altered Fibrin Clot Properties in Patients with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Association with Thrombin Generation and Eosinophilia.

Science.gov (United States)

Mastalerz, Lucyna; Celińska-Lӧwenhoff, Magdalena; Krawiec, Piotr; Batko, Bogdan; Tłustochowicz, Witold; Undas, Anetta

2015-01-01

Given reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome), we investigated whether fibrin clot properties are unfavorably altered in EGPA. Ex vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male), aged 48 (range, 21-80) years. The control group comprised 34 age- and sex- matched volunteers. Compared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30±0.93 vs 10.14±1.07 10-9 cm2), faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8±3.6 vs 47.4±2.9 s), thicker fibrin fibers (maximum absorbance, ΔAbs, 0.87±0.09 vs 0.72±0.07), higher maximum levels of D-dimer released from clots (DDmax 4.10±0.46 vs 3.54±0.35 mg/L), and prolonged clot lysis time (t50%; 9.50±1.45 vs 7.56±0.87 min); all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C-reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%. This study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease.

Unfavorably Altered Fibrin Clot Properties in Patients with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome: Association with Thrombin Generation and Eosinophilia.

Directory of Open Access Journals (Sweden)

Lucyna Mastalerz

Full Text Available Given reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome, we investigated whether fibrin clot properties are unfavorably altered in EGPA.Ex vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male, aged 48 (range, 21-80 years. The control group comprised 34 age- and sex- matched volunteers.Compared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30±0.93 vs 10.14±1.07 10-9 cm2, faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8±3.6 vs 47.4±2.9 s, thicker fibrin fibers (maximum absorbance, ΔAbs, 0.87±0.09 vs 0.72±0.07, higher maximum levels of D-dimer released from clots (DDmax 4.10±0.46 vs 3.54±0.35 mg/L, and prolonged clot lysis time (t50%; 9.50±1.45 vs 7.56±0.87 min; all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C-reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%.This study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease.

Blood Clotting and Pregnancy

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Full Text Available ... with Your Doctor Patient Group Links Advocacy Toolkit Home For Patients Blood Disorders Blood Clots Blood Clotting & Pregnancy If you are pregnant, or you have just had a baby, you are at greater risk of developing a blood clot. Blood clots in pregnant women tend to form in the deep veins of ...

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Full Text Available ... all publications For Patients Blood Basics Blood Disorders Anemia Bleeding Disorders Blood Cancers Blood Clots Blood Clotting and Pregnancy Clots and Travel DVT Myths vs. Facts Blood ...

Acquired hypofibrinogenemia: current perspectives

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Besser MW

2016-09-01

Full Text Available Martin W Besser,1 Stephen G MacDonald2 1Department of Haematology, 2Department of Specialist Haemostasis, The Pathology Partnership, Addenbrooke’s Hospital, Cambridge, UK Abstract: Acquired hypofibrinogenemia is most frequently caused by hemodilution and consumption of clotting factors. The aggressive replacement of fibrinogen has become one of the core principles of modern management of massive hemorrhage. The best method for determining the patient’s fibrinogen level remains controversial, and particularly in acquired dysfibrinogenemia, could have major therapeutic implications depending on which quantification method is chosen. This review introduces the available laboratory and point-of-care methods and discusses the relative advantages and limitations. It also discusses current strategies for the correction of hypofibrinogenemia. Keywords: Clauss fibrinogen assay, fibrinogen antigen, viscoelastic testing, ­gravimetric fibrinogen assay, PT-derived fibrinogen, functional fibrinogen, direct oral anticoagulant, dysfibrinogenemia, afibrinogenemia

Blood Clotting and Pregnancy

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Full Text Available ... resource to help stay current with the latest advances in the field Hematology 2017 A collection of articles ... Disorders Blood Cancers Blood Clots Blood Clotting and Pregnancy Clots and ...

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Full Text Available ... blood clots are treated with an anticoagulant, a medicine that prevents the blood from clotting. Certain anticoagulants are safe to use during pregnancy. back to top Are Blood Clots Preventable? There ...

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Full Text Available ... of articles from the 2017 ASH Annual Meeting Education Program Blood: How I Treat A compendium of Blood articles updated ... Clots Blood Clotting and Pregnancy Clots and Travel DVT Myths vs. Facts Blood ...

In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures

Science.gov (United States)

2007-11-01

is co- agulopathy, particularly when it is associated with metabolic acidosis and hypothermia, often referred to as the “lethal triad”.3–5 Substantial...that rFVIIa may be able to improve early survival of mas- sively bleeding trauma patients.27 It is also suggested that the correction of acidosis and...ratio and clotting time was measured. Fibrinogen in plasma was also determined based on a clotting assay in which a large excess of bovine thrombin (50

Blood Clotting and Pregnancy

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Full Text Available ... Blood Clots Blood Clotting and Pregnancy Clots and Travel DVT Myths vs. Facts Blood Disorder Fact Sheets ... that occurs when a DVT breaks off and travels to the blood vessels of the lungs. DVT ...

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Full Text Available ... Section Action Alerts Advocacy Toolkit Policy News Sickle Cell Disease Initiative Policy Statements Congressional Fellowship Testimony and ... Blood Basics Blood Disorders Anemia Bleeding Disorders Blood Cancers Blood Clots Blood Clotting and Pregnancy Clots and ...

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Full Text Available ... back to top How are Blood Clots in Pregnant Women Treated? Typically, blood clots are treated with ... you think you have one. If you are pregnant and have concerns about blood clots, talk with ...

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Full Text Available ... clot. Blood clots in pregnant women tend to form in the deep veins of the legs or ... potentially dangerous to your baby. Blood clots can form inside the placenta, cutting off blood flow and ...

Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

Science.gov (United States)

Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

2009-03-01

Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

Technetium-99m-human fibrinogen

International Nuclear Information System (INIS)

Wong, D.W.; Mishkin, F.S.

1975-01-01

Exogenous fibrinogen has been successfully labeled with /sup 99m/Tc using a modified electrolytic method. The exact labeling mechanism has not been determined. Experimental data suggest that the labeling process of /99m/Tc-fibrinogen is quite similar to that of /sup 99m/Tc-human serum albumin as reported earlier by Benjamin. Technetium-99m-fibrinogen is stable in human plasma or in 1 percent buffered human serum albumin. A binding efficiency of 76 percent has been achieved with approximately 25 percent clottable protein. The entire labeling procedure requires less than 1 hr of preparation time. This short labeling time in a closed system may allow development of a practical method for labeling autologous fibrinogen, thus eliminating the risk of hepatitis transmission. (U.S.)

Ex-vivo response to blood products and haemostatic agents after paediatric cardiac surgery

DEFF Research Database (Denmark)

Hvas, Anne-Mette; Andreasen, Jo B; Christiansen, Kirsten

2013-01-01

cardiac surgery. The haemostatic potential of various factor concentrates (fibrinogen concentrate, recombinant factor VIIa and factor XIII), fresh frozen plasma (FFP), pooled platelets and tranexamic acid was investigated. After surgery, the coagulation profiles revealed significantly prolonged clotting...... of fibrinogen concentrate, FFP or tranexamic acid improved clot stability significantly. Whole blood coagulation was significantly impaired after cardiac surgery in children. Ex-vivo studies showed a total reversal of the coagulopathy after addition of pooled platelets and significantly improved clot stability...... after addition of fibrinogen concentrate, FFP and tranexamic acid, respectively....

Platelet fibrinogen binding in Basset Hound Hereditary Thrombopathy

International Nuclear Information System (INIS)

Patterson, W.; Estry, D.; Schwartz, K.; Bell, T.

1986-01-01

Platelets from dogs with Basset Hound Hereditary Thrombopathy (BHT) display a thrombasthenia-like aggregation defect but have been shown to have normal amounts of platelet membrane glycoproteins IIb and IIIa (GP IIb-IIIa). In order to investigate the possibility of a functionally abnormal GPIIb-IIIa complex, which might be unable to bind fibrinogen after stimulation, fibrinogen binding in BHT was evaluated. Two canine fibrinogen preparations were used, one from BHT dogs and one from normal control dogs, as well as a human fibrinogen preparation. Platelets from BHT and normal dogs were activated with 1 x 10 -5 M ADP in the presence of 125 I-labeled fibrinogen and the surface bound radioactivity quantitated. For all fibrinogen preparations, the amount of fibrinogen bound by BHT platelets was not significantly different than that bound by normal dog platelets. BHT platelets bound 23,972 +/- 3612 and normal dog platelets bound 23,033 +/- 3971 molecules of fibrinogen per platelet. The BHT platelet aggregation defect does not seem to be caused by a functionally abnormal GP IIb-IIIa complex, since BHT platelets bind normal amounts of fibrinogen. The results suggest that fibrinogen binding is not sufficient for platelet aggregation, and other factors, perhaps receptor mobility and membrane phospholipid content should be investigated in BHT

Limitations of using synthetic blood clots for measuring in vitro clot capture efficiency of inferior vena cava filters

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Robinson RA

2013-05-01

Full Text Available Ronald A Robinson, Luke H Herbertson, Srilekha Sarkar Das, Richard A Malinauskas, William F Pritchard, Laurence W GrossmanOffice of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USAAbstract: The purpose of this study was first to evaluate the clot capture efficiency and capture location of six currently-marketed vena cava filters in a physiological venous flow loop, using synthetic polyacrylamide hydrogel clots, which were intended to simulate actual blood clots. After observing a measured anomaly for one of the test filters, we redirected the focus of the study to identify the cause of poor clot capture performance for large synthetic hydrogel clots. We hypothesized that the uncharacteristic low clot capture efficiency observed when testing the outlying filter can be attributed to the inadvertent use of dense, stiff synthetic hydrogel clots, and not as a result of the filter design or filter orientation. To study this issue, sheep blood clots and polyacrylamide (PA synthetic clots were injected into a mock venous flow loop containing a clinical inferior vena cava (IVC filter, and their captures were observed. Testing was performed with clots of various diameters (3.2, 4.8, and 6.4 mm, length-to-diameter ratios (1:1, 3:1, 10:1, and stiffness. By adjusting the chemical formulation, PA clots were fabricated to be soft, moderately stiff, or stiff with elastic moduli of 805 ± 2, 1696 ± 10 and 3295 ± 37 Pa, respectively. In comparison, the elastic moduli for freshly prepared sheep blood clots were 1690 ± 360 Pa. The outlying filter had a design that was characterized by peripheral gaps (up to 14 mm between its wire struts. While a low clot capture rate was observed using large, stiff synthetic clots, the filter effectively captured similarly sized sheep blood clots and soft PA clots. Because the stiffer synthetic clots remained straight when approaching the

Fibrinogen concentrate in bleeding patients

DEFF Research Database (Denmark)

Wikkelsø, Anne; Lunde, Jens; Johansen, Mathias

2013-01-01

Hypofibrinogenaemia is associated with increased morbidity and mortality, but the optimal treatment level, the use of preemptive treatment and the preferred source of fibrinogen remain disputed. Fibrinogen concentrate is increasingly used and recommended for bleeding with acquired haemostatic...

Blood Clotting and Pregnancy

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... blood clots A genetic predisposition to blood clots Obesity Prolonged immobility (e.g., bedrest, long distance travel) Multiple births Increased maternal age Other medical illness (e.g., cancer, infection) ...

Blood Clotting and Pregnancy

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Full Text Available ... blood clots A genetic predisposition to blood clots Obesity Prolonged immobility (e.g., bedrest, long distance travel) Multiple births Increased maternal age Other medical illness (e.g., cancer, infection) ...

Composition comprising radioactive labeled-fibrinogen and albumin

International Nuclear Information System (INIS)

Charlton, J.C.; Gravett, D.L.

1976-01-01

The stability of fibrinogen is improved by mixing it with albumin, preferably at least 5 parts by weight of albumin per part by weight of fibrinogen. By this invention, iodinated ( 125 I) human fibrinogen can be stabilized with human serum albumin for use in the diagnosis of thrombi

Study of radioactive fibrinogen metabolism in renal allotransplantation

International Nuclear Information System (INIS)

Akiyama, Takahiro; Nagai, Nobuo; Kaneko, Shigeo; Matsuura, Takeshi; Iguchi, Masanori

1979-01-01

Turn over administrated radioactive fibrinogen and uptake to renal allograft were studied in 9 cases of renal allotransplanted patients. In patients with acute rejection crisis biological half-time (T 1/2) of 131 I-fibrinogen were shortened and allograft/heart counts ratio of 125 I-fibrinogen were elevated up to 125 - 140 percent at 24 - 48 hours after administration; these parameters seemed to be useful in aid of diagnosis of acute rejection. It is suggested that deposition of fibrinogen into allograft and increased turn over of plasma fibrinogen occurred in acute rejection. (author)

Fibrinogen-binding and platelet-aggregation activities of a Lactobacillus salivarius septicaemia isolate are mediated by a novel fibrinogen-binding protein.

Science.gov (United States)

Collins, James; van Pijkeren, Jan-Peter; Svensson, Lisbeth; Claesson, Marcus J; Sturme, Mark; Li, Yin; Cooney, Jakki C; van Sinderen, Douwe; Walker, Alan W; Parkhill, Julian; Shannon, Oonagh; O'Toole, Paul W

2012-09-01

The marketplace for probiotic foods is burgeoning, measured in billions of euro per annum. It is imperative, however, that all bacterial strains are fully assessed for human safety. The ability to bind fibrinogen is considered a potential pathogenicity trait that can lead to platelet aggregation, serious medical complications, and in some instances, death. Here we examined strains from species frequently used as probiotics for their ability to bind human fibrinogen. Only one strain (CCUG 47825), a Lactobacillus salivarius isolate from a case of septicaemia, was found to strongly adhere to fibrinogen. Furthermore, this strain was found to aggregate human platelets at a level comparable to the human pathogen Staphylococcus aureus. By sequencing the genome of CCUG 47825, we were able to identify candidate genes responsible for fibrinogen binding. Complementing the genetic analysis with traditional molecular microbiological techniques enabled the identification of the novel fibrinogen receptor, CCUG_2371. Although only strain CCUG 47825 bound fibrinogen under laboratory conditions, homologues of the novel fibrinogen binding gene CCUG_2371 are widespread among L. salivarius strains, maintaining their potential to bind fibrinogen if expressed. We highlight the fact that without a full genetic analysis of strains for human consumption, potential pathogenicity traits may go undetected. © 2012 Blackwell Publishing Ltd.

Blood Clotting and Pregnancy

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Plasma Fibrinogen in Patients With Bell Palsy.

Science.gov (United States)

Zhao, Hua; Zhang, Xin; Tang, Yinda; Li, Shiting

2016-10-01

To determine the plasma fibrinogen level in patients with Bell palsy and explore the significances of it in Bell palsy. One hundred five consecutive patients with facial paralysis were divided into 3 groups: group I (Bell palsy), group II (temporal bone fractures), and group III (facial nerve schwannoma). In addition, 22 volunteers were defined as control group. Two milliliters fasting venous blood from elbow was collected, and was evaluated by CA-7000 Full-Automatic Coagulation Analyzer. The plasma fibrinogen concentration was significantly higher in the group of patients with Bell palsy (HB IV-VI) than that in the control group (P 0.05); similarly, there was also no marked difference between group III and control group (P >0.05). In group I, the plasma fibrinogen levels became higher with the HB grading increase. The plasma fibrinogen level of HB-VI was highest. Plasma fibrinogen has an important clinical meaning in Bell palsy, which should be used as routine examination items. Defibrinogen in treatment for patients with high plasma fibrinogen content also should be suggested.

Blood Clotting and Pregnancy

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Full Text Available ... an immediate impact on your practice Summit on Emerging Immunotherapies Registration Schedule & Program Meeting on Lymphoma Biology ... blood clots are treated with an anticoagulant, a medicine that prevents the blood from clotting. Certain anticoagulants ...

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Full Text Available ... In This Section Agenda for Hematology Research Precision Medicine Initiative Research Registry Research Recommendations Research Programs and ... blood clots are treated with an anticoagulant, a medicine that prevents the blood from clotting. Certain anticoagulants ...

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Full Text Available ... these blood conditions and increase research on the causes, prevention, and treatment. Blood clots are also potentially ... Increased maternal age Other medical illness (e.g., cancer, infection) back to top How are Blood Clots ...

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Human plasma fibrinogen adsorption and platelet adhesion to polystyrene.

Science.gov (United States)

Tsai, W B; Grunkemeier, J M; Horbett, T A

1999-02-01

The purpose of this study was to further investigate the role of fibrinogen adsorbed from plasma in mediating platelet adhesion to polymeric biomaterials. Polystyrene was used as a model hydrophobic polymer; i.e., we expected that the role of fibrinogen in platelet adhesion to polystyrene would be representative of other hydrophobic polymers. Platelet adhesion was compared to both the amount and conformation of adsorbed fibrinogen. The strategy was to compare platelet adhesion to surfaces preadsorbed with normal, afibrinogenemic, and fibrinogen-replenished afibrinogenemic plasmas. Platelet adhesion was determined by the lactate dehydrogenase (LDH) method, which was found to be closely correlated with adhesion of 111In-labeled platelets. Fibrinogen adsorption from afibrinogenemic plasma to polystyrene (Immulon I(R)) was low and polystyrene preadsorbed with fibrinogen-replenished afibrinogenemic plasma. Addition of even small, subnormal concentrations of fibrinogen to afibrinogenemic plasma greatly increased platelet adhesion. In addition, surface-bound fibrinogen's ability to mediate platelet adhesion was different, depending on the plasma concentration from which fibrinogen was adsorbed. These differences correlated with changes in the binding of a monoclonal antibody that binds to the Aalpha chain RGDS (572-575), suggesting alteration in the conformation or orientation of the adsorbed fibrinogen. Platelet adhesion to polystyrene preadsorbed with blood plasma thus appears to be a strongly bivariate function of adsorbed fibrinogen, responsive to both low amounts and altered states of the adsorbed molecule. Copyright 1999 John Wiley & Sons, Inc.

Endogenous fibrinolysis facilitates clot retraction in vivo.

Science.gov (United States)

Samson, Andre L; Alwis, Imala; Maclean, Jessica A A; Priyananda, Pramith; Hawkett, Brian; Schoenwaelder, Simone M; Jackson, Shaun P

2017-12-07

Clot retraction refers to the process whereby activated platelets transduce contractile forces onto the fibrin network of a thrombus, which over time increases clot density and decreases clot size. This process is considered important for promoting clot stability and maintaining blood vessel patency. Insights into the mechanisms regulating clot retraction at sites of vascular injury have been hampered by a paucity of in vivo experimental models. By pairing localized vascular injury with thrombin microinjection in the mesenteric circulation of mice, we have demonstrated that the fibrin network of thrombi progressively compacts over a 2-hour period. This was a genuine retraction process, as treating thrombi with blebbistatin to inhibit myosin IIa-mediated platelet contractility prevented shrinkage of the fibrin network. Real-time confocal analysis of fibrinolysis after recombinant tissue-type plasminogen activator (tPA) administration revealed that incomplete proteolysis of fibrin polymers markedly facilitated clot retraction. Similarly, inhibiting endogenous fibrinolysis with tranexamic acid reduced retraction of fibrin polymers in vivo. In vitro clot retraction experiments indicated that subthreshold doses of tPA facilitated clot retraction through a plasmin-dependent mechanism. These effects correlated with changes in the elastic modulus of fibrin clots. These findings define the endogenous fibrinolytic system as an important regulator of clot retraction, and show that promoting clot retraction is a novel and complementary means by which fibrinolytic enzymes can reduce thrombus size. © 2017 by The American Society of Hematology.

Clinical and prognostic significance of plasma fibrinogen in lung cancer

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Chen YS

2014-01-01

Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

The Effect of a Simulated Commercial Flight Environment with Hypoxia and Low Humidity on Clotting, Platelet, and Endothelial Function in Participants with Type 2 Diabetes – A Cross-over Study

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Judit Konya

2018-02-01

Full Text Available AimsTo determine if clotting, platelet, and endothelial function were affected by simulated short-haul commercial air flight conditions (SF in participants with type 2 diabetes (T2DM compared to controls.Methods10 participants with T2DM (7 females, 3 males and 10 controls (3 females, 7 males completed the study. Participants were randomized to either spend 2 h in an environmental chamber at sea level conditions (temperature: 23°C, oxygen concentration 21%, humidity 45%, or subject to a simulated 2-h simulated flight (SF: temperature: 23°C, oxygen concentration 15%, humidity 15%, and crossed over 7 days later. Main outcome measures: clot formation and clot lysis parameters, functional platelet activation markers, and endothelial function measured by reactive hyperemia index (RHI by EndoPAT and serum microparticles.ResultsComparing baseline with SF conditions, clot maximal absorption was increased in controls (0.375 ± 0.05 vs. 0.39 ± 0.05, p < 0.05 and participants with T2DM (0.378 ± 0.089 vs. 0.397 ± 0.089, p < 0.01, while increased basal platelet activation for both fibrinogen binding and P-selectin expression (p < 0.05 was seen in participants with T2DM. Parameters of clot formation and clot lysis, stimulated platelet function (stimulated platelet response to ADP and sensitivity to prostacyclin, and endothelial function were unchanged.ConclusionWhile SF resulted in the potential of denser clot formation with enhanced basal platelet activation in T2DM, the dynamic clotting, platelet, and endothelial markers were not affected, suggesting that short-haul commercial flying adds no additional hazard for venous thromboembolism for participants with T2DM compared to controls.

Turnover of radio-iodinated and biosynthetically labelled fibrinogen in rhesus monkeys

International Nuclear Information System (INIS)

Moza, A.K.

1982-01-01

Successful radio-iodination of monkey fibrinogen using a previously documented method for rabbit fibrinogen is reported. The label was securely bound to fibrinogen without any evidence of polymerisation. Turnover rates and other kinetic parameters of fibrinogen using 125 I-fibrinogen have been compared with those obtained with biosynthetically labelled donor 75 Se-fibrinogen. Both studies yielded identical results. The values for normal monkeys showed a half life of 43.8 +- 1.03 h with 125 I-fibrinogen and 47.15 +- 1.24 with 75 Se-fibrinogen. The turnover rate of endogenous 75 Se-fibrinogen following administration of 75 Se-selenomethionine has also been studied. The half disappearance time value of 100.34 h was much longer than the t1/2 values obtained with either 125 I or 75 Se-fibrinogen. This is believed to be due the staggered input of fibrinogen molecules from the liver. (author)

Fluid Mechanics of Blood Clot Formation.

Science.gov (United States)

Fogelson, Aaron L; Neeves, Keith B

2015-01-01

Intravascular blood clots form in an environment in which hydrodynamic forces dominate and in which fluid-mediated transport is the primary means of moving material. The clotting system has evolved to exploit fluid dynamic mechanisms and to overcome fluid dynamic challenges to ensure that clots that preserve vascular integrity can form over the wide range of flow conditions found in the circulation. Fluid-mediated interactions between the many large deformable red blood cells and the few small rigid platelets lead to high platelet concentrations near vessel walls where platelets contribute to clotting. Receptor-ligand pairs with diverse kinetic and mechanical characteristics work synergistically to arrest rapidly flowing cells on an injured vessel. Variations in hydrodynamic stresses switch on and off the function of key clotting polymers. Protein transport to, from, and within a developing clot determines whether and how fast it grows. We review ongoing experimental and modeling research to understand these and related phenomena.

Biological variation in tPA-induced plasma clot lysis time.

Science.gov (United States)

Talens, Simone; Malfliet, Joyce J M C; Rudež, Goran; Spronk, Henri M H; Janssen, Nicole A H; Meijer, Piet; Kluft, Cornelis; de Maat, Moniek P M; Rijken, Dingeman C

2012-10-01

Hypofibrinolysis is a risk factor for venous and arterial thrombosis, and can be assessed by using a turbidimetric tPA-induced clot lysis time (CLT) assay. Biological variation in clot lysis time may affect the interpretation and usefulness of CLT as a risk factor for thrombosis. Sufficient information about assay variation and biological variation in CLT is not yet available. Thus, this study aimed to determine the analytical, within-subject and between-subject variation in CLT. We collected blood samples from 40 healthy individuals throughout a period of one year (average 11.8 visits) and determined the CLT of each plasma sample in duplicate. The mean (± SD) CLT was 83.8 (± 11.1) minutes. The coefficients of variation for total variation, analytical variation, within-subject variation and between-subject variation were 13.4%, 2.6%, 8.2% and 10.2%, respectively. One measurement can estimate the CLT that does not deviate more than 20% from its true value. The contribution of analytical variation to the within-subject variation was 5.0%, the index of individuality was 0.84 and the reference change value was 23.8%. The CLT was longer in the morning compared to the afternoon and was slightly longer in older individuals (> 40 years) compared to younger (≤40 years) individuals. There was no seasonal variation in CLT and no association with air pollution. CLT correlated weakly with fibrinogen, C-reactive protein, prothrombin time and thrombin generation. This study provides insight into the biological variation of CLT, which can be used in future studies testing CLT as a potential risk factor for thrombosis.

Bacteroides gingivalis and Bacteroides intermedius recognize different sites on human fibrinogen

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Lantz, M.S.; Allen, R.D.; Bounelis, P.; Switalski, L.M.; Hook, M. (Univ. of Alabama, Birmingham (USA))

1990-02-01

Bacteroides (Porphyromonas) gingivalis and Bacteroides (Porphyromonas) intermedius have been implicated in the etiology of human periodontal diseases. These organisms are able to bind and degrade human fibrinogen, and these interactions may play a role in the pathogenesis of periodontal disease. In attempts to map the bacterial binding sites along the fibrinogen molecule, we have found that strains of B. gingivalis and B. intermedius, respectively, recognize spatially distant and distinct sites on the fibrinogen molecule. Isolated reduced and alkylated alpha-, beta-, and gamma-fibrinogen chains inhibited binding of 125I-fibrinogen to both Bacteroides species in a concentration-dependent manner. Plasmin fragments D and to some extent fragment E, however, produced a concentration-dependent inhibition of 125I-fibrinogen binding to B. intermedius strains but did not affect binding of 125I-fibrinogen to B. gingivalis strains. Radiolabeled fibrinogen chains and fragments were compared with 125I-fibrinogen with respect to specificity and reversibility of binding to bacteria. According to these criteria, gamma chain most closely resembled the native fibrinogen molecule in behavior toward B. gingivalis strains and fragments D most closely resembled fibrinogen in behavior toward B. intermedius strains. The ability of anti-human fibrinogen immunoglobulin G (IgG) to inhibit binding of 125I-fibrinogen to B. intermedius strains was greatly reduced by absorbing the IgG with fragments D. Absorbing the IgG with fragments D had no effect on the ability of the antibody to inhibit binding of 125I-fibrinogen to B. gingivalis strains. A purified staphylococcal fibrinogen-binding protein blocked binding of 125I-fibrinogen to B. intermedius strains but not to B. gingivalis strains.

Bacteroides gingivalis and Bacteroides intermedius recognize different sites on human fibrinogen

International Nuclear Information System (INIS)

Lantz, M.S.; Allen, R.D.; Bounelis, P.; Switalski, L.M.; Hook, M.

1990-01-01

Bacteroides (Porphyromonas) gingivalis and Bacteroides (Porphyromonas) intermedius have been implicated in the etiology of human periodontal diseases. These organisms are able to bind and degrade human fibrinogen, and these interactions may play a role in the pathogenesis of periodontal disease. In attempts to map the bacterial binding sites along the fibrinogen molecule, we have found that strains of B. gingivalis and B. intermedius, respectively, recognize spatially distant and distinct sites on the fibrinogen molecule. Isolated reduced and alkylated alpha-, beta-, and gamma-fibrinogen chains inhibited binding of 125I-fibrinogen to both Bacteroides species in a concentration-dependent manner. Plasmin fragments D and to some extent fragment E, however, produced a concentration-dependent inhibition of 125I-fibrinogen binding to B. intermedius strains but did not affect binding of 125I-fibrinogen to B. gingivalis strains. Radiolabeled fibrinogen chains and fragments were compared with 125I-fibrinogen with respect to specificity and reversibility of binding to bacteria. According to these criteria, gamma chain most closely resembled the native fibrinogen molecule in behavior toward B. gingivalis strains and fragments D most closely resembled fibrinogen in behavior toward B. intermedius strains. The ability of anti-human fibrinogen immunoglobulin G (IgG) to inhibit binding of 125I-fibrinogen to B. intermedius strains was greatly reduced by absorbing the IgG with fragments D. Absorbing the IgG with fragments D had no effect on the ability of the antibody to inhibit binding of 125I-fibrinogen to B. gingivalis strains. A purified staphylococcal fibrinogen-binding protein blocked binding of 125I-fibrinogen to B. intermedius strains but not to B. gingivalis strains

Fibrinogen Reduction During Selective Plasma Exchange due to Membrane Fouling.

Science.gov (United States)

Ohkubo, Atsushi; Okado, Tomokazu; Miyamoto, Satoko; Hashimoto, Yurie; Komori, Shigeto; Yamamoto, Motoki; Maeda, Takuma; Itagaki, Ayako; Yamamoto, Hiroko; Seshima, Hiroshi; Kurashima, Naoki; Iimori, Soichiro; Naito, Shotaro; Sohara, Eisei; Uchida, Shinichi; Rai, Tatemitsu

2017-06-01

Fibrinogen is substantially reduced by most plasmapheresis modalities but retained in selective plasma exchange using Evacure EC-4A10 (EC-4A). Although EC-4A's fibrinogen sieving coefficient is 0, a session of selective plasma exchange reduced fibrinogen by approximately 19%. Here, we investigated sieving coefficient in five patients. When the mean processed plasma volume was 1.15 × plasma volume, the mean reduction of fibrinogen during selective plasma exchange was approximately 15%. Fibrinogen sieving coefficient was 0 when the processed plasma volume was 1.0 L, increasing to 0.07 when the processed plasma volume was 3.0 L, with a mean of 0.03 during selective plasma exchange. When fibrinogen sieving coefficient was 0, selective plasma exchange reduced fibrinogen by approximately 10%. Scanning electron microscopy images revealed internal fouling of EC-4A's hollow fiber membrane by substances such as fibrinogen fibrils. Thus, fibrinogen reduction by selective plasma exchange may be predominantly caused by membrane fouling rather than filtration. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Complementary effect of fibrinogen and rFVIIa on clotting ex vivo in Bernard-Soulier syndrome and combined use during three deliveries

DEFF Research Database (Denmark)

Palsson, Ragnar; Vidarsson, Brynjar; Gudmundsdottir, Brynja R

2014-01-01

Women with Bernard-Soulier syndrome (BSS) are considered to be at high risk of serious bleeding during childbirth. Due to the frequently occurring platelet transfusion refractoriness, alternative prophylactic therapy is required. Using rotational thromboelastometry, we evaluated the whole blood......, the findings were confirmed on blood from a non-pregnant woman and three men suffering from BSS. During delivery, bleeding refractory to platelets occurred and immediately following delivery she received both rFVIIa and fibrinogen intravenously. Immediate cessation of bleeding occurred, and no postpartum...

Conformational changes of fibrinogen in dispersed carbon nanotubes

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Park SJ

2012-08-01

Full Text Available Sung Jean Park,1 Dongwoo Khang21College of Pharmacy, Gachon University, Yeonsu-gu, Incheon, South Korea; 2School of Nano and Advanced Materials Science Engineering and Center for PRC and RIGET, Gyeongsang National University, Jinju, South KoreaAbstract: The conformational changes of plasma protein structures in response to carbon nanotubes are critical for determining the nanotoxicity and blood coagulation effects of carbon nanotubes. In this study, we identified that the functional intensity of carboxyl groups on carbon nanotubes, which correspond to the water dispersity or hydrophilicity of carbon nanotubes, can induce conformational changes in the fibrinogen domains. Also, elevation of carbon nanotube density can alter the secondary structures (ie, helices and beta sheets of fibrinogen. Furthermore, fibrinogen that had been in contact with the nanoparticle material demonstrated a different pattern of heat denaturation compared with free fibrinogen as a result of a variation in hydrophilicity and concentration of carbon nanotubes. Considering the importance of interactions between carbon nanotubes and plasma proteins in the drug delivery system, this study elucidated the correlation between nanoscale physiochemical material properties of carbon nanotubes and associated structural changes in fibrinogen.Keywords: carbon nanotubes, fibrinogen, nanotoxicity, conformational change, denaturation

Granulocyte-platelet interactions and platelet fibrinogen receptor exposure

International Nuclear Information System (INIS)

Kornecki, E.; Ehrlich, Y.H.; Egbring, R.; Gramse, M.; Seitz, R.; Eckardt, A.; Lukasiewicz, H.; Niewiarowski, S.

1988-01-01

The authors have examined the interaction of human granulocyte elastase with human platelets. Incubation of human platelets with human granulocyte elastase exposed active fibrinogen-binding sites as evidenced by 125 I-labeled fibrinogen binding and spontaneous fibrinogen-induced platelet aggregation. The aggregation of platelets by fibrinogen occurred at low concentrations of human granulocyte elastase. Platelets pretreated with human granulocyte elastase exposed an average of 10,500 fibrinogen-binding sites per platelet, i.e., about one-third the number of binding sites exposed by optimal concentrations of ADP. With the use of a polyclonal antiplatelet membrane antibody, the glycoproteins IIb (GPIIb), IIIa (GPIIIa), and a 60,000-Da (60 kDa) protein (66 kDa in a reduced system) derived from GPIIIa were immunoprecipitated from the surface of detergent extracts of human 125 I-radiolabeled platelets pretreated with increasing concentrations of human granulocyte elastase. They conclude that (1) the proteolytic action of human granulocyte elastase on platelet GPIIIa results in the formation of two major hydrolytic products, and (2) human granulocyte elastase exposes active fibrongen-binding sites associated with the GPIIb/GPIIIa complex, resulting in direct platelet aggregation by fibrinogen

Thrombin like activity of Asclepias curassavica L. latex: action of cysteine proteases.

Science.gov (United States)

Shivaprasad, H V; Rajesh, R; Nanda, B L; Dharmappa, K K; Vishwanath, B S

2009-05-04

To validate the scientific basis of plant latex to stop bleeding on fresh cuts. Cysteine protease(s) from Asclepias curassavica (Asclepiadaceae) plant latex was assessed for pro-coagulant and thrombin like activities. A waxy material from the latex of Asclepias curassavica latex was removed by freezing and thawing. The resulted latex enzyme fraction was assayed for proteolytic activity using denatured casein as substrate. Its coagulant activity and thrombin like activity were determined using citrated plasma and pure fibrinogen, respectively. Inhibition studies were performed using specific protease inhibitors to know the type of protease. The latex enzyme fraction exhibited strong proteolytic activity when compared to trypsin and exerted pro-coagulant action by reducing plasma clotting time from 195 to 58 s whereas trypsin reduced clotting time marginally from 195 to 155 s. The pro-coagulant activity of this enzyme fraction was exerted by selectively hydrolyzing A alpha and B beta subunits of fibrinogen to form fibrin clot when pure fibrinogen was used as substrate as assessed by fibrinogen-agarose plate method and fibrinogen polymerization assay. Trypsin failed to induce any fibrin clot under similar conditions. The electrophoretic pattern of latex enzyme fraction-induced fibrin clot was very much similar to that of thrombin-induced fibrin clot and mimic thrombin like action. The proteolytic activity including thrombin like activity of Asclepias curassavica latex enzyme fraction was completely inhibited by iodoaceticacid (IAA). Cysteine proteases from Asclepias curassavica latex exhibited strong pro-coagulant action and were found to be specific in its action (Thrombin like). This could be the basis for the use of plant latex in pharmacological applications that justify their use as folk medicine.

21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fibrinogen/fibrin degradation products assay. 864.7320 Section 864.7320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....7320 Fibrinogen/fibrin degradation products assay. (a) Identification. A fibrinogen/fibrin degradation...

Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage

DEFF Research Database (Denmark)

Wikkelsø, A J; Edwards, H M; Afshari, A

2015-01-01

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients...... and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin ... concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence...

Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

Science.gov (United States)

Zhao, Xiaoyan; Okeke, Nwora Lance; Sharpe, Orr; Batliwalla, Franak M; Lee, Annette T; Ho, Peggy P; Tomooka, Beren H; Gregersen, Peter K; Robinson, William H

2008-01-01

Introduction There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised. Methods We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusion Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients. PMID:18710572

A novel fibrin gel derived from hyaluronic acid-grafted fibrinogen

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Yang, Chiung L; Chen, Hui W; Wang, Tzu C; Wang, Yng J, E-mail: wang@ym.edu.tw [Institute of Biomedical Engineering, National Yang Ming University, No. 155, Sec. 2, Li-Nung St., Shih-Pai, Taipei, Taiwan 112 (China)

2011-04-15

Fibrinogen is a major plasma protein that forms a three-dimensional fibrin gel upon being activated by thrombin. In this study, we report the synthesis and potential applications of hybrid molecules composed of fibrinogen coupled to the reducing ends of short-chain hyaluronic acids (sHAs) by reductive amination. The grafting of sHAs to fibrinogen was verified by analyzing particle size, zeta potential and gel-electrophoretic mobility of the hybrid molecules. The sHA-fibrinogen hybrid molecules with graft ratios (sHA/fibrinogen) of up to 6.5 retained the ability to form gels in response to thrombin activation. The sHA-fibrin gels were transparent in appearance and exhibited high water content, which were characteristics distinct from those of gels formed by mixtures of sHAs and fibrinogen. The potential applications of the sHA-fibrin gels were evaluated. The sHA-fibrinogen gel with a graft ratio of 3.6 (S3.6F) was examined for its ability to encapsulate and support the differentiation of ATDC5 chondrocyte-like cells. Compared with the fibrinogen-formed gel, cells cultured in the S3.6F gel exhibited increased lacunae formation; moreover, the abundance of cartilaginous extracellular matrix molecules and the expression of chondrocyte marker genes, such as aggrecan, collagen II and Sox9, were also significantly increased. Our data suggest that the three-dimensional gel formed by the sHA-fibrinogen hybrid is a better support than the fibrin gel for chondrogenesis induction.

A novel fibrin gel derived from hyaluronic acid-grafted fibrinogen

International Nuclear Information System (INIS)

Yang, Chiung L; Chen, Hui W; Wang, Tzu C; Wang, Yng J

2011-01-01

Fibrinogen is a major plasma protein that forms a three-dimensional fibrin gel upon being activated by thrombin. In this study, we report the synthesis and potential applications of hybrid molecules composed of fibrinogen coupled to the reducing ends of short-chain hyaluronic acids (sHAs) by reductive amination. The grafting of sHAs to fibrinogen was verified by analyzing particle size, zeta potential and gel-electrophoretic mobility of the hybrid molecules. The sHA-fibrinogen hybrid molecules with graft ratios (sHA/fibrinogen) of up to 6.5 retained the ability to form gels in response to thrombin activation. The sHA-fibrin gels were transparent in appearance and exhibited high water content, which were characteristics distinct from those of gels formed by mixtures of sHAs and fibrinogen. The potential applications of the sHA-fibrin gels were evaluated. The sHA-fibrinogen gel with a graft ratio of 3.6 (S3.6F) was examined for its ability to encapsulate and support the differentiation of ATDC5 chondrocyte-like cells. Compared with the fibrinogen-formed gel, cells cultured in the S3.6F gel exhibited increased lacunae formation; moreover, the abundance of cartilaginous extracellular matrix molecules and the expression of chondrocyte marker genes, such as aggrecan, collagen II and Sox9, were also significantly increased. Our data suggest that the three-dimensional gel formed by the sHA-fibrinogen hybrid is a better support than the fibrin gel for chondrogenesis induction.

Risk Factors for Postoperative Fibrinogen Deficiency after Surgical Removal of Intracranial Tumors.

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Naili Wei

Full Text Available Higher levels of fibrinogen, a critical element in hemostasis, are associated with increased postoperative survival rates, especially for patients with massive operative blood loss. Fibrinogen deficiency after surgical management of intracranial tumors may result in postoperative intracranial bleeding and severely worsen patient outcomes. However, no previous studies have systematically identified factors associated with postoperative fibrinogen deficiency. In this study, we retrospectively analyzed data from patients who underwent surgical removal of intracranial tumors in Beijing Tiantan Hospital date from 1/1/2013to12/31/2013. The present study found that patients with postoperative fibrinogen deficiency experienced more operative blood loss and a higher rate of postoperative intracranial hematoma, and they were given more blood transfusions, more plasma transfusions, and were administered larger doses of hemocoagulase compared with patients without postoperative fibrinogen deficiency. Likewise, patients with postoperative fibrinogen deficiency had poorer extended Glasgow Outcome Scale (GOSe, longer hospital stays, and greater hospital expenses than patients without postoperative fibrinogen deficiency. Further, we assessed a comprehensive set of risk factors associated with postoperative fibrinogen deficiency via multiple linear regression. We found that body mass index (BMI, the occurrence of postoperative intracranial hematoma, and administration of hemocoagulasewere positively associated with preoperative-to-postoperative plasma fibrinogen consumption; presenting with a malignant tumor was negatively associated with fibrinogen consumption. Contrary to what might be expected, intraoperative blood loss, the need for blood transfusion, and the need for plasma transfusion were not associated with plasma fibrinogen consumption. Considering our findings together, we concluded that postoperative fibrinogen deficiency is closely associated with

Blood Clots

Science.gov (United States)

... sitting for long periods. If you travel by airplane, walk the aisle periodically. For long car trips, ... Your-Risk-for-Excessive-Blood-Clotting_UCM_448771_Article.jsp. Accessed April 18, 2016. What causes excessive ...

A study on human serum albumin influence on glycation of fibrinogen

International Nuclear Information System (INIS)

Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr

2013-01-01

Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [ 13 C 6 ] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein

A study on human serum albumin influence on glycation of fibrinogen

Energy Technology Data Exchange (ETDEWEB)

Kielmas, Martyna; Szewczuk, Zbigniew; Stefanowicz, Piotr, E-mail: Piotr.stefanowicz@chem.uni.wroc.pl

2013-09-13

Highlights: •The glycation of fibrinogen was investigated by isotopic labeling method. •The potential glycation sites in fibrinogen were identified. •Human serum albumin (HSA) inhibits the glycation of fibrinogen. •The effect of HSA on fibrinogen glycation is sequence-dependent. -- Abstract: Although in vivo glycation proceeds in complex mixture of proteins, previous studies did not take in consideration the influence of protein–protein interaction on Maillard reaction. The aim of our study was to test the influence of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling using [{sup 13}C{sub 6}] glucose combined with LC-MS were applied as tool for identification possible glycation sites in fibrinogen and for evaluation the effect of HSA on the glycation level of selected amino acids in fibrinogen. The obtained data indicate that the addition of HSA protects the fibrinogen from glycation. The level of glycation in presence of HSA is reduced by 30–60% and depends on the location of glycated residue in sequence of protein.

Two novel fibrinogen variants in the C-terminus of the B.beta.-chain: fibrinogen Rokycany and fibrinogen Znojmo

Czech Academy of Sciences Publication Activity Database

Kotlín, R.; Reicheltová, Z.; Suttnar, J.; Salaj, P.; Hrachovinová, I.; Riedel, Tomáš; Malý, M.; Oravec, M.; Kvasnička, J.; Dyr, J. E.

2010-01-01

Roč. 30, č. 3 (2010), s. 311-318 ISSN 0929-5305 R&D Projects: GA AV ČR KAN200670701 Institutional research plan: CEZ:AV0Z40500505 Keywords : fibrinogen * missense mutation * hypofibrinogenemia Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.539, year: 2010

[Perioperative fibrinogen concentrations in cardiac surgery with cardiopulmonary bypass].

Science.gov (United States)

Uji, Makiko; Terada, Yuki; Noguchi, Teruo; Nishida, Takaya; Hasuwa, Kyoko; Shinohara, Kozue; Kumano, Hotaka; Ishimura, Naoko; Nishiwada, Makoto

2012-08-01

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) need many blood products due to deficiency of coagulation factors. Blood transfusion therapy in patients with excessive bleeding after CPB is generally empiric. We checked and studied the fibrinogen concentration and transfusion, as well as bleeding amount in the perioperative period. The study was approved by our institutional ethics committee. Thirty patients were studied. Blood samples were obtained at the induction of anesthesia (before CPB), at the end of CPB, at the end of operation, and on the next morning, or before the patient was given fresh frozen plasma in the intensive care unit. For all cases, fibrinogen concentration and platelet concentration were lowest at the end of CPB. Fibrinogen concentration rose up to before CPB level on the next morning. The group in which fibrinogen concentration was less than 150 mg x dl(-1) at the end of CPB consumed more blood products than the group with fibrinogen concentration of over 150 mg x dl(-1). Blood transfusion therapy based on fibrinogen concentration is needed to maintain adequacy of the perioperative blood transfusion and blood conservation in cardiac surgery.

Ultrastructure of clots during isometric contraction

OpenAIRE

1982-01-01

We explored the retraction or contraction of platelet-fibrin clots under isometric conditions. In the presence of micromolar calcium clots of normal platelet-rich plasma developed tension at an initial rate of 0.1 to 0.2 g/min per cm2 (initial cross-sectional area). Electron microscopy of clots fixed after attaining a force of 1.6 g/cm2 revealed platelets with elongated bodies and pseudopods in close apposition to fibrin strands which were oriented in cablelike fashion in the direction of ten...

Blood Clots

Science.gov (United States)

... Pregnancy Immobility (including prolonged inactivity, long trips by plane or car ) Smoking Oral contraceptives Certain cancers Trauma Certain surgeries Age (increased risk for people over age 60) A family history of blood clots Chronic inflammatory diseases Diabetes High ...

The mechanical properties of dry, electrospun fibrinogen fibers

Energy Technology Data Exchange (ETDEWEB)

Baker, Stephen; Sigley, Justin; Helms, Christine C. [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States); Stitzel, Joel [Department of Biomedical Engineering, Wake Forest University Health Sciences, Winston-Salem, NC, 27157 (United States); Berry, Joel; Bonin, Keith [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States); Guthold, Martin, E-mail: gutholdm@wfu.edu [Department of Physics, Wake Forest University, Winston-Salem, NC 27109 (United States)

2012-02-01

Due to their low immunogenicity, biodegradability and native cell-binding domains, fibrinogen fibers may be good candidates for tissue engineering scaffolds, drug delivery vehicles and other medical devices. We used a combined atomic force microscope (AFM)/optical microscope technique to study the mechanical properties of individual, electrospun fibrinogen fibers in dry, ambient conditions. The AFM was used to stretch individual fibers suspended over 13.5 {mu}m wide grooves in a transparent substrate. The optical microscope, located below the sample, was used to monitor the stretching process. Electrospun fibrinogen fibers (diameter, 30-200 nm) can stretch to 74% beyond their original length before rupturing at a stress of 2.1 GPa. They can stretch elastically up to 15% beyond their original length. Using incremental stress-strain curves the viscoelastic behavior of these fibers was determined. The total stretch modulus was 4.2 GPa while the relaxed elastic modulus was 3.7 GPa. When held at constant strain, fibrinogen fibers display stress relaxation with a fast and slow relaxation time of 1.2 s and 11 s. In comparison to native and electrospun collagen fibers, dry electrospun fibrinogen fibers are significantly more extensible and elastic. In comparison to wet electrospun fibrinogen fibers, dry fibers are about 1000 times stiffer. - Highlights: Black-Right-Pointing-Pointer Fabricated dry, electrospun, fibrinogen fibers; average diameter, D{sub avg.} = 95 nm. Black-Right-Pointing-Pointer Determined mechanical properties with combined atomic force/optical microscope. Black-Right-Pointing-Pointer Fibers are very extensible ({epsilon}{sub max} = 74%) and elastic ({epsilon}{sub elastic} = 15%). Black-Right-Pointing-Pointer Fiber total modulus, E{sub tot.} = 4.2 GPa; elastic modulus, E{sub el.} = 3.7 GPa. Black-Right-Pointing-Pointer Fiber stress relaxation times: {tau}{sub 1} = 1.2 s and {tau}{sub 2} = 11 s.

The mechanical properties of dry, electrospun fibrinogen fibers

International Nuclear Information System (INIS)

Baker, Stephen; Sigley, Justin; Helms, Christine C.; Stitzel, Joel; Berry, Joel; Bonin, Keith; Guthold, Martin

2012-01-01

Due to their low immunogenicity, biodegradability and native cell-binding domains, fibrinogen fibers may be good candidates for tissue engineering scaffolds, drug delivery vehicles and other medical devices. We used a combined atomic force microscope (AFM)/optical microscope technique to study the mechanical properties of individual, electrospun fibrinogen fibers in dry, ambient conditions. The AFM was used to stretch individual fibers suspended over 13.5 μm wide grooves in a transparent substrate. The optical microscope, located below the sample, was used to monitor the stretching process. Electrospun fibrinogen fibers (diameter, 30–200 nm) can stretch to 74% beyond their original length before rupturing at a stress of 2.1 GPa. They can stretch elastically up to 15% beyond their original length. Using incremental stress–strain curves the viscoelastic behavior of these fibers was determined. The total stretch modulus was 4.2 GPa while the relaxed elastic modulus was 3.7 GPa. When held at constant strain, fibrinogen fibers display stress relaxation with a fast and slow relaxation time of 1.2 s and 11 s. In comparison to native and electrospun collagen fibers, dry electrospun fibrinogen fibers are significantly more extensible and elastic. In comparison to wet electrospun fibrinogen fibers, dry fibers are about 1000 times stiffer. - Highlights: ► Fabricated dry, electrospun, fibrinogen fibers; average diameter, D avg. = 95 nm. ► Determined mechanical properties with combined atomic force/optical microscope. ► Fibers are very extensible (ε max = 74%) and elastic (ε elastic = 15%). ► Fiber total modulus, E tot. = 4.2 GPa; elastic modulus, E el. = 3.7 GPa. ► Fiber stress relaxation times: τ 1 = 1.2 s and τ 2 = 11 s.

Moringa oleifera Lam.: Protease activity against blood coagulation cascade.

Science.gov (United States)

Satish, A; Sairam, Sudha; Ahmed, Faiyaz; Urooj, Asna

2012-01-01

The present study evaluated the protease activity of aqueous extracts of Moringa oleifera (Moringaceae) leaf (MOL) and root (MOR). Protease activity was assayed using casein, human plasma clot and human fibrinogen as substrates. Caseinolytic activity of MOL was significantly higher (P ≤ 0.05) than that of MOR. Similar observations were found in case of human plasma clot hydrolyzing activity, wherein MOL caused significantly higher (P ≤ 0.05) plasma clot hydrolysis than MOR. Zymographic techniques were used to detect proteolytic enzymes following electrophoretic separation in gels. Further, both the extracts exhibited significant procoagulant activity as reflected by a significant decrease (P ≤ 0.05) in recalcification time, accompanied by fibrinogenolytic and fibrinolytic activities; clotting time was decreased from 180 ± 10 sec to 119 ± 8 sec and 143 ± 10 sec by MOL and MOR, respectively, at a concentration of 2.5 mg/mL. Fibrinogenolytic (human fibrinogen) and fibrinolytic activity (human plasma clot) was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), plate method and colorimetric method. Zymographic profile indicated that both the extracts exerted their procoagulant activity by selectively hydrolyzing Aα and Bβ subunits of fibrinogen to form fibrin clot, thereby exhibiting fibrinogenolytic activity. However, prolonged incubation resulted in degradation of the formed fibrin clot, suggesting fibrinolytic like activity. These findings support the traditional usage of M. oleifera extracts for wound healing.

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

International Nuclear Information System (INIS)

Beyerle, Andrea; Nolte, Marc W.; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

2014-01-01

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

Energy Technology Data Exchange (ETDEWEB)

Beyerle, Andrea, E-mail: andrea.beyerle@cslbehring.com [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Nolte, Marc W. [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Solomon, Cristina [CSL Behring GmbH, Medical Affairs, Marburg (Germany); Department of Anaesthesiology, Perioperative Medicine and General Intensive Care, Paracelsus Medical University, Salzburg (Austria); Herzog, Eva; Dickneite, Gerhard [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany)

2014-10-01

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

Formation of blood clot on biomaterial implants influences bone healing.

Science.gov (United States)

Shiu, Hoi Ting; Goss, Ben; Lutton, Cameron; Crawford, Ross; Xiao, Yin

2014-12-01

The first step in bone healing is forming a blood clot at injured bones. During bone implantation, biomaterials unavoidably come into direct contact with blood, leading to a blood clot formation on its surface prior to bone regeneration. Despite both situations being similar in forming a blood clot at the defect site, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Dental implantology has long demonstrated that the fibrin structure and cellular content of a peri-implant clot can greatly affect osteoconduction and de novo bone formation on implant surfaces. This article reviews the formation of a blood clot during bone healing in relation to the use of platelet-rich plasma (PRP) gels. It is implicated that PRP gels are dramatically altered from a normal clot in healing, resulting in conflicting effect on bone regeneration. These results indicate that the effect of clots on bone regeneration depends on how the clots are formed. Factors that influence blood clot structure and properties in relation to bone healing are also highlighted. Such knowledge is essential for developing strategies to optimally control blood clot formation, which ultimately alter the healing microenvironment of bone. Of particular interest are modification of surface chemistry of biomaterials, which displays functional groups at varied composition for the purpose of tailoring blood coagulation activation, resultant clot fibrin architecture, rigidity, susceptibility to lysis, and growth factor release. This opens new scope of in situ blood clot modification as a promising approach in accelerating and controlling bone regeneration.

Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen

Energy Technology Data Exchange (ETDEWEB)

Lantz, M.S.; Allen, R.D.; Vail, T.A.; Switalski, L.M.; Hook, M. (Univ. of Alabama at Birmingham (USA))

1991-01-01

Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains. The authors now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37{degree}C. A functional fibrinogen-binding component (M{sub r}, 150 000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with {sup 125}I-fibrinogen. Fibrinogen degradation did not occur at 4{degree}C but did occur at 22 and 37{degree}C. When bacteria and iodinated fibrinogen were incubated at 37{degree}C, two major fibrinogen fragments (M{sub r}, 97 000 and 50 000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (M{sub r}, 120 000 and 150 000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the M{sub r}-120 000 and -150 000 proteases was enhanced by reducing agents, completely inhibited by N-{alpha}-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate.

Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen

International Nuclear Information System (INIS)

Lantz, M.S.; Allen, R.D.; Vail, T.A.; Switalski, L.M.; Hook, M.

1991-01-01

Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains. The authors now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37 degree C. A functional fibrinogen-binding component (M r , 150 000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with 125 I-fibrinogen. Fibrinogen degradation did not occur at 4 degree C but did occur at 22 and 37 degree C. When bacteria and iodinated fibrinogen were incubated at 37 degree C, two major fibrinogen fragments (M r , 97 000 and 50 000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (M r , 120 000 and 150 000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the M r -120 000 and -150 000 proteases was enhanced by reducing agents, completely inhibited by N-α-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate

Two novel mutations in the fibrinogen .gamma. nodule

Czech Academy of Sciences Publication Activity Database

Kotlín, R.; Pastva, O.; Štikarová, J.; Hlaváčková, A.; Suttnar, J.; Chrastinová, L.; Riedel, Tomáš; Salaj, P.; Dyr, J. E.

2014-01-01

Roč. 134, č. 4 (2014), s. 901-908 ISSN 0049-3848 R&D Projects: GA ČR GBP205/12/G118 Institutional support: RVO:61389013 Keywords : abnormal fibrinogens * hereditary coagulation disorders * fibrinogen Subject RIV: BO - Biophysics Impact factor: 2.447, year: 2014

Time-dependent association between platelet-bound fibrinogen and the Triton X-100 insoluble cytoskeleton

International Nuclear Information System (INIS)

Peerschke, E.I.

1991-01-01

Previous studies indicated a correlation between the formation of EDTA-resistant (irreversible) platelet-fibrinogen interactions and platelet cytoskeleton formation. The present study explored the direct association of membrane-bound fibrinogen with the Triton X-100 insoluble cytoskeleton of aspirin-treated, gel-filtered platelets, activated but not aggregated with 20 mumol/L adenosine diphosphate (ADP) or 150 mU/mL human thrombin (THR) when bound fibrinogen had become resistant to dissociation by EDTA. Conversion of exogenous 125I-fibrinogen to fibrin was prevented by adding Gly-Pro-Arg and neutralizing THR with hirudin before initiating binding studies. After 60 minutes at 22 degrees C, the cytoskeleton of ADP-treated platelets contained 20% +/- 12% (mean +/- SD, n = 14) of membrane-bound 125I-fibrinogen, representing 10% to 50% of EDTA-resistant fibrinogen binding. The THR-activated cytoskeleton contained 45% +/- 15% of platelet bound fibrinogen, comprising 80% to 100% of EDTA-resistant fibrinogen binding. 125I-fibrinogen was not recovered with platelet cytoskeletons if binding was inhibited by the RGDS peptide, excess unlabeled fibrinogen, or disruption of the glycoprotein (GP) IIb-IIIa complex by EDTA-treatment. Both development of EDTA-resistant fibrinogen binding and fibrinogen association with the cytoskeleton were time dependent and reached maxima 45 to 60 minutes after fibrinogen binding to stimulated platelets. Although a larger cytoskeleton formed after platelet stimulation with thrombin as compared with ADP, no change in cytoskeleton composition was noted with development of EDTA-resistant fibrinogen binding

Exploration by radioactive fibrinogen of intrarenal coagulation phenomena. Preliminary results

International Nuclear Information System (INIS)

Simon, Jacques.

1974-01-01

The participation of fibrin deposits in kidney pathology was studied by the use of a radioactive tracer involved in the coagulation phenomenon: iodine 131-labelled fibrinogen. The isotopic exploration consists of a fibrinogen kinetics study combined with external counting over the kidney regions. The different stages of the procedure are described: separation, purification and labelling of fibrinogen; characteristics of the radioactive fibrinogen used; practical details of the examination itself; data analysis method. A chapter devoted to verifications and discussions of the procedure is followed by a report on the exploration of intrarenal coagulation phenomena in 30 kidney disease patients. In conclusion, the study of fibrinogen kinetics is considered as the most suitable method to detect local or slight intravascular coagulation phenomena. The sensitivity of the isotopic exploration is very satisfactory. The main criticism directed against this method is that the exploration is general and therefore blind [fr

Fibrinogen concentrate for bleeding - a systematic review

DEFF Research Database (Denmark)

Lunde, J; Stensballe, J; Wikkelsø, A

2014-01-01

Fibrinogen concentrate as part of treatment protocols increasingly draws attention. Fibrinogen substitution in cases of hypofibrinogenaemia has the potential to reduce bleeding, transfusion requirement and subsequently reduce morbidity and mortality. A systematic search for randomised controlled...... trials (RCTs) and non-randomised studies investigating fibrinogen concentrate in bleeding patients was conducted up to November 2013. We included 30 studies of 3480 identified (7 RCTs and 23 non-randomised). Seven RCTs included a total of 268 patients (165 adults and 103 paediatric), and all were...... determined to be of high risk of bias and none reported a significant effect on mortality. Two RCTs found a significant reduction in bleeding and five RCTs found a significant reduction in transfusion requirements. The 23 non-randomised studies included a total of 2825 patients, but only 11 of 23 studies...

Evaluation of fibrinogen-DTPA-99mTc. Biodistribution and imaging studies

International Nuclear Information System (INIS)

Lungu, V.; Mihailescu, G.; Fugaru, V.; Preda, A.

1998-01-01

Labelling with 99m Tc of fibrinogen, using DTPA anhydride as the bifunctional chelating agent, was studied in animals with venous thrombi. The parameters studied were: i) coupled reaction of 99m Tc with the fibrinogen-DTPA-Sn(II) in lyophilised form; ii) biodistribution studies of fibrinogen- 99m Tc in animals with venous thrombi, and iii) imaging studies by scintigraphic methods. The present study showed that the radiochemical purity of fibrinogen-DTPA- 99m Tc is > 95% for a maximum of 5 mCi (185 MBq) radioactivity of 99m Tc in the 1.5-2 ml volume. Above this level of radioactivity we found a drastic decrease in the radiochemical purity. The radioactivity ratio of the venous thrombi to the blood was 2.32+-0.45. The scintigraphic images showed a significant accumulation of fibrinogen-DTPA- 99m Tc in 1-hour-old thrombi, 1 hour after injection. From this results the diagnostic potential of fibrinogen-DTPA-Sn(II) in kit form was evaluated. (author)

Correlating structure and function during the evolution of fibrinogen-related domains

Science.gov (United States)

Doolittle, Russell F; McNamara, Kyle; Lin, Kevin

2012-01-01

Fibrinogen-related domains (FReDs) are found in a variety of animal proteins with widely different functions, ranging from non-self recognition to clot formation. All appear to have a common surface where binding of one sort or other occurs. An examination of 19 completed animal genomes—including a sponge and sea anemone, six protostomes, and 11 deuterostomes—has allowed phylogenies to be constructed that show where various types of FReP (proteins containing FReDs) first made their appearance. Comparisons of sequences and structures also reveal particular features that correlate with function, including the influence of neighbor-domains. A particular set of insertions in the carboxyl-terminal subdomain was involved in the transition from structures known to bind sugars to those known to bind amino-terminal peptides. Perhaps not unexpectedly, FReDs with different functions have changed at different rates, with ficolins by far the fastest changing group. Significantly, the greatest amount of change in ficolin FReDs occurs in the third subdomain (“P domain”), the very opposite of the situation in most other vertebrate FReDs. The unbalanced style of change was also observed in FReDs from non-chordates, many of which have been implicated in innate immunity. PMID:23076991

Electrospun nanofibre fibrinogen for urinary tract tissue reconstruction

International Nuclear Information System (INIS)

McManus, Michael; Boland, Eugene; Sell, Scott; Bowen, Whitney; Koo, Harry; Simpson, David; Bowlin, Gary

2007-01-01

The purpose of this study was to demonstrate that human bladder smooth muscle cells (HBSM) remodel electrospun fibrinogen mats. Fibrinogen scaffolds were electrospun and disinfected using standard methods. Scaffolds were seeded with 5 x 10 4 HBSM per scaffold. Cultures were supplemented with aprotinin concentrations of 0 KIU ml -1 (no aprotinin), 100 KIU ml -1 or 1000 KIU ml -1 and incubated with twice weekly media changes. Samples were removed for evaluation at 1, 3, 7 and 14 days. Cultured scaffolds were evaluated with a WST-1 cell proliferation assay, scanning electron microscopy and histology. Cell culture demonstrated that HBSM readily migrated into and initiated remodelling of the electrospun fibrinogen scaffolds by deposition of collagen. Proliferation was suppressed during this initial phase with respect to a 2D control due to cell migration. Histology confirmed that proliferation increased during the later stages of remodelling. Remodelling was slower at higher aprotinin concentrations. These results demonstrate that HBSM rapidly remodel an electrospun fibrinogen scaffold and deposit native collagen. The process can be modulated using aprotinin, a protease inhibitor. These initial findings indicate that there is tremendous potential for electrospun fibrinogen as a urologic tissue engineering scaffold with the ultimate goal of producing an implantable acellular product that would promote cellular in-growth and in situ tissue regeneration

Positive imaging of venous thrombi and thromboemboli with Ga-67 DFO-DAS-fibrinogen

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Kazutaka; Senda, Michio; Fujita, Toru; Yonekura, Yoshiharu; Kumada, Kaoru; Yokoyama, Akira; Torizuka, Kanji

1988-05-01

A newly developed thrombus imaging agent, /sup 67/Ga-DFO-DAS-fibrinogen (/sup 67/Ga-fibrinogen), was used for 22 studies in 20 cases of suspected deep venous thrombosis. Increased accumulation of /sup 67/Ga-fibrinogen in venous thrombi was depicted at 48 h after injection in 10 of the 15 cases (10 of 17 studies) who showed abnormal findings in radionuclide venography. A hot spot in the lung emboli was visualized in two cases. Seven of the eight cases having anticoagulant therapy showed increased /sup 67/Ga-fibrinogen uptake, while follow-up /sup 67/Ga-fibrinogen scintigraphy after the administration of heparin and urokinase did not reveal an abnormal hot spot in one case. /sup 67/Ga-fibrinogen can be made available simply by adding /sup 67/Ga solution to a vial containing fibrinogen-DAS-DFO conjugate. In conclusion, /sup 67/Ga-fibrinogen is considered to be a promising agent for detecting active venous thrombi and to assess the effect of anticoagulant therapy.

Beta fibrinogen gene polymorphisms are associated with plasma fibrinogen and coronary artery disease in patients with myocardial infarction. The ECTIM Study. Etude Cas-Temoins sur l'Infarctus du Myocarde.

Science.gov (United States)

Behague, I; Poirier, O; Nicaud, V; Evans, A; Arveiler, D; Luc, G; Cambou, J P; Scarabin, P Y; Bara, L; Green, F; Cambien, F

1996-02-01

Polymorphisms of the beta fibrinogen gene have been shown to affect plasma fibrinogen levels and the risk of peripheral arterial disease. We now present the results of a detailed analysis of the beta fibrinogen gene in relation to plasma fibrinogen and to the severity of coronary artery disease (CAD) in patients with myocardial infarction (MI) in the ECTIM Study. Ten polymorphisms of the beta fibrinogen gene, including five new polymorphisms identified by single-strand conformation polymorphism analysis, and one polymorphism in the 3' flanking region of the alpha fibrinogen gene were investigated in 565 patients with MI and 668 control subjects. The polymorphisms were in tight linkage disequilibrium and the genotype frequencies were similar in patients with MI and control subjects. In the multivariate analysis, only two polymorphisms, beta Hae III (P 50% stenosis was estimated by angiography and used as a criterion for severity of CAD. Presence of the less frequent allele of the beta Bcl I (P < .0003) and of other polymorphisms was positively associated with the severity of CAD. Genetic variants of the beta fibrinogen gene are associated with an increased plasma level of fibrinogen, especially in smokers. The association with CAD appears to be the consequence of an increased risk of MI in subjects with severe CAD who carry the predisposing beta fibrinogen genotypes.

Fibrinogen-Induced Streptococcus mutans Biofilm Formation and Adherence to Endothelial Cells

Directory of Open Access Journals (Sweden)

Telma Blanca Lombardo Bedran

2013-01-01

Full Text Available Streptococcus mutans, the predominant bacterial species associated with dental caries, can enter the bloodstream and cause infective endocarditis. The aim of this study was to investigate S. mutans biofilm formation and adherence to endothelial cells induced by human fibrinogen. The putative mechanism by which biofilm formation is induced as well as the impact of fibrinogen on S. mutans resistance to penicillin was also evaluated. Bovine plasma dose dependently induced biofilm formation by S. mutans. Of the various plasma proteins tested, only fibrinogen promoted the formation of biofilm in a dose-dependent manner. Scanning electron microscopy observations revealed the presence of complex aggregates of bacterial cells firmly attached to the polystyrene support. S. mutans in biofilms induced by the presence of fibrinogen was markedly resistant to the bactericidal effect of penicillin. Fibrinogen also significantly increased the adherence of S. mutans to endothelial cells. Neither S. mutans cells nor culture supernatants converted fibrinogen into fibrin. However, fibrinogen is specifically bound to the cell surface of S. mutans and may act as a bridging molecule to mediate biofilm formation. In conclusion, our study identified a new mechanism promoting S. mutans biofilm formation and adherence to endothelial cells which may contribute to infective endocarditis.

Quality asurance of iodinated (125 I) human fibrinogen

International Nuclear Information System (INIS)

Vines, E.J.

1980-05-01

The radiopharmaceutical iodinated ( 125 I) human fibrinogen is currently used for the detection of deep vein thrombosis in the legs, a fairly common post-surgical complication. A comprehensive quality assurance programme for ( 125 I) - human fibrinogen has been determined for routine use at the Australian Radiation Laboratory, with adaptions necessary for hospital quality control testing

Developing Mesoscale Model of Fibrin-Platelet Network Representing Blood Clotting =

Science.gov (United States)

Sun, Yueyi; Nikolov, Svetoslav; Bowie, Sam; Alexeev, Alexander; Lam, Wilbur; Myers, David

Blood clotting disorders which prevent the body's natural ability to achieve hemostasis can lead to a variety of life threatening conditions such as, excessive bleeding, stroke, or heart attack. Treatment of these disorders is highly dependent on understanding the underlying physics behind the clotting process. Since clotting is a highly complex multi scale mechanism developing a fully atomistic model is currently not possible. We develop a mesoscale model based on dissipative particle dynamics (DPD) to gain fundamental understanding of the underlying principles controlling the clotting process. In our study, we examine experimental data on clot contraction using stacks of confocal microscopy images to estimate the crosslink density in the fibrin networks and platelet location. Using this data we reconstruct the platelet rich fibrin network and study how platelet-fibrin interactions affect clotting. Furthermore, we probe how different system parameters affect clot contraction. ANSF CAREER Award DMR-1255288.

The effective control of a bleeding injury using a medical adhesive containing batroxobin

International Nuclear Information System (INIS)

You, Kyung Eun; Koo, Min-Ah; Lee, Dae-Hyung; Kwon, Byeong-Ju; Lee, Mi Hee; Park, Jong-Chul; Hyon, Suong-Hyu; Seomun, Young; Kim, Jong-Tak

2014-01-01

Many types of hemostatic agents have been studied for the effective control of bleeding. In this study, a powdery medical adhesive composed of aldehyded dextran and ε-poly (L-lysine) was used with the recombinant batroxobin. Batroxobin is a venomous component from the snake Bothrops atrox moojeni and catalyzes fibrinogen conversion to form soluble fibrin clots. This research aims to examine the performance of the batroxobin-containing adhesive for hemostasis, and evaluate its potential as a novel hemostatic adhesive. The fibrinogen conversion ability of batroxobin was evaluated by a fibrinogen clotting assay and a whole blood clotting assay. Both experiments demonstrated the effectiveness of the batroxobin-containing adhesive for blood clot formation. Animal experiments were also conducted. After a pricking wound was made in an ICR (imprinting control region) mouse liver, the adhesive and various concentrations of batroxobin were applied. The total amount of blood loss was reduced with increasing concentrations of batroxobin. For excessive bleeding conditions, the femoral artery wound model of SD (Sprague-Dawley) rats was adopted. With higher concentrations of batroxobin, hemostasis was more rapidly achieved. Histological analysis of the liver model also supports the hemostatic effects through fibrin clot formation. In conclusion, batroxobin and medical adhesive effectively facilitate blood coagulation, and could be developed for clinical use. (paper)

Clot friction variation with fibrin content; implications for resistance to thrombectomy.

Science.gov (United States)

Gunning, Gillian M; McArdle, Kevin; Mirza, Mahmood; Duffy, Sharon; Gilvarry, Michael; Brouwer, Patrick A

2018-01-01

Despite significant advancements in the procedural efficacy of mechanical thrombectomy in patients with ischemic stroke in recent years, there still remains a portion of the population that does not achieve good recanalization. The reasons for this may be varied. We hypothesized that static friction between the clot and the vessel, or catheter wall might contribute to the difficulty in removing the clot. To determine if there is a relationship between clot composition and the resistance to sliding (friction) which might contribute to resistance to clot removal. As clot composition can vary significantly, we investigated five different types of clot in order to measure their respective frictional properties. To do this, a custom-made testing apparatus was created, consisting of various replaceable low-friction surfaces on which the clots could be placed. The surface was then gradually tilted until the clots began to slide; the angle at which this occurred is related to the coefficient of friction of the clots. The experiment was repeated on a bovine aortic surface in order to confirm the results. We found that fibrin-rich clots (friction than clots with a red blood cell content >20%. This result was confirmed by repeating the experiment on a bovine aortic surface as a representation of the interaction between clots and the arterial wall. The friction properties of clots were found to be related to the content ratio of fibrin to red blood cells. Future imaging techniques that could show fibrin and red blood cell content might help us to predict the 'stickiness' of a clot. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Capture of lipopolysaccharide (endotoxin) by the blood clot: a comparative study.

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Armstrong, Margaret T; Rickles, Frederick R; Armstrong, Peter B

2013-01-01

In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot) and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument. Here we show that, in addition to these passive functions in immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus, and both the platelet thrombus and the fibrin clot of mammals (human, mouse) operate to capture lipopolysaccharide (LPS, endotoxin). The lipid A core of LPS is the principal agent of gram-negative septicemia, which is responsible for more than 100,000 human deaths annually in the United States and is similarly toxic to arthropods. Quantification using the Limulus Amebocyte Lysate (LAL) test shows that clots capture significant quantities of LPS and fluorescent-labeled LPS can be seen by microscopy to decorate the clot fibrils. Thrombi generated in the living mouse accumulate LPS in vivo. It is suggested that capture of LPS released from gram-negative bacteria entrapped by the blood clot operates to protect against the disease that might be caused by its systemic dispersal.

Capture of lipopolysaccharide (endotoxin by the blood clot: a comparative study.

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Margaret T Armstrong

Full Text Available In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument. Here we show that, in addition to these passive functions in immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus, and both the platelet thrombus and the fibrin clot of mammals (human, mouse operate to capture lipopolysaccharide (LPS, endotoxin. The lipid A core of LPS is the principal agent of gram-negative septicemia, which is responsible for more than 100,000 human deaths annually in the United States and is similarly toxic to arthropods. Quantification using the Limulus Amebocyte Lysate (LAL test shows that clots capture significant quantities of LPS and fluorescent-labeled LPS can be seen by microscopy to decorate the clot fibrils. Thrombi generated in the living mouse accumulate LPS in vivo. It is suggested that capture of LPS released from gram-negative bacteria entrapped by the blood clot operates to protect against the disease that might be caused by its systemic dispersal.

Behaviour of homologous 125I fibrinogen after thrombin and ancrod infusion in rabbits

International Nuclear Information System (INIS)

Setter, R.

1977-01-01

The behaviour of radioactively labelled fibrinogen after infusion of thrombin or ancrod is investigated. Common factors and differences in the behaviour of fibrinogen after infusion of these two enzymes, which act proteolytically on the fibrinogen, are dealt with. Rabbits received an i.v. injection of homologous 125 I-fibrinogen 3 days before ancrod or thrombin infusion. On the day of the experiments, one group of animals received an ancrod infusion (1.5 U/kg body weight for 30 minutes), the other a thrombin infusion (600 U/kg body weight for 60 minutes). Intravenous ancrod and thrombin infusions lowered the fibrinogen level to 30% or 50% of the initial value due to intravascular coagulation. About 50% of the 125 I fibrinogen was transformed after ancrod exposure into a non-coagulating fraction of fibrinogen derivatives which produces no fibrinolytic decomposition products. (orig./AJ) [de

Postpartum Blood Clots

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... Video) Fetal Ultrasound Scanning Additional Content Medical News Postpartum Blood Clots By Julie S. Moldenhauer, MD, Associate Professor ... Professional Version Postdelivery Period Overview of the Postdelivery (Postpartum) Period Postpartum Infections Postpartum Infections of the Uterus ...

In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

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Zelda de Lange

Full Text Available Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT. We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009 but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central obesity was the biggest contributor to PAI-1act variance (12.5%. Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

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de Lange, Zelda; Rijken, Dingeman C; Hoekstra, Tiny; Conradie, Karin R; Jerling, Johann C; Pieters, Marlien

2013-01-01

Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

The binding of fibrinogen to platelets in diabetes mellitus

International Nuclear Information System (INIS)

Minno, G. di; Cerbone, A.M.; Iride, C.; Mancini, M.

1986-01-01

Platelets from diabetics are known to be more sensitive in vitro to a variety of aggregating agents, to produce more prostaglandin endoperoxides and thromboxane and to bind more 125 I-fibrinogen than platelets from normal controls. Fibrinogen binding to platelets is a pre-requisite for platelet aggregation. Previous studies suggested a role for prostaglandins and/or thrombaxane A 2 in the exposure of fibrinogen receptors on platelets. The present study compares fibrinogen binding to hyperaggregable platelets from diabetic patients and to normal platelets when prostaglandin/thromboxane formation is suppressed by aspirin. It was found that pre-treatment with aspirin reduced collagen or thrombin-induced binding to platelets from none-retinopathic diabetics to the values seen in controls. By contrast, aspirin did not normalize binding to platelets obtained from retinopathic diabetics. The combination of aspirin with apyrase (an ADP scavenger) almost completely inhibited binding and aggregation of platelets from normal controls or non-retinophatic diabetics exposed to collagen or thrombin, whereas it only partially affected binding and aggregation of platelets from retinopathics. By using a monoclonal antibody (B59.2) to the platelet receptor for fibrinogen, we determined that this receptor was quantitatively and qualitatively the same on platelets from normal controls and diabetics. We conclude that increased fibrinogen binding and hyperaggregability of platelets from none-retinopathic diabetics is related to their capacity to form more prostaglandin endoperoxides/thromboxane than normal platelets. In contrast, hyperaggregability and increased binding of platelets from retinopathics appear at least partly related to a mechanism independent of ADP release and thromboxane synthesis. (Author)

Influence of low- and high-dose radioiodine therapy on oxidative modification of fibrinogen

International Nuclear Information System (INIS)

Schweeger-Exeli, I.J.

2001-10-01

Fibrinogen plays a central role in the course of thrombosis and hemostasis. It is soluble in blood and tissue extracts and transformed into the insoluble fibrin network structure in the presence of thrombin. Fibrinogen in circulating blood consists of a population of slightly different molecules with a half-life of 3.5-4.5 days. Various environmental conditions may cause different types of modifications of the molecule leading to a different functional behavior. Introduction of carbonyl groups in amino acid side chains is known as a marker for protein oxidation. Radioiodine therapy, applied in patients suffering from hyperthyroidism or differentiated thyroid carcinoma, may cause an oxidative modification of fibrinogen by formation of free radicals in blood exposed to the radioactive agent 131I. The topic of my thesis was i. to develop a simple and not time consuming method for isolation of fibrinogen from small volumes of human plasma (∼ 6ml), ii. to assess, whether radioiodine therapy causes detectable introduction of carbonyl groups into the fibrinogen molecule, and iii. to analyze an association between thyroid hormone function, fibrinogen levels and protein oxidation by means of carbonyl content. Purification of fibrinogen from human plasma was possible by three different methods (ammonium sulphate/ethanol; glycine/ethanol; glycine). Plasma levels of fibrinogen (Clauss method) and protein carbonyl group content (2,4-DNPH - assay) were determined before and after radioiodine therapy. The results demonstrate a significant increase (p = 0.05) in carbonyl content of human fibrinogen in cancer patients treated with 131I. However, in patients with diagnosed hyperthyroidism values were not significantly altered. In carcinoma patients, baseline fT4 levels and the relative increase in carbonyl content of fibrinogen after radioiodine therapy were correlated (r = 0.83; p 0.005), whereas no such correlation was found in patients with hyperthyroidism. Plasma fibrinogen

Electrospray ionisation mass spectrometry facilitates detection of fibrinogen (Bbeta 14 Arg --> Cys) mutation in a family with thrombosis.

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Brennan, S O; Hammonds, B; Spearing, R; George, P M

1997-12-01

We report the first direct detection of a fibrinogen mutation by electrospray ionisation mass spectrometry. The propositus, from a family with a history of thrombosis, came to attention after a pulmonary embolism subsequent to a spontaneous abortion. Prolonged thrombin (41 s) and reptilase times (26 s) together with an impairment of fibrinopeptide B release suggested a mutation at the thrombin cleavage site of the Bbeta chain. Direct mass analysis of purified fibrin chains from a thrombin induced clot showed that 50% of the Bbeta chains remained uncleaved. The measured mass of the mono sialo isoform of this uncleaved chain was 54150 Da, compared to a value of 54198 Da for normal Bbeta chains. This decrease of 48 Da in the intact protein is indicative of either a Bbeta 14 Arg to Cys, or Arg to Leu substitution. Heterozygosity for the Bbeta 14 Arg --> Cys mutation was verified by PCR amplification and DNA sequence analysis.

A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots.

Science.gov (United States)

Seo, Junyoung; Al-Hilal, Taslim A; Jee, Jun-Goo; Kim, Yong-Lim; Kim, Ha-Jeong; Lee, Byung-Heon; Kim, Soyoun; Kim, In-San

2018-04-01

The use of thrombolytic therapies is limited by an increased risk of systemic hemorrhage due to lysis of hemostatic clots. We sought to develop a plasmin-based thrombolytic nanocage that efficiently dissolves the clot without causing systemic fibrinolysis or disrupting hemostatic clots. Here, we generated a double chambered short-length ferritin (sFt) construct that has an N-terminal region fused to multivalent clot targeting peptides (CLT: CNAGESSKNC) and a C-terminal end fused to a microplasmin (μPn); CLT recognizes fibrin-fibronectin complexes in clots, μPn efficiently dissolves clots, and the assembly of double chambered sFt (CLT-sFt-μPn) into nanocage structure protects the activated-μPn from its circulating inhibitors. Importantly, activated CLT-sFt-μPn thrombolytic nanocage showed a prolonged circulatory life over activated-μPn and efficiently lysed the preexisting clots in both arterial and venous thromboses models. Thus, CLT-sFt-μPn thrombolytic nanocage platform represents the prototype of a targeted clot-busting agent with high efficacy and safety over existing thrombolytic therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

The Primary Role of Fibrinogen-Related Proteins in Invertebrates Is Defense, Not Coagulation

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Hanington, Patrick C.; Zhang, Si-Ming

2010-01-01

In vertebrates, the conversion of fibrinogen into fibrin is an essential process that underlies the establishment of the supporting protein framework required for coagulation. In invertebrates, fibrinogen-domain-containing proteins play a role in the defense response generated against pathogens; however, they do not function in coagulation, suggesting that this role has been recently acquired. Molecules containing fibrinogen motifs have been identified in numerous invertebrate organisms, and most of these molecules known to date have been linked to defense. Moreover, recent genome projects of invertebrate animals have revealed surprisingly high numbers of fibrinogen-like loci in their genomes, suggesting important and perhaps diverse functions of fibrinogen-like proteins in invertebrates. The ancestral role of molecules containing fibrinogen-related domains (FReDs) with immunity is the focus of this review, with emphasis on specific FReDs called fibrinogen-related proteins (FREPs) identified from the schistosome-transmitting mollusc Biomphalaria glabrata. Herein, we outline the range of invertebrate organisms FREPs can be found in, and detail the roles these molecules play in defense and protection against infection. PMID:21063081

Intrinsic clotting factors in dependency of age, sex, body mass index, and oral contraceptives: definition and risk of elevated clotting factor levels.

Science.gov (United States)

Luxembourg, Beate; Schmitt, Joern; Humpich, Marek; Glowatzki, Matthias; Seifried, Erhard; Lindhoff-Last, Edelgard

2009-10-01

Elevated clotting factors have been demonstrated to be a risk factor for venous thromboembolism (VTE). The aim of our study was to investigate the impact of age, sex, body mass index, and oral contraceptives on the clotting factor activities of factors VIII, IX, XI, and XII and their impact on the cutoff definition and risk of VTE associated with elevated clotting factors. Factor VIII, IX, XI, and XII activities were measured in 499 blood donors and 286 patients with VTE. Age and body mass index predicted significantly and independently the clotting factor activities of factors VIII, IX, and XI, whereas use of oral contraceptives predicted factor IX, XI, and XII levels. Percentiles of clotting factor activities, which are often used for the cutoff definition of elevated clotting factors, varied due to the effect of age, body mass index, and oral contraceptives. The adjusted odds ratios for VTE were 10.3 [95% confidence interval (CI) 5.1-20.7], 6.1 (95% CI 3.1-12.0), and 3.3 (95% CI 1.9-5.8) for elevated factors VIII, IX, and XI, respectively. Furthermore, our study demonstrates for the first time that elevated factor XII is associated with an increased risk of VTE (adjusted odds ratio 2.9, 95% CI 1.6-5.3).

BOVINE PLASMA FIBRINOGEN AS MARKER IN CLINICAL AND SUB-CLINICAL MASTITIS

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R. Ali

2018-06-01

Full Text Available Plasma samples were collected from healthy as well as clinical and sub-clinical mastitis affected cows from Barasat, West Bengal, India. Plasma samples, after ammonium sulphate precipitation, were dialyzed against several changes of PBS (pH 7.2 to remove the excess ammonium sulphate. Then plasma fibrinogens were purified by gel filtration chromatography on Sephacryl S-200 HR. SDS-PAGE (10% of purified fibrinogen from plasma of healthy cow revealed polypeptide bands of 74, 67 and 57 kDa which represent the α (alpha, β (beta and γ (gamma- chains respectively. On the other hand, purified fibrinogen from plasma of sub-clinical and clinical mastitis affected cow revealed polypeptide bands of 73 (α-chain, 68 kDa (β-chain and 72 (γ-chain, 68 kDa (β-chain respectively. The SDS-PAGE analysis showed the absence of gamma (γ- chain of fibrinogen in both the samples of sub-clinical and clinical mastitis positive cow. Single precipitin line was observed in double immunodiffusion test when purified fibrinogen from healthy, clinical and subclinical mastitis positive cows reacted with hyper immune sera raised in rabbit. No precipitin line was found against the normal control serum. These purified fibrinogens also showed cross reactivity against antibody raised in rabbit when analyzed by western blot technique.

Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders.

Science.gov (United States)

Fenger-Eriksen, Christian; Moore, Gary W; Rangarajan, Savita; Ingerslev, Jørgen; Sørensen, Benny

2010-12-01

Measurement of plasma fibrinogen is often required in critically ill patients or massively bleeding patients being resuscitated with colloid plasma expander. This study aimed at evaluating different assays of plasma fibrinogen after in vitro dilution with commonly used plasma expanders and challenged the hypothesis that levels of fibrinogen are estimated significantly higher in plasma diluted with colloid plasma expander compared with isotonic saline. Fibrinogen measurements were established in plasma samples each diluted in vitro to 30 or 50% with isotonic saline, hydroxyethyl starch (HES) 130/0.4, and human albumin. Fibrinogen levels were assessed using an antigen determination, three photo-optical Clauss methods, one mechanical Clauss method, a prothrombin-derived method, and viscoelastic measurement through thromboelastometry. Measurement of fibrinogen levels was significantly different when performed on alternate analytical platforms. By 30 and 50% dilution with HES 130/0.4 coagulation analyzers using the photo-optical Clauss methods significantly overestimated levels of fibrinogen. Dilution with human albumin did not affect fibrinogen levels except from one analyzer by 50% dilution level. Viscoelastic measurement of fibrin polymerization was reduced at both dilution levels and appeared to reflect the impairment of fibrin polymerization induced by HES 130/0.4 and to a lesser extent human albumin. This study demonstrated that different automated coagulation analyzers revealed significantly different levels of fibrinogen. The presence of colloid plasma expander gave rise to erroneous high levels of fibrinogen returned from some coagulation analyzers employing the method of Clauss. © 2010 American Association of Blood Banks.

Case series: Bladder clot evacuation using a prostate morcellation device.

Science.gov (United States)

Doersch, Karen M; Navetta, Andrew F; Bird, Erin T; El Tayeb, Marawan M

2017-07-01

We sought to provide a technical update on the use of a prostate morcellator device (PMD) to manage organized blood clots of the bladder following laser prostatectomy. Herein, we describe our experience in using the Wolf Piranha morcellator in managing organized bladder blood clots supplemented with a retrospective chart review of the patients in whom this procedure was performed. Six patients, all male with a mean age of 75 ± 8.9 years, had organized bladder clots following either holmium laser enucleation or photoselective vaporization of the prostate managed with a PMD. Clots were recognized based on hematuria or urinary retention a median of 3.5 days following the aforementioned procedures. Initial management was attempted with more conservative measures, including a three-way Foley catheter, followed by cystoscopy with an Ellik evacuator, or a glass Tommey syringe. Morcellation times were a mean of 10.2 ± 6.15 minutes (range 2-18). This technique was able to manage clots that were an average of 173.3 ± 115.9 cc in size. The procedure was well-tolerated. No patients experienced intraoperative or morcellator-related complications. Benign prostatic hypertrophy frequently requires surgical endoscopic management and can be complicated by hematuria and bladder blood clot formation. When these clots become organized, this can lead to urinary retention and the required management, evacuation, may be difficult. The use of a Wolf Piranha PMD is a safe, well-tolerated, and effective in evacuating organized blood clots of the bladder.

Sucralfate protects blood clots from peptic digestion by gastric juice in vitro.

Science.gov (United States)

Nysaeter, Gunnar; Berstad, Arnold

2006-01-01

To test in vitro the ability of sucralfate to protect a blood clot from peptic digestion by gastric juice. Blood clots adhering to the bottom of plastic tubes were exposed to native acidic gastric juice or gastric juice to which Al-Mg antacids, sucralfate or alkali had been added. The tubes were tilted regularly at room temperature and clot digestion monitored by measuring the diameters of the clots. After 15 h, the liquids, but not the adherent clots, were poured out and the tubes refilled with native acidic gastric juice. Further clot digestion was measured, as before. Native gastric juice digested the clots completely during approximately 7 h, while in neutralized gastric juice or in gastric juice containing antacids or sucralfate no digestion was seen. In the second experiment, native gastric juice completely digested all remaining clots, except those previously exposed to sucralfate. A dose-response study indicated that gastric juice containing 3% or more of sucralfate had this long-lasting, clot-protective effect. In vitro, sucralfate adheres to and protects blood clots from digestion by gastric juice pepsin. This unique effect of sucralfate may be of clinical relevance in the treatment of bleeding peptic ulcers. Copyright 2006 S. Karger AG, Basel.

Distribution of iodine-labelled fibrinogen in rat during endotoxin shock

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Toth, J [Semmelweis Orvostudomanyi Egyetem, Budapest (Hungary); Spett, B; Bertok, L; Kocsar, L [Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, Budapest (Hungary)

1978-10-01

Animals of the experimental and control groups received 10-10 microcurie i.v. /sup 125/I-fibrinogen. The fibrinogen forms a deposit on the surface of the microthrombi and we can find more activity where the thrombi were formed. 60 minutes after administering endotoxin the activity of the ilium of the shocked animals increased significantly (exceeding that of the control group by 37%). A considerable difference may be observed also 120 minutes later, and the activity of the liver amounts to twice the activity of control animals two hours after i.v. /sup 125/I-fibrinogen injection.

Two cases of congenital dysfibrinogenemia associated with thrombosis - Fibrinogen Praha III and Fibrinogen Plzen

Czech Academy of Sciences Publication Activity Database

Kotlín, R.; Reicheltová, Z.; Malý, M.; Suttnar, J.; Sobotková, A.; Salaj, P.; Hirmerová, J.; Riedel, Tomáš; Dyr, J. E.

2009-01-01

Roč. 102, č. 3 (2009), s. 479-486 ISSN 0340-6245 R&D Projects: GA AV ČR KAN200670701 Institutional research plan: CEZ:AV0Z40500505 Keywords : dysfibrinogenemia * fibrinogen * missense mutation Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.451, year: 2009

Fibrinogen and alpha(1)-antitrypsin in COPD exacerbations

DEFF Research Database (Denmark)

Sylvan Ingebrigtsen, Truls; Marott, J. L.; Rode, L.

2015-01-01

Background We tested the hypotheses that fibrinogen and alpha(1)-antitrypsin are observationally and genetically associated with exacerbations in COPD. Methods We studied 13 591 individuals with COPD from the Copenhagen General Population Study (2003-2013), of whom 6857 were genotyped for FGB -455...... and exacerbations in instrumental variable analyses. Results Elevated fibrinogen and alpha(1)-antitrypsin levels were associated with increased risk of exacerbations in COPD, HR=1.14 (1.07 to 1.22, p...

Blood Clotting and Pregnancy

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Blood Clotting and Pregnancy

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Blood Clotting and Pregnancy

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Association of fibrinogen with HbA1C in diabetic foot ulcer

Science.gov (United States)

Pase, M. A.; Gatot, D.; Lindarto, D.

2018-03-01

Fibrinogen is one of the inflammatory markers of vascular changes and endothelial dysfunction in diabetic patients. The aim of this study to associate serum fibrinogen levels with HbA1C in diabetic foot ulcer (DFU). This study was cross-sectional and retrospective in DFU patients from January to July 2017 in Haji Adam Malik Central General Hospital. The patients enrolled in the study were T2DM with DFU as a complication. The grading of DFU was evaluated according to the Wagner’s Classification. Serum fibrinogen level, HbA1C and ankle-brachial index (ABI) were carried out directly in the patients. Fibrinogen serum levels were found significantly with HbA1C (P=0.001, r=0.387) and ABI (P=0.008, r=-0.454). Fibrinogen serum levels in DFU patients were positively correlated with HbA1C and significantly higher in patients with poor glycemic control.

Consumption coagulopathy in acute aortic dissection: principles of management.

Science.gov (United States)

Liu, Yuyong; Han, Lu; Li, Jiachen; Gong, Ming; Zhang, Hongjia; Guan, Xinliang

2017-06-12

The effect of acute aortic dissection itself on coagulopathy or surgery-related coagulopathy has never been specifically studied. The aim of the present study was to perioperatively describe consumption coagulopathy in patients with acute aortic dissection. Sixty-six patients with acute type A aortic dissection were enrolled in this study from January 2015 to September 2016. Thirty-six patients with thoracic aortic aneurysms were used as a control group during the same period. Consumption coagulopathy was evaluated using standard laboratory tests, enzyme-linked immunosorbent assay and thromboelastograghy at five perioperative time-points. A significant reduction in clotting factors and fibrinogen was observed at the onset of acute aortic dissection. Enzyme-linked immunosorbent assay and thromboelastograghy also revealed a persistent systemic activation of the coagulation system and the consumption of clotting factors. In contrast, although platelet counts were consistently low, we did not find that platelet function was more impaired in the acute aortic dissection group than the control group. After surgery, clotting factors and fibrinogen were more impaired than platelet function. Thus, we proposed that hemostatic therapy should focus on the rapid and sufficient supplementation of clotting factors and fibrinogen to improve consumption coagulopathy in patients with acute aortic dissection.

Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

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Ehling Rainer

2011-10-01

Full Text Available Abstract Background Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF of acute and chronic central (CNS and peripheral nervous system (PNS diseases is unclear. Findings We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS, acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM and PNS (Guillain-Barré syndrome; GBS, as well as in non-inflammatory neurological controls (OND in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture. CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p Conclusions Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment.

Blood Clotting and Pregnancy

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Blood Clotting and Pregnancy

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Blood Clotting and Pregnancy

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Full Text Available ... harming your baby. Jump To: Am I at Risk? The risk of developing a blood clot during ... Advances The Hematologist ASH Clinical News ASH Self-Assessment Program Hematology , ASH Education Program About Awards Membership ...

Quality of Clotting Factor Activity in Fresh Frozen Plasma at Thaw with a Microwave System and after Storage at 4 degrees C for 48 Hours.

Science.gov (United States)

Kuta, Piotr; Hauck-Dlimi, Barbara; Strobel, Julian; Zimmermann, Robert; Eckstein, Reinhold

2016-01-01

Uncontrolled hemorrhage in polytrauma patients usually results in rapid need of blood products. Despite the shorter thawing times of microwave devices for heating fresh frozen plasma (FFP), their use has remained controversial, and just a few laboratory analyses have been published on this topic. The aim of this study was to analyse the quality of clotting factors immediately after thawing FFP with a microwave device and after 48-hour post thaw storage at 4 degrees C. 24 FFP units of all four ABO blood groups (six of each blood group) were thawed with a Transfusio-therm 2000 and later stored at 4 degrees C for 48 hours. Samples were drawn aseptically and investigated on various clotting factors and protein proteases (fibrinogen, antithrombin, FII, FV, FVII, FVIII, FIX, FX, FXI, FXIII, vWF antigen and activity, protein S, and protein C) using standard coagulation and chromogenic assays immediately after thawing and again after a 48-hour storage period at 4 degrees C. All units were tested for both anaerobic and aerobic microbial contamination using standard operating procedures immediately after thawing. After thawing, all coagulation factors and protein protease activities were within normal ranges. Blood group O individuals had approximately 25% lower plasma levels of vWF antigen and activity. After a 48-hour storage period at 4 degrees C, FVIII and FIX activities declined significantly in all blood groups, whereas the remaining clotting factors remained comparably stable. Immediately after rapid thawing using a microwave system, all FFP units contained adequate coagulation factor activities to maintain hemostatic activity at the time of product thaw. The post thaw refrigerated storage caused an anticipated decrease in factor VIII and IX activities, but retained normal coagulation factor levels of many plasma proteins. Therefore we conclude that the Transfusio-therm 2000 has no clinically significant influence on the activity of clotting factors and plasma

Blood Clotting and Pregnancy

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Full Text Available ... known as venous thromboembolism, are highly preventable (see prevention tips below). The U.S. Surgeon General has issued ... blood conditions and increase research on the causes, prevention, and treatment. Blood clots are also potentially dangerous ...

Detection of tPA-Induced Hyperfibrinolysis in Whole Blood by RapidTEG, KaolinTEG, and Functional FibrinogenTEG in Healthy Individuals

DEFF Research Database (Denmark)

Genét, Gustav Folmer; Ostrowski, Sisse Rye; Sørensen, Anne Marie

2012-01-01

hyperfibrinolysis, as compared to standard KaolinTEG, is unknown. To investigate this, the ability of RapidTEG, KaolinTEG, and functional fibrinogenTEG (FFTEG) to detect tPA-induced (tissue plasminogen activator) lysis in whole blood from healthy individuals was investigated. Our hypothesis was that the initial...... powerful clot formation in the RapidTEG assay would reduce the sensitivity as compared to the normally used KaolinTEG assay. We also evaluated the FFTEG assay. Methods: In vitro comparison of the sensitivity of RapidTEG, KaolinTEG, and FFTEG to 1.8 nmol/L tPA in citrated whole blood (299 ± 23 ng/mL plasma......) induced hyperfibrinolysis in 10 healthy individuals and duplicate titration of the tPA whole blood (WB) concentration from 0.09 to 7.2 nmol/L (14-1144 ng/mL plasma) in 1 healthy donor. Results: At 1.8 nmol/L tPA, KaolinTEG, RapidTEG, and FFTEG all detected fibrinolysis but with different sensitivities...

Blood Clotting and Pregnancy

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Full Text Available ... to help stay current with the latest advances in the field Hematology 2017 A collection of articles from ... Blood clots in pregnant women tend to form in the deep veins of the legs or in the ...

Study of some parameters of the fibrinogen - fibrin transformation reaction

International Nuclear Information System (INIS)

Hollard, D.; Suscillon, M.; Marcille, G.; Rambaud, F.; Baloyan, M.

1966-01-01

The authors studied the action of some parameters on the reaction of transformation fibrinogen-fibrin. The five parameters studied are: the concentration of substratum: a certain quantity of enzyme determines an optimum quantity of fibrinogen; the concentration of enzyme: a certain quantity of substratum defines an optimum quantity of enzyme, beyond which the excess of enzyme is unable to act, the substratum being saturated by the enzyme; the concentration of Ca ions: between 0,07 and 0,10 mg of Ca by mg of fibrinogen, the reaction appears with a great speed. Between 0,02 and 0,40 mg of Ca by mg of fibrinogen the fibrin stabilisation is possible, the FSF can act only inside the definite bounds; the ph of the solution: the reaction of the transformation appears with its maximum intensity on physiological ph, the polymerisation is not possible on acid ph; the temperature has an effect which could not really be verified owing to the fact that the technical realisation is difficult. (author) [fr

Changes in fibrin D-dimer, fibrinogen, and protein S during pregnancy

DEFF Research Database (Denmark)

Hansen, Anette Tarp; Andreasen, Birgitte Horst; Salvig, Jannie Dalby

2010-01-01

Background. Pregnancy is a hypercoagulable state with a 5- to 10- fold higher risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen (protein S) are based on non-pregnant patients and reference...... intervals for pregnant patients are warranted. Objectives. The aim of the present study was to contribute to the establishment of reference intervals for D-dimer, fibrinogen and protein S during pregnancy and to discuss the use of the analyses during pregnancy. Methods. We included 55 healthy pregnant women...... in gestational week 11–17, with normal current pregnancy. Blood samples were collected in gestational weeks 11–17, 21–27 and 34–37. The three plasma parameters D-dimer, fibrinogen and protein S were analysed by STA-R Evolution®. Results. A significant rise in D-dimer was found from first to second trimester (p...

Consumption of 125I labelled fibrinogen in normal subjects

International Nuclear Information System (INIS)

Langer, B.; Camargo, E.E.; Reis, J.M.M. dos; Carvalho, N.; Leao, L.E.P.

1978-01-01

The metabolism of iodine- 125 labeled human fibrinogen is studied by using three different sets of the radiopharmaceutical (0.9, 1.3 and 1.84 iodine atoms/fibrinogen molecule ratios) in 19 normal subjects. An aliquot of 40 μCi of fibrinogem- 125 I is injected in each subject, on normal dietary conditions and blood samples are withdrawn at 30, 60, 180, 36 and 720 minutes after the injection and, thereafter, one daily sample during 10 days. The compartmental distribution of the tracer is defined by plotting plasma and serum sample counts on a semilogarithmic graph paper. A rapid phase and 3 compartments are obtained. A 'rapid' consumption half-life and a 'real' consumption half-life are defined. The fibrinogen clottability is followed up to the last blood sample by checking the ratios of serum and plasma radioactivities [pt

Radio-iodination of a rabbit fibrinogen by the chloramine-T method

Energy Technology Data Exchange (ETDEWEB)

Moza, A K; Kumar, M; Belavalgidad, M I; Sapru, R P [Post-Graduate Inst. of Medical Education and Research, Chandigarh (India). Dept. of Experimental Medicine

1974-01-01

A method for radio-iodination of fibrinogen using chloramine-T has been described. Samples of greater than 90% clottable counts were obtained. Electrophoretic mobility and immunodiffusion showed that the entire radioactivity was present in the fibrinogen band. In vivo studies on the turnover of this labelled product in rabbits showed a half-life of 52.8 to 61.7 hrs in two batches of animals. The results compare very well with the reported results obtained from fibrinogen labelled with radioactive iodine by the iodine-monochloride method. The advantages of the new method have been pointed out.

Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots.

Science.gov (United States)

Zubairova, Laily D; Nabiullina, Roza M; Nagaswami, Chandrasekaran; Zuev, Yuriy F; Mustafin, Ilshat G; Litvinov, Rustem I; Weisel, John W

2015-12-04

Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1-0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis.

Fibrinogen concentrate as a treatment for postpartum haemorrhage-induced coagulopathy: A study protocol for a randomised multicentre controlled trial. The fibrinogen in haemorrhage of DELivery (FIDEL) trial.

Science.gov (United States)

Ducloy-Bouthors, Anne-Sophie; Mignon, Alexandre; Huissoud, Cyril; Grouin, Jean-Marie; Mercier, Frédéric J

2016-08-01

Postpartum haemorrhage (PPH) remains the leading cause for maternal mortality worldwide. Hypofibrinogenaemia has been identified as a major risk factor for progress towards severe PPH. The efficacy of fibrinogen concentrate supplementation in PPH has been shown in various clinical settings but the level of evidence is not sufficient to prove the benefit, evaluate the risks, and determine the value, timing and dose of fibrinogen supplementation in PPH. The FIDEL trial objective is to evaluate the impact of a therapeutic strategy based on the early administration of human fibrinogen concentrate compared to the current practice based on late administration in severe PPH patients requiring second line uterotonics. This is a prospective multicentre, randomised, double-blind, placebo-controlled trial. A total of 412 patients will be randomised if they meet the following criteria: female patients≥18 years old, vaginal delivery, PPH requiring IV administration of prostaglandins (sulprostone) after 20 to 30minutes of oxytocin failure. The participants are assigned to receive either fibrinogen 3g or placebo infusions. The primary endpoint is a composite endpoint defined as the percentage of patients losing at least 4g/dL of Hb, and/or requiring a transfusion of at least 2 units of packed red blood cells, within the 48hours following fibrinogen administration. The purpose of this study is to demonstrate the efficacy and safety of an early fibrinogen concentrate infusion in uncontrolled active PPH. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Changes in fibrinogen availability and utilization in an animal model of traumatic coagulopathy

DEFF Research Database (Denmark)

Hagemo, Jostein S; Jørgensen, Jørgen; Ostrowski, Sisse R

2013-01-01

Impaired haemostasis following shock and tissue trauma is frequently detected in the trauma setting. These changes occur early, and are associated with increased mortality. The mechanism behind trauma-induced coagulopathy (TIC) is not clear. Several studies highlight the crucial role of fibrinogen...... in posttraumatic haemorrhage. This study explores the coagulation changes in a swine model of early TIC, with emphasis on fibrinogen levels and utilization of fibrinogen....

Clinical applications of Ga-67 DFO-DAS-fibrinogen

International Nuclear Information System (INIS)

Iio, Masahiro; Ohtake, Tohru; Nishikawa, Junichi; Watanabe, Toshiaki; Yasuhara, Hiroshi; Ohashi, Shigenobu; Takayama, Yutaka; Tada, Yusuke; Shirakawa, Motoaki

1987-01-01

Ga-67 DFO-DAS-fibrinogen scanning was performed in 15 patients to detect fresh arterial thrombus. Seven patients were preoperative cases of aortic aneurysm and eight were postoperative cases of graft bypass. Scanning was performed on the first and second days after the injection. Nine of 13 grafts in eight cases were visualized by 67 Ga-DFO-DAS-fibrinogen scan. Velour Dacron grafts were more strongly visualized compared with woven Dacron or Goatex. In three patients with aortic aneurysm in whom fresh thrombus was identified by operative findings, arterial thrombus was clearly visualized by 67 Ga-DFO-DAS-fibrinogen scan, whereas in three other patients with aortic aneurysm, thrombus was not visualized, although it was identified by other examinations. In one case, a marked accumulation was observed in the abdominal aorta, although no arterial thrombus was found at operation. This was thought to be an accumulation in a blood pool because it decreased on the second day. We think it important to observe the relative changes of accumulation. (author)

Blood Clotting and Pregnancy

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Full Text Available ... are pregnant and have concerns about blood clots, talk with your doctor about your risks and prevention. Depending on your condition, your OB-GYN may refer you to a hematologist, a doctor who specializes in treating blood conditions. back to top ...

The efficacy of fibrinogen concentrate compared with cryoprecipitate in major obstetric haemorrhage - an observational study.

LENUS (Irish Health Repository)

Ahmed, S

2012-10-01

Fibrinogen replacement is critical in major obstetric haemorrhage (MOH). Purified, pasteurised fibrinogen concentrate appears to have benefit over cryoprecipitate in ease of administration and safety but is unlicensed in pregnancy. In July 2009, the Irish Blood Transfusion Service replaced cryoprecipitate with fibrinogen.

Early fibrinogen degradation coagulopathy: a predictive factor of parenchymal hematomas in cerebral rt-PA thrombolysis.

Science.gov (United States)

Sun, Xuhong; Berthiller, Julien; Trouillas, Paul; Derex, Laurent; Diallo, Laho; Hanss, Michel

2015-04-15

The purpose of this study was to systematically determine the correlations between the post-thrombolytic changes of hemostasis parameters and the occurrence of early intracerebral hemorrhage (ICH). In 72 consecutive patients with cerebral infarcts treated with rt-PA, plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, factor XIII, fibrin(ogen) degradation products (FDPs) and d-Dimers were measured at baseline, 2 and 24h after thrombolysis. Correlations were studied between the hemostasis events and early (less than 24h) hemorrhagic infarcts (HIs) or parenchymatous hematomas (PH). Of 72 patients, 6 patients (8.3%) had early PHs, 11 (15.3%) had early HIs, and 55 (76.4%) had no bleeding. Early HIs were not linked to any hemostasis parameter at any time. Univariate comparison of patients having early PHs with non-bleeding patients showed hemostasis abnormalities at 2h: high FDP (p=0.01), high Log FDP (p=0.01), low fibrinogen (p=0.01), and low Log fibrinogen (p=0.01). Logistic regression adjusted for age, NIHSS and diabetes confirmed these 2hour predictors: Log FDP (OR: 7.50; CI: 1.26 to 44.61, p=0.03), and Log fibrinogen (OR: 19.32; CI: 1.81 to 205.98, p=0.01). The decrease in fibrinogen less than 2g/L multiplies the odds of early PH by a factor 12.82. An early fibrinogen degradation coagulopathy involving an increase of FDP and a massive consumption of circulating fibrinogen is predictive of early parenchymal hematomas, indicating the occurrence of a particularly intense lysis of circulating fibrinogen. These results, if confirmed by future studies, suggest that early assays of fibrinogen and FDP may be useful in predicting the risk of post-thrombolytic intracerebral hematoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Circulating fibrinogen but not D-dimer level is associated with vital exhaustion in school teachers.

Science.gov (United States)

Kudielka, Brigitte M; Bellingrath, Silja; von Känel, Roland

2008-07-01

Meta-analyses have established elevated fibrinogen and D-dimer levels in the circulation as biological risk factors for the development and progression of coronary artery disease (CAD). Here, we investigated whether vital exhaustion (VE), a known psychosocial risk factor for CAD, is associated with fibrinogen and D-dimer levels in a sample of apparently healthy school teachers. The teaching profession has been proposed as a potentially high stressful occupation due to enhanced psychosocial stress at the workplace. Plasma fibrinogen and D-dimer levels were measured in 150 middle-aged male and female teachers derived from the first year of the Trier-Teacher-Stress-Study. Log-transformed levels were analyzed using linear regression. Results yielded a significant association between VE and fibrinogen (p = 0.02) but not D-dimer controlling for relevant covariates. Further investigation of possible interaction effects resulted in a significant association between fibrinogen and the interaction term "VE x gender" (p = 0.05). In a secondary analysis, we reran linear regression models for males and females separately. Gender-specific results revealed that the association between fibrinogen and VE remained significant in males but not females. In sum, the present data support the notion that fibrinogen levels are positively related to VE. Elevated fibrinogen might be one biological pathway by which chronic work stress may impact on teachers' cardiovascular health in the long run.

Identification of fibrinogen-binding proteins of Aspergillus fumigatus using proteomic approach.

Science.gov (United States)

Upadhyay, Santosh Kumar; Gautam, Poonam; Pandit, Hrishikesh; Singh, Yogendra; Basir, Seemi Farhat; Madan, Taruna

2012-03-01

Aspergillus fumigatus, the main etiological agent for various forms of human aspergillosis, gets access to the respiratory system of human host by inhalation of airborne conidia. These conidia possibly adhere to extracellular matrix (ECM) proteins. Among the ECM proteins involved in adherence, fibrinogen is thought to be crucial. Here, we studied whether A. fumigatus three-week culture filtrate (3wcf) proteins promote binding of A. fumigatus to ECM proteins and promote fungal growth. We observed that incubation of ECM with 3wcf proteins led to dose- and time-dependent increase in adherence of conidia to the ECM. In order to identify the catalogue of fibrinogen-binding A. fumigatus proteins, we carried out fibrinogen affinity blotting using two-dimensional gel electrophoresed 3wcf proteins. A total of 15 fibrinogen-binding protein spots corresponding to 7 unique proteins were identified in 3wcf using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF-TOF). Among these, 4 proteins, namely, beta-glucosidase, alpha-mannosidase, pectate lyase A and oryzin precursor were predicted to have cell wall or extracellular localization, whereas amidase family protein and two hypothetical proteins did not display the signal sequence. This study reports seven novel fibrinogen-binding proteins of A. fumigatus, some of which could be further explored for targeting the adhesion phenomenon as antifungal strategy.

Extraction, radioiodination, and in vivo catabolism of equine fibrinogen

International Nuclear Information System (INIS)

Coyne, C.P.; Hornof, W.J.; Kelly, A.B.; O'Brien, T.R.; DeNardo, S.J.

1985-01-01

Equine fibrinogen was isolated and aliquots were stored frozen at -70 C before radiolabeling with 125I (half-life = 60.2 days; gamma = 35 keV, using monochloroiodine reagent. Radioiodination efficiencies were 49% to 53%, resulting in a labeled product with 98% protein-bound activity and 91% clottable radioactivity. In 6 equine in vivo investigations, plasma half-lives of 125I-labeled fibrinogen were from 4.1 to 5.2 days, corresponding to a mean daily plasma elimination rate of approximately 15%

Contribution to the study of plasmatic fibrinogen and serum albumin: effects of irradiation; Contribution a l'etude du fibrinogene et de la serum-albumine plasmatiques - effets de l'irradiation

Energy Technology Data Exchange (ETDEWEB)

Suscillon, M [Commissariat a l' Energie Atomique, Centre d' Etudes Nucleaires de Grenoble, 38 (France)

1967-07-01

The author studies the modifications of properties and structure of serum albumin and fibrinogen solution when subjected to radiation of low energy (X rays). On the other hand, two original techniques are exposed: 1. Amperometric determination of fibrin stabilizing factor or factor XIII of hemostasis. 2. Spectrophotometric study of fibrin formation kinetics. Then showing off and quantitative determination of platelets fibrinogen is exposed. (author) [French] L'auteur etudie les modifications des proprietes et de la structure des molecules de serum-albumine et de fibrinogene en solution soumise a un flux de RX de basse energie. D'autre part deux techniques originales sont exposees : 1. Dosage amperometrique du facteur stabilisant de la fibrine. 2. Etude spectrophotometrique de la cinetique de la fibro-formation. Enfin une mise en evidence et un dosage du fibrinogene plaquettaire sont presentes. (auteur)

Clumping factor A-mediated virulence during Staphylococcus aureus infection is retained despite fibrinogen depletion.

Science.gov (United States)

Palmqvist, Niklas; Josefsson, Elisabet; Tarkowski, Andrzej

2004-02-01

Clumping factor A (ClfA), a fibrinogen-binding protein expressed on the Staphylococcus aureus cell surface, has previously been shown to act as a virulence factor in experimental septic arthritis. Although the interaction between ClfA and fibrinogen is assumed to be of importance for the virulence of S. aureus, this has not been demonstrated in any in vivo model of infection. Therefore, the objective of this study was to investigate the contribution of this interaction to ClfA-mediated virulence in murine S. aureus-induced arthritis. Ancrod, a serine protease with thrombin-like activity, was used to induce in vivo depletion of fibrinogen in mice. Ancrod treatment significantly aggravated septic arthritis following inoculation with a ClfA-expressing strain (Newman) compared to control treatment. Also, ancrod treatment tended to enhance the arthritis induced by a clfA mutant strain (DU5876), indicating that fibrinogen depletion exacerbates septic arthritis in a ClfA-independent manner. Most importantly, the ClfA-expressing strain was much more arthritogenic than the isogenic clfA mutant, following inoculation of fibrinogen-depleted mice. This finding indicates that the interaction between ClfA and free fibrinogen is not required for ClfA-mediated functions contributing to S. aureus virulence. It is conceivable that ClfA contributes to the virulence of S. aureus through interactions with other host ligands than fibrinogen.

A randomized, double blind trial of prophylactic fibrinogen to reduce bleeding in cardiac surgery

Directory of Open Access Journals (Sweden)

Mostafa Sadeghi

2014-07-01

Full Text Available BACKGROUND AND OBJECTIVES: Postoperative bleeding has a great clinical importance and can contribute to increased mortality and morbidity in patients undergoing coronary artery bypass graft surgery. In this prospective, randomized, double-blind study, we evaluated the effect of prophylactic administration of fibrinogen concentrate on post-coronary artery bypass graft surgery bleeding. METHODS: A total of 60 patients undergoing coronary artery bypass surgery were randomly divided into two groups. Patients in the fibrinogen group received 1 g of fibrinogen concentrate 30 min prior to the operation, while patients in the control group received placebo. Post-operative bleeding volumes, prothrombin time, partial thromboplastin time, INR, hemoglobin and transfused blood products in both groups were recorded. A strict red blood cell transfusion protocol was used in all patients. RESULTS: There were no significant differences between intra-operative packed red blood cells infusion in the studied groups (1.0 ± 1.4 in fibrinogen group, and 1.3 ± 1.1 in control group. Less postoperative bleeding was observed in the fibrinogen group (477 ± 143 versus 703 ± 179, p = 0.0001. Fifteen patients in the fibrinogen group and 21 in the control group required post-op packed red blood cells infusion (p = 0.094. No thrombotic event was observed through 72 h after surgery. CONCLUSION: Prophylactic fibrinogen reduces post-operative bleeding in patients undergoing coronary artery bypass graft.

Identification of quantitative trait loci for fibrin clot phenotypes: the EuroCLOT study

DEFF Research Database (Denmark)

Williams, Frances M K; Carter, Angela M; Kato, Bernet

2009-01-01

OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs as...

Modulation of plasma fibrinogen levels by ciprofibrate and gemfibrozil in primary hyperlipidaemia

NARCIS (Netherlands)

de Maat, M. P.; Knipscheer, H. C.; Kastelein, J. J.; Kluft, C.

1997-01-01

An elevated plasma fibrinogen level is increasingly accepted as an independent risk indicator of cardiovascular disease. This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels. One group of agents with this capacity are the fibric acid derivatives,

Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

Science.gov (United States)

de Moerloose, P; Schved, J-F; Nugent, D

2016-07-01

Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

Plasma circulating fibrinogen stability and moderate beer consumption.

Science.gov (United States)

Gorinstein, Shela; Caspi, Abraham; Zemser, Marina; Libman, Imanuel; Goshev, Ivan; Trakhtenberg, Simon

2003-12-01

MODERATE BEER CONSUMPTION (MBC) IS CARDIOPROTECTIVE: it positively influences plasma lipid levels and plasma antioxidant activity in beer-consuming individuals. The connection between MBC and blood coagulation is not clearly defined. Forty-two volunteers were equally divided into experimental (EG) and control (CG) groups following coronary bypass surgery. For 30 consecutive days, only patients of the EG consumed 330 mL of beer per day (about 20 g of alcohol). A comprehensive clinical investigation of 42 patients was done. Blood samples were collected before and after the investigation for a wide range of laboratory tests. The plasma fibrinogen was denatured with 8 M urea and intrinsic fluorescence (IF), hydrophobicity and differential scanning calorimetry (DSC) were used to reveal possible qualitative changes. After 30 days of moderate beer consumption, positive changes in the plasma lipid levels, plasma anticoagulant and plasma antioxidant activities were registered in patients of the EG group. In 17 out of 21 patients of the same group, differences in plasma circulating fibrinogen's (PCF), secondary and tertiary structures were found. The stability of fibrinogen, expressed in thermodynamic parameters, has shown that the loosening of the structure takes place under ethanol and urea denaturation. Also fluorescence stability of PCF was decreased. No changes in the lipid levels, anticoagulant and antioxidant activity or changes in PCF were detected in patients of CG. In conclusion, for the first time after a short term of moderate beer consumption some qualitative changes in the plasma circulating fibrinogen were detected: differences in the emission peak response, fluorescence intensity and all thermodynamic data. Together, with the decrease in the PCF concentration it may lead to an elevation of the blood anticoagulant activity.

Laser-assisted fibrinogen bonding of umbilical vein grafts.

Science.gov (United States)

Oz, M C; Williams, M R; Souza, J E; Dardik, H; Treat, M R; Bass, L S; Nowygrod, R

1993-06-01

Despite success with autologous tissue welding, laser welding of synthetic vascular prostheses has not been possible. The graft material appears inert and fails to allow the collagen breakdown and electrostatic bonding that results in tissue welding. To develop a laser welding system for graft material, we repaired glutaraldehyde-tanned human umbilical cord vein graft incisions using laser-assisted fibrinogen bonding (LAFB) technology. Modified umbilical vein graft was incised transversely (1.2 cm). Incisions were repaired using sutures, laser energy alone, or LAFB. For LAFB, indocyanine green dye was mixed with human fibrinogen and the compound applied with forceps onto the weld site prior to exposure to 808 nm diode laser energy (power density 4.8 W/cm 2). Bursting pressures for sutured repairs (126.6 +/- 23.4 mm Hg) were similar to LAFB anastomoses (111.6 +/- 55.0 mm Hg). No evidence of collateral thermal injury to the graft material was noted. In vivo evaluation of umbilical graft bonding with canine arteries demonstrates that LAFB can reliably reinforce sutured anastomoses. The described system for bonding graft material with laser exposed fibrinogen may allow creation or reinforcement of vascular anastomoses in procedures where use of autologous tissue is not feasible.

The hydraulic permeability of blood clots as a function of fibrin and platelet density.

Science.gov (United States)

Wufsus, A R; Macera, N E; Neeves, K B

2013-04-16

Interstitial fluid flow within blood clots is a biophysical mechanism that regulates clot growth and dissolution. Assuming that a clot can be modeled as a porous medium, the physical property that dictates interstitial fluid flow is the hydraulic permeability. The objective of this study was to bound the possible values of the hydraulic permeability in clots formed in vivo and present relationships that can be used to estimate clot permeability as a function of composition. A series of clots with known densities of fibrin and platelets, the two major components of a clot, were formed under static conditions. The permeability was calculated by measuring the interstitial fluid velocity through the clots at a constant pressure gradient. Fibrin gels formed with a fiber volume fraction of 0.02-0.54 had permeabilities of 1.2 × 10(-1)-1.5 × 10(-4)μm(2). Platelet-rich clots with a platelet volume fraction of 0.01-0.61 and a fibrin volume fraction of 0.03 had permeabilities over a range of 1.1 × 10(-2)-1.5 × 10(-5)μm(2). The permeability of fibrin gels and of clots with platelet volume fraction of platelet volume fraction of >0.2 were modeled as a Brinkman medium of coarse solids (platelets) embedded in a mesh of fine fibers (fibrin). Our data suggest that the permeability of clots formed in vivo can vary by up to five orders of magnitude, with pore sizes that range from 4 to 350 nm. These findings have important implications for the transport of coagulation zymogens/enzymes in the interstitial spaces during clot formation, as well as the design of fibrinolytic drug delivery strategies. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Preparation of 99 sup(m)Tc labeled fibrinogen

International Nuclear Information System (INIS)

Almeida, M.A.T.M. de; Silva, C.P.G. da.

1984-01-01

A simple method for the preparation of 99 sup(m) TC labelled Fibrinogen using stannous chloride as reducing agent of 99 sup(m) TcO- 4 ion is presented. A sample of 20 mg of Fibrinogen is dissolved in 2 ml of buffer carbonate (pH=8) and 0.3 ml stannous chloride 0.2% is added. A sterile solution of sodium pertechnetate 99 sup(m) Tc eluted from a Mo-Tc generator is immediately added. The mixture rests for 30 minutes and after this period, the obtained yield is about 70%. The lyophilized kits also presented a yield of 70%, being therefore suitable for medical applications. (Author) [pt

The changes in the fibrinogen concentration and coagulation pathways in winter and summer in cattle

Directory of Open Access Journals (Sweden)

ameneh khoshvaghti

2013-08-01

Full Text Available Fibrinogen is an important coagulation factor and a positive acute phase protein and its levels increases in cases of inflammation infection and stress. The present research was done to determine whether the fibrinogen concentration, prothrombin time (PT and activated partial thromboplastin time (APTT can be affected by seasonal changes. In this study, the blood of ten apparently healthy cows from around Yasouj city were taken under aseptic conditions and, then the plasma was separated. The fibrinogen concentration, was assayed by sedimentation refractometry method, PT and APTT were measurement by coagolometric method. The statistical analysis indicated that there was significant difference between the mean concentration of fibrinogen in summer and winter (P0.05. It is concluded that seasonal changes can affect the fibrinogen concentration but does no affect PT and APTT significantly.

Fibrinogen concentrates for bleeding trauma patients: what is the evidence?

DEFF Research Database (Denmark)

Meyer, Martin; Ostrowski, S R; Windeløv, N A

2011-01-01

A balanced transfusion of red blood cells, fresh frozen plasma and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for fresh frozen plasma and/or platelet transfusions.......A balanced transfusion of red blood cells, fresh frozen plasma and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for fresh frozen plasma and/or platelet transfusions....

In vitro evaluation of the effect of haemodilution with dextran 40 on coagulation profile as measured by thromboelastometry and multiple electrode aggregometry.

Science.gov (United States)

Kam, Pca; Liou, Jpc; Yang, Kxf

2017-09-01

We evaluated the effects of haemodilution with either dextran 40 or 0.9% normal saline on coagulation in vitro using rotational thromboelastometry (ROTEM®, Pentapharm Co., Munich, Germany) and multiple electrode aggregometry (Multiplate® Platelet Function Analyser, Dynabyte, Munich, Germany). Venous blood samples obtained from 20 healthy volunteers were diluted in vitro with dextran 40 or normal saline by 5%, 10% and 15%. Fibrinogen concentration, ROTEM-EXTEM® (screening test for the extrinsic coagulation pathway), FIBTEM® (an EXTEM-based assay of the fibrin component of clot) parameters including coagulation time, clot formation time, alpha angle, maximum clot firmness and lysis index were measured in the undiluted sample and at each level of haemodilution. Dextran 40 at 15% haemodilution significantly prolonged coagulation time, clot formation time and significantly decreased the alpha angle and maximal clot firmness (EXTEM amplitude at five minutes [A5] and ten minutes [A10]) compared with normal saline. The FIBTEM assay (maximal clot firmness and FIBTEM A5 and A10) showed a marked decrease in maximal clot firmness at all dilutions suggesting impaired fibrinogen activity and a risk of bleeding. Multiple electrode aggregometry did not demonstrate any platelet dysfunction. Haemodilution with dextran 40 causes significant impairment in clot formation and strength compared to saline haemodilution and undiluted blood. At the levels of in vitro haemodilution designed to reflect the clinical use of dextran infusions, no significant fibrinolysis or platelet inhibition was observed.

Fibrates suppress fibrinogen gene expression in rodents via activation of the peroxisome proliferator-activated receptor-α

NARCIS (Netherlands)

Kockx, M.; Gervois, P.P.; Poulain, P.; Derudas, B.; Peters, J.M.; Gonzalez, F.J.; Princen, H.M.G.; Kooistra, T.; Staels, B.

1999-01-01

Plasma fibrinogen levels have been identified as an important risk factor for cardiovascular diseases. Among the few compounds known to lower circulating fibrinogen levels in humans are certain fibrates. We have studied the regulation of fibrinogen gene expression by fibrates in rodents. Treatment

Effect of chitosan and coagulation factors on the wound repair phenotype of bioengineered blood clots.

Science.gov (United States)

Hoemann, Caroline D; Marchand, Catherine; Rivard, Georges-Etienne; El-Gabalawy, Hani; Poubelle, Patrice E

2017-11-01

Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B 4 (LTB 4 ) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB 4 or inflammatory factors. Only 80% DDA chitosan clots produced around 15-fold more LTB 4 over other clots including 95% DDA chitosan clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots produced very low type I cytokines compared to lipopolysaccharide clots, with even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots. Coagulation factors had no detectable effect on clot phenotype. Conclusion In blood clots from healthy individuals, 80% DDA chitosan has a unique influence of inducing more LTB 4 , a potent neutrophil chemoattractant, with similar production of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots. Copyright © 2017 Elsevier B.V. All rights reserved.

Pitfalls of radioisotope diagnosis of deep venous thromboses with 125I-fibrinogen in traumatology

International Nuclear Information System (INIS)

Novak, K.; Pestal, M.

1984-01-01

Experience is described with the examination of deep venous thromboses of the lower extremities using 125 I-fibrinogen. Intravenously administered labelled fibrinogen is taken up into the forming thrombus which may then be detected. Experience is presented with preparations of various makes. It was proved that in injured patients the biological half-life of 125 I-fibrinogen is reduced to 50 hrs and less as against the standard half-life of 96.2 hrs. This is caused by fibrinogen losses owing to the injury, increased intensity of metabolic processes and the quality of the preparation being used. Injured patients should be examined using a highest quality preparation without denaturation damage to the labelled protein. (Ha)

Elevated plasma fibrinogen, psychological distress, antidepressant use, and hospitalization with depression

DEFF Research Database (Denmark)

Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nordestgaard, Børge Grønne

2013-01-01

with depression in the general population. METHODS: We examined 73,367 20-100 year old men and women from two large population-based studies, the Copenhagen General Population Study and the Copenhagen City Heart Study. We measured plasma fibrinogen and recorded symptoms of psychological distress, use......OBJECTIVES: Low-grade systemic inflammation may contribute to the development of depression. We tested the hypothesis that elevated plasma levels of the inflammatory marker fibrinogen are associated with psychological distress, use of antidepressant medication, and with hospitalization...... of antidepressant medication, and hospitalization with depression in both cross-sectional and prospective studies. RESULTS: In cross-sectional analyses, a stepwise increase in fibrinogen percentile categories was associated with a stepwise increase in risk of psychological distress, use of antidepressant medication...

Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen (plasmin fragments Y)

NARCIS (Netherlands)

Nieuwenhuizen, W.; Voskuilen, M.; Hermans, J.

1982-01-01

The present study was undertaken as a step to delineate further the localization of the calcium-binding sites in fibrinogen and to assess the anticlotting properties of fibrinogen degradation products. To this purpose, fragments Y were prepared by plasmin digestion of human fibrinogen in the

Fibrinogen titer and glycemic status in women using contraceptives

International Nuclear Information System (INIS)

Syed, S.; Qureshi, M.A.

2002-01-01

Objective: To assess the coagulation and glycemic status in Pakistani women using contraceptives. Design: The study was conducted prospectively on 70 women and compared with 10 age-matched controls. Place and Duration of Study: The study was conducted at Karachi. Period of study was 18 month. Subjects and Methods: Eighty women aged between 20-45 years selected from low socioeconomic class and poor family background were categorized in control (n=10) and oral and injectable contraceptive users (n = 70). The contraceptives used were tablet Lofemenal, injection Norigest and Norplant implant. Their blood was tested for fibrinogen titer and random blood glucose. Results: There was no appreciable difference either in fibrinogen titer or plasma glucose levels in injectable users as compared to controls, but increased incidence of high fibrinogen titer and borderline blood glucose was observed in oral contraceptive users 25% and 20 % respectively. Conclusion: It was concluded that long-term use of oral contraceptives (> 3 years) might increase the thrombotic tendency and elevate the plasma glucose levels especially in women above 30 years of age. (author)

Contribution to the study of plasmatic fibrinogen and serum albumin: effects of irradiation; Contribution a l'etude du fibrinogene et de la serum-albumine plasmatiques - effets de l'irradiation

Energy Technology Data Exchange (ETDEWEB)

Suscillon, M. [Commissariat a l' Energie Atomique, Centre d' Etudes Nucleaires de Grenoble, 38 (France)

1967-07-01

The author studies the modifications of properties and structure of serum albumin and fibrinogen solution when subjected to radiation of low energy (X rays). On the other hand, two original techniques are exposed: 1. Amperometric determination of fibrin stabilizing factor or factor XIII of hemostasis. 2. Spectrophotometric study of fibrin formation kinetics. Then showing off and quantitative determination of platelets fibrinogen is exposed. (author) [French] L'auteur etudie les modifications des proprietes et de la structure des molecules de serum-albumine et de fibrinogene en solution soumise a un flux de RX de basse energie. D'autre part deux techniques originales sont exposees : 1. Dosage amperometrique du facteur stabilisant de la fibrine. 2. Etude spectrophotometrique de la cinetique de la fibro-formation. Enfin une mise en evidence et un dosage du fibrinogene plaquettaire sont presentes. (auteur)

Thrombus scintigraphy with Ga-67 DFO-DAS-Fibrinogen, 2

International Nuclear Information System (INIS)

Kawasaki, Yukiko

1987-01-01

In our previous in vivo study 67 Ga DFO-DAS-Fibrinogen was assessed for its usefulness as a radiopharmaceutical for the detection of thrombin in experimental animals (Report 1). The present study was undertaken to appraise the diagnostic value of 67 Ga DFO-DAS-Fibrinogen in human disease, especially in relation to blood coagulability as well as to thrombolytic drug regimen being given, in an effort to investigate its clinical applicability. Involved in this study were 48 patients with thrombosis proven by X-ray CT and other examinations. Of these 48, 42 had arterial thrombosis (20 with aortic aneurysm including the dissecting form, 11 in postoperative condition following vascular surgery with a prosthesis, 9 with intracardiac thrombosis accompanying heart disease, and 1 each with occlusive arteriosclerosis and cerebral infarction) and 6 had venous thrombosis. The 67 Ga DFO-DAS-Fibrinogen test proved to be positive in 55 % of arterial thrombin and in 50 % of venous thrombin. It is interesting to note that as high a positivity rate as 80 % was obtained for aortic aneurysm, although the positivity rate was disappointingly low for left atrial thrombin. No distinct correlation was noted to exist between the degree of accumulation of the tracer in thrombotic lesions and any of factors conceivably of clinical releavance, i.e. time elapsing from onset till testing, thrombolytic medication being given, and hematological factors. 67 Ga DFO-DAS-Fibrinogen appeared to be a radiodiagnostic agent that could possibly indicate the existing activity status of thrombosis. (author)

In situ assembly of fibrinogen/hyaluronic acid hydrogel via knob-hole interaction for 3D cellular engineering

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Shengjie Huang

2017-12-01

Full Text Available Hyaluronic acid (HA-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability. However, the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the biocompatibility. Inspired by the crosslinking mechanism of fibrin gel, a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA (knob-g-HA in this study. The knob-grafted HA was synthesized by coupling knob peptides (GPRPAAC, a mimic peptide of fibrin knob A to HA via Michael addition. Then the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of 1.2. The rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50, 100 and 200 mg/mL were evaluated, and it was found that the dynamic storage moduli (G′ were higher than the loss moduli (G″ over the whole frequency range for all the groups. The SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/MA-HA hydrogels. Correspondingly, a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA hydrogel. Finally, the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation test. All these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering.

In vitro sealing of iatrogenic fetal membrane defects by a collagen plug imbued with fibrinogen and plasma.

Science.gov (United States)

Engels, A C; Hoylaerts, M F; Endo, M; Loyen, S; Verbist, G; Manodoro, S; DeKoninck, P; Richter, J; Deprest, J A

2013-02-01

We aimed to demonstrate local thrombin generation by fetal membranes, as well as its ability to generate fibrin from fibrinogen concentrate. Furthermore, we aimed to investigate the efficacy of collagen plugs, soaked with plasma and fibrinogen, to seal iatrogenic fetal membrane defects. Thrombin generation by homogenized fetal membranes was measured by calibrated automated thrombography. To identify the coagulation caused by an iatrogenic membrane defect, we analyzed fibrin formation by optical densitometry, upon various concentrations of fibrinogen. The ability of a collagen plug soaked with fibrinogen and plasma was tested in an ex vivo model for its ability to seal an iatrogenic fetal membrane defect. Fetal membrane homogenates potently induced thrombin generation in amniotic fluid and diluted plasma. Upon the addition of fibrinogen concentrate, potent fibrin formation was triggered. Measured by densiometry, fibrin formation was optimal at 1250 µg/mL fibrinogen in combination with 4% plasma. A collagen plug soaked with fibrinogen and plasma sealed an iatrogenic membrane defect about 35% better than collagen plugs without these additives (P = 0.037). These in vitro experiments suggest that the addition of fibrinogen and plasma may enhance the sealing efficacy of collagen plugs in closing iatrogenic fetal membrane defects. © 2013 John Wiley & Sons, Ltd.

Blood coagulation and fibrinolysis of the whole-body irradiated rabbits

International Nuclear Information System (INIS)

Hishikawa-Itoh, Youko; Ayakawa, Yoshio; Miyata, Nobuki

1984-01-01

To study the effects of irradiation on blood coagulation and fibrinolysis, rabbits were irradiated with 60 Co γ-rays (whole-body: 0, 100, 400, 800, 1200 rads). Clotting time, activity of plasmin and plasminogen, and fibrinogen contents of irradiated rabbit plasma were measured at 4 days before, immediately after, and at 1, 3, 7, 10, and 14 days after irradiation. Both clotting times obtained by addition of (kaolin+phospholipid) which expressed effects on the total intrinsic coagulation system, and by addition of (Ca 2+ ) which expressed effects on the total extrinsic coagulation system, were prolonged with small dose irradiation (100 rads) immediately and 3 days after irradiation. However, with high dose irradiation (400-1200 rads), these clotting times were prolonged 1 day after irradiation. The times of manifestation of irradiation effects on clotting time were different in small and high dose irradiation. Plasmin activity was decreased immediately, 1 day after and recovered 3 days after irradiation. Plasminogen activity was markedly increased in 800 and 1200 rads irradiated groups from 3 days after irradiation. Conversion of plasminogen into plasmin was impaired by irradiation. Fibrinogen contents increased rapidly in all irradiated rabbits except for 100 rads from 1 day after irradiation. These results revealed decreased coagulation and fibrinolysis activities in rabbit blood, irradiation injury of both coagulation and fibrinolysis activation systems, and accumulation of the precursors of fibrin and plasmin (i.e., fibrinogen and plasminogen). (author)

Massive clot formation after tooth extraction

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Santosh Hunasgi

2015-01-01

Full Text Available Oral surgical procedures mainly tooth extraction can be related with an extended hemorrhage owed to the nature of the process resulting in an "open wound." The attempt of this paper is to present a case of massive postoperative clot formation after tooth extraction and highlight on the oral complications of surgical procedures. A 32-year-old male patient reported to the Dental Clinic for evaluation and extraction of grossly decayed 46. Clinical evaluation of 46 revealed root stumps. Extraction of the root stumps was performed, and it was uneventful. Hemostasis was achieved and postsurgical instructions were specified to the patient. The patient reported to the clinic, the very subsequent morning with a criticism of bleeding at the extraction site. On clinical examination, bleeding was noted from the socket in relation to 46. To control bleeding, oral hemostatic drugs Revici - E (Ethamsylate 500 mg was prescribed and bleeding was stopped in 2 h. However, a massive clot was formed at the extraction site. Further, this clot resolved on its own in 1-week time. Despite the fact that dental extraction is considered to be a minor surgical procedure, some cases may present with life-threatening complications including hemorrhage. Vigilant and significant history taking, physical and dental examinations prior to dental procedures are a must to avoid intraoperative and postoperative complications.

Plasma fibrinogen and factor VII concentrations in adults after prenatal exposure to famine

NARCIS (Netherlands)

Roseboom, T. J.; van der Meulen, J. H.; Ravelli, A. C.; Osmond, C.; Barker, D. J.; Bleker, O. P.

2000-01-01

To assess the effect of maternal malnutrition during different stages of gestation on plasma concentrations of fibrinogen and factor VII, we investigated 725 people, aged 50 years, born around the time of the Dutch famine 1944-5. After adjustment for sex, plasma fibrinogen concentrations differed by

Pitfalls of radioisotope diagnosis of deep venous thromboses with /sup 125/I-fibrinogen in traumatology

Energy Technology Data Exchange (ETDEWEB)

Novak, K.; Pestal, M. (Vyzkumny Ustav Traumatologicky, Brno (Czechoslovakia))

1984-05-25

Experience is described with the examination of deep venous thromboses of the lower extremities using /sup 125/I-fibrinogen. Intravenously administered labelled fibrinogen is taken up into the forming thrombus which may then be detected. Experience is presented with preparations of various makes. It was proved that in injured patients the biological half-life of /sup 125/I-fibrinogen is reduced to 50 hrs and less as against the standard half-life of 96.2 hrs. This is caused by fibrinogen losses owing to the injury, increased intensity of metabolic processes and the quality of the preparation being used. Injured patients should be examined using a highest quality preparation without denaturation damage to the labelled protein.

Plasma clot lysis time and its association with cardiovascular risk factors in black Africans.

Directory of Open Access Journals (Sweden)

Zelda de Lange

Full Text Available Studies in populations of European descent show longer plasma clot lysis times (CLT in patients with cardiovascular disease (CVD than in controls. No data are available on the association between CVD risk factors and fibrinolytic potential in black Africans, a group undergoing rapid urbanisation with increased CVD prevalence. We investigated associations between known CVD risk factors and CLT in black Africans and whether CLTs differ between rural and urban participants in light of differences in CVD risk.Data from 1000 rural and 1000 urban apparently healthy black South Africans (35-60 years were cross-sectionally analysed.Increased PAI-1(act, BMI, HbA1c, triglycerides, the metabolic syndrome, fibrinogen concentration, CRP, female sex and positive HIV status were associated with increased CLTs, while habitual alcohol consumption associated with decreased CLT. No differences in CLT were found between age and smoking categories, contraceptive use or hyper- and normotensive participants. Urban women had longer CLT than rural women while no differences were observed for men.CLT was associated with many known CVD risk factors in black Africans. Differences were however observed, compared to data from populations of European descent available in the literature, suggesting possible ethnic differences. The effect of urbanisation on CLT is influenced by traditional CVD risk factors and their prevalence in urban and rural communities.

Plasma clot lysis time and its association with cardiovascular risk factors in black Africans.

Science.gov (United States)

de Lange, Zelda; Pieters, Marlien; Jerling, Johann C; Kruger, Annamarie; Rijken, Dingeman C

2012-01-01

Studies in populations of European descent show longer plasma clot lysis times (CLT) in patients with cardiovascular disease (CVD) than in controls. No data are available on the association between CVD risk factors and fibrinolytic potential in black Africans, a group undergoing rapid urbanisation with increased CVD prevalence. We investigated associations between known CVD risk factors and CLT in black Africans and whether CLTs differ between rural and urban participants in light of differences in CVD risk.Data from 1000 rural and 1000 urban apparently healthy black South Africans (35-60 years) were cross-sectionally analysed.Increased PAI-1(act), BMI, HbA1c, triglycerides, the metabolic syndrome, fibrinogen concentration, CRP, female sex and positive HIV status were associated with increased CLTs, while habitual alcohol consumption associated with decreased CLT. No differences in CLT were found between age and smoking categories, contraceptive use or hyper- and normotensive participants. Urban women had longer CLT than rural women while no differences were observed for men.CLT was associated with many known CVD risk factors in black Africans. Differences were however observed, compared to data from populations of European descent available in the literature, suggesting possible ethnic differences. The effect of urbanisation on CLT is influenced by traditional CVD risk factors and their prevalence in urban and rural communities.

Fibrinogen plasma concentration is an independent marker of haemodynamic impairment in chronic thromboembolic pulmonary hypertension

Science.gov (United States)

Hennigs, Jan K.; Baumann, Hans Jörg; Lüneburg, Nicole; Quast, Gesine; Harbaum, Lars; Heyckendorf, Jan; Sydow, Karsten; Schulte-Hubbert, Bernhard; Halank, Michael; Klose, Hans

2014-01-01

Fibrinogen has a crucial role in both inflammation and coagulation, two processes pivotal for the pathogenesis of pulmonary hypertension. We therefore aimed to investigate whether fibrinogen plasma concentrations a) are elevated in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) and b) may serve as a novel biomarker for haemodynamic impairment. In a dual-centre, retrospective analysis including 112 patients with PAH (n = 52), CTEPH (n = 49) and a control cohort of patients with suspected PAH ruled out by right heart catheterisation (n = 11), we found fibrinogen plasma concentrations to be increased in patients with PAH (4.1 ± 1.4 g/l) and CTEPH (4.3 ± 1.2 g/l) compared to control patients (3.4 ± 0.5 g/l, p = 0.0035 and p = 0.0004, respectively). In CTEPH patients but not in PAH patients fibrinogen was associated with haemodynamics (p < 0.036) and functional parameters (p < 0.041). Furthermore, fibrinogen was linked to disease severity (WHO functional class, p = 0.017) and independently predicted haemodynamic impairment specifically in CTEPH (p < 0.016). Therefore, fibrinogen seems to represent an important factor in CTEPH pathophysiology and may have the potential to guide clinical diagnosis and therapy. PMID:24770447

Pre-delivery fibrinogen predicts adverse maternal or neonatal outcomes in patients with placental abruption.

Science.gov (United States)

Wang, Liangcheng; Matsunaga, Shigetaka; Mikami, Yukiko; Takai, Yasushi; Terui, Katsuo; Seki, Hiroyuki

2016-07-01

Placental abruption is a severe obstetric complication of pregnancy that can cause disseminated intravascular coagulation and progress to massive post-partum hemorrhage. Coagulation disorder due to extreme consumption of fibrinogen is considered the main pathogenesis of disseminated intravascular coagulation in patients with placental abruption. The present study sought to determine if the pre-delivery fibrinogen level could predict adverse maternal or neonatal outcomes in patients with placental abruption. This retrospective medical chart review was conducted in a center for maternal, fetal, and neonatal medicine in Japan with 61 patients with placental abruption. Fibrinogen levels prior to delivery were collected and evaluated for the prediction of maternal and neonatal outcomes. The main outcome measures for maternal outcomes were disseminated intravascular coagulation and hemorrhage, and the main outcome measures for neonatal outcomes were Apgar score at 5 min, umbilical artery pH, and stillbirth. The receiver-operator curve and multivariate logistic regression analyses indicated that fibrinogen significantly predicted overt disseminated intravascular coagulation and the requirement of ≥6 red blood cell units, ≥10 fresh frozen plasma units, and ≥20 fresh frozen plasma units for transfusion. Moderate hemorrhage occurred in 71.5% of patients with a decrease in fibrinogen levels to 155 mg/dL. Fibrinogen could also predict neonatal outcomes. Umbilical artery pH neonatal outcomes with placental abruption. © 2016 Japan Society of Obstetrics and Gynecology. © 2016 Japan Society of Obstetrics and Gynecology.

Reaction of plasmic degradation products of fibrinogen in the radioimmunoassay of human fibrinopeptide A

International Nuclear Information System (INIS)

Budzynski, A.Z.; Marder, V.J.; Sherry, S.

1975-01-01

A radioimmunoassay (RIA) technique has been devised for the measurement of human fibrinopeptide A (FPA). The system utilizes rabbit antiserum to native human FPA and a synthetic fibrinopeptide, with tyrosine substituted for phenylanine in amino acid position 8. The test detects native human FPA at a concentration of 0.1 ng/ml, but does not cross react with human fibrinopeptide B or with fibrinopeptides A from canine, porcine, or bovine fibrinogen. Fibrinogen and chemical or plasmic degradation products with 2 moles of FPA per mole react fully in this test system. This includes the large-molecular-weight intermediate fragments X and Y and the NH 2 -terminal disulfide knot, and indicates that this antibody recognizes and reacts with FPA in the presence of the contiguous peptide structures presents in fibrinogen. Fragment E, which is derived from the NH 2 -terminal portion of fibrinogen, loses most of its FPA content after its liberation from its precursor derivative and reacts to a lesser extent in the RIA than do fragments X and Y. This correlates with the recovery of FPA-positive material from ultrafiltrates of extensive but not partial plasmic digests of fibrinogen. Although FPA immunoreactivity liberated from fibrinogen does not necessarily reflect thrombin activity and/or fibrin formation, only extensive plasmic degradation yields peptide material which reacts in this RIA system. This should not be a serious limitation to the application of the RIA in the detection of venous thrombosis. (U.S.)

Thermal Blood Clot Formation and use in Microfluidic Device Valving Applications

Science.gov (United States)

Tai, Yu-Chong (Inventor); Shi, Wendian (Inventor); Guo, Luke (Inventor)

2014-01-01

The present invention provides a method of forming a blood-clot microvalve by heating blood in a capillary tube of a microfluidic device. Also described are methods of modulating liquid flow in a capillary tube by forming and removing a blood-clot microvalve.

A French National Survey on Clotting Disorders in Mastocytosis.

Science.gov (United States)

Carvalhosa, Ana B; Aouba, Achille; Damaj, Gandhi; Canioni, Danielle; Brouzes, Chantal; Gyan, Emmanuel; Durupt, Stéphane; Durieu, Isabelle; Cathebras, Pascal; Costédoat-Chalumeau, Nathalie; Launay, David; Pilmis, Benoit; Barete, Stephane; Frenzel, Laurent; Lortholary, Olivier; Hermine, Olivier; Hermans, Cedric; Chandesris, Marie-Olivia

2015-10-01

Mastocytosis is characterized by a clonal mast cell proliferation with organ infiltration and uncontrolled degranulation. Although not characteristic and poorly explained, some patients develop clotting abnormalities. We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the national French Reference Centre for Mastocytosis database. From our cohort of 14 adult patients with clotting abnormalities (median age 46 years [range 26-75]), 4 had a presentation suggestive of a primary hemostasis disorder alone (by their symptoms and/or abnormal clotting tests [PFA, von Willebrand's disease [vWD] screening]) and 10 had a laboratory impairment of secondary hemostasis. Among these, 7 had bleeds characteristic of a coagulation cascade disorder (severe/life-threatening in 5 and mild in 2 patients). Clotting abnormalities were of variable severity, typically related to intense crisis of degranulation, such as anaphylactic reactions, and/or to severe organ infiltration by mast cells. Importantly, classical hemostatic management with platelet transfusion, fresh frozen plasma, or vitamin K infusions was unsuccessful, as opposed to the use of agents inhibiting mast cell activity, particularly steroids. This illustrates the crucial role of mast cell mediators such as tryptase and heparin, which interfere both with primary (mainly via inhibition of von Willebrand factor) and secondary hemostasis. There was interestingly an unusually high number of aggressive mastocytosis (particularly mast cell leukemia) and increased mortality in the group with secondary hemostasis disorders (n = 5, 36% of the whole cohort). Mast cell degranulation and/or high tumoral burden induce both specific biologic antiaggregant and anticoagulant states with a wide clinical spectrum ranging from asymptomatic to life-threatening bleeds. Hemostatic control is achieved by mast cell inhibitors such as steroids.

Fibrinogen measurements in plasma and whole blood: a performance evaluation study of the dry-hematology system.

Science.gov (United States)

Ogawa, Satoru; Tanaka, Kenichi A; Nakajima, Yasufumi; Nakayama, Yoshinobu; Takeshita, Jun; Arai, Masatoshi; Mizobe, Toshiki

2015-01-01

An accurate and rapid determination of fibrinogen level is important during hemorrhage to establish a timely hemostatic intervention. The accuracy of fibrinogen measurements may be affected by the specific methodology for its determination, fluid therapies, and anticoagulant agents. The dry-hematology method (DRIHEMATO®) is a novel approach to determine fibrinogen levels in plasma and whole blood based on thrombin-activated coagulation time. We hypothesized that plasma or whole blood fibrinogen level using the dry-hematology method would be similar to those measured with conventional plasma fibrinogen assays. Acquired hypofibrinogenemia was modeled by serial dilutions of blood samples obtained from 12 healthy volunteers. Citrated whole blood samples were diluted with either normal saline, 5% human albumin, or 6% hydroxyethyl starch to achieve 25%, 50%, and 75% volume replacement. The dry-hematology method, the Clauss method, the prothrombin time (PT)-derived method, determination of antigen levels, and thromboelastometric fibrin formation were compared in plasma or whole blood samples. The effect of heparin on each assay was examined (0 to 6 IU/mL). Comparisons of dry-hematology and other methods were also conducted using ex vivo samples obtained from cardiac surgical patients (n = 60). In plasma samples, there were no significant differences between dry-hematology and the Clauss method, while dry-hematology showed lower fibrinogen levels compared with PT-derived and antigen level methods. The dry-hematology method yielded acceptable concordance correlation coefficients (Pc) with the Clauss method, the PT-derived method, and fibrinogen antigen levels (Pc = 0.91-0.99). The type of diluents and heparin affected the results of the PT-derived method and thromboelastometric assay, but not the dry-hematology method. In cardiac surgical patients, the overall correlation in fibrinogen levels between dry-hematology and the other methods was comparable to the results from

Evaluation of plasma fibrinogen concentration as a diagnostic indicator of inflammation in red-eared sliders (Trachemys scripta elegans).

Science.gov (United States)

Moore, A Russell; Allender, Matthew C; Mitchell, Mark A; MacNeill, Amy L

2015-01-15

To critically evaluate plasma fibrinogen concentration as a diagnostic indicator of inflammation in red-eared sliders (Trachemys scripta elegans). Prospective induced-disease model and prospective cross-sectional study. Plasma samples from 12 purpose-bred red-eared sliders and 153 farm-raised red-eared sliders. A modification of the Jacobsson method was developed to measure fibrinogen concentration in platelet-poor plasma from red-eared sliders. Purpose-bred turtles had been inoculated with a ranavirus (n = 4) or sterile PBS solution (8) as part of another study. Farm-raised red-eared sliders were categorized as healthy (n = 138) or overtly ill (15) on the basis of physical examination findings at the time of blood sample collection. Samples from 124 of the 138 healthy red-eared sliders were used to establish a fibrinogen concentration reference interval as measured by the modified Jacobsson method. Fibrinogen concentrations in ranavirus-infected and physically ill turtles were compared with those of healthy turtles to determine whether fibrinogen concentration would be a useful diagnostic indicator of inflammation in red-eared sliders. The modified Jacobsson method was reliably used to measure fibrinogen concentration. The fibrinogen concentration reference interval from healthy reproductively active female red-eared sliders was right skewed. Fibrinogen concentration did not differ significantly between healthy red-eared sliders and ranavirus-infected or overtly ill red-eared sliders. A reference interval for red-eared slider plasma fibrinogen concentration was established and partitioned by sex to account for considerable right skewing observed for females. Fibrinogen concentration was not a useful indicator of inflammation in red-eared sliders with ranavirus infection or other overt illnesses.

Blood coagulation abnormalities in multibacillary leprosy patients.

Science.gov (United States)

Silva, Débora Santos da; Teixeira, Lisandra Antonia Castro; Beghini, Daniela Gois; Ferreira, André Teixeira da Silva; Pinho, Márcia de Berredo Moreira; Rosa, Patricia Sammarco; Ribeiro, Marli Rambaldi; Freire, Monica Di Calafiori; Hacker, Mariana Andrea; Nery, José Augusto da Costa; Pessolani, Maria Cristina Vidal; Tovar, Ana Maria Freire; Sarno, Euzenir Nunes; Perales, Jonas; Bozza, Fernando Augusto; Esquenazi, Danuza; Monteiro, Robson Queiroz; Lara, Flavio Alves

2018-03-01

Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities. In the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional multibacillary leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 leprosy patients identified 35 leprosy patients (5.48%) which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named 'leprosum clot'. Most of these patients (n = 16, 45.7%) belonged to the lepromatous leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP). In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro. We demonstrated that leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of leprosy reactions, generating tools for earlier diagnosis and treatment of these events.

Albumin and fibrinogen levels′ relation with orthopedics traumatic patients′ outcome after massive transfusion

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Mohammadreza Bazavar

2014-01-01

Full Text Available Background: Severe bleeding is common during limb trauma. It can lead to hemorrhagic shock required to massive blood transfusion. Coagulopathy is the major complication of massive transfusion-induced increased mortality rate. Aim of this study was evaluation of fibrinogen and albumin levels association with orthopedics traumatic patients′ outcome who received massive transfusion. Methods: In a cross sectional study, 23 patients with severe limb injury admitted to orthopedic emergency department were studied. All the patients received massive transfusion, that is, >10 unit blood. Albumin and fibrinogen levels are measured at admission and 24 h later, and compared according to final outcome. Results: Twenty-three traumatic patients with severe limb injuries were studied, out of which ten (43.2% died and 13 (56.8% were alive. There was significant difference between patients outcome in fibrinogen level after 24 h, but no difference was observed in albumin levels. Based on regression model, fibrinogen after 24 h had a significant role in determining the final outcome in traumatic patients who received massive transfusion (odds ratio 0.48, 95% confidence interval 0.15-0.92, P = 0.02. Conclusions: According to our results, fibrinogen level is the most important factor in determination of orthopedics traumatic patients when received massive transfusion. However, serum albumin does not play any role in patients′ outcome.

Polymorphism in beta fibrinogen -455 g/a gene was associated with diabetic in severe ischemic stroke patients

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Ritarwan, Kiking; Kadri, Alfansuri; Juwita Sembiring, Rosita

2018-03-01

There is a association of polymorphism in the promoter region of the beta fibrinogen gene -455 G/A with enhancement plasma fibrinogen level. Diabetes mellitus is a risk factor for early neurologic deterioration in acute ischemic stroke. The prothrombotic fibrinogen protein is frequently elevated in patients with diabetes and may be association with poorer prognosis. This study evaluated the association of beta fibrinogen gene -455 G/A promoter polymorphism on modified Ranking Scale of Ischemic Stroke patients treated with diabetic and nondiabetic group. In a Cohort study design comprises 200 consecutive patients diabetic and a nondiabetic who, three months using completed a detailed outcome stroke. Of 200 samples genotype distribution were 27.1% for GG+GA and 0% for AA with diabetic and than 4.4% for GG+GA and 0.05% diabetic patients. Fibrinogen levels were higher in diabetic than nondiabetic group patients (307.7 + 106.3 vs 278 + 84 gr/dl, p=0.002). Fibrinogen level was found to be an independent predictor for diabetic patients. On Genotype GG+GA were associated wth diabetic and nondiabetic group patients. Modified Rankin Scale on day 90 were found associated with diabetic and nondiabetic patients. Conclusion: Elevated fibrinogen level is dose-dependently associated with 90 days outcome severity stroke with diabetic following ischemic stroke

Association of Fibrinogen with Severity of Stable Coronary Artery Disease in Patients with Type 2 Diabetic Mellitus

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Li-Feng Hong

2014-01-01

Full Text Available Background. Some studies have suggested a relation of plasma fibrinogen to the severity of coronary artery disease (CAD. However, whether plasma fibrinogen can predict the presence and severity of CAD in patients with diabetes mellitus has not been determined. Methods. A total of consecutive 373 diabetic patients with typical angina pectoris who received coronary angiography were enrolled and classified into three groups by tertiles of Gensini score (GS, low group 28. The relationship between fibrinogen and GS was evaluated. Results. There were correlations of fibrinogen with hemoglobin A1c, C-reactive protein, and GS (r=0.17, r=0.52, and r=0.21, resp.; all P<0.001. Area under the receivers operating characteristic curve of fibrinogen was 0.62 (95% CI 0.56–0.68, P<0.001 for predicting a high GS. Multivariate analysis suggested that plasma fibrinogen was an independent predictor of a high GS for diabetic patients (OR=1.40, 95% CI 1.04–1.88, and P=0.026 after adjusting for traditional risk factors of CAD. Conclusions. The present data indicated that plasma fibrinogen, a readily measurable systematic inflammatory marker, appeared to be an independent predictor for the severity of CAD in diabetic patients.

Fibrinogen and thrombin concentrations are critical for fibrin glue adherence in rat high-risk colon anastomoses

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Eliseo Portilla-de Buen

2014-04-01

Full Text Available OBJECTIVE: Fibrin glues have not been consistently successful in preventing the dehiscence of high-risk colonic anastomoses. Fibrinogen and thrombin concentrations in glues determine their ability to function as sealants, healers, and/or adhesives. The objective of the current study was to compare the effects of different concentrations of fibrinogen and thrombin on bursting pressure, leaks, dehiscence, and morphology of high-risk ischemic colonic anastomoses using fibrin glue in rats. METHODS: Colonic anastomoses in adult female Sprague-Dawley rats (weight, 250-350 g treated with fibrin glue containing different concentrations of fibrinogen and thrombin were evaluated at post-operative day 5. The interventions were low-risk (normal or high-risk (ischemic end-to-end colonic anastomoses using polypropylene sutures and topical application of fibrinogen at high (120 mg/mL or low (40 mg/mL concentrations and thrombin at high (1000 IU/mL or low (500 IU/mL concentrations. RESULTS: Ischemia alone, anastomosis alone, or both together reduced the bursting pressure. Glues containing a low fibrinogen concentration improved this parameter in all cases. High thrombin in combination with low fibrinogen also improved adherence exclusively in low-risk anastomoses. No differences were detected with respect to macroscopic parameters, histopathology, or hydroxyproline content at 5 days post-anastomosis. CONCLUSIONS: Fibrin glue with a low fibrinogen content normalizes the bursting pressure of high-risk ischemic left-colon anastomoses in rats at day 5 after surgery.

21 CFR 864.7340 - Fibrinogen determination system.

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2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fibrinogen determination system. 864.7340 Section 864.7340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7340...

Mapping of residues of fibrinogen cleaved by protease II of Bacillus thuringiensis var. israelensis IMV B-7465

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E. M. Stohniy

2016-04-01

Full Text Available The limited proteolysis of macromolecules allows obtaining the fragments that preserve the structure and functional properties of the whole molecule and could be used in the study of proteins structure and function. Proteases targeted to fibrinogen and fibrin are of interest as the tool for obtaining of functionally active fragments of fibrin(ogen and for the direct defibrination in vivo. That is why the aim of the present work was to study the proteolytic action of Protease II (PII purified from Bacillus thuringiensis var. israelensis IMV B-7465 on fibrinogen. Hydrolysis products of fibrinogen by PII were analysed by SDS-PAGE under reducing conditions with further immunoprobing using the mouse monoclonal 1-5A (anti-Aα509-610 and ІІ-5С (anti-Aα20-78 antibodies. It was shown that PII cleaved preferentially the Aα-chain of fibrinogen splitting off the peptide with apparent molecular weight of 10 kDa that corresponded the C-terminal part of Aα-chain of fibrinogen molecule. MALDI-TOF analysis of hydrolysis of fibrinogen was performed using a Voyager-DE. Results analyzed by Data Explorer 4.0.0.0 allowed to detect the main peak occurring at mass/charge (M/Z ratio of 11 441 Da. According to “Peptide Mass Calculator” this peptide corresponded to fragment Аα505-610 of fibrinogen molecule. The result showed that PII cleaves the peptide bond AαAsp-Thr-Ala504-Ser505. Thus, PII can be used for the obtaining of unique fragments of fibrinogen molecule. As far as αC-domain contains numerous sites of fibrin intermolecular interactions we can consider PII as a prospective agent for their study and for the defibrination.

Iodine based radiopacity of experimental blood clots for testing of mechanical thrombectomy devices

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Luo, Zhong Hua; Chung, Alex; Choi, Gibok; Lin, Yih Huie; Pang, Huajin; Uchida, Barry T.; Pavcnik, Dusan; Jeromel, Miran; Keller, Frederick S.; Rösch, Josef

2013-01-01

Barium sulfate powder used for radiopacity of experimental blood clots (EBCs) for testing mechanical thrombectomy devices (MTD) has negative effects on EBCs mechanical properties. In vitro and in vivo exploration was performed to determine if the iodine based contrast medium will have less negative effects on the EBCs than barium. Fresh blood from 2 swine was used to create fibrinogen enhanced and thrombin initiated EBC in tubes. Iodine radiopacity was achieved by mixing the blood with 65% Iohexol or by soaking the EBCs for 2 or 24 hours in Iohexol. The EBCs opacified with barium served as controls. In vitro study: The EBCs were subjected to four tests, manual elongation, catheter injection, radiopacity and contrast wash out tests. In vivo study: The common carotid arteries of 2 swine were embolized by either barium EBC or EBC soaked for 24 hours in Iohexol. The duration of radiopacity of the different EBCs was compared. The EBCs opacified with Iohexol initially had higher radiopacity than the barium opacified EBCs. However, their opacity rapidly decreased with saline soaking and, particularly, after they were embolized in live animals. The mechanical properties of Iohexol opacified EBCs were inferior to barium opacified EBCs. The Iohexol mixed EBCs were less firm and elastic and half of them fragmented during catheter injection. The Iohexol soaked EBCs exhibited decreased tensile strength and elasticity compared to the barium EBCs. Compared to barium, iodine based contrast medium does not offer any advantage for opacifying EBCs

Leptospira Immunoglobulin-Like Protein B (LigB Binds to Both the C-Terminal 23 Amino Acids of Fibrinogen αC Domain and Factor XIII: Insight into the Mechanism of LigB-Mediated Blockage of Fibrinogen α Chain Cross-Linking.

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Ching-Lin Hsieh

2016-09-01

Full Text Available The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII. The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12, a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC. In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8. The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12 and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12. Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis.

Leptospira Immunoglobulin-Like Protein B (LigB) Binds to Both the C-Terminal 23 Amino Acids of Fibrinogen αC Domain and Factor XIII: Insight into the Mechanism of LigB-Mediated Blockage of Fibrinogen α Chain Cross-Linking.

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Hsieh, Ching-Lin; Chang, Eric; Tseng, Andrew; Ptak, Christopher; Wu, Li-Chen; Su, Chun-Li; McDonough, Sean P; Lin, Yi-Pin; Chang, Yung-Fu

2016-09-01

The coagulation system provides a primitive but effective defense against hemorrhage. Soluble fibrinogen (Fg) monomers, composed of α, β and γ chains, are recruited to provide structural support for the formation of a hemostatic plug. Fg binds to platelets and is processed into a cross-linked fibrin polymer by the enzymatic clotting factors, thrombin and Factor XIII (FXIII). The newly formed fibrin-platelet clot can act as barrier to protect against pathogens from entering the bloodstream. Further, injuries caused by bacterial infections can be confined to the initial wound site. Many pathogenic bacteria have Fg-binding adhesins that can circumvent the coagulation pathway and allow the bacteria to sidestep containment. Fg expression is upregulated during lung infection providing an attachment surface for bacteria with the ability to produce Fg-binding adhesins. Fg binding by leptospira might play a crucial factor in Leptospira-associated pulmonary hemorrhage, the main factor contributing to lethality in severe cases of leptospirosis. The 12th domain of Leptospira immunoglobulin-like protein B (LigB12), a leptospiral adhesin, interacts with the C-terminus of FgαC (FgαCC). In this study, the binding site for LigB12 was mapped to the final 23 amino acids at the C-terminal end of FgαCC (FgαCC8). The association of FgαCC8 with LigB12 (ELISA, KD = 0.76 μM; SPR, KD = 0.96 μM) was reduced by mutations of both charged residues (R608, R611 and H614 from FgαCC8; D1061 from LigB12) and hydrophobic residues (I613 from FgαCC8; F1054 and A1065 from LigB12). Additionally, LigB12 bound strongly to FXIII and also inhibited fibrin formation, suggesting that LigB can disrupt coagulation by suppressing FXIII activity. Here, the detailed binding mechanism of a leptospiral adhesin to a host hemostatic factor is characterized for the first time and should provide better insight into the pathogenesis of leptospirosis.

Correlation between Packed Cell Volume and ‎Concentration of Clotting Factors FI, FVII, and ‎FVIII in Smokers Polycythemic males in Babylon ‎Province

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Dakhel Ghani Omran

2017-11-01

Full Text Available Smoking represents a worldwide problem and affects various body functions. The present study was conducted to evaluate the available concentration of some clotting factors in smokers polycythemic male patients. A total number of subjects was 120, 80 smokers males were affected with polycythemia and the remainders 40 males were healthy and served as a control group. The polycythemic patients were subdivided into two groups according to their ages (first group ranged between 30-40 years old and the second group ranged between 41-50 years old. PCV, clotting factor (FI, FVII and FVIII were detected. The results of present study indicated that the levels of prothrombin time (PT and activated partial thromboplastine time (APTT were significantly increased (p˂ 0.05 in both groups of polycythemia in comparison with control group. Regarding concentration of fibrinogen factor (FI and serum prothrombin conversion accelerator factor (FVII were elevated (P˂ 0.05 in both groups and pointed  out a positive correlation (r = 0.437, r = 0.378, respectively with packed cell volume (PCV when compared with those of control group. On the other hand, concentration of antihemophilic factor (FVIII recorded a significant fall (p˂ 0.05 in both tested groups and indicated a low correlation (r = 0.292. The possible explanation to the changes mentioned above is based on the fact that confirm smoking is a dangerous material containing different toxic substances that affect the vital organs of the body and induce abnormalities of hemostatic mechanism

Biochemical and biological properties of the binding of human fibrinogen to M protein in group A streptococci

International Nuclear Information System (INIS)

Whitnack, E.; Beachey, E.H.

1985-01-01

Fibrinogen is known to bind to group A streptococci and precipitate with extracts containing streptococcal M protein. The authors have previously shown that the binding of fibrinogen to M-positive streptococci prevents opsonization by complement and protects that organism from phagocytosis in nonimmune blood. In the present study, they used 3 H-labeled fibrinogen, a highly purified peptide fragment of type 24 M protein (pep M24), and anti-pep M sera to show that fibrinogen binds to M-positive streptococci with high affinity; occupation of the high-affinity binding sites suffices to protect the organism from phagocytosis; proteolytic treatments that remove M protein from streptococcal cells abolish binding; binding is competitively inhibited by anti-pep M sera; pep M24 precipitates fibrinogen; and binding to type 24 cells is inhibited by pep M24. They conclude that M protein is the cell surface structure principally responsible for binding fibrinogen on the surface of M-positive streptococci and that this binding contributes to the known antiopsonic property of M proteins

Hydroxyl radical-modified fibrinogen as a marker of thrombosis: the role of iron.

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Lipinski, B; Pretorius, E

2012-07-01

Excessive free iron in blood and in organ tissues (so called iron overload) has been observed in degenerative diseases such as atherosclerosis, cancer, neurological, and certain autoimmune diseases, in which fibrin-like deposits are also found. Although most of the body iron is bound to hemoglobin and myoglobin in a divalent ferrous form, a certain amount of iron exists in blood as a trivalent (ferric) ion. This particular chemical state of iron has been shown to be toxic to the human body when not controlled by endogenous and/or dietary chelating agents. Experiments described in this paper show for the first time that ferric ions (Fe(3+)) can generate hydroxyl radicals without participation of any redox agent, thus making it a special case of the Fenton reaction. Ferric chloride was also demonstrated to induce aggregation of purified fibrinogen at the same molar concentrations that were used for the generation of hydroxyl radicals. Iron-aggregated fibrinogen, by contrast to native molecule, could not be dissociated into polypeptide subunit chains as shown in a polyacrylamide gel electrophoresis. The mechanism of this phenomenon is very likely based on hydroxyl radical-induced modification of fibrinogen tertiary structure with the formation of insoluble aggregates resistant to enzymatic and chemical degradations. Soluble modified fibrinogen species can be determined in blood of thrombotic patients by the reaction with protamine sulfate and/or by scanning electron microscopy. In view of these findings, it is postulated that iron-induced alterations in fibrinogen structure is involved in pathogenesis of certain degenerative diseases associated with iron overload and persistent thrombosis. It is concluded that the detection of hydroxyl radical-modified fibrinogen may be utilized as a marker of a thrombotic condition in human subjects.

Reduced clot debris size using standing waves formed via high intensity focused ultrasound

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Guo, Shifang; Du, Xuan; Wang, Xin; Lu, Shukuan; Shi, Aiwei; Xu, Shanshan; Bouakaz, Ayache; Wan, Mingxi

2017-09-01

The feasibility of utilizing high intensity focused ultrasound (HIFU) to induce thrombolysis has been demonstrated previously. However, clinical concerns still remain related to the clot debris produced via fragmentation of the original clot potentially being too large and hence occluding downstream vessels, causing hazardous emboli. This study investigates the use of standing wave fields formed via HIFU to disintegrate the thrombus while achieving a reduced clot debris size in vitro. The results showed that the average diameter of the clot debris calculated by volume percentage was smaller in the standing wave mode than in the travelling wave mode at identical ultrasound thrombolysis settings. Furthermore, the inertial cavitation dose was shown to be lower in the standing wave mode, while the estimated cavitation bubble size distribution was similar in both modes. These results show that a reduction of the clot debris size with standing waves may be attributed to the particle trapping of the acoustic potential well which contributed to particle fragmentation.

Pro blood clotting activity of Scoparia dulcis in rats.

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Ediriweera, E R H S S; Jayakody, J R A C; Ratnasooriya, W D

2011-04-01

Scoparia dulcis Linn (Family: Scrophulariaceae, Sinhala: WalKoththamalli) is a perennial herb growing in many tropical countries including Sri Lanka. Traditional Physicians in rural down south areas apply crushed S. dulcis plant on cuts and bruises to stop bleeding. S. dulcis may also have Rakta Sthambhana property. The study on effect of decoction (water extract) of S. dulcis on blood clotting time in rats was carried out to investigate this. Two groups of rats, 12 males and 42 females were used in this experimental study. Forty-two female rats were assigned into seven equal groups (n = 6/gp). Different doses of DE (25, 50, 100, 1000, 1500 mg/kg) (group 1-5) or 2 ml of distilled water (DW) (group 6) were orally administered. 0.1 ml of vitamin K was injected intramuscularly (group 7) as reference drug to seventh the group. Twelve male rats were assigned into two equal groups (n = 6/gp), 2 ml of distilled water (DW) and doses of DE (1500 mg/kg) were orally administered. Clotting time was determined on the Days 1, 2, and 7 using Lee and White method. In the DE treated groups with all doses, there was no reduction in clotting time on the Day 1 but a significant reduction of clotting time (P dulcis has proclotting activity (rakthasthambhana property) and this was faster than vitamin K.

Pathology Report for Intraperitoneal Sodium Dichromate Exposure in Rats

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2015-08-12

injury resulting from exposure to specific metal intoxication . The investigators aim was to validate hypothesized adverse outcome pathways in rats...vessels causing them to become leaky. Injured or inflamed vessels lead to extravasated fibrinogen which rapidly clots into a cross-linked fibrin gel...Sprague-Dawley rats appear to include direct injury to the exposed, capsular surface of the liver, leading to fibrinogen leakage, fibrin formation

Coagulation abnormalities in patients with chronic liver disease in Pakistan

International Nuclear Information System (INIS)

Siddiqui, S.A.; Ghani, M.H.; Ghori, M.A.; Ahmed, M.

2011-01-01

Objective: To determine the coagulation abnormalities and relationship between abnormal clotting tests and the risk of gastrointestinal bleeding (GI) among chronic liver disease (CLD) patients admitted at a tertiary care hospital in Pakistan. Methods: Adult CLD patients admitted at Liaquat University Hospital Jamshoro, during Nov 2004 - Oct 2005, were included in the study. The patients blood were tested for coagulation abnormalities including prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count and plasma fibrinogen. Association was seen between the abnormal clotting tests and the gastrointestinal bleeding by calculating relative risk (RR) with 95% confidence interval. Results: PT was prolonged in 88% and aPTT was raised in 71% cases of CLD. Both PT and aPTT were prolonged in 67% CLD cases. Approximately 37% CLD cases had decreased platelet count and 15% cases had decreased serum fibrinogen level. Relative risk of GI bleeding with abnormal clotting tests in CLD cases were weakly positive for PT (RR = 1.02; 95% CI, 0.49-2.10), negative for aPTT (RR=0.83; 95% CI, 0.47-1.45), strongly positive for decreased platelet counts (RR = 1.96; 95% CI, 1.08-3.56) and also for decreased fibrinogen level (RR = 1.47; 95% CI, 0.64-3.35). Conclusion: Coagulation abnormalities were profound in CLD. Decrease platelet counts and fibrinogen levels were related with GI bleeding but PT and aPTT were not significantly related with GI bleeding in patients with chronic liver disease. Nevertheless, these parameters (PT and aPTT) were still used as prognostic markers. (author)

A constitutive model for developing blood clots with various compositions and their nonlinear viscoelastic behavior.

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van Kempen, Thomas H S; Donders, Wouter P; van de Vosse, Frans N; Peters, Gerrit W M

2016-04-01

The mechanical properties determine to a large extent the functioning of a blood clot. These properties depend on the composition of the clot and have been related to many diseases. However, the various involved components and their complex interactions make it difficult at this stage to fully understand and predict properties as a function of the components. Therefore, in this study, a constitutive model is developed that describes the viscoelastic behavior of blood clots with various compositions. Hereto, clots are formed from whole blood, platelet-rich plasma and platelet-poor plasma to study the influence of red blood cells, platelets and fibrin, respectively. Rheological experiments are performed to probe the mechanical behavior of the clots during their formation. The nonlinear viscoelastic behavior of the mature clots is characterized using a large amplitude oscillatory shear deformation. The model is based on a generalized Maxwell model that accurately describes the results for the different rheological experiments by making the moduli and viscosities a function of time and the past and current deformation. Using the same model with different parameter values enables a description of clots with different compositions. A sensitivity analysis is applied to study the influence of parameter variations on the model output. The relative simplicity and flexibility make the model suitable for numerical simulations of blood clots and other materials showing similar behavior.

Reduced Transfusion During OLT by POC Coagulation Management and TEG Functional Fibrinogen: A Retrospective Observational Study.

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De Pietri, Lesley; Ragusa, Francesca; Deleuterio, Annalisa; Begliomini, Bruno; Serra, Valentina

2016-01-01

Patients undergoing orthotopic liver transplantation are at high risk of bleeding complications. Several Authors have shown that thromboelastography (TEG)-based coagulation management and the administration of fibrinogen concentrate reduce the need for blood transfusion. We conducted a single-center, retrospective cohort observational study (Modena Polyclinic, Italy) on 386 consecutive patients undergoing liver transplantation. We assessed the impact on resource consumption and patient survival after the introduction of a new TEG-based transfusion algorithm, requiring also the introduction of the fibrinogen functional thromboelastography test and a maximum amplitude of functional fibrinogen thromboelastography transfusion cutoff (7 mm) to direct in administering fibrinogen (2012-2014, n = 118) compared with a purely TEG-based algorithm previously used (2005-2011, n = 268). After 2012, there was a significant decrease in the use of homologous blood (1502 ± 1376 vs 794 ± 717 mL, P < 0.001), fresh frozen plasma (537 ± 798 vs 98 ± 375 mL, P < 0.001), and platelets (158 ± 280 vs 75 ± 148 mL, P < 0.005), whereas the use of fibrinogen increased (0.1 ± 0.5 vs 1.4 ± 1.8 g, P < 0.001). There were no significant differences in 30-day and 6-month survival between the 2 groups. The implementation of a new coagulation management method featuring the addition of the fibrinogen functional thromboelastography test to the TEG test according to an algorithm which provides for the administration of fibrinogen has helped in reducing the need for transfusion in patients undergoing liver transplantation with no impact on their survival.

Beta-fibrinogen allele frequencies in Peruvian Quechua, a high-altitude native population.

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Rupert, J L; Devine, D V; Monsalve, M V; Hochachka, P W

1999-06-01

Elevated hematocrits, which are found in many high-altitude populations, increase the oxygen-carrying capacity of blood and may represent an adaptation to hypoxic environments. However, as high hematocrit increases blood viscosity, which in turn is associated with hypertension and heart disease, it may be advantageous for high-altitude populations to limit other factors that contribute to increased blood viscosity. One such factor is the plasma concentration of the coagulation protein fibrinogen. Several common polymorphisms in the beta-fibrinogen gene have been identified that affect fibrinogen concentrations. We determined the allele frequencies of three of these polymorphisms (G/A-455(HaeIII), C/T-148(HindIII), and G/A+448(MnlI)) in sample groups drawn from three populations: Quechua-speaking natives living at over 3,200 m in the Peruvian Andes, North American natives (Na-Dene) from coastal British Columbia, and Caucasian North Americans. The frequencies of the alleles previously shown to be associated with increased fibrinogen levels were so low in the Quechuas that their presence could be accounted for solely by genetic admixture with Caucasians. Frequencies in the Na-Dene, a Native American group unrelated to the Quechua, were not significantly different from those in Caucasians.

Serum bilirubin levels are inversely associated with PAI-1 and fibrinogen in Korean subjects.

Science.gov (United States)

Cho, Hyun Sun; Lee, Sung Won; Kim, Eun Sook; Shin, Juyoung; Moon, Sung Dae; Han, Je Ho; Cha, Bong Yun

2016-01-01

Oxidative stress may contribute to atherosclerosis and increased activation of the coagulation pathway. Bilirubin may reduce activation of the hemostatic system to inhibit oxidative stress, which would explain its cardioprotective properties shown in many epidemiological studies. This study investigated the association of serum bilirubin with fibrinogen and plasminogen activator inhibitor-1 (PAI-1), respectively. A cross-sectional analysis was performed on 968 subjects (mean age, 56.0 ± 11.2 years; 61.1% men) undergoing a general health checkup. Serum biochemistry was analyzed including bilirubin subtypes, insulin resistance (using homeostasis model of assessment [HOMA]), C-reactive protein (CRP), fibrinogen, and PAI-1. Compared with subjects with a total bilirubin (TB) concentration of 17.1 μmol/L had a smaller waist circumference, a lower triglyceride level, a lower prevalence of metabolic syndrome, and decreased HOMA-IR and CRP levels. Correlation analysis revealed linear relationships of fibrinogen with TB and direct bilirubin (DB), whereas PAI-1 was correlated with DB. After adjustment for confounding factors, bilirubin levels were inversely associated with fibrinogen and PAI-1 levels, respectively. Multivariate regression models showed a negative linear relationship between all types of bilirubin and fibrinogen, whereas there was a significant linear relationship between PAI-1 and DB. High bilirubin concentrations were independently associated with low levels of fibrinogen and PAI-1, respectively. The association between TB and PAI-1 was confined to the highest TB concentration category whereas DB showed a linear association with PAI-1. Bilirubin may protect against the development of atherothrombosis by reducing the hemostatic response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Diagnostic value of radioactive fibrinogen and rheography in phlebitis

International Nuclear Information System (INIS)

Serradimigni, A.; Bory, M.; Djiane, P.; Sacerdote, P.; Mathieu, P.; Leonetti, J.; Egre, A.

1975-01-01

In 212 patients the diagnostic value of radioactive fibrinogen and rheography in deep venous thrombosis in the leg was studied by comparing the results from these two methods with phlebography. Radioactive fibrinogen seems the better means of diagnosis in early distal phlebitis. However, the method is expensive, the radioactive substance can only be manipulated in certain specialized centers, and is useless in the presence of hematoma. Rheography is less expensive, more easily manipulated, yet less sensitive as only proximal phlebitis can be detected especially when completely occlusive. In addition, active patient cooperation is necessary. The time needed to realize the two methods is a major obstacle; however, they can be fruitful if integrated into a specialized department for the diagnosis and treatment of thrombo-embolic disease [fr

Artificial Stroke Clots: How Wide is the Gap to the Real World?

Science.gov (United States)

Berndt, Maria; Prothmann, Sascha; Maegerlein, Christian; Oberdieck, Paul; Zimmer, Claus; Hegge, Barbara; Pelisek, Jaroslav; Schirmer, Lucas; Poppert, Holger; Boeckh-Behrens, Tobias

2018-02-01

Especially since the establishment of mechanical thrombectomy as part of standard stroke therapy, artificial thrombi have become important in the training of interventionalists as well as for the development and testing of devices. So far, these in vitro clots have lacked direct comparisons with ex vivo thrombi. We therefore compared the histologic appearance of dynamically produced clots with that of stroke thrombi acquired during mechanical recanalization. Thrombi of 145 consecutive patients with stroke with large-vessel occlusions were histologically compared with 10 artificial clots, dynamically created from human blood and pig's blood using a Chandler loop system. Quantified FP/RBC ratios (fibrin/platelets divided by red blood cell fraction) and white blood cell (WBC) fractions were identified and compared between artificial (human and pig) and ex vivo thrombi obtained from patients with various stroke causes. There were no significant differences in the analysis of FP/RBC ratios between artificial thrombi and ex vivo thrombi (P = 0.42) or in the more precise analyses considering etiologic subgroups. Distinct differences were observed for the WBC fraction, with lower values in artificial thrombi (median, 1.34%) than in ex vivo thrombi (median, 5%) (P < 0.001). The main clot components, FP and RBC, are presumably the most influential factors for clot stability and mechanical resistance. Similarities between artificially generated and ex vivo stroke clots (and when considering different stroke subgroups) support the usefulness of these artificial thrombi in the pre-evaluation of thrombus extraction devices and as appropriate training material. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical Stability and Fibrinolytic Resistance of Clots Containing Fibrin, DNA, and Histones*

Science.gov (United States)

Longstaff, Colin; Varjú, Imre; Sótonyi, Péter; Szabó, László; Krumrey, Michael; Hoell, Armin; Bóta, Attila; Varga, Zoltán; Komorowicz, Erzsébet; Kolev, Krasimir

2013-01-01

Neutrophil extracellular traps are networks of DNA and associated proteins produced by nucleosome release from activated neutrophils in response to infection stimuli and have recently been identified as key mediators between innate immunity, inflammation, and hemostasis. The interaction of DNA and histones with a number of hemostatic factors has been shown to promote clotting and is associated with increased thrombosis, but little is known about the effects of DNA and histones on the regulation of fibrin stability and fibrinolysis. Here we demonstrate that the addition of histone-DNA complexes to fibrin results in thicker fibers (increase in median diameter from 84 to 123 nm according to scanning electron microscopy data) accompanied by improved stability and rigidity (the critical shear stress causing loss of fibrin viscosity increases from 150 to 376 Pa whereas the storage modulus of the gel increases from 62 to 82 pascals according to oscillation rheometric data). The effects of DNA and histones alone are subtle and suggest that histones affect clot structure whereas DNA changes the way clots are lysed. The combination of histones + DNA significantly prolongs clot lysis. Isothermal titration and confocal microscopy studies suggest that histones and DNA bind large fibrin degradation products with 191 and 136 nm dissociation constants, respectively, interactions that inhibit clot lysis. Heparin, which is known to interfere with the formation of neutrophil extracellular traps, appears to prolong lysis time at a concentration favoring ternary histone-DNA-heparin complex formation, and DNase effectively promotes clot lysis in combination with tissue plasminogen activator. PMID:23293023

The Phosphatase Inhibitor Calyculin-A Impairs Clot Retraction, Platelet Activation, and Thrombin Generation

Directory of Open Access Journals (Sweden)

Renáta Hudák

2017-01-01

Full Text Available The aim of this study was to investigate the effect of the serine/threonine protein phosphatase inhibitor, calyculin-A (CLA, on clot formation and on the procoagulant activity of human platelets. Platelet-rich plasma (PRP samples were preincubated with buffer or CLA and subsequently platelets were activated by the protease-activated receptor 1 (PAR-1 activator, thrombin receptor activating peptide (TRAP. Clot retraction was detected by observing clot morphology up to 1 hour, phosphatidylserine- (PS- expression was studied by flow cytometry, and thrombin generation was measured by a fluorimetric assay. For the intracellular Ca2+ assay, platelets were loaded with calcium-indicator dyes and the measurements were carried out using a ratiometric method with real-time confocal microscopy. CLA preincubation inhibited clot retraction, PS-expression, and thrombin formation. TRAP activation elicited Ca2+ response and PS-expression in a subset of platelets. The activated PRP displayed significantly faster and enhanced thrombin generation compared to nonactivated samples. CLA pretreatment abrogated PS-exposure and clot retraction also in TRAP-activated samples. As a consequence of the inhibitory effect on calcium elevation and PS-expression, CLA significantly downregulated thrombin generation in PRP. Our results show that CLA pretreatment may be a useful tool to investigate platelet activation mechanisms that contribute to clot formation and thrombin generation.

Blood coagulation abnormalities in multibacillary leprosy patients.

Directory of Open Access Journals (Sweden)

Débora Santos da Silva

2018-03-01

Full Text Available Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities.In the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional multibacillary leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 leprosy patients identified 35 leprosy patients (5.48% which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named 'leprosum clot'. Most of these patients (n = 16, 45.7% belonged to the lepromatous leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP. In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro.We demonstrated that leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of leprosy reactions, generating tools for earlier diagnosis and treatment of these events.

A Novel Inflammation-Based Prognostic Score: The Fibrinogen/Albumin Ratio Predicts Prognoses of Patients after Curative Resection for Hepatocellular Carcinoma

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Qiaodong Xu

2018-01-01

Full Text Available Background. Inflammation is an important hallmark of cancer. Fibrinogen and albumin are both vital factors in systemic inflammation. This study investigated the prognostic value of the fibrinogen/albumin ratio in HCC patients who underwent curative resection. Methods. HCC patients (n=151 who underwent curative resection were evaluated retrospectively. The optimal cutoff value for the fibrinogen/albumin ratio was selected by receiver operating characteristic (ROC curve analysis. Correlations between preoperative fibrinogen/albumin ratios and clinicopathologic characteristics were analyzed by χ2 test. The area under the receiver operating characteristic curve (AUC was calculated to compare the prognostic value of the fibrinogen/albumin ratio with other prognostic scores (neutrophil to lymphocyte ratio (NLR, platelet to lymphocyte ratio (PLR, and albumin-bilirubin (ALBI score. The overall survival (OS and time to recurrence (TTR were assessed by the log-rank test and the Cox proportional hazard regression model. Results. An optimal cutoff value of the preoperative fibrinogen/albumin ratio (0.062 was determined for 151 patients who underwent curative resection for HCC via a ROC curve analysis. Fibrinogen/albumin ratio > 0.062 was significantly associated with microvascular invasion, an advanced BCLC stage, and ALBI grade. Multivariate analyses revealed that fibrinogen/albumin ratio was an independent predictor for OS (P=0.003 and TTR (P=0.035. The prognostic ability of fibrinogen/albumin ratio was comparable to other prognostic scores (NLR, PLR, and ALBI score by AUC analysis. Patients with a fibrinogen/albumin ratio > 0.062 had lower 1-, 3-, and 5-year OS rates (66.0%, 41.8%, and 28.2% versus 81.9%, 69.3%, and 56.1%, resp., P<0.001 and higher 1-, 3-, and 5-year recurrence rates (60.9%, 79.2%, and 90.5% versus 49.5%, 69.1%, and 77.1%, resp., P=0.008 compared with patients with fibrinogen/albumin ratio ≤ 0.062. Conclusion. The

The binding of 125I-fibrinogen to blood platelets in patients with chronic uraemia

International Nuclear Information System (INIS)

Komarnicki, M.; Zozulinska, M.; Zawilska, K.

1987-01-01

The binding of 125 I-fibrinogen to blood platelets was assessed in 41 patients with chronic uremia. The study was performed in three groups of subjects: treated conservatively, with hemodialysis and with peritoneal dialysis. Platelets from uremic patients were shown to be more susceptible to fibrinogen binding than platelets from healthy subjects. (author)

Relationship between physical activity and plasma fibrinogen concentrations in adults without chronic diseases.

Directory of Open Access Journals (Sweden)

Manuel A Gomez-Marcos

Full Text Available To analyze the relationship between regular physical activity, as assessed by accelerometer and 7-day physical activity recall (PAR, and plasma fibrinogen concentrations.A cross-sectional study in a previously established cohort of healthy subjects was performed. This study analyzed 1284 subjects who were included in the EVIDENT study (mean age 55.0±13.6 years; 60.90% women. Fibrinogen concentrations were measured in blood plasma. Physical activity was assessed with a 7-day PAR (metabolic equivalents (METs/hour/week and GT3X ActiGraph accelerometer (counts/minute for 7 days.Physical exercise, which was evaluated with both an accelerometer (Median: 237.28 counts/minute and 7-day PAR (Median: 8 METs/hour/week. Physical activity was negatively correlated with plasma fibrinogen concentrations, which was evaluated by counts/min (r = -0.100; p<0.001 and METs/hour/week (r = -0.162; p<0.001. In a multiple linear regression analysis, fibrinogen concentrations of the subjects who performed more physical activity (third tertile of count/minute and METs/hour/week respect to subjects who performed less (first tertile, maintained statistical significance after adjustments for age and others confounders (β = -0.03; p = 0.046 and β = -0.06; p<0.001, respectively.Physical activity, as assessed by accelerometer and 7-day PAR, was negatively associated with plasma fibrinogen concentrations. This relation is maintained in subjects who performed more exercise even after adjusting for age and other confounders.

Contribution to the study of plasmatic fibrinogen and serum albumin: effects of irradiation

International Nuclear Information System (INIS)

Suscillon, M.

1967-01-01

The author studies the modifications of properties and structure of serum albumin and fibrinogen solution when subjected to radiation of low energy (X rays). On the other hand, two original techniques are exposed: 1. Amperometric determination of fibrin stabilizing factor or factor XIII of hemostasis. 2. Spectrophotometric study of fibrin formation kinetics. Then showing off and quantitative determination of platelets fibrinogen is exposed. (author) [fr

42 CFR 410.63 - Hepatitis B vaccine and blood clotting factors: Conditions.

Science.gov (United States)

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Hepatitis B vaccine and blood clotting factors... Other Health Services § 410.63 Hepatitis B vaccine and blood clotting factors: Conditions... under § 410.10, subject to the specified conditions: (a) Hepatitis B vaccine: Conditions. Effective...

Extracellular fibrinogen-binding protein (Efb) from staphylococcus aureus Inhibits the formation of platelet-leukocyte complexes

NARCIS (Netherlands)

Posner, M.G; Upadhyay, A.; Abubaker, A.A.; Fortunato, T.M.; Vara, D.; Canobbio, I.; Bagby, S.; Pula, G.

2016-01-01

Extracellular fibrinogen-binding protein (Efb) from Staphylococcus aureus inhibits platelet activation, although its mechanism of action has not been established. In this study, we discovered that the N-terminal region of Efb (Efb-N) promotes platelet binding of fibrinogen and that Efb-N binding to

Prognostic implications of plasma fibrinogen and serum Creactive ...

African Journals Online (AJOL)

Purpose: To investigate the prognostic implications of plasma fibrinogen and serum C-reactive protein (CRP) levels in tumour resection and survival following successful tumour resection in patients with nonsmall cell lung cancer (NSCLC). Methods: One hundred and fifty-three NSCLC patients who underwent surgical ...

Identification and characterization of milk-clotting proteases ...

African Journals Online (AJOL)

SAM

2014-03-12

Mar 12, 2014 ... Two strains of fungi were isolated and identified as Aspergillus tamarii and Penicillium pinophilum ... for milk clotting enzymes by fermentation at acid pH on culture medium containing whey ..... Rhizopus oryzae NBRC 4749.

Effects of tibolone on fibrinogen and antithrombin III: A systematic review and meta-analysis of controlled trials.

Science.gov (United States)

Bała, Małgorzata; Sahebkar, Amirhossein; Ursoniu, Sorin; Serban, Maria-Corina; Undas, Anetta; Mikhailidis, Dimitri P; Lip, Gregory Y H; Rysz, Jacek; Banach, Maciej

2017-10-01

Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII) has not been conclusive. We assessed the impact of tibolone on fibrinogen and ATIII through a systematic review and meta-analysis of available randomized controlled trials (RCTs). The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2016) to identify controlled clinical studies investigating the effects of oral tibolone treatment on fibrinogen and ATIII. Overall, the impact of tibolone on plasma fibrinogen concentrations was reported in 10 trials comprising 11 treatment arms. Meta-analysis did not suggest a significant reduction of fibrinogen levels following treatment with tibolone (WMD: -5.38%, 95% CI: -11.92, +1.16, p=0.107). This result was robust in the sensitivity analysis and not influenced after omitting each of the included studies from meta-analysis. When the studies were categorized according to the duration of treatment, there was no effect in the subsets of trials lasting either analysis. There was no differential effect of tibolone on plasma ATIII concentrations in trials with either analysis, meta-regression did not suggest any significant association between the changes in plasma concentrations of fibrinogen (slope: +0.40; 95% CI: -0.39, +1.19; p=0.317) and ATIII (slope: -0.17; 95% CI: -0.54, +0.20; p=0.374) with duration of treatment. In conclusion, meta-analysis did not suggest a significant reduction of fibrinogen and ATIII levels following treatment with tibolone. Copyright © 2017 Elsevier Ltd. All rights reserved.

Associations of overall sitting time and TV viewing time with fibrinogen and C reactive protein: the AusDiab study.

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Howard, Bethany J; Balkau, Beverley; Thorp, Alicia A; Magliano, Dianna J; Shaw, Jonathan E; Owen, Neville; Dunstan, David W

2015-02-01

Sedentary behaviour is associated with increased risk for all-cause and cardiovascular mortality. Plasma fibrinogen and C reactive protein (CRP)-key inflammatory and/or haemostatic markers-may contribute to this association; however, few studies have examined their relationships with sedentary behaviours. We examined associations of overall sitting and TV viewing time with fibrinogen and high-sensitivity CRP (hsCRP). Plasma fibrinogen and hsCRP were measured in 3086 Australian adults (mean age: 55±12 years) who participated in the 2004-2005 AusDiab (Australian Diabetes, Obesity and Lifestyle) study. Multiple linear regression analyses examined cross-sectional associations of self-reported overall sitting and TV viewing time (h/day) with plasma fibrinogen and hsCRP, adjusting for sociodemographic, behavioural and medical treatments and conditions as potential covariates. Overall sitting time and TV viewing time were positively associated with plasma fibrinogen (sitting: β: 0.02 g/L, 95% CI (0.01 to 0.02); TV time: 0.03 g/L (0.02 to 0.05)) and hsCRP (sitting: 2.4% (1.2% to 3.6%); TV time: 4.5% (1.7% to 7.4%)). Associations were independent of leisure-time physical activity, but after adjusting for waist circumference, they remained for fibrinogen, but for hsCRP were attenuated to the null. Interactions were observed for gender×TV (p=0.011) with fibrinogen (associations in women only) and for waist circumference×TV (p=0.084) with hsCRP (associations in low-risk only). Overall sitting time was positively associated with plasma fibrinogen and hsCRP in men and women; associations of TV viewing time with fibrinogen were observed in women only. Abdominal adiposity-mediated associations for hsCRP but not for fibrinogen. Prospective and intervention studies are needed to establish likely causality and elucidate potential mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Dahl, Morten; Tybjaerg-Hansen, A; Vestbo, J

2001-01-01

We tested whether increased concentrations of the acute-phase reactant fibrinogen correlate with pulmonary function and rate of chronic obstructive pulmonary disease (COPD) hospitalization. We measured plasma fibrinogen and forced expiratory volume in 1 s (FEV(1)), and assessed prospectively COPD...

Antibody functionalized graphene biosensor for label-free electrochemical immunosensing of fibrinogen, an indicator of trauma induced coagulopathy.

Science.gov (United States)

Saleem, Waqas; Salinas, Carlos; Watkins, Brian; Garvey, Gavin; Sharma, Anjal C; Ghosh, Ritwik

2016-12-15

An antibody, specific to fibrinogen, has been covalently attached to graphene and deposited onto screen printed electrodes using a chitosan hydrogel binder to prepare an inexpensive electrochemical fibrinogen biosensor. Fourier Transform Infrared (FT-IR) spectroscopy has been utilized to confirm the presence of the antibody on the graphene scaffold. Electrochemical Impedance Spectroscopy (EIS) has been utilized to demonstrate that the biosensor responds in a selective manner to fibrinogen in aqueous media even in the presence of plasminogen, a potentially interfering molecule in the coagulopathy cascade. Furthermore, the biosensor was shown to reliably sense fibrinogen in the presence of high background serum albumin levels. Finally, we demonstrated detection of clinically relevant fibrinogen concentrations (938-44,542μg/dL) from human serum and human whole blood samples using this biosensor. This biosensor can potentially be used in a point-of-care device to detect the onset of coagulopathy and monitor response following therapeutic intervention in trauma patients. Thus this biosensor may improve the clinical management of patients with trauma-induced coagulopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

International Nuclear Information System (INIS)

Zhao, Jun; Zheng, Shuang; Zhou, Qiyin; Li, Heming; Liu, Yunpeng; Qu, Xiujuan; Zhao, Mingfang; Jin, Bo; Yu, Ping; Hu, Xuejun; Teng, Yuee; Zhang, Jingdong; Luo, Ying; Zhang, Lingyun

2012-01-01

Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. This study showed that the reduction in plasma fibrinogen levels

The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

Science.gov (United States)

Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

2015-12-01

Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Group B streptococcal serine-rich repeat proteins promote interaction with fibrinogen and vaginal colonization.

Science.gov (United States)

Wang, Nai-Yu; Patras, Kathryn A; Seo, Ho Seong; Cavaco, Courtney K; Rösler, Berenice; Neely, Melody N; Sullam, Paul M; Doran, Kelly S

2014-09-15

Group B streptococcus (GBS) can cause severe disease in susceptible hosts, including newborns, pregnant women, and the elderly. GBS serine-rich repeat (Srr) surface glycoproteins are important adhesins/invasins in multiple host tissues, including the vagina. However, exact molecular mechanisms contributing to their importance in colonization are unknown. We have recently determined that Srr proteins contain a fibrinogen-binding region (BR) and hypothesize that Srr-mediated fibrinogen binding may contribute to GBS cervicovaginal colonization. In this study, we observed that fibrinogen enhanced wild-type GBS attachment to cervical and vaginal epithelium, and that this was dependent on Srr1. Moreover, purified Srr1-BR peptide bound directly to host cells, and peptide administration in vivo reduced GBS recovery from the vaginal tract. Furthermore, a GBS mutant strain lacking only the Srr1 "latching" domain exhibited decreased adherence in vitro and decreased persistence in a mouse model of GBS vaginal colonization, suggesting the importance of Srr-fibrinogen interactions in the female reproductive tract. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Utility of single-energy and dual-energy computed tomography in clot characterization: An in-vitro study.

Science.gov (United States)

Brinjikji, Waleed; Michalak, Gregory; Kadirvel, Ramanathan; Dai, Daying; Gilvarry, Michael; Duffy, Sharon; Kallmes, David F; McCollough, Cynthia; Leng, Shuai

2017-06-01

Background and purpose Because computed tomography (CT) is the most commonly used imaging modality for the evaluation of acute ischemic stroke patients, developing CT-based techniques for improving clot characterization could prove useful. The purpose of this in-vitro study was to determine which single-energy or dual-energy CT techniques provided optimum discrimination between red blood cell (RBC) and fibrin-rich clots. Materials and methods Seven clot types with varying fibrin and RBC densities were made (90% RBC, 99% RBC, 63% RBC, 36% RBC, 18% RBC and 0% RBC with high and low fibrin density) and their composition was verified histologically. Ten of each clot type were created and scanned with a second generation dual source scanner using three single (80 kV, 100 kV, 120 kV) and two dual-energy protocols (80/Sn 140 kV and 100/Sn 140 kV). A region of interest (ROI) was placed over each clot and mean attenuation was measured. Receiver operating characteristic curves were calculated at each energy level to determine the accuracy at differentiating RBC-rich clots from fibrin-rich clots. Results Clot attenuation increased with RBC content at all energy levels. Single-energy at 80 kV and 120 kV and dual-energy 80/Sn 140 kV protocols allowed for distinguishing between all clot types, with the exception of 36% RBC and 18% RBC. On receiver operating characteristic curve analysis, the 80/Sn 140 kV dual-energy protocol had the highest area under the curve for distinguishing between fibrin-rich and RBC-rich clots (area under the curve 0.99). Conclusions Dual-energy CT with 80/Sn 140 kV had the highest accuracy for differentiating RBC-rich and fibrin-rich in-vitro thrombi. Further studies are needed to study the utility of non-contrast dual-energy CT in thrombus characterization in acute ischemic stroke.

The effect of 8-week low impact aerobic exercise on plasma fibrinogen concentration in old women

Directory of Open Access Journals (Sweden)

Shahla Dehghan

2013-09-01

Full Text Available Applied Exercise Physiology focuses on the physiological effects of exercise training on physiological processes, health, and physical well-being. The aim of this study was investigation of effects of 8-week low impact aerobic exercise on plasma fibrinogen concentration in old women. Fibrinogen is one of the most important inflammation factors and a prediction index in cardio vascular diseases. Iranian women especially older ones are generally sedentary because of their traditional and religious believes. Samples were 23 healthy and enable to do physical activity old women of Shahrekord (Chaharmahal va bakhtiary province, Iran retirement home. Subjects were randomly divided to two groups including experimental (n=14 individuals and control (n=11 individuals. First, for assessment of fibrinogen level, 5cc blood samples were obtained after 8 hours nightly fasting from anterior vein in resting condition. Experimental group was participated in 8 week (three times a week LIA training program (15 min in first day with 40% of maximum heart rate until 40 min in last day with 65% of maximum heart rate. All of mentioned measurements repeated at the end of 8 week training. The obtained results showed that 8 week LIA program has significant effect on reduction of old women plasma fibrinogen level (P=0.02. It seems that use of 8 week LIA training has positive effects on improvement of cardiovascular health and prevention of inflammation disease related to plasma fibrinogen level in Iranian old women. Key words: aerobic exercises, old women, fibrinogen.

The role of fibrinogen and haemostatic assessment in postpartum haemorrhage

DEFF Research Database (Denmark)

Wikkelsø, Anne Juul

2015-01-01

Pregnancy is a state of hypercoagulobility that might be an evolutionary way of protecting parturients from exsanguination following child birth. Observational studies suggest an association between a low level of fibrinogen (coagulation factor I) at the start of postpartum haemorrhage (PPH....... Paper III was based on two national Danish registries evaluating the predictability of postpartum blood transfusion. Prediction was found difficult. However, retained placental parts seemed to be the strongest predictor. Since this diagnosis is made very late and often in association with the onset...... describes the protocol for a RCT of early fibrinogen supplementation in women with severe postpartum haemorrhage. Several practical, ethical and trial management challenges need to be addressed when conducting independent clinical research involving parturients with severe bleeding, placebo...

Paradoxical bleeding and thrombosis in a patient with afibrinogenemia and fibrinogen Mumbai mutation.

Science.gov (United States)

Mukaddam, Alfiya; Patil, Rucha; Jadli, Anshul; Chandrakala, S; Ghosh, Kanjaksha; Shetty, Shrimati

2015-05-01

Thrombosis is rarely reported in cases of afibrinogenemia and is generally associated with thrombophilia or replacement therapy. Often, it is difficult to predict whether the patients will bleed or whether they are exposed to the risk of thrombosis. We report a patient with afibrinogenemia who presented with complete thrombosis of right hepatic, portal, and splenic veins and who described a lifelong history of bleeding. Direct sequencing of the three fibrinogen genes was performed to identify the mutation. DNA sequencing showed the presence of a homozygous for G8017A substitution in exon 8 of the fibrinogen β-chain gene, resulting in a G434D missense mutation (Fibrinogen Mumbai). Presence of both bleeding and thrombotic manifestations in a patient with afibrinogenemia in the presence of other associated risk factors warrants a very careful individualized approach in the management of patients with afibrinogenemia. Copyright© by the American Society for Clinical Pathology.

Phase transitions during compression and decompression of clots from platelet-poor plasma, platelet-rich plasma and whole blood.

Science.gov (United States)

Liang, Xiaojun; Chernysh, Irina; Purohit, Prashant K; Weisel, John W

2017-09-15

Blood clots are required to stem bleeding and are subject to a variety of stresses, but they can also block blood vessels and cause heart attacks and ischemic strokes. We measured the compressive response of human platelet-poor plasma (PPP) clots, platelet-rich plasma (PRP) clots and whole blood clots and correlated these measurements with confocal and scanning electron microscopy to track changes in clot structure. Stress-strain curves revealed four characteristic regions, for compression-decompression: (1) linear elastic region; (2) upper plateau or softening region; (3) non-linear elastic region or re-stretching of the network; (4) lower plateau in which dissociation of some newly made connections occurs. Our experiments revealed that compression proceeds by the passage of a phase boundary through the clot separating rarefied and densified phases. This observation motivates a model of fibrin mechanics based on the continuum theory of phase transitions, which accounts for the pre-stress caused by platelets, the adhesion of fibrin fibers in the densified phase, the compression of red blood cells (RBCs), and the pumping of liquids through the clot during compression/decompression. Our experiments and theory provide insights into the mechanical behavior of blood clots that could have implications clinically and in the design of fibrin-based biomaterials. The objective of this paper is to measure and mathematically model the compression behavior of various human blood clots. We show by a combination of confocal and scanning electron microscopy that compression proceeds by the passage of a front through the sample that separates a densified region of the clot from a rarefied region, and that the compression/decompression response is reversible with hysteresis. These observations form the basis of a model for the compression response of clots based on the continuum theory of phase transitions. Our studies may reveal how clot rheology under large compression in vivo due

Study of albumin and fibrinogen membranes formed by interfacial crosslinking using microfluidic flow

Energy Technology Data Exchange (ETDEWEB)

Chang Hong; Khan, Rachel; Rong, Zimei; Vadgama, Pankaj [IRC in Biomedical Materials, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); Sapelkin, Andrei, E-mail: p.vadgama@qmul.ac.u [Department of Physics, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom)

2010-09-15

Microfluidics enables scale reduction in sample volume with obvious benefits for reagent conservation. In contrast to conventional macro-scale flow, microfluidics also offers unprecedented control over flow dynamics. In particular, laminar flow is readily achieved, allowing for new analytical and synthetic strategies. Here, two parallel flows of buffer and xylene were used to create a stable liquid-liquid interface within linear micro-channels. These, respectively, carried protein (albumin or fibrinogen) and an acyl chloride to effect protein crosslinking. This created robust, micro-membranes at the interface that bisected the fluid channel. Membrane formation was self-limiting, with fibrinogen membranes showing greater solute permeability than albumin, based on dye transport (Ponceau S, Meldola Blue). The crosslinker isophthaloyl dichloride led to thinner, less permeable membranes than terephthaloyl chloride. Larger surface area membranes formed at a static liquid-liquid interface served as a more physically accessible model and allowed precise electrochemical determination of acetaminophen, catechol and peroxide diffusion coefficients, which confirmed the greater fibrinogen permeability. Scanning electron microscopy (SEM) of the membranes also indicated a higher population of discrete nanopores at the fibrinogen surface. A crosslinking pH had a strong effect on overall permeability. Adhesion of B50 neuronal cells was demonstrated, and it is proposed that the membranes could facilitate cell growth through bidirectional nutrient supply in a micrbioreactor format.

Familial hypofibrinogenaemia associated with heterozygous substitution of a conserved arginine residue; Bbeta255 Arg-->His (Fibrinogen Merivale).

Science.gov (United States)

Maghzal, Ghassan J; Brennan, Stephen O; Fellowes, Andrew P; Spearing, Ruth; George, Peter M

2003-02-21

Sequencing of all three fibrinogen genes from an individual with hypofibrinogenaemia led to the identification of two new point mutations in the Bbeta gene. Family studies showed the mutations Bbeta255 Arg-->His (Fibrinogen Merivale) and Bbeta148 Lys-->Asn (Fibrinogen Merivale II) were on different alleles and that only the Bbeta255 Arg-->His mutation segregated with hypofibrinogenaemia. Three simple heterozygotes for this mutation had mean fibrinogen concentrations of 1.4 mg/ml, while heterozygotes for the Bbeta148 Lys-->Asn mutation had normal fibrinogen concentrations. ESI MS analysis of endoproteinase Asp-N digests of Bbeta chains showed that the Bbeta255 Arg-->His substitution was not expressed in plasma, confirming it as the cause of the hypofibrinogenaemia. The Bbeta148 Lys-->Asn chains, on the other hand, were equally expressed with wild-type Bbeta chains in simple heterozygotes. Genotype analysis failed to detect either substitution in 182 healthy controls. Arg(255) is located in the first strand of the five-stranded sheet that forms the main feature of the betaD domain and appears to form an essential H bond with Gly(414). Both the Arg and Gly are absolutely conserved, not only in all known Bbeta chains, but also in all homologous alphaE and gamma chains and in all fibrinogen-related proteins. Protein instability from loss of this contact could easily explain the association of this mutation with hypofibrinogenaemia.

7 CFR 58.436 - Rennet, pepsin, other milk clotting enzymes and flavor enzymes.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Rennet, pepsin, other milk clotting enzymes and flavor enzymes. 58.436 Section 58.436 Agriculture Regulations of the Department of Agriculture (Continued... clotting enzymes and flavor enzymes. Enzyme preparations used in the manufacture of cheese shall be safe...

Iodine-labelling of albumin and fibrinogen and application in selecting implantable material-titanium oxide

International Nuclear Information System (INIS)

Liu Fangyan; Zhou Meiying; Zhang Feng

1998-01-01

Human serum albumin and fibrinogen were successfully labelled with 125 I. The labelled proteins were further applied to carry out a background study on the selection of the blood-compatible materials. The protein adsorption of four kinds of titanium oxide film was determined and compared. It was found that Sample B can adsorb more albumin and less fibrinogen than other three samples and hold the adsorbed albumin most stably

Prognostic implications of plasma fibrinogen and serum C- reactive ...

African Journals Online (AJOL)

Key words: Plasma fibrinogen, serum C-reactive protein, biomarker, non-small cell lung cancer. Tropical Journal of Pharmaceutical Research ... demonstrated in colorectal [11], cervical, oesophageal [12], and pancreatic cancers .... demographic and clinical characteristic features of the patients involved are shown in Table ...

Fibrinogen Vicenza and Genova II: two new cases of congenital dysfibrinogenemia with isolated defect of fibrin monomer polymerization and inhibitory activity on normal coagulation.

Science.gov (United States)

Rodeghiero, F; Castaman, G C; Dal Belin Peruffo, A; Dini, E; Galletti, A; Barone, E; Gastaldi, G

1987-06-03

Two new cases of congenital dysfibrinogenemia are presented in which defective fibrin monomer polymerization and inhibitory activity on normal coagulation were observed. They have been tentatively called fibrinogen Vicenza and Genova II. The first was discovered in a family with mild bleeding diathesis, the second in an asymptomatic family. In almost all reported cases of fibrinogens with defective fibrin monomer polymerization, additional functional or structural defects have been detected. In our cases, on the contrary, detailed investigations failed to show any other abnormality. Fibrinogen Genova II is apparently identical to fibrinogen Baltimore IV, whereas fibrinogen Vicenza is similar to fibrinogen Troyes and Genova I, but also exerts an evident inhibitory activity on normal coagulation and differs from fibrinogen Genova II and Baltimore IV showing a different kinetic pattern of fibrin monomer polymerization.

Effect of low frequency ultrasound on combined rt-PA and eptifibatide thrombolysis in human clots.

Science.gov (United States)

Meunier, Jason M; Holland, Christy K; Pancioli, Arthur M; Lindsell, Christopher J; Shaw, George J

2009-01-01

Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment. However, little is known of the efficacy of combined GP IIb-IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in-vitro human clot model. Blood was drawn from 15 subjects after IRB approval. Clots were made in 20 microL pipettes, and placed in a water tank for microscopic visualization during lytic treatment. Clots were exposed to control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA + Epf), with (+US) or without (-US) ultrasound for 30 minutes at 37 degrees C in human plasma. Clot lysis was measured over time, using a microscopic imaging technique. The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify lytic efficacy. LR values for (- US) treated clots were 0.8+/-0.1(control), 1.8+/-0.3 (Epf), 1.5+/-0.2 (rt-PA), and 1.3+/-0.4 (rt-PA + Epf) (% clot width/minute) respectively. In comparison, the (+ US) group exhibited LR values of 1.6+/-0.2 (control), 4.3+/-0.4 (Epf), 6.3+/-0.4 (rt-PA), and 4.6+/-0.6 (rt-PA + Epf). For (- US) treated clots, FCL was 6.0+/-0.8 (control), 9.2+/-2.5 (Epf), 15.6+/-1.7 (rt-PA), and 28.0+/-2.2% (rt-PA + Epf) respectively. FCL for (+ US) clots was 13.5+/-2.4 (control), 20.7+/-6.4 (Epf), 44.4+/-3.6 (rt-PA) and 30.3+/-3.6% (rt-PA + Epf) respectively. Although the addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that of combined

EVALUATION OF THE COMPUTED TOMOGRAPHIC "SENTINEL CLOT SIGN" TO IDENTIFY BLEEDING ABDOMINAL ORGANS IN DOGS WITH HEMOABDOMEN.

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Specchi, Swan; Auriemma, Edoardo; Morabito, Simona; Ferri, Filippo; Zini, Eric; Piola, Valentina; Pey, Pascaline; Rossi, Federica

2017-01-01

The CT "sentinel clot sign" has been defined as the highest attenuation hematoma adjacent to a bleeding organ in humans with hemoabdomen. The aims of this retrospective descriptive multicenter study were to describe CT findings in a sample of dogs with surgically or necropsy confirmed intra-abdominal bleeding and determine prevalence of the "sentinel clot sign" adjacent to the location of bleeding. Medical records between 2012 and 2014 were searched for dogs with hemoabdomen and in which the origin of the bleeding was confirmed either with surgery or necropsy. Retrieved CT images were reviewed for the presence and localization of the "sentinel clot sign," HU measurements of the "sentinel clot sign" and hemoabdomen, and presence of extravasation of contrast media within the abdominal cavity. Nineteen dogs were included. Three dogs were excluded due to the low amount of blood that did not allow the identification of a "sentinel clot sign." A "sentinel clot sign" was detected in the proximity of the confirmed bleeding organ in 14/16 (88%) of the patients. The mean HU of the "sentinel clot sign" was 56 (range: 43-70) while that of the hemoabdomen was 34 (range: 20-45). Active hemorrhage was identified as extravasation of contrast medium within the peritoneal cavity from the bleeding organ in three dogs. In conclusion, the CT "sentinel clot sign" may be helpful for identifying the source of bleeding in dogs with hemoabdomen. © 2016 American College of Veterinary Radiology.

The down-regulation of the mitogenic fibrinogen receptor (MFR) in serum-containing medium does not occur in defined medium.

Science.gov (United States)

Levesque, J P; Hatzfeld, A; Domart, I; Hatzfeld, J

1990-02-01

Normal human hemopoietic cells such as early bone marrow progenitors, or lymphoma-derived cell lines such as Raji or JM cells, possess a low-affinity receptor specific for fibrinogen. This receptor triggers a mitogenic effect. It differs from the glycoprotein IIb-IIIa which is involved in fibrinogen-induced platelet aggregation. We demonstrate here that this mitogenic fibrinogen receptor (MFR) can be internalized or reexpressed, depending on culture conditions. Internalization was temperature-dependent. At 37 degrees C in the presence of cycloheximide or actinomycin D, the half-life of cell surface MFRs was 2 h, independent of receptor occupancy. Binding of fibrinogen to the MFR resulted in a down-regulation which was fibrinogen dose-dependent. This occurred in serum-supplemented medium but not in defined medium supplemented with fatty acids. Reexpression of MFRs could be induced in 28 to 42 h by serum removal. The down-regulation of mitogenic receptors in plasma or serum could explain why normal cells do not proliferate in the peripheral blood.

111In-platelet and 125I-fibrinogen deposition in the lungs in experimental acute pancreatitis

International Nuclear Information System (INIS)

Goulbourne, I.A.; Watson, H.; Davies, G.C.

1987-01-01

An experimental model of acute pancreatitis in rats has been used to study intrapulmonary 125 I-fibrinogen and 111 In-platelet deposition. Pancreatitis caused a significant increase in wet lung weight compared to normal, and this could be abolished by heparin or aspirin pretreatment. 125 I-fibrinogen was deposited in the lungs of animals to a significantly greater degree than in controls (P less than 0.01). 125 I-fibrinogen deposition was reduced to control levels by pretreatment with aspirin or heparin (P less than 0.05). The uptake of radiolabeled platelets was greater in pancreatitis than in controls (P less than 0.001). Pancreatitis appears to be responsible for platelet entrapment in the lungs. Platelet uptake was reduced by heparin treatment but unaffected by aspirin therapy

Use of labelled fibrinogen for the detection of phlebitis

International Nuclear Information System (INIS)

Serradimigni, A.; Mathieu, P.; Leonetti, J.; Sacerdote, P.; Bory, M.; Djiane, P.; Egre, A.

The value of 125 I-labelled fibrinogen as a diagnostic tool in the detection of deep vein thrombosis is discussed. The results are compared to those obtained with phlebography and with the clinical symptomatology. The technical problems are described: examination method and interpretation [fr

Prognostic implications of plasma fibrinogen and serum C- reactive ...

African Journals Online (AJOL)

reactive protein levels in non-small cell lung cancer resection and ... Abstract. Purpose: To investigate the prognostic implications of plasma fibrinogen and serum C-reactive protein ... The possibility of complete resection and associated findings are reported. Results: ... operable using pre-operative chemotherapy and/or ...

Plasma fibrinogen in relation to serum insulin, smoking habits and adipose tissue fatty acids in healthy men

NARCIS (Netherlands)

Cigolini, M; Targher, G; de Sandre, G; Muggeo, M; Seidell, J C

Recent prospective studies have reported an independent association between fibrinogen plasma levels and risk of cardiovascular events. Aim of this study was to investigate the relationships between fibrinogen level and conventional cardiovascular risk factors in a random sample of 38 year-old

Identification and characterization of the fibrinogen-like domain of fibrinogen-related proteins in the mosquito, Anopheles gambiae, and the fruitfly, Drosophila melanogaster, genomes

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Zhao Qin

2005-09-01

Full Text Available Abstract Background The fibrinogen-like (FBG domain, which consists of approximately 200 amino acid residues, has high sequence similarity to the C-terminal halves of fibrinogen β and γ chains. Fibrinogen-related proteins (FREPs, which contain FBG domains in their C-terminal region, are found universally in vertebrates and invertebrates. In invertebrates, FREPs are involved in immune responses and other aspects of physiology. To understand the complexity of this family in insects, we analyzed FREPs in the mosquito genome and made comparisons to FREPs in the fruitfly genome. Results By using the genome data of the mosquito, Anopheles gambiae, 53 FREPs were identified, whereas only 20 members were found in the Drosophila melanogaster genome. Using sequence profile analysis, we found that FBG domains have high sequence similarity and are highly conserved throughout the FBG domain region. By secondary structure analysis and comparison, the FBG domains of FREPs are predicted to function in recognition of carbohydrates and their derivatives on the surface of microorganisms in innate immunity. Conclusion Detailed sequence and structural analysis discloses that the FREP family contains FBG domains that have high sequence similarity in the A. gambiae genome. Expansion of the FREP family in mosquitoes during evolutionary history is mainly accounted for by a major expansion of the FBG domain architecture. The characterization of the FBG domains in the FREP family is likely to aid in the experimental analysis of the ability of mosquitoes to recognize parasites in innate immunity and physiologies associated with blood feeding.

The application of large amplitude oscillatory stress in a study of fully formed fibrin clots

Science.gov (United States)

Lamer, T. F.; Thomas, B. R.; Curtis, D. J.; Badiei, N.; Williams, P. R.; Hawkins, K.

2017-12-01

The suitability of controlled stress large amplitude oscillatory shear (LAOStress) for the characterisation of the nonlinear viscoelastic properties of fully formed fibrin clots is investigated. Capturing the rich nonlinear viscoelastic behaviour of the fibrin network is important for understanding the structural behaviour of clots formed in blood vessels which are exposed to a wide range of shear stresses. We report, for the first time, that artefacts due to ringing exist in both the sample stress and strain waveforms of a LAOStress measurement which will lead to errors in the calculation of nonlinear viscoelastic properties. The process of smoothing the waveforms eliminates these artefacts whilst retaining essential rheological information. Furthermore, we demonstrate the potential of LAOStress for characterising the nonlinear viscoelastic properties of fibrin clots in response to incremental increases of applied stress up to the point of fracture. Alternating LAOStress and small amplitude oscillatory shear measurements provide detailed information of reversible and irreversible structural changes of the fibrin clot as a consequence of elevated levels of stress. We relate these findings to previous studies involving large scale deformations of fibrin clots. The LAOStress technique may provide useful information to help understand why some blood clots formed in vessels are stable (such as in deep vein thrombosis) and others break off (leading to a life threatening pulmonary embolism).

Platelet Counts in Insoluble Platelet-Rich Fibrin Clots: A Direct Method for Accurate Determination

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Yutaka Kitamura

2018-02-01

Full Text Available Platelet-rich fibrin (PRF clots have been used in regenerative dentistry most often, with the assumption that growth factor levels are concentrated in proportion to the platelet concentration. Platelet counts in PRF are generally determined indirectly by platelet counting in other liquid fractions. This study shows a method for direct estimation of platelet counts in PRF. To validate this method by determination of the recovery rate, whole-blood samples were obtained with an anticoagulant from healthy donors, and platelet-rich plasma (PRP fractions were clotted with CaCl2 by centrifugation and digested with tissue-plasminogen activator. Platelet counts were estimated before clotting and after digestion using an automatic hemocytometer. The method was then tested on PRF clots. The quality of platelets was examined by scanning electron microscopy and flow cytometry. In PRP-derived fibrin matrices, the recovery rate of platelets and white blood cells was 91.6 and 74.6%, respectively, after 24 h of digestion. In PRF clots associated with small and large red thrombi, platelet counts were 92.6 and 67.2% of the respective total platelet counts. These findings suggest that our direct method is sufficient for estimating the number of platelets trapped in an insoluble fibrin matrix and for determining that platelets are distributed in PRF clots and red thrombi roughly in proportion to their individual volumes. Therefore, we propose this direct digestion method for more accurate estimation of platelet counts in most types of platelet-enriched fibrin matrix.

High risk of coagulopathy among Type-2 Diabetes Mellitus clients at ...

African Journals Online (AJOL)

Background: Persistent hyperglycaemia in diabetes mellitus causes coagulopathies due to glycation of haemoglobin, prothrombin, fibrinogen and other proteins involved in the clotting mechanism. Shortened activated partial thromboplastin time (APTT) and prothrombin time (PT) reflect hypercoagulable state, which is ...

Pre-analytical variation in glucose concentration due to atmospheric temperature and clot in blood specimens

International Nuclear Information System (INIS)

Butt, T.; Masud, K.; Khan, J.A.; Bhatti, M.S.

2016-01-01

Objective: To determine the effect of temperature and contact of clot with serum on laboratory results of glucose concentration in blood. Study Design: Quasi-experimental study. Place and Duration of Study: December 2014 to August 2015 at the laboratory of Shoaib Hospital, Fateh Jang, Attock Pakistan. Material and Methods: Samples were collected for estimation of blood glucose (Random) concentration from patients reporting to the hospital. Blood specimens (n=94) of such volunteers were analyzed for glucose level. Each sample was put up in five tubes. When the blood clotted the serum from tube-1 was analyzed for glucose level within 30 minutes. In tube-2 and tube-3 serum was kept for 24 hours at room temperature and refrigerator temperature respectively before glucose estimation. In tube-4 and tube-5 serum was not separated from clot and kept at room temperature and refrigerator temperature respectively before glucose estimation. The value of tube 1 was taken as reference value for comparison with other parts of the specimen. The equipment used for blood glucose level estimation was semi auto chemistry analyzer (Rayto, China). The kit used for analysis was Glucose - Liquizyme (Germany). Results: The difference between the mean reference value (tube-1) and refrigerated serum without clot (tube-3) was 4.63 mg/100 ml while that of unrefrigerated portion (tube-2) had a difference of 10.68 mg/100 ml. The mean of unrefrigerated (tube-4) and refrigerated (tube-5) portions of serum kept with the clot had difference of 42.05 mg/100 ml and 25.84 mg/100 ml respectively. The fall in the blood glucose level in all (n=94) the samples in the tube number 3 (serum separated and kept at refrigerated temperature) was 4.63 mg/100 ml +- 3.68 (Mean +- SD) and it ranged from 0 to 20 mg/100 ml whereas fall was maximum in the tube number 4 (serum with clotted blood and kept at room temperature) was 42.04 mg/100 ml +- 10.61 (Mean +- SD) and it ranged from 13 to 82 mg/100 ml. The sample in

Identification and characterization of milk-clotting proteases ...

African Journals Online (AJOL)

SAM

2014-03-12

Mar 12, 2014 ... Biochem. Soc. Trans. 10:285. Hashem AM (2000). Purification and properities of a milk-clotting enzyme produced by Penicillium oxalicum. J. Bioresour. Technol. 75:219-222. Laemmli UK (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227: 680-685.

Thrombin generation assay as a possible tool for assessment of reduced activity of clotting factors induced by antiphospholipid antibodies and in-vitro evaluation of treatment options.

Science.gov (United States)

Livnat, Tami; Zivelin, Ariella; Tamarin, Ilia; Guetta, Victor; Salomon, Ophira

2009-12-01

Bleeding is a rare manifestation of antiphospholipid syndrome, unless associated with reduced clotting factors or severe thrombocytopenia. Accurate assessment of the autoantibodies in plasma is very important since the autoantibodies can lead to bleeding or thrombosis. The objective of the present study was to define the inhibitors causing reduced clotting activity in a patient with antiphospholipids antibodies and to assess the potential of thrombin generation assay to assist in establishment of optimal treatment in case of major bleeding. Levels of clotting factors as well as inhibitors to factors II, V, VII, VIII, IX, X and XI were defined. For detection of inhibitors to prothrombin crossed immunoelectrophoresis was used. IgG was purified by commercial protein A column. Thrombin generation was measured using a fluorometric assay in platelet-poor and platelet-rich plasma. Inhibitors toward the activity of factors V, VII, VIII, IX, X and XI were defined and also an inhibitor to prothrombin antigen. No thrombin generation was induced in the patient's plasma by recalcification even in the presence of recombinant factor VIIa or factor VIII inhibitor bypassing activity. In contrast, addition of platelets from either donor or patient or synthetic phospholipids normalized the thrombin generation. The thrombin generation model showed that the addition of platelets and no recombinant factor VIIa or factor VIII inhibitor bypassing activity would correct thrombin generation in vitro. On this basis, platelet concentrates were administered to a patient with bleeding caused by lupus anticoagulant and low clotting factors activity.

Interaction of fibrinogen and albumin with titanium dioxide nanoparticles of different crystalline phases

International Nuclear Information System (INIS)

Marucco, Arianna; Fenoglio, Ivana; Turci, Francesco; Fubini, Bice

2013-01-01

TiO 2 nanoparticles (NPs) are contained in different kinds of industrial products including paints, self-cleaning glasses, sunscreens. TiO 2 is also employed in photocatalysis and it has been proposed for waste water treatment. Micrometric TiO 2 is generally considered a safe material, while there is concern on the possible health effects of nanometric titania. Due to their small size NPs may migrate within the human body possibly entering in the blood stream. Therefore studies on the interaction of NPs with plasma proteins are needed. In fact, the interaction with proteins is believed to ultimately influences the NPs biological fate. Fibrinogen and albumin are two of the most abundant plasma proteins. They are involved in several important physiological functions. Furthermore, fibrinogen is known to trigger platelet adhesion and inflammation. For these reasons the study of the interaction between these protein and nanoparticles is an important step toward the understanding of the behavior of NPs in the body. In this study we investigated the interaction of albumin and fibrinogen with TiO 2 nanoparticles of different crystal phases (rutile and anatase) using an integrated set of techniques. The amount of adsorbed fibrinogen and albumin for each TiO 2 surface was investigated by using the bicinchoninic acid assay (BCA). The variation of the surface charge of the NP-protein conjugates respect to the naked NPs was used to indirectly estimate both surface coverage and reversibility of the adsorption upon dilution. Surface charge was monitored by measuring the ζ potential with a conventional electrophoretic light scattering (ELS) system. The extent of protein deformation was evaluated by Raman Spectroscopy. We found that both proteins adsorb irreversibly against electrostatic repulsion, likely undergoing conformational changes or selective orientation upon adsorption. The size of primary particles and the particles aggregation rather than the crystal phase modulate the

Trimeric autotransporter DsrA is a major mediator of fibrinogen binding in Haemophilus ducreyi.

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Fusco, William G; Elkins, Christopher; Leduc, Isabelle

2013-12-01

Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. In both natural and experimental chancroid, H. ducreyi colocalizes with fibrin at the base of the ulcer. Fibrin is obtained by cleavage of the serum glycoprotein fibrinogen (Fg) by thrombin to initiate formation of the blood clot. Fg binding proteins are critical virulence factors in medically important Gram-positive bacteria. H. ducreyi has previously been shown to bind Fg in an agglutination assay, and the H. ducreyi Fg binding protein FgbA was identified in ligand blotting with denatured proteins. To better characterize the interaction of H. ducreyi with Fg, we examined Fg binding to intact, viable H. ducreyi bacteria and identified a novel Fg binding protein. H. ducreyi bound unlabeled Fg in a dose-dependent manner, as measured by two different methods. In ligand blotting with total denatured cellular proteins, digoxigenin (DIG)-Fg bound only two H. ducreyi proteins, the trimeric autotransporter DsrA and the lectin DltA; however, only the isogenic dsrA mutant had significantly less cell-associated Fg than parental strains in Fg binding assays with intact bacteria. Furthermore, expression of DsrA, but not DltA or an empty vector, rendered the non-Fg-binding H. influenzae strain Rd capable of binding Fg. A 13-amino-acid sequence in the C-terminal section of the passenger domain of DsrA appears to be involved in Fg binding by H. ducreyi. Taken together, these data suggest that the trimeric autotransporter DsrA is a major determinant of Fg binding at the surface of H. ducreyi.

Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population.

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Wang, Zongkui; Dou, Miaomiao; Du, Xi; Ma, Li; Sun, Pan; Cao, Haijun; Ye, Shengliang; Jiang, Peng; Liu, Fengjuan; Lin, Fangzhao; Zhang, Rong; Li, Changqing

2017-01-01

ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII) and von Willebrand factor (VWF). Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg), and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13). We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag), collagen-binding activity (VWF:CBA), and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof) was performed by agglutination of platelets with ristocetin. Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof) were significantly higher in non-O than in O type subjects ( p  blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups.

Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban.

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Janion-Sadowska, Agnieszka; Natorska, Joanna; Siudut, Jakub; Ząbczyk, Michal; Stanisz, Andrzej; Undas, Anetta

2017-08-30

We sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (K s ) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2-6 hours (h) after and 20-25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (K s -12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for K s and CLT before rivaroxaban intake. At 2-6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (K s +38 %, and +37 %, CLT -25 % and -25 %, CLT-TAFI -20 % and -24 %, respectively, all pCLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20-25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.

Clot formation and lysis in platelet rich plasma of healthy donors and patients with resistant hypertension

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I. I. Patalakh

2018-04-01

Full Text Available Hemostatic balance in blood is affected by numerous factors, including coagulation and fibrinolytic proteins, the wide spectrum of their inhibitors, and blood cells. Since platelets can participate in contradictory processes, they significantly complicate the whole picture. Therefore, nowadays the development of global assays of hemostasis, which can reflect the physiological process of hemostasis and can be used for point-of-care diagnosis of thrombosis, is crucial. This paper outlines a new approach we used to analyze the capabilities of clot waveform analysis tools to distinguish the response of platelet-rich plasma from healthy donors and patients with arterial hypertension caused by stimulation of coagulation and lysis (with exogenous thrombin and recombinant tissue-type plasminogen activator, respectively. In donor plasma, when the clot degradation was accompanied by 40 IU/ml of recombinant tissue-type plasminogen activator, platelets potentiated fibrinolysis more than coagulation, which ultimately shifts the overall balance to a profibrinolytic state. At the same time, for patients with hypertension, platelets, embedded in clot obtained from platelet-rich plasma, showed a weaker ability to stimulate fibrinolysis. The obtained data gives the evidence that platelets can act not only as procoagulants but also as profibrinolytics. By simultaneously amplifying coagulation and fibrinolysis, making their rates comparable, platelets would control plasma procoagulant activity, thereby regulating local hemostatic balance, the size and lifetime of the clot. Moreover, clot waveform analysis may be used to distinguish the effects of platelet-rich plasma on clotting or lysis of fibrin clots in healthy donors and patients with essential hypertension.

Cushing`s disease: Fibrinogen and D-dimer levels fail to normalize despite early postoperative remission - a prospective, controlled study.

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Witek, Przemysław; Zieliński, Grzegorz; Szamotulska, Katarzyna; Witek, Joanna; Kamiński, Grzegorz

2016-01-01

Effective transsphenoidal surgery (TSS) for Cushing`s disease (CD) normalizes cortisol levels and reduces complications of hypercortisolism. However, there is evidence of increased cardiovascular morbidity even after successful surgery. A prospective, controlled study on the dynamics of fibrinogen and D-dimer levels with a six-month follow-up after an effective TSS for CD. Forty patients with CD and forty healthy age- and sex-matched subjects were included. We assessed ACTH, urinary and serum cortisol, and fibrinogen and D-dimer levels before TSS and during follow-up. Baseline BMI (P < 0.001), fibrinogen (P = 0.002), and D-dimer (P = 0.001) levels in CD patients were significantly higher than those in healthy controls. High fibrinogen levels in the CD group were independent of BMI, and were positively associated with hsCRP (rS = 0.61, P < 0.001) and arterial hypertension (P = 0.029). After the six-month follow-up we confirmed a sustained difference between the remission group and controls in fibrinogen and D-dimer levels (P = 0.001 and P = 0.017, respectively). Despite early biochemical remission of CD the levels of fibrinogen and D-dimer failed to decrease. This probably contributes to the high risk of thrombotic events and indicates the need for a close follow-up for signs of thromboembolic and cardiovascular complications in patients with early CD remission. (Endokrynol Pol 2016; 67 (3): 283-291).

Identification and characterization of milk-clotting proteases ...

African Journals Online (AJOL)

Two strains of fungi were isolated and identified as Aspergillus tamarii and Penicillium pinophilum which showed good enzymatic activity on casein, 1933.33U and 1822, 21U, respectively. The search for milk clotting enzymes by fermentation at acid pH on culture medium containing whey and, after purification by molecular ...

Evaluation of the Characteristics of the Adsorption of Fibrinogen ...

African Journals Online (AJOL)

... with calcium and magnesium ions increased the amount of fibrinogen adsorbed onto it as against treatment with potassium ion (a monovalent ion). Electrostatic attraction on the surface of the treated HAP and hydrogen are responsible for the adsorption. The results are useful in fabricating bone and teeth implants that are ...

External quality assurance of fibrinogen assays using normal plasma: results of the 2008 College of American Pathologists proficiency testing program in coagulation.

Science.gov (United States)

Cunningham, Mark T; Olson, John D; Chandler, Wayne L; Van Cott, Elizabeth M; Eby, Charles S; Teruya, Jun; Hollensead, Sandra C; Adcock, Dorothy M; Allison, Paul M; Kottke-Marchant, Kandice K; Smith, Marc D

2012-07-01

Proper diagnosis and therapy of fibrinogen deficiency requires high-quality fibrinogen assays. To assess the interlaboratory bias, precision, and grading of fibrinogen assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in coagulation. Two identical vials of normal plasma were sent to more than 3500 laboratories. Participants measured fibrinogen levels using local methods. Fifty different fibrinogen methods were evaluated. All-method bias was 8.3% (range of method-specific biases, 0.0%-27.0%) and all-method coefficient of variation was 7.7% (range of method-specific coefficients of variation, 0.7%-25.8%). After controlling for reagent/instrument type, mean fibrinogen levels were 11.6% higher for prothrombin time-based reagents compared to Clauss (P graded as pass or fail using a target range of ±20% from the method mean (total pass rate, 98.8%). Total fail rate was 3.0-fold lower for mechanical instruments compared to photo-optical (0.5% versus 1.5%, P  =  .001). Nonetheless many photo-optical methods had very high precision and very low fail rates. Fibrinogen assays showed highly variable methodology and performance characteristics. Bias, precision, and grading were affected by the type of reagent or instrument used.

Binding of glycoprotein Srr1 of Streptococcus agalactiae to fibrinogen promotes attachment to brain endothelium and the development of meningitis.

Directory of Open Access Journals (Sweden)

Ho Seong Seo

Full Text Available The serine-rich repeat glycoprotein Srr1 of Streptococcus agalactiae (GBS is thought to be an important adhesin for the pathogenesis of meningitis. Although expression of Srr1 is associated with increased binding to human brain microvascular endothelial cells (hBMEC, the molecular basis for this interaction is not well defined. We now demonstrate that Srr1 contributes to GBS attachment to hBMEC via the direct interaction of its binding region (BR with human fibrinogen. When assessed by Far Western blotting, Srr1 was the only protein in GBS extracts that bound fibrinogen. Studies using recombinant Srr1-BR and purified fibrinogen in vitro confirmed a direct protein-protein interaction. Srr1-BR binding was localized to amino acids 283-410 of the fibrinogen Aα chain. Structural predictions indicated that the conformation of Srr1-BR is likely to resemble that of SdrG and other related staphylococcal proteins that bind to fibrinogen through a "dock, lock, and latch" mechanism (DLL. Deletion of the predicted latch domain of Srr1-BR abolished the interaction of the BR with fibrinogen. In addition, a mutant GBS strain lacking the latch domain exhibited reduced binding to hBMEC, and was significantly attenuated in an in vivo model of meningitis. These results indicate that Srr1 can bind fibrinogen directly likely through a DLL mechanism, which has not been described for other streptococcal adhesins. This interaction was important for the pathogenesis of GBS central nervous system invasion and subsequent disease progression.

Association of β-fibrinogen promoter gene polymorphism (−148C/T), hyperfibrinogenemia and ischemic stroke in young adult patients

OpenAIRE

Imran, Imran; Lamsudin, Rusdi; Idjradinata, Ponpon; Achmad, Tri Hanggono; Maskoen, Amelani; Wibowo, Samekto; Harapan, Harapan

2015-01-01

Background: Single nucleotide polymorphism (SNP) −148C/T which is located in β-fibrinogen gene (FGB) promoter has correlation with fibrinogen levels; however, the association of SNP −148C/T and ischemic stroke in young adult patients is contradictory. Aim: To determine the association of SNP −148C/T in FGB promoter with plasma fibrinogen levels and ischemic stroke in young adults. Subjects and methods: In this case-control study, SNP −148C/T among 107 ischemic stroke patients and 94 con...

Clinical study of 67Ga labelled human fibrinogen for detection of thrombi

International Nuclear Information System (INIS)

Katsuura, Yutaka

1988-01-01

The usefulness to detect thrombi by Ga-67 labelled human fibrinogen (Ga-F) was investigated in 22 patients with various diseases who had thrombi or were suspected to have thrombi. In 5 of 9 patients with aortic aneurysm, images of thrombi were obtained by Ga-F. In 1 of 2 patients with myocardial infarction, left ventricular thrombi were detected. In 1 of 5 patients with mitral stenosis, left atrial thrombus was recognized. Of these patients, in 2 patients who have no evidence of thrombi confirmed at another methods, thrombi were detected by Ga-F. In 6 out of 8 patients with thrombi confirmed at echocardiography or computed tomography, thrombi were detected by Ga-F. In these patients, 2 patients with negative images were treated by antithromboticdrugs. In 7 patients, both Ga-F and In-111 labelled platelets (In-P) were comparatively studied simultaniuosly. No difference in the sensitivity of the detection of thrombi were recognized between two groups. The images of thrombi by both Ga-F and In-P were detected positively in 3 patients and were not found in 4 patients. However, the handling of Ga-F method was much easier than that of In-P method. In conclusion, Ga-F could be useful for the detection of thrombi in various thrombotic diseases. Fibrinogen kinetic studies using Ga-F were performed. Fibrinogen turnover rates (FTR) in the cases with positive image by Ga-F were higher than those in the cases with Ga-F negative image. (positive : 24.3 ± 9.5 mg/kg/day, negative : 19.7 ± 8.5 mg/kg/day) The results of kinetic studies by Ga-F were similar to those by 1 - 125 fibrinogen. (author)

Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time.

Science.gov (United States)

Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

2015-12-01

Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro.

Honey Bee Venom (Apis mellifera Contains Anticoagulation Factors and Increases the Blood-clotting Time

Directory of Open Access Journals (Sweden)

Hossein Zolfagharian

2015-12-01

Full Text Available Objectives: Bee venom (BV is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50, and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Blood samples were obtained from 10 rabbits, and the prothrombin time (PT and the partial thromboplastin time (PTT tests were conducted. The approximate lethal dose (LD values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa, respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2 and melittin, and that can increase the blood clotting times in vitro.

Fibrinogen species as resolved by HPLC-SAXS data processing within the UltraScan Solution Modeler (US-SOMO) enhanced SAS module.

Science.gov (United States)

Brookes, Emre; Pérez, Javier; Cardinali, Barbara; Profumo, Aldo; Vachette, Patrice; Rocco, Mattia

2013-12-01

Fibrinogen is a large heterogeneous aggregation/degradation-prone protein playing a central role in blood coagulation and associated pathologies, whose structure is not completely resolved. When a high-molecular-weight fraction was analyzed by size-exclusion high-performance liquid chromatography/small-angle X-ray scattering (HPLC-SAXS), several composite peaks were apparent and because of the stickiness of fibrinogen the analysis was complicated by severe capillary fouling. Novel SAS analysis tools developed as a part of the UltraScan Solution Modeler ( US-SOMO ; http://somo.uthscsa.edu/), an open-source suite of utilities with advanced graphical user interfaces whose initial goal was the hydrodynamic modeling of biomacromolecules, were implemented and applied to this problem. They include the correction of baseline drift due to the accumulation of material on the SAXS capillary walls, and the Gaussian decomposition of non-baseline-resolved HPLC-SAXS elution peaks. It was thus possible to resolve at least two species co-eluting under the fibrinogen main monomer peak, probably resulting from in-column degradation, and two others under an oligomers peak. The overall and cross-sectional radii of gyration, molecular mass and mass/length ratio of all species were determined using the manual or semi-automated procedures available within the US-SOMO SAS module. Differences between monomeric species and linear and sideways oligomers were thus identified and rationalized. This new US-SOMO version additionally contains several computational and graphical tools, implementing functionalities such as the mapping of residues contributing to particular regions of P ( r ), and an advanced module for the comparison of primary I ( q ) versus q data with model curves computed from atomic level structures or bead models. It should be of great help in multi-resolution studies involving hydrodynamics, solution scattering and crystallographic/NMR data.

Prothrombin Time, Activated Partial Thromboplastin Time, Fibrinogen, dan D-dimer Sebagai Prediktor Decompensated Disseminated Intravascular Coagulation Sisseminated pada Sepsis

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Fenny

2011-03-01

Full Text Available Sepsis is a systemic response to infection especially in pneumonia case. Sepsis can cause complications such as disseminated intravascular coagulation (DIC which can be divided into compensated and decompensated DIC. The purpose of this study was to assess whether the value of prothrombin time (PT, activated partial thromboplastin time (aPTT, fibrinogen, and D-dimer levels can be used as predictors of decompensated DIC in sepsis patients. This study was conducted at the Laboratory of Clinical Pathology Rumah Sakit Hasan Sadikin Bandung since September 2008 to June 2010. Subjects were patients with sepsis caused by pneumonia. PT and aPTT values, fibrinogen, and D-dimer levels was recorded from all sepsis patients then patients were observed until diagnosed decompensated or non-decompensated DIC, then the value of PT, aPTT, fibrinogen and D-dimer levels in the group of decompensated DIC and non-decompensated DIC were analysed. This study used cohort design. Subjects were 39 sepsis patients (58% with outcome decompensated DIC and 28 sepsis patients (42% with outcome non-decompensated DIC. From the hemostasis parameter test out, it was found that PT, aPTT, and fibrinogen were the predictor of decompensated DIC in patients with sepsis with relative risk 240.500, 7.157, and 6.421; respectively. Conclusions, prothrombin time, aPTT, fibrinogen are the test to know coagulation activation. Hemostasis parameter to predict decompensated DIC in sepsis patients are the shorten PT, aPTT, and the increased fibrinogen

High-Quality and -Quantity DNA Extraction from Frozen Archival Blood Clots for Genotyping of Single-Nucleotide Polymorphisms

DEFF Research Database (Denmark)

Bank, Steffen; Nexø, Bjørn Andersen; Andersen, Vibeke

2013-01-01

the efficiency of commercial purification kits for extracting DNA from long-term frozen clotted blood. Methods: Serum tubes with clotted blood were stored at −20°C for 1 to 2.5 years before DNA extraction. DNA was extracted from 10 blood clot samples using PureGene (Qiagen) with and without glycogen, the QIAamp...... with a median of 0.65 μg (range 0.5–2.6 μg) pr 300 μL total blood. Conclusion: The yield obtained by the different commercial kits varied considerably. Our work demonstrates that high-quality and -quantity DNA can be extracted with the Maxwell 16 Blood purification kit (Promega) from cryopreserved blood clots...

Preparation and quality control of fibrinogen 99mTc

International Nuclear Information System (INIS)

Noto, M.G.; Rabiller, Graciela; Garrie Faget, Claudio; Fisman, Carlos; Manzini, Alberto

1987-01-01

A method of fibrinogen preparation is presented in order to label it with 99m Tc employing Sn as reducing agent in alkaline medium. Purity controls by chromatography, coagulation in rabbits and biodistribution in rats were performed. It is concluded that optimal time incubation is between 22 and 23 hs. (M.E.L.) [es

Makers of clotting medicine not entitled to liability shield.

Science.gov (United States)

1996-02-23

The Indiana Court of Appeals, Second District, reversed a ruling that protected the manufacturer of a hemophilia blood clotting medicine from legal liability. A boy with hemophilia, known in court records as J.K.B. Jr., contracted HIV from the blood clotting medicine, Factor VIII. His parents sued four pharmaceutical companies, Armour Pharmaceutical Company, Cutter Laboratories, Baxter Healthcare Corporation, and Alpha Therapeutics Corporation, alleging that their products caused J.K.B. Jr.'s death. The companies convinced a Superior Court judge that they were protected under the Indiana Blood Shield Statute. The appeals court ruled that pharmaceutical companies are not included in the Blood Shield Statute. The statute was originally established to protect state-approved blood banks, hospitals, and blood storage facilities because they provide a vital public service.

Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study

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Larsen Claus F

2011-10-01

Full Text Available Abstract Background Severe injury induces an acute coagulopathy associated with increased mortality. This study compared the Thrombelastography (TEG and biomarker profiles upon admission in trauma patients. Methods Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry including standard coagulation tests, hematology, transfusions, Injury Severity Score (ISS and TEG were recorded. Retrospective analysis of thawed plasma/serum for biomarkers reflecting tissue injury (histone-complexed DNA fragments, sympathoadrenal activation (adrenaline, noradrenaline, coagulation activation/inhibition and fibrinolysis (sCD40L, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer, prothrombinfragment 1+2, plasmin/α2-antiplasmin complex, thrombin/antithrombin complex, tissue factor pathway inhibitor, antithrombin, von willebrand factor, factor XIII. Comparison of patients stratified according to ISS/TEG maximum clot strength. Linear regression analysis of variables associated with clot strength. Results Trauma patients had normal (86%, hypercoagulable (11% or hypocoagulable (1% TEG clot strength; one had primary hyperfibrinolysis. Hypercoagulable patients had higher age, fibrinogen and platelet count (all p 10 red blood cells the initial 24 h. Patients with normal or hypercoagulable TEG clot strength had comparable biomarker profiles, but the few patients with hypocoagulable TEG clot strength and/or hyperfibrinolysis had very different biomarker profiles. Increasing ISS was associated with higher levels of catecholamines, histone-complexed DNA fragments, sCD40L, activated protein C and D-dimer and reduced levels of non-activated protein C, antithrombin, fibrinogen and factor XIII (all p 26. In patients with ISS > 26, adrenaline and sCD40L were independently negatively associated with clot strength. Conclusions Trauma patients displayed

Quantitative Proteomic Approach Targeted to Fibrinogen β Chain in Tissue Gastric Carcinoma

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Ombretta Repetto

2018-03-01

Full Text Available Elevated plasma fibrinogen levels and tumor progression in patients with gastric cancer (GC have been largely reported. However, distinct fibrinogen chains and domains have different effects on coagulation, inflammation, and angiogenesis. The aim of this study was to characterize fibrinogen β chain (FGB in GC tissues. Retrospectively we analyzed the data of matched pairs of normal (N and malignant tissues (T of 28 consecutive patients with GC at diagnosis by combining one- and two-dimensional electrophoresis (1DE and 2DE with immunoblotting and mass spectrometry together with two-dimensional difference in gel electrophoresis (2D-DIGE. 1DE showed bands of the intact FGB at 50 kDa and the cleaved forms containing the fragment D at ~37–40 kDa, which corresponded to 19 spots in 2DE. In particular, spot 402 at ~50 kDa and spots 526 and 548 at ~37 kDa were of interest by showing an increased expression in tumor tissues. A higher content of spot 402 was associated with stomach antrum, while spots 526 and 548 amounts correlated with corpus and high platelet count (>208 × 109/L. The quantification of FGB and cleaved products may help to further characterize the interconnections between GC and platelet/coagulation pathways.

Cloning and expression of clt genes encoding milk-clotting proteases from Myxococcus xanthus 422.

Science.gov (United States)

Poza, M; Prieto-Alcedo, M; Sieiro, C; Villa, T G

2004-10-01

The screening of a gene library of the milk-clotting strain Myxococcus xanthus 422 constructed in Escherichia coli allowed the description of eight positive clones containing 26 open reading frames. Only three of them (cltA, cltB, and cltC) encoded proteins that exhibited intracellular milk-clotting ability in E. coli, Saccharomyces cerevisiae, and Pichia pastoris expression systems.

A constitutive model for developing blood clots with various compositions and their nonlinear viscoelastic behavior

NARCIS (Netherlands)

van Kempen, T. H. S.; Donders, W. P.; van de Vosse, F. N.; Peters, G. W. M.

2016-01-01

The mechanical properties determine to a large extent the functioning of a blood clot. These properties depend on the composition of the clot and have been related to many diseases. However, the various involved components and their complex interactions make it difficult at this stage to fully

Plasma levels of C-Reactive Protein and Fibrinogen in Pulmonary ...

African Journals Online (AJOL)

In this study, we determined the changes in plasma C- reactive protein (C-RP) and Fibrinogen levels in Drug sensitive Tuberculosis (DSTB) patients at diagnosis, Multi drug resistant tuberculosis (MDRTB) patients at diagnosis and during chemotherapy. Twenty-four (24) patients MDRTB patients and 24 newly diagnosed ...

Relation between lung perfusion defects and intravascular clots in acute pulmonary thromboembolism: assessment with breath-hold SPECT-CT pulmonary angiography fusion images.

Science.gov (United States)

Suga, Kazuyoshi; Yasuhiko, Kawakami; Iwanaga, Hideyuki; Tokuda, Osamu; Matsunaga, Naofumi

2008-09-01

The relation between lung perfusion defects and intravascular clots in acute pulmonary thromboembolism (PTE) was comprehensively assessed on deep-inspiratory breath-hold (DIBrH) perfusion SPECT-computed tomographic pulmonary angiography (CTPA) fusion images. Subjects were 34 acute PTE patients, who had successfully performed DIBrH perfusion SPECT using a dual-headed SPECT and a respiratory tracking system. Automated DIBrH SPECT-CTPA fusion images were used to assess the relation between lung perfusion defects and intravascular clots detected by CTPA. DIBrH SPECT visualized 175 lobar/segmental or subsegmental defects in 34 patients, and CTPA visualized 61 intravascular clots at variable locations in 30 (88%) patients, but no clots in four (12%) patients. In 30 patients with clots, the fusion images confirmed that 69 (41%) perfusion defects (20 segmental, 45 subsegmental and 4 lobar defects) of total 166 defects were located in lung territories without clots, although the remaining 97 (58%) defects were located in lung territories with clots. Perfusion defect was absent in lung territories with clots (one lobar branch and three segmental branches) in four (12%) of these patients. In four patients without clots, nine perfusion defects including four segmental ones were present. Because of unexpected dissociation between intravascular clots and lung perfusion defects, the present fusion images will be a useful adjunct to CTPA in the diagnosis of acute PTE.

Effect of Metformin on Plasma Fibrinogen Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

Science.gov (United States)

Simental-Mendia, Luis E; Pirro, Matteo; Atkin, Stephen L; Banach, Maciej; Mikhailidis, Dimitri P; Sahebkar, Amirhossein

2018-01-01

Fibrinogen is a key mediator of thrombosis and it has been implicated in the pathogenesis of atherosclerosis. Because metformin has shown a potential protective effect on different atherothrombotic risk factors, we assessed in this meta-analysis its effect on plasma fibrinogen concentrations. A systematic review and meta-analysis was carried out to identify randomized placebo-controlled trials evaluating the effect of metformin administration on fibrinogen levels. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases (by June 2, 2017) and quality of studies was performed according to Cochrane criteria. Quantitative data synthesis was conducted using a random-effects model and sensitivity analysis by the leave-one-out method. Meta-regression analysis was performed to assess the modifiers of treatment response. Meta-analysis of data from 9 randomized placebo-controlled clinical trials with 2302 patients comprising 10 treatment arms did not suggest a significant change in plasma fibrinogen concentrations following metformin therapy (WMD: -0.25 g/L, 95% CI: -0.53, 0.04, p = 0.092). The effect size was robust in the leave-one-out sensitivity analysis and remained non-significant after omission of each single study from the meta-analysis. No significant effect of metformin on plasma fibrinogen concentrations was demonstrated in the current meta-analysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of vitamins C and E alone and in combination with each other on LDL and fibrinogen in streptozotocin induced diabetic rats

International Nuclear Information System (INIS)

Talat, A.; Khan, T.B.; Mahmood, S.

2011-01-01

Diabetes mellitus is a heterogeneous group of disorders, manifested by raised plasma glucose concentration and disturbances of glucose metabolism Diabetes mellitus is a complex of metabolic disorders affecting different systems of body. The main etiology of mortality and high percentage of morbidity in patients with diabetes mellitus is atherosclerosis. The vascular endothelium overlying lesion - prone arterial sites shows increased permeability to plasma proteins, LDL and fibrinogen. High plasma fibrinogen concentration in adults is associated with elevated risk of coronary heart disease and stroke. Treatment with antioxidants like vitamin C and vitamin E reduces diabetic complications. The aim of this study was to determine the effect of antioxidants vitamin C and E in lowering the fibrinogen and LDL levels. Present study was conducted on 48 albino rats. They were divided into four groups. Dia-betes was induced in all rats by giving streptozotocin 65 mg/kg intraperitoneally. First group was control diabetic. Second group was given vitamin C in a dose of 150 mg/kg b.w/day and third group was given vita-min E in a dose of 100 mg/kg b.w/day. Fourth group was given vitamin C with vitamin E intraperitoneally in the same doses. Effects of vitamin C and E were observed on serum LDL and plasma fibrinogen level by using commercially available kits. LDL cholesterol was decreased in groups B, C and D as compared to group A. Fibrinogen level was decreased in - group B and D and increased in group C. Vitamin C alone and in combination with vitamin E help in ameliorating atherosclerosis by decreasing LDL and fibrinogen levels. Vitamin E lowers LDL level but not fibrinogen level. There is a synergistic action of vitamin E and C in lowering fibrinogen and LDL level. (author)

Acquired dysfibrinogenemia secondary to multiple myeloma

Czech Academy of Sciences Publication Activity Database

Kotlín, R.; Sobotková, A.; Riedel, Tomáš; Salaj, P.; Suttnar, J.; Reicheltová, Z.; Májek, P.; Khaznadar, T.; Dyr, J. E.

2008-01-01

Roč. 120, č. 2 (2008), s. 75-81 ISSN 0001-5792 R&D Projects: GA AV ČR KAN200670701 Institutional research plan: CEZ:AV0Z40500505 Keywords : acquired dysfibrinogenemia * amorphous clot * fibrinogen Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.191, year: 2008

Distinct Adsorption Configurations and Self-Assembly Characteristics of Fibrinogen on Chemically Uniform and Alternating Surfaces including Block Copolymer Nanodomains

Science.gov (United States)

2015-01-01

Understanding protein–surface interactions is crucial to solid-state biomedical applications whose functionality is directly correlated with the precise control of the adsorption configuration, surface packing, loading density, and bioactivity of protein molecules. Because of the small dimensions and highly amphiphilic nature of proteins, investigation of protein adsorption performed on nanoscale topology can shed light on subprotein-level interaction preferences. In this study, we examine the adsorption and assembly behavior of a highly elongated protein, fibrinogen, on both chemically uniform (as-is and buffered HF-treated SiO2/Si, and homopolymers of polystyrene and poly(methyl methacrylate)) and varying (polystyrene-block-poly(methyl methacrylate)) surfaces. By focusing on high-resolution imaging of individual protein molecules whose configurations are influenced by protein–surface rather than protein–protein interactions, fibrinogen conformations characteristic to each surface are identified and statistically analyzed for structural similarities/differences in key protein domains. By exploiting block copolymer nanodomains whose repeat distance is commensurate with the length of the individual protein, we determine that fibrinogen exhibits a more neutral tendency for interaction with both polystyrene and poly(methyl methacrylate) blocks relative to the case of common globular proteins. Factors affecting fibrinogen–polymer interactions are discussed in terms of hydrophobic and electrostatic interactions. In addition, assembly and packing attributes of fibrinogen are determined at different loading conditions. Primary orientations of fibrinogen and its rearrangements with respect to the underlying diblock nanodomains associated with different surface coverage are explained by pertinent protein interaction mechanisms. On the basis of two-dimensional stacking behavior, a protein assembly model is proposed for the formation of an extended fibrinogen network

Characterisation of clotting factors, anticoagulant protein activities and viscoelastic analysis in healthy donkeys.

Science.gov (United States)

Perez-Ecija, A; Mendoza, F J

2017-11-01

Studies have demonstrated differences in commonly measured haemostatic parameters between donkeys and horses. Whether clotting factors, anticoagulant protein activities and thromboelastography parameters also differ between species is still unknown. To characterise haemostatic parameters in healthy donkeys and to compare these with those in horses. Cross-sectional study. Clotting factors (V, VII, VIII, IX, X, XI and XII), and antithrombin III, Protein C and Protein S activities were measured in 80 healthy Andalusian and crossbred donkeys and 40 healthy Andalusian crossbred horses with assays based on human deficient plasmas. Thromboelastography was performed in 34 donkeys using a coagulation and platelet function analyser. Donkeys had shorter activated partial thromboplastin time (mean ± s.d. 33.4 ± 5.2 s vs. 38.8 ± 4.2 s; P0.05) and XII (96 ± 21 vs. 108 ± 15; Pdonkeys. Activated clot time (175 [159-189]), time to peak (6.5 [5.8-7.8]) and clot formation rate (26.9 [16.9-36.4]) in donkeys were shorter than reported values in horses. Haemostatic pathways could not be fully evaluated in donkeys because some tests are unavailable. Certain fibrinolytic parameters (plasmin, plasminogen, etc.) have not been characterised in donkeys and this may have affected our results. The haemostatic system in donkeys differs from that in horses and extrapolation of reference values between these species is not appropriate. © 2017 EVJ Ltd.

Thrombin-Accelerated Quick Clotting Serum Tubes: An Evaluation with 22 Common Biochemical Analytes

Directory of Open Access Journals (Sweden)

Wai-Yoong Ng

2013-01-01

Full Text Available Clot activator serum tubes have significantly improved turnaround times for result reporting compared to plain tubes. With increasing workload and service performance expectations confronting clinical laboratories with high-volume testing and with particular emphasis on critical analytes, attention has focussed on preanalytical variables that can be improved. We carried out a field study on the test performance of BD vacutainer rapid serum tubes (RSTs compared to current institutional issued BD vacutainer serum separator tubes (SSTs in its test result comparability, clotting time, and stability on serum storage. Data from the study population (n=160 of patients attending outpatient clinics and healthy subjects showed that results for renal, liver, lipids, cardiac, thyroid, and prostate biochemical markers were comparable between RSTs and SSTs. Clotting times of the RSTs were verified to be quick with a median time of 2.05 min. Analyte stability on serum storage at 4°C showed no statistically significant deterioration except for bicarbonate, electrolytes, and albumin over a period of 4 days. In conclusion, RSTs offered savings in the time required for the clotting process of serum specimens. This should translate to further trimming of the whole process from blood collection to result reporting without too much sacrifice on test accuracy and performance compared to the current widely used SSTs in most clinical laboratories.

Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets

Directory of Open Access Journals (Sweden)

Marcinkiewicz C

2017-05-01

Full Text Available Cezary Marcinkiewicz,1,2 Jonathan A Gerstenhaber,1 Mark Sternberg,2 Peter I Lelkes,1 Giora Feuerstein1,2 1Department of Bioengineering, College of Engineering, Temple University, Philadelphia, 2Debina Diagnostic, Inc., Newton Square, PA, USA Abstract: Thromboembolic events (TEE underwrite key causes of death in developed countries. While advanced imaging technologies such as computed tomography scans serve to diagnose blood clots during acute cardiovascular events, no such technology is available in routine primary care for TEE risk assessment. Here, we describe an imaging platform technology based on bioengineered fluorescent nanodiamond particles (F-NDPs functionalized with bitistatin (Bit, a disintegrin that specifically binds to the αIIbβ3 integrin, platelet fibrinogen receptor (PFR on activated platelets. Covalent linkage of purified Bit to F-NDP was concentration-dependent and saturable, as validated by enzyme-linked immunosorbent assay using specific anti-Bit antibodies. F-NDP–Bit interacted with purified PFR, either in immobilized or soluble form. Lotrafiban, a nonpeptide, αIIbβ3 receptor antagonist, specifically blocked F-NDP–Bit–PFR complex formation. Moreover, F-NDP–Bit specifically binds to activated platelets incorporated into a clot generated by thrombin-activated rat platelet-rich plasma (PRP. Our results suggest that engineered F-NDP–Bit particles could serve as noninvasive, “real-time” optical diagnostics for clots present in blood vessels. Keywords: carbon nanoparticles, blood clots, imaging, platelet fibrinogen receptor, fluorescence, disintegrin, thromboembolic complications, thrombosis

Fibronectin alters the rate of formation and structure of the fibrin matrix.

Science.gov (United States)

Ramanathan, Anand; Karuri, Nancy

2014-01-10

Plasma fibronectin is a vital component of the fibrin clot; however its role on clot structure is not clearly understood. The goal of this study was to examine the influence of fibronectin on the kinetics of formation, structural characteristics and composition of reconstituted fibrin clots or fibrin matrices. Fibrin matrices were formed by adding thrombin to 1, 2 or 4 mg/ml fibrinogen supplemented with 0-0.4 mg/ml fibronectin. The rate of fibrin matrix formation was then monitored by measuring light absorbance properties at different time points. Confocal microscopy of fluorescein conjugated fibrinogen was used to visualize the structural characteristics of fibrin matrices. The amount of fibronectin in fibrin matrices was determined through electrophoresis and immunoblotting of solubilized matrices. Fibronectin concentration positively correlated with the initial rate of fibrin matrix formation and with steady state light absorbance values of fibrin matrices. An increase in fibronectin concentration resulted in thinner and denser fibers in the fibrin matrices. Electrophoresis and immunoblotting showed that fibronectin was covalently and non-covalently bound to fibrin matrices and in the form of high molecular weight multimers. The formation of fibronectin multimers was attributed to cross-linking of fibronectin by trace amounts Factor XIIIa. These findings are novel because they link results from light absorbance studies to microcopy analyses and demonstrate an influence of fibronectin on fibrin matrix structural characteristics. This data is important in developing therapies that destabilize fibrin clots. Copyright © 2014. Published by Elsevier Inc.

A family of cell-adhering peptides homologous to fibrinogen C-termini

International Nuclear Information System (INIS)

Levy-Beladev, Liron; Levdansky, Lilia; Gaberman, Elena; Friedler, Assaf; Gorodetsky, Raphael

2010-01-01

Research highlights: → Cell-adhesive sequences homologous to fibrinogen C-termini exist in other proteins. → The extended homologous cell-adhesive C-termini peptides family is termed Haptides. → In membrane-like environment random coiled Haptides adopt a helical conformation. → Replacing positively charged residues with alanine reduces Haptides activity. -- Abstract: A family of cell-adhesive peptides homologous to sequences on different chains of fibrinogen was investigated. These homologous peptides, termed Haptides, include the peptides Cβ, preCγ, and CαE, corresponding to sequences on the C-termini of fibrinogen chains β, γ, and αE, respectively. Haptides do not affect cell survival and rate of proliferation of the normal cell types tested. The use of new sensitive assays of cell adhesion clearly demonstrated the ability of Haptides, bound to inert matrices, to mediate attachment of different matrix-dependent cell types including normal fibroblasts, endothelial, and smooth muscle cells. Here we present new active Haptides bearing homologous sequences derived from the C-termini of other proteins, such as angiopoietin 1 and 2, tenascins C and X, and microfibril-associated glycoprotein-4. The cell adhesion properties of all the Haptides were found to be associated mainly with their 11 N-terminal residues. Mutated preCγ peptides revealed that positively charged residues account for their attachment effect. These results suggest a mechanism of direct electrostatic interaction of Haptides with the cell membrane. The extended Haptides family may be applied in modulating adhesion of cells to scaffolds for tissue regeneration and for enhancement of nanoparticulate transfection into cells.

Pilot study of Alteplase (tissue plasminogen activator) for treatment of urinary clot retention in an in vitro model.

Science.gov (United States)

Ritch, Chad R; Ordonez, Maria A; Okhunov, Zhamshid; Araujo, Juan; Walsh, Rhonda; Baudin, Vania; Lee, Daniel; Badani, Ketan K; Gupta, Mantu; Landman, Jaime

2009-08-01

The management of urinary clot retention and hematuria involves manual irrigation with sterile water or normal saline via a Foley catheter followed by continuous bladder irrigation. Irrigation may become difficult because of the formation of dense blood clots. Tissue plasminogen activator (t-PA/Alteplase) may be a useful pharmacological agent to improve the efficacy of manual irrigation of large, dense clots. The goal of the current study was to compare t-PA to sterile water for clot irrigation in an in vitro model. In vitro models of clot retention were created using 500-cc urinary leg bags each filled with 80 cc of unpreserved whole blood from a healthy volunteer. Each model was incubated at 25 degrees C for 24 hours to allow clot formation. Four models each with 25 mL solution of t-PA at concentrations of 2, 1, 0.5, and 0.25 mg/mL were evaluated and compared to a control (25 mL sterile water). Models were instilled with solution (t-PA or control) and incubated for 30 minutes at 37 degrees C, and then irrigated with sterile water via 18F Foley by a blinded investigator. Three separate experiments were conducted, and statistical analysis was performed comparing various irrigation parameters. Clot evacuation with 25 mL of t-PA at a concentration of 2 mg/mL (50 mg) was significantly easier (p = 0.05) and faster (p < 0.05) than the sterile water control. The mean time for clot evacuation in this model was 2.7 minutes for t-PA solution 2 mg/mL versus 7.3 minutes for the control (p < 0.05). Compared to the control, irrigation with t-PA solution 2 mg/mL also required less irrigant (180 mL vs. 500 mL) (p < 0.05) for complete evacuation. There was a similar trend in efficacy for the lower doses of t-PA, but this was not statistically significant. In this in vitro study, a single 25 mL instillation of t-PA solution 2 mg/mL is significantly better than sterile water alone for clot evacuation. In vivo animal studies are pending.

The effect of Ramadan fasting and physical activity on homocysteine and fibrinogen concentrations in overweight women

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Seyyed Reza Attarzadeh Hosseini

2014-12-01

Full Text Available Introduction: Increased levels of certain markers like fibrinogen and Homocysteine are independently associated with an increased risk of cardiovascular diseases. Considering the numerous favorable effects of healthful nutrition and physical activity on reducing the risk of atherosclerosis, in this study we intend to take into account fasting and physical activity during the month of Ramadan and their impacts on Homocysteine and fibrinogen concentrations in overweight women. Materials and Methods: In this experiment, 22 overweight and obese women with a body mass index (BMI of greater than 25 kg/m2 aging from 20 to 45 years were enrolled into two groups by means of targeted-sampling method. One group involved fasting accompanied with regular physical activity (12 subjects and the other group involved only fasting (10 subjects. The protocol for the physical activity group consisted of three 60-minute sessions of aerobic exercise per week with a 50%- 65% heart rate reserved. Towards the end of Ramadan, the anthropometric and blood levels of Homocysteine and fibrinogen were closely measured. Data were analyzed using repeated measures and the significance level of P≤0 /05 was considered. Findings: A month of fasting along with regular physical activity did not prove to have any noticeable effects on the level of fibrinogen while a significant increase in the Homocysteine levels was discovered (P

Synthesis of New DNA G-Quadruplex Constructs with Anthraquinone Insertions and Their Anticoagulant Activity

DEFF Research Database (Denmark)

Gouda, Alaa S.; Amine, Mahasen S.; Pedersen, Erik Bjerregaard

2016-01-01

1,4-Dihydroxyanthraquinone and 1,8-dihydroxyanthraquinone were alkylated with 3-bromopropan-1-ol and subsequently transformed into the corresponding DMT protected phosphoramidite building blocks for insertion into loops of the Gquadruplex of the thrombin binding aptamer (TBA). The 1,4-disubstituted...... potassium buffer conditions as previously observed for TBA. Although the majority of the anthraquinone modified TBA analogues showed a decrease in clotting times in a fibrinogen clotting assay when compared to TBA, modified aptamers containing a 1,8-disubstituted anthraquinone linker replacing G8 or T9...

C-reactive protein and fibrinogen of bedridden older patients in a six-month vitamin D supplementation trial.

Science.gov (United States)

Bjorkman, M P; Sorva, A J; Tilvis, R S

2009-05-01

To elucidate the association between vitamin D status, C-reactive protein (CRP) and fibrinogen. Secondary analysis of a randomised double-blind placebo controlled trial. Four longterm care hospitals (1215 beds) in Helsinki, Finland. 218 long-term inpatients aged over 65 years. Eligible patients (n = 218) were randomized to receive 0 IU/d, 400 IU/d, or 1200 IU/d cholecalciferol for six months. Plasma 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), high sensitive CRP, fibrinogen, amino-terminal propeptide of type I procollagen (PINP), and carboxy-terminal telopeptide of type I collagen (ICTP) were measured. The patients were aged (84.5 +/- 7.5 years), vitamin D deficient (25-OHD = 23 +/- 10 nmol/l), chronically bedridden and in stable general condition. The mean baseline CRP and fibrinogen were 10.86 mg/l (0.12 mg/l - 125.00 mg/l) and 4,7 g/l (2.3 g/l - 8.6 g/l), respectively. CRP correlated with ICTP (r = 0.217, p = 0.001), but not with vitamin D status. Supplementation significantly increased 25-OHD concentrations, but the changes in CRP and fibrinogen were insignificant and inconsistent. The post-trial CRP concentrations (0.23 mg/l -138.00 mg/l) correlated with ICTP (r = 0.156, p bedridden older patients.

Intracameral air injection during Ahmed glaucoma valve implantation in neovascular glaucoma for the prevention of tube obstruction with blood clot: Case Report.

Science.gov (United States)

Hwang, Sung Ha; Yoo, Chungkwon; Kim, Yong Yeon; Lee, Dae Young; Nam, Dong Heun; Lee, Jong Yeon

2017-12-01

Glaucoma drainage implant surgery is a treatment option for the management of neovascular glaucoma. However, tube obstruction by blood clot after Ahmed glaucoma valve (AGV) implantation is an unpredictable clinically challenging situation. We report 4 cases using intracameral air injection for the prevention of the tube obstruction of AGV by blood clot. The first case was a 57-year-old female suffering from ocular pain because of a tube obstruction with blood clot after AGV implantation in neovascular glaucoma. Surgical blood clot removal was performed. However, intractable bleeding was noted during the removal of the blood clot, and so intracameral air injection was performed to prevent a recurrent tube obstruction. After the procedure, although blood clots formed around the tube, the tube opening where air could touch remained patent. In 3 cases of neovascular glaucoma with preoperative severe intraocular hemorrhages, intracameral air injection and AGV implantation were performed simultaneously. In all 3 cases, tube openings were patent. It appears that air impeded the blood clots formation in front of the tube opening. Intracameral air injection could be a feasible option to prevent tube obstruction of AGV implant with a blood clot in neovascular glaucoma with high risk of tube obstruction. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Elevated NT-proBNP is associated with unfavorably altered plasma fibrin clot properties in atrial fibrillation.

Science.gov (United States)

Matusik, Paweł T; Matusik, Patrycja S; Kornacewicz-Jach, Zdzisława; Małecka, Barbara; Ząbek, Andrzej; Undas, Anetta

2017-09-15

Dense fibrin clot formation and hypofibrinolysis have been reported in atrial fibrillation (AF). It is unclear which factors affect fibrin clot properties in AF. We investigated plasma fibrin clot permeability (K s ), clot lysis time (CLT), endogenous thrombin potential (ETP) as well as other coagulation and fibrinolysis parameters along with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in 160 AF patients (median age, 70.5years). Previous stroke (n=15; 9.4%) was associated with decreased K s (P=0.04) and longer CLT (P=0.005), together with higher antiplasmin (P=0.03) and lower tissue-type plasminogen activator (P=0.01). Lower K s (P=0.04) and tendency towards longer CLT (P=0.10) were observed in patients with a left atrium diameter>40mm. Patients with a CHA 2 DS 2 -VASc score of 3 or more (82.5%) were characterized by higher thrombin-activatable fibrinolysis inhibitor antigen (P=0.009). K s was inversely correlated with log NT-proBNP (r=-0.34, PCLT was positively correlated with log NT-proBNP (R=0.61, PCLT (the top quartile,≥109min). In AF patients prothrombotic fibrin clot properties assessed ex vivo are determined by PAI-1 and NT-proBNP and this phenotype is associated with prior ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

The acute effect of cigarette smoking on the high-sensitivity CRP and fibrinogen biomarkers in chronic obstructive pulmonary disease patients.

Science.gov (United States)

van Dijk, Wouter D; Akkermans, Reinier; Heijdra, Yvonne; Weel, Chris van; Schermer, Tjard R J; Scheepers, Paul T J; Lenders, Jacques W M

2013-04-01

The evidence on the acute effects of smoking on biomarkers is limited. Our aim was to study the acute effect of smoking on disease-related biomarkers. The acute effect of smoking on serum high sensitivity CRP (hs-CRP) and plasma fibrinogen and its association with disease severity was studied by challenging 31 chronic obstructive pulmonary disease patients with cigarette smoking and repeatedly measuring these biomarkers before and after smoking. Fibrinogen and hs-CRP increased directly after smoking by 9.4 mg/dl (95% CI: 4.2-14.5) and 0.13 mg/l (95% CI: 0.03-0.23), respectively. Fibrinogen levels remained elevated after 35 min, whereas hs-CRP normalized. Pearson's correlation coefficient between the hs-CRP change and chronic obstructive pulmonary disease severity was 0.25 (p = 0.06). Fibrinogen and hs-CRP increased directly after smoking in the chronic obstructive pulmonary disease patients. Their association with disease risk and/or progression remains to be demonstrated.

Discrepant fibrinolytic response in plasma and whole blood during experimental endotoxemia in healthy volunteers.

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Sisse R Ostrowski

Full Text Available Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG.Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour, with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest were recorded. Mixed models with Tukey post hoc tests and correlations were applied.Endotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05. Platelet aggregation decreased (all tests, p<0.05, whereas TEG whole blood clot firmness increased (G, p = 0.05. Furthermore, during endotoxemia (4 h, whole blood fibrinolysis increased (clot lysis time (CLT, p<0.001 and Functional Fibrinogen clot strength decreased (p = 0.049. After endotoxemia (6 h, whole blood fibrinolysis was reduced (CLT, p<0.05. In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001.Endotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are

Genetic associations between fibrinogen and cognitive performance in three Scottish cohorts.

Science.gov (United States)

Marioni, Riccardo E; Deary, Ian J; Murray, Gordon D; Lowe, Gordon D O; Strachan, Mark W J; Luciano, Michelle; Houlihan, Lorna M; Gow, Alan J; Harris, Sarah E; Rumley, Ann; Stewart, Marlene C; Fowkes, F Gerry R; Price, Jackie F

2011-09-01

There is increasing evidence to suggest that elevated plasma levels of fibrinogen are associated with late-life cognitive performance. This study tested the association of single nucleotide polymorphisms in the fibrinogen α (FGA) and β (FGB) genes with cognitive performance. Data were analysed from three community-dwelling populations of older persons (>50 years) in central Scotland: the Aspirin for Asymptomatic Atherosclerosis (AAA) Trial (n = 2,091), the Edinburgh Type 2 Diabetes Study (ET2DS, n = 1,066), and the Lothian Birth Cohort 1936 (LBC1936, n = 1,091). Cognition was assessed using a battery of five, seven, and four psychometric tests, respectively. This information was used to derive a general cognitive factor. Weakly significant associations were found between the rs4220 (FGB), and rs2227412 (FGB) SNPs and a single test of cognitive performance in the AAA Trial (p determinant of late-life cognitive performance and justify further attempts at replication in older persons.

Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study.

Science.gov (United States)

Malan, Nicolaas T; von Känel, Roland; Schutte, Alta E; Huisman, Hugo W; Schutte, Rudolph; Smith, Wayne; Mels, Carina M; Kruger, Ruan; Meiring, Muriel; van Rooyen, Johannes M; Malan, Leoné

2013-10-12

Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R(2) 0.24-0.28; p≤0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R(2) 0.24; pstress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels. © 2013.

Acetylation and glycation of fibrinogen in vitro occur at specific lysine residues in a concentration dependent manner: A mass spectrometric and isotope labeling study

International Nuclear Information System (INIS)

Svensson, Jan; Bergman, Ann-Charlotte; Adamson, Ulf; Blombäck, Margareta; Wallén, Håkan; Jörneskog, Gun

2012-01-01

Highlights: ► Fibrinogen was incubated in vitro with glucose or aspirin. ► Acetylations and glycations were found at twelve lysine sites by mass spectrometry. ► The labeling by aspirin and glucose occurred dose-dependently. ► No competition between glucose and aspirin for binding to fibrinogen was found. -- Abstract: Aspirin may exert part of its antithrombotic effects through platelet-independent mechanisms. Diabetes is a condition in which the beneficial effects of aspirin are less prominent or absent – a phenomenon called “aspirin resistance”. We investigated whether acetylation and glycation occur at specific sites in fibrinogen and if competition between glucose and aspirin in binding to fibrinogen occurs. Our hypothesis was that such competition might be one explanation to “aspirin resistance” in diabetes. After incubation of fibrinogen in vitro with aspirin (0.8 mM, 24 h) or glucose (100 mM, 5–10 days), we found 12 modified sites with mass spectrometric techniques. Acetylations in the α-chain: αK191, αK208, αK224, αK429, αK457, αK539, αK562, in the β-chain: βK233, and in the γ-chain: γK170 and γK273. Glycations were found at βK133 and γK75, alternatively γK85. Notably, the lysine 539 is a site involved in FXIII-mediated cross-linking of fibrin. With isotope labeling in vitro, using [ 14 C-acetyl]salicylic acid and [ 14 C]glucose, a labeling of 0.013–0.084 and 0.12–0.5 mol of acetylated and glycated adduct/mol fibrinogen, respectively, was found for clinically (12.9–100 μM aspirin) and physiologically (2–8 mM glucose) relevant plasma concentrations. No competition between acetylation and glycation could be demonstrated. Thus, fibrinogen is acetylated at several lysine residues, some of which are involved in the cross-linking of fibrinogen. This may mechanistically explain why aspirin facilitates fibrin degradation. We find no support for the idea that glycation of fibrin(ogen) interferes with acetylation of

Acetylation and glycation of fibrinogen in vitro occur at specific lysine residues in a concentration dependent manner: A mass spectrometric and isotope labeling study

Energy Technology Data Exchange (ETDEWEB)

Svensson, Jan, E-mail: jan.svensson@ki.se [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden); Bergman, Ann-Charlotte [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Adamson, Ulf [Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden); Blombaeck, Margareta [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Wallen, Hakan; Joerneskog, Gun [Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden)

2012-05-04

Highlights: Black-Right-Pointing-Pointer Fibrinogen was incubated in vitro with glucose or aspirin. Black-Right-Pointing-Pointer Acetylations and glycations were found at twelve lysine sites by mass spectrometry. Black-Right-Pointing-Pointer The labeling by aspirin and glucose occurred dose-dependently. Black-Right-Pointing-Pointer No competition between glucose and aspirin for binding to fibrinogen was found. -- Abstract: Aspirin may exert part of its antithrombotic effects through platelet-independent mechanisms. Diabetes is a condition in which the beneficial effects of aspirin are less prominent or absent - a phenomenon called 'aspirin resistance'. We investigated whether acetylation and glycation occur at specific sites in fibrinogen and if competition between glucose and aspirin in binding to fibrinogen occurs. Our hypothesis was that such competition might be one explanation to 'aspirin resistance' in diabetes. After incubation of fibrinogen in vitro with aspirin (0.8 mM, 24 h) or glucose (100 mM, 5-10 days), we found 12 modified sites with mass spectrometric techniques. Acetylations in the {alpha}-chain: {alpha}K191, {alpha}K208, {alpha}K224, {alpha}K429, {alpha}K457, {alpha}K539, {alpha}K562, in the {beta}-chain: {beta}K233, and in the {gamma}-chain: {gamma}K170 and {gamma}K273. Glycations were found at {beta}K133 and {gamma}K75, alternatively {gamma}K85. Notably, the lysine 539 is a site involved in FXIII-mediated cross-linking of fibrin. With isotope labeling in vitro, using [{sup 14}C-acetyl]salicylic acid and [{sup 14}C]glucose, a labeling of 0.013-0.084 and 0.12-0.5 mol of acetylated and glycated adduct/mol fibrinogen, respectively, was found for clinically (12.9-100 {mu}M aspirin) and physiologically (2-8 mM glucose) relevant plasma concentrations. No competition between acetylation and glycation could be demonstrated. Thus, fibrinogen is acetylated at several lysine residues, some of which are involved in the cross-linking of

The β fibrinogen gene G-455A polymorphism in Asian subjects with ...

African Journals Online (AJOL)

Jonny Karunia Fajar

2016-08-10

Aug 10, 2016 ... Conclusions: In the Asian population, the b fibrinogen gene G-455A polymorphism was associ- ..... Kazakhstan, Kuwait, Kyrgyzstan, Laos, Lebanon, Malaysia, ... Thailand, Timor-Leste, Turkey, Turkmenistan, United Arab.

Changes in clot lysis levels of reteplase and streptokinase following continuous wave ultrasound exposure, at ultrasound intensities following attenuation from the skull bone

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Roijer Anders

2008-08-01

Full Text Available Abstract Background Ultrasound (US has been used to enhance thrombolytic therapy in the treatment of stroke. Considerable attenuation of US intensity is however noted if US is applied over the temporal bone. The aim of this study was therefore to explore possible changes in the effect of thrombolytic drugs during low-intensity, high-frequency continuous-wave ultrasound (CW-US exposure. Methods Clots were made from fresh venous blood drawn from healthy volunteers. Each clot was made from 1.4 ml blood and left to coagulate for 1 hour in a plastic test-tube. The thrombolytic drugs used were, 3600 IU streptokinase (SK or 0.25 U reteplase (r-PA, which were mixed in 160 ml 0.9% NaCl solution. Continuous-wave US exposure was applied at a frequency of 1 MHz and intensities ranging from 0.0125 to 1.2 W/cm2. For each thrombolytic drug (n = 2, SK and r-PA and each intensity (n = 9 interventional clots (US-exposed, n = 6 were submerged in thrombolytic solution and exposed to CW-US while control clots (also submerged in thrombolytic solution, n = 6 were left unexposed to US. To evaluate the effect on clot lysis, the haemoglobin (Hb released from each clot was measured every 20 min for 1 hour (20, 40 and 60 min. The Hb content (mg released was estimated by spectrophotometry at 540 nm. The difference in effect on clot lysis was expressed as the difference in the amount of Hb released between pairs of US-exposed clots and control clots. Statistical analysis was performed using Wilcoxon's signed rank test. Results Continuous-wave ultrasound significantly decreased the effects of SK at intensities of 0.9 and 1.2 W/cm2 at all times (P 2 and at 1.2 W/cm2, following 40 min exposure at 0.3, 0.6, 0.9 and at 1.2 W/cm2, and following 60 min of exposure at 0.05 0.3, 0.6, 0.9 and at 1.2 W/cm2 (all P Conclusion Increasing intensities of CW-US exposure resulted in increased clot lysis of r-PA-treated blood clots, but decreased clot lysis of SK-treated clots.

Diagnosis of hemoparasitosis trough the spread-smear technique using a drop of blood clot

OpenAIRE

Neusa Saltiél Stobbe; Eunice Leonora Chaplin; Maria das Graças de Souza Paiva; Nilton Rogério Santos Silva; Flávio A. Pacheco Araújo; Elinor Fortes

1992-01-01

The spread-smear technique using a drop of blood clot and stained by diluted and undimitcd Giemsa stain was evaluated for the search of blood cell types and recognition of Babesia bovis, Babesia bigemina and Anaplasma marginale hemoparasites. The blood clot samples were taken from a 6 month-old calf experimentally inoculated with the blood from a Cattle Tick Fever carrier. The Technique was sumitable for the observation of different blood cells and for the recognition of the hemoparasites.

14-Day thawed plasma retains clot enhancing properties and inhibits tPA-induced fibrinolysis.

Science.gov (United States)

Huebner, Benjamin R; Moore, Ernest E; Moore, Hunter B; Shepherd-Singh, Raymond; Sauaia, Angela; Stettler, Gregory R; Nunns, Geoffrey R; Silliman, Christopher C

2017-11-01

Plasma-first resuscitation attenuates trauma-induced coagulopathy (TIC); however, the logistics of plasma-first resuscitation require thawed plasma (TP) be readily available due to the obligatory thawing time of fresh frozen plasma (FFP). The current standard is storage of TP for up to 5 days at 4°C, based on factor levels at outdate, for use in patients at risk for TIC, but there remains a 2.2% outdated wastage rate. However, the multitude of plasma proteins in attenuating TIC remains unknown. We hypothesize that TP retains the ability to enhance clotting and reduce tPA-induced fibrinolysis at 14-day storage. FFP was thawed and stored at 4°C at the following intervals: 14, 10, 7, 5, 3, and 1-day prior to the experiment. Healthy volunteers underwent blood draws followed by 50% dilution with TP stored at previously mentioned intervals as well as FFP, normal saline (NS), albumin, and whole blood (WB) control. Samples underwent tPA-modified (75 ng/mL) thrombelastography (TEG) with analysis of R-time, angle, maximum amplitude (MA), and LY30. TEG properties did not change significantly over the thawed storage. 14-day TP retained the ability to inhibit tPA-induced hyperfibrinolysis (median LY30% 9.6%) similar to FFP (5.6%), WB (14.6%), and superior to albumin (59.3%) and NS (58.1%). 14-day TP also retained faster clot formation (median angle, 66.2°) and superior clot strength (MA, 61.5 mm) to albumin (34.8°, 21.6 mm) and NS (41.6°, 32.2 mm). TP plasma stored for 14 days retains clot-enhancing ability and resistance to clot degradation similar to FFP. A clinical trial is needed to validate these in vitro results. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the effects of levobupivacaine on clotting and fibrinolysis using thromboelastography.

LENUS (Irish Health Repository)

Leonard, S A

2012-02-03

Amide local anaesthetics inhibit platelet function. We hypothesized that residual anaesthetic in the epidural space could decrease efficacy of an epidural blood patch in preventing postdural puncture headache. Levobupivacaine has recently been approved for epidural anaesthesia. Its effects on coagulation have not previously been studied. The aim of this study was to determine the effects of levobupivacaine on clotting using thromboelastography. Ten ASA Class I volunteers were studied. Venous blood samples were analysed using a Haemoscope 2000D TEG analyser. Whole blood, a 50% saline control and two levobupivacaine solutions (2.5 mg mL(-1) and 2.5 microg mL(-1) in blood) were compared. The former reproduces that produced in the epidural space by blood (20 mL for an epidural blood patch) and levobupivacaine 0.5% (20 mL). The latter approximates plasma concentrations following epidural injection of levobupivacaine 0.5% (20 mL). P < 0.05 was considered significant. Maximum amplitude (MA), a measure of clot strength, is decreased by levobupivacaine 2.5 mg mL(-1). Levobupivacaine 2.5 mg mL(-1) decreases clot strength and may reduce efficacy of a prophylactic epidural blood patch.

Beyond genetic factors in familial amyloidotic polyneuropathy: protein glycation and the loss of fibrinogen's chaperone activity.

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Gonçalo da Costa

Full Text Available Familial amyloidotic polyneuropathy (FAP is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR. This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease.

The use of alteplase for the resolution of an intravesical clot in a neonate receiving extracorporeal membrane oxygenation.

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Olarte, J L; Glover, M L; Totapally, B R

2001-01-01

We present a case of the use of alteplase for the lysis of a large urinary bladder clot. A neonate presented with respiratory failure, secondary to a left diaphragmatic hernia necessitating the need for extracorporeal membrane oxygenation (ECMO) support. On day 3 of ECMO support, hematuria was noted, and a subsequent urinary bladder ultrasound revealed a significant urinary bladder clot. Alteplase (0.5-1 mg) was instilled into the urinary bladder via a 10 French Foley catheter (Sherwood Medical, St. Louis, MO). The catheter was clamped for 1 hour, followed by irrigation with normal saline. Multiple doses of alteplase were administered, resulting in complete resolution of the bladder clot. No adverse effects were attributed to the use of the intravesical alteplase. Alteplase seems to be safe and effective for the resolution of bladder clots, thereby potentially avoiding more invasive surgical procedures.

Evaluation of the coagulometer STA R Max® (Stago) for routine coagulation parameters.

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Brulé, Justine; Sinegre, Thomas; Pereira, Bruno; Berger, Marc G; Serre-Sapin, Anne-Françoise; Lebreton, Aurélien

2018-04-01

The STA R Max ® is a fully automated multiparameter coagulometer using clotting (viscosity-based detection system), chromogenic and immunologic assays. STA R Max ® is equipped with an innovative software (STA Coag Expert ® ) designed to assist laboratory in accreditation. The aim of this study was to evaluate its performances for the certification according to ISO 15189 quality standard in the haemostasis unit of our university hospital. The following tests were evaluated: prothrombin time (PT), activated partial thromboplastin time (aPTT), kaolin cephalin clotting time (KCCT), fibrinogen, anti-Xa assay and D-dimers. In normal and pathological range, the intra-assay coefficients of variation (CV) for PT, aPTT, KCCT and fibrinogen were below 4.0%. Intra-assay CV was of 4.0% for the anti-Xa assay and intra-assay CV was of 7.9% for D-dimers. Inter-assay CV were below 5.0% for PT, aPPT, KCCT and fibrinogen, 14.9% for anti-Xa assay and 8.6% for D-dimers. The interlaboratory comparisons were below 8.7% for PT, aPPT and KCCT, 5.0% for fibrinogen and 15.5% for anti-Xa assay. All results were acceptable according to suitable CV established by GFHT and the provider. The concordance between all coagulometers was excellent, with correlation coefficient close to 1 (0.99 for all parameters except for aPPT which was 0.98) calculated thanks to an intra-class correlation study. In conclusion, the STA R Max ® analyser is suitable for haemostasis laboratories and facilitates certification of a laboratory.

The effect of sepsis and septic shock on the viscoelastic properties of clot quality and mass using rotational thromboelastometry: A prospective observational study.

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Davies, Gareth R; Lawrence, Matthew; Pillai, Suresh; Mills, Gavin M; Aubrey, Robert; Thomas, Dafydd; Williams, Rhodri; Morris, Keith; Evans, Phillip Adrian

2018-04-01

The study purpose was to define changes in coagulation across the sepsis spectrum using rotational thromboelastometry (ROTEM). Sepsis patients were recruited on admission to the Emergency Department and Intensive Care Units of a large teaching hospital in Wales. ROTEM markers of clot development and fibrinolysis were determined, as well as standard coagulation markers. A healthy control group matched for age and gender was also recruited (n=44). 100 patients were recruited (50 sepsis, 20 severe sepsis and 30 septic shock). Maximum clot firmness was significantly higher in the sepsis (p<0.001) and severe sepsis (p=0.012) groups than the healthy control (71.6±4.5 and 70.4±4.1 vs 64.4 respectively). In septic shock there was prolonged clot development; however, maximum clot firmness remained normal. Fibrinolytic function was significantly impaired in septic shock, which was also significantly associated with 28-day mortality (p<0.001). ROTEM indicated significantly enhanced clot structural development in sepsis and severe sepsis, which could be indicative of a hypercoagulable phase. In septic shock, despite there being a prolongation of clotting pathways and impaired fibrinolysis, clot mass was comparably normal, suggestive of the development of a clot with healthy characteristics. Copyright © 2017 Elsevier Inc. All rights reserved.

Rapidly produced /sup 125/I labelled autologous fibrinogen: in vitro properties and preliminary metabolic studies in man

Energy Technology Data Exchange (ETDEWEB)

Hawker, R J; Hawker, L M [Birmingham Univ. (UK)

1976-06-01

The properties of fibrinogen extracted by a precipitation method using glycine at ambient temperatures near neutral pH are described. The simple and reproducible method gave a 73% yield of high purity plasminogen-free fibrinogen in 45 minutes from small volumes of plasma. The protein extract was labelled with /sup 125/I using chloramine-T under conditions optimal for fibrinogen stability. The extraction procedure, radio-iodination, desalting, and sterilization take only 70 minutes for completion from the time donor blood is received in the laboratory. The methods, using a specially developed extraction vessel and desalting/sterilizing column, can be used in a small hospital laboratory. Autologous fibrinogen can thus be extracted from patients' blood, eliminating the risk of transmitting hepatitis when it is re-administered. The autologous material, which is 97% clottable and contains less than 0.05% free iodide, is being routinely used as a diagnostic tool in the detection of deep vein thrombosis. The high purity of the preparation facilitates metabolic studies and in vitro experimental work. In vivo results showed a mean half-life in three normal volunteers of 3.95 days and a catabolic rate of 25.23% per day with the extravascular space estimated as 24.86%. In 30 surgical patients an expected reduced half-life in plasma was determined with a mean of 3.1 days.

Diagnosis of hemoparasitosis trough the spread-smear technique using a drop of blood clot

Directory of Open Access Journals (Sweden)

Neusa Saltiél Stobbe

1992-12-01

Full Text Available The spread-smear technique using a drop of blood clot and stained by diluted and undimitcd Giemsa stain was evaluated for the search of blood cell types and recognition of Babesia bovis, Babesia bigemina and Anaplasma marginale hemoparasites. The blood clot samples were taken from a 6 month-old calf experimentally inoculated with the blood from a Cattle Tick Fever carrier. The Technique was sumitable for the observation of different blood cells and for the recognition of the hemoparasites.

Fibrinogen binding sites P336 and Y338 of clumping factor A are crucial for Staphylococcus aureus virulence.

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Josefsson, Elisabet; Higgins, Judy; Foster, Timothy J; Tarkowski, Andrej

2008-05-21

We have earlier shown that clumping factor A (ClfA), a fibrinogen binding surface protein of Staphylococcus aureus, is an important virulence factor in septic arthritis. When two amino acids in the ClfA molecule, P(336) and Y(338), were changed to serine and alanine, respectively, the fibrinogen binding property was lost. ClfAP(336)Y(338) mutants have been constructed in two virulent S. aureus strains Newman and LS-1. The aim of this study was to analyze if these two amino acids which are vital for the fibrinogen binding of ClfA are of importance for the ability of S. aureus to generate disease. Septic arthritis or sepsis were induced in mice by intravenous inoculation of bacteria. The clfAP(336)Y(338) mutant induced significantly less arthritis than the wild type strain, both with respect to severity and frequency. The mutant infected mice developed also a much milder systemic inflammation, measured as lower mortality, weight loss, bacterial growth in kidneys and lower IL-6 levels. The data were verified with a second mutant where clfAP(336) and Y(338) were changed to alanine and serine respectively. When sepsis was induced by a larger bacterial inoculum, the clfAP(336)Y(338) mutants induced significantly less septic death. Importantly, immunization with the recombinant A domain of ClfAP(336)SY(338)A mutant but not with recombinant ClfA, protected against septic death. Our data strongly suggest that the fibrinogen binding activity of ClfA is crucial for the ability of S. aureus to provoke disease manifestations, and that the vaccine potential of recombinant ClfA is improved by removing its ability to bind fibrinogen.

Effects of kiwi consumption on plasma lipids, fibrinogen and insulin resistance in the context of a normal diet.

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Recio-Rodriguez, Jose I; Gomez-Marcos, Manuel A; Patino-Alonso, Maria C; Puigdomenech, Elisa; Notario-Pacheco, Blanca; Mendizabal-Gallastegui, Nere; de la Fuente, Aventina de la Cal; Otegui-Ilarduya, Luis; Maderuelo-Fernandez, Jose A; de Cabo Laso, Angela; Agudo-Conde, Cristina; Garcia-Ortiz, Luis

2015-09-15

Among fruits, kiwi is one of the richest in vitamins and polyphenols and has strong anti-oxidant effects. We aimed to analyze the relationship between the consumption of kiwi and plasma lipid values, fibrinogen, and insulin resistance in adults within the context of a normal diet and physical-activity. Cross-sectional study. Participants (N = 1469), who were free of cardiovascular diseases, completed a visit, which included the collection of information concerning the participant's usual diet and kiwi consumption using a previously validated, semi-quantitative, 137-item food-frequency-questionnaire. Fasting laboratory determinations included plasma lipids, fibrinogen and insulin resistance. Regular physical-activity was determined using accelerometry. Consumers of at least 1 kiwi/week presented higher plasma values of HDL-cholesterol (mean difference 4.50 [95% CI: 2.63 to 6.36]) and lower triglyceride values (mean difference -20.03 [95% CI: -6.77 to -33.29]), fibrinogen values (mean difference -13.22 [95% CI: -2.18 to -24.26]) and HOMAir values (mean difference -0.30 [95% CI: -0.09 to -0.50]) (p Consumption of at least one kiwi/week is associated with lower plasma concentrations of fibrinogen and improved plasma lipid profile in the context of a normal diet and regular exercise.

Clotting mechanism in beagles irradiated by 4.5 Gy γ-rays

International Nuclear Information System (INIS)

Zhao Zhenhu; Wang Ning; Li Ming; Xing Shuang; Huang Haixiao; Ou Hongling; Xiong Guolin; Zhao Yanfang; Xie Ling; Wang Jinxiang; Miao Jingcheng; Zhu Nankang; Zhang Xueguang; Luo Qingliang; Cong Yuwen

2010-01-01

Objective: To explore the clotting mechanism in beagles irradiated by 4.5 Gy γ-rays after treatment with supportive care, or supportive care and combined cytokines. Methods: Sixteen beagles were divided into irradiation control group, Supportive care group and combined cytokines treatment group. Platelet aggregation test, thrombelastography (TEG) and the time measurement were analyzed in vitro. Results: In irradiation group and supportive care group, the platelet aggregation rates in beagles were decreased markedly and the k value of TEG was increased 7 d post-irradiation, while those indexes in combined cytokines treatment group changed little. At 14 d post-irradiation, each parameter of TEG in irradiated group changed obviously. The values of r, k, r + k and M were elevated significantly, clotting time and the maximum coagulation time of thrombus delayed, the Ma value was decreased markedly, and the maximum elasticity amplitude of thrombus was diminished. All parameters in combined cytokines treatment group were better than those in supportive care group. The thrombin time was prolonged obviously in irradiated group 14 d post-irradiation, while the thrombin time was the longest at 2-3 weeks post irradiation in supportive care group and combined cytokines treatment group (P>0.05). Conclusions: Cytokines could improve the platelet aggregation and the blood clotting functions of beagles suffering from acute radiation sickness. (authors)

A hypothesis: factor VII governs clot formation, tissue repair and apoptosis.

Science.gov (United States)

Coleman, Lewis S

2007-01-01

A hypothesis: thrombin is a "Universal Enzyme of Energy Transduction" that employs ATP energy in flowing blood to activate biochemical reactions and cell effects in both hemostasis and tissue repair. All cells possess PAR-1 (thrombin) receptors and are affected by thrombin elevations, and thrombin effects on individual cell types are determined by their unique complement of PAR-1 receptors. Disruption of the vascular endothelium (VE) activates a tissue repair mechanism (TRM) consisting of the VE, tissue factor (TF), and circulating Factors VII, IX and X that governs localized thrombin elevations to activate clot formation and cellular effects that repair tissue damage. The culmination of the repair process occurs with the restoration of the VE followed by declines in thrombin production that causes Apoptosis ("programmed cell death") in wound-healing fibroblasts, which functions as a mechanism to draw wound edges together. The location and magnitude of TRM activity governs the location and magnitude of Factor VIII activity and clot formation, but the large size of Factor VIII prevents it from penetrating the clot formed by its activity, so that its effects are self-limiting. Factors VII, IX and X function primarily as tissue repair enzymes, while Factor VIII and Factor XIII are the only serine protease enzymes in the "Coagulation Cascade" that are exclusively associated with hemostasis.

What is this chocolate milk in my circuit? A cause of acute clotting of a continuous renal replacement circuit: Questions.

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Kakajiwala, Aadil; Chiotos, Kathleen; Brothers, Julie; Lederman, April; Amaral, Sandra

2016-12-01

One of the greatest problems associated with continuous renal replacement therapy (CRRT) is the early clotting of filters. A literature search revealed three case reports of lipemic blood causing recurrent clotting and reduced CRRT circuit survival time in adult patients, but no reports of cases in children. A 23-month-old male infant with Martinez-Frias syndrome and multivisceral transplant was admitted to the hospital with severe sepsis and hemolytic anemia. He developed acute kidney injury, fluid overload and electrolyte imbalances requiring CRRT and was also administered total parenteral nutrition (TPN) and fat emulsion. The first circuit lasted 60 h before routine change was required. The second circuit showed acute clotting after only 18 h, and brownish-milky fluid was found in the circuit tubing layered between the clotted blood. The patient's serum triglyceride levels were elevated at 988 mg/dL. The lipid infusion was stopped and CRRT restarted. Serum triglyceride levels improved to 363 mg/dL. The new circuit lasted 63 h before routine change was required. Clotting of CRRT circuits due to elevated triglyceride levels is rare and has not been reported in the pediatric population. Physicians should be mindful of this risk in patients receiving TPN who have unexpected clotting of CRRT circuits.

Source of fibrin/fibrinogen degradation products in the CSF after subarachnoid hemorrhage

NARCIS (Netherlands)

Vermeulen, M.; van Vliet, H. H.; Lindsay, K. W.; Hijdra, A.; van Gijn, J.

1985-01-01

In 48 patients with a subarachnoid hemorrhage, levels of fibrin/fibrinogen degradation products (FDP's), total protein, and plasminogen were measured in the cerebrospinal fluid (CSF) between Days 9 and 15 after the bleed. Of these 48 patients, 22 received tranexamic acid. Despite a significant

Reference values for rotational thromboelastometry (ROTEM) in clinically healthy cats.

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Marly-Voquer, Charlotte; Riond, Barbara; Jud Schefer, Rahel; Kutter, Annette P N

2017-03-01

To establish reference intervals for rotational thromboelastometry (ROTEM) using feline blood. Prospective study. University teaching hospital. Twenty-three clinically healthy cats between 1 and 15 years. For each cat, whole blood was collected via jugular or medial saphenous venipuncture, and blood was placed into a serum tube, a tube containing potassium-EDTA, and tubes containing 3.2% sodium citrate. The tubes were maintained at 37°C for a maximum of 30 minutes before coagulation testing. ROTEM tests included the EXTEM, INTEM, FIBTEM, and APTEM assays. In addition, prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen concentration (Clauss method) were analyzed for each cat. Reference intervals for ROTEM were calculated using the 2.5-97.5 th percentile for each parameter, and correlation with the standard coagulation profile was performed. Compared to people, clinically healthy cats had similar values for the EXTEM and INTEM assays, but had lower plasma fibrinogen concentrations (0.9-2.2 g/L), resulting in weaker maximum clot firmness (MCF, 3-10 mm) in the FIBTEM test. In 18 cats, maximum lysis (ML) values in the APTEM test were higher than in the EXTEM test, which seems unlikely to have occurred in the presence of aprotinin. It is possible that the observed high maximum lysis values were due to clot retraction rather than true clot lysis. Further studies will be required to test this hypothesis. Cats have a weaker clot in the FIBTEM test, but have a similar clot strength to human blood in the other ROTEM assays, which may be due to a stronger contribution of platelets compared to that found in people. In cats, careful interpretation of the results to diagnose hyperfibrinolysis is advised, especially with the APTEM test, until further data are available. © Veterinary Emergency and Critical Care Society 2017.

A simple clot based assay for detection of procoagulant cell-derived microparticles.

Science.gov (United States)

Patil, Rucha; Ghosh, Kanjaksha; Shetty, Shrimati

2016-05-01

Cell-derived microparticles (MPs) are important biomarkers in many facets of medicine. However, the MP detection methods used till date are costly and time consuming. The main aim of this study was to standardize an in-house clot based screening method for MP detection which would not only be specific and sensitive, but also inexpensive. Four different methods of MP assessment were performed and the results correlated. Using the flow cytometry technique as the gold standard, 25 samples with normal phosphatidylserine (PS) expressing MP levels and 25 samples with elevated levels were selected, which was cross checked by the commercial STA Procoag PPL clotting time (CT) assay. A simple recalcification time and an in-house clot assay were the remaining two tests. The in-house test measures the CT after the addition of calcium chloride to MP rich plasma, following incubation with Russell viper venom and phospholipid free plasma. The CT obtained by the in-house assay significantly correlated with the results obtained by flow cytometry (R2=0.87, p<0.01). Though preliminary, the in-house assay seems to be efficient, inexpensive and promising. It could definitely be utilized routinely for procoagulant MP assessment in various clinical settings.

Radioiodinated (I{sup 131} and I{sup 125}) Fibrinogen for the Detection of Malignant Tumours in Man; Emploi de Fibrinogene Marque avec {sup 131}I ou {sup 125}I pour la Detection de Tumeurs Malignes chez l'Homme; Primenenie mechennogo radioaktivnym Jodom-131 i Jodom-125 fibrinogena dlya obnaruzheniya zlokachestvennykh opukholej u cheloveka; Empleo el Fibrinogeno Radioyodado ({sup 131}I y {sup 125}I) para la Deteccion de Tumores Malignos en el Hombre

Energy Technology Data Exchange (ETDEWEB)

Monasterio, G.; Becchini, M. F.; Riccioni, N. [Centre of Nuclear Medicine, Medical Clinic, University of Pisa (Italy)

1964-10-15

A high fibrin content has been shown in a large number of malignant tumours, both experimental and human; this finding has been referred to the high thromboplastin content within the tumour, inducing the polymerization of fibrinogen into fibrin. On the basis of these data, human fibrinogen labelled with I{sup 131} and I{sup 125} has been tested as a possible agent for detecting malignant tumours in man. The uptake of radioiodinate fibrinogen has been studied in malignant and benign tumours, as well as non-neoplastic space-occupying lesions. Seventy-three cases have been so far examined; 53 of these were represented by malignant tumours localized in the skeleton, lungs, brain, abdominal organs etc. The I{sup 131}- fibrinogen uptake test gave correct results in 79% of the cases examined; no false positive results were obtained in the whole series. The technique and the results are briefly discussed. From the data obtained, it seems that fibrinogen-I{sup 131} may be usefully applied for the early detection of malignancies in man; possible improvements of the detection technique may markedly increase the diagnostic value of the method. (author) [French] Une teneur elevee en fibrine a ete mise en evidence dans un grand nombre de tumeurs malignes, tant chez l'homme que chez des animaux de laboratoire; on a impute ce phenomene au fait que la tumeur contient une forte proportion de thromboplastine qui provoque la formation de fibrine par polymerisation du fibrinogene. Sur cette base, les auteurs ont utilise du fibrinogene humain marque avec {sup 1}'3{sup 1}I ou {sup 125}I pour la detection de tumeurs malignes chez l'homme. Ils ont etudie la fixation du fibrinogene marque dans des tumeurs malignes et des tumeurs benignes, ainsi que dans des lesions en volume non-neoplastiques. Sur les 73 cas examines jusqu'a present, 53 etaient constitues par des tumeurs malignes localisees dans le squelette, les poumons, le cerveau, les organes abdominaux, etc. Le test de fixation du

Pilot Randomized trial of Fibrinogen in Trauma Haemorrhage (PRooF-iTH)

DEFF Research Database (Denmark)

Steinmetz, Jacob; Henriksen, Hanne Hee; Sørensen, Anne Marie

2016-01-01

bleeding related to trauma, so scientific guardians will co-sign the informed consent form. Next of kin and the patients’ general practitioner or the patients will co-sign as soon as possible.This trial will test whether immediate pre-emptive fibrinogen concentrate administered to adult trauma patients...

Fibrinogen binding sites P336 and Y338 of clumping factor A are crucial for Staphylococcus aureus virulence.

Directory of Open Access Journals (Sweden)

Elisabet Josefsson

Full Text Available We have earlier shown that clumping factor A (ClfA, a fibrinogen binding surface protein of Staphylococcus aureus, is an important virulence factor in septic arthritis. When two amino acids in the ClfA molecule, P(336 and Y(338, were changed to serine and alanine, respectively, the fibrinogen binding property was lost. ClfAP(336Y(338 mutants have been constructed in two virulent S. aureus strains Newman and LS-1. The aim of this study was to analyze if these two amino acids which are vital for the fibrinogen binding of ClfA are of importance for the ability of S. aureus to generate disease. Septic arthritis or sepsis were induced in mice by intravenous inoculation of bacteria. The clfAP(336Y(338 mutant induced significantly less arthritis than the wild type strain, both with respect to severity and frequency. The mutant infected mice developed also a much milder systemic inflammation, measured as lower mortality, weight loss, bacterial growth in kidneys and lower IL-6 levels. The data were verified with a second mutant where clfAP(336 and Y(338 were changed to alanine and serine respectively. When sepsis was induced by a larger bacterial inoculum, the clfAP(336Y(338 mutants induced significantly less septic death. Importantly, immunization with the recombinant A domain of ClfAP(336SY(338A mutant but not with recombinant ClfA, protected against septic death. Our data strongly suggest that the fibrinogen binding activity of ClfA is crucial for the ability of S. aureus to provoke disease manifestations, and that the vaccine potential of recombinant ClfA is improved by removing its ability to bind fibrinogen.

Author Details

African Journals Online (AJOL)

Achinike, P N. Vol 2, No 1 (2007) - Articles The effects of Aloe vera [gel] on clotting time, prothrombin time and plasma fibrinogen concentration in albino Wistar rats. Abstract. ISSN: 0795-3038. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL ...

A sensitive HPLC-MS/MS method for the simultaneous detection of microbial transglutaminase, and bovine and porcine fibrinogen/thrombin in restructured meat.

Science.gov (United States)

Jira, Wolfgang; Schwägele, Fredi

2017-12-15

A sensitive HPLC-MS/MS method for the simultaneous detection of microbial transglutaminase (TG) from Streptomyces mobaraensis, and bovine and porcine fibrinogen/thrombin in restructured meat was developed using tryptic marker peptides of TG (five markers), and bovine and porcine fibrinogen (six markers each). Meat binding experiments with beef and pork were performed using a technical TG mixture (Activa, Ajinomoto), and bovine and porcine plasmapowder FG (PPFG; Sonac B.V.). The method developed allows the simultaneous detection of the use of these cold-set binders in raw and heated samples. The peak areas of the fibrinogen marker peptides were increased by a factor of about 100, compared to blank values originating from the occurrence of residual blood in meat, using a concentration of 0.6% bovine and porcine PPFG. A differentiation between the use of blood plasma powder and PPFG using the ratios of fibrinogen to serotransferrin peptide peak areas seems to be possible. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between job characteristics and plasma fibrinogen in a normal working population: a cross sectional analysis in referents of the SHEEP Study. Stockholm Heart Epidemiology Program.

Science.gov (United States)

Tsutsumi, A; Theorell, T; Hallqvist, J; Reuterwall, C; de Faire, U

1999-06-01

To explore the association between job characteristics and plasma fibrinogen concentrations. Cross sectional design. The Greater Stockholm area. A total of 1018 men and 490 women aged 45-70 who were randomly selected from the general population during 1992-1994. They were all employed and had no history of myocardial infarction. The self reported job characteristics were measured by a Swedish version of the Karasek demand-control questionnaire. For inferred scoring of job characteristics, psychosocial exposure categories (job control and psychological demands) were assigned by linking each subject's occupational history with a work organisation exposure matrix. Job strain was defined as the ratio between demands and control. In univariate analyses, expected linear trends were found in three of four tests of association between high plasma fibrinogen and low control (the self reported score for women and the inferred score for both sexes), in one of four tests of association between high plasma fibrinogen and high demands (the inferred score for women) and in two of four tests of association between high plasma fibrinogen and job strain (the inferred score for both sexes). Multiple logistic regression analyses showed that men in the inferred job strain group have an increased risk of falling into the increased plasma fibrinogen concentration group (above median level of the distribution) (odds ratio (OR) 1.2; 95% CI 1.0, 1.5) after adjustment for the variables that were associated with plasma fibrinogen in the univariate analyses. In women, low self reported control, high inferred demand, and inferred job strain were significantly associated with increased plasma fibrinogen concentration (OR 1.3; 95% CI 1.0, 1.8, OR 1.5; 95% CI 1.0, 2.2, OR 1.5; 95% CI 1.1, 2.2, respectively). These results indicate that adverse job characteristics may be related to plasma fibrinogen concentrations and this relation is more relevant in female workers. The clearest evidence for

Extraction, radiolabeling, and in vivo catabolism of autologous-origin equine fibrinogen and platelets in the healthy and exercise-stressed horse

International Nuclear Information System (INIS)

Coyne, C.P.

1986-01-01

Three separate techniques were evaluated for the extraction of autologous-origin fibrinogen from whole equine plasma. Rapid extraction of equine fibrinogen with ammonium sulfate-sodium phosphate buffer, in combination with saturated glycine buffer, provided the most practical means of obtaining a protein extract with the highest degree of biological activity and sufficiently high iodine-125 ( 125 I) radiolabeling efficiencies using monochloroiodine reagent (ICI). A technique was developed for the in vitro radiolabeling of equine platelets suspended in plasma. This entailed the use of the isotope, indium-111 ( 111 In), together with the lipophilic ligand, 2-(mercaptopyridine-N-oxide). This labeling technique achieved labeling efficiencies between 75% and 96%, and in vitro aggregability of 111 In-merc radiolabeled platelets was comparable to that of unlabeled cell isolates. In the final phase of the investigation, autologous-origin 125 I-labeled fibrinogen and 111 In-labeled platelets were applied in a series of equine exercise physiology studies. Elimination of these two radiobiologicals was evaluated in the resting and exercise-stressed horse. Results from these investigations revealed no long-term influence of exercise conditioning on the in vivo kinetics of radiolabeled fibrinogen or platelets

21 CFR 864.7140 - Activated whole blood clotting time tests.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Activated whole blood clotting time tests. 864.7140 Section 864.7140 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864...

Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease

NARCIS (Netherlands)

Sabater-Lleal, M.; Huang, J.; Chasman, D.I.; Naitza, S.; Dehghan, A.; Johnson, A.D.; Teumer, A.; Reiner, A.P.; Folkersen, L.; Basu, S.; Rudnicka, A.R.; Trompet, S.; Mälarstig, A.; Baumert, J.; Bis, J.C.; Guo, X.; Hottenga, J.J.; Shin, S.Y.; Lopez, L.M.; Lahti, J.; Tanaka, T.; Yanek, L.R.; Oudot-Mellakh, T.; Wilson, J.F.; Navarro, P.; Huffman, J.E.; Zemunik, T.; Redline, S.; Mehra, R.; Pulanic, D.; Rudan, I.; Wright, A.F.; Kolcic, I.; Polasek, O.; Wild, S.H.; Campbell, H.; Curb, J.D.; Wallace, R.; Liu, S.; Eaton, C.B.; Becker, D.M.; Becker, L.C.; Bandinelli, S.; Räikkönen, K.; Widén, E.; Palotie, A.; Fornage, M.; Green, D.; Gross, M.; Davies, G.E.; Harris, S.E.; Liewald, D.C.; Starr, J.M.; Williams, F.M.; Grant, P.J.; Spector, T.D.; Strawbridge, R.J.; Silveira, A.; Sennblad, B.; Rivadeneira, F.; Uitterlinden, A.G.; Franco, O.H.; Hofman, A.; van Dongen, J.; Willemsen, G.; Boomsma, D.I.; Yao, J.; Swords Jenny, N.; Haritunians, T.; McKnight, B.; Lumley, T.; Taylor, K.D.; Rotter, J.I.; Psaty, B.M.; Peters, A.; Gieger, C.; Illig, T.; Grotevendt, A.; Homuth, G.; Völzke, H.; Kocher, T.; Goel, A.; Franzosi, M.G.; Seedorf, U.; Clarke, R.; Steri, M.; Tarasov, K.V.; Sanna, S.; Schlessinger, D.; Stott, D.J.; Sattar, N.; Buckley, B.M.; Rumley, A.; Lowe, G.D.; McArdle, W.L.; Chen, M.H.; Tofler, G.H.; Song, J.; Boerwinkle, E.; Folsom, A.R.; Rose, L.M.; Franco-Cereceda, A.; Teichert, M.; Ikram, M.A.; Mosley, T.H.; Bevan, S.; Dichgans, M.; Rothwell, P.M.; Sudlow, C.L.; Hopewell, J.C.; Chambers, J.C.; Saleheen, D.; Kooner, J.S.; Danesh, J.; Nelson, C.P.; Erdmann, J.; Reilly, M.P.; Kathiresan, S.; Schunkert, H.; Morange, P.E.; Ferrucci, L.; Eriksson, J.G.; Jacobs, D.; Deary, I.J.; Soranzo, N.; Witteman, J.C.; de Geus, E.J.C.; Tracy, R.P.; Hayward, C.; Koenig, W.; Cucca, F.; Jukema, J.W.; Eriksson, P.; Seshadri, S.; Markus, H.S.; Watkins, H.; Samani, N.J.; Wallaschofski, H.; Smith, N.L.; Tregouet, D.A.; Ridker, P.M.; Tang, W.; Strachan, D.P.; Hamsten, A.; O'Donnell, C.J.

2013-01-01

BACKGROUND-: Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. METHODS AND

Long-term cytokine and growth factor release from equine platelet-rich fibrin clots obtained with two different centrifugation protocols.

Science.gov (United States)

Jiménez-Aristizabal, Román F; López, Catalina; Álvarez, María E; Giraldo, Carlos; Prades, Marta; Carmona, Jorge U

2017-09-01

To compare the temporal release (over three weeks) of tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-1 receptor antagonist (IL-1ra), platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta-1 (TGF-β 1 ) from two platelet-rich fibrin (PRF) preparations from equine blood obtained at either 240g/8min or 416g/10min. Whole blood from 10 horses was used to obtain PRF clots by two different centrifugation protocols. After 1h of rest, PRF clots were deposited in wells with culture medium, which was changed at 6h, 24h and then every 48h to 21days. Cytokines and GFs were measured by ELISA at 1h (serum supernatants from PRF clots) and all time points of culture medium change. A negative control (plasma) and a positive control (blood lysate) were also included. There were no relevant differences between the two protocols for the temporal release of proteins. However, a significant (p=0.01) effect of time was noted. All cytokines were detected after 6h of PRF clot culture until day 21. GF were detected at 1h until day 21. The concentrations for these proteins diminished gradually over time. A highly significant (p=0.01) correlation was noticed between all the proteins evaluated. Leukocytes enmeshed in PRF clots were able to produce cytokines, TGF-β 1 and PDGF-BB. These findings demonstrate a paramount role of leukocytes in wound healing induced or modified by PRF clots in mammals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Purification and characterization of a milk-clotting protease from ...

African Journals Online (AJOL)

Crude enzymatic extract obtained from five fermentations (300 g of wheat bran) was characterized by a clotting activity of 0.34 ± 0.08 UP/ml with a strength ratio of 1/1: 200. The comparative study of the summaries from 2 purification protocols showed that it is possible to recover 6% of the initial proteins with a 44.54% activity ...

Release of peptides from Fibrinogen in vitro and in vivo

International Nuclear Information System (INIS)

Weibel, S.

1986-01-01

The dissertation deals experimentally with the following problem fields: The attempt was made to obtain extremely pure, native peptides from fibrinogen with micropreparation with the help of high-pressure liquid chromatography (HPLC); a HPLC-pure antigen which could be labelled (DAT-FPA) was also to be produced and a HPLC-purified, labelled antigen (J 125 DAT-FPA) for the radioimmunoassay was to be prepared. By applying HPLC-purified FPA-material to immunise rabbits, a highly specific antibody against FPA was obtained, and the radioimmunoassay was decisively improved. Furthermore, a method with a high recovery rate specific for the A-peptides could be found. A procedure was developed which is able to separate the modifications from the plasma from one another and to prove them specifically in ng-quantities. This is the first time that the sensitive method of high-pressure liquid chromatography is used to observe the effects of the snake venom enzymes on fibrinogen over a period of 20 hrs. The kinetics of intravenously administered J 123 DAT-FPA and, in comparison, J 123 FPB β 15-42 in vivo in rabbits with the help of a scintiscanning method, was investigated and the distribution in the organism and the ways of elimination were determined. (orig./MG) [de

Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease

NARCIS (Netherlands)

Sabater-Lleal, M.; Huang, J.; Chasman, D.; Naitza, S.; Dehghan, A.; Johnson, A.D.; Teumer, A.; Reiner, A.P.; Folkersen, L.; Basu, S.; Rudnicka, A.R.; Trompet, S.; Malarstig, A.; Baumert, J.; Bis, J.C.; Guo, X.; Hottenga, J.J.; Shin, S.Y.; Lopez, L.M.; Lahti, J.; Tanaka, T.; Yanek, L.R.; Oudot-Mellakh, T.; Wilson, J.F.; Navarro, P.; Huffman, J.E.; Zemunik, T.; Redline, S.; Mehra, R.; Pulanic, D.; Rudan, I.; Wright, A.F.; Kolcic, I.; Polasek, O.; Wild, S.H.; Campbell, H.; Curb, J.D.; Wallace, R.; Liu, S.; Eaton, C.B.; Becker, D.M.; Becker, L.C.; Bandinelli, S.; Raikkonen, K.; Widen, E.; Palotie, A.; Fornage, M.; Green, D.; Gross, M.; Davies, G.; Harris, S.E.; Liewald, D.C.; Starr, J.M.; Williams, F.M.; Grant, P.J.; Spector, T.D.; Strawbridge, R.J.; Silveira, A.; Sennblad, B.; Rivadeneira, F.; Uitterlinden, A.G.; Franco, O.H.; Hofman, A.; Dongen, J. Van; Willemsen, G.; Boomsma, D.I.; Yao, J.; Jenny, N. Swords; Haritunians, T.; McKnight, B.; Lumley, T.; Taylor, K.D.; Rotter, J.I.; Psaty, B.M.; Peters, A.; Gieger, C.; Illig, T.; Grotevendt, A.; Homuth, G.; Volzke, H.; Kocher, T.; Goel, A.; Franzosi, M.G.; Seedorf, U.; Clarke, R.; Steri, M.; Tarasov, K.V.; Sanna, S.; Schlessinger, D.; Stott, D.J.; Sattar, N.; Buckley, B.M.; Rumley, A.; Lowe, G.D.; McArdle, W.L.; Chen, M.H.; Tofler, G.H.; Song, J.; Boerwinkle, E.; Folsom, A.R.; Teichert, M.; et al.,

2013-01-01

BACKGROUND: Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. METHODS AND RESULTS:

Browse Title Index

African Journals Online (AJOL)

Items 351 - 400 of 400 ... Vol 2, No 1 (2007), The effects of Aloe vera [gel] on clotting time, prothrombin time and plasma fibrinogen concentration in albino Wistar rats, Abstract. D V Dapper, P N Achinike, M D Gwotmut. Vol 8, No 3 (2014), The effects of body mass index on some electrocardiographic parameters in young adults: ...

An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation.

Science.gov (United States)

Blasi, Annabel; Beltran, Joan; Pereira, Arturo; Martinez-Palli, Graciela; Torrents, Abiguei; Balust, Jaume; Zavala, Elizabeth; Taura, Pilar; Garcia-Valdecasas, Juan-Carlos

2012-09-01

Rotation thromboelastometry (TEM) has been proposed as a convenient alternative to standard coagulation tests in guiding the treatment of coagulopathy during orthotopic liver transplantation (OLT). This study was aimed at assessing the value of TEM in monitoring blood coagulation and guide transfusion support in OLT. Standard coagulation and TEM (EXTEM and FIBTEM) tests were performed at four preestablished intraoperative time points in 236 OLTs and prospectively recorded in a dedicated database together with the main operative and transfusion data. Transfusion thresholds were based on standard coagulation tests. Spearman's rank correlation (ρ), linear regression, and receiver operating characteristic curves were used when appropriate. EXTEM maximum clot firmness (MCF(EXTEM)) was the TEM variable that best correlated with the platelet (PLT) and fibrinogen levels (ρ = 0.62 and ρ = 0.69, respectively). MCF(FIBTEM) correlated with fibrinogen level (ρ = 0.70). EXTEM clot amplitude at 10 minutes (A10(EXTEM)) was a good linear predictor of MCF(EXTEM) (R(2) =0.93). The cutoff values that best predicted the transfusion threshold for PLTs and fibrinogen were A10(EXTEM) = 35 mm and A10(FIBTEM) = 8 mm. At these values, the negative and positive predictive accuracies of TEM to predict the transfusion thresholds were 95 and 27%, respectively. A10(EXTEM) is an adequate TEM variable to guide therapeutic decisions during OLT. Patients with A10(EXTEM) of greater than 35 mm are unlikely to bleed because of coagulation deficiencies, but using A10(EXTEM) of not more than 35 mm as the sole transfusion criterion can lead to unnecessary utilization of PLTs and fibrinogen-rich products. © 2012 American Association of Blood Banks.

A novel fibrinogen variant - Praha I: hypofibrinogenemia associated with .gamma. Gly351Ser substitution

Czech Academy of Sciences Publication Activity Database

Kotlín, R.; Chytilová, M.; Suttnar, J.; Salaj, P.; Riedel, Tomáš; Šantrůček, J.; Klener, P.; Dyr, J. E.

2007-01-01

Roč. 78, č. 5 (2007), s. 410-416 ISSN 0902-4441 Institutional research plan: CEZ:AV0Z40500505 Keywords : fibrinogen * missense mutation * hypofibrinogenemia Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.163, year: 2007

A novel fibrinogen variant - Liberec: dysfibrinogenaemia associated with gamma Tyr262Cys substitution

Czech Academy of Sciences Publication Activity Database

Kotlín, R.; Sobotková, A.; Suttnar, J.; Salaj, P.; Walterová, L.; Riedel, Tomáš; Reicheltová, Z.; Dyr, J. E.

2008-01-01

Roč. 81, č. 2 (2008), s. 123-129 ISSN 0902-4441 R&D Projects: GA AV ČR KAN200670701 Institutional research plan: CEZ:AV0Z40500505 Keywords : fibrinogen * missense mutation * dysfibrinogenaemia Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.237, year: 2008

The conversion of fibrinogen to fibrin: A brief history of some key events.

Science.gov (United States)

Doolittle, Russell F

2017-07-01

The conversion of fibrinogen to fibrin is a process that has long fascinated an army of researchers. In this brief review some early break-through observations are noted and a few later unexpected results described. Copyright © 2016 Elsevier B.V. All rights reserved.

Lipid profile and levels of homocysteine, leptin, fibrinogen and C-reactive protein in hyperthyroid patients before and after treatment

Directory of Open Access Journals (Sweden)

Emine Sütken

2010-03-01

Full Text Available Objectives: The present study was carried out to determine whether thyroid hormones affect lipid profile and levels of erithrocyte sedimentation rate (ESR, serum total homocysteine (t-hcy, leptin, fibrinogen, C-reactive protein (CRP in patients with hyperthyroidism.Materials and methods: This study was carried out on 23 hyperthroid subjects (3 men / 20 women, mean age 41.8 ± 2.4 years. Serum levels of homocysteine, leptin, fibrinogen, CRP, total cholesterol (TC, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C and ESR were measured and body mass index (BMI were calculated before and after treatment of hyperthyroidism.Results: Pretreatment t-hcy, TC, LDL-C, HDL-C levels and BMI of patients were significantly lower than those of the post-treatment (p<0.001, for each variable. However, fibrinogen and ESR decreased after the treatment (p<0.001 and p<0.05, respectively. There were no differences in leptin and CRP levels between pre- and post-treatment periods. Pre and post treatment TC and LDL-C levels were negatively correlated with free triiodothyronine (fT3 levels (r=-0.588, p<0.01; r=-0.534, p<0.01; r=-0.543, p<0.01 and r =-0.653, p<0.01, respectively. Pre-treatment HDL-C was inversely correlated with TSH (r=-0.423, p<0.05. Pre-post- treatment LDL-C was negatively correlated with free thyroxine (fT4 levels (r=-0.536, p<0.001 and r=- 0.422, p<0.05 respectively. Pre-treatment TC was inversely correlated with fT4 (r=-0.590, p<0.01.Conclusion: Hyperthyroidism is associated with high plasma fibrinogen and ESR levels. Elevated plasma fibrinogen and ESR levels may be a possible explanation for the high cardiovascular morbidity among hyperthyroidic subjects. These changes may reflect low-grade inflammation or disturbances in coagulation in hyperthyroidism.

Three-dimensional architecture and cell composition of a Choukroun's platelet-rich fibrin clot and membrane.

Science.gov (United States)

Dohan Ehrenfest, David M; Del Corso, Marco; Diss, Antoine; Mouhyi, Jaafar; Charrier, Jean-Baptiste

2010-04-01

Platelet-rich fibrin (PRF; Choukroun's technique) is a second-generation platelet concentrate for surgical use. This easy protocol allows the production of leukocyte and platelet-rich fibrin clots and membranes starting from 10-ml blood samples. The purposes of this study were to determine the cell composition and three-dimensional organization of this autologous biomaterial and to evaluate the influence of different collection tubes (dry glass or glass-coated plastic tubes) and compression procedures (forcible or soft) on the final PRF-membrane architecture. After centrifugation, blood analyses were performed on the residual waste plasmatic layers after collecting PRF clots. The PRF clots and membranes were processed for examination by light microscopy and scanning electron microscopy. Approximately 97% of the platelets and >50% of the leukocytes were concentrated in the PRF clot and showed a specific three-dimensional distribution, depending on the centrifugation forces. Platelets and fibrin formed large clusters of coagulation in the first millimeters of the membrane beyond the red blood cell base. The fibrin network was very mature and dense. Moreover, there was no significant difference in the PRF architecture between groups using the different tested collection tubes and compression techniques, even if these two parameters could have influenced the growth factor content and biologic matrix properties. The PRF protocol concentrated most platelets and leukocytes from a blood harvest into a single autologous fibrin biomaterial. This protocol offers reproducible results as long as the main production principles are respected.

Cross-linking methods of electrospun fibrinogen scaffolds for tissue engineering applications

International Nuclear Information System (INIS)

Sell, Scott A; Garg, Koyal; McClure, Michael J; Bowlin, Gary L; Francis, Michael P; Simpson, David G

2008-01-01

The purpose of this study was to enhance the mechanical properties and slow the degradation of an electrospun fibrinogen scaffold, while maintaining the scaffold's high level of bioactivity. Three different cross-linkers were used to achieve this goal: glutaraldehyde vapour, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in ethanol and genipin in ethanol. Scaffolds with a fibrinogen concentration of 120 mg ml -1 were electrospun and cross-linked with one of the aforementioned cross-linkers. Mechanical properties were determined through uniaxial tensile testing performed on scaffolds incubated under standard culture conditions for 1 day, 7 days and 14 days. Cross-linked scaffolds were seeded with human foreskin fibroblasts (BJ-GFP-hTERT) and cultured for 7, 14 and 21 days, with histology and scanning electron microscopy performed upon completion of the time course. Mechanical testing revealed significantly increased peak stress and modulus values for the EDC and genipin cross-linked scaffolds, with significantly slowed degradation. However, cross-linking with EDC and genipin was shown to have some negative effect on the bioactivity of the scaffolds as cell migration throughout the thickness of the scaffold was slowed.

Alkali treatment of microrough titanium surfaces affects macrophage/monocyte adhesion, platelet activation and architecture of blood clot formation

Directory of Open Access Journals (Sweden)

V Milleret

2011-05-01

Full Text Available Titanium implants are most commonly used for bone augmentation and replacement due to their favorable osseointegration properties. Here, hyperhydrophilic sand-blasted and acid-etched (SBA titanium surfaces were produced by alkali treatment and their responses to partially heparinized whole human blood were analyzed. Blood clot formation, platelet activation and activation of the complement system was analyzed revealing that exposure time between blood and the material surface is crucial as increasing exposure time results in higher amount of activated platelets, more blood clots formed and stronger complement activation. In contrast, the number of macrophages/monocytes found on alkali-treated surfaces was significantly reduced as compared to untreated SBA Ti surfaces. Interestingly, when comparing untreated to modified SBA Ti surfaces very different blood clots formed on their surfaces. On untreated Ti surfaces blood clots remain thin (below 15 mm, patchy and non-structured lacking large fibrin fiber networks whereas blood clots on differentiated surfaces assemble in an organized and layered architecture of more than 30 mm thickness. Close to the material surface most nucleated cells adhere, above large amounts of non-nucleated platelets remain entrapped within a dense fibrin fiber network providing a continuous cover of the entire surface. These findings might indicate that, combined with findings of previous in vivo studies demonstrating that alkali-treated SBA Ti surfaces perform better in terms of osseointegration, a continuous and structured layer of blood components on the blood-facing surface supports later tissue integration of an endosseous implant.

An increase in the cerebral infarction area during fatigue is mediated by il-6 through an induction of fibrinogen synthesis

Directory of Open Access Journals (Sweden)

Hong Lei

2014-06-01

Full Text Available OBJECTIVES:Our study aimed to investigate the impact of fatigue on the severity of stroke and to explore the underlying mechanisms.METHODS:Fatigued male rats underwent middle cerebral artery occlusion and the infarcted brain area was determined. Then, coagulation parameters were assessed in the fatigued group and a control group. In addition, the level of fibrinogen was determined in rats deprived of sleep for various numbers of days. To study whether interleukin-6 was involved in fibrinogen synthesis during fatigue, we also measured levels of interleukin-6 in rats deprived of sleep for various numbers of days. Furthermore, brain injury by middle cerebral artery occlusion was measured in wild-type mice, interleukin-6-/- mice and wild-type mice treated with bezafibrate.RESULTS:More severe cerebral infarction was observed in the fatigued rats, resulting in an infarct ratio of 23.4%. The infarct ratio was significantly increased in the fatigued rats compared with that in the control group (8%, p<0.05. The level of fibrinogen was increased significantly in the fatigued rats compared with that in the control group. In addition, a marked reduction in fibrinogen level was observed in the fatigued interleukin-6-/- mice compared to their wild-type counterparts, whereas no difference was observed between fatigued wild-type mice and interleukin-6-/- rats treated with recombinant human interleukin-6. The reduction in brain injury due to middle cerebral artery occlusion during fatigue was observed in interleukin-6-/- mice and wild-type mice treated with bezafibrate.CONCLUSION:Fatigue could increase stroke severity and was associated with the interleukin-6-induced expression of fibrinogen.

Fibrinogen Demonstration in Oral Lichen Planus: An Immunofluorescence Study on Archival Tissues.

Science.gov (United States)

Shirol, Pallavi D; Naik, Veena; Kale, Alka

2015-10-01

Lichen planus is a premalignant condition with minimal diagnostic aids. This study is an attempt to use paraffin embedded sections of lichen planus with immunofluorescein stain and to evaluate the immunofluorescent sections to establish pattern of fibrinogen deposition. Thirty-five paraffin embedded sections of old and new cases of oral lichen planus (study group) and five normal oral mucosa (control group) were chosen. Two sections of each (H & E) case were taken, one was stained with hematoxylin and eosin and another with fluorescein isothiocynate conjugate (FITC) polyclonal rabbit antibody against fibrinogen. Fluorescent findings were examined with a fluorescent microscope. A high statistical significant correlation was found in respect to fluorescence positivity, intensity of fluorescence and distribution of fluorescence each with p < 0.0001 and fluorescence at blood vessel walls (p = 0.0003). This study suggested that paraffin embedded sections can be successfully used in direct immunofluorescence staining in routine set up where only formalin fixed tissues are received. Paraffin embedded sections can be successfully used in direct immunofluorescence staining when only formalin fixed tissues are received.

Thin films growth parameters in MAPLE; application to fibrinogen

International Nuclear Information System (INIS)

Jelinek, M; Cristescu, R; Kocourek, T; Vorlicek, V; Remsa, J; Stamatin, L; Mihaiescu, D; Stamatin, I; Mihailescu, I N; Chrisey, D B

2007-01-01

Increasingly requirements on the thin film quality of functionalized materials are efficiently met by a novel laser processing technique - Matrix Assisted Pulsed Laser Evaporation (MAPLE). Examples of deposition conditions and main features characteristic to film growth rate of MAPLE-fabricated organic materials are summarized. MAPLE experimental results are compared with ones corresponding to the classical Pulsed Laser Deposition (PLD). In particular, the results of investigation of MAPLE-deposited fibrinogen blood protein thin films using a KrF* excimer laser and characterized by FTIR and Raman spectrometry are reported

Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen.

Science.gov (United States)

Wu, T; Trevisan, M; Genco, R J; Falkner, K L; Dorn, J P; Sempos, C T

2000-02-01

Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the relation between periodontal health and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. A total of 10,146 participants were included in the analyses of cholesterol and C-reactive protein and 4,461 in the analyses of fibrinogen. Periodontal health indicators included the gingival bleeding index, calculus index, and periodontal disease status (defined by pocket depth and attachment loss). While cholesterol and fibrinogen were analyzed as continuous variables, C-reactive protein was dichotomized into two levels. The results show a significant relation between indicators of poor periodontal status and increased C-reactive protein and fibrinogen. The association between periodontal status and total cholesterol level is much weaker. No consistent association between periodontal status and high density lipoprotein cholesterol was detectable. Similar patterns of association were observed for participants aged 17-54 years and those 55 years and older. In conclusion, this study suggests that total cholesterol, C-reactive protein, and fibrinogen are possible intermediate factors that may link periodontal disease to elevated cardiovascular risk.

A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

DEFF Research Database (Denmark)

de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria

2016-01-01

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. W...

A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

NARCIS (Netherlands)

P.S. de Vries (Paul); D.I. Chasman (Daniel); M. Sabater-Lleal (Maria); M.-H. Chen (Ming-Huei); J.E. Huffman (Jennifer E.); M. Steri (Maristella); W. Tang (Weihong); A. Teumer (Alexander); R.E. Marioni (Riccardo); V. Grossmann (Vera); J.J. Hottenga (Jouke Jan); S. Trompet (Stella); M. Müller-Nurasyid (Martina); J.H. Zhao (Jing Hua); J. Brody (Jennifer); M.E. Kleber (Marcus); X. Guo (Xiuqing); J.J. Wang (Jie Jin); P. Auer (Paul); J. Attia (John); L.R. Yanek (Lisa); T.S. Ahluwalia (Tarunveer Singh); J. Lahti (Jari); C. Venturini (Cristina); T. Tanaka (Toshiko); L.F. Bielak (Lawrence F.); P.K. Joshi (Peter); A. Rocanin-Arjo (Ares); I. Kolcic (Ivana); P. Navarro (Pau); L.M. Rose (Lynda); C. Oldmeadow (Christopher); H. Riess (Helene); J. Mazur (Johanna); S. Basu (Saonli); A. Goel (Anuj); Q. Yang (Qiong); M. Ghanbari (Mohsen); Gonnekewillemsen; A. Rumley (Ann); E. Fiorillo (Edoardo); A.J. de Craen (Anton); A. Grotevendt (Anne); R.A. Scott (Robert); K.D. Taylor (Kent D.); G.E. Delgado (Graciela E.); J. Yao (Jie); A. Kifley (Annette); C. Kooperberg (Charles); Q. Qayyum (Rehan); L. Lopez (Lornam); T.L. Berentzen (Tina L.); K. Räikkönen (Katri); Massimomangino; S. Bandinelli (Stefania); P.A. Peyser (Patricia A.); S. Wild (Sarah); D.-A. Tregouet (David-Alexandre); A.F. Wright (Alan); J. Marten (Jonathan); T. Zemunik (Tatijana); A.C. Morrison (Alanna); B. Sennblad (Bengt); G.H. Tofler (Geoffrey); M.P.M. de Maat (Moniek); E.J.C. de Geus (Eco); G.D. Lowe (Gordon D.); M. Zoledziewska (Magdalena); N. Sattar (Naveed); H. Binder (Harald); U. Völker (Uwe); M. Waldenberger (Melanie); K.-T. Khaw (Kay-Tee); B. McKnight (Barbara); J. Huang (Jian); N.S. Jenny (Nancy); E.G. Holliday (Elizabeth); L. Qi (Lihong); M.G. Mcevoy (Mark G.); D.M. Becker (Diane); J.M. Starr (John); A.-P. Sarin; P.G. Hysi (Pirro); D.G. Hernandez (Dena); M.A. Jhun (Min A.); H. Campbell (Harry); A. Hamsten (Anders); F. Sarin (Fernando); W.L. McArdle (Wendy); P. Eline Slagboom; T. Zeller (Tanja); W. Koenig (Wolfgang); B. Psaty (Brucem); T. Haritunians (Talin); J. Liu (Jingmin); A. Palotie (Aarno); A.G. Uitterlinden (André); D.J. Stott (David J.); A. Hofman (Albert); O.H. Franco (Oscar); O. Polasek (Ozren); I. Rudan (Igor); P.-E. Morange (P.); J.F. Wilson (James F.); S.L. Kardia (Sharon L.r); L. Ferrucci (Luigi); T.D. Spector (Timothy); J.G. Eriksson (Johan G.); T. Hansen (Torben); I.J. Deary (Ian); L.C. Becker (Lewis); R.J. Scott (Rodney); P. Mitchell (Paul); W. März (Winfried); N.J. Wareham (Nick J.); A. Peters (Annette); A. Greinacher (Andreas); P.S. Wild (Philipp S.); J.W. Jukema (Jan Wouter); D.I. Boomsma (Dorret I.); C. Hayward (Caroline); F. Cucca (Francesco); R.P. Tracy (Russell); H. Watkins (Hugh); A.P. Reiner (Alex P.); A.R. Folsom (Aaron); P.M. Ridker (Paul); C.J. O'Donnell (Christopher J.); N.L. Smith (Nicholas L.); D.P. Strachan (David P.); A. Dehghan (Abbas)

2016-01-01

textabstractGenome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes

Embolus radiolabelling in a new canine model

International Nuclear Information System (INIS)

Kaufman, H.H.; Huchton, J.D.; Woo, J.; Cannon, D.C.; Anderson, J.H.

1980-01-01

Embolus radiolabelling with 131 I fibrinogen was studied in a canine model of internal carotid artery embolization. The dog was chosen as the experimental animal because of its maxillocarotid artery which permits collateral flow round the occlusion and helps to prevent strokes. Clot was prepared by incubating blood at room temperature to inactivate plasminogen activators and then refrigerating it to promote clot retraction. Emboli persisting 48 hours were seen in 80% of animals. Major strokes were not seen when 0.25 to 0.30 cm 3 were used. Autoradiography and well counting revealed uptake of isotope. The test, when refined, should provide a tool for the investigation of thromboemboli. (author)

Chitosan inhibits platelet-mediated clot retraction, increases platelet-derived growth factor release, and increases residence time and bioactivity of platelet-rich plasma in vivo.

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Deprés-Tremblay, Gabrielle; Chevrier, Anik; Tran-Khanh, Nicolas; Nelea, Monica; Buschmann, Michael D

2017-11-10

Platelet-rich plasma (PRP) has been used to treat different orthopedic conditions, however, the clinical benefits of using PRP remain uncertain. Chitosan (CS)-PRP implants have been shown to improve meniscus, rotator cuff and cartilage repair in pre-clinical models. The purpose of this current study was to investigate in vitro and in vivo mechanisms of action of CS-PRP implants. Freeze-dried formulations containing 1% (w/v) CS (80% degree of deacetylation and number average molar mass 38 kDa), 1% (w/v) trehalose as a lyoprotectant and 42.2 mM calcium chloride as a clot activator were solubilized in PRP. Gravimetric measurements and molecular/cellular imaging studies revealed that clot retraction is inhibited in CS-PRP hybrid clots through physical coating of platelets, blood cells and fibrin strands by chitosan, which interferes with platelet aggregation and platelet-mediated clot retraction. Flow cytometry and ELISA assays revealed that platelets are activated and granules secreted in CS-PRP hybrid clots and that cumulative release of platelet-derived growth factor (PDGF-AB) and epidermal growth factor is higher from CS-PRP hybrid clots compared to PRP clots in vitro. Finally, CS-PRP implants resided for up to 6 weeks in a subcutaneous implantation model and induced cell recruitment and granulation tissue synthesis, confirming greater residency and bioactivity compared to PRP in vivo.

RESULTS OF QUALITY COMPREHENSIVE EVALUATION OF DENTAL CARE FOR CHILDREN WITH BLOOD CLOTTING (PATHOLOGY

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M. A. Gavrilenko

2014-04-01

Full Text Available Background. Treatment methods for diseases of teeth hard tissues and periodontium for children with blood clotting pathology are described in modern literature. But in practice we are faced with the problem of providing dental treatment for these children. Work of pediatric dentist is prevented by the risk of bleeding, fear of dental procedures, child’s psychoemotional tension and refusal of treatment because of bleeding. Taking into account the specificity of blood clotting pathology, surgical methods of dental treatment prevail for these children, which is evidenced by the early loss of deciduous and permanent teeth, occlusal surface disturbances, dentoalveolar anomalies, inflammatory diseases of periodontal tissues. Aim. To evaluate the level of dental care for children with the diseases of blood clotting. Materials and methods. 120 children between 2 and 18 years old with blood clotting disorders (hemophilia A, B, thrombocytopenia, thrombocytopathy were examined. Children were divided into groups: I group – 2-5 years old (40 children, II group – 6-10 years old (40 children, III group – 11-18 years old (40 children, according to the periods of tooth development, with an equal number of children in groups according to diagnoses. Clinical examination was carried out according to the standard scheme, including the analysis of complaints, anamnesis of treatment at the dentist, objective data with the use of statistical method of masticatory efficiency (according to N.I. Agapov, the level of dental care (according to P.A. Leus. Results. During clinical dental examination of children with blood clotting pathology it was found that destruction of crowns of maxillary front teeth, the first deciduous molars and the second deciduous molars, as well as their loss, prevails in the temporary occlusion. During the examination of 2-5 years old children with blood clotting pathology, loss of less than 25% of masticatory efficiency was revealed for 25

Development of a tool for prediction of ovarian cancer in patients with adnexal masses: Value of plasma fibrinogen.

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Veronika Seebacher

Full Text Available To develop a tool for individualized risk estimation of presence of cancer in women with adnexal masses, and to assess the added value of plasma fibrinogen.We performed a retrospective analysis of a prospectively maintained database of 906 patients with adnexal masses who underwent cystectomy or oophorectomy. Uni- and multivariate logistic regression analyses including pre-operative plasma fibrinogen levels and established predictors were performed. A nomogram was generated to predict the probability of ovarian cancer. Internal validation with split-sample analysis was performed. Decision curve analysis (DCA was then used to evaluate the clinical net benefit of the prediction model.Ovarian cancer including borderline tumours was found in 241 (26.6% patients. In multivariate analysis, elevated plasma fibrinogen, elevated CA-125, suspicion for malignancy on ultrasound, and postmenopausal status were associated with ovarian cancer and formed the basis for the nomogram. The overall predictive accuracy of the model, as measured by AUC, was 0.91 (95% CI 0.87-0.94. DCA revealed a net benefit for using this model for predicting ovarian cancer presence compared to a strategy of treat all or treat none.We confirmed the value of plasma fibrinogen as a strong predictor for ovarian cancer in a large cohort of patients with adnexal masses. We developed a highly accurate multivariable model to help in the clinical decision-making regarding the presence of ovarian cancer. This model provided net benefit for a wide range of threshold probabilities. External validation is needed before a recommendation for its use in routine practice can be given.

Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies.

Science.gov (United States)

Yarnell, J W; Baker, I A; Sweetnam, P M; Bainton, D; O'Brien, J R; Whitehead, P J; Elwood, P C

1991-03-01

Recent studies have suggested that hemostatic factors and white blood cell count are predictive of ischemic heart disease (IHD). The relations of fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. The two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count. Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count. Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both. Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors. Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index. Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD.

Fibrinogen: a novel predictor of responsiveness in metastatic melanoma patients treated with bio-chemotherapy: IMI (italian melanoma inter-group) trial

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Guida, Michele; Ravaioli, Alessandra; Sileni, Vanna Chiarion; Romanini, Antonella; Labianca, Roberto; Freschi, Antonio; Brugnara, Salvatore; Casamassima, Addolorata; Lorusso, Vito; Nanni, Oriana; Ridolfi, Ruggero

2003-01-01

Purpose To evaluate a panel of pretreatment clinical and laboratory parameters in metastatic melanoma (MM) in order to verify their impact on response and survival in a single prospective multi-institutional phase III study comparing out-patient chemotherapy (CT) vs bioCT. Methods A total of 176 patients were randomised to receive CT (cisplatin, dacarbazine, optional carmustine) or bioCT (the same CT followed by subcutaneous IL-2 plus intramuscular α-IFN-2b). Pretreatment total leucocytes, lymphocytes, eosinophyls, C-reactive protein (CRP), lactate dehydrogenase (LDH), erytrosedimentation rate (ESR), and fibrinogen were analyzed. Some clinical parameters (performance status, age, sex, and disease site) were also considered. As we found a positive trend for bio-CT with no statistical significance in OR (25.3% vs 20.2%) and OS (11 Mo vs 9.5 Mo), all analyses are stratified by treatment arm. Results In univariate analysis, higher value of lymphocytes percentage (P < .0001), lower value of total leucocytes (P=.005), CRP (P=.003), LHD (P < .0001), ESR (P < .027), fibrinogen (P < .0001), and no liver disease were strongly related to a better survival. In a multivariate analysis, using the Cox proportional hazards model, only fibrinogen (P=.004), LDH (P=.009) and liver disease (P=.04) were found to have an independent role on clinical outcome in metastatic melanoma patients. Conclusion Liver disease and higher LDH and fibrinogen levels had an important impact on survival in MM patients. In particular, fibrinogen has been recently reconsidered both for its determinant role in the host hemostatic system, and for its capability to provide protection against NK and LAK-cell-induced lysis. These observations could have some important implications for therapeutic approaches, in particular when immunological strategies are used. PMID:14690541

Abnormal fibrinogen Zlín (.gamma.Thr21Ile) with missense mutation causing hypofibrinogenemia

Czech Academy of Sciences Publication Activity Database

Riedelová-Reicheltová, Z.; Riedel, Tomáš; Májek, P.; Kotlín, R.; Geierová, V.; Suttnar, J.; Dyr, J. E.

2014-01-01

Roč. 132, č. 2 (2014), s. 140-143 ISSN 0001-5792 R&D Projects: GA ČR GBP205/12/G118 Institutional support: RVO:61389013 Keywords : fibrinogen * missense mutation * hypofibrinogenemia Subject RIV: BO - Biophysics Impact factor: 1.116, year: 2014

Thromboelastographic study of the snakebite-related coagulopathy in Djibouti.

Science.gov (United States)

Larréché, Sébastien; Jean, François-Xavier; Benois, Alain; Mayet, Aurélie; Bousquet, Aurore; Vedy, Serge; Clapson, Patrick; Dehan, Céline; Rapp, Christophe; Kaiser, Eric; Mérens, Audrey; Mion, Georges; Martinaud, Christophe

2018-03-01

: Hemostasis disorders are one of the major clinical conditions of snakebites and are because of mechanisms which may disrupt vessels, platelets, clotting factors and fibrinolysis. Thromboelastography (TEG) could help to understand these effects in the clinical practice. A retrospective study reports a series of patients presenting a snakebite-related coagulopathy, treated with antivenom and monitored with conventional tests and TEG in a French military treatment facility (Republic of Djibouti, East Africa) between August 2011 and September 2013. Conventional coagulation assays (platelets, prothrombin time, activated partial thromboplastin time, fibrinogen) and TEG measurements were taken on arrival and at various times during the first 72 h of hospitalization, at the discretion of the physician. The study included 14 patients (median age 28 years). Bleedings were present in five patients. All patients received antivenom. A coagulopathy was present in all patients and was detected by both conventional assays and TEG. None exhibited thrombocytopenia. Prothrombin time and fibrinogen remained abnormal for most of patients during the first 72 h. The TEG profiles of 11 patients (79%) showed incoagulability at admission (R-time > 60 min). TEG distinguished 10 patients with a generalized clotting factor deficiency and 4 patients with an isolated fibrinogen deficiency after an initial profile of incoagulability. Hyperfibrinolysis was evident for 12 patients (86%) after Hour 6. Snake envenomations in Djibouti involve a consumption coagulopathy in conjunction with delayed hyperfibrinolysis. TEG could improve medical management of the condition and assessment of additional therapeutics associated with the antivenom.

Hemostasia normal y coagulación intravascular diseminada en obstetricia Normal hemostasis and disseminated intravascular clotting in Obstetrics

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Danilo Nápoles Méndez

2012-03-01

Full Text Available En el período gravido - puerperal, la coagulación sanguínea sufre cambios que se impone conocer para interpretar correctamente esos trastornos cuando se presentan en esta etapa, teniendo en cuenta las posibles complicaciones y el peligro para la vida que pueden presentarse. El objetivo del presente artículo es proporcionar a los obstetras una revisión bibliográfica que les permita actualizarse acerca del tema y facilite su modo de actuación ante pacientes con coagulación intravascular diseminada. Se concluye que es preciso diagnosticar tempranamente el proceso en la fase bioquímica de bajo grado y aplicar en las féminas el tratamiento expedito de la enfermedad de base para eliminar las complicaciones o disminuir su ocurrenciaIn the period from pregnancy to puerperium, blood clotting suffers changes which are important to be known in order to interpret correctly those dysfunctions when they appear in this stage, keeping in mind the possible complications and the danger for life which can take place. The objective of the present work is to provide the obstetricians a literature review that allows them to be updated about the topic and facilitate their performance in case of patients with disseminated intravascular clotting. It is concluded that it is necessary to have an early diagnosis on the process during the low grade biochemical phase and to apply in these women the expedite treatment of the base disease to eliminate complications or to decrease their occurrence.

99mTc-NC100668, a new tracer for imaging venous thromboemboli: pre-clinical biodistribution and incorporation into plasma clots in vivo and in vitro

International Nuclear Information System (INIS)

Edwards, David; Lewis, Joanne; Battle, Mark; Lear, Rochelle; Farrar, Gill; Barnett, D.J.; Godden, Vanessa; Oliveira, Alexandra; Coombes, Catherine; Ahlstroem, Haakan

2006-01-01

99m Tc-NC100668 is a new radiotracer being developed to aid the diagnosis of thromboembolism. The structure of NC100668 is similar to a region of human α 2 -antiplasmin, which is a substrate for factor XIIIa (FXIIIa). The purpose of this study was to confirm the uptake of 99m Tc-NC100668 into forming plasma clot and to establish the biodistribution of 99m Tc-NC100668 in Wistar rats. The in vitro plasma clot uptake of 99m Tc-NC100668 and other compounds with known affinities to FXIIIa was measured using a plasma clot assay. The biodistribution and blood clot uptake of radioactivity of 99m Tc-NC100668 in normal Wistar rats and those bearing experimentally induced deep vein thrombi were investigated. The in vitro uptake of 99m Tc-NC100668 was greater than that for [ 14 C]dansyl cadaverine, a known substrate of FXIIIa in the plasma clot assay. The biodistribution of 99m Tc-NC100668 in male and female Wistar rats up to 24 h p.i. showed that radioactivity was rapidly excreted, predominantly into the urine, with very little background tissue retention. In vivo the uptake and retention of 99m Tc-NC100668 into the blood clot was greater than could be accounted for by non-specific accumulation of the radiotracer within the blood clot. 99m Tc-NC100668 was retained by plasma clots in vitro and blood clots in vivo. No significant tissue retention which could interfere with the ability to image thrombi in vivo was observed. This evidence suggests that 99m Tc-NC100668 might be useful in the detection of thromboembolism. (orig.)

Cloning, expression and characterization of a gene from earthworm Eisenia fetida encoding a blood-clot dissolving protein.

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GangQiang Li

Full Text Available A lumbrokinase gene encoding a blood-clot dissolving protein was cloned from earthworm (Eisenia fetida by RT-PCR amplification. The gene designated as CST1 (GenBank No. AY840996 was sequence analyzed. The cDNA consists of 888 bp with an open reading frame of 729 bp, which encodes 242 amino acid residues. Multiple sequence alignments revealed that CST1 shares similarities and conserved amino acids with other reported lumbrokinases. The amino acid sequence of CST1 exhibits structural features similar to those found in other serine proteases, including human tissue-type (tPA, urokinase (uPA, and vampire bat (DSPAα1 plasminogen activators. CST1 has a conserved catalytic triad, found in the active sites of protease enzymes, which are important residues involved in polypeptide catalysis. CST1 was expressed as inclusion bodies in Escherichia coli BL21(DE3. The molecular mass of recombinant CST1 (rCST was 25 kDa as estimated by SDS-PAGE, and further confirmed by Western Blot analysis. His-tagged rCST1 was purified and renatured using nickel-chelating resin with a recovery rate of 50% and a purity of 95%. The purified, renatured rCST1 showed fibrinolytic activity evaluated by both a fibrin plate and a blood clot lysis assay. rCST1 degraded fibrin on the fibrin plate. A significant percentage (65.7% of blood clot lysis was observed when blood clot was treated with 80 mg/mL of rCST1 in vitro. The antithrombotic activity of rCST1 was 912 units/mg calculated by comparison with the activity of a lumbrokinase standard. These findings indicate that rCST1 has potential as a potent blood-clot treatment. Therefore, the expression and purification of a single lumbrokinase represents an important improvement in the use of lumbrokinases.

Staphylococcus chromogenes, a Coagulase-Negative Staphylococcus Species That Can Clot Plasma

OpenAIRE

dos Santos, Danielle Cabral; Lange, Carla Christine; Avellar-Costa, Pedro; dos Santos, Katia Regina Netto; Brito, Maria Aparecida Vasconcelos Paiva; Giambiagi-deMarval, Marcia

2016-01-01

Staphylococcus chromogenes is one of the main coagulase-negative staphylococci isolated from mastitis of dairy cows. We describe S. chromogenes isolates that can clot plasma. Since the main pathogen causing mastitis is coagulase-positive Staphylococcus aureus, the coagulase-positive phenotype of S. chromogenes described here can easily lead to misidentification.

Staphylococcus chromogenes, a Coagulase-Negative Staphylococcus Species That Can Clot Plasma

Science.gov (United States)

dos Santos, Danielle Cabral; Lange, Carla Christine; Avellar-Costa, Pedro; dos Santos, Katia Regina Netto; Brito, Maria Aparecida Vasconcelos Paiva

2016-01-01

Staphylococcus chromogenes is one of the main coagulase-negative staphylococci isolated from mastitis of dairy cows. We describe S. chromogenes isolates that can clot plasma. Since the main pathogen causing mastitis is coagulase-positive Staphylococcus aureus, the coagulase-positive phenotype of S. chromogenes described here can easily lead to misidentification. PMID:26912749

Effects of temperature on bleeding time and clotting time in normal male and female volunteers.

Science.gov (United States)

Valeri, C R; MacGregor, H; Cassidy, G; Tinney, R; Pompei, F

1995-04-01

This study was done to assess the effects of temperature on bleeding time and clotting time in normal male and female volunteers. Open study utilizing normal volunteers. University research laboratory. Fifty-four healthy male and female volunteers, ranging in age from 19 to 35 yrs, who were not receiving medications. The study was done and the samples of venous blood and shed blood collected at the template bleeding time site were obtained at a convenient time for each volunteer. Skin temperature was changed from +20 degrees to +38 degrees C and blood samples were obtained from the antecubital vein of each volunteer. The effect of local skin temperature ranging from +20 degrees to +38 degrees C on bleeding time was evaluated in 38 normal volunteers (19 male and 19 female). Skin temperature was maintained at +20 degrees to +38 degrees C by cooling or warming the forearm. At each temperature, measurements were made of complete blood count, bleeding time, and thromboxane B2 concentrations in shed blood collected at the template bleeding time site and in serum and plasma isolated from blood collected from the antecubital vein. Clotting time studies were measured in 16 normal volunteers (eight male and eight female) at temperatures ranging from +22 degrees to +37 degrees C. At +32 degrees C, the bleeding time was longer and hematocrit was lower in female than in male volunteers. However, at local skin temperatures of < +32 degrees C, both the males and females exhibited significantly increased bleeding times, which were associated with a reduction in shed blood thromboxane B2. Each 1 degree C decrease in temperature was associated with a 15% decrease in the shed blood thromboxane B2 concentration. Clotting times were three times longer at +22 degrees C than at +37 degrees C. Each 1 degree C reduction in the temperature of the clotted blood was associated with a 15% reduction in the serum thromboxane B2 concentration. Our data indicate that during surgical procedures, it

Technetium-99m labeling of antibodies to cardiac myosin Fab and to human fibrinogen

International Nuclear Information System (INIS)

Khaw, B.A.; Strauss, H.W.; Carvalho, A.; Locke, E.; Gold, H.K.; Haber, E.

1982-01-01

A method of labeling biologically active labile macromolecules, such as human fibrinogen (HF) and anticardiac-myosin Fab (AM-Fab), with Tc-99m at neutral pH was developed. This method uses dithionite reduction of pertechnetate and subsequent labeling to test the method with acid-labile macromolecules. Complexes of diethylene triamine pentaacetic acid with macromolecules such as human fibrinogen (D-HF) and anticardiac-myosin Fab (D-AM-Fab) were labeled and utilized in in vitro and in vivo studies. In biodistribution studies, the Tc-99m D-HF had a two-component blood clearance (half-times 1 hr and 15 hr) and was 80-88% coagulable. The Tc-99m AM-Fab retained its immunoreactivity as tested by affinity chromatography; also during in vivo localization in experimental myocardial infarction. This labeling technique provides an easy and efficient approach to the Tc-99m labeling of other biologically active and acid-labile macromolecules

Real-time monitoring of human blood clotting using a lateral excited film bulk acoustic resonator

Science.gov (United States)

Chen, Da; Wang, Jingjng; Wang, Peng; Guo, Qiuquan; Zhang, Zhen; Ma, Jilong

2017-04-01

Frequent assay of hemostatic status is an essential issue for the millions of patients using anticoagulant drugs. In this paper, we presented a micro-fabricated film bulk acoustic sensor for the real-time monitoring of blood clotting and the measurement of hemostatic parameters. The device was made of an Au/ZnO/Si3N4 film stack and excited by a lateral electric field. It operated under a shear mode resonance with the frequency of 1.42 GHz and had a quality factor of 342 in human blood. During the clotting process of blood, the resonant frequency decreased along with the change of blood viscosity and showed an apparent step-ladder curve, revealing the sequential clotting stages. An important hemostatic parameter, prothrombin time, was quantitatively determined from the frequency response for different dilutions of the blood samples. The effect of a typical anticoagulant drug (heparin) on the prothrombin time was exemplarily shown. The proposed sensor displayed a good consistency and clinical comparability with the standard coagulometric methods. Thanks to the availability of direct digital signals, excellent potentials of miniaturization and integration, the proposed sensor has promising application for point-of-care coagulation technologies.

{sup 99m}Tc-NC100668, a new tracer for imaging venous thromboemboli: pre-clinical biodistribution and incorporation into plasma clots in vivo and in vitro

Energy Technology Data Exchange (ETDEWEB)

Edwards, David [Grove Centre, Research and Development, GE Healthcare Bio-Sciences, Little Chalfont (United Kingdom); Uppsala University Hospital, Institution of Oncology, Radiology and Clinical Immunology, Section of Radiology, Uppsala (Sweden); Lewis, Joanne; Battle, Mark; Lear, Rochelle; Farrar, Gill; Barnett, D.J.; Godden, Vanessa; Oliveira, Alexandra; Coombes, Catherine [Grove Centre, Research and Development, GE Healthcare Bio-Sciences, Little Chalfont (United Kingdom); Ahlstroem, Haakan [Uppsala University Hospital, Institution of Oncology, Radiology and Clinical Immunology, Section of Radiology, Uppsala (Sweden)

2006-11-15

{sup 99m}Tc-NC100668 is a new radiotracer being developed to aid the diagnosis of thromboembolism. The structure of NC100668 is similar to a region of human {alpha}{sub 2}-antiplasmin, which is a substrate for factor XIIIa (FXIIIa). The purpose of this study was to confirm the uptake of {sup 99m}Tc-NC100668 into forming plasma clot and to establish the biodistribution of {sup 99m}Tc-NC100668 in Wistar rats. The in vitro plasma clot uptake of {sup 99m}Tc-NC100668 and other compounds with known affinities to FXIIIa was measured using a plasma clot assay. The biodistribution and blood clot uptake of radioactivity of {sup 99m}Tc-NC100668 in normal Wistar rats and those bearing experimentally induced deep vein thrombi were investigated. The in vitro uptake of {sup 99m}Tc-NC100668 was greater than that for [{sup 14}C]dansyl cadaverine, a known substrate of FXIIIa in the plasma clot assay. The biodistribution of {sup 99m}Tc-NC100668 in male and female Wistar rats up to 24 h p.i. showed that radioactivity was rapidly excreted, predominantly into the urine, with very little background tissue retention. In vivo the uptake and retention of {sup 99m}Tc-NC100668 into the blood clot was greater than could be accounted for by non-specific accumulation of the radiotracer within the blood clot. {sup 99m}Tc-NC100668 was retained by plasma clots in vitro and blood clots in vivo. No significant tissue retention which could interfere with the ability to image thrombi in vivo was observed. This evidence suggests that {sup 99m}Tc-NC100668 might be useful in the detection of thromboembolism. (orig.)

No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

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Jens Baumert

Full Text Available Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI. Genome-wide association studies (GWAS have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2 × 10(-8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

Application of actuator-driven pulsed water jet in aneurysmal subarachnoid hemorrhage surgery: its effectiveness for dissection around ruptured aneurysmal walls and subarachnoid clot removal.

Science.gov (United States)

Endo, Hidenori; Endo, Toshiki; Nakagawa, Atsuhiro; Fujimura, Miki; Tominaga, Teiji

2017-07-01

In clipping surgery for aneurysmal subarachnoid hemorrhage (aSAH), critical steps include clot removal and dissection of aneurysms without premature rupture or brain injuries. To pursue this goal, a piezo actuator-driven pulsed water jet (ADPJ) system was introduced in this study. This study included 42 patients, who suffered aSAH and underwent clipping surgery. Eleven patients underwent surgery with the assistance of the ADPJ system (ADPJ group). In the other 31 patients, surgery was performed without the ADPJ system (Control group). The ADPJ system was used for clot removal and aneurysmal dissection. The clinical impact of the ADPJ system was judged by comparing the rate of premature rupture, degree of clot removal, and clinical outcomes. Intraoperatively, a premature rupture was encountered in 18.2 and 25.8% of cases in the ADPJ and control groups, respectively. Although the differences were not statistically significant, intraoperative observation suggested that the ADPJ system was effective in clot removal and dissection of aneurysms in a safe manner. Computed tomography scans indicated the achievement of higher degrees of clot removal, especially when the ADPJ system was used for cases with preoperative clot volumes of more than 25 ml (p = 0.047, Mann-Whitney U test). Clinical outcomes, including incidence of postoperative brain injury or symptomatic vasospasm, were similar in both groups. We described our preliminary surgical results using the ADPJ system for aSAH. Although further study is needed, the ADPJ system was considered a safe and effective tool for clot removal and dissection of aneurysms.

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

International Nuclear Information System (INIS)

Zielinsky, A.; Hirsh, J.; Straumanis, G.; Carter, C.J.; Gent, M.; Sackett, D.L.; Hull, R.; Kelton, J.G.; Powers, P.; Turpie, A.G.

1982-01-01

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

International Nuclear Information System (INIS)

Zielinsky, A.; Hirsh, J.; Straumanis, G.; Carter, C.J.; Gent, M.; Sackett, D.L.; Hull, R.; Kelton, J.G.; Powers, P.

1982-01-01

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice

Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis.

Science.gov (United States)

Pawlowski, Christa L; Li, Wei; Sun, Michael; Ravichandran, Kavya; Hickman, DaShawn; Kos, Clarissa; Kaur, Gurbani; Sen Gupta, Anirban

2017-06-01

Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger. Specifically, the PMINs can anchor onto thrombus via heteromultivalent ligand-mediated binding to active platelet integrin GPIIb-IIIa and P-selectin, and release the thrombolytic payload due to vesicle destabilization triggered by clot-relevant enzyme phospholipase-A 2 . Here we report on the evaluation of clot-targeting efficacy, lipase-triggered drug release and resultant thrombolytic capability of the PMINs in vitro, and subsequently demonstrate that intravenous delivery of thrombolytic-loaded PMINs can render targeted fibrinolysis without affecting systemic hemostasis, in vivo, in a carotid artery thrombosis model in mice. Our studies establish significant promise of the PMIN technology for safe and site-targeted nanomedicine therapies in the vascular compartment. Copyright © 2017. Published by Elsevier Ltd.

Clotting of cow (Bos taurus) and goat milk ( Capra hircus ) using ...

African Journals Online (AJOL)

The ease to locally produce kid rennet contrary to that of calve has led us to compare the proteolytic and clotting activities of these two rennets depending on their action on goat (Capra hircus) milk and cow (Bos taurus) milk. The proteolysis was measured by determining the increase of non-protein nitrogen according to the ...

Factors Affecting the Growth and Production of Milk-Clotting Enzyme by Amylomyces rouxii in Rice Liquid Medium

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Pei-Jing Yu

2005-01-01

Full Text Available Amylomyces rouxii is one of the main fungi usually coexisting with yeasts in Chinese yeast ball, the starter of chiu-niang, a traditional Chinese fermented product from rice. In the present study, growth and production of milk-clotting enzyme (MCE in gelatinous rice liquid culture of A. rouxii as influenced by waxy (gelatinous rice content in the medium (5–20 %, temperature (25–40 °C, cultivation time (1–6 days, shaking speeds (0–150 rpm and metal ions (Na+, K+, Zn2+, Mg2+, Mn2+, Cu2+, Ca2+, Fe3+ and Al3+ were investigated. Results revealed that rice content in the medium, shaking speed, temperature and cultivation time all affected the mycelial propagation and the production of milk-clotting enzyme by A. rouxii in the rice liquid culture. The maximum milk-clotting enzyme activity of ca. 1.22 unit/mL of medium was observed in the 3-day static culture of test organism grown at 30 °C in the medium containing 20 % of gelatinous rice, while mycelial propagation increased with the increase of cultivation time and shaking speed. Furthermore, a significant increase (p<0.05 in the milk-clotting enzyme activity of ca. 1.90 unit/mL of medium, which was about 1.55-fold of the control, was observed when Al3+ was added to the rice liquid medium.

Googling Service Boundaries for Endovascular Clot Retrieval Hub Hospitals in a Metropolitan Setting: Proof-of-Concept Study.

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Phan, Thanh G; Beare, Richard; Chen, Jian; Clissold, Benjamin; Ly, John; Singhal, Shaloo; Ma, Henry; Srikanth, Velandai

2017-05-01

There is great interest in how endovascular clot retrieval hubs provide services to a population. We applied a computational method to objectively generate service boundaries for such endovascular clot retrieval hubs, defined by traveling time to hub. Stroke incidence data merged with population census to estimate numbers of stroke in metropolitan Melbourne, Australia. Traveling time from randomly generated addresses to 4 endovascular clot retrieval-capable hubs (Royal Melbourne Hospital [RMH], Monash Medical Center [MMC], Alfred Hospital [ALF], and Austin Hospital [AUS]) estimated using Google Map application program interface. Boundary maps generated based on traveling time at various times of day for combinations of hubs. In a 2-hub model, catchment was best distributed when RMH was paired with MMC (model 1a, RMH 1765 km 2 and MMC 1164 km 2 ) or with AUS (model 1c, RMH 1244 km 2 and AUS 1685 km 2 ), with no statistical difference between models ( P =0.20). Catchment was poorly distributed when RMH was paired with ALF (model 1b, RMH 2252 km 2 and ALF 676 km 2 ), significantly different from both models 1a and 1c (both P AUS was superior to that of RMH, MMC, and ALF in catchment distribution and travel time. The method was also successfully applied to the city of Adelaide demonstrating wider applicability. We provide proof of concept for a novel computational method to objectively designate service boundaries for endovascular clot retrieval hubs. © 2017 American Heart Association, Inc.

Production of milk-clotting enzyme by Bacillus subtilis B1 from wheat ...

African Journals Online (AJOL)

Three strains, Bacillus subtilis B1, B. subtilis B18 and Bacillus thuringiensis B12, were screened from wheat bran to produce milk-clotting enzyme. Among them, B. subtilis B1 exhibited considerable milkclotting activity with low proteolytic activity. After response surface methodology optimization, milkclotting activity was ...

Research and clinical applications of iodine-123 fibrinogen in coagulation disorders

International Nuclear Information System (INIS)

DeNardo, G.L.; DeNardo, S.J.; Swanson, M.A.; Wortman, J.A.; Twardock, A.R.; Colcher, D.

1985-01-01

A great many proteins are available to serve as molecular substrates suitable for investigation of normal and diseased states. These proteins, labeled with the appropriate radioisotope of iodine, can be used for immunoassays, imaging, and systemic radiotherapy. The authors describe 12 years experience using coagulation proteins for the investigation of cancer, venous thrombosis, renal transplant rejection, and other coagulopathies. Scintigraphy with 123 I-fibrinogen and immunoassays for circulating antigens such as fibrinopeptide A appear to be promising diagnostic, as well as investigative, tools

Travail et pouvoir d’agir d’Yves Clot

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Jacques Leplat

2008-11-01

Full Text Available Yves Clot est titulaire de la Chaire de psychologie du travail du Conservatoire National des Arts et Métiers (CNAM au sein duquel il dirige l’équipe de clinique de l’activité. Cet ouvrage est le second qu’il publie dans cette collection, le premier « La fonction psychologique du travail » est paru en 1999. Entre les deux s’inscrivent un grand nombre de publications, dont beaucoup avec d’autres chercheurs, comme on pourra le constater en consultant la bibliographie de ce livre. Ce denier réun...

Effects of neutron-gamma or gamma irradiations on plasma clotting factors. Effect of a treatment by substituted factors

International Nuclear Information System (INIS)

Mestries, J.C.; Martin, S.; Janodet, D.; Herodin, F.; Gourmelon, P.; Fatome, M.

1991-01-01

Neutron-gamma irradiation of the baboon at lethal dose altered the plasma clotting factors and induced a fibrinoformation alteration which occurred shortly before death. These disturbances, which were not found after gamma irradiation, could explain the importance of the haemorrhagic syndrome. Treatment by P.P.S.B. (factors II, VII, X and IX) counteracted the alterations of the plasma clotting factors, but had no influence on the lethality nor on the fibrinoformation alteration which seems to be an important cause of death [fr

Use of a Fibrinogen/Thrombin-Based Collagen Fleece (TachoComb, TachoSil) With a Stapled Closure to Prevent Pancreatic Fistula Formation Following Distal Pancreatectomy.

Science.gov (United States)

Mita, Kazuhito; Ito, Hideto; Murabayashi, Ryo; Asakawa, Hideki; Nabetani, Masashi; Kamasako, Akira; Koizumi, Kazuya; Hayashi, Takashi

2015-12-01

Postoperative pancreatic fistula formation remains a source of significant morbidity following distal pancreatectomy. The aim of this study was to evaluate the rate of clinically significant fistulas (International Study Group on Pancreatic Fistula grade B and grade C) after distal pancreatectomy using a fibrinogen/thrombin-based collagen fleece (TachoComb, TachoSil) with a stapled closure. Seventy-five patients underwent distal pancreatectomy at our institution between January 2005 and March 2014. A fibrinogen/thrombin-based collagen fleece was applied to the staple line of the pancreas before stapling. Twenty-six patients (34.7%) developed a pancreatic fistula, 8 patients (10.7%) developed a grade B fistula, and no patients developed a grade C fistula. The duration of the drain was significantly different in patients with or without a pancreatic fistula (8.0 ± 4.5 vs. 5.4 ± 1.3 days, P = .0003). Histological analysis showed that there was a tight covering with the fibrinogen/thrombin-based collagen fleece. The fibrinogen/thrombin-based collagen fleece (TachoComb, TachoSil) with a stapled closure has low rates of fistula formation and provides a safe alternative to the conventional stapled technique in distal pancreatectomy. © The Author(s) 2015.

Effects of carprofen and meloxicam on C-reactive protein, ceruloplasmin, and fibrinogen concentrations in dogs undergoing ovariohysterectomy.

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Kum, Cavit; Voyvoda, Huseyin; Sekkin, Selim; Karademir, Umit; Tarimcilar, Tugrul

2013-10-01

To evaluate the effects of perioperative oral administration of carprofen and meloxicam on concentrations of 3 acute-phase proteins in dogs undergoing elective ovariohysterectomy (OVH). 18 healthy adult anestrous female dogs undergoing elective OVH. Dogs were allocated to 3 groups (6 dogs/group). A placebo treatment, carprofen (2.0 mg/kg), or meloxicam (0.2 mg/kg) was orally administered to the dogs of the respective groups. The initial doses were administered 30 minutes before premedication prior to OVH; additional doses were administered once daily for 4 days after surgery. Blood samples were collected 45 minutes before premedication and 4, 8, 12, 24, 36, 48, 72, 96, and 120 hours after the end of OVH; samples were used for measurement of total WBC and neutrophil counts and concentrations of C-reactive protein (CRP), ceruloplasmin, and fibrinogen. Values did not differ significantly among groups for WBC and neutrophil counts, serum concentrations of CRP and ceruloplasmin, and plasma concentrations of fibrinogen. Concentrations of all inflammatory markers, except serum ceruloplasmin, increased significantly following OVH, but in a similar manner for each group. No significant changes were detected in serum ceruloplasmin concentrations over time. Perioperative administration of both carprofen and meloxicam did not significantly affect the concentrations of CRP, ceruloplasmin, and fibrinogen in dogs undergoing OVH. Thus, use of carprofen or meloxicam should not affect clinical interpretation of results for these 3 acute-phase proteins.

Staphylococcus chromogenes, a Coagulase-Negative Staphylococcus Species That Can Clot Plasma.

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Dos Santos, Danielle Cabral; Lange, Carla Christine; Avellar-Costa, Pedro; Dos Santos, Katia Regina Netto; Brito, Maria Aparecida Vasconcelos Paiva; Giambiagi-deMarval, Marcia

2016-05-01

Staphylococcus chromogenes is one of the main coagulase-negative staphylococci isolated from mastitis of dairy cows. We describe S. chromogenes isolates that can clot plasma. Since the main pathogen causing mastitis is coagulase-positive Staphylococcus aureus, the coagulase-positive phenotype of S. chromogenes described here can easily lead to misidentification. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing.

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Zuliani-Alvarez, Lorena; Midwood, Kim S

2015-05-01

Significance: Fibrinogen-related proteins (FRePs) comprise an intriguing collection of extracellular molecules, each containing a conserved fibrinogen-like globe (FBG). This group includes the eponymous fibrinogen as well as the tenascin, angiopoietin, and ficolin families. Many of these proteins are upregulated during tissue repair and exhibit diverse roles during wound healing. Recent Advances: An increasing body of evidence highlights the specific expression of a number of FRePs following tissue injury and infection. Upon induction, each FReP uses its FBG domain to mediate quite distinct effects that contribute to different stages of tissue repair, such as driving coagulation, pathogen detection, inflammation, angiogenesis, and tissue remodeling. Critical Issues: Despite a high degree of homology among FRePs, each contains unique sequences that enable their diversification of function. Comparative analysis of the structure and function of FRePs and precise mapping of regions that interact with a variety of ligands has started to reveal the underlying molecular mechanisms by which these proteins play very different roles using their common domain. Future Directions: Fibrinogen has long been used in the clinic as a synthetic matrix serving as a scaffold or a delivery system to aid tissue repair. Novel therapeutic strategies are now emerging that harness the use of other FRePs to improve wound healing outcomes. As we learn more about the underlying mechanisms by which each FReP contributes to the repair response, specific blockade, or indeed potentiation, of their function offers real potential to enable regulation of distinct processes during pathological wound healing.

The value of combined strain gauge plethysmography and radioactive iodine fibrinogen scan of the leg in the diagnosis of deep vein thrombosis

International Nuclear Information System (INIS)

AbuRahma, A.F.; Lawton, W.E. Jr.; Osborne, L.

1983-01-01

The fallibility of the clinical diagnosis of deep venous thrombosis has led to a variety of noninvasive diagnostic methods, for example, Doppler ultrasound, plethysmography, 125 I fibrinogen and radionuclide phlebography. This study was undertaken to analyze the value of combined strain gauge plethysmography and 125 I fibrinogen scan of the leg in the diagnosis of deep venous thrombosis. The study was carried out upon 368 patients with suggestive findings of venous thrombosis. Four hundred and fifty strain gauge plethysmograms were reviewed. Venograms were done upon 106 limbs and 125 I fibrinogen leg scans, on 136 limbs. Of the 64 limbs with normal strain gauge plethysmograms which had venograms, 58 were normal, five had incompetent perforators and one limb had deep venous thrombosis. Of the 42 legs with abnormal strain gauge plethysmograms which had venograms, 25 had deep venous thrombosis, 15 had incompetent perforators and two were normal. Twenty-three of 24 legs having both abnormal strain gauge plethysmograms and leg scans were confirmed to have deep venous thrombosis at venography. Fourteen of 18 legs with abnormal strain gauge plethysmograms but normal scans were found to have incompetent perforators. We conclude, that the strain gauge plethysmogram is a reliable test in excluding deep venous thrombosis and, when combined with the fibrinogen leg scan, is reliable in its diagnosis

Incorporation of albumin fusion proteins into fibrin clots in vitro and in vivo: comparison of different fusion motifs recognized by factor XIIIa

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Sheffield William P

2011-12-01

Full Text Available Abstract Background The transglutaminase activated factor XIII (FXIIIa acts to strengthen pathological fibrin clots and to slow their dissolution, in part by crosslinking active α2-antiplasmin (α2AP to fibrin. We previously reported that a yeast-derived recombinant fusion protein comprising α2AP residues 13-42 linked to human serum albumin (HSA weakened in vitro clots but failed to become specifically incorporated into in vivo clots. In this study, our aims were to improve both the stability and clot localization of the HSA fusion protein by replacing α2AP residues 13-42 with shorter sequences recognized more effectively by FXIIIa. Results Expression plasmids were prepared encoding recombinant HSA with the following N-terminal 23 residue extensions: H6NQEQVSPLTLLAG4Y (designated XL1; H6DQMMLPWAVTLG4Y (XL2; H6WQHKIDLPYNGAG4Y (XL3; and their 17 residue non-His-tagged equivalents (XL4, XL5, and XL6. The HSA moiety of XL4- to XL6-HSA proteins was C-terminally His-tagged. All chimerae were efficiently secreted from transformed Pichia pastoris yeast except XL3-HSA, and following nickel chelate affinity purification were found to be intact by amino acid sequencing, as was an N-terminally His-tagged version of α2AP(13-42-HSA. Of the proteins tested, XL5-HSA was cross-linked to biotin pentylamine (BPA most rapidly by FXIIIa, and was the most effective competitor of α2AP crosslinking not only to BPA but also to plasma fibrin clots. In the mouse ferric chloride vena cava thrombosis model, radiolabeled XL5-HSA was retained in the clot to a greater extent than recombinant HSA. In the rabbit jugular vein stasis thrombosis model, XL5-HSA was also retained in the clot, in a urea-insensitive manner indicative of crosslinking to fibrin, to a greater extent than recombinant HSA. Conclusions Fusion protein XL5-HSA (DQMMLPWAVTLG4Y-HSAH6 was found to be more active as a substrate for FXIIIa-mediated transamidation than seven other candidate fusion proteins in

/sup 99m/Tc labeling of antibodies to cardiac myosin Fab and to human fibrinogen

International Nuclear Information System (INIS)

Khaw, B.A.; Strauss, H.W.; Carvalho, A.; Locke, E.; Gold, H.K.; Haber, E.

1982-01-01

We have developed a method of labeling biologically active labile macromolecules, such as human fibrinogen (HF) and anticardiac-myosin Fab (AM-Fab), with /sup 99m/Tc at neutral pH. This method uses dithionite reduction of pertechnetate and subsequent labeling, to test the method with acid-labile macromolecules. Complexes of diethylene triamine pentaacetic acid with macromolecules such as human fibrinogen (D-HF) and anticardiac-myosin Fab (D-AM-Fab) were labeled and utilized in in vitro and in vivo studies. In biodistribution studies, the /sup 99m/Tc D-HF had a two-component blood clearance (half-times 1 hr and 15 hr) and was 80--88% coagulable. The /sup 99m/Tc AM-Fab retained its immunoreactivity as tested by affinity chromatography; also during in vivo localization in experimental myocardial infarction. This labeling technique provides an easy and efficient approach to the /sup 99m/Tc labeling of other biologically active and acid-labile macromolecules

Characterization of lxodes ricinus fibrinogen-related proteins (Ixoderins) discloses their function in the tick innate immunity

Czech Academy of Sciences Publication Activity Database

Hönig Mondeková, Helena; Šíma, R.; Urbanová, V.; Kovář, V.; Rego, R.O.M.; Grubhoffer, L.; Kopáček, P.; Hajdušek, O.

2017-01-01

Roč. 7, DEC 8 (2017), č. článku 509. ISSN 2235-2988 Institutional support: RVO:61388971 Keywords : fibrinogen-related protein * ixoderin * lectin * lxodes Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.300, year: 2016

Availability of the B beta(15-21) epitope on cross-linked human fibrin and its plasmic degradation products

Science.gov (United States)

Chen, F.; Haber, E.; Matsueda, G. R.

1992-01-01

The binding of radiolabeled monoclonal antifibrin antibody 59D8 (specific for fibrin but not fibrinogen) to a series of degraded fibrin clots showed that the availability of the B beta(15-21) epitope (against which 59D8 had been raised) was inversely proportional to the extent of clot lysis. Examination of digest supernatants revealed that the B beta(15-21) epitope was released from clots as a high molecular weight degradation product in the presence of calcium ions but that the generation of low molecular weight peptides occurred in the absence of calcium ions. To address the question of epitope accessibility, we compared levels of fibrin clot binding among four radioactively labeled antibodies: antifibrin monoclonal antibody 59D8, two antifibrinogen monoclonal antibodies that cross-reacted with fibrin, and an affinity-purified polyclonal antifibrinogen antibody. We expected that the antifibrinogen antibodies would show enhanced binding to clots in comparison with the antifibrin antibody. However, the epitope accessibility experiments showed that all four antibody preparations bound fibrin clots at comparable levels. Taken together, these studies demonstrated that one fibrin-specific epitope, B beta(15-21), remains available on clots as they undergo degradation by plasmin and, importantly, that the epitope is not solubilized at a rate faster than the rate at which the clot is itself solubilized. The availability of the B beta(15-21) epitope during the course of plasminolysis assures the potential utility of antifibrin antibodies such as 59D8 for detecting thrombi and targeting plasminogen activators.

Translation of cell therapy into clinical practice: validation of an application procedure for bone marrow progenitor cells and platelet rich plasma.

Science.gov (United States)

Nowotny, Joerg; Farack, Jana; Vater, Corina; Johnsen, Matthias; Gelinsky, Michael; Tonn, Torsten; Kasten, Philip

2016-04-06

Tissue regeneration can be improved by local application of autologous bone marrow derived progenitor cells (BMSC) and platelet rich plasma (PRP). However, there is a lack of standardized application procedures for clinical use. Therefore, a technique in accordance with the guidelines for advanced therapies medical products of the European Medicine Agency was developed and established. In detail, a process for the isolation and formulation of autologous bone marrow cells (BMC) and PRP in a clinical setting was validated. To investigate the influence of storage time and temperature on gel formation and gel stability, different concentrations of BMC were stored with and without additional platelets, thrombin and fibrinogen and analyzed over a period of 28 days. In addition, cell vitality using a live-dead staining and migration ability of human mesenchymal stem cells (hMSC) in the gel clot was investigated. For an optimized stable gel clot, human BMC and PRP should be combined with 10% to 20% fibrinogen (9 mg/mL to 18 mg/mL) and 5% to 20% thrombin (25 I.E. to 100 I.E.). Both freshly prepared and stored cells for 1 to 7 days had a stable consistence over 28 days at 37°C. Different platelet concentrations did not influence gel clot formation. The ratio of living cells did not decrease significantly over the observation period of 5 days in the live-dead staining. The study identified an optimal gel texture for local application of BMC and PRP. Seeded hMSC could migrate therein and were able to survive to initiate a healing cascade.

Comparison of Hemostasis Times With a Kaolin-Based Hemostatic Pad (QuikClot Radial) vs Mechanical Compression (TR Band) Following Transradial Access: A Pilot Prospective Study.

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Roberts, Jonathan S; Niu, Jianli; Pastor-Cervantes, Juan A

2017-10-01

Hemostasis following transradial access (TRA) is usually achieved by mechanical compression. We investigated use of the QuikClot Radial hemostasis pad (Z-Medica) compared with the TR Band (Terumo Medical) to shorten hemostasis after TRA. Thirty patients undergoing TRA coronary angiography and/or percutaneous coronary intervention were randomized into three cohorts post TRA: 10 patients received mechanical compression with the TR Band, 10 patients received 30 min of compression with the QuikClot Radial pad, and 10 patients received 60 min of compression with the QuikClot Radial pad. Times to hemostasis and access-site complications were recorded. Radial artery patency was evaluated 1 hour after hemostasis by the reverse Barbeau's test. There were no differences in patient characteristics, mean dose of heparin (7117 ± 1054 IU), or mean activated clotting time value (210 ± 50 sec) at the end of procedure among the three groups. Successful hemostasis was achieved in 100% of patients with both the 30-min and 60-min compression groups using the QuikClot pad. Hemostasis failure occurred in 50% of patients when the TR Band was initially weaned at the protocol-driven time (40 min after sheath removal). Mean compression time for hemostasis with the TR Band was 149.4 min compared with 30.7 min and 60.9 min for the 30-min and 60-min QuikClot groups, respectively. No radial artery occlusion occurred in any subject at the end of the study. Use of the QuikClot Radial pad following TRA in this pilot trial significantly shortened hemostasis times when compared with the TR Band, with no increased complications noted.

Periodontal therapy reduces plasma levels of interleukin-6, C-reactive protein, and fibrinogen in patients with severe periodontitis and refractory arterial hypertension.

Science.gov (United States)

Vidal, Fábio; Figueredo, Carlos Marcelo S; Cordovil, Ivan; Fischer, Ricardo G

2009-05-01

Recent epidemiologic studies suggest that inflammation is the link between periodontal diseases and cardiovascular complications. This study aimed to evaluate the effects of non-surgical periodontal treatment on plasma levels of inflammatory markers (interleukin [IL]-6, C-reactive protein [CRP], and fibrinogen) in patients with severe periodontitis and refractory arterial hypertension. Twenty-two patients were examined and randomly divided into two groups. The test group was composed of 11 patients (mean age, 48.9 +/- 3.9 years) who received periodontal treatment, whereas the control group had 11 patients (mean age, 49.7 +/- 6.0 years) whose treatment was delayed for 3 months. Demographic and clinical periodontal data were collected, and blood tests were performed to measure the levels of IL-6, CRP, and fibrinogen at baseline and 3 months later. The clinical results showed that the mean percentages of sites with bleeding on probing, probing depth (PD) 4 to 5 mm, PD > or =6 mm, clinical attachment loss (CAL) 4 to 5 mm, and CAL > or =6 mm were significantly reduced in the test group 3 months after periodontal treatment. There were no significant differences between the data at baseline and 3 months in the control group. Periodontal treatment significantly reduced the blood levels of fibrinogen, CRP, and IL-6 in the test group. Non-surgical periodontal therapy was effective in improving periodontal clinical data and in reducing the plasma levels of IL-6, CRP, and fibrinogen in hypertensive patients with severe periodontitis.

The effect of mucin, fibrinogen and IgG on the corrosion behaviour of Ni-Ti alloy and stainless steel.

Science.gov (United States)

Chao, Zhang; Yaomu, Xiao; Chufeng, Liu; Conghua, Liu

2017-06-01

In this study, Ni-Ti alloy and stainless steal were exposed to artificial saliva containing fibrinogen, IgG or mucin, and the resultant corrosion behavior was studied. The purpose was to determine the mechanisms by which different types of protein contribute to corrosion. The effect of different proteins on the electrochemical resistance of Ni-Ti and SS was tested by potentiodynamic polarization, and the repair capacity of passivation film was tested by cyclic polarization measurements. The dissolved corrosion products were determined by ICP-OES, and the surface was analyzed by SEM and AFM. The results showed fibrinogen, IgG or mucin could have different influences on the susceptibility to corrosion of the same alloy. Adding protein lead to the decrease of corrosion resistance of SS, whereas protein could slow down the corrosion process of Ni-Ti. For Ni-Ti, adding mucin could enhance the corrosion stability and repair capacity of passivation film. The susceptibility to pitting corrosion of Ni-Ti and stainless steal in fibrinogen AS is not as high as mucin and IgG AS. There are different patterns of deposition formation on the metal surface by different types of protein, which is associated with their effects on the corrosion process of the alloys.

Evaluation of C-Reactive Protein and Fibrinogen in Patients with Chronic and Aggressive Periodontitis: A Clinico-Biochemical Study.

Science.gov (United States)

Chandy, Swaroop; Joseph, Kiran; Sankaranarayanan, Anila; Issac, Annie; Babu, George; Wilson, Bobby; Joseph, Jumol

2017-03-01

Periodontal disease is characterised by chronic infection and inflammation in periodontal tissues leading to destruction of alveolar bone with subsequent tooth loss. Periodontal infections are the result of an interaction between tooth associated microbial biofilms and the host defences. Periodontal pathogens can affect local and systemic immune and inflammatory responses. The aim of the present study was to evaluate serum C-Reactive Protein (CRP), plasma fibrinogen and peripheral blood levels in healthy subjects, chronic and aggressive periodontitis patients. A total of 55 subjects, 27 males and 28 females were selected for the study. Blood samples were taken from healthy controls (n=20) and patients with chronic periodontitis (n=20) and aggressive periodontitis (n=15). The periodontal status of each patient was assessed by recording Oral Hygiene Index-Simplified (OHI-S), Bleeding Index (BI), Probing Pocket Depth (PPD) and Clinical Attachment Level (CAL). The levels of serum CRP were measured using high sensitivity Enzyme Linked Immunosorbent Assay (ELISA) and levels of plasma fibrinogen were measured using Quantitative Immunoturbidimetric assay. Data description was done in the form of mean and standard deviation and analysis of data was done using one way ANOVA (Analysis of Variance) and Students t-test to test the statistical significance between groups. The levels of serum CRP and plasma fibrinogen was increased in patients with chronic and aggressive periodontitis when compared to healthy controls (pperiodontitis and cardiovascular diseases.

High-throughput proteomic characterization of plasma rich in growth factors (PRGF-Endoret)-derived fibrin clot interactome.

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Anitua, Eduardo; Prado, Roberto; Azkargorta, Mikel; Rodriguez-Suárez, Eva; Iloro, Ibon; Casado-Vela, Juan; Elortza, Felix; Orive, Gorka

2015-11-01

Plasma rich in growth factors (PRGF®-Endoret®) is an autologous technology that contains a set of proteins specifically addressed to wound healing and tissue regeneration. The scaffold formed by using this technology is a clot mainly composed of fibrin protein, forming a three-dimensional (3D) macroscopic network. This biomaterial is easily obtained by biotechnological means from blood and can be used in a range of situations to help wound healing and tissue regeneration. Although the main constituent of this clot is the fibrin scaffold, little is known about other proteins interacting in this clot that may act as adjuvants in the healing process. The aim of this study was to characterize the proteins enclosed by PRGF-Endoret scaffold, using a double-proteomic approach that combines 1D-SDS-PAGE approach followed by LC-MS/MS, and 2-DE followed by MALDI-TOF/TOF. The results presented here provide a description of the catalogue of key proteins in close contact with the fibrin scaffold. The obtained lists of proteins were grouped into families and networks according to gene ontology. Taken together, an enrichment of both proteins and protein families specifically involved in tissue regeneration and wound healing has been found. Copyright © 2013 John Wiley & Sons, Ltd.

Determination of enoxaparin with rotational thrombelastometry using the prothrombinase-induced clotting time reagent.

Science.gov (United States)

Schaden, Eva; Schober, Andreas; Hacker, Stefan; Spiss, Christian; Chiari, Astrid; Kozek-Langenecker, Sibylle

2010-04-01

Drug monitoring of low molecular weight heparin is generally not recommended, but could be reasonable in critically ill patients, whose risk for bleeding or thrombosis shows a high interpatient variability. Anti-Xa assays are not available around the clock even in central hospitals, whereas rotational thrombelastometry (ROTEM) becomes increasingly used at the bedside. Prothrombinase-induced clotting time (PiCT) reagent allows determination of factor Xa-inhibition in plasma. The aim of our study was to evaluate enoxaparin determination in whole blood with the ROTEM using specific test modifications, including PiCT. After ethics committee's approval, citrated whole blood obtained from overall 16 healthy volunteers was incubated with enoxaparin at 16 different anti-Xa concentrations. Main endpoint was the clotting time (CT) in ROTEM representing initial activation of clot formation. CT was determined in the new PiCT-ROTEM test, in a low-tissue factor-activated modification (LowTF-ROTEM) as well as in the commercially available heparin-sensitive ROTEM assays (HEPTEM and INTEM). In the absence of enoxaparin, CT values were 168.6 +/- 6.1 s (PiCT-ROTEM), 247.3 +/- 18.6 s (LowTF-ROTEM), and -6.2 +/- 7.9 s (INTEM-HEPTEM). A linear dependency (P anti-Xa concentration and CT was found for PiCT-ROTEM, LowTF-ROTEM, and for INTEM-HEPTEM with correlation coefficients of 0.93 for PiCT-ROTEM, 0.94 for LowTF-ROTEM, and 0.81 for INTEM-HEPTEM. This in-vitro experiment demonstrates a strong correlation between enoxaparin anti-Xa concentrations and specific ROTEM tests. These promising assays should be further evaluated for monitoring anticoagulation in high-risk patients in clinical studies.

Does prior administration of enoxaparin influence the effects of levobupivacaine on blood clotting? Assessment using the Thrombelastograph.

LENUS (Irish Health Repository)

Leonard, S A

2012-02-03

The low molecular weight heparin, enoxaparin (by inhibition of factors Xa and IIa) and amide local anaesthetics (by altering platelet function) exert anti-clotting effects. Although these agents are often used in combination during the perioperative period, their potential interactive effect on clotting has not been defined. Blood from 10 ASA I-II patients who received enoxaparin 0.5 mg kg(-1) s.c. was studied using a Thrombelastograph (TEG) either alone or in combination with levobupivacaine (2.5 mg ml(-1) or 2.5 microg ml(-1)) or saline (50% dilution). In blood from patients who had received enoxaparin 0.5 mg kg(-1) s.c. 12 h previously, levobupivacaine 2.5 mg ml(-1) (but not 2.5 microg ml(-1)) produced significant changes in TEG clotting parameters (mean (SD) 15.7 (4.8) mm, 29.6 (25.6) mm, 34.4 (14.6) mm, 34.3 (12.2) degrees compared with control values of 6.1 (1.3) mm, 2.5 (0.5) mm, 63.5 (6.4) mm and 74.1 (2.9) degrees for r, K, MA, and alpha angle respectively).

Comparative evaluation of Bacillus licheniformis 5A5 and Aloe variegata milk-clotting enzymes

Directory of Open Access Journals (Sweden)

S. A. Ahmed

2012-03-01

Full Text Available The properties of a milk clotting enzyme (MCE produced by bacteria (Bacillus licheniformis 5A5 were investigated and compared to those of rennet extracted from a plant (Aloe variegata. Production of MCE by B. licheniformis 5A5 was better in static than in shaken cultures. Maximum activity (98.3 and 160.3 U/ml of clotting was obtained at 75ºC and 80ºC with bacterial and plant rennet, respectively. In the absence of substrate, the clotting activity of Aloe MCE was found to be less sensitive to heat inactivation up to 80ºC for 75 min, retaining 63.8% of its activity, while bacterial MCE was completely inhibited. CaCl2 stimulated milk clotting activity (MCA up to 2% and 1.5% for bacterial and plant enzymes. NaCl inhibited MCA for both enzymes, even at low concentration (1%. Plant MCE was more sensitive to NaCl at 3% concentration it retained 30.2% of its activity, whereas bacterial MCE retained 64.1%. Increasing skim milk concentration caused a significant increase in MCA up to 6% for both enzymes. Mn2+ stimulated the activity of bacterial and plant enzymes to 158.6 and 177.9%, respectively. EDTA and PMSF increased the activity of plant MCE by 34.4 and 41.1%, respectively, which is higher than those for the bacterial MCE (19.1 and 20.9%. Some natural materials activated MCE, the highest activation of bacterial MCE (128.1% was obtained in the presence of Fenugreek (with acid extraction. However Lupine Giza 1 (with neutral extraction gave the highest activation of plant MCE (137.9%. All extracts from Neem plant increased MCA at range from 105.6% to 136.4%. Plant MCE exhibited much better stability when stored at room temperature (25-30ºC for 30 days, retaining 51.2% of its activity. Bacterial MCE was highly stabile when stored under freezing (-18ºC, retaining 100% of its activity after 30 days. Moreover, bacterial MCE was highly tolerant to repeated freezing and thawing without loss of activity for 8 months.

Prognostic significance of pretreatment plasma fibrinogen level in patients with digestive system tumors: a meta-analysis.

Science.gov (United States)

Ji, Rui; Ren, Qian; Bai, Suyang; Wang, Yuping; Zhou, Yongning

2018-06-01

High pretreatment levels of plasma fibrinogen have been widely reported to be a potential predictor of prognosis in digestive system tumors; however, the conclusions are not consistent. Therefore, we performed a meta-analysis to comprehensively assess the prognostic roles of high pretreatment plasma fibrinogen levels in digestive system tumors. We searched for eligible studies in the PubMed, Embase, and Web of Science electronic databases for publications from the database inception to 1 September 2017. The endpoints of interest included overall survival, disease-free survival, and recurrence-free survival. We investigated the relationship between fibrinogenemia and overall survival in colorectal cancer (10 studies), gastric cancer (6), pancreatic cancer (6), hepatocellular carcinoma (7), and esophageal squamous cell carcinoma (10); the pooled results indicated that fibrinogenemia was significantly related to a worse overall survival (hazard ratio (HR) 1.73; 95% confidence interval (CI) 1.52, 1.97; P digestive system tumors, indicating that it could be a useful prognostic marker in these types of tumors.

Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy.

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Balvers, K; van Dieren, S; Baksaas-Aasen, K; Gaarder, C; Brohi, K; Eaglestone, S; Stanworth, S; Johansson, P I; Ostrowski, S R; Stensballe, J; Maegele, M; Goslings, J C; Juffermans, N P

2017-02-01

The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma-induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing fibrinogen on the outcome of injured patients with bleeding. A prospective multicentre observational study was performed in six level 1 trauma centres. Injured patients who received at least 4 units of red blood cells (RBCs) were analysed and divided into groups receiving a low (less than 1 : 1) or high (1 or more : 1) ratio of plasma or platelets to RBCs, and in receipt or not of tranexamic acid or fibrinogen products (fibrinogen concentrates or cryoprecipitate). Logistic regression models were used to assess the effect of transfusion strategies on the outcomes 'alive and free from massive transfusion' (at least 10 units of RBCs in 24 h) and early 'normalization of coagulopathy' (defined as an international normalized ratio of 1·2 or less). A total of 385 injured patients with ongoing bleeding were included in the study. Strategies that were independently associated with an increased number of patients alive and without massive transfusion were a high platelet to RBC ratio (odds ratio (OR) 2·67, 95 per cent c.i. 1·24 to 5·77; P = 0·012), a high plasma to RBC ratio (OR 2·07, 1·03 to 4·13; P = 0·040) and treatment with tranexamic acid (OR 2·71, 1·29 to 5·71; P = 0·009). No strategies were associated with correction of coagulopathy. A high platelet or plasma to RBC ratio, and use of tranexamic acid were associated with a decreased need for massive transfusion and increased survival in injured patients with bleeding. Early normalization of coagulopathy was not seen for any transfusion ratio, or for use of tranexamic acid or fibrinogen products. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Tracheal anastomosis using indocyanine green dye enhanced fibrinogen with a near-infrared diode laser

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Auteri, Joseph S.; Jeevanandam, Valluvan; Oz, Mehmet C.; Libutti, Steven K.; Kirby, Thomas J.; Smith, Craig R.; Treat, Michael R.

1990-06-01

A major obstacle to lung transplantation and combined heart- lung transplantation is dehiscence of the tracheobronchial anastomosis. We explored the possibility of laser welded anastomoses in canine tracheas in vivo. Laser anastomoses were performed on three-quarter circumferential anterior tracheotomies. A continous wave diode laser (808 +1 nm) at a power density of 9.6 watts/cm was used. Human fibrinogen was mixed with indocyanine green dye (ICG, max absorbance 805 nm) and applied to the anastomosis site prior to laser exposure. Animals were sacrificed at 0, 21 and 28 days post-operatively. At sacrifice weld bursting pressures were measured by raising intratracheal pressure using forced ventilation via an endotracheal tube. Sutured and laser welded anastomoses had similar bursting pressures, and exhibited satisfactory histologic evidence of healing. However, compared to polypropylene sutured controls, the laser welded anastomoses exhibited less peritracheal inflammatory reaction and showed visibly smoother luminal surfaces at 21 and 28 days post- operatively. Tracheal anastomosis using ICG dye enhanced fibrinogen combined with the near-infrared diode laser is a promising extension of the technology of laser tissue fusion and deserves further study.

Adsorption and covalent binding of fibrinogen as a method for probing the chemical composition of poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) microsphere surfaces.

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Gosecka, Monika; Chehimi, Mohamed M; Basinska, Teresa; Slomkowski, Stanislaw; Makowski, Tomasz

2017-12-01

We investigated the distribution of polyglycidol and polystyrene on the surface of poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) microspheres (random distribution or segregated into hydrophilic and hydrophobic patches), using fibrinogen (Fb) as a macromolecular probe. The fibrinogen was adsorbed or covalently attached to the surface of the poly(styrene-co-α-tert-butoxy-ω-vinylbenzyl-polyglycidol) (P(S/PGLy)) microspheres. The P(S/PGLy) particles were prepared by emulsion copolymerization of styrene and α-tert-butoxy-ω-vinylbenzyl-polyglycidol (PGLy) macromonomer initiated with potassium persulfate. The polymerizations yielded P(S/PGLy) particles with various surface fractions of polyglycidol, depending on the amount of added macromonomer and the addition process. In some syntheses, the entire macromonomer amount was added once at the beginning of the polymerization, while in others, the macromonomer was added gradually after the formation of particle seeds from pure polystyrene. XPS studies revealed that the fraction of polyglycidol in the interfacial layer of the microspheres was larger when the entire amount of macromonomer was added at the beginning of the polymerization than when it was added after formation of the polystyrene seeds. Studies of fibrinogen adsorption provided the first evidence of segregation of the hydrophobic (polystyrene) and hydrophilic (polyglycidol) components at the surface of the composite P(S/PGLy) microspheres into patches. The hydrophobic patches are composed mainly of polystyrene. However, they also contain a small amount of polyglycidol chains, making the adsorption of fibrinogen weaker than the adsorption onto the pure polystyrene. Studies of covalent immobilization of fibrinogen on the microspheres via 1,3,5-trichlorotriazine confirmed these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasma Clot Lysis Time and Its Association with Cardiovascular Risk Factors in Black Africans

NARCIS (Netherlands)

Z. de Lange (Zelda); M. Pieters (Marlien); J.C. Jerling (Johann); A. Kruger (Annamarie); D.C. Rijken (Dingeman)

2012-01-01

textabstractStudies in populations of European descent show longer plasma clot lysis times (CLT) in patients with cardiovascular disease (CVD) than in controls. No data are available on the association between CVD risk factors and fibrinolytic potential in black Africans, a group undergoing rapid

Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels : a randomized, diet-controlled intervention study

NARCIS (Netherlands)

Sierksma, A.; Gaag, M.S. van der; Kluft, C.; Hendriks, H.F.J.

2002-01-01

Objective: To evaluate the effect of moderate alcohol consumption on the acute phase proteins C-reactive protein and fibrinogen. Design: Randomized, diet-controlled, cross-over study. Setting: The study was performed at TNO Nutrition and Food Research, Zeist, The Netherlands. Subjects: Ten

Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins.

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Halper, Jaroslava; Kjaer, Michael

2014-01-01

Collagens are the most abundant components of the extracellular matrix and many types of soft tissues. Elastin is another major component of certain soft tissues, such as arterial walls and ligaments. Many other molecules, though lower in quantity, function as essential components of the extracellular matrix in soft tissues. Some of these are reviewed in this chapter. Besides their basic structure, biochemistry and physiology, their roles in disorders of soft tissues are discussed only briefly as most chapters in this volume deal with relevant individual compounds. Fibronectin with its muldomain structure plays a role of "master organizer" in matrix assembly as it forms a bridge between cell surface receptors, e.g., integrins, and compounds such collagen, proteoglycans and other focal adhesion molecules. It also plays an essential role in the assembly of fibrillin-1 into a structured network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of fibrinogen is in clot formation, after conversion to fibrin by thrombin, it also binds to a variety of compounds, particularly to various growth factors, and as such fibrinogen is a player in cardiovascular and extracellular matrix physiology. Elastin, an insoluble polymer of the monomeric soluble precursor tropoelastin, is the main component of elastic fibers in matrix tissue where it provides elastic recoil and resilience to a variety of connective tissues, e.g., aorta and ligaments. Elastic fibers regulate activity of TGFβs through their association with fibrillin microfibrils. Elastin also plays a role in cell adhesion, cell migration, and has the ability to participate in cell signaling. Mutations in the elastin gene lead to cutis laxa. Fibrillins represent the predominant core of the microfibrils in elastic as well as non

Superior integrin activating capacity and higher adhesion to fibrinogen matrix in buffy coat-derived platelet concentrates (PCs) compared to PRP-PCs.

Science.gov (United States)

Beshkar, Pezhman; Hosseini, Ehteramolsadat; Ghasemzadeh, Mehran

2018-02-01

Regardless of different sources, methods or devices which are applied for preparation of therapeutic platelets, these products are generally isolated from whole blood by the sedimentation techniques which are based on PRP or buffy coat (BC) separation. As a general fact, platelet preparation and storage are also associated with some deleterious changes that known as platelet storage lesion (PSL). Although these alternations in platelet functional activity are aggravated during storage, whether technical issues within preparation can affect integrin activation and platelet adhesion to fibrinogen were investigated in this study. PRP- and BC-platelet concentrates (PCs) were subjected to flowcytometry analysis to examine the expression of platelet activation marker, P-selectin as well as active confirmation of the GPIIb/IIIa (α IIb β 3 ) on day 0, 1, 3 and 5 post-storage. Platelet adhesion to fibrinogen matrix was evaluated by fluorescence microscopy. Glucose concentration and LDH activity were also measured by colorimetric methods. The increasing P-selectin expression during storage was in a reverse correlation with PAC-1 binding (r = -0.67; p = .001). PRP-PCs showed the higher level of P-selectin expression than BC-PCs, whereas the levels of PAC-1 binding and platelet adhesion to fibrinogen matrix were significantly lower in PRP-PCs. Higher levels of active confirmation of the GPIIb/IIIa in BC-PCs were also associated with greater concentration of glucose in these products. We demonstrated the superior capacities of integrin activation and adhesion to fibrinogen for BC-PCs compared to those of PRP-PCs. These findings may provide more advantages for BC method of platelet preparation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen.

Science.gov (United States)

Thompson, Aaron M S; Zanobetti, Antonella; Silverman, Frances; Schwartz, Joel; Coull, Brent; Urch, Bruce; Speck, Mary; Brook, Jeffrey R; Manno, Michael; Gold, Diane R

2010-01-01

Systemic inflammation may be one of the mechanisms mediating the association between ambient air pollution and cardiovascular morbidity and mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic inflammation that are independent risk factors for cardio-vascular disease. We investigated the association between ambient air pollution and systemic inflammation using baseline measurements of IL-6 and fibrinogen from controlled human exposure studies. In this retrospective analysis we used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and particulate matter pollutants on systemic IL-6 and fibrinogen. Effect modification by season was considered. We observed a positive association between IL-6 and O3 [0.31 SD per O3 interquartile range (IQR); 95% confidence interval (CI), 0.080.54] and between IL-6 and SO2 (0.25 SD per SO2 IQR; 95% CI, 0.060.43). We observed the strongest effects using 4-day moving averages. Responses to pollutants varied by season and tended to be higher in the summer, particularly for O3 and PM2.5. Fibrinogen was not associated with pollution. This study demonstrates a significant association between ambient pollutant levels and baseline levels of systemic IL-6. These findings have potential implications for controlled human exposure studies. Future research should consider whether ambient pollution exposure before chamber exposure modifies IL-6 response.

Ex vivo addition of fibrinogen concentrate improves the fibrin network structure in plasma samples taken during liver transplantation

NARCIS (Netherlands)

Groeneveld, D. J.; Adelmeijer, J.; Hugenholtz, G. C. G.; Ariens, R. A. S.; Porte, R. J.; Lisman, T.

2015-01-01

Background: Optimal hemostatic management during orthotopic liver transplantation (OLT) remains a challenge. The cause of bleeding during OLT is multifactorial, and may include hemostatic imbalance. Fibrinogen concentrates are increasingly being used to control perioperative bleeding during OLT.

Thrombus detection using 125I-fibrinogen and a CdTe probe

International Nuclear Information System (INIS)

Garcia, D.A.; Frisbie, J.H.; Tow, D.E.; Sasahara, A.A.; Entine, G.

1976-01-01

A compact CdTe detector system was developed for use in a clinical screening test for venous thrombosis of the legs. Patients given intravenously administered autologous 125 I-fibrinogen were probed externally at selected points on the thighs and calves for abnormal accumulations of radioactivity. Measurements made with the CdTe probe were compared to those obtained with a standard portable NaI detector system. The CdTe probe was the equal of the NaI detector in diagnostic capability. The compact design of the semiconductor system considerably eased the probing procedure, especially in bedridden patients with limited mobility of the extremities

Prediction of recurrent venous thromboembolism by clot lysis time: a prospective cohort study.

Science.gov (United States)

Traby, Ludwig; Kollars, Marietta; Eischer, Lisbeth; Eichinger, Sabine; Kyrle, Paul A

2012-01-01

Venous thromboembolism (VTE) is a chronic disease, which tends to recur. Whether an abnormal fibrinolytic system is associated with an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic capacity (reflected by clot lysis time [CLT]) and risk of recurrent VTE. We followed 704 patients (378 women; mean age 48 yrs) with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, homozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. Study endpoint was symptomatic recurrent VTE. For measurement of CLT, a tissue factor-induced clot was lysed by adding tissue-type plasminogen activator. Time between clot formation and lysis was determined by measuring the turbidity. 135 (19%) patients had recurrent VTE. For each increase in CLT of 10 minutes, the crude relative risk (RR) of recurrence was 1.13 (95% CI 1.02-1.25; p = 0.02) and was 1.08 (95% CI 0.98-1.20; p = 0.13) after adjustment for age and sex. For women only, the adjusted RR was 1.14 (95% CI, 0.91-1.42, p = 0.22) for each increase in CLT of 10 minutes. CLT values in the 4(th) quartile of the female patient population, as compared to values in the 1(st) quartile, conferred a risk of recurrence of 3.28 (95% CI, 1.07-10.05; p = 0.04). No association between CLT and recurrence risk was found in men. Hypofibrinolysis as assessed by CLT confers a moderate increase in the risk of recurrent VTE. A weak association between CLT and risk of recurrence was found in women only.

Prediction of recurrent venous thromboembolism by clot lysis time: a prospective cohort study.

Directory of Open Access Journals (Sweden)

Ludwig Traby

Full Text Available Venous thromboembolism (VTE is a chronic disease, which tends to recur. Whether an abnormal fibrinolytic system is associated with an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic capacity (reflected by clot lysis time [CLT] and risk of recurrent VTE. We followed 704 patients (378 women; mean age 48 yrs with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, homozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. Study endpoint was symptomatic recurrent VTE. For measurement of CLT, a tissue factor-induced clot was lysed by adding tissue-type plasminogen activator. Time between clot formation and lysis was determined by measuring the turbidity. 135 (19% patients had recurrent VTE. For each increase in CLT of 10 minutes, the crude relative risk (RR of recurrence was 1.13 (95% CI 1.02-1.25; p = 0.02 and was 1.08 (95% CI 0.98-1.20; p = 0.13 after adjustment for age and sex. For women only, the adjusted RR was 1.14 (95% CI, 0.91-1.42, p = 0.22 for each increase in CLT of 10 minutes. CLT values in the 4(th quartile of the female patient population, as compared to values in the 1(st quartile, conferred a risk of recurrence of 3.28 (95% CI, 1.07-10.05; p = 0.04. No association between CLT and recurrence risk was found in men. Hypofibrinolysis as assessed by CLT confers a moderate increase in the risk of recurrent VTE. A weak association between CLT and risk of recurrence was found in women only.

A portable blood plasma clot micro-elastometry device based on resonant acoustic spectroscopy.

Science.gov (United States)

Krebs, C R; Li, Ling; Wolberg, Alisa S; Oldenburg, Amy L

2015-07-01

Abnormal blood clot stiffness is an important indicator of coagulation disorders arising from a variety of cardiovascular diseases and drug treatments. Here, we present a portable instrument for elastometry of microliter volume blood samples based upon the principle of resonant acoustic spectroscopy, where a sample of well-defined dimensions exhibits a fundamental longitudinal resonance mode proportional to the square root of the Young's modulus. In contrast to commercial thromboelastography, the resonant acoustic method offers improved repeatability and accuracy due to the high signal-to-noise ratio of the resonant vibration. We review the measurement principles and the design of a magnetically actuated microbead force transducer applying between 23 pN and 6.7 nN, providing a wide dynamic range of elastic moduli (3 Pa-27 kPa) appropriate for measurement of clot elastic modulus (CEM). An automated and portable device, the CEMport, is introduced and implemented using a 2 nm resolution displacement sensor with demonstrated accuracy and precision of 3% and 2%, respectively, of CEM in biogels. Importantly, the small strains (diagnostics and therapeutic monitoring.

Effect of Cold Storage on Shear-induced Platelet Aggregation and Clot Strength

Science.gov (United States)

2014-09-01

hemostasis and are lifesavingwhen transfused to treat thrombocytopenia. In response to vascular injury, platelets adhere, aggregate, and along with fibrin ...Handling Platelet - rich plasma (PRP) was obtained from phlebot- omized blood or AP collection. Blood was drawn in acid cit- rate dextroseYcontaining...aging and senes- cence during storage.35,38 Platelet activation and aggregation lead to clot formation, beginning with the linear polymerization of fibrin

The effect of regular aerobic training with weight loss on concentrations of fibrinogen and resistin in healthy and overweight men

Directory of Open Access Journals (Sweden)

Rashidlamir A

2011-03-01

Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Coronary heart disease is one of the most common causes of death in developed countries. Fibrinogen and resistin are two inflammatory markers used for atherosclerosis risk prediction. The aim of this study was to examine the effects of eight weeks of aerobic exercise on the concentrations of fibrinogen and resistin in healthy overweight middle-aged men."n"nMethods: Thirty inactive middle-aged men with a body mass index of 25-30 were randomly assigned into two experimental and control groups. The participants in the experimental group, accomplished eight weeks (3 sessions per week, of aerobic exercise with an intensity of 50-70% of their maximum heart rate while the control group remained sedentary. Weight, body fat percentage, fibrinogen and resistin levels of the participants were measured 48 hours before the first and after the last training sessions. The obtained data were analyzed using Independent Samples T-tests."n"nResults: There were significant reductions in weight, body mass index, body fat percentage and fibrinogen and a significant elevation in resistin concentration in the experimental group (p<0.05 upon the exercises relative to the control group."n"nConclusion: It seems that eight weeks of

Building and validation of a prognostic model for predicting extracorporeal circuit clotting in patients with continuous renal replacement therapy.

Science.gov (United States)

Fu, Xia; Liang, Xinling; Song, Li; Huang, Huigen; Wang, Jing; Chen, Yuanhan; Zhang, Li; Quan, Zilin; Shi, Wei

2014-04-01

To develop a predictive model for circuit clotting in patients with continuous renal replacement therapy (CRRT). A total of 425 cases were selected. 302 cases were used to develop a predictive model of extracorporeal circuit life span during CRRT without citrate anticoagulation in 24 h, and 123 cases were used to validate the model. The prediction formula was developed using multivariate Cox proportional-hazards regression analysis, from which a risk score was assigned. The mean survival time of the circuit was 15.0 ± 1.3 h, and the rate of circuit clotting was 66.6 % during 24 h of CRRT. Five significant variables were assigned a predicting score according to the regression coefficient: insufficient blood flow, no anticoagulation, hematocrit ≥0.37, lactic acid of arterial blood gas analysis ≤3 mmol/L and APTT R (2) = 0.232; P = 0.301). A risk score that includes the five above-mentioned variables can be used to predict the likelihood of extracorporeal circuit clotting in patients undergoing CRRT.

Investigation of the effect of kaolin and tissue factor-activated citrated whole blood, on clot forming variables, as evaluated by thromboelastograph

DEFF Research Database (Denmark)

Johansson, Per Ingemar; Bochsen, L.; Andersen, S.

2008-01-01

), and maximum clot strength (amplitude [MA]) were evaluated, together with day-to-day variation, the coefficient of variance (CV%), and the effect of citrate storage time. RESULTS: Clot formation variables were equally affected by TF 1:17,000 and kaolin activation, whereas R was significantly longer when TF 1......:42,500 was used. The CV for the different variables varied from 3 to 13 percent with no significant differences between assays. Storage of citrated WB significantly affected the TEG variables in a hypercoagulable direction. Only the R, however, was significantly affected (12%) when samples rested for 0 and 30...... minutes were evaluated with kaolin as the activator. CONCLUSION: The TEG assays evaluated were reproducible and present with an acceptable CV% for routine clinical practice. Kaolin and TF 1:17,000 equally affected the clot formation variables. Storage of WB for up to 30 minutes in citrate did not, except...

Less impairment of hemostasis and reduced blood loss in pigs after resuscitation from hemorrhagic shock using the small-volume concept with hypertonic saline/hydroxyethyl starch as compared to administration of 4% gelatin or 6% hydroxyethyl starch solution.

Science.gov (United States)

Haas, Thorsten; Fries, Dietmar; Holz, Carmen; Innerhofer, Petra; Streif, Werner; Klingler, Anton; Hanke, Alexander; Velik-Salchner, Corinna

2008-04-01

Small-volume resuscitation using hypertonic saline/hydroxyethyl starch 200/0.62 (HS-HES) has been shown to be an effective alternative to the administration of crystalloids or colloids in trauma patients. All i.v. fluids cause dose-related dilutional coagulopathy and show intrinsic effects on the hemostatic system, but only few data refer to functional consequences after small-volume resuscitation. Using thrombelastometry (ROTEM), we studied 30 pigs (weighing 35-45 kg) after withdrawal of 60% of blood volume [1484 mL (1369-1624 mL)] and receiving 4 mL/kg HS-HES for compensation of blood loss or 4% gelatin or 6% HES 130/0.4 in a 1:1 ratio to lost blood volume. To compare the ROTEM variables (coagulation time, clot formation time, alpha angle, clot firmness, and fibrinogen polymerization) with bleeding tendency, a hepatic incision was made and blood loss was measured. Median (25th, 75th percentile) fibrinogen polymerization was significantly higher after HS-HES infusion [11 mm (10, 11), P = 0.0034] when compared with administration of 4% gelatin [4.5 mm (3.0, 5.8)] or HES 130/0.4 [3.5 mm (2.3, 4.0)]. Median blood loss after liver incision was 725 mL (900, 375) after HS-HES, 1625 mL (1275, 1950) after 4% gelatin, and 1600 mL (1500, 1800) after 6% HES 130/0.4 (P = 0.004). Hemodynamic stabilization was traceable in all groups but showed differences regarding filling pressures. Resuscitation from hemorrhagic shock with HS-HES 200/0.62 results in less impairment of clot formation when compared with compensation of blood loss by administering 6% HES 130/0.4 or 4% gelatin.

Platelet glycoprotein VI binds to polymerized fibrin and promotes thrombin generation.

Science.gov (United States)

Mammadova-Bach, Elmina; Ollivier, Véronique; Loyau, Stéphane; Schaff, Mathieu; Dumont, Bénédicte; Favier, Rémi; Freyburger, Geneviève; Latger-Cannard, Véronique; Nieswandt, Bernhard; Gachet, Christian; Mangin, Pierre H; Jandrot-Perrus, Martine

2015-07-30

Fibrin, the coagulation end product, consolidates the platelet plug at sites of vascular injury and supports the recruitment of circulating platelets. In addition to integrin αIIbβ3, another as-yet-unidentified receptor is thought to mediate platelet interaction with fibrin. Platelet glycoprotein VI (GPVI) interacts with collagen and several other adhesive macromolecules. We evaluated the hypothesis that GPVI could be a functional platelet receptor for fibrin. Calibrated thrombin assays using platelet-rich plasma (PRP) showed that tissue factor-triggered thrombin generation was impaired in GPVI-deficient patients and reduced by the anti-GPVI Fab 9O12. Assays on reconstituted PRP and PRP from fibrinogen-deficient patients revealed a fibrinogen-dependent enhancement of thrombin generation, which relied on functional GPVI. The effect of GPVI was found to depend on fibrin polymerization. A binding assay showed a specific interaction between GPVI-Fc and fibrin, inhibited by the Fab 9O12. This Fab also reduced platelet adhesion to fibrin at low (300 s(-1)) and high (1500 s(-1)) wall shear rates. Platelets adherent to fibrin displayed shape change, exposure of procoagulant phospholipids, and the formation of small clots. When hirudinated blood was perfused at 1500 s(-1) over preformed fibrin-rich clots, the Fab 9O12 decreased the recruitment of platelets by up to 85%. This study identifies GPVI as a platelet receptor for polymerized fibrin with 2 major functions: (1) amplification of thrombin generation and (2) recruitment of circulating platelets to clots. These so-far-unrecognized properties of GPVI confer on it a key role in thrombus growth and stabilization. © 2015 by The American Society of Hematology.

Development and comparison of a minimally-invasive model of autologous clot pulmonary embolism in Sprague-Dawley and Copenhagen rats

Directory of Open Access Journals (Sweden)

Sanapareddy Nina

2010-02-01

Full Text Available Abstract Background Experimental models of pulmonary embolism (PE that produce pulmonary hypertension (PH employ many different methods of inducing acute pulmonary occlusion. Many of these models induce PE with intravenous injection of exogenous impervious objects that may not completely reproduce the physiological properties of autologous thromboembolism. Current literature lacks a simple, well-described rat model of autlogous PE. Objective: Test if moderate-severity autologous PE in Sprague-Dawley (SD and Copenhagen (Cop rats can produce persistent PH. Methods blood was withdrawn from the jugular vein, treated with thrombin-Ca++ and re-injected following pretreatment with tranexamic acid. Hemodynamic values, clot weights and biochemical measurements were performed at 1 and 5 days. Results Infusion of clot significantly increased the right ventricular peak systolic pressure to 45-55 mm Hg, followed by normalization within 24 hours in SD rats, and within 5 days in COP rats. Clot lysis was 95% (24 hours and 97% (5 days in SD rats and was significantly lower in COP rats (70%, 24 hours; 87% 5 days. Plasma D-dimer was elevated in surgical sham animals and was further increased 8 hours after pulmonary embolism. Neither strain showed a significant increase in bronchoalveolar chemotactic activity, myeloperoxidase activity, leukocyte infiltration, or chemokine accumulation, indicating that there was no significant pulmonary inflammation. Conclusions Both SD and COP rats exhibited near complete fibrinolysis of autologous clot PE within 5 days. Neither strain developed persistent PH. Experimental models of PE designed to induce sustained PH and a robust inflammatory response appear to require significant, persistent pulmonary vascular occlusion.

Interindividual variation in the response by fibrinogen, C-reactive protein and interleukin-6 to yellow fever vaccination

NARCIS (Netherlands)

Verschuur, M.; Beek, M.T. van der; Tak, H.S.; Visser, L.G.; Maat, M.P.M. de

2004-01-01

The acute phase reaction is important in many disease processes. Habitual levels of the acute phase proteins fibrinogen, C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with an increased risk of cardiovascular disease, but the dynamic variation of plasma levels of acute phase

Fibrinogen, homocyst(e)ine, and C-reactive protein concentrations relative to sex and socioeconomic status in British young people.

Science.gov (United States)

Thomas, Non-Eleri; Cooper, Stephen-Mark; Williams, Simon R P; Baker, Julien S; Davies, Bruce

2005-01-01

This study assesses the prevalence of recently identified coronary heart disease (CHD) risk factors in young people of differing socioeconomic status (SES). From November 2001 through March 2002, 100 boys and 108 girls, of age 12.9 +/- 0.3 years, selected from differing SES were assessed for CHD risk factors. Measurements included fibrinogen (Fg), homocyst(e)ine (Hcy), and C-reactive protein (CRP). Fibrinogen was significantly greater among boys from a higher SES compared with those from a low SES (P < or = 0.05). Differences according to sex (P < or = 0.05) were identified for Fg and CRP. The data indicate the prevalence of recently identified CHD risk factors in this cohort of British schoolchildren. For the purpose of this article, the phrase "young people" embraces both children and adolescents. Copyright 2005 Wiley-Liss, Inc

Variation of fibrinogen oligosaccharide structure in the acute phase response: Possible haemorrhagic implications

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Stephen O. Brennan

2015-06-01

Conclusions and implications: The failure of incorporation Gal excludes the possibility of the hepatic NAcNeu Gal transferase capping the oligosaccharides with sialic acid. This has two desirable haemostatic outcomes: fibrin monomers will polymerise and form clots more rapidly, and two galactose residues can never be exposed diminishing uptake of the protein by the asialoglycoprotein receptor and ramping up concentration at a time of challenge.

A novel clot lysis assay for recombinant plasminogen activator.

Science.gov (United States)

Jamialahmadi, Oveis; Fazeli, Ahmad; Hashemi-Najafabadi, Sameereh; Fazeli, Mohammad Reza

2015-03-01

Recombinant plasminogen activator (r-PA, reteplase) is an engineered variant of alteplase. When expressed in E. coli, it appears as inclusion bodies that require refolding to recover its biological activity. An important step following refolding is to determine the activity of refolded protein. Current methods for enzymatic activity of thrombolytic drugs are costly and complex. Here a straightforward and low-cost clot lysis assay was developed. It quantitatively measures the activity of the commercial reteplase and is also capable of screening refolding conditions. As evidence for adequate accuracy and sensitivity of the current assay, r-PA activity measurements are shown to be comparable to those obtained from chromogenic substrate assay.

Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen, produced by plasmin (fragments X)

NARCIS (Netherlands)

Nieuwenhuizen, W.; Gravesen, M.

1981-01-01

Early plasmin degradation products (X fragments) of human fibrinogen were prepared in the presence of calcium-ions or EGTA, and purified on Sepharose 6B-CL. X fragments were characterized with respect to amino-terminal amino acids, polypeptide-chain composition, anticlotting properties and

MATHEMATICAL MODELING OF SELF-EXCITED VIBRATION OF PIPES CONTAINING MOBILE BOILING FLUID CLOTS

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Yevgeniy Tolbatov

2015-06-01

Full Text Available Numerical modeling dynamic behavior of a pipe containing inner nonhomogeneous flows of a boiling fluid has been carried out. The system vibrations at different values of the parameters of the flow nonhomogeneity and its velocity are observed. The possibility of forming stable and unstable flows depending on the character ofnonhomogeneity and the velocity of fluid clots has been found.

Fibrinogen: a novel predictor of responsiveness in metastatic melanoma patients treated with bio-chemotherapy: IMI (italian melanoma inter-group trial

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Casamassima Addolorata

2003-12-01

Full Text Available Abstract Purpose To evaluate a panel of pretreatment clinical and laboratory parameters in metastatic melanoma (MM in order to verify their impact on response and survival in a single prospective multi-institutional phase III study comparing out-patient chemotherapy (CT vs bioCT. Methods A total of 176 patients were randomised to receive CT (cisplatin, dacarbazine, optional carmustine or bioCT (the same CT followed by subcutaneous IL-2 plus intramuscular α-IFN-2b. Pretreatment total leucocytes, lymphocytes, eosinophyls, C-reactive protein (CRP, lactate dehydrogenase (LDH, erytrosedimentation rate (ESR, and fibrinogen were analyzed. Some clinical parameters (performance status, age, sex, and disease site were also considered. As we found a positive trend for bio-CT with no statistical significance in OR (25.3% vs 20.2% and OS (11 Mo vs 9.5 Mo, all analyses are stratified by treatment arm. Results In univariate analysis, higher value of lymphocytes percentage (P Conclusion Liver disease and higher LDH and fibrinogen levels had an important impact on survival in MM patients. In particular, fibrinogen has been recently reconsidered both for its determinant role in the host hemostatic system, and for its capability to provide protection against NK and LAK-cell-induced lysis. These observations could have some important implications for therapeutic approaches, in particular when immunological strategies are used.

Monoaminylation of Fibrinogen and Glia-Derived Proteins: Indication for Similar Mechanisms in Posttranslational Protein Modification in Blood and Brain.

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Hummerich, René; Costina, Victor; Findeisen, Peter; Schloss, Patrick

2015-07-15

Distinct proteins have been demonstrated to be posttranslationally modified by covalent transamidation of serotonin (5-hydropxytryptamin) to glutamine residues of the target proteins. This process is mediated by transglutaminase (TGase) and has been termed "serotonylation." It has also been shown that other biogenic amines, including the neurotransmitters dopamine and norepinephrine, can substitute for serotonin, implying a more general mechanism of "monoaminylation" for this kind of protein modification. Here we transamidated the autofluorescent monoamine monodansylcadaverine (MDC) to purified plasma fibrinogen and to proteins from a primary glia cell culture. Electrophoretic separation of MDC-conjugated proteins followed by mass spectrometry identified three fibrinogen subunits (Aα, Bβ, γ), a homomeric Aα2 dimer, and adducts of >250 kDa molecular weight, as well as several glial proteins. TGase-mediated MDC incorporation was strongly reduced by serotonin, underlining the general mechanism of monoaminylation.

Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets.

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Marcinkiewicz, Cezary; Gerstenhaber, Jonathan A; Sternberg, Mark; Lelkes, Peter I; Feuerstein, Giora

2017-01-01

Thromboembolic events (TEE) underwrite key causes of death in developed countries. While advanced imaging technologies such as computed tomography scans serve to diagnose blood clots during acute cardiovascular events, no such technology is available in routine primary care for TEE risk assessment. Here, we describe an imaging platform technology based on bioengineered fluorescent nanodiamond particles (F-NDPs) functionalized with bitistatin (Bit), a disintegrin that specifically binds to the α IIb β 3 integrin, platelet fibrinogen receptor (PFR) on activated platelets. Covalent linkage of purified Bit to F-NDP was concentration-dependent and saturable, as validated by enzyme-linked immunosorbent assay using specific anti-Bit antibodies. F-NDP-Bit interacted with purified PFR, either in immobilized or soluble form. Lotrafiban, a nonpeptide, α IIb β 3 receptor antagonist, specifically blocked F-NDP-Bit-PFR complex formation. Moreover, F-NDP-Bit specifically binds to activated platelets incorporated into a clot generated by thrombin-activated rat platelet-rich plasma (PRP). Our results suggest that engineered F-NDP-Bit particles could serve as noninvasive, "real-time" optical diagnostics for clots present in blood vessels.

Radioiodine-fibrinogen test in the early diagnosis of venous thrombosis in the leg

Energy Technology Data Exchange (ETDEWEB)

Dahlgruen, H [Medizinische Hochschule Hannover (F.R. Germany). Dept. Radiologie

1976-04-01

As long as there is no satisfactory prophylaxis for thrombosis, the radioiodine-fibrinogen test is a good supplement for the supervision of patients with a 'high thrombosis risk' since the clinical symptomatology is not specific enough and phlebography cannot be used so extensively. The risk of hepatitis can be reduced when the selection of spenders is large enough. As a radionuclide, /sup 125/iodine does not appear to be any less effective than /sup 131/iodine. The postoperative injection is preferred to the preoperative injection.

Investigations on blood coagulation in the green iguana (Iguana iguana).

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Kubalek, S; Mischke, R; Fehr, M

2002-05-01

The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, kaolin clotting time (KCT), dilute Russell's viper venom time (DRVVT) and reptilase time, as well as five different plasma fibrinogen assays [gravimetry, Jacobsson method (extinction at 280 nm), Millar method (heat precipitation), kinetic turbidometry, Clauss method] and resonance thrombography were performed in 26 clinically healthy green iguanas. All assays were carried out in comparison with pooled normal canine plasma. In iguana plasma, the PT [median (x0.50) = 453-831 s, dependent on the reagent], APTT (x0.50 = 170-242 s, dependent on the reagent), thrombin time (x0.50 = 118 - > 1000 s, dependent on thrombin activity), KCT (x0.50 = 274 s), DRVVT (x0.50 = 349 s) and reptilase time (all samples > 1000 s) were widely scattered at the limit of measurability. Only fibrinogen concentrations measured using the Jacobsson method (x0.50 = 4.40 g/l) correlated well (r = 0.91) with gravimetry (x0.50 = 4.22 g/l). The results of this study indicate a limited suitability and a confined diagnostic significance of the selected methods in the green iguana. This may be caused by the species specificity of certain components of the reagents used, as well as a less optimal test system, i.e. relationship of test reagent to clotting factor concentrations in iguana plasma.

Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.

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Dirkmann, Daniel; Britten, Martin W; Pauling, Henning; Weidle, Juliane; Volbracht, Lothar; Görlinger, Klaus; Peters, Jürgen

2016-06-01

Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays. Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Sugammadex increased PT (+9.1%; P Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.

Effects of Long-Term Developmental Patterns of Adiposity on Levels of C-Reactive Protein and Fibrinogen among North-American Men and Women: The Spokane Heart Study

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Trynke Hoekstra

2014-06-01

Full Text Available This study examined the heterogeneity in BMI development by identifying distinct developmental trajectories. These trajectories were further investigated by relating them to markers of low-grade inflammation later in life. Data from approximately 400 healthy volunteers participating in the Spokane Heart Study were collected in 2-year intervals, and four waves of data were available for the current analyses. Body weight was measured by BMI and low-grade inflammation by high-sensitivity C-reactive protein (CRP and fibrinogen. Up to date statistical techniques, i.e. latent class growth models, were used to analyse heterogeneity in body weight, and linear regressions were run to analyse possible associations between trajectories of body weight and CRP/fibrinogen levels. Six trajectories were identified (three stable, two increasing, and one decreasing which differed significantly on CRP/fibrinogen levels, highlighting the importance of weight trajectories. The differences were only partly explained by variations in lifestyle habits.

Study on sup(99m)Tc-colloid accumulation of in vitro clots and thrombi in rats

Energy Technology Data Exchange (ETDEWEB)

Ohguchi, Manabu [Kanazawa Univ. (Japan). School of Medicine

1983-02-01

The accumulation of different sup(99m)Tc-colloids in vitro clot, venous thrombi and intravascular fibrin deposits in rats was studied. Blood clot was produced by incubating fresh blood at room temperature for three hours. The mean value of % uptake of sup(99m)Tc-Sn colloid in clot was 96.2 % and higher than that of any other sup(99m)Tc-colloids. Venous thrombi in rats were made by clamping the left femoral vein segments for 5 minutes. With sup(99m)Tc-Sn colloid, the mean value of the ratio of the radioactivity in the clamped vein segment to the control segment (L/R ratio) was 54.5. L/R ratios of others were 24.2 with sup(99m)Tc-phytate, 12.1 with sup(99m)Tc-sulfur colloid, 3.9 with sup(99m)Tc-rhenium colloid, 2.4 with sup(99m)Tc-millimicrosphere albumin. L/R ratios were higher for the fresh thrombi, significant uptake was also observed up to seven days. Intravascular fibrin deposits were induced by i.p. injection of endotoxin into rats. Three hours after injection of endotoxin, sup(99m)Tc-colloids were i.v. injected. Significant lung uptake was observed in sup(99m)Tc-colloids except in sup(99m)Tc-rhenium colloid. And the most remarkable change of lung uptake was observed in sup(99m)Tc-Sn colloid. Significant kidney uptake was observed in sup(99m)Tc-Sn colloid and sup(99m)Tc-sulfur colloid. And the most remarkable change of kidney uptake was also observed in sup(99m)Tc-Sn colloid. When heparin was injected i.v. at the same time as endotoxin injection, lung uptake of sup(99m)Tc-Sn colloid was significantly decreased. However, the heparin effect on kidney uptake of sup(99m)Tc-Sn colloid was more significant than on lung uptake. The results in this study indicated that sup(99m)Tc-Sn colloid showed the greatest affinity to in vitro clots, venous thrombi and intravascular fibrin deposits.

Association Between Inflammatory Markers and Progression to Kidney Dysfunction: Examining Different Assessment Windows in Patients With Type 1 Diabetes.

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Baker, Nathaniel L; Hunt, Kelly J; Stevens, Danielle R; Jarai, Gabor; Rosen, Glenn D; Klein, Richard L; Virella, Gabriel; Lopes-Virella, Maria F

2018-01-01

To determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association. Biomarkers were measured at four time points during 28 years of treatment and follow-up in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. In addition to traditional biomarkers of inflammation (C-reactive protein and fibrinogen), we measured interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]). Renal outcomes were defined as progression to incident chronic kidney disease (stage 3 or more severe) or macroalbuminuria (albumin excretion rate ≥300 mg/24 h). Prospective multivariate event-time analyses were used to determine the association of each biomarker with each subsequent event within prespecified intervals (3-year and 10-year windows). Multivariate event-time models indicated that several markers of inflammation (sTNFR-1/2), endothelial dysfunction (sE-selectin), and clotting/fibrinolysis (fibrinogen and PAI-1) are significantly associated with subsequent development of kidney dysfunction. Although some markers showed variations in the associations between the follow-up windows examined, the results indicate that biomarkers (sTNFR-1/2, sE-selectin, PAI-1, and fibrinogen) are associated with progression to chronic kidney disease in both the 3-year and the 10-year windows. Plasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up. © 2017 by the American Diabetes Association.

Fabrication and physical and biological properties of fibrin gel derived from human plasma

Science.gov (United States)

Zhao, Haiguang; Ma, Lie; Zhou, Jie; Mao, Zhengwei; Gao, Changyou; Shen, Jiacong

2008-03-01

The fast development of tissue engineering and regenerative medicine drives the old biomaterials, for example, fibrin glue, to find new applications in these areas. Aiming at developing a commercially available hydrogel for cell entrapment and delivery, in this study we optimized the fabrication and gelation conditions of fibrin gel. Fibrinogen was isolated from human plasma by a freeze-thaw circle. Gelation of the fibrinogen was accomplished by mixing with thrombin. Absorbance of the fibrinogen/thrombin mixture at 550 nm as a function of reaction time was monitored by UV-VIS spectroscopy. It was found that the clotting time is significantly influenced by the thrombin concentration and the temperature, while less influenced by the fibrinogen concentration. After freeze-drying, the fibrin gel was characterized by scanning electron microscopy (SEM), revealing fibrous microstructure. Thermal gravimetric analysis found that the degradation temperature of the crosslinked fibrin gel starts from 288 °C, which is about 30 °C higher than that of the fibrinogen. The hydrogel has an initial water-uptake ratio of ~50, decreased to 30-40 after incubation in water for 11 h depending on the thrombin concentration. The fibrin gels lost their weights in PBS very rapidly, while slowly in DMEM/fetal bovine serum and DMEM. In vitro cell culture found that human fibroblasts could normally proliferate in the fibrin gel with spreading morphology. In conclusion, the fibrin gel containing higher concentration of fibrinogen (20 mg ml-1) and thrombin (5 U ml-1) has suitable gelation time and handling properties, and thus is applicable as a delivery vehicle for cells such as fibroblasts.

Indium-111 platelet scintigraphy and two-dimensional echocardiography for detection of left ventricular thrombus: influence of clot size and age

International Nuclear Information System (INIS)

Seabold, J.E.; Schroeder, E.C.; Conrad, G.R.

1987-01-01

Two-dimensional echocardiography and indium-111 platelet scintigraphy were performed on 50 dogs to determine the influence of clot age and size on the detection of experimentally induced left ventricular mural thrombus. Thrombus was induced by apical infarction and injection of a sclerosing agent and thrombin. The animals were classified into four groups according to the time of indium-111 platelet injection after thrombus induction: Group I (17 dogs, 1/2 hour after induction; 3 dogs, before induction), Group II (12 dogs, 24 hours after induction) and Group III (12 dogs, 1 week after induction). In Group IV (six control dogs) apical infarction was produced, but thrombin was not injected; indium-111 platelets were injected 1/2 to 1 hour after infarction. The dogs were studied by indium-111 platelet scintigraphy and by two-dimensional echocardiography 1/2 to 5 hours (Group I) and 1 to 5 and up to 72 hours (Groups II to IV) after platelet administration and before death was induced. Two-dimensional echocardiography showed the best overall sensitivity for detection of acute thrombus (97%; 29 of 30). The sensitivity of indium-111 platelet scintigraphy was 86% (18 of 21) for clots greater than or equal to 0.08 ml in size, and 67% (20 of 30) for detection of all clots. Thrombus did not form in 14 dogs of Groups I to III and in 6 of 6 control dogs. The specificity of scintigraphy was 100% (20 of 20) compared with 80% (16 of 20) for echocardiography. Echocardiography was more sensitive than scintigraphy for detecting very small clots in this experimental model

Prolonged Activated Clotting Time after Protamine Administration Does Not Indicate Residual Heparinization after Cardiopulmonary Bypass in Pediatric Open Heart Surgery.

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Yamamoto, Tomohiro; Wolf, Hans-Gerd; Sinzobahamvya, Nicodème; Asfour, Boulos; Hraska, Victor; Schindler, Ehrenfried

2015-08-01

In open heart surgery, heparinization is commonly neutralized using an empirical heparin:protamine ratio ranging between 1:1 and 1:1.5. However, these ratios may result in protamine overdose that should be avoided for its negative side effects on the coagulation system. This study aimed to indicate the appropriate treatment for prolonged activated clotting time (ACT) after protamine administration following cardiopulmonary bypass (CPB) in pediatric open heart surgery by investigating the underlying reasons for it. Twenty-seven children (open heart surgery were included. Heparin was administered only before CPB (400 IU/kg) and in the pump priming volume for CPB (2,000 IU) and was neutralized by 1:1 protamine after CPB. The blood heparin concentration was measured using anti-Xa assay. ACT and blood concentrations of heparin, coagulation factors, thrombin-antithrombin complex, and prothrombin fragment 1 + 2 were assessed. A rotational thromboelastometry (ROTEM; Tem International GmbH, München, Bayern, Germany) was used to confirm the coagulation status and residual heparin after protamine administration. Anti-Xa assay showed that there is no residual heparin in the blood after 1:1 protamine administration. Nevertheless, ACT (128.89 ± 3.09 seconds before heparin administration) remained prolonged (177.14 ± 5.43 seconds at 10 minutes after protamine, 182.00 ± 5.90 seconds at 30 minutes after protamine). The blood concentrations of coagulation factors were significantly lower than those before heparin administration (p < 0.01). The low FIBTEM MCF of ROTEM (4.43 ± 0.32 mm) at 10 minutes after protamine indicated low fibrinogen concentration. Prolonged ACT after heparin neutralization by 1:1 protamine administration does not necessarily indicate residual heparin, but low blood concentrations of coagulation factors should be considered as a reason as well. Accordingly, supply of coagulation factors instead of additional protamine should be

Measuring factor IX activity of nonacog beta pegol with commercially available one-stage clotting and chromogenic assay kits: a two-center study.

Science.gov (United States)

Bowyer, A E; Hillarp, A; Ezban, M; Persson, P; Kitchen, S

2016-07-01

Essentials Validated assays are required to precisely measure factor IX (FIX) activity in FIX products. N9-GP and two other FIX products were assessed in various coagulation assay systems at two sites. Large variations in FIX activity measurements were observed for N9-GP using some assays. One-stage and chromogenic assays accurately measuring FIX activity for N9-GP were identified. Background Measurement of factor IX activity (FIX:C) with activated partial thromboplastin time-based one-stage clotting assays is associated with a large degree of interlaboratory variation in samples containing glycoPEGylated recombinant FIX (rFIX), i.e. nonacog beta pegol (N9-GP). Validation and qualification of specific assays and conditions are necessary for the accurate assessment of FIX:C in samples containing N9-GP. Objectives To assess the accuracy of various one-stage clotting and chromogenic assays for measuring FIX:C in samples containing N9-GP as compared with samples containing rFIX or plasma-derived FIX (pdFIX) across two laboratory sites. Methods FIX:C, in severe hemophilia B plasma spiked with a range of concentrations (from very low, i.e. 0.03 IU mL(-1) , to high, i.e. 0.90 IU mL(-1) ) of N9-GP, rFIX (BeneFIX), and pdFIX (Mononine), was determined at two laboratory sites with 10 commercially available one-stage clotting assays and two chromogenic FIX:C assays. Assays were performed with a plasma calibrator and different analyzers. Results A high degree of variation in FIX:C measurement was observed for one-stage clotting assays for N9-GP as compared with rFIX or pdFIX. Acceptable N9-GP recovery was observed in the low-concentration to high-concentration samples tested with one-stage clotting assays using SynthAFax or DG Synth, or with chromogenic FIX:C assays. Similar patterns of FIX:C measurement were observed at both laboratory sites, with minor differences probably being attributable to the use of different analyzers. Conclusions These results suggest that, of the

N-terminal Pro-brain Natriuretic Peptide, High-sensitivity Troponin and Pulmonary Artery Clot Score as Predictors of Right Ventricular Dysfunction in Echocardiography.

Science.gov (United States)

Granér, Marit; Harjola, Veli-Pekka; Selander, Tuomas; Laiho, Mia K; Piilonen, Anneli; Raade, Merja; Mustonen, Pirjo

2016-06-01

We investigated the ability of cardiac biomarkers and total pulmonary artery (PA) clot score to predict right ventricular dysfunction (RVD) on admission and at seven-month follow-up in subjects with acute pulmonary embolism (APE). Sixty-three normotensive patients with APE were divided into two groups: patients with (n= 32, age 58±19 years) and without (n=31, age 55±16 years) echocardiographic RVD. Transthoracic echocardiography (TTE), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) were assessed upon arrival and repeated at seven months. Total PA clot score was determined on admission. The age- and sex dependent NT-proBNP on admission, on day 5, and at seven months exhibited the best sensitivity (admission 94%, day 5 100%, seven months 100%) and negative predictive value (NPV) (89%, 100%, 100%) for detecting RVD. Six patients (10%) had persistent RVD at seven months. Total PA clot score showed only low to moderate sensitivity (77%) and PPV (7%) for detection of RVD at seven months. Normal age- and sex dependent NT-proBNP on admission or measured five days later seems to be useful in exclusion of RVD at follow up. Total PA clot score shows only to be of modest benefit for predicting persistent RVD. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

RESEARCH ON THE QUALITY INDICATORS OF CURD PRODUCTS BASED ON PROTEIN-HERBAL CLOTS

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Olena GREK

2017-12-01

Full Text Available The article presents the research of qualitative indicators of curd products with different nutritional ingredients based on protein-herbal clots. The effect of the number of Rumex juice and the duration of thermoacid processing on the process of precipitation of milk proteins was determined. It was established that the introduction of vegetative coagulant in the amount (9 ± 0.5% at a temperature (93 ... 95 °C and endurance (3 ... 5 min - provides the optimal yield of protein-herbal clot taking into account restrictions according to organoleptic parameters. The effect of white sugar and apple pectin in fiber on the organoleptic, physico-chemical and rheological indicators curd products was investigated. The dietary fibers increase moisture-proof ability and effective viscosity of samples, and white sugar reduces these indexes due to dehydrating properties. The optimal option is to add to the protein-herbal bunch at the same time two components when mixing - white sugar and apple pectin in fiber in quantities of 15% and 2% respectively. Taking into account the influence of individual non-dairy ingredients - Rumex juice of white sugar and apple pectin in fiber on curd products, the performance of the finished product can purposefully be affected.

Purification and characterization of a milk-clotting aspartic proteinase from globe artichoke (Cynara scolymus L.).

Science.gov (United States)

Llorente, Berta E; Brutti, Cristina B; Caffini, Néstor O

2004-12-29

The study of proteinase expression in crude extracts from different organs of the globe artichoke (Cynara scolymus L.) disclosed that enzymes with proteolytic and milk-clotting activity are mainly located in mature flowers. Maximum proteolytic activity was recorded at pH 5.0, and inhibition studies showed that only pepstatin, specific for aspartic proteinases, presented a significant inhibitory effect. Such properties, in addition to easy enzyme inactivation by moderate heating, make this crude protease extract potentially useful for cheese production. Adsorption with activated carbon, together with anion exchange and affinity chromatography, led to the isolation of a heterodimeric milk-clotting proteinase consisting of 30- and 15-kDa subunits. MALDI-TOF MS of the 15-kDa chain determined a 15.358-Da mass, and the terminal amino sequence presented 96% homology with the smaller cardosin A subunit. The amino terminal sequence of the 30-kDa chain proved to be identical to the larger cardosin A subunit. Electrophoresis evidenced proteinase self-processing that was confirmed by immunoblots presenting 62-, 30-, and 15-kDa bands.

Fibrinogen novy Jicin and Praha II: Cases of hereditary A alpha 16 Arg -> Cys and A alpha 16 Arg -> His dysfibrinogenemia

Czech Academy of Sciences Publication Activity Database

Kotlín, R.; Chytilová, M.; Suttnar, J.; Riedel, Tomáš; Salaj, P.; Blatný, J.; Šantrůček, J.; Klener, P.; Dyr, J. E.

2007-01-01

Roč. 121, č. 1 (2007), s. 75-84 ISSN 0049-3848 Institutional research plan: CEZ:AV0Z40500505 Keywords : dysfibrinogenemia * fibrinogen * fibrinopeptide A Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.038, year: 2007

Early detection of venous thromboses of the lower limb in traumatology using labelled fibrinogen

International Nuclear Information System (INIS)

Pasteyer, J.; Lanata, E.; Bonnard, P.; Jean, N.; Kher, A.; Patel, A.

1975-01-01

In emergency traumatology, the iodine 125 labelled fibrinogen test is useful in the early detection of phlebitis in patients in whom the routine use of heparin is not possible: fractures of the cervical spine, severe cranial trauma, elderly subjects. It makes possible the institution of appropriate heparin therapy, whithout waiting for clinical signs to become evident. Isotopic venous thromboses occured very frequently and very early and clinical signs, when present (50% of cases) occured 24 to 48 hours after the appearance of isotopic signs [fr

Computational Study of Thrombus Formation and Clotting Factor Effects under Venous Flow Conditions

Science.gov (United States)

2016-04-26

domain used in our thrombus formation simulations. Fig. 2 B shows the 3D geometry of the flow-chamber section consisting of two channels measuring 250 60...ArticleComputational Study of Thrombus Formation and Clotting Factor Effects under Venous Flow ConditionsVijay Govindarajan,1 Vineet Rakesh,1 Jaques...understanding of thrombus formation as a physicochemical process that has evolved to protect the integrity of the human vasculature is critical to our ability to

Influence of spacer length on heparin coupling efficiency and fibrinogen adsorption of modified titanium surfaces

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Gbureck Uwe

2007-07-01

Full Text Available Abstract Background Chemical bonding of the drug onto surfaces by means of spacer molecules is accompanied with a reduction of the biological activity of the drug due to a constricted mobility since normally only short spacer molecule like aminopropyltrimethoxysilane (APMS are used for drug coupling. This work aimed to study covalent attachment of heparin to titanium(oxide surfaces by varying the length of the silane coupling agent, which should affect the biological potency of the drug due to a higher mobility with longer spacer chains. Methods Covalent attachment of heparin to titanium metal and TiO2 powder was carried out using the coupling agents 3-(Trimethoxysilyl-propylamine (APMS, N- [3-(Trimethoxysilylpropyl]ethylenediamine (Diamino-APMS and N1- [3-(Trimethoxy-silyl-propyl]diethylenetriamine (Triamino-APMS. The amount of bound coupling agent and heparin was quantified photometrically by the ninhydrin reaction and the tolidine-blue test. The biological potency of heparin was determined photometrically by the chromogenic substrate Chromozym TH and fibrinogen adsorption to the modified surfaces was researched using the QCM-D (Quartz Crystal Microbalance with Dissipation Monitoring technique. Results Zeta-potential measurements confirmed the successful coupling reaction; the potential of the unmodified anatase surface (approx. -26 mV shifted into the positive range (> + 40 mV after silanisation. Binding of heparin results in a strongly negatively charged surface with zeta-potentials of approx. -39 mV. The retaining biological activity of heparin was highest for the spacer molecule Triamino-APMS. QCM-D measurements showed a lower viscosity for adsorbed fibrinogen films on heparinised surfaces by means of Triamino-APMS. Conclusion The remaining activity of heparin was found to be highest for the covalent attachment with Triamino-APMS as coupling agent due to the long chain of this spacer molecule and therefore the highest mobility of the drug

Renal Amyloidosis Associated With 5 Novel Variants in the Fibrinogen A Alpha Chain Protein

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Dorota Rowczenio

2017-05-01

Discussion: We report 6 novel mutations in the FGA gene: 5 were associated with renal fibrinogen A alpha chain amyloidosis and 1 was found to be incidental to light-chain amyloid deposits discovered in a patient with a plasma cell dyscrasia. Clinical awareness and suspicion of hereditary amyloidosis corroborated by genetic analysis and adequate typing using combined immunohistochemistry and laser microdissection and mass spectrometry is valuable to avoid misdiagnosis, especially when a family history of amyloidosis is absent.

Diastolic timed Vibro-Percussion at 50 Hz delivered across a chest wall sized meat barrier enhances clot dissolution and remotely administered Streptokinase effectiveness in an in-vitro model of acute coronary thrombosis

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Hoffmann Andrew

2012-11-01

Full Text Available Abstract Background Low Frequency Vibro-Percussion (LFVP assists clearance of thrombi in catheter systems and when applied to the heart and timed to diastole is known to enhance coronary flow. However LFVP on a clotted coronary like vessel given engagement over a chest wall sized barrier (to resemble non-invasive heart attack therapy requires study. Methods One hour old clots (n=16 were dispensed within a flexible segment of Soft-Flo catheter (4 mm lumen, weighted, interfaced with Heparinized Saline (HS, secured atop a curved dampening base, and photographed. A ~4 cm meat slab was placed over the segment and randomized to receive intermittent LFVP (engaged, - disengaged at 1 second intervals, or no LFVP for 20 minutes. HS was pulsed (~120/80 mmHg, with the diastolic phase coordinated to match LFVP delivery. The segment was then re-photographed and aspirated of fluid to determine post clot weight. The trial was then repeated with 0.5 mls of Streptokinase (15,000 IU/100 microlitre delivered ~ 2 cm upstream from the clot. Results LFVP - HS only samples (vs. controls showed; a development of clot length fluid channels absent in the control group (p Conclusion Diastolic timed LFVP (50 Hz engaged across a chest wall sized barrier enhances clot disruptive effects to an underlying coronary like system.

Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

Science.gov (United States)

Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F

1999-04-01

Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A

DEFF Research Database (Denmark)

Hvas, Anne-Mette; Sørensen, Hanne Thykjær; Norengaard, Lisbeth

2007-01-01

examined whether the clot stability in hemophiliacs could be improved by treatment with tranexamic acid (TXA) in combination with recombinant factor VIII (rFVIII). PATIENTS/METHODS: Baseline blood samples were obtained from eight males with severe hemophilia A. Thereafter, a bolus injection of r...