Sample records for blood coagulation disorders inherited

  1. Blood coagulation factor VIII: An overview

    Indian Academy of Sciences (India)

    Factor VIII (FVIII) functions as a co-factor in the blood coagulation cascade for the proteolytic activation of factor X by factor IXa. Deficiency of FVIII causes hemophilia A, the most commonly inherited bleeding disorder. This review highlights current knowledge on selected aspects of FVIII in which both the scientist and the ...

  2. [Severe blood coagulation disorder as the first sign of a peritoneal hemangio-endothelioma: a new therapeutic approach (author's transl)]. (United States)

    Debray, P; Girot, R; Josso, F; Mselati, J C; Hubert, P; Lavaud, J; Cloup, M


    The authors describe a 3 1/2 month old infant with hemangio-endothelioma and a severe blood coagulation disorder. The tumor was inoperable and the severe blood coagulation disorder posed considerable therapeutic problem. After treatment with massive amounts of blood clotting factors, an antifibrinolytic drug and radiotherapy, the child's condition improved.

  3. Coagulation and Mental Disorders

    Directory of Open Access Journals (Sweden)

    Silvia Hoirisch-Clapauch


    Full Text Available The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders. The current review focuses on emerging data linking coagulation and some psychiatric disorders.

  4. Coagulation disorders in intensive care

    NARCIS (Netherlands)

    Levi, Marcel


    Coagulation disorders are common in intensive care patients and may range from isolated thrombocytopenia or prolonged clotting times to disseminated intravascular coagulation. There are many causes of disturbed coagulation in critically ill patients and each may require specific treatment

  5. Correction of disorders in tissue perfusion, blood coagulation and fibrinolysis with Orbita apparatus on terahertz waves of cell metabolites

    Directory of Open Access Journals (Sweden)

    Vyacheslav F. Kirichuk


    Full Text Available This article contains information on principle of operation, technical parameters and possible application of Orbita {transliteration from Russian} apparatus for hemodynamic, fibrinolytic and peripheral perfusion disorders treatment. A single exposure to terahertz waves emitted by Orbita apparatus, corresponding to frequencies of molecular absorption and emission spectra of atmospheric oxygen (129.0 GHz, completely cures coagulant and fibrinolytic disorders of animals with acute immobilization stress. A course of treatment with electromagnetic waves corresponding to frequencies of molecular absorption and emission spectra of nitrogen oxide (150.176 – 150.664 leads to normalization of disrupted peripheral tissue perfusion parameters of animal undergoing treatment and stimulates basal and induced output of nitrogen oxide. This leads to decrease in peripheral vascular resistance to microcirculation and increase in blood flow to microvasculature. Experimental data provided in this article serves as a proof of viability of Orbita apparatus for treatment of coagulant, fibrinolytic and tissue perfusion disorders.

  6. Blood coagulation factors as inflammatory mediators

    NARCIS (Netherlands)

    Schoenmakers, Saskia H. H. F.; Reitsma, Pieter H.; Spek, C. Arnold


    After the first observations about blood coagulation by Hippocrates, it took until the early 1900s before the classic theory of blood coagulation was presented. As more and more other coagulation factors were discovered, the four-factor coagulation scheme became more complex, but better understood,

  7. Intravascular blood coagulation after irradiation

    International Nuclear Information System (INIS)

    Sushkevich, G.N.


    The problems of activation of intravascular blood coagulation (JVBC) at different stages after irradiation, are considered. JVBC peculiarities (disseminated intravascular syndrome (DIV) or thrombo hemorrhagic syndrome) are investigated. Literature on alterations which take place in the organism under effect of ionizing irradiation is analyzed. This analysis proves the characteristic features of thrombinogenesis activation and development of DIV syndrome not only in the early post-radiation period, but in the middle of radiation disease, as well. It is also shown that ionizing radiation activizes the hemocoagulation process and causes IVBC in the case of both local and general irradiation [ru

  8. Nanoparticles and the blood coagulation system. Part II: safety concerns (United States)

    Ilinskaya, Anna N; Dobrovolskaia, Marina A


    Nanoparticle interactions with the blood coagulation system can be beneficial or adverse depending on the intended use of a nanomaterial. Nanoparticles can be engineered to be procoagulant or to carry coagulation-initiating factors to treat certain disorders. Likewise, they can be designed to be anticoagulant or to carry anticoagulant drugs to intervene in other pathological conditions in which coagulation is a concern. An overview of the coagulation system was given and a discussion of a desirable interface between this system and engineered nanomaterials was assessed in part I, which was published in the May 2013 issue of Nanomedicine. Unwanted pro- and anti-coagulant properties of nanoparticles represent significant concerns in the field of nanomedicine, and often hamper the development and transition into the clinic of many promising engineered nanocarriers. This part will focus on the undesirable effects of engineered nanomaterials on the blood coagulation system. We will discuss the relationship between the physicochemical properties of nanoparticles (e.g., size, charge and hydrophobicity) that determine their negative effects on the blood coagulation system in order to understand how manipulation of these properties can help to overcome unwanted side effects. PMID:23730696

  9. Thrombosis in Inherited Fibrinogen Disorders (United States)

    Korte, Wolfgang; Poon, Man-Chiu; Iorio, Alfonso; Makris, Michael


    Although inherited fibrinogen disorders (IFD) are primarily considered to be bleeding disorders, they are associated with a higher thrombotic complication risk than defects in other clotting factors. Managing IFD patients with thrombosis is challenging as anticoagulant treatment may exacerbate the underlying bleeding risk which can be life-threatening. Due to the low prevalence of IFD, there is little information on pathophysiology or optimal treatment of thrombosis in these patients. We searched the literature for cases of thrombosis among IFD patients and identified a total of 128 patient reports. In approximately half of the cases, thromboses were spontaneous, while in the others trauma, surgery, and parturition contributed to the risk. The true mechanism(s) of thrombosis in IFD patients remain to be elucidated. A variety of anticoagulant treatments have been used in the treatment or prevention of thrombosis, sometimes with concurrent fibrinogen replacement therapy. There is no definite evidence that fibrinogen supplementation increases the risk of thrombosis, and it may potentially be effective in the treatment and prevention of both thrombosis and hemorrhage in IFD patients. PMID:28503122

  10. [Preoperative monitoring of blood coagulation in urologic operations: diagnosis of familial factor XI deficiency within the scope of preoperative blood coagulation studies]. (United States)

    Haushofer, A; Halbmayer, W M; Toth, E; Pflüger, H


    Presurgical coagulation diagnosis should--apart from coagulation monitoring in the laboratory based on a stepwise diagnosis for detection of coagulations disorders, starting with global tests (NT/APTT) followed by appropriate specific investigation in case of pathological findings--consist of an adequate hemostaseological anamnesis and physical checkup of the patient. This would allow detection of important signs of hemostaseological impairment during the pre-analytical phase already and permit subsequent initiation of more specific coagulation tests. The casuistics of a patient with factor XI-deficiency ("Minor Form"), a condition which is extremely infrequent in our country, demonstrates the coagulation diagnostic procedure which led to detection of his inherited factor XI-deficiency. In addition the pre-, peri- and postsurgical therapeutical management of this particular patient using an antifibrinolytic drug (tranexamic acid) is presented.

  11. Blood Coagulation and Asthma Exacerbation in Children. (United States)

    Manuyakorn, Wiparat; Mairiang, Dara; Sirachainan, Nongnuch; Kadegasem, Praguywan; Kamchaisatian, Wasu; Benjaponpitak, Suwat; Chuansumrit, Ampaiwan


    Recent studies have demonstrated the activation of coagulation pathways in asthmatic airways. This study aimed to determine systemic blood coagulation during asthma exacerbation compared with the stable state in children. Pediatric patients (aged between 5 and 15 years) suffering from asthma exacerbation were enrolled. von Willebrand factor (vWF), plasminogen activator inhibitor type-1 (PAI-1), protein C, D-dimer, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and C-reactive protein (CRP) levels were measured during asthma exacerbation and stable state. A total of 22 patients were enrolled. The median vWF, PAI-1, and CRP during asthma exacerbation were significantly higher than those of the stable state: 147.5% (interquartile range, IQR: 111.05-196.57) versus 94% (IQR: 69.72-109.62, p coagulation in asthma exacerbation. © 2016 S. Karger AG, Basel.

  12. Diagnosis Of Inherited Neurometabolic Disorders : A Biochemical Approach

    Directory of Open Access Journals (Sweden)

    Christopher R


    Full Text Available The past two decades have witnessed a rapid increase in the knowledge of the inherited neurometabolic disorders. The precise diagnosis of these disorders which is a challenge to the physician can be best accomplished by biochemical methods. Screening of clinically selected patients with simple chemical urine tests and routine blood chemistry investigations followed by measurement of specific metabolites and assay of the relevant enzymes confirms the diagnosis in most cases. Biochemical diagnosis of inherited neurometabolic disorders although expensive is rapid and confirmatory and therefore aids in treatment and further prevention of these rare disorders.

  13. Assessing blood coagulation status with laser speckle rheology (United States)

    Tripathi, Markandey M.; Hajjarian, Zeinab; Van Cott, Elizabeth M.; Nadkarni, Seemantini K.


    We have developed and investigated a novel optical approach, Laser Speckle Rheology (LSR), to evaluate a patient’s coagulation status by measuring the viscoelastic properties of blood during coagulation. In LSR, a blood sample is illuminated with laser light and temporal speckle intensity fluctuations are measured using a high-speed CMOS camera. During blood coagulation, changes in the viscoelastic properties of the clot restrict Brownian displacements of light scattering centers within the sample, altering the rate of speckle intensity fluctuations. As a result, blood coagulation status can be measured by relating the time scale of speckle intensity fluctuations with clinically relevant coagulation metrics including clotting time and fibrinogen content. Our results report a close correlation between coagulation metrics measured using LSR and conventional coagulation results of activated partial thromboplastin time, prothrombin time and functional fibrinogen levels, creating the unique opportunity to evaluate a patient’s coagulation status in real-time at the point of care. PMID:24688816

  14. Treatable inherited rare movement disorders

    NARCIS (Netherlands)

    Jinnah, H A; Albanese, Alberto; Bhatia, Kailash P; Cardoso, Francisco; Da Prat, Gustavo; de Koning, Tom J; Espay, Alberto J; Fung, Victor; Garcia-Ruiz, Pedro J; Gershanik, Oscar; Jankovic, Joseph; Kaji, Ryuji; Kotschet, Katya; Marras, Connie; Miyasaki, Janis M; Morgante, Francesca; Munchau, Alexander; Pal, Pramod Kumar; Rodriguez Oroz, Maria C; Rodríguez-Violante, Mayela; Schöls, Ludger; Stamelou, Maria; Tijssen, Marina; Uribe Roca, Claudia; de la Cerda, Andres; Gatto, Emilia M

    There are many rare movement disorders, and new ones are described every year. Because they are not well recognized, they often go undiagnosed for long periods of time. However, early diagnosis is becoming increasingly important. Rapid advances in our understanding of the biological mechanisms

  15. Contact activation of blood-plasma coagulation (United States)

    Golas, Avantika

    Surface engineering of biomaterials with improved hemocompatibility is an imperative, given the widespread global need for cardiovascular devices. Research summarized in this dissertation focuses on contact activation of FXII in buffer and blood plasma frequently referred to as autoactivation. The extant theory of contact activation imparts FXII autoactivation ability to negatively charged, hydrophilic surfaces. According to this theory, contact activation of plasma involves assembly of proteins comprising an "activation complex" on activating surfaces mediated by specific chemical interactions between complex proteins and the surface. This work has made key discoveries that significantly improve our core understanding of contact activation and unravel the existing paradigm of plasma coagulation. It is shown herein that contact activation of blood factor XII (FXII, Hageman factor) in neat-buffer solution exhibits a parabolic profile when scaled as a function of silanized-glass-particle activator surface energy (measured as advancing water adhesion tension t°a=g° Iv costheta in dyne/cm, where g°Iv is water interfacial tension in dyne/cm and theta is the advancing contact angle). Nearly equal activation is observed at the extremes of activator water-wetting properties --36 < t°a < 72 dyne/cm (O° ≤ theta < 120°), falling sharply through a broad minimum within the 20 < t°a < 40 dyne/cm (55° < theta < 75°). Furthermore, contact activation of FXII in buffer solution produces an ensemble of protein fragments exhibiting either procoagulant properties in plasma (proteolysis of blood factor XI or prekallikrein), amidolytic properties (cleavage of s-2302 chromogen), or the ability to suppress autoactivation through currently unknown biochemistry. The relative proportions of these fragments depend on activator surface chemistry/energy. We have also discovered that contact activation is moderated by adsorption of plasma proteins unrelated to coagulation through an

  16. Novel approaches for diagnosing inherited platelet disorders. (United States)

    Bastida Bermejo, José María; Hernández-Rivas, Jesús María; González-Porras, José Ramón


    Inherited platelet disorders diagnosis is based on the clinical history and bleeding assessment tools. The laboratory functional assays as well as the molecular test to identify the pathogenic genetic variant are essential to confirm the accurate diagnosis of these disorders. Nowadays, the main challenges to developing a new diagnostic system are involved in reducing the samples' volume, and faster and more helpful analysis. Moreover, there are no widely available and standardised global tests. High throughput genetic testing such as next-generation sequencing has revolutionised DNA sequencing technologies as it allows the simultaneous and faster investigation of multiple genes at a manageable cost. This technology has improved the molecular characterisation of inherited platelet disorders and has been implemented in the research studies and the clinical routine practice. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  17. Imaging of blood plasma coagulation at supported lipid membranes. (United States)

    Faxälv, Lars; Hume, Jasmin; Kasemo, Bengt; Svedhem, Sofia


    The blood coagulation system relies on lipid membrane constituents to act as regulators of the coagulation process upon vascular trauma, and in particular the 2D configuration of the lipid membranes is known to efficiently catalyze enzymatic activity of blood coagulation factors. This work demonstrates a new application of a recently developed methodology to study blood coagulation at lipid membrane interfaces with the use of imaging technology. Lipid membranes with varied net charges were formed on silica supports by systematically using different combinations of lipids where neutral phosphocholine (PC) lipids were mixed with phospholipids having either positively charged ethylphosphocholine (EPC), or negatively charged phosphatidylserine (PS) headgroups. Coagulation imaging demonstrated that negatively charged SiO(2) and membrane surfaces exposing PS (obtained from liposomes containing 30% of PS) had coagulation times which were significantly shorter than those for plain PC membranes and EPC exposing membrane surfaces (obtained from liposomes containing 30% of EPC). Coagulation times decreased non-linearly with increasing negative surface charge for lipid membranes. A threshold value for shorter coagulation times was observed below a PS content of ∼6%. We conclude that the lipid membranes on solid support studied with the imaging setup as presented in this study offers a flexible and non-expensive solution for coagulation studies at biological membranes. It will be interesting to extend the present study towards examining coagulation on more complex lipid-based model systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Adherence and Coagulation Assays in Dabigatran-treated Patients With Atrial Fibrillation (United States)


    Atrial Fibrillation; Medication Adherence; Blood Coagulation Tests; Anticoagulants; Circulating, Hemorrhagic Disorder; Drug Effect; Drug Use; Drug Toxicity; Drug Intolerance; Blood Clot; Blood Coagulation Disorder; Laboratory Problem; Bleeding; Thrombosis

  19. In Vitro Assessment of Nanoparticle Effects on Blood Coagulation. (United States)

    Potter, Timothy M; Rodriguez, Jamie C; Neun, Barry W; Ilinskaya, Anna N; Cedrone, Edward; Dobrovolskaia, Marina A


    Blood clotting is a complex process which involves both cellular and biochemical components. The key cellular players in the blood clotting process are thrombocytes or platelets. Other cells, including leukocytes and endothelial cells, contribute to clotting by expressing the so-called pro-coagulant activity (PCA) complex on their surface. The biochemical component of blood clotting is represented by the plasma coagulation cascade, which includes plasma proteins also known as coagulation factors. The coordinated interaction between platelets, leukocytes, endothelial cells, and plasma coagulation factors is necessary for maintaining hemostasis and for preventing excessive bleeding. Undesirable activation of all or some of these components may lead to pathological blood coagulation and life-threatening conditions such as consumptive coagulopathy or disseminated intravascular coagulation (DIC). In contrast, unintended inhibition of the coagulation pathways may lead to hemorrhage. Thrombogenicity is the property of a test material to induce blood coagulation by affecting one or more elements of the clotting process. Anticoagulant activity refers to the property of a test material to inhibit coagulation. The tendency to cause platelet aggregation, perturb plasma coagulation, and induce leukocyte PCA can serve as an in vitro measure of a nanomaterial's likelihood to be pro- or anticoagulant in vivo. This chapter describes three procedures for in vitro analyses of platelet aggregation, plasma coagulation time, and activation of leukocyte PCA. Platelet aggregation and plasma coagulation procedures have been described earlier. The revision here includes updated details about nanoparticle sample preparation, selection of nanoparticle concentration for the in vitro study, and updated details about assay controls. The chapter is expanded to describe a method for the leukocyte PCA analysis and case studies demonstrating the performance of these in vitro assays.

  20. Effect of rivaroxaban on blood coagulation using the viscoelastic coagulation test ROTEM™. (United States)

    Casutt, M; Konrad, C; Schuepfer, G


    This study investigated the influence of the oral direct inhibitor of factor Xa rivaroxaban on blood coagulation measured by rotation thrombelastometry ROTEM™. Blood was obtained from 11 healthy male volunteers before and 2.5 h after oral administration of 10 mg rivaroxaban. In addition to standard coagulation tests clot formation was measured by ROTEM™ analyzing extrinsic (Extem) and intrinsic thrombelastometry (Intem). Significant differences to the baseline values were found in the Extem clotting time (Extem-CT, 58 ± 9 s and 87 ± 17 s, p coagulation by rivaroxaban.

  1. Influence of blood flow on the coagulation cascade

    DEFF Research Database (Denmark)

    The influence of diffusion and convetive flows on the blood coagulation cascade is investigated for a controlled perfusion experiment. We present a cartoon model and reaction schemes for parts of the coagulation cascade with sunsequent set up of a mathematical model in two space dimensions plus one...

  2. Inventive activity of the Department of Protein Structure and Function of the Palladin Institute of Biochemistry of NAS of Ukraine. Part I. Development of the diagnostic methods for detection of hemostasis disorders and characterization of certain blood coagulation factors

    Directory of Open Access Journals (Sweden)

    V. M. Danilova


    Full Text Available The practical aspects of inventive activity of the Department of Protein Structure and Function of the Palladin Institute of Biochemistry, NAS of Ukraine are highlighted in this article. Through years of fundamental and applied researches of blood coagulation system proteins, initiated by luminaries of the world biochemistry O. V. Palladin and V. O. Belitser, the Department staff have developed a considerable number of methods, techniques and tests for the assessment of the state of the hemostasis system, which were approved in many clinics. In the first part of this work the authors describe the development of the diagnostic methods for identifying the homeostasis system disorders in detail, as well as characterize certain coagulation factors.

  3. Newborn Screening for inherited metabolic disorders; news and views

    Directory of Open Access Journals (Sweden)

    Morteza Pourfarzam


    Full Text Available Newborn screening is important for the early detection of many congenital genetic and metabolic disorders, aimed at the earliest possible recognition and management of affected newborns, to prevent the morbidity, mortality, and disabilities associated with an inherited metabolic disorder. This comprehensive system includes; testing, education, follow up, diagnosis, treatment, management, and evaluation. There are major differences among many of the disorders being considered for inclusion in newborn screening programs. In recent times, advances in laboratory technology such as tandem mass spectrometry (MS/MS, which is more specific, sensitive, reliable, and comprehensive than traditional assays, has increased the number of genetic conditions that can be diagnosed through neonatal screening programs at birth. With a single dried filter paper blood spot, MS/MS can identify more than 30 inherited metabolic disorders in around two to three minutes. Advances in the diagnosis and treatment and an increased understanding of the natural history of inborn errors of metabolism have produced pressure to implement expanded newborn screening programs in many countries. Even as many countries throughout the world have made newborn screening mandatory, in Iran, nationwide newborn screening for inherited metabolic disorders other than hypothyroidism has not been initiated, hence, there is little information about these diseases. This article aims to review the recent advances in newborn metabolic screening and its situation in Iran and other countries.

  4. Activation of blood coagulation in cancer: implications for tumour progression (United States)

    Lima, Luize G.; Monteiro, Robson Q.


    Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies. PMID:23889169

  5. Bio-responsive polymer hydrogels homeostatically regulate blood coagulation. (United States)

    Maitz, Manfred F; Freudenberg, Uwe; Tsurkan, Mikhail V; Fischer, Marion; Beyrich, Theresa; Werner, Carsten


    Bio-responsive polymer architectures can empower medical therapies by engaging molecular feedback-response mechanisms resembling the homeostatic adaptation of living tissues to varying environmental constraints. Here we show that a blood coagulation-responsive hydrogel system can deliver heparin in amounts triggered by the environmental levels of thrombin, the key enzyme of the coagulation cascade, which--in turn--becomes inactivated due to released heparin. The bio-responsive hydrogel quantitatively quenches blood coagulation over several hours in the presence of pro-coagulant stimuli and during repeated incubation with fresh, non-anticoagulated blood. These features enable the introduced material to provide sustainable, autoregulated anticoagulation, addressing a key challenge of many medical therapies. Beyond that, the explored concept may facilitate the development of materials that allow the effective and controlled application of drugs and biomolecules.

  6. Does whole blood coagulation analysis reflect developmental haemostasis?

    DEFF Research Database (Denmark)

    Ravn, Hanne Berg; Andreasen, Jo Bnding; Hvas, Anne-Mette


    : Developmental haemostasis has been well documented over the last 3 decades and age-dependent reference ranges have been reported for a number of plasmatic coagulation parameters. With the increasing use of whole blood point-of-care tests like rotational thromboelastometry (ROTEM) and platelet...... function tests, an evaluation of age-dependent changes is warranted for these tests as well. We obtained blood samples from 149 children, aged 1 day to 5.9 years, and analysed conventional plasmatic coagulation tests, including activated partial prothrombin time, prothrombin time, and fibrinogen...... (functional). Whole blood samples were analysed using ROTEM to assess overall coagulation capacity and Multiplate analyzer to evaluate platelet aggregation. Age-dependent changes were analysed for all variables. We found age-dependent differences in all conventional coagulation tests (all P values

  7. [Evaluation of coagulation disorders with thrombelastography in patients with sepsis]. (United States)

    Zhong, Shengjian; Zhang, Chunbao; Hu, Juntao; Tang, Zhanhong


    To compare the results of thrombelastography (TEG) and the conventional coagulability test in patients with sepsis, and to discuss the value of TEG in monitoring blood coagulation dysfunction in patients with sepsis. The clinical data of 92 adult patients with sepsis admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The patients were divided into sequential organ failure assessment (SOFA) score ≥ 12 group (n = 47) and SOFA coagulation function served as control group. The venous blood was collected for conventional blood coagulation test and routine examination of blood, D-dimer, procalcitonin (PCT), and TEG, and the differences were compared among three groups. Correlations between SOFA and various indexes of patients with sepsis were analyzed by Spearman rank correlation method. As shown in the results of the conventional blood coagulation test, D-dimer was gradually increased with the aggravation of the disease, the values in non-sepsis, SOFA coagulation test might not respond quickly to the change in coagulation status of sepsis patients. As shown in the results of TEG, the values of reaction time (R value) and kinetics time (K value) in SOFA 0.05; K value (minutes): 4.2 (3.4, 7.1) vs. 1.5 (1.3, 1.8), P coagulation index (CI) in SOFA coagulation in patients with sepsis, and distinguish the hypercoagulable and hypocoagulable state. TEG may be a valuable tool to evaluate degree and risk of sepsis objectively.

  8. Symptoms of Blood Disorders (United States)

    ... In This Article Generic Name Select Brand Names aspirin No US brand name Symptoms and Diagnosis of Blood Disorders Overview of Blood Disorders Symptoms of Blood Disorders Medical History and Physical Examination for Blood Disorders Laboratory Tests ...

  9. Mathematical Modeling of Intravascular Blood Coagulation under Wall Shear Stress (United States)

    Rukhlenko, Oleksii S.; Dudchenko, Olga A.; Zlobina, Ksenia E.; Guria, Georgy Th.


    Increased shear stress such as observed at local stenosis may cause drastic changes in the permeability of the vessel wall to procoagulants and thus initiate intravascular blood coagulation. In this paper we suggest a mathematical model to investigate how shear stress-induced permeability influences the thrombogenic potential of atherosclerotic plaques. Numerical analysis of the model reveals the existence of two hydrodynamic thresholds for activation of blood coagulation in the system and unveils typical scenarios of thrombus formation. The dependence of blood coagulation development on the intensity of blood flow, as well as on geometrical parameters of atherosclerotic plaque is described. Relevant parametric diagrams are drawn. The results suggest a previously unrecognized role of relatively small plaques (resulting in less than 50% of the lumen area reduction) in atherothrombosis and have important implications for the existing stenting guidelines. PMID:26222505

  10. Phage display technology: a tool to explore the diversity of inhibitors to blood coagulation factor VIII

    NARCIS (Netherlands)

    Voorberg, J.; van den Brink, E. N.


    Hemophilia A is a X-linked bleeding disorder that is caused by the functional absence of blood coagulation factor VIII. The bleeding tendency in hemophilia A patients can be corrected by the administration of plasma-derived or recombinant factor VIII concentrates. A serious complication in

  11. Principles of dielectric blood coagulometry as a comprehensive coagulation test. (United States)

    Hayashi, Yoshihito; Brun, Marc-Aurèle; Machida, Kenzo; Nagasawa, Masayuki


    Dielectric blood coagulometry (DBCM) is intended to support hemostasis management by providing comprehensive information on blood coagulation from automated, time-dependent measurements of whole blood dielectric spectra. We discuss the relationship between the series of blood coagulation reactions, especially the aggregation and deformation of erythrocytes, and the dielectric response with the help of clot structure electron microscope observations. Dielectric response to the spontaneous coagulation after recalcification presented three distinct phases that correspond to (P1) rouleau formation before the onset of clotting, (P2) erythrocyte aggregation and reconstitution of aggregates accompanying early fibrin formation, and (P3) erythrocyte shape transformation and/or structure changes within aggregates after the stable fibrin network is formed and platelet contraction occurs. Disappearance of the second phase was observed upon addition of tissue factor and ellagic acid for activation of extrinsic and intrinsic pathways, respectively, which is attributable to accelerated thrombin generation. A series of control experiments revealed that the amplitude and/or quickness of dielectric response reflect platelet function, fibrin polymerization, fibrinolysis activity, and heparin activity. Therefore, DBCM sensitively measures blood coagulation via erythrocytes aggregation and shape changes and their impact on the dielectric permittivity, making possible the development of the battery of assays needed for comprehensive coagulation testing.

  12. Genetics of inherited primary arrhythmia disorders

    Directory of Open Access Journals (Sweden)

    Spears DA


    Full Text Available Danna A Spears, Michael H Gollob Division of Cardiology – Electrophysiology, University Health Network, Toronto General Hospital, Toronto, ON, Canada Abstract: A sudden unexplained death is felt to be due to a primary arrhythmic disorder when no structural heart disease is found on autopsy, and there is no preceding documentation of heart disease. In these cases, death is presumed to be secondary to a lethal and potentially heritable abnormality of cardiac ion channel function. These channelopathies include congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome. In certain cases, genetic testing may have an important role in supporting a diagnosis of a primary arrhythmia disorder, and can also provide prognostic information, but by far the greatest strength of genetic testing lies in the screening of family members, who may be at risk. The purpose of this review is to describe the basic genetic and molecular pathophysiology of the primary inherited arrhythmia disorders, and to outline a rational approach to genetic testing, management, and family screening. Keywords: long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, short QT syndrome, genetics

  13. Empowering international canine inherited disorder management. (United States)

    Wilson, Bethany J; Wade, Claire M


    The mapping of the canine genome and the study of canine breed genomic architecture has revolutionized the discovery of genetic tests for inherited disorders in dogs. As the genetics underlying complex disorders are revealed, canine breeders and their registering organisations will be required to understand genetics in a much more sophisticated way. To facilitate the management of genetic disorders in the era of new complex information, we consider how best to apply the results of new research and analytical techniques to benefit the wider canine breeding community with the aims of improving canine health and maintaining benevolent genetic diversity. If this is not done, there is a serious risk that expensive and valuable genetic research will remain unused or be misused to the detriment of breeds. In this review, we make a case for the formation of an international organisation that will exist as a central repository for breed-based genetic analysis and information sharing. This organisation ("Inter-Dog") could be modelled on a similar organisation that is monitoring genetic improvement of dairy cattle. The formation of such an organisation will require the collaboration of international kennel management organisations, researchers, and agencies offering genetic testing services.

  14. Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory and Coagulation Pathways (United States)

    Muralidharan-Chari, Vandhana; Kim, Jaehan; Abuawad, Ahlam; Naeem, Mubeena; Cui, Huadong; Mousa, Shaker A.


    Thymoquinone (THQ) is a major component of black seeds. Given that both THQ and black seeds exhibit anti-cancer and anti-inflammatory activities, we hypothesized that THQ will affect cancer-associated thrombosis (CAT), which is primarily triggered by tissue factor (TF) and inflammation. The effect of both black seed-extracted and purchased (“pure”) THQ on normal blood coagulation was tested with in vitro thromboelastography (TEG) and activated partial thromboplastin time (aPTT) coagulation assays. The effect of pure THQ on CAT was tested with aPTT assay using pancreatic cancer cell lines that are either positive or negative for TF, and with TEG assay using lipopolysaccharide as an inflammatory trigger. Additionally, the direct effect of THQ on the inactivation of factors IIa and Xa was assessed. Since TNF-α facilitates crosstalk between inflammation and thrombosis by triggering the NF-κB pathway, we tested THQ’s ability to interfere with this communication with a luciferase assay. Both extracted and pure THQ had minimal effects on normal blood coagulation. Pure THQ reversed CAT initiated by both TF and inflammation to basal levels (p coagulation and can reverse CAT in vitro, possibly by interfering with the crosstalk between inflammation and coagulation. This study suggests the utility of THQ as a preventative anticoagulant and/or as a supplement to existing chemotherapies and anticoagulant therapies. PMID:27043539

  15. Adaptive force sonorheometry for assessment of whole blood coagulation. (United States)

    Mauldin, F William; Viola, Francesco; Hamer, Theresa C; Ahmed, Eman M; Crawford, Shawna B; Haverstick, Doris M; Lawrence, Michael B; Walker, William F


    Viscoelastic diagnostics that monitor the hemostatic function of whole blood (WB), such as thromboelastography, have been developed with demonstrated clinical utility. By measuring the cumulative effects of all components of hemostasis, viscoelastic diagnostics have circumvented many of the challenges associated with more common tests of blood coagulation. We describe a new technology, called sonorheometry, that adaptively applies acoustic radiation force to assess coagulation function in WB. The repeatability (precision) of coagulation parameters was assessed using citrated WB samples. A reference range of coagulation parameters, along with corresponding measurements from prothrombin time (PT) and partial thromboplastin time (PTT), were obtained from WB samples of 20 healthy volunteers. In another study, sonorheometry monitored anticoagulation with heparin (0-5 IU/ml) and reversal from varied dosages of protamine (0-10 IU/ml) in heparinized WB (2 IU/ml). Sonorheometry exhibited low CVs for parameters: clot initiation time (TC1), 0.98 for all coagulation parameters. We observed maximum reversal of heparin anticoagulation at protamine to heparin ratios of 1.4:1 from TC1 (P=0.6) and 1.2:1 from theta (P=0.55). Sonorheometry is a non-contact method for precise assessment of WB coagulation. Copyright 2010 Elsevier B.V. All rights reserved.

  16. Sonoclot evaluation of whole blood coagulation in healthy adult dogs. (United States)

    Babski, Danielle M; Brainard, Benjamin M; Krimer, Paula M; Ralph, Alan G; Pittman, Jennifer R; Koenig, Amie


    To establish a standard protocol for analysis of canine whole blood and generate reference intervals for healthy dogs using the Sonoclot analyzer, and to compare Sonoclot values to standard and viscoelastic coagulation tests. Prospective study. Veterinary University research facility and teaching hospital. Twelve healthy random source dogs and 52 healthy dogs from the general veterinary school population. Blood sampling for viscoelastic coagulation testing. Blood was collected from 12 healthy adult dogs by jugular venipuncture. After a rest period at room temperature of 30, 60, or 120 minutes, 340 μL of citrated blood was added to 20 μL of 0.2 M CaCl(2) in 1 of 2 cuvette types warmed to 37° C. Cuvettes contained a magnetic stir-bar with glass beads (gbACT+) or only a magnetic stir-bar (nonACT). Reference interval samples were collected from 52 healthy adult dogs and analyzed in duplicate. The ACT, CR, and PF were not affected by duration of rest period for either cuvette type. ACT variability was decreased when using gbACT+ cuvettes (P coagulation tests. Sonoclot provides viscoelastic evaluation of canine whole blood coagulation and correlated to several TEG parameters and fibrinogen. A standard protocol and reference intervals were established. © Veterinary Emergency and Critical Care Society 2012.

  17. Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation (United States)

    Kang, Yoo Goo; Martin, Douglas J.; Marquez, Jose; Lewis, Jessica H.; Bontempo, Franklin A.; Shaw, Byers W.; Starzl, Thomas E.; Winter, Peter M.


    The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30–60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors. PMID:3896028

  18. Mathematical modelling in blood coagulation : simulation and parameter estimation

    NARCIS (Netherlands)

    W.J.H. Stortelder (Walter); P.W. Hemker (Piet); H.C. Hemker


    textabstractThis paper describes the mathematical modelling of a part of the blood coagulation mechanism. The model includes the activation of factor X by a purified enzyme from Russel's Viper Venom (RVV), factor V and prothrombin, and also comprises the inactivation of the products formed. In this

  19. Blood coagulation in hemophilia A and hemophilia C

    NARCIS (Netherlands)

    Cawthern, K. M.; van 't Veer, C.; Lock, J. B.; DiLorenzo, M. E.; Branda, R. F.; Mann, K. G.


    Tissue factor (TF)-induced coagulation was compared in contact pathway suppressed human blood from normal, factor VIII-deficient, and factor XI-deficient donors. The progress of the reaction was analyzed in quenched samples by immunoassay and immunoblotting for fibrinopeptide A (FPA),

  20. Whole blood coagulation time, haematocrit, haemoglobin and total ...

    African Journals Online (AJOL)

    The study was carried out to determine the values of whole blood coagulation time (WBCT), haematocrit (HM), haemaglobin (HB) and total protein (TP) of one hundred and eighteen apparently healthy turkeys reared under an extensive management system in Zaria. The mean values for WBCT, HM, HB and TP were 1.12 ...


    Directory of Open Access Journals (Sweden)

    M. A. Gavrilenko


    Full Text Available Background. Actuality of the problem is determined by the high prevalence of periodontal tissues inflammatory diseases in children with blood pathology (100%. Primary prevention of dental caries and periodontal diseases has the exceptional importance in the dentist’s work with children who have blood coagulability disorders. Prevention of dental diseases of the oral cavity in this category of patients has a number of features because there is risk of bleeding during both home oral hygiene and professional hygiene. Exogenous prevention (fluoride-containing gels, varnishes, solutions, sealants also has its own peculiarities in these children. On the other hand, the impossibility of preventive measures implementation is the significant factor in the pathogenesis of gingivitis and subsequently periodontitis in children with disorders of blood coagulability. Aim. To examine the status of oral hygiene in children with blood coagulability disorders. To examine the severity of inflammatory and destructive changes in the periodontal tissues in children with disorders of blood coagulability. To investigate timing and frequency of oral hygiene implementation in children with disorders of blood coagulability. To reveal the interrelations between the intensity, prevalence of periodontal tissues disorders in children with blood coagulability pathology and the periods of tooth development, taking into account the influence of risk factors and frequency of oral hygiene. Materials and methods. 120 children between 2 and 18 years old with blood coagulability disorders (hemophilia A, B, thrombocytopenia, thrombocytopathy were examined. Children were divided into following age groups: I – 2-5 years old (40 children, II – 6-10 years old (40 children, III – 11-18 years old (40 children, according to the periods of tooth development, with an equal number of children in groups according to diagnoses. Hygiene index value was determined according to Fedorov and


    Directory of Open Access Journals (Sweden)

    M. A. Gavrilenko


    Full Text Available Background. Actuality of the problem is determined by the high prevalence of inflammatory diseases of periodontal tissues in children with blood pathology (100%. Primary prevention of dental caries and periodontal diseases has the exceptional importance in the dentist’s work with children who have blood coagulability disorders. Prevention of dental diseases of the oral cavity in this category of patients has a number of features because there is the risk of bleeding during both home oral hygiene and professional hygiene. Exogenous prevention (fluoride-containing gels, varnishes, solutions, sealants also has its own peculiarities in these children. On the other hand, the impossibility of preventive measures implementation is the significant factor in the pathogenesis of gingivitis and subsequently periodontitis in children with disorders of blood coagulability. Aim. To examine the status of oral hygiene in children with blood coagulability disorders. To examine the severity of inflammatory and destructive changes in the periodontal tissues in children with disorders of blood coagulability. To investigate timing and frequency of oral hygiene implementation in children with disorders of blood coagulability. To reveal the interrelations between the intensity, prevalence of periodontal tissues disorders in children with blood coagulability pathology and the periods of tooth development, taking into account the influence of risk factors and frequency of oral hygiene. Materials and methods. 120 children between 2 and 18 years old with blood coagulability disorders (hemophilia A, B, thrombocytopenia, thrombocytopathy were examined. Children were divided into following age groups: I – 2-5 years old (40 children, II – 6-10 years old (40 children, III – 11-18 years old (40 children, according to the periods of tooth development, with an equal number of children in groups according to diagnoses. Hygiene index value was determined according to

  3. Evaluation of periodontal tissues condition in children with blood coagulability pathology

    Directory of Open Access Journals (Sweden)

    M. A. Gavrilenko


    Full Text Available Background. Actuality of the problem is determined by the high prevalence of inflammatory diseases of periodontal tissues in children with blood pathology (100%. Primary prevention of dental caries and periodontal diseases has the exceptional importance in the dentist’s work with children who have blood coagulability disorders. Prevention of dental diseases of the oral cavity in this category of patients has a number of features because there is the risk of bleeding during both home oral hygiene and professional hygiene. Exogenous prevention (fluoride-containing gels, varnishes, solutions, sealants also has its own peculiarities in these children. On the other hand, the impossibility of preventive measures implementation is the significant factor in the pathogenesis of gingivitis and subsequently periodontitis in children with disorders of blood coagulability. Aim.To examine the status of oral hygiene in children with blood coagulability disorders.To examine the severity of inflammatory and destructive changes in the periodontal tissues in children with disorders of blood coagulability. To investigate timing and frequency of oral hygiene implementation in children with disorders of blood coagulability. To reveal the interrelations between the intensity, prevalence of periodontal tissues disorders in children with blood coagulability pathology and the periods of tooth development, taking into account the influence of risk factors and frequency of oral hygiene. Materials and methods. 120 children between 2 and 18 years old with blood coagulability disorders (hemophilia A, B, thrombocytopenia, thrombocytopathy were examined. Children were divided into following age groups: I – 2-5 years old (40 children, II – 6-10 years old (40 children, III – 11-18 years old (40 children, according to the periods of tooth development, with an equal number of children in groups according to diagnoses. Hygiene index value was determined according to Fedorov

  4. Blood coagulation and platelet adhesion on polyaniline films. (United States)

    Humpolíček, Petr; Kuceková, Zdenka; Kašpárková, Věra; Pelková, Jana; Modic, Martina; Junkar, Ita; Trchová, Miroslava; Bober, Patrycja; Stejskal, Jaroslav; Lehocký, Marián


    Polyaniline is a promising conducting polymer with still increasing application potential in biomedicine. Its surface modification can be an efficient way how to introduce desired functional groups and to control its properties while keeping the bulk characteristics of the material unchanged. The purpose of the study was to synthetize thin films of pristine conducting polyaniline hydrochloride, non-conducting polyaniline base and polyaniline modified with poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPSA) and investigate chosen parameters of their hemocompatibility. The modification was performed either by introduction of PAMPSA during the synthesis or by reprotonation of polyaniline base. The polyaniline hydrochloride and polyaniline base had no impact on blood coagulation and platelet adhesion. By contrast, the polyaniline reprotonated with PAMPSA completely hindered coagulation thanks to its interaction with coagulation factors Xa, Va and IIa. The significantly lower platelets adhesion was also found on this surface. Moreover, this film maintains its conductivity at pH of 6, which is an improvement in comparison with standard polyaniline hydrochloride losing most of its conductivity at pH of 4. Polyaniline film with PAMPSA introduced during synthesis had an impact on platelet adhesion but not on coagulation. The combined conductivity, anticoagulation activity, low platelet adhesion and improved conductivity at pH closer to physiological, open up new possibilities for application of polyaniline reprotonated by PAMPSA in blood-contacting devices, such as catheters or blood vessel grafts. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. [Comparison of thromboelastography and routine coagulation tests for evaluation of blood coagulation function in patients]. (United States)

    Chen, Guan-Yi; Ou Yang, Xi-Lin; Wu, Jing-Hui; Wang, Li-Hua; Yang, Jin-Hua; Gu, Li-Nan; Lu, Zhu-Jie; Zhao, Xiao-Zi


    To investigate the correlation and consistency between thromboelastography(TEG) and routine coagulation tests, and to evaluate the value of the two methods in determining the blood coagulation of patients. The TEG, routine coagulation tests and platelet counts of 182 patients from the Intensive Care Unit(ICU) and Department of Gastroenterology in our hospital from January to September 2014 were performed and analyzed retrospectively for their correlation, Kappa identity test analysis and chi-square test, and the diagnostic sensitivity and specificity of both methods in the patients with bleeding were evaluated. The TEG R time and PT, R time and APTT showed a linear dependence (P0.05) and 0.061 (P>0.05), respectively. The chi-square test values of the TEG R time with PT and APTT were 35.309 (Pcoagulation tests, but the consistency is weak. Moreover, the diagnostic sensitivity of two methods in the patients with bleeding is low. It was concluded that the TEG cannot replace the conventional coagulation tests, and the preferable method remains uncertain which could reflect the risk of bleeding.

  6. Cardiac sodium channels and inherited electrophysiologic disorders: a pharmacogenetic overview

    NARCIS (Netherlands)

    Smits, Jeroen P. P.; Blom, Marieke T.; Wilde, Arthur A. M.; Tan, Hanno L.


    Sodium (Na) channels are essential for cardiac electrical activity. Cardiac Na channel dysfunction, inherited or acquired, can induce life-threatening conduction and arrhythmia disorders. Inherited Na channel dysfunction may put affected patients at a greater risk for these complications when

  7. Nanoparticles and the blood coagulation system. Part I: benefits of nanotechnology. (United States)

    Ilinskaya, Anna N; Dobrovolskaia, Marina A


    Nanotechnology is proven to provide certain benefits in drug delivery by improving solubility, increasing uptake to target sites and changing pharmacokinetics profiles of traditional drugs. Since properties of many materials change tremendously at the nanoscale levels, nanotechnology is also being explored in various industrial applications. As such, nanoparticles are rapidly entering various areas of industry, biology and medicine. The benefits of using nanotechnology for industrial and biomedical applications are often tempered by concerns about the safety of these new materials. One such area of concern includes their effect on the immune system. While nanoparticle interactions with various constituents of the immune system have been reviewed before, little attention was given to nanoparticle effects on the blood coagulation system. Nanoparticle interface with the blood coagulation system may lead to either benefits to the host or adverse reactions. This article reviews recent advances in our understanding of nanoparticle interactions with plasma coagulation factors, platelets, endothelial cells and leukocytes. Part I is focused on desirable interactions between nanoparticles and the coagulation system, and discusses benefits of using nanotechnology to intervene in coagulation disorders. Undesirable interactions posing safety concerns are covered in part II, which will be published in the June issue of Nanomedicine.

  8. Blood viscosity during coagulation at different shear rates (United States)

    Ranucci, Marco; Laddomada, Tommaso; Ranucci, Matteo; Baryshnikova, Ekaterina


    Abstract During the coagulation process, blood changes from a liquid to a solid gel phase. These changes are reflected by changes in blood viscosity; however, blood viscosity at different shear rates (SR) has not been previously explored during the coagulation process. In this study, we investigated the viscosity changes of whole blood in 10 subjects with a normal coagulation profile, using a cone‐on‐plate viscosimeter. For each subject, three consecutive measurements were performed, at a SR of 20, 40, 80 sec−1. On the basis of the time‐dependent changes in blood viscosity, we identified the gel point (GP), the time‐to‐gel point (TGP), the maximum clot viscosity (MCV), and the clot lysis half‐time (CLH). The TGP significantly (P = 0.0023) shortened for increasing SR, and was significantly associated with the activated partial thromboplastin time at a SR of 20 sec−1 (P = 0.038) and 80 sec−1 (P = 0.019). The MCV was significantly lower at a SR of 80 sec−1 versus 40 sec−1 (P = 0.027) and the CLH significantly (P = 0.048) increased for increasing SR. These results demonstrate that measurement of blood viscosity during the coagulation process offers a number of potentially useful parameters. In particular, the association between the TGP and the activated partial thromboplastin time is an expression of the clotting time (intrinsic and common pathway), and its shortening for increasing SR may be interpreted the well‐known activating effects of SR on platelet activation and thrombin generation. Further studies focused on the TGP under conditions of hypo‐ or hypercoagulability are required to confirm its role in the clinical practice. PMID:24994896

  9. Blood coagulation factor VIII: An overview

    Indian Academy of Sciences (India)


    Santagostina E and Castaman G 2001 TT virus contaminates first generation recombinant factor VIII concentrates; Blood. 98 2571–2573. Azzi A, Morfini M and Mannucci P M 1999 The transfusion associated transmission of parvovirus B19; Transfus. Med. Rev. 13 194–204. Bowen D J 2002 Haemophilia A and Haemophilia ...

  10. Tulathromycin disturbs blood oxidative and coagulation status

    African Journals Online (AJOL)



    Apr 18, 2011 ... Tulathromycin increased (P < 0.05) the levels of malondialdehyde, nitric oxide and superoxide dismutase activity, and decreased (P < 0.05) ... are present in the blood, a direct protease inhibitor system that includes ..... synthase and xanthine oxidase activities and malondialdehyde level in erythrocyte of the ...

  11. Interplay between coagulation and vascular inflammation in sickle cell disease (United States)

    Sparkenbaugh, Erica; Pawlinski, Rafal


    Sickle cell disease is the most common inherited hematologic disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease the importance of hemolytic anemia and vasculopathy has been recently recognized. Hypercoagulation state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease. PMID:23593937

  12. Coagulation disorders in dogs with hepatic disease

    NARCIS (Netherlands)

    Prins, M.|info:eu-repo/dai/nl/304836176; Schellens, C.J.M.M.; van Leeuwen, M; Rothuizen, J.|info:eu-repo/dai/nl/071276033; Teske, E.|info:eu-repo/dai/nl/114300240


    The Veterinary Journal Volume 185, Issue 2, August 2010, Pages 163-168 -------------------------------------------------------------------------------- doi:10.1016/j.tvjl.2009.05.009 | How to Cite or Link Using DOI Copyright © 2009 Elsevier Ltd All rights reserved. Permissions & Reprints Coagulation

  13. Influence of blood lipids on global coagulation test results. (United States)

    Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon; Kim, Hyun Kyung


    High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.

  14. Application of Molecular Genetics to the Investigation of Inherited Bleeding Disorders

    DEFF Research Database (Denmark)

    Lethagen, Stefan Rune; Dunø, Morten; Nielsen, Lars Bo


    Hemophilia is an inherited bleeding disorder primarily caused by deficiency of coagulation factor (F)VIII (hemophilia A) or FIX (hemophilia B). Both conditions are X-linked. More than 2100 different F8 mutations have been described, the most common being a 500 kb inversion involving exon 1 to exon...... 22. In hemophilia B, more than 1100 unique F9 mutations have been described scattered all over the gene. Carrier analysis, genetic counseling, prenatal and pre-implantation genetic diagnosis are all based on correct identifying the disease-causing mutation. Linkage analysis can be considered when...

  15. Effect of Heptral on Blood Coagulant Activity in Pancreonecrosis

    Directory of Open Access Journals (Sweden)

    M. S. Sukach


    Full Text Available Objective: to attempt to reduce the hemostatic, detoxifying, and antioxidant dysfunctions of the liver in experimental pancreonecrosis and the degree of pancreatogenic endotoxemia, by using the hepatoprotector heptral. Materials and methods. Experiments were carried out on 142 outbred male rats divided into 3 groups: 1 control (n=20; 2 study (n=69; 3 comparison (n=53. Pancreonecrosis was simulated in the study and comparison groups. In Stage 1, coagulation hemostatic parameters were studied and the levels of low and medium molecular weight substances and the rate of free radical oxidation processes were determined. In Stage 2, five minutes after stimulation of pancreonecrosis, heptral was given in a dose of 11.4 mg/kg to the comparison animals, by studying the same parameters as in the study and control groups. The results were processed using the nonparametric statistical methods. Results. It has been found that hepatic detoxifying and antioxidant functions are impaired and free radical oxidation processes activated within 2 days after simulation of pancreonecrosis. Blood coagulation activity is considerably higher due to activated coagulation factors. Heptral increases the capacity of the liver to synthesize blood coagulation factors, which proves improvement of some of the study parameters of the hemostatic system. Furthermore, its administration preserves the antitoxic function of hepatocytes, as shown by the decreased concentrations of low and median molecular weight substances in plasma and red blood cells. At the same time, there is an increase in antioxidant system activity detectable by chemiluminescence which also testifies that hepatic functional and metabolic impairments are ameliorated. Key words: pancreonecrosis, liver, endotoxemia, hemo-stasis, free radical oxidation, heptral.

  16. Modelling of the Blood Coagulation Cascade in an In Vitro Flow System

    DEFF Research Database (Denmark)

    Andersen, Nina Marianne; Sørensen, Mads Peter; Efendiev, Messoud A.


    We derive a mathematical model of a part of the blood coagulation cascade set up in a perfusion experiment. Our purpose is to simulate the influence of blood flow and diffusion on the blood coagulation pathway. The resulting model consists of a system of partial differential equations taking...... and flow equations, which guarantee non negative concentrations at all times. The criteria is applied to the model of the blood coagulation cascade....

  17. The coagulation system in endocrine disorders: a narrative review

    NARCIS (Netherlands)

    Squizzato, A.; Gerdes, V. E. A.; Ageno, W.; Büller, H. R.


    Endocrine disorders can influence the haemostatic balance. Abnormal coagulation test results have been observed in patients with abnormal hormone levels. Also unprovoked bleeding or thrombotic events have been associated with endocrine disease. The aim of the present review is to summarise the

  18. Clinical approach to inherited peroxisomal disorders

    NARCIS (Netherlands)

    Poggi-Travert, F.; Fournier, B.; Poll-The, B. T.; Saudubray, J. M.


    At least 21 genetic disorders have now been found that are linked to peroxisomal dysfunction. Whatever the genetic defect might be, peroxisomal disorders should be considered in various clinical conditions, dependent on the age of onset. The prototype of peroxisomal disorders is represented by

  19. Screening of Inherited Metabolic Disorders in Infants with Infantile Spasms. (United States)

    Liu, Xiao-Ming; Li, Rui; Chen, Sheng-Zhi; Sang, Yan; Chen, Jiao; Fan, Cong-Hai


    The objective of this study is to explore the incidence of inherited metabolic disorders (IMD) in infants with infantile spasms (IS), with an attempt to improve the early diagnosis and etiological and symptomatic treatment. Urine and blood samples were collected from 60 IS patients and analyzed for the quantification of amino acids, organic acids, and fatty acids by gas chromatography-mass spectrometry and tandem mass spectrum. Routine urine tests, hepatic function tests, blood biochemistry, brain imaging, as well as examinations of the brain stem auditory/visual evoked potentials were also examined. In addition to antiepileptic therapy, etiological and symptomatic treatments were also conducted in infants with confirmed IMD and the follow-up lasted for 6 months in these pediatric patients. Metabolic disorders were found in 28 (46.67 %) of 60 IS infants, among them 13 (21.67 %) were confirmed to be with IMD. Twelve of these 13 IS patients with definite IMD diagnoses (92.31 %) experienced varying degrees of delayed development of intelligence and motor function, 8 patients (61.54 %) had abnormal cranial CT or MRI findings, 11 patients (84.61 %) had abnormal brain stem evoked potentials, 4 patients (30.77 %) had abnormal hepatic functions, 3 patients (23.07 %) had abnormal blood biochemistry, 2 patients (15.38 %) had positive (+ to ++) results for routine urine ketones, and 2 patients (15.38 %) had skin lesions. After treatment in children who were diagnosed IMD, the well controlled epileptic seizures and the satisfactory developments in mental and motor were found in 4 cases of methylmalonic acidemia, 2 cases of classical phenylketonuria, and one case of biotin deficiency disease, glutaric acidemia type I, and 4-hydroxybutyric aciduria in each. IMD is a key biological cause in IS. Early screening for IMD is warranted in IS infants to facilitate the improvement for the prognosis and an early etiological treatment.

  20. Causes and consequences of inherited cone disorders

    NARCIS (Netherlands)

    Roosing, S.; Thiadens, A.A.H.J.; Hoyng, C.B.; Klaver, C.C.; Hollander, A.I. den; Cremers, F.P.M.


    Hereditary cone disorders (CDs) are characterized by defects of the cone photoreceptors or retinal pigment epithelium underlying the macula, and include achromatopsia (ACHM), cone dystrophy (COD), cone-rod dystrophy (CRD), color vision impairment, Stargardt disease (STGD) and other maculopathies.

  1. [Recurrent thrombophlebitis and ulcera crurum as manifestations of hereditary blood coagulation disorders and Klinefelter syndrome. Discussion based on 4 case examples]. (United States)

    Ramaker, J; Goerdt, S; Zouboulis, C C; Schramm, W; Orfanos, C E


    Recurrent phlebothromboses in young patients with subsequent severe postthrombotic syndrome and chronic venous leg ulcers may be caused by underlying hereditary disorders of hemostasis or may occur as part of other congenital syndromes. The most common hereditary disorders of hemostasis in this respect appear to be deficiencies of antithrombin III, protein C, and protein S, and activated protein C resistance (mutations of factor V). Less frequently, dysfibrinogenemia, increased plasminogen activator inhibitor levels, or deficiencies of tissue plasminogen activator or heparin cofactor II may be found. Klinefelter's syndrome and homocystinuria are prime examples of those rare congenital disorders indirectly associated with an elevated risk of thrombosis in young individuals. Early diagnosis of these disorders will allow timely treatment, preventive care and counselling of patients as well as family members.




  3. Blood coagulation parameters and activity indices in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    A. A. Arshinov


    Full Text Available Objective. To assess coagulation parameters and activity indices in pts with systemic lupus erythematosus (SLE. Material and methods . 86 pts with SLE (83 female and 3 male were examined. 12 of them had antiphospholipid syndrome. Mean age was 35,9±1,5 years (from 18 to 58 years, mean disease duration was 9,8+1,4 years. Control group consisted of 60 healthy volunteers with mean age 37,1+4,1 years. SLE activity assessment was performed with SLAM, SLEDAI and ECLAM indices. Results. SLE pts showed 5-fold (p<0,01 increase of spontaneous platelets aggregation and more than 3-fold increase of factor von Willebrand antigen (FWA concentration. Platelet activation in pts was accompanied by decrease of platelet aggregation with collagen (on 27%, p<0,01. Characteristic sign of coagulation hemostasis activation was significant increase of soluble fibrin-monomer complexes (SFMC concentration on 81 % (p<0,01 so as increase D-dimers level in 53,3% of pts. Fibrinogen concentration was increased on 29%, spontaneous fibrinolysis parameters were decreased on 20%, antithrombin (AT 111 - on 21% in comparison with control. Direct correlation between activity indiccs and SFMC(ECLAM, r=0,5, fibrinogen concentration (SLAM, r=0,34, D- dimers level (ECLAM, r=0,5, spontaneous platelet aggregation (ECLAM, r=0,5 so as inverse correlation with AT III activity (SLEDAI, r-0,73 was revealed. Conclusion. Changes of hemostasis parameters in SLE may serve as predictors of thrombotic disorders development and indication to drug correction of blood coagulation disorders. Direct correlation between blood coagulation system activity and indices of SLE activity.

  4. Blood is thicker than water: coagulation challenges in the ...

    African Journals Online (AJOL)

    This manuscript serves to highlight some novel approaches to perioperative coagulation abnormalities and to address unanswered questions. Keywords: coagulation; point-of-care monitor; prothrombin complex concentrate; pharmacological procoagulants ...

  5. Coagulation management in trauma-associated coagulopathy: allogenic blood products versus coagulation factor concentrates in trauma care. (United States)

    Klages, Matthias; Zacharowski, Kai; Weber, Christian Friedrich


    Coagulation management by transfusion of allogenic blood products and coagulation factors are competing concepts in current trauma care. Rapid and adequate therapy of trauma-associated coagulopathy is crucial to survival of severely injured patients. Standard coagulation tests such as prothrombin time and activated partial thromboplastin time are commonly used, but these tests are inappropriate for monitoring and guiding therapy in trauma patients. Coagulation factor-based treatment showed promising results, but randomized trials have not yet been performed. In addition, viscoelastic tests are needed to guide therapy, although there is in fact limited evidence for these in tests in trauma care. Regarding transfusion therapy with allogenic blood products, plasma transfusion has been associated with improved survival in trauma patients following massive transfusion. In contrast, patients not requiring massive transfusion seem to be at risk for suffering complications with increasing volumes of plasma transfused. The collective of trauma patients is heterogeneous. Despite the lack of evidence, there are strong arguments for individualized patient treatment with coagulation factors for some indications and to abstain from the use of fresh frozen plasma. In patients with severe trauma and major bleeding, plasma, platelets, and red blood cells should be considered to be administered at a ratio of 1 : 1 : 1.

  6. Inherited disorders of brain neurotransmitters: pathogenesis and diagnostic approach. (United States)

    Szymańska, Krystyna; Kuśmierska, Katarzyna; Demkow, Urszula


    Neurotransmitters (NTs) play a central role in the efficient communication between neurons necessary for normal functioning of the nervous system. NTs can be divided into two groups: small molecule NTs and larger neuropeptide NTs. Inherited disorders of NTs result from a primary disturbance of NTs metabolism or transport. This group of disorders requires sophisticated diagnostic procedures. In this review we discuss disturbances in the metabolism of tetrahydrobiopterin, biogenic amines, γ-aminobutyric acid, foliate, pyridoxine-dependent enzymes, and also the glycine-dependent encephalopathy. We point to pathologic alterations of proteins involved in synaptic neurotransmission that may cause neurological and psychiatric symptoms. We postulate that synaptic receptors and transporter proteins for neurotransmitters should be investigated in unresolved cases. Patients with inherited neurotransmitters disorders present various clinical presentations such as mental retardation, refractory seizures, pyramidal and extrapyramidal syndromes, impaired locomotor patterns, and progressive encephalopathy. Every patient with suspected inherited neurotransmitter disorder should undergo a structured interview and a careful examination including neurological, biochemical, and imaging.

  7. Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes. (United States)

    Heinz, Stefan; Braspenning, Joris


    An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro. Hepatocyte cultures indeed provide a valuable tool to study blood coagulation factors. In addition, the generation and expansion of hepatocytes or hepatocyte-like cells may be used in future for cell-based therapies of liver diseases, including blood coagulation factor deficiencies.

  8. Benign intracranial hypertension associated to blood coagulation derangements

    Directory of Open Access Journals (Sweden)

    Niglio Alferio


    Full Text Available Abstract Background Benign Intracranial Hypertension (BIH may be caused, at least in part, by intracranial sinus thrombosis. Thrombosis is normally due to derangements in blood coagulation cascade which may predispose to abnormal clotting activation or deficiency in natural inhibitors' control. The aim of the study is to examine the strength of the association between risk factors for thrombosis and BIH. Patients and methods The incidence of prothrombotic abnormalities among a randomly investigated cohort of 17 patients with BIH, was compared with 51 healthy subjects matched for sex, age, body mass index, height and social background. Results The number of subjects with protein C deficiency was significantly higher in patients than in controls (3 vs 1, p Increased plasma levels of prothrombin fragment 1+2, fibrinopeptide A (FPA, and PAI-1 were demonstrated in patients group (5.7 ± 1.15 nM vs 0.45 ± 0.35 nM; 8.7 ± 2.5 ng/mL vs 2.2 ± 1.25 ng/mL; 45.7 ± 12.5 ng/mL vs 8.5 ± 6.7 ng/mL, respectively; p Discussion In agreement with other authors our data suggest a state of hypercoagulability in BIH associated with gene polymorphisms. Our findings also showed that mutations in cardiovascular genes significantly discriminate subjects with a BIH history. The association between coagulation and gene derangements, usually regarded to as cryptogenic, may suggest a possible pathogenetic mechanism in BIH. So, a prothrombotic tendency may exist that would, at least in part, explain some cases of BIH. Although based on a small population, these findings raise the exciting possibility of using these haemostatic factors as markers for selecting high-risk subjects in BIH disease.

  9. Effects of dietary fat quality and quantity on postprandial activation of blood coagulation factor VII

    DEFF Research Database (Denmark)

    Larsen, L F; Bladbjerg, E-M; Jespersen, J


    Acute elevation of the coagulant activity of blood coagulation factor VII (FVIIc) is observed after consumption of high-fat meals. This elevation is caused by an increase in the concentration of activated FVII (FVIIa). In a randomized crossover study, we investigated whether saturated...

  10. Evaluation of the Efficacy and Safety of Rivaroxaban Using a Computer Model for Blood Coagulation (United States)

    Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg


    Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration–effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies. PMID:21526168

  11. Photoacoustic discrimination of viable and thermally coagulated blood using a two-wavelength method for burn injury monitoring (United States)

    Talbert, Robert J.; Holan, Scott H.; Viator, John A.


    Discriminating viable from thermally coagulated blood in a burn wound can be used to profile burn depth, thus aiding the removal of necrotic tissue. In this study, we used a two-wavelength photoacoustic imaging method to discriminate coagulated and non-coagulated blood in a dermal burn phantom. Differences in the optical absorption spectra of coagulated and non-coagulated blood produce different values of the ratio of peak photoacoustic amplitude at 543 and 633 nm. The absorption values obtained from spectroscopic measurements indicate that the ratio of photoacoustic pressure for 543 and 633 nm for non-coagulated blood was 15.7:1 and 1.6:1 for coagulated blood. Using planar blood layers, we found the photoacoustic ratios to be 13.5:1 and 1.6:1, respectively. Using the differences in the ratios of coagulated and non-coagulated blood, we propose a scheme using statistical classification analysis to identify the different blood samples. Based upon these distinctly different ratios, we identified the planar blood samples with an error rate of 0%. Using a burn phantom with cylindrical vessels containing coagulated and non-coagulated blood, we achieved an error rate of 11.4%. These results have shown that photoacoustic imaging could prove to be a valuable tool in the diagnosis of burns.

  12. Photoacoustic discrimination of viable and thermally coagulated blood using a two-wavelength method for burn injury monitoring

    International Nuclear Information System (INIS)

    Talbert, Robert J; Holan, Scott H; Viator, John A


    Discriminating viable from thermally coagulated blood in a burn wound can be used to profile burn depth, thus aiding the removal of necrotic tissue. In this study, we used a two-wavelength photoacoustic imaging method to discriminate coagulated and non-coagulated blood in a dermal burn phantom. Differences in the optical absorption spectra of coagulated and non-coagulated blood produce different values of the ratio of peak photoacoustic amplitude at 543 and 633 nm. The absorption values obtained from spectroscopic measurements indicate that the ratio of photoacoustic pressure for 543 and 633 nm for non-coagulated blood was 15.7:1 and 1.6:1 for coagulated blood. Using planar blood layers, we found the photoacoustic ratios to be 13.5:1 and 1.6:1, respectively. Using the differences in the ratios of coagulated and non-coagulated blood, we propose a scheme using statistical classification analysis to identify the different blood samples. Based upon these distinctly different ratios, we identified the planar blood samples with an error rate of 0%. Using a burn phantom with cylindrical vessels containing coagulated and non-coagulated blood, we achieved an error rate of 11.4%. These results have shown that photoacoustic imaging could prove to be a valuable tool in the diagnosis of burns

  13. [Abnormality of blood coagulation indexes in patients with de novo acute leukemia and its clinical significance]. (United States)

    Xiao, Fang-Fang; Hu, Kai-Xun; Guo, Mei; Qiao, Jian-Hui; Sun, Qi-Yun; Ai, Hui-Sheng; Yu, Chang-Lin


    To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated intravenous coagulation, which will provide experiment evidences for early intervention and medication.

  14. No effect of isolated long-term supine immobilization or profound prolonged hypoxia on blood coagulation. (United States)

    Venemans-Jellema, A; Schreijer, A J M; Le Cessie, S; Emmerich, J; Rosendaal, F R; Cannegieter, S C


    Long-distance air travel is associated with an increased risk of venous thrombosis. The most obvious factor that can explain air travel-related thrombosis is prolonged seated immobilization. In addition, hypobaric hypoxia has been shown to affect coagulation, and the lowered atmospheric pressures present in the cabin during the flight may therefore play an etiologic role. Because immobilization and hypoxic conditions are usually present simultaneously in airplanes or hypobaric chambers, their separate effects on the coagulation system or on thrombosis risk have not been studied extensively. To investigate the separate effects of long-term immobilization and profound prolonged hypoxia on blood coagulation. We performed two studies in collaboration with European Space Agency/European Space Research and Technology Centre. In the first study, 24 healthy, non-smoking, adult women underwent 60 days of -6° head-down bed rest. In the second study, we took blood samples from 25 healthy men who participated during their stay in the Concordia station in Antarctica, where, due to the atmospheric conditions, continuous severe hypobaric hypoxia is present. In both studies, we measured markers of blood coagulation at baseline and at several time points during the exposures. We observed no increase in coagulation markers during immobilization or in the hypobaric environment, compared with baseline measurements. Our results indicate that neither immobilization nor hypoxia per se affects blood coagulation. These results implicate that a combination of risk factors is necessary to induce the coagulation system during air travel. © 2014 International Society on Thrombosis and Haemostasis.

  15. Real-time electrical impedimetric monitoring of blood coagulation process under temperature and hematocrit variations conducted in a microfluidic chip.

    Directory of Open Access Journals (Sweden)

    Kin Fong Lei

    Full Text Available Blood coagulation is an extremely complicated and dynamic physiological process. Monitoring of blood coagulation is essential to predict the risk of hemorrhage and thrombosis during cardiac surgical procedures. In this study, a high throughput microfluidic chip has been developed for the investigation of the blood coagulation process under temperature and hematocrit variations. Electrical impedance of the whole blood was continuously recorded by on-chip electrodes in contact with the blood sample during coagulation. Analysis of the impedance change of the blood was conducted to investigate the characteristics of blood coagulation process and the starting time of blood coagulation was defined. The study of blood coagulation time under temperature and hematocrit variations was shown a good agreement with results in the previous clinical reports. The electrical impedance measurement for the definition of blood coagulation process provides a fast and easy measurement technique. The microfluidic chip was shown to be a sensitive and promising device for monitoring blood coagulation process even in a variety of conditions. It is found valuable for the development of point-of-care coagulation testing devices that utilizes whole blood sample in microliter quantity.

  16. [Modification of plasma blood coagulation factor activity by physical stress]. (United States)

    Lutze, G; Buhl, H; Häcker, R; Socha, C; Socha, U; Urbahn, H


    The influence of physical stress (bicycle ergometer and track) on 13 parameters of the plasmatic coagulation system was investigated in trained and untrained test persons. Shortenings of the coagulation times as well as distinct increases of the activity or concentration were observed in the partial thromboplastin time (PTT), the factor VIII activity (VIII:C) and the factor VIII-associated antigen (VIIIR:Ag). The results are discussed with regard to their causes and their clinical importance.

  17. Peculiarities of coagulation hemostasis disorders in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Yakovlieva V.H.


    Full Text Available The violation of blood coagulation properties is observed in many diseases of the respiratory system, including chronic obstructive pulmonary disease (COPD. It is known that in a stable COPD phase release of proinflammatory cytokines in blood is observed, it leads to disturbance of hemostasis parameters toward hypercoagulation. The aim of our study was to determine possibility of coagulation disorders formation in patients with COPD in a stable phase of pathological process at different stages of disease course and identify relationship between coagulation parameters levels and degree of violation of ventilation lung function. Materials and methods. We examined 30 patients with COPD in a stable disease phase, included in the main group (FEV1 =49,5±15,5% of the due, there were 27 men (90.0%, 3 (30.0% women, mean age was 61,8±7,9 years, level of pack /years index - 34,2±15,3. The control group consisted of 10 healthy subjects matched with the patients of the main group by age and sex. All patients were divided into 2 subgroups. Subgroup 1 included 16 patients with moderate COPD, that is the level of FEV1>50% (61,8±7,4% of predicted, and subgroup 2 - 14 COPD patients with severe COPD, that is the level of FEV1 <50% (35,3±8,2% of predicted. Patients received standard treatment according to the disease stage. Main indicators of coagulation levels: prothrombin index (PI, prothrombin ratio (PR, international normalized ratio (INR, activated partial thromboplastin time (APTT, thrombin time (TT and antithrombin III (AT III were identified in all patients. Results. The levels of PI, PR and INR in the subgroup 1 differed significantly from those of in the subgroup 2, control group (p<0,05 and pointed at hypercoagulation, whereas in the subgroup 2 all indicators were absolutely identical with control group. Correlation link between the level of INR levels and FEV1 (r=-0,73; p<0.01 in patients of the main group was determined. Levels of APTT, TT and AT

  18. Coagulation is more affected by quick than slow bleeding in patients with massive blood loss. (United States)

    Zhao, Juan; Yang, Dejuan; Zheng, Dongyou


    Profuse blood loss affects blood coagulation to various degrees. However, whether bleeding speed affects coagulation remains uncertain. This study aimed to evaluate the effect of bleeding speed on coagulation function. A total of 141 patients in the Department of Thoracic Surgery of our hospital were evaluated between January 2007 and February 2014. There are two groups of patients, those who received decortication for chronic encapsulated empyema were called the slow-bleeding group, and those who received thoracoscopic upper lobectomy were called the fast bleeding group; each group was further subdivided into three: group A, 1000 ml ≤ bleeding amount coagulation function was assessed in all patients before and during surgery and at 1, 2, and 24 h after surgery, measuring prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, blood pressure, hematocrit, hemoglobin, and platelets. Bleeding duration was overtly longer in the slow-bleeding group than that in quick bleeding individuals (2.3 ± 0.25 h vs. 0.41 ± 0.13 h, P coagulation indices at each time point and bleeding amounts had significant differences in the quick bleeding group.Increased consumption of coagulation factors in quick bleeding may have greater impact on coagulation function.

  19. Effects of haemodilution on the optical properties of blood during coagulation studied by optical coherence tomography (United States)

    Liu, B.; Liu, Y.; Wei, H.; Yang, X.; Wu, G.; Guo, Z.; Yang, H.; He, Y.; Xie, S.


    We report an investigation of the effects of blood dilution with hypertonic (7.5 %) and normal (0.9 %) saline on its optical properties during coagulation in vitro using optical coherence tomography. The light penetration depth and attenuation coefficient are obtained from the dependences of reflectance on the depth. Normal whole blood has served as the control group. The average coagulation time is equal to 420 +/- 16, 418 +/- 16 and 358 +/- 14 {\\text{s}} with blood volume replacement of 2 %, 11 %, and 20 % by 0.9 % normal saline, respectively. With 2 %, 11% and 20% blood volume replacement with 7.5 % hypertonic saline, the average coagulation time is 422 +/- 17, 1160 +/- 45 and 1730 +/- 69 {\\text{s}}, respectively. For normal whole blood, the average coagulation time amounts to 425 +/- 19 {\\text{s}}. it is shown that dilution with normal saline has a procoagulant effect when it replaces 20 % of blood volume, and hypertonic saline has an anticoagulant effect if it replaces 11 % or more of blood volume. It is concluded that optical coherence tomography is a potential technique to quantify and monitor the liquid - gel transition during the coagulation process of blood diluted by normal and hypertonic saline.

  20. Effect of fibrinogen on blood coagulation detected by optical coherence tomography. (United States)

    Xu, Xiangqun; Teng, Xiangshuai


    Our previous work demonstrated that an optical coherence tomography (OCT) technique and the parameter 1/e light penetration depth (d1/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 d1/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.

  1. Effect of fibrinogen on blood coagulation detected by optical coherence tomography

    International Nuclear Information System (INIS)

    Xu, Xiangqun; Teng, Xiangshuai


    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)

  2. Communication of genetic information to families with inherited rhythm disorders. (United States)

    Burns, Charlotte; James, Cynthia; Ingles, Jodie


    Given the dynamic nature of the electrical activity of the heart and ongoing challenges in the diagnostics of inherited heart rhythm disorders, genetic information can be a vital aspect of family management. Communication of genetic information is complex, and the responsibility to convey this information to the family lies with the proband. Current practice falls short, requiring additional support from the clinician and multidisciplinary team. Communication is a 2-part iterative process, reliant on both the understanding of the probands and their ability to effectively communicate with relatives. With the surge of high-throughput genetic testing, results generated are increasingly complex, making the task of communication more challenging. Here we discuss 3 key issues. First, the probabilistic nature of genetic test results means uncertainty is inherent to the practice. Second, secondary findings may arise. Third, personal preferences, values, and family dynamics also come into play and must be acknowledged when considering how best to support effective communication. Here we provide insight into the challenges and provide practical advice for clinicians to support effective family communication. These strategies include acknowledging and managing genetic uncertainty, genetic counseling and informed consent, and consideration of personal and familial barriers to effective communication. We will explore the potential for developing resources to assist clinicians in providing patients with sufficient knowledge and support to communicate complex information to their at-risk relatives. Specialized multidisciplinary clinics remain the best equipped to manage patients and families with inherited heart rhythm disorders given the need for a high level of information and support. Copyright © 2017 Heart Rhythm Society. All rights reserved.

  3. Blood coagulation parameters and platelet indices: changes in normal and preeclamptic pregnancies and predictive values for preeclampsia.

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    Lei Han

    Full Text Available Preeclampsia (PE is an obstetric disorder with high morbidity and mortality rates but without clear pathogeny. The dysfunction of the blood coagulation-fibrinolysis system is a salient characteristic of PE that varies in severity, and necessitates different treatments. Therefore, it is necessary to find suitable predictors for the onset and severity of PE.We aimed to evaluate blood coagulation parameters and platelet indices as potential predictors for the onset and severity of PE.Blood samples from 3 groups of subjects, normal pregnant women (n = 79, mild preeclampsia (mPE (n = 53 and severe preeclampsia (sPE (n = 42, were collected during early and late pregnancy. The levels of coagulative parameters and platelet indices were measured and compared among the groups. The receiver-operating characteristic (ROC curves of these indices were generated, and the area under the curve (AUC was calculated. The predictive values of the selected potential parameters were examined in binary regression analysis.During late pregnancy in the normal pregnancy group, the activated partial thromboplastin time (APTT, prothrombin time (PT, thrombin time (TT and platelet count decreased, while the fibrinogen level and mean platelet volume (MPV increased compared to early pregnancy (p<0.05. However, the PE patients presented with increased APTT, TT, MPV and D-dimer (DD during the third trimester. In the analysis of subjects with and without PE, TT showed the largest AUC (0.743 and high predictive value. In PE patients with different severities, MPV showed the largest AUC (0.671 and ideal predictive efficiency.Normal pregnancy causes a maternal physiological hypercoagulable state in late pregnancy. PE may trigger complex disorders in the endogenous coagulative pathways and consume platelets and FIB, subsequently activating thrombopoiesis and fibrinolysis. Thrombin time and MPV may serve as early monitoring markers for the onset and severity of PE

  4. Expression of human blood coagulation factor XI: characterization of the defect in factor XI type III deficiency

    NARCIS (Netherlands)

    Meijers, J. C.; Davie, E. W.; Chung, D. W.


    Human factor XI (FXI) is a blood coagulation factor participating in the early phase of the intrinsic pathway of blood coagulation. It circulates in blood as a glycoprotein composed of two identical chains held together by a single disulfide bond between the fourth apple domains. FXI has been


    Directory of Open Access Journals (Sweden)

    Negrin Negrev


    Full Text Available Thymus peptides (thymulin, thymosin alpha 1 and thymosin beta 4 inhibiting effects on the intrinsic blood coagulation pathway in rats Background and purpose: Hemostasis is a basic homeostatic mechanism protecting the body from thrombosis or haemorrhage. A number of pathological conditions, including multiple endocrine disorders modulate the balance between pro- and anticoagulation factors and establish conditions of hyper- or hypocoagulability. Endocrine effects of thymus gland on blood coagulation are not completely elucidated, and data existing on the theme are relatively scarce and partially controversial. The present study was designed to investigate thymus peptides (thymulin, thymosin alpha 1 and thymosin beta 4 effects on key intrinsic pathway plasma clotting factors XII, XI, IX, X and activated partial thromboplastin time (aPTT – a principal marker of blood coagulation via intrinsic pathway of hemocoagulation, in rats. Materials and methods: Plasma clotting factor activities and aPTT were studied on 52 male Wistar intact rats after 3 day s.c. application of the thymic peptides envisaged using routine kinetic coagulometry. Results of the study indicate a significant reduction of FXII activity by thymulin and thymosin alpha 1, and FXI and FIX activity by thymulin and thymosin beta 4. Conclusion: Upper results support the conclusion that thymus peptides thymulin, thymosin alpha 1 and thymosin beta 4 application in rats imposes a distinct tendency of hypocoagulability.

  6. Blood coagulation screening using a paper-based microfluidic lateral flow device. (United States)

    Li, H; Han, D; Pauletti, G M; Steckl, A J


    A simple approach to the evaluation of blood coagulation using a microfluidic paper-based lateral flow assay (LFA) device for point-of-care (POC) and self-monitoring screening is reported. The device utilizes whole blood, without the need for prior separation of plasma from red blood cells (RBC). Experiments were performed using animal (rabbit) blood treated with trisodium citrate to prevent coagulation. CaCl2 solutions of varying concentrations are added to citrated blood, producing Ca(2+) ions to re-establish the coagulation cascade and mimic different blood coagulation abilities in vitro. Blood samples are dispensed into a paper-based LFA device consisting of sample pad, analytical membrane and wicking pad. The porous nature of the cellulose membrane separates the aqueous plasma component from the large blood cells. Since the viscosity of blood changes with its coagulation ability, the distance RBCs travel in the membrane in a given time can be related to the blood clotting time. The distance of the RBC front is found to decrease linearly with increasing CaCl2 concentration, with a travel rate decreasing from 3.25 mm min(-1) for no added CaCl2 to 2.2 mm min(-1) for 500 mM solution. Compared to conventional plasma clotting analyzers, the LFA device is much simpler and it provides a significantly larger linear range of measurement. Using the red colour of RBCs as a visible marker, this approach can be utilized to produce a simple and clear indicator of whether the blood condition is within the appropriate range for the patient's condition.

  7. Bioassay-directed fractionation of a blood coagulation factor Xa inhibitor, betulinic acid from Lycopus lucidus

    Directory of Open Access Journals (Sweden)

    Tan Yin-Feng


    Full Text Available Thrombosis is a major cause of morbidity and mortality worldwide and plays a pivotal role in the pathogenesis of several cardiovascular disorders, including acute coronary syndrome, unstable angina, myocardial infarction, sudden cardiac death, peripheral arterial occlusion, ischemic stroke, deep-vein thrombosis, and pulmonary embolism. Anticoagulants, antiplatelet agents, and fibrinolytics can reduce the risks of these clinical events. Especially, the blood coagulation factor Xa (FXa inhibitor is a proven anticoagulant. Promoting blood circulation, using traditional Chinese medicine (TCM, for the treatment of these diseases has been safely used for thousands of years in clinical practice. Therefore, highly safe and effective anticoagulant ingredients, including FXa inhibitors, could be found in TCM for activating the blood circulation. One FXa inhibitor, a pentacyclic triterpene (compound 1, betulinic acid characterized by IR, MS and NMR analyses, was isolated from the ethyl acetate fraction of Lycopus lucidus by bioassay-directed fractionation. Compound 1 exhibited an inhibitory effect on FXa with IC50 25.05 μmol/L and reduced the thrombus weight in an animal model at 25-100 mg/kg. These results indicate that betulinic acid could be the potential for anticoagulant therapy.

  8. Micro-electromechanical film bulk acoustic sensor for plasma and whole blood coagulation monitoring. (United States)

    Chen, Da; Song, Shuren; Ma, Jilong; Zhang, Zhen; Wang, Peng; Liu, Weihui; Guo, Qiuquan


    Monitoring blood coagulation is an important issue in the surgeries and the treatment of cardiovascular diseases. In this work, we reported a novel strategy for the blood coagulation monitoring based on a micro-electromechanical film bulk acoustic resonator. The resonator was excited by a lateral electric field and operated under the shear mode with a frequency of 1.9GHz. According to the apparent step-ladder curves of the frequency response to the change of blood viscoelasticity, the coagulation time (prothrombin time) and the coagulation kinetics were measured with the sample consumption of only 1μl. The procoagulant activity of thromboplastin and the anticoagulant effect of heparin on the blood coagulation process were illustrated exemplarily. The measured prothrombin times showed a good linear correlation with R 2 =0.99969 and a consistency with the coefficient of variation less than 5% compared with the commercial coagulometer. The proposed film bulk acoustic sensor, which has the advantages of small size, light weight, low cost, simple operation and little sample consumption, is a promising device for miniaturized, online and automated analytical system for routine diagnostics of hemostatic status and personal health monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The effects of nanomaterials on blood coagulation in hemostasis and thrombosis. (United States)

    Simak, Jan; De Paoli, Silvia


    The blood coagulation balance in the organism is achieved by the interaction of the blood platelets (PLTs) with the plasma coagulation system (PCS) and the vascular endothelial cells. In healthy organism, these systems prevent thrombosis and, in events of vascular damage, enable blood clotting to stop bleeding. The dysregulation of hemostasis may cause serious thrombotic and/or hemorrhagic pathologies. Numerous engineered nanomaterials are being investigated for biomedical purposes and are unavoidably exposed to the blood. Also, nanomaterials may access vascular system after occupational, environmental, or other types of exposure. Thus, it is essential to evaluate the effects of engineered nanomaterials on hemostasis. This review focuses on investigations of nanomaterial interactions with the blood components involved in blood coagulation: the PCS and PLTs. Particular emphases include the pathophysiology of effects of nanomaterials on the PCS, including the kallikrein-kinin system, and on PLTs. Methods for investigating these interactions are briefly described, and a review of the most important studies on the interactions of nanomaterials with plasma coagulation and platelets is provided. WIREs Nanomed Nanobiotechnol 2017, 9:e1448. doi: 10.1002/wnan.1448 For further resources related to this article, please visit the WIREs website. © Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  10. Rapid evaluation of fibrinogen levels using the CG02N whole blood coagulation analyzer. (United States)

    Hayakawa, Mineji; Gando, Satoshi; Ono, Yuichi; Mizugaki, Asumi; Katabami, Kenichi; Maekawa, Kunihiko; Miyamoto, Daisuke; Wada, Takeshi; Yanagida, Yuichiro; Sawamura, Atsushi


    Rapid evaluation of fibrinogen (Fbg) levels is essential for maintaining homeostasis in patients with massive bleeding during severe trauma and major surgery. This study evaluated the accuracy of fibrinogen levels measured by the CG02N whole blood coagulation analyzer (A&T Corporation, Kanagawa, Japan) using heparinized blood drawn for blood gas analysis (whole blood-Fbg). A total of 100 matched pairs of heparinized blood samples and citrated blood samples were simultaneously collected from patients in the intensive care unit. Whole blood-Fbg results were compared with those of citrated plasma (standard-Fbg). The whole blood coagulation analyzer measured fibrinogen levels within 2 minutes. Strong correlations between standard-Fbg and whole blood-Fbg were observed (ρ = 0.91, p coagulation analyzer can rapidly measure fibrinogen levels in heparinized blood and could be useful in critical care settings where excessive bleeding is a concern. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.


    Nishimura, Koji; Kuzume, Kazuyo; Kagata, Yuki


    Recently, an association between coagulation dysfunction and the pathology of urticaria has been reported, but research in children is scarce. We measured levels of prothrombin fragments 1+2 (PTF1+2), fibrin degradation product (FDP), D-dimer, and mean platelet volume (MPV) in 32 children with urticaria. The study cohort comprised 18 cases of chronic and active urticaria, 7 cases of chronic and inactive urticaria, and 7 cases of acute urticaria. PTF1+2 levels in the chronic and active urticaria group were higher than those in the chronic and inactive urticaria group (purticaria group were higher than those in the chronic and inactive group (purticaria.

  12. [Reference values for the blood coagulation tests in Mexico: usefulness of the pooled plasma from blood donors]. (United States)

    Calzada-Contreras, Adriana; Moreno-Hernández, Manuel; Castillo-Torres, Noemi Patricia; Souto-Rosillo, Guadalupe; Hernández-Juárez, Jesús; Ricardo-Moreno, María Tania; Sánchez-Fernández, Maria Guadalupe de Jesús; García-González, América; Majluf-Cruz, Abraham


    The blood coagulation system maintains the blood in a liquid state and bleeding and thrombosis are the manifestations of its malfunction. Blood coagulation laboratory evaluates the physiology of this system. To establish both, the reference values for several tests performed at the blood coagulation laboratory as well as the utility of the pooled plasma to perform these assays. MATERIAL AND: In this descriptive, cross-sectional, randomized study, we collected plasma from Mexican Mestizos. Each pooled plasma was prepared with the plasma from at least 20 blood donors. We performed screening and special tests and the Levey-Jennings graphs were built and interpreted after each pass. Results of the tests were analyzed and their distribution was established using the Kolmogorov-Smirnov test. To establish the reference values we used 95% confidence intervals. We collected 72 pooled plasmas. The distribution for PT, APTT, and TT tests was abnormal. Although the PT test showed a bimodal distribution it was normal for factor VII. The reference values for the hemostatic, anticoagulant, and fibrinolytic factors were different from those suggested by the manufacturers. We established the reference values for the blood coagulation tests in the adult Mexican population. We have shown that the pooled plasma must be used for the screening tests. We suggest that each clinical laboratory should establish its own reference values (at least for the screening tests). To reach this objective, we encourage the use of the pooled plasma.

  13. Blood coagulation and fibrinolysis of the whole-body irradiated rabbits

    International Nuclear Information System (INIS)

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


    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)

  14. A high fat meal activates blood coagulation factor VII in rats

    DEFF Research Database (Denmark)

    Olsen, Aage K; Bladbjerg, Else M; Hansen, Axel K


    In humans, high fat meals cause postprandial activation of blood coagulation factor VII (FVII), but human studies have not provided definite evidence for a prothrombotic effect of dietary FVII activation. An animal model would be an attractive way to pursue this question and therefore we tested...

  15. Tissue factor-dependent blood coagulation is enhanced following delivery irrespective of the mode of delivery

    NARCIS (Netherlands)

    Boer, K.; den Hollander, I. A.; Meijers, J. C. M.; Levi, M. [=Marcel M.


    BACKGROUND: The risk of thrombosis is clearly increased in the postpartum period. Mice with a targeted deletion of the transmembrane domain of tissue factor (TF) develop serious activation of blood coagulation and widespread thrombosis after delivery. OBJECTIVE AND METHODS: We hypothesized that TF,

  16. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. (United States)

    Ribas, Graziela S; Vargas, Carmen R; Wajner, Moacir


    In recent years increasing evidence has emerged suggesting that oxidative stress is involved in the pathophysiology of a number of inherited metabolic disorders. However the clinical use of classical antioxidants in these diseases has been poorly evaluated and so far no benefit has been demonstrated. l-Carnitine is an endogenous substance that acts as a carrier for fatty acids across the inner mitochondrial membrane necessary for subsequent beta-oxidation and ATP production. Besides its important role in the metabolism of lipids, l-carnitine is also a potent antioxidant (free radical scavenger) and thus may protect tissues from oxidative damage. This review addresses recent findings obtained from patients with some inherited neurometabolic diseases showing that l-carnitine may be involved in the reduction of oxidative damage observed in these disorders. For some of these diseases, reduced concentrations of l-carnitine may occur due to the combination of this compound to the accumulating toxic metabolites, especially organic acids, or as a result of protein restricted diets. Thus, l-carnitine supplementation may be useful not only to prevent tissue deficiency of this element, but also to avoid oxidative damage secondary to increased production of reactive species in these diseases. Considering the ability of l-carnitine to easily cross the blood-brain barrier, l-carnitine supplementation may also be beneficial in preventing neurological damage derived from oxidative injury. However further studies are required to better explore this potential. © 2013 Elsevier B.V. All rights reserved.

  17. Coagulation defects. (United States)

    Soliman, Doreen E; Broadman, Lynn M


    The present understanding of the coagulation process emphasizes the final common pathway and the proteolytic systems that result in the degradation of formed clots and the prevention of unwanted clot formations, as well as a variety of defense systems that include tissue repair, autoimmune processes, arteriosclerosis, tumor growth, the spread of metastases, and defense systems against micro-organisms. This article discusses diagnosis and management of some of the most common bleeding disorders. The goals are to provide a simple guide on how best to manage patients afflicted with congenital or acquired clotting abnormalities during the perioperative period, present a brief overview of the methods of testing and monitoring the coagulation defects, and discuss the appropriate pharmacologic or blood component therapies for each disease.

  18. Coagulation changes during lower body negative pressure and blood loss in humans. (United States)

    van Helmond, Noud; Johnson, Blair D; Curry, Timothy B; Cap, Andrew P; Convertino, Victor A; Joyner, Michael J


    We tested the hypothesis that markers of coagulation activation are greater during lower body negative pressure (LBNP) than those obtained during blood loss (BL). We assessed coagulation using both standard clinical tests and thrombelastography (TEG) in 12 men who performed a LBNP and BL protocol in a randomized order. LBNP consisted of 5-min stages at 0, -15, -30, and -45 mmHg of suction. BL included 5 min at baseline and following three stages of 333 ml of blood removal (up to 1,000 ml total). Arterial blood draws were performed at baseline and after the last stage of each protocol. We found that LBNP to -45 mmHg is a greater central hypovolemic stimulus versus BL; therefore, the coagulation markers were plotted against central venous pressure (CVP) to obtain stimulus-response relationships using the linear regression line slopes for both protocols. Paired t-tests were used to determine whether the slopes of these regression lines fell on similar trajectories for each protocol. Mean regression line slopes for coagulation markers versus CVP fell on similar trajectories during both protocols, except for TEG α° angle (-0.42 ± 0.96 during LBNP vs. -2.41 ± 1.13°/mmHg during BL; P coagulation was accelerated as evidenced by shortened R-times (LBNP, 9.9 ± 2.4 to 6.2 ± 1.1; BL, 8.7 ± 1.3 to 6.4 ± 0.4 min; both P coagulation markers observed during BL. Copyright © 2015 the American Physiological Society.

  19. Familial mediterranean fever: a fascinating model of inherited autoinflammatory disorder. (United States)

    Portincasa, Piero; Scaccianoce, Giuseppe; Palasciano, Giuseppe


    Familial Mediterranean fever (FMF) is a rare inherited autosomal recessive autoinflammatory disorder characterized by recurrent and self-limited episodes of fever and painful serositis, lasting 1-3 days. FMF occurs almost exclusively among ethnic groups of the Mediterranean basin, although cases have also been found in Japan and Korean populations. Diagnosis is based on clinical features, response to colchicine and genetic analysis. Novel drugs are emerging, allowing better management of colchicine-resistant/colchicine-intolerant patients. This review aims to attract the attention of the readers on differential diagnosis and management of patients with FMF. The current state-of-the-art on FMF is outlined, with respect to epidemiological, genetic, pathophysiological and therapeutic characteristics, based on critical analysis of solid scientific literature. FMF is more frequent than it was thought before. The phenotypic expression of M694V is more severe than that of V726A. Patients with M694V/M694V homozygosity are exposed to a higher risk of developing renal amyloidosis, arthritis, dermatologic and oral lesions, higher fever and more frequent painful attacks. Life-long therapy with colchicine (1·0-2·4 mg/day) is effective and safe to prevent recurrent attacks and renal amyloidosis and to reverse proteinuria. In nonresponder patients, alternative novel approaches include interleukin-1 receptor antagonist anakinra and the interleukin-1 decoy receptor rilonacept. The prognosis of FMF is normal if AA amyloidosis is prevented. Colchicine remains the first-line therapy to treat pain and prevent amyloidosis. A follow-up should include clinical evaluation, therapeutic adjustments, measurement of serum amyloid A and proteinuria. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  20. Tulathromycin disturbs blood oxidative and coagulation status | Er ...

    African Journals Online (AJOL)

    ... amylase, total protein, albumin, glucose and calcium), haemacell counts (white and red blood cells) and arterial blood gas parameters (packed cell volume, hemoglobin, pH, partial pressure of carbon dioxide, partial pressure of oxygen, actual bicarbonate, standard bicarbonate, total carbon dioxide, base excess in vivo, ...

  1. Coagulation indices in very preterm infants from cord blood and postnatal samples. (United States)

    Neary, E; McCallion, N; Kevane, B; Cotter, M; Egan, K; Regan, I; Kirkham, C; Mooney, C; Coulter-Smith, S; Ní Áinle, F


    Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests. The primary objective of this study was to measure standard plasma coagulation tests and thrombin generation in very premature infants compared with term infants. The secondary objective was to evaluate whether an association existed between coagulation indices and intraventricular hemorrhage (IVH). Cord and peripheral blood of neonates coagulation factor levels were measured and tissue factor-stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates. One hundred and sixteen infants were recruited. Median (range) GA was 27.7 (23.7-29.9) weeks and mean (SD) birth weight was 1020 (255) g. Median (5th-95th percentile) day 1 PT, APTT and fibrinogen were 17.5 (12.7-26.6) s, 78.7 (48.7-134.3) s and 1.4 (0.72-3.8) g L(-1) , respectively. No difference in endogenous thrombin potential between preterm and term plasma was observed, where samples were available. Levels of coagulation factors II, VII, IX and X, protein C, protein S and antithrombin were reduced in preterm compared with term plasma. Day 1 APTT and PT were not associated with IVH. In the largest cross-sectional study to date of very preterm infants, typical ranges for standard coagulation tests were determined. Despite long clotting times, thrombin generation was observed to be similar in very preterm and term infants. © 2015 International Society on Thrombosis and Haemostasis.

  2. A ¤high-fat meal does not activate blood coagulation factor vii in minipigs

    DEFF Research Database (Denmark)

    Olsen, A. K.; Larsen, L. F.; Bladbjerg, E.-M.


    tool. We studied postprandial FVII activation in seven non-fasting Göttingen minipigs. Intralipid (4 g/kg) was administered through a gastric tube in two fractions at 9.00 a.m. (one-third of total dose) and 10.30 a.m. (two-thirds of total dose). Blood samples were drawn 0.5 h before (baseline) and 2, 3......It is a matter of debate whether postprandial activation of blood coagulation factor VII (FVII) is associated with an increased risk of thrombosis. To clarify this question, an animal model in which consequences of dietary FVII activation can be studied in a more detailed way would be an important...... to activate blood coagulation FVII in minipigs, the pig is apparently not a relevant model for the study of dietary FVII activation and thrombin generation. Udgivelsesdato: 2001-Mar...

  3. Hydroxyethyl Starch Reduces Coagulation Competence and Increases Blood Loss During Major Surgery

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten C; Johansson, Pär I; Højskov, Michael


    OBJECTIVE: This study evaluated whether administration of hydroxyethyl starch (HES) 130/0.4 affects coagulation competence and influences the perioperative blood loss. BACKGROUND: Artificial colloids substitute blood volume during surgery; with the administration of HES 130/0.4 (Voluven, Fresenius...... Kabi, Uppsala, Sweden) only a minor effect on coagulation competence is expected. METHODS: Eighty patients were scanned for enrollment in the study, and 40 patients fulfilled the inclusion criteria. Two patients withdrew their consent to participate in the study, and 5 patients were excluded. Thus, 16...... patients were randomized to receive lactated Ringer's solution and 17 to receive HES 130/0.4. RESULTS: Among the patients receiving HES 130/0.4, thrombelastography indicated reduced clot strength (P evaluation of the perioperative blood loss was 2.2 (range 0.5 to 5.0) versus 1.4 (range...

  4. Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro. (United States)

    Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong


    To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca(2+) concentration, while Na(+) and K(+) concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca(2+) and Na(+) concentrations. Si(4+) (0.2434 g/L) and Al(3+) (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca(2+) concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Zeolite releases Ca(2+) into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.


    Directory of Open Access Journals (Sweden)

    Rasha ElAshry


    Full Text Available

    Hemophilia represent the most severe inherited bleeding  disorder (INB , it’s thought to affect inviduals from all geographical areas in equal frequency. In Egypt which has a population of approximately (80million consanguineous marriage are frequent, therefore autosomal recessive coagulation disorders reach a higher prevalence than in many other countries.

    The primary aim of this study was to describe the epidemiological situation of hemophilia in Mansoura, Egypt ,as based on retrospective analysis of clinical records Mansoura University Children Hospital between years 2000 and 2008. The second aim was to assess the orthopedic complications and occurrence of hepatitis C in those patients and relate this status to the type of replacement therapy received prior to the study.

    The study included 72 children with hematological disorders registered from 2000 to 2008 in MUCH. The hemophilic patient was defined as a person with physician-diagnosed hemophilia A or B and a measured factor VIII or IX activity level of 30% or less. Persons with acquired inhibitors of FVIII or FIX excluded. Severity level was categorized as mild if the factor activity level was 6

  6. The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet

    Directory of Open Access Journals (Sweden)

    Min Hee Kim


    Conclusion: These results suggest the possibility that GBx can ameliorate blood flow by decreasing intima-media thickness via the regulation of blood coagulation factors related to lipid metabolites in rats fed a HFD.

  7. In vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch. (United States)

    Hanke, Alexander A; Maschler, Stephanie; Schöchl, Herbert; Flöricke, Felix; Görlinger, Klaus; Zanger, Klaus; Kienbaum, Peter


    Hypertonic saline hydroxyethyl starch (HH) has been recommended for first line treatment of hemorrhagic shock. Its effects on coagulation are unclear. We studied in vitro effects of HH dilution on whole blood coagulation and platelet function. Furthermore 7.2% hypertonic saline, 6% hydroxyethylstarch (as ingredients of HH), and 0.9% saline solution (as control) were tested in comparable dilutions to estimate specific component effects of HH on coagulation. The study was designed as experimental non-randomized comparative in vitro study. Following institutional review board approval and informed consent blood samples were taken from 10 healthy volunteers and diluted in vitro with either HH (HyperHaes, Fresenius Kabi, Germany), hypertonic saline (HT, 7.2% NaCl), hydroxyethylstarch (HS, HAES6%, Fresenius Kabi, Germany) or NaCl 0.9% (ISO) in a proportion of 5%, 10%, 20% and 40%. Coagulation was studied in whole blood by rotation thrombelastometry (ROTEM) after thromboplastin activation without (ExTEM) and with inhibition of thrombocyte function by cytochalasin D (FibTEM), the latter was performed to determine fibrin polymerisation alone. Values are expressed as maximal clot firmness (MCF, [mm]) and clotting time (CT, [s]). Platelet aggregation was determined by impedance aggregrometry (Multiplate) after activation with thrombin receptor-activating peptide 6 (TRAP) and quantified by the area under the aggregation curve (AUC [aggregation units (AU)/min]). Scanning electron microscopy was performed to evaluate HyperHaes induced cell shape changes of thrombocytes. 2-way ANOVA for repeated measurements, Bonferroni post hoc test, p coagulation and thrombocyte aggregation in all dilutions in a dose dependent fashion. In contrast to dilution with ISO and HS, respectively, dilution with HH as well as HT almost abolished coagulation (MCFExTEM from 57.3 ± 4.9 mm (native) to 1.7 ± 2.2 mm (HH 40% dilution; p coagulation is significant after 10% dilution or more. This effect can

  8. Coagulation competence and fluid recruitment after moderate blood loss in young men

    DEFF Research Database (Denmark)

    Zaar, Morten; Mørkeberg, Jakob; Pott, Frank C


    and redistribution of the blood volume. In eight supine male volunteers (24 ± 3 years, blood volume of 6.9 ± 0.7 l; mean ± SD), 2 × 450 ml blood was withdrawn over ∼ 30 min while cardiovascular variables were monitored. Coagulation was evaluated by thrombelastography, and fluid recruitment was estimated by red blood...... cell count. Withdrawing 900 ml blood increased heart rate (62 ± 7 to 69 ± 13 bpm, P SD) and reduced stroke volume (113 ± 12 to 96 ± 14 ml, P ... of 900 ml blood (α-Angle: 66 ± 4 to 70 ± 3 deg, P lysis 30 min after maximal amplitude (LY30: 0.8% [0-3.5%] (median [range])), and platelet count (218 ± 25 × 10(9) l(-1)) were unaffected. For supine males, ∼ 25% of a moderate blood loss...

  9. Air quality improvement during 2010 Asian games on blood coagulability in COPD patients. (United States)

    Zhang, Zili; Wang, Jian; Guo, Meihua; Xiong, Mingmei; Zhou, Qipeng; Li, Defu; Shu, Jiaze; Lu, Wenju; Sun, Dejun


    Exposure to elevated levels of ambient air pollutants can lead to adverse cardiovascular effects. Perturbation of the coagulation balance is one of the potential mechanisms. However, evidence regarding the impact of improvement in air pollution on blood coagulability in COPD patients has never been reported. Coagulation processes are known to be of relevance for cardiovascular pathology; therefore, this study aimed to investigate the association of short-term air pollution exposure with blood marker (D-dimer) of coagulation. A 3-year (through the Asian game) cohort study based on the GIRD COPD Biobank Project was conducted in 36 COPD patients to estimate whether changes in measurements of D-dimer were associated with changes in pollutant concentration, comparing for 51 intervention days (November 1-December 21) in 2010 with the same calendar date of baseline years (2009 and 2011). Daily mean concentrations of air pollutants and meteorological variables were measured during the time. Daily PM10 decreased from 65.86 μg/m(3) during the baseline period to 62.63 μg/m(3) during the Asian Games period; daily NO2 decreased from 51.33 to 42.63 μg/m(3). SO2 and other weather variables did not differ substantially. We did not observe statistically significant improvements in D-dimer levels by 9.86% from a pre-Asian game mean of 917 ng/ml to a during-Asian game mean of 1007 ng/ml, platelet number by 11.66%, PH by -0.15%, PCO2 by -6.54%, and PO2 by -1.16%. In the post-Asian game period, when pollutant concentrations increased, most outcomes approximated pre-Asian game levels, and similar effects were also demonstrated in D-dimer, platelet number, and arterial blood gas. For D-dimer and platelet number, we observed statistically significant increases associated with increases in NO2 at lag 1-3 and SO2 at lag 2-4. For PH, PCO2, and PO2, any significant effect was not demonstrated. This study gives no support to the hypothesis that reduction in air pollution levels during the

  10. Hydroxyethyl Starch Reduces Coagulation Competence and Increases Blood Loss During Major Surgery

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten C; Johansson, Pär I; Højskov, Michael


    OBJECTIVE: This study evaluated whether administration of hydroxyethyl starch (HES) 130/0.4 affects coagulation competence and influences the perioperative blood loss. BACKGROUND: Artificial colloids substitute blood volume during surgery; with the administration of HES 130/0.4 (Voluven, Fresenius...... patients were randomized to receive lactated Ringer's solution and 17 to receive HES 130/0.4. RESULTS: Among the patients receiving HES 130/0.4, thrombelastography indicated reduced clot strength (P blood loss was 2.2 (range 0.5 to 5.0) versus 1.4 (range...

  11. Surface-mediated molecular events in material-induced blood-plasma coagulation (United States)

    Chatterjee, Kaushik

    Coagulation and thrombosis persist as major impediments associated with the use of blood-contacting medical devices. We are investigating the molecular mechanism underlying material-induced blood-plasma coagulation focusing on the role of the surface as a step towards prospective development of improved hemocompatible biomaterials. A classic observation in hematology is that blood/blood-plasma in contact with clean glass surface clots faster than when in contact with many plastic surfaces. The traditional biochemical theory explaining the underlying molecular mechanism suggests that hydrophilic surfaces, like that of glass, are specific activators of the coagulation cascade because of the negatively-charged groups on the surface. Hydrophobic surfaces are poor procoagulants or essentially "benign" because they lack anionic groups. Further, these negatively-charged surfaces are believed to not only activate blood factor XII (FXII), the key protein in contact activation, but also play a cofactor role in the amplification and propagation reactions that ultimately lead to clot formation. In sharp contrast to the traditional theory, our investigations indicate a need for a paradigm shift in the proposed sequence of contact activation events to incorporate the role of protein adsorption at the material surfaces. These studies have lead to the central hypothesis for this work proposing that protein adsorption to hydrophobic surfaces attenuates the contact activation reactions so that poorly-adsorbent hydrophilic surfaces appear to be stronger procoagulants relative to hydrophobic surfaces. Our preliminary studies measuring the plasma coagulation response of activated FXII (FXIIa) on different model surfaces suggested that the material did not play a cofactor role in the processing of this enzyme dose through the coagulation pathway. Therefore, we focused our efforts on studying the mechanism of initial production of enzyme at the procoagulant surface. Calculations for the

  12. Calcium channelopathies in inherited neurological disorders: relevance to drug screening for acquired channel disorders. (United States)

    Lory, Philippe; Mezghrani, Alexandre


    Mutations located in the human genes encoding voltage-gated calcium channels are responsible for a variety of diseases referred to as calcium channelopathies, including familial hemiplegic migraine, episodic ataxia type 2, spinocerebellar ataxia type 6, childhood absence epilepsy and autism spectrum disorder, all of which are rare inherited forms of common neurological disorders. The genetic basis of these calcium channelopathies provides a unique opportunity to investigate their underlying mechanisms from the molecular to whole-organism levels. Studies of channelopathies provide insight on the relationships between channel structure and function, and reveal diverse and unexpected physiological roles for the channels. Importantly, these studies may also lead to the identification of drugs for the treatment of genetically acquired channel disorders, as well as to novel therapeutic practices. In this feature review, recent findings regarding neurological calcium channelopathies are discussed.

  13. Coagulation measurement from whole blood using vibrating optical fiber in a disposable cartridge. (United States)

    Yaraş, Yusuf Samet; Gündüz, Ali Bars; Sağlam, Gökhan; Ölçer, Selim; Civitçi, Fehmi; Baris, İbrahim; Yaralioğlu, Göksenin; Urey, Hakan


    In clinics, blood coagulation time measurements are performed using mechanical measurements with blood plasma. Such measurements are challenging to do in a lab-on-a-chip (LoC) system using a small volume of whole blood. Existing LoC systems use indirect measurement principles employing optical or electrochemical methods. We developed an LoC system using mechanical measurements with a small volume of whole blood without requiring sample preparation. The measurement is performed in a microfluidic channel where two fibers are placed inline with a small gap in between. The first fiber operates near its mechanical resonance using remote magnetic actuation and immersed in the sample. The second fiber is a pick-up fiber acting as an optical sensor. The microfluidic channel is engineered innovatively such that the blood does not block the gap between the vibrating fiber and the pick-up fiber, resulting in high signal-to-noise ratio optical output. The control plasma test results matched well with the plasma manufacturer's datasheet. Activated-partial-thromboplastin-time tests were successfully performed also with human whole blood samples, and the method is proven to be effective. Simplicity of the cartridge design and cost of readily available materials enable a low-cost point-of-care device for blood coagulation measurements. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  14. Coagulation measurement from whole blood using vibrating optical fiber in a disposable cartridge (United States)

    Yaraş, Yusuf Samet; Gündüz, Ali Bars; Saǧlam, Gökhan; Ölçer, Selim; Civitçi, Fehmi; Baris, İbrahim; Yaralioǧlu, Göksenin; Urey, Hakan


    In clinics, blood coagulation time measurements are performed using mechanical measurements with blood plasma. Such measurements are challenging to do in a lab-on-a-chip (LoC) system using a small volume of whole blood. Existing LoC systems use indirect measurement principles employing optical or electrochemical methods. We developed an LoC system using mechanical measurements with a small volume of whole blood without requiring sample preparation. The measurement is performed in a microfluidic channel where two fibers are placed inline with a small gap in between. The first fiber operates near its mechanical resonance using remote magnetic actuation and immersed in the sample. The second fiber is a pick-up fiber acting as an optical sensor. The microfluidic channel is engineered innovatively such that the blood does not block the gap between the vibrating fiber and the pick-up fiber, resulting in high signal-to-noise ratio optical output. The control plasma test results matched well with the plasma manufacturer's datasheet. Activated-partial-thromboplastin-time tests were successfully performed also with human whole blood samples, and the method is proven to be effective. Simplicity of the cartridge design and cost of readily available materials enable a low-cost point-of-care device for blood coagulation measurements.

  15. Effects on fibrinogen, fibrin, and blood coagulation of proteolytic extracts from fruits of Pseudananas macrodontes, Bromelia balansae, and B. hieronymi (Bromeliaceae) in comparison with bromelain. (United States)

    Errasti, María E; Prospitti, Anabela; Viana, Carolina A; Gonzalez, Mariana M; Ramos, Márcio V; Rotelli, Alejandra E; Caffini, Néstor O


    Extracts rich in cysteine proteases obtained from fruits of Pseudananas macrodontes (Pm), Bromelia balansae (Bb), and B. hieronymi (Bh) have previously shown an anti-inflammatory effect on animal models. Given the close relationship between hemostasis and inflammation, it is attractive to investigate therapeutic agents capable of modulating both systems. The aim of this work was to study the effect of Pm, Bb, and Bh on fibrin(ogen) and blood coagulation compared with stem bromelain (Bro). Action on fibrinogen was electrophoretically and spectrophotometrically evaluated, fibrinolytic activity was measured both electrophoretically and by the fibrin plate assay, and the effect on blood coagulation was studied by conventional coagulation tests (PT and APPT). All extracts showed the same proteolytic preference for fibrinogen subunits, that is Aα > Bβ, whereas γ was partially hydrolyzed by 100-fold concentration increase. Unlike Bro, cysteine proteases of Pm, Bb, and Bh increased absorbance at 540 nm of fibrinogen solution, suggesting thrombin-like activity, which was time-dependent and reached maximum values at lower concentration. All extracts showed the same proteolytic preference for fibrin subunits; however Pm, Bb, and Bh showed lower fibrinolytic activity than Bro at the assayed concentrations. Although Bb acted only as anticoagulant, Pm, Bh, and unexpectedly Bro showed dual action on blood coagulation: at low concentration showed procoagulant effect and at high concentration anticoagulant effect. Results reveal new plant species as potential sources of pharmacological agents for the treatment of a wide range of hemostatic disorders as well as to wound healing.

  16. Rotational Thromboelastometry or Conventional Coagulation Tests in Liver Transplantation: Comparing Blood Loss, Transfusions, and Cost. (United States)

    Smart, Laura; Mumtaz, Khalid; Scharpf, Danielle; Gray, Nicole O'Bleness; Traetow, Daniel; Black, Sylvester; Michaels, Anthony J; Elkhammas, Elmahdi; Kirkpatrick, Robert; Hanje, A James

    Orthotopic liver transplantation (OLT) can be associated with significant bleeding requiring multiple blood product transfusions. Rotational thromboelastometry (ROTEM) is a point-of-care device that has been used to monitor coagulation during OLT. Whether it reduces blood loss/transfusions during OLT remains controversial. We aim to compare ROTEM with conventional coagulation tests (aPTT, PT, INR, platelet count, fibrinogen) to guide transfusion of platelets, cryoprecipitate, and fresh frozen plasma (FFP) during OLT over 3 years. Thirty-four patients who had transfusions guided by ROTEM were compared to 34 controls who received transfusions guided by conventional coagulation tests (CCT). Intraoperative blood loss, type/ amount of blood products transfused, and direct costs were compared between the two groups. The ROTEM group had significantly less intra-operative blood loss (2.0 vs. 3.0 L, p = 0.04) and fresh frozen plasma (FFP) transfusion (4 units vs. 6.5 units, p = 0.015) compared to the CCT group (2.0L vs. 3.0L, p = 0.04). However, total number of patients transfused cryoprecipitate was increased in ROTEM (n = 25;73%) as compared to CCT (n = 19; 56%), p = 0.033. The direct cost of blood products plus testing was reduced in the ROTEM group ($113,142.89 vs. $127,814.77). In conclusion implementation of a ROTEM-guided transfusion algorithm resulted in a reduction in intra-operative blood loss, FFP transfusion and a decrease in direct cost during OLT. ROTEM is a useful and safe point of care device in OLT setting.

  17. Extensive small-angle X-ray scattering studies of blood coagulation factor VIIa reveal interdomain flexibility

    DEFF Research Database (Denmark)

    Mosbæk, Charlotte Rode; Nolan, David; Persson, Egon


    Blood coagulation factor VIIa (FVIIa) is used in the treatment of replacement therapy resistant hemophilia patients, and FVIIa is normally activated upon complex formation with tissue factor (TF), potentially in context with structural rearrangements. The solution behavior of uncomplexed FVIIa...

  18. Effects of Hemoglobin-Based Oxygen Carriers on Blood Coagulation

    Directory of Open Access Journals (Sweden)

    Kimia Roghani


    Full Text Available For many decades, Hemoglobin-based oxygen carriers (HBOCs have been central in the development of resuscitation agents that might provide oxygen delivery in addition to simple volume expansion. Since 80% of the world population lives in areas where fresh blood products are not available, the application of these new solutions may prove to be highly beneficial (Kim and Greenburg 2006. Many improvements have been made to earlier generation HBOCs, but various concerns still remain, including coagulopathy, nitric oxide scavenging, platelet interference and decreased calcium concentration secondary to volume expansion (Jahr et al. 2013. This review will summarize the current challenges faced in developing HBOCs that may be used clinically, in order to guide future research efforts in the field.

  19. Global Carrier Rates of Rare Inherited Disorders Using Population Exome Sequences.

    Directory of Open Access Journals (Sweden)

    Kohei Fujikura

    Full Text Available Exome sequencing has revealed the causative mutations behind numerous rare, inherited disorders, but it is challenging to find reliable epidemiological values for rare disorders. Here, I provide a genetic epidemiology method to identify the causative mutations behind rare, inherited disorders using two population exome sequences (1000 Genomes and NHLBI. I created global maps of carrier rate distribution for 18 recessive disorders in 16 diverse ethnic populations. Out of a total of 161 mutations associated with 18 recessive disorders, I detected 24 mutations in either or both exome studies. The genetic mapping revealed strong international spatial heterogeneities in the carrier patterns of the inherited disorders. I next validated this methodology by statistically evaluating the carrier rate of one well-understood disorder, sickle cell anemia (SCA. The population exome-based epidemiology of SCA [African (allele frequency (AF = 0.0454, N = 2447, Asian (AF = 0, N = 286, European (AF = 0.000214, N = 4677, and Hispanic (AF = 0.0111, N = 362] was not significantly different from that obtained from a clinical prevalence survey. A pair-wise proportion test revealed no significant differences between the two exome projects in terms of AF (46/48 cases; P > 0.05. I conclude that population exome-based carrier rates can form the foundation for a prospectively maintained database of use to clinical geneticists. Similar modeling methods can be applied to many inherited disorders.

  20. Origin of serpin-mediated regulation of coagulation and blood pressure.

    Directory of Open Access Journals (Sweden)

    Yunjie Wang

    Full Text Available Vertebrates evolved an endothelium-lined hemostatic system and a pump-driven pressurized circulation with a finely-balanced coagulation cascade and elaborate blood pressure control over the past 500 million years. Genome analyses have identified principal components of the ancestral coagulation system, however, how this complex trait was originally regulated is largely unknown. Likewise, little is known about the roots of blood pressure control in vertebrates. Here we studied three members of the serpin superfamily that interfere with procoagulant activity and blood pressure of lampreys, a group of basal vertebrates. Angiotensinogen from these jawless fish was found to fulfill a dual role by operating as a highly selective thrombin inhibitor that is activated by heparin-related glycosaminoglycans, and concurrently by serving as source of effector peptides that activate type 1 angiotensin receptors. Lampreys, uniquely among vertebrates, thus use angiotensinogen for interference with both coagulation and osmo- and pressure regulation. Heparin cofactor II from lampreys, in contrast to its paralogue angiotensinogen, is preferentially activated by dermatan sulfate, suggesting that these two serpins affect different facets of thrombin's multiple roles. Lampreys also express a lineage-specific serpin with anti-factor Xa activity, which demonstrates that another important procoagulant enzyme is under inhibitory control. Comparative genomics suggests that orthologues of these three serpins were key components of the ancestral hemostatic system. It appears that, early in vertebrate evolution, coagulation and osmo- and pressure regulation crosstalked through antiproteolytically active angiotensinogen, a feature that was lost during vertebrate radiation, though in gnathostomes interplay between these traits is effective.

  1. Analysis of blood coagulation in mice: pre-analytical conditions and evaluation of a home-made assay for thrombin-antithrombin complexes

    Directory of Open Access Journals (Sweden)

    Meijers Joost CM


    Full Text Available Abstract Background The use of mouse models for the study of thrombotic disorders has gained increasing importance. Methods for measurement of coagulation activation in mice are, however, scarce. The primary aim of this study was to develop a specific mouse thrombin-antithrombin (TAT ELISA for measurement of coagulation activation and to compare it with two commercially available assays for human TAT complexes. In addition, we aimed to improve methods for mouse plasma anticoagulation and preparation. Methods and results First, for the measurement of TAT-complexes in plasma a mouse specific TAT-ELISA was developed using rabbit polyclonal antibodies raised against mouse thrombin and rat antithrombin, respectively. This ELISA detected an increase in TAT levels in a mouse model of endotoxemia. Two commercial human TAT ELISAs appeared to be less specific for mouse thrombin-rat antithrombin complexes. Second, to prevent clotting of mouse blood sodium citrate was either mixed with blood during collection in a syringe or was injected intravenously immediately prior to blood collection. Intravenous sodium citrate completely inhibited blood coagulation resulting in plasma with consistently low TAT levels. Sodium citrate mixed with blood during collection resulted in increased TAT levels in 4 out of 16 plasma samples. Third, heparinase was added to plasma samples after in vivo injection of different heparin doses to test its neutralizing effect. Heparinase neutralized up to a 20 U of heparin/mouse and resulted in accurate APTT and factor VIII determinations. Conclusion These procedures and reagents for plasma preparation and coagulation testing will improve studies on thrombotic disorders in mice.

  2. Differential action of medically important Indian BIG FOUR snake venoms on rodent blood coagulation. (United States)

    Hiremath, Vilas; Nanjaraj Urs, A N; Joshi, Vikram; Suvilesh, K N; Savitha, M N; Urs Amog, Prathap; Rudresha, G V; Yariswamy, M; Vishwanath, B S


    Snakebite is a global health problem affecting millions of people. According to WHO, India has the highest mortality and/or morbidity due to snakebite. In spite of commendable research on Indian BIG FOUR venomous species; Naja naja and Bungarus caeruleus (elapid); Daboia russelii and Echis carinatus (viperid), no significant progress has been achieved in terms of diagnosis and management of biting species with appropriate anti-snake venom. Major hurdle is identification of offending species. Present study aims at differentiation of Indian BIG FOUR snake venoms based on their distinguish action on rodent blood coagulation. Assessment of coagulation alterations by elapid venoms showed negligible effect on re-calcification time, prothrombin time, activated partial thromboplastin time and factors assay (I, II, V, VIII and X) both in vitro and in vivo. However, viperid venoms demonstrated significant anticoagulant status due to their remarkable fibrinogen degradation potentials as supported by fibrinogenolytic activity, fibrinogen zymography and rotational thromboelastometry. Though results provide hint on probable alterations of Indian BIG FOUR snake venoms on blood coagulation, the study however needs validation from human victim's samples to ascertain its reliability for identification of biting snake species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. A link between blood coagulation and prophenol oxidase activation in arthropod host defense. (United States)

    Nagai, T; Kawabata, S


    Phenol oxidase, a copper-containing enzyme, is widely distributed not only in animals but also in plants and fungi, which is responsible for initiating the biosynthesis of melanin. Activation of prophenol oxidase in arthropods is important in host defense. However, the prophenol oxidase-activating system remains poorly understood at the molecular level. Here we show that the coagulation cascade of the horseshoe crab Tachypleus tridentatus is linked to prophenol oxidase activation, with the oxygen carrier hemocyanin functioning as a substitute for prophenol oxidase. Tachypleus clotting enzyme functionally transforms hemocyanin to phenol oxidase, and the conversion reaches a plateau at 1:1 stoichiometry without proteolytic cleavage. The active site-masked clotting enzyme also has the same effect, suggesting that complex formation of the clotting enzyme with hemocyanin is critical for the conversion. The two systems of blood coagulation and prophenol oxidase activation may have evolved from a common ancestral protease cascade.

  4. Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders (United States)


    Mucopolysaccharidosis; Hurler Syndrome; Hunter Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy (ALD); Krabbe Disease; Metachromatic Leukodystrophy (MLD); Sphingolipidoses; Peroxisomal Disorders

  5. Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases. (United States)

    De Luca, Ciro; Virtuoso, Assunta; Maggio, Nicola; Papa, Michele


    Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.

  6. Increased activation of blood coagulation in pregnant women with the Factor V Leiden mutation. (United States)

    Kjellberg, Ulla; van Rooijen, Marianne; Bremme, Katarina; Hellgren, Margareta


    The risk of venous thromboembolism is enhanced in pregnant carriers of the Factor V Leiden mutation. The primary aim of the study was to compare prothrombin fragments 1+2, soluble fibrin and D-dimer levels in pregnant Factor V Leiden mutation carriers with those in non-carriers. Secondary aims were to evaluate whether these biomarkers could predict placenta-mediated complications or venous thromboembolism, and to study blood coagulation after caesarean section with thromboprophylaxis and after vaginal delivery without thromboprophylaxis. Prothrombin fragments 1+2, soluble fibrin and D-dimer levels were studied longitudinally in 476 carriers with singleton pregnancies from gestational weeks 23-25 until 8-10 weeks postpartum. Prothrombin fragments 1+2 and D-dimer levels gradually increased during pregnancy. D-dimer levels were higher in carriers, both during pregnancy and puerperium, compared to non-carriers. D-dimer levels above 0.5mg/l were found in about 30% and 20% of the heterozygous carriers at 4-5 and 8-10 weeks postpartum, respectively. Soluble fibrin levels were mainly unchanged during pregnancy, with no difference between carriers and non-carriers. Biomarker levels were similar in carriers with uncomplicated and complicated pregnancies. Higher D-dimer levels indicate increased blood coagulation and fibrinolysis activity in carriers. The high proportion of carriers with D-dimer levels exceeding 0.5mg/l postpartum must be considered when assessing the probability of venous thromboembolism. Large overlaps in biomarker levels in normal and complicated pregnancies suggest that these biomarkers cannot be used as predictors. Thromboprophylaxis following caesarean section may prevent increased activation of blood coagulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Prevalence and Mode of Inheritance of the Dal Blood Group in Dogs in North America. (United States)

    Goulet, S; Giger, U; Arsenault, J; Abrams-Ogg, A; Euler, C C; Blais, M-C


    The Dal blood group system was identified a decade ago by the accidental sensitization of a Dal- Dalmatian with a Dal+ blood transfusion. Similar Dal-related blood incompatibilities have been suspected in other Dalmatians, Doberman Pinschers, and other breeds. To determine the prevalence and mode of inheritance of the Dal antigen expression in dogs. A total of 1130 dogs including 128 Dalmatians, 432 Doberman Pinschers, 21 Shih Tzus, and 549 dogs of other breeds including 228 blood donors were recruited from North America between 2008 and 2015. Prospectively, dogs were blood typed for Dal applying a gel column technique using polyclonal canine anti-Dal sera. Pedigrees from 8 typed families were analyzed. The prevalence of the Dal+ blood type varied between 85.6 and 100% in Dalmatians and 43.3-78.6% in Doberman Pinschers depending on geographical area. Dal- dogs were identified mostly in Dalmatians (15/128; 11.7%), Doberman Pinschers (183/432; 42.4%), and Shih Tzus (12/21; 57.1%), and sporadically in mixed-breed dogs (3/122; 2.5%), Lhasa Apsos (1/6) and Bichon Frises (1/3). Only 6/245 (2.4%) blood donors were found to be Dal-, including 5 Doberman Pinschers. The mode of inheritance of the Dal+ phenotype was determined to be autosomal dominant. The high percentage of Dal- Doberman Pinchers, Dalmatians and Shih Tzus increases their risk of being sensitized by a blood transfusion from the common Dal+ donor. Extended Dal typing is recommended in those breeds and in dogs when blood incompatibility problems arise after initial transfusions. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  8. [Traditional Chinese medicine inheritance system analysis of professor Ding Yuanqing in treating tic disorder medication based on experience]. (United States)

    Sun, Lu-yan; Li, Qing-peng; Zhao, Li-li; Ding, Yuan-qing


    In recent years, the incidence of tic disorders has increased, and it is not uncommon for the patients to treat the disease. The pathogenesis and pathogenesis of Western medicine are not yet clear, the clinical commonly used western medicine has many adverse reactions, traditional Chinese medicine (TCM) research is increasingly valued. Based on the software of TCM inheritance assistant system, this paper discusses Ding Yuanqing's experience in treating tic disorder with Professor. Collect yuan Qing Ding professor in treating tic disorder of medical records by association rules Apriori algorithm, complex system entropy clustering without supervision and data mining method, carries on the analysis to the selected 800 prescriptions, to determine the frequency of use of prescription drugs, the association rules between the drug and digging out the 12 core combination and the first six new prescription, medication transferred to the liver and extinguish wind, cooling blood and relieving convulsion, Qingxin soothe the nerves, with the card cut, flexible application, strict compatibility.

  9. Inherited eye-related disorders due to mitochondrial dysfunction. (United States)

    Yu-Wai-Man, Patrick; Newman, Nancy J


    Genetic disorders due to mitochondrial dysfunction are not uncommon and the majority of these patients will have eye-related manifestations, including visual loss from the optic nerve and retinal disease, visual field loss from retrochiasmal visual pathway damage, and ptosis and ocular dysmotility from extraocular muscle involvement. Defects in both the nuclear and mitochondrial genomes cause mitochondrial dysfunction via several mechanisms, including impaired mitochondrial energy production, oxidative stress, mitochondrial DNA instability, abnormalities in the regulation of mitochondrial dynamics and mitochondrial quality control, and disturbed cellular interorganellar communication. Advances in our understanding of the molecular genetic basis of mitochondrial disease have not only improved genetic diagnosis, but they have provided important insights into the pathophysiologic basis of these disorders and potential therapeutic targets. In parallel, more sophisticated techniques for genetic manipulation are facilitating the development of animal and in vitro models that should prove powerful and versatile tools for disease modelling and therapeutic experimentation. Effective therapies for mitochondrial disorders are beginning to translate from bench to bedside along the paths of neuroprotection, gene replacement and stem cell-based regenerative paradigms. Additionally, preventing the transmission of pathogenic mtDNA mutations from mother to child is now a reality with in vitro fertilization mitochondrial replacement techniques. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  10. Coagulation disorders in the patients with deep vein thrombosis of lower extremity

    Directory of Open Access Journals (Sweden)

    Milić Dragan J.


    Full Text Available PURPOSE Venous thromboembolism is a relevant social and health care problem for its high incidence, pulmonary embolism-related mortality and long-term sequelae which may be disabling (post-thrombotic syndrome and ulceration. PROCEDURES The aim of our work was to establish the presence of coagulation disorders (hypercoagulable states in the patients with deep vein thrombosis (DVT of the leg. Prospectively we have analyzed a group of 30 patients with echosono-graphicaly verified DVT of the leg who were admitted to the department of vascular surgery from August 1st 2000 to July 31st 2001.The following parameters were monitored: prothrombin time (PT partial thromboplastin time (PTT, fibrinogen (Fib, alpha 2 antiplasmin (A-2 AP, D-dimer (DD, antithrombin III (AT III and factor VII. FINDINGS Activation of the coagulation process was registered. The values of monitored coagulation parameters are shown in table 1. Plasma levels of monitored parameters in the patients with DVT of the leg were significantly higher than in the control subjects. CONCLUSION In patients with a DVT a hypercoagulable state is common finding. Some parameters of coagulation activity such as D-dimer might be of great interest in the diagnostic strategy of DVT.

  11. Fusaric acid, a mycotoxin, and its influence on blood coagulation and platelet function. (United States)

    Devaraja, Sannaningaiah; Girish, Kesturu S; Santhosh, Martin S; Hemshekhar, Mahadevappa; Nayaka, Siddaiah C; Kemparaju, Kempaiah


    The current study intended to explore the effect of fusaric acid on blood coagulation including plasma coagulation and platelet aggregation. Fusaric acid exhibited biphasic effects on citrated human plasma recalcification time. At concentrations below 50 ng, fusaric acid decreased the clotting time of plasma dose-dependently from 130 ± 3s control value to 32 ± 3s; however, above 50 ng, fusaric acid increased the clotting time from 32 ± 3s and reached a maximum of 152 s at 100 ng and remained unaltered thereafter for the increased dose of fusaric acid. Fusaric acid without damaging red blood cells and platelets, inhibited agonists such as collagen, ADP, thrombin, and epinephrine-induced aggregation of both platelet-rich plasma (PRP) and washed platelets preparations of human. Interestingly, fusaric acid showed biphasic effects only in thrombin-induced platelet aggregation of washed platelets, and at lower concentration (below 900 ng) it activated platelet aggregation; however, in increased concentration (above 900 ng) it inhibited the platelet aggregation of washed platelets. In addition, fusaric acid also inhibited the agonist ADP-induced platelet aggregation of washed platelet suspension but did not show biphasic effect. Further, fusaric acid did not induce the platelets to generate reactive oxygen species (ROS) that clearly suggests that the induction of platelet function could be the result of the fusaric acid-mediated receptor interaction but not through the morphological shape change.

  12. A high-fat meal does not activate blood coagulation factor VII in minipigs

    DEFF Research Database (Denmark)

    Olsen, A K; Larsen, L F; Bladbjerg, E-M


    It is a matter of debate whether postprandial activation of blood coagulation factor VII (FVII) is associated with an increased risk of thrombosis. To clarify this question, an animal model in which consequences of dietary FVII activation can be studied in a more detailed way would be an important...... tool. We studied postprandial FVII activation in seven non-fasting Göttingen minipigs. Intralipid (4 g/kg) was administered through a gastric tube in two fractions at 9.00 a.m. (one-third of total dose) and 10.30 a.m. (two-thirds of total dose). Blood samples were drawn 0.5 h before (baseline) and 2, 3....../l (baseline) to 2.56 mmol/l 5 h postprandially (P meal does not seem...

  13. Early Blood Transfusion and Resolution of Disseminated Intravascular Coagulation Associated with Massive Subgaleal Hemorrhage. (United States)

    Modanlou, Houchang; Hutson, Shandee; Merritt, Allan Thurman


    A male infant delivered to a primipara woman following vacuum applications. He was vigorous at birth, with small caput and scalp bruising. His head was enlarging; he became pale with respiratory distress. Subgaleal hemorrhage (SGH) was suspected. His hematocrit was noted to be 26.2 percent prior to transfusion of O, Rh-negative blood (40 mL/kg). Moderate disseminated intravascular coagulation (DIC) was noted at 12 hours of age. Posttransfusion of fresh frozen plasma (FFP), his condition became stable, and DIC gradually resolved. Head magnetic resonance imaging did not show intracranial hemorrhage. Although one episode of seizures was noted, electroencephalogram was normal. With the application of obstetric vacuum, we recommend that the neonatal health care professionals frequently evaluate the infant's condition. In light of developing fluctuant subgaleal fluid associated with pallor, anemia, metabolic acidosis, and respiratory distress, immediate blood transfusion is warranted. In the presence of DIC, transfusion of FFP is beneficial.

  14. Theories About Blood Coagulation in the Writings of Ancient Greek Medico-philosophers. (United States)

    Tsoucalas, Gregory; Karamanou, Marianna; Papaioannou, Theodoros G; Sgantzos, Markos


    Anaxagoras and Empedocles both established during the Presocratic era a pioneering theory for the creation of everything in the universe. Macrocosmos' impact through the "Four Elements Theory" explained the conglomeration of the blood inside the vessels. Hippocrates, who instituted the "Four Humours theory", clearly understood blood's coagulation and introduced the term "thrombus". Plato, Aristotle and Galen, all engaged with the clotting phenomenon trying to interpret it. After eons of inquiry, it was the innovative thinking of the ancient Greek medico philosophers that set the scientific bases towards the understanding of a process that had been analyzing until our era. Copyright© Bentham Science Publishers; For any queries, please email at

  15. Should children with inherited metabolic disorders receive varicella vaccination?

    LENUS (Irish Health Repository)

    Varghese, M


    The aim was to determine the rate of varicella infection and complications in children with disorders of intermediary metabolism (IEM) between the ages of 1 and 16 years attending our national metabolic referral centre. Of 126 children identified, a response was received from 122. A history of previous varicella infection was identified in 64 cases (53%) and of varicella vaccination in 5 (4%). Fifty-three (43%) patients apparently did not have a history of clinical varicella infection. Of the 64 children with a history of varicella infection, five required hospitalisation for complications, including life-threatening lactic acidosis in one patient with mitochondrial disease and metabolic decompensation in four patients. In conclusion, varicella infection may cause an increased risk of metabolic decompensation in patients with IEMs. We propose that a trial of varicella vaccination be considered for this cohort of patients with monitoring of its safety and efficacy.

  16. Duvernoy's gland secretion of Philodryas patagoniensis from the northeast of Argentina: its effects on blood coagulation. (United States)

    Peichoto, M E; Leiva, L C; Guaimás Moya, L E; Rey, L; Acosta, O


    Duvernoy's gland secretion of Philodryas patagoniensis exhibits high hemorrhagic activity, containing enzymes that are able to degrade the vascular wall. In this work we aim to determine if the secretion can also affect the hemostatic system by causing changes in blood coagulation. Procoagulant and coagulant activities were evaluated on plasma and fibrinogen, respectively. The delay in the thrombin clotting time of fibrinogen previously incubated with the secretion was also determined. Specific hydrolysis of fibrinogen and fibrin incubated with the secretion at different time intervals was shown by electrophoresis on polyacrylamide gel. To determine the structural characteristics of the enzymes degrading fibrinogen and fibrin, secretion were incubated in the presence of 45 mM Na(2)EDTA, 40 mM Benzamidine, and/or 2 mM PMSF before the incubation with fibrinogen or fibrin, respectively. The effect in vivo was investigated in adult male rats injected with different dose of secretion, aliquots of blood were withdrawn at different time intervals, and the fibrinogen concentration was determined. Duvernoy's gland secretion of P. patagoniensis did not clot plasma or fibrinogen. It exhibited a potent fibrinogenolytic activity degrading the Aalpha-chain faster than the Bbeta-chain, whereas gamma-chain was resistant. This latter corresponded with a strong delay in the thrombin clotting time of fibrinogen (4 mg/ml) pre-incubated with the secretion, being 9.53 microg the amount of protein from Duvernoy's gland secretion that increased the thrombin clotting time from 20 to 60 s. In vivo, the loss of rat plasma fibrinogen was proportional to the amount of secretion injected. The secretion also hydrolyzed fibrin degrading the alpha-monomer. Inhibition studies with Na(2)EDTA, Benzamidine, and/or PMSF showed that metalloproteinases and serinoproteinases are the main enzymes responsible for the hydrolyzing activity on fibrinogen and fibrin. All these results demonstrate that Duvernoy

  17. The feed gas composition determines the degree of physical plasma-induced platelet activation for blood coagulation (United States)

    Bekeschus, Sander; Brüggemeier, Janik; Hackbarth, Christine; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Partecke, Lars-Ivo; van der Linde, Julia


    Cold atmospheric (physical) plasma has long been suggested to be a useful tool for blood coagulation. However, the clinical applicability of this approach has not been addressed sufficiently. We have previously demonstrated the ability of a clinically accepted atmospheric pressure argon plasma jet (kINPen® MED) to coagulate liver incisions in mice with similar performance compared to the gold standard electrocauterization. We could show that plasma-mediated blood coagulation was dependent on platelet activation. In the present work, we extended on this by investigating kINPen®-mediated platelet activation in anticoagulated human donor blood ex vivo. With focus on establishing high-throughput, multi-parametric platelet activation assays and performing argon feed gas parameter studies we achieved the following results: (i) plasma activated platelets in heparinized but not in EDTA-anticoagulated blood; (ii) plasma decreased total platelet counts but increased numbers of microparticles; (iii) plasma elevated the expression of several surface activation markers on platelets (CD62P, CD63, CD69, and CD41/61); (iv) in platelet activation, wet and dry argon plasma outperformed feed gas admixtures with oxygen and/or nitrogen; (v) plasma-mediated platelet activation was accompanied by platelet aggregation. Platelet aggregation is a necessary requirement for blood clot formation. These findings are important to further elucidate molecular details and clinical feasibility of cold physical plasma-mediated blood coagulation.

  18. Effect of hemodilution on coagulation and recombinant factor VIIa efficacy in human blood in vitro. (United States)

    Darlington, Daniel N; Delgado, Angel V; Kheirabadi, Bijan S; Fedyk, Chriselda G; Scherer, Michael R; Pusateri, Anthony E; Wade, Charles E; Cap, Andrew P; Holcomb, John B; Dubick, Michael A


    This study evaluates the effect of hemodilution by various common resuscitation fluids, and the efficacy of activated recombinant factor VII (rFVIIa) on coagulation parameters in human blood in vitro. Samples from normal healthy volunteers (n = 9) were hemodiluted from 0% to 90% with normal saline, or 0%, 40%, 60%, and 80% with 5% albumin, Hespan, Hextend, normal saline, or lactated Ringer's, and incubated at 37°C ± 1°C for 30 minutes with and without rFVIIa (1.26 μg/mL). There was a strong correlation between the dilution of hemoglobin (Hb), platelets, or fibrinogen and coagulation parameters. Hemodilution 0% to 90% changed coagulation parameters (prothrombin time [PT], activated partial thromboplastin time [aPTT], and thromboelastography) in an exponential fashion; the greatest changes occurred after hemodilution lowered Hb time (K). Hemodilution with Hextend and Hespan decreased maximum amplitude and α angle >5% albumin, lactated Ringer's, or normal saline. rFVIIa significantly improved PT at 60% and 80% dilutions, and aPTT at 80% dilution. There was a significant effect of dilution, but not fluid type, on the efficacy of rFVIIa to change PT and aPTT, and the onset of clotting (R). We have strong in vitro evidence that Hb 5% albumin or the crystalloids. rFVIIa significantly decreased PT at all dilutions and aPTT at the highest dilution. The effectiveness of rFVIIa on PT and aPTT was significantly affected by the degree of dilution, but not by the type of fluid.

  19. Acoustic radiation force induced resonance elastography of coagulating blood: theoretical viscoelasticity modeling and ex vivo experimentation (United States)

    Bhatt, Manish; Montagnon, Emmanuel; Destrempes, François; Chayer, Boris; Kazemirad, Siavash; Cloutier, Guy


    Deep vein thrombosis is a common vascular disease that can lead to pulmonary embolism and death. The early diagnosis and clot age staging are important parameters for reliable therapy planning. This article presents an acoustic radiation force induced resonance elastography method for the viscoelastic characterization of clotting blood. The physical concept of this method relies on the mechanical resonance of the blood clot occurring at specific frequencies. Resonances are induced by focusing ultrasound beams inside the sample under investigation. Coupled to an analytical model of wave scattering, the ability of the proposed method to characterize the viscoelasticity of a mimicked venous thrombosis in the acute phase is demonstrated. Experiments with a gelatin-agar inclusion sample of known viscoelasticity are performed for validation and establishment of the proof of concept. In addition, an inversion method is applied in vitro for the kinetic monitoring of the blood coagulation process of six human blood samples obtained from two volunteers. The computed elasticity and viscosity values of blood samples at the end of the 90 min kinetics were estimated at 411  ±  71 Pa and 0.25  ±  0.03 Pa · s for volunteer #1, and 387  ±  35 Pa and 0.23  ±  0.02 Pa · s for volunteer #2, respectively. The proposed method allowed reproducible time-varying thrombus viscoelastic measurements from samples having physiological dimensions.

  20. Laser speckle contrast imaging of skin blood perfusion responses induced by laser coagulation

    Energy Technology Data Exchange (ETDEWEB)

    Ogami, M; Kulkarni, R; Wang, H; Reif, R; Wang, R K [University of Washington, Department of Bioengineering, Seattle, Washington 98195 (United States)


    We report application of laser speckle contrast imaging (LSCI), i.e., a fast imaging technique utilising backscattered light to distinguish such moving objects as red blood cells from such stationary objects as surrounding tissue, to localise skin injury. This imaging technique provides detailed information about the acute perfusion response after a blood vessel is occluded. In this study, a mouse ear model is used and pulsed laser coagulation serves as the method of occlusion. We have found that the downstream blood vessels lacked blood flow due to occlusion at the target site immediately after injury. Relative flow changes in nearby collaterals and anastomotic vessels have been approximated based on differences in intensity in the nearby collaterals and anastomoses. We have also estimated the density of the affected downstream vessels. Laser speckle contrast imaging is shown to be used for highresolution and fast-speed imaging for the skin microvasculature. It also allows direct visualisation of the blood perfusion response to injury, which may provide novel insights to the field of cutaneous wound healing. (laser biophotonics)

  1. The effect of corn trypsin inhibitor and inhibiting antibodies for FXIa and FXIIa on coagulation of plasma and whole blood. (United States)

    Hansson, K M; Nielsen, S; Elg, M; Deinum, J


    Corn trypsin inhibitor (CTI), an inhibitor of FXIIa, is used to prevent plasma coagulation by contact activation, to specifically investigate tissue factor (TF)-initiated coagulation. In the present work the specificity of CTI for factor (F) XIIa is questioned. In the commercial available plasma coagulation assays CTI was found to double activated partial thromboplastin time (APTT) at a plasma concentration of 7.3 ± 1.5 μm CTI (assay concentration 2.4 μm). No effect was found on the prothrombin time (PT) when high TF concentrations were used. Also, with specific antibodies for FXIIa and for FXIa only APTT was found to be extended but not PT. With specific enzyme assays using chromogenic substrates CTI was shown to be a strong inhibitor of FXIIa and a competitive inhibitor of FXIa with Ki  = 8.1 ± 0.3 μm, without effect on the coagulation factors FVIIa, FIXa, FXa and thrombin. In thrombin generation and coagulation (free oscillation rheometry, FOR) assays, initiated with low TF concentrations, no effect of CTI (plasma concentrations of 4.4 and 13.6 μm CTI, 25 resp. 100 mg L(-1) in blood) was found with ≥ 1 pm TF. At ≤ 0.1 pm TF in the FOR whole blood assay the coagulation time (CT) concentration dependently increased while the plasma CT became longer than the observation time. To avoid inhibition of FXIa and the thrombin feedback loop we recommend that for coagulation assays the concentration of CTI in blood should be below 20 mg L(-1) (1.6 μm) and in plasma below 3 μm. © 2014 International Society on Thrombosis and Haemostasis.

  2. Spectrum Of Inherited Metabolic Disorders In Pakistani Children Presenting At A Tertiary Care Centre

    International Nuclear Information System (INIS)

    Cheema, H. A.; Malik, H. S.; Parkash, A.; Fayyaz, Z.


    Objective: To determine the frequency, presentation and outcome of various inherited metabolic diseases in children presenting in a tertiary care hospital, Lahore, Pakistan. Study Design: An observational study. Place and Duration of Study: Gastroenterology, Hepatology and Nutrition Department of The Children Hospital and Institute of Child Health, Lahore, from January 2011 to October 2014. Methodology: All children aged < 14 years with high suspicion of a metabolic disorder were inducted. Routine and radiological investigation were carried out at the study place. Comprehensive diagnostic testing of particular metabolic disorder was sent abroad. Those with a specific metabolic disorder were included in the study while those with normal metabolic work-up were excluded. All data was collected on preformed proforma. Result: A total of 239 patients were enrolled. Nineteen different types of inherited metabolic disorders were diagnosed in 180 patients; age ranged from 8 days to 14 years. Consanguinity was positive in 175 (97 percentage) among the parents of the affected children, with previously affected siblings in 64 (35.5 percentage). The most frequent disorders were inherited disorders of carbohydrate metabolism (92, 51 percentage), lipid storage disease (59, 32.7 percentage), organic acidemia and energy defects (18, 10 percentage), amino acid disorder (6, 3.3 percentage), and miscellaneous (4, 2.2 percentage). Fifty-eight (32.2 percentage) presented with acute metabolic crisis, 28 (15.5 percentage) patients presented with early onset liver failure, and 24 (13.3 percentage) with mental retardation. Out of these, 16 (8.8 percentage) expired. Conclusion: Glycogen storage disorders being the commonest followed by Gaucher disease and Galactosemia. The associated complications resulted in high morbidity and mortality. (author)

  3. Interferon-free treatment of chronic hepatitis C virus infection in patients with inherited bleeding disorders. (United States)

    Wiegand, Johannes; Schiefke, Ingolf; Stein, Kerstin; Berg, Thomas; Kullig, Ulrike; Ende, Katrin


    Chronic hepatitis C virus (HCV) infection causes significant mortality in patients with inherited bleeding disorders, however, data of interferon-free antiviral regimes are scarce in this population. Real-life data of interferon-free therapies of 18 patients with inherited bleeding disorders and chronic HCV genotype 1 infection (94% male, liver cirrhosis Child A/B n = 4/1). Treatment naïve patients were treated for eight weeks with sofosbuvir (SOF)/ledipasvir (n = 3) or for 12 weeks with SOF/ledipasvir (n = 4), SOF/ledipasvir/ribavirin (n = 1), or paritaprevir/r, ombitasvir, dasabuvir (n = 1). Treatment experienced patients without cirrhosis received SOF/ledipasvir (n = 3) or paritaprevir/r, ombitasvir, dasabuvir ± ribavirin (n = 2) for 12 weeks. Re-treated cirrhotic individuals were treated for 24 weeks with SOF/ledipasvir (n = 2) and SOF/daclatasvir (n = 1), or for 12 weeks SOF/simeprevir/1200 mg/d ribavirin (n = 1). Sustained virologic response (SVR-12) was achieved by 17/18 individuals without severe on-treatment side effects. In real-life, HCV-infected patients with inherited bleeding disorders can be effectively and safely treated with interferon-free therapies.

  4. [Determination of fibrinogen content in human blood plasma using thrombin-like enzyme of ancistron N and analysis of hemostasis under presence of blood coagulation inhibitors]. (United States)

    Platonova, T N; Sushko, O O; Colovĭov, D O; Iena, Ia M


    The cases of non-coagulation or only partial coagulation of blood plasma fibrinogen under the effect of thrombin have been revealed while examining the homeostasis-state in practically healthy elderly and old people and those with hypertonic disease. These cases have been analyzed. It is shown that the suggested method of fibrinogen determination in blood plasma using thrombin-like enzyme ancistrone-H extracted from venom of snakes (Agkistrodon halys halys) permits determining the fibrinogen content in blood plasma even in the cases connected with the presence of circulating coagulation inhibitors in plasma. The determination is not hindered by the introduction of exogenous heparin, including low-molecular heparins of the fraxiparin type.

  5. Extraction of mRNA from coagulated horse blood and analysis of inflammation-related cytokine responses to coagulation

    DEFF Research Database (Denmark)

    Bovbjerg, Kirsten Katrine Lindegaard; Heegaard, Peter M. H.; Skovgaard, Kerstin


    available. Here, a protocol for RNA extraction from highly clotted blood was optimized and the regulation of a number of cytokine genes compared to stabilized blood was studied. Whole blood samples from 10 clinically healthy horses were incubated for 24 hours at 37°C and RNA was extracted from...

  6. [Diagnosis and therapy of blood coagulation disorders in intrahepatic cholestasis]. (United States)

    Herre, H D; Engelmann, C; Wiken, H P


    The reduction of prothrombin level below 5% in a patient with intrahepatic cholestasis of pregnancy is reported. The necessity of controlling the Quick level or better factors II, VII, IX and X is discussed. A well-timed Vitamin K therapy in all cases with impaired secretion of bile during pregnancy is recommended.

  7. Food triggers and inherited metabolic disorders: a challenge to the pediatrician. (United States)

    Maines, Evelina; Di Palma, Annunziata; Burlina, Alberto


    Several disorders should be considered in the case of newborns and infants experiencing acute or recurrent symptoms after food ingestion. Immune-mediated adverse food reactions are the most frequent and always to be considered. Nevertheless, in the extensive differential diagnosis, clinicians should also include inherited metabolic disorders (IMDs).This review reports clinical features and diagnostic aspects of the most common IMDs that may present with acute manifestations triggered by food intake. Major focus will be amino acid and protein metabolism defects and carbohydrate disorders.Nowadays, for many of these disorders the risk of an acute presentation triggered by food has been decreased by the introduction of expanded newborn screening (NBS). Nevertheless, clinical suspicion remains essential because some IMDs do not have still reliable markers for NBS and a false negative screening result may occur.The aim of this review is to help pediatricians to take these rare inherited disorders into account in the differential diagnosis of acute or recurrent gastrointestinal symptoms related to food intake, which may avoid delayed diagnosis and potentially life-threatening consequences.

  8. Effects of astaxanthin on blood coagulation, fibrinolysis and platelet aggregation in hyperlipidemic rats. (United States)

    Deng, Zu-Yue; Shan, Wei-Guang; Wang, Shen-Feng; Hu, Meng-Mei; Chen, Yan


    Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear. The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats. Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively. ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold). ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats

  9. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

    DEFF Research Database (Denmark)

    Højlund, Kurt


    . These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

  10. Viscoelastic blood coagulation measurement with Sonoclot predicts postoperative bleeding in cardiac surgery after heparin reversal. (United States)

    Bischof, Dominique B; Ganter, Michael T; Shore-Lesserson, Linda; Hartnack, Sonja; Klaghofer, Richard; Graves, Kirk; Genoni, Michele; Hofer, Christoph K


    The aim of the study was to determine if Sonoclot with its sensitive glass bead-activated, viscoelastic test can predict postoperative bleeding in patients undergoing cardiac surgery at predefined time points. A prospective, observational clinical study. A teaching hospital, single center. Consecutive patients undergoing cardiac surgery (N = 300). Besides routine laboratory coagulation studies and heparin management with standard (kaolin) activated clotting time, additional native blood samples were analyzed on a Sonoclot using glass bead-activated tests. Glass bead-activated clotting time, clot rate, and platelet function were recorded immediately before anesthesia induction and at the end of surgery after heparin reversal but before chest closure. Primary outcome was postoperative blood loss (chest tube drainage at 4, 8, and 12 hours postoperatively). Secondary outcome parameters were transfusion requirements, need for surgical re-exploration, time of mechanical ventilation, length of intensive care unit and hospital stay, and hospital morbidity and mortality. Patients were categorized into "bleeders" and "nonbleeders." Patient characteristics, operations, preoperative standard laboratory parameters, and procedural times were comparable between bleeders and nonbleeders except for sex and age. Bleeders had higher rates of transfusions, surgical re-explorations, and complications. Only glass bead measurements by Sonoclot after heparin reversal before chest closure but not preoperatively were predictive for increased postoperative bleeding. Sonoclot with its glass bead-activated tests may predict the risk for postoperative bleeding in patients undergoing cardiac surgery at the end of surgery after heparin reversal but before chest closure. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Comparison of pneumatic tube system with manual transport for routine chemistry, hematology, coagulation and blood gas tests. (United States)

    Pupek, Alex; Matthewson, Beverly; Whitman, Erin; Fullarton, Rachel; Chen, Yu


    The pneumatic tube system (PTS) is commonly used in modern clinical laboratories to provide quick specimen delivery. However, its impact on sample integrity and laboratory testing results are still debatable. In addition, each PTS installation and configuration is unique to its institution. We sought to validate our Swisslog PTS by comparing routine chemistry, hematology, coagulation and blood gas test results and sample integrity indices between duplicate samples transported either manually or by PTS. Duplicate samples were delivered to the core laboratory manually by human courier or via the Swisslog PTS. Head-to-head comparisons of 48 routine chemistry, hematology, coagulation and blood gas laboratory tests, and three sample integrity indices were conducted on 41 healthy volunteers and 61 adult patients. The PTS showed no impact on sample hemolysis, lipemia, or icterus indices (all pcoagulation and blood gas (in syringe and capillary tube) laboratory tests.

  12. In-traffic air pollution exposure and CC16, blood coagulation, and inflammation markers in healthy adults. (United States)

    Zuurbier, Moniek; Hoek, Gerard; Oldenwening, Marieke; Meliefste, Kees; Krop, Esmeralda; van den Hazel, Peter; Brunekreef, Bert


    Exposure to traffic-related air pollution is a risk factor for cardiovascular events, probably involving mechanisms of inflammation and coagulation. Little is known about effects of the short exposures encountered while participating in traffic. The objective of the study was to examine effects of exposure of commuters to air pollution on cardiovascular biomarkers. Thirty-four healthy adult volunteers commuted for 2 hr by bus, car, or bicycle during the morning rush hour. During the commute, exposure to particle number, particulate matter (PM) ≤ 2.5 µm in aerodynamic diameter (PM2.5), PM ≤ 10 µm in diameter (PM10), and soot was measured. We estimated inhaled doses based on heart rate monitoring. Shortly before exposure and 6 hr after exposure, blood samples were taken and analyzed for CC16 (Clara cell protein 16), blood cell count, coagulation markers, and inflammation markers. Between June 2007 and June 2008, 352 pre- and postexposure blood samples were collected on 47 test days. We used mixed models to analyze the associations between exposure and changes in health parameters. We observed no consistent associations between the air pollution exposures and doses and the various biomarkers that we investigated. Air pollution exposure during commuting was not consistently associated with acute changes in inflammation markers, blood cell counts, or blood coagulation markers.

  13. Blood Coagulation and Acid-Base Balance at Craniocerebral Hypothermia in Patients with Severe Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    V. E. Avakov


    Full Text Available Systemic therapeutic hypothermia has gained a negative reputation in treating multiple trauma patients and is regarded as one of the factors in the lethal triad of shock, acidosis, and hypothermia. This fact owes to no relationship between acidosis and hypothermia; the effects of the latter on coagulation are evident and complexly reversible in the presence of acidosis.Objective: to determine the impact of noninvasive local brain cooling on the metabolic and blood coagulation indicators of a patient with acute cerebral ischemia.Subjects and methods. The subjects of the study were 113 patients with severe brain injury, including that complicated by the involvement of stem structures, who underwent brain cooling in different modifications. In so doing, the val ues of acidbase balance and coagulation system in arterial and venous blood were investigated.Results. Local brain hypother mia was not found to affect coagulation while the baseline negative values of excess buffer bases showed positive values (a right shift by the end of cooling. Recommendations were given to prevent metabolic shifts.Conclusion. Patients at very high risk for bleeding may be safely cooled to a brain temperature of 32—34°C even in the presence of moderatetosevere acidosis. This is a great advantage of local hypothermia over systemic one.

  14. Midterm outcome of valve-sparing aortic root replacement in inherited connective tissue disorders. (United States)

    Tanaka, Hiroshi; Ogino, Hitoshi; Matsuda, Hitoshi; Minatoya, Kenji; Sasaki, Hiroaki; Iba, Yutaka


    This study determined the midterm outcome of valve-sparing aortic root replacement for patients with inherited connective tissue disorders. From 1993 to 2008, 94 patients underwent valve-sparing aortic root replacement. Sixty patients (64%), average age 33 years (range, 15 to 61 years), had inherited connective tissue disorders: Marfan syndrome, 54 (92%); Loeys-Dietz syndrome, 5 (8%); and smooth muscle α-actin (ACTA2) mutation in 1. Median preoperative sinus diameter was 52 mm (range, 42 to 76 mm), and moderate/severe aortic regurgitation was present in 14 (23%). Seven (12%, 1993 to 1999) underwent remodeling procedures, and 53 had reimplantation procedures. Cusp repair was performed in 4. Median follow-up was 55 months (range, 1 to 149 months). There were 15 patients in the early term (1993 to 2000) and 45 in the late term (2001 to 2008). Four late deaths occurred (cardiac, 3; aortic, 1), with 10-year survival of 86%. Rates of freedom from aortic valve replacement at 5 and 10 years were 85% and 58% in remodeling and 96% and 58% in reimplantation. Risk factors for reoperations were postprocedure intraoperative aortic insufficiency greater than mild (p = 0.046), remodeling procedure (p = 0.016), and early term (p = 0.0002). One patient (2%) with none/trivial postprocedure aortic insufficiency required aortic valve replacement. Freedom from reoperation in patients with none/trivial postprocedure aortic insufficiency at 5 and 10 years was 100% and 67%. Meticulous control of aortic insufficiency during operation would bring favorable midterm durability in valve-sparing aortic root replacement using a reimplantation technique, even in patients with inherited connective tissue disorders. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Clinical Implications of Digenic Inheritance and Epistasis in Primary Immunodeficiency Disorders

    Directory of Open Access Journals (Sweden)

    Rohan Ameratunga


    Full Text Available The existence of epistasis in humans was first predicted by Bateson in 1909. Epistasis describes the non-linear, synergistic interaction of two or more genetic loci, which can substantially modify disease severity or result in entirely new phenotypes. The concept has remained controversial in human genetics because of the lack of well-characterized examples. In humans, it is only possible to demonstrate epistasis if two or more genes are mutated. In most cases of epistasis, the mutated gene products are likely to be constituents of the same physiological pathway leading to severe disruption of a cellular function such as antibody production. We have recently described a digenic family, who carry mutations of TNFRSF13B/TACI as well as TCF3 genes. Both genes lie in tandem along the immunoglobulin isotype switching and secretion pathway. We have shown they interact in an epistatic way causing severe immunodeficiency and autoimmunity in the digenic proband. With the advent of next generation sequencing, it is likely other families with digenic inheritance will be identified. Since digenic inheritance does not always cause epistasis, we propose an epistasis index which may help quantify the effects of the two mutations. We also discuss the clinical implications of digenic inheritance and epistasis in humans with primary immunodeficiency disorders.

  16. Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure

    International Nuclear Information System (INIS)

    Lombó, Marta; Fernández-Díez, Cristina; González-Rojo, Silvia; Navarro, Claudia; Robles, Vanesa; Herráez, María Paz


    Bisphenol A (BPA) is an endocrine disruptor used in manufacturing of plastic devices, resulting in an ubiquitous presence in the environment linked to human infertility, obesity or cardiovascular diseases. Both transcriptome and epigenome modifications lie behind these disorders that might be inherited transgenerationally when affecting germline. To assess potential effects of paternal exposure on offspring development, adult zebrafish males were exposed to BPA during spermatogenesis and mated with non-treated females. Results showed an increase in the rate of heart failures of progeny up to the F2, as well as downregulation of 5 genes involved in cardiac development in F1 embryos. Moreover, BPA causes a decrease in F0 and F1 sperm remnant mRNAs related to early development. Results reveal a paternal inheritance of changes in the insulin signaling pathway due to downregulation of insulin receptor β mRNAs, suggesting a link between BPA male exposure and disruption of cardiogenesis in forthcoming generations. - Highlights: • We examine the effects of adult male exposure to BPA on the progeny (F1 and F2). • Paternal exposure promotes similar cardiac malformations to those caused by direct exposure. • BPA applied during spermatogenesis decrease the insra and insrb transcripts in spermatozoa. • Sperm insrb transcript controls embryonic expression being the downregulation inherited by F1. • Paternal BPA exposure impairs heart development in F1 and F2 disrupting insulin signaling pathway. - Paternal bisphenol A exposure impairs cardiac development throughout generations.

  17. Contact activation of blood coagulation on a defined kaolin/collagen surface in a microfluidic assay. (United States)

    Zhu, Shu; Diamond, Scott L


    Generation of active Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular thrombosis. We developed a patterned kaolin (0 to 0.3 pg/μm(2))/type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level of 4 μg/mL of the XIIa inhibitor, corn trypsin inhibitor) drove platelet deposition followed by fibrin formation. At venous wall shear rate (100 s(-1)), kaolin accelerated onset of fibrin formation by ~100 sec when compared to collagen alone (250 sec vs. 350 sec), with little effect on platelet deposition. Even with kaolin present, arterial wall shear rate (1000 s(-1)) delayed and suppressed fibrin formation compared to venous wall shear rate. A comparison of surfaces for extrinsic activation (tissue factor TF/collagen) versus contact activation (kaolin/collagen) that each generated equal platelet deposition at 100 s(-1) revealed: (1) TF surfaces promoted much faster fibrin onset (at 100 sec) and more endpoint fibrin at 600 sec at either 100 s(-1) or 1000 s(-1), and (2) kaolin and TF surfaces had a similar sensitivity for reduced fibrin deposition at 1000 s(-1) (compared to fibrin formed at 100 s(-1)) despite differing coagulation triggers. Anti-platelet drugs inhibiting P2Y1, P2Y12, cyclooxygenase-1 or activating IP-receptor or guanylate cyclase reduced platelet and fibrin deposition on kaolin/collagen. Since FXIIa or FXIa inhibition may offer safe antithrombotic therapy, especially for biomaterial thrombosis, these defined collagen/kaolin surfaces may prove useful in drug screening tests or in clinical diagnostic assays of blood under flow conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Application of Molecular Genetics to the Investigation of Inherited Bleeding Disorders

    DEFF Research Database (Denmark)

    Lethagen, Stefan Rune; Dunø, Morten; Nielsen, Lars Bo


    22. In hemophilia B, more than 1100 unique F9 mutations have been described scattered all over the gene. Carrier analysis, genetic counseling, prenatal and pre-implantation genetic diagnosis are all based on correct identifying the disease-causing mutation. Linkage analysis can be considered when...... the causative mutation is unknown. More rare bleeding disorders are generally recessively inherited, and are often caused by mutations that are specific for individual families, and mutations are scattered throughout the genes. Laboratories performing molecular genetic analyses must have validated internal...

  19. Pulsed cold plasma-induced blood coagulation and its pilot application in stanching bleeding during rat hepatectomy (United States)

    Keping, YAN; Qikang, JIN; Chao, ZHENG; Guanlei, DENG; Shengyong, YIN; Zhen, LIU


    This paper presents plasma-induced blood coagulation and its pilot application in rat hepatectomy by using a home-made pulsed cold plasma jet. Experiments were conducted on blood coagulation in vitro, the influence of plasma on tissue in vivo, and the pilot application of rat hepatectomy. Experimental results show that the cold plasma can lead to rapid blood coagulation. Compared with the control sample, the plasma-induced agglomerated layer of blood is thicker and denser, and is mostly composed of broken platelets. When the surface of the liver was treated by plasma, the influence of the plasma can penetrate into the liver to a depth of about 500 μm. During the rat hepatectomy, cold plasma was proved to be effective for stanching bleeding on incision. No obvious bleeding was found in the abdominal cavities of all six rats 48 h after the hepatectomy. This implies that cold plasma can be an effective modality to control bleeding during surgical operation.

  20. Massive Exploration of Perturbed Conditions of the Blood Coagulation Cascade through GPU Parallelization

    Directory of Open Access Journals (Sweden)

    Paolo Cazzaniga


    high-performance computing solutions is motivated by the need of performing large numbers of in silico analysis to study the behavior of biological systems in different conditions, which necessitate a computing power that usually overtakes the capability of standard desktop computers. In this work we present coagSODA, a CUDA-powered computational tool that was purposely developed for the analysis of a large mechanistic model of the blood coagulation cascade (BCC, defined according to both mass-action kinetics and Hill functions. coagSODA allows the execution of parallel simulations of the dynamics of the BCC by automatically deriving the system of ordinary differential equations and then exploiting the numerical integration algorithm LSODA. We present the biological results achieved with a massive exploration of perturbed conditions of the BCC, carried out with one-dimensional and bi-dimensional parameter sweep analysis, and show that GPU-accelerated parallel simulations of this model can increase the computational performances up to a 181× speedup compared to the corresponding sequential simulations.

  1. Progestational agents and blood coagulation. IV. Changes induced by progestogen alone. (United States)

    Mink, I B; Courey, N G; Moore, R H; Ambrus, C M; Ambrus, J L


    To evaluate the effects of chlormadinone acetate upon the coagulation of blood and fibrinolysin systems, 35 healthy, young women voluntarily using some form of birth control were studied. 10 women who served as controls used intrauterine devices; 25 women took either a progestin-estrogen (1 mg norethindrone acetate and 1 mg mestranol) combination or a synthetic progestational agent (0.5 mg chlormadinone acetate) on a coded, double-blind basis. Platelet counts, thrombelastograms, and plasma assays were performed prior to and after 3 and 6 months of treatment. After 3 months, those taking progestin-estrogen showed a highly significant increase toward hypercoagulability in Quick time, Factors II, VII, and X, and increased levels in the thromboplastin generation time (TGT), Factors V and IX, and plasminogen. At 6 months all levels remained elevated except for TGT. Those on chlormadinone acetate had only a slightly significant change toward hypercoagulability in Quick time and Factor VIII, an increase in Factor IX, and a decrease in Factor X. In the control group only TGT was elevated. The progestin alone induced only minimal changes in comparison to the marked rises accompanied with progestin-estrogen therapy.

  2. [The pathogenesis of subclinical laminitis in dairy cattle: studies of the hoof status, rumen status and blood coagulation factors]. (United States)

    Brandejsky, F; Stanek, C; Schuh, M


    In 50 dairy cows of the breed "Braunvieh" (36 heifers, 14 cows) of one herd the claw score was recorded over a period of 2 months before parturition until 6 months after parturition. The claw scores were correlated with the clinical findings, the ruminal function and the blood coagulation factors calcium-thromboplastin (TPZ), partial thromboplastin time (PTT), thrombin time (TZ) and antithrombin III (AT III) evaluated one day and one week after calving. The claw score increased from the first to the second examination, remaining on the same level in the postpartal period. No correlation between the claw scores and the ruminal function was evident. In comparison with a control group, TPZ and PTT were found higher one day and one week after parturition in the experimental group. Blood coagulation factors and claw scores were found uncorrelated.

  3. Clinical validation of targeted next-generation sequencing for inherited disorders. (United States)

    Yohe, Sophia; Hauge, Adam; Bunjer, Kari; Kemmer, Teresa; Bower, Matthew; Schomaker, Matthew; Onsongo, Getiria; Wilson, Jon; Erdmann, Jesse; Zhou, Yi; Deshpande, Archana; Spears, Michael D; Beckman, Kenneth; Silverstein, Kevin A T; Thyagarajan, Bharat


    Although next-generation sequencing (NGS) can revolutionize molecular diagnostics, several hurdles remain in the implementation of this technology in clinical laboratories. To validate and implement an NGS panel for genetic diagnosis of more than 100 inherited diseases, such as neurologic conditions, congenital hearing loss and eye disorders, developmental disorders, nonmalignant diseases treated by hematopoietic cell transplantation, familial cancers, connective tissue disorders, metabolic disorders, disorders of sexual development, and cardiac disorders. The diagnostic gene panels ranged from 1 to 54 genes with most of panels containing 10 genes or fewer. We used a liquid hybridization-based, target-enrichment strategy to enrich 10 067 exons in 568 genes, followed by NGS with a HiSeq 2000 sequencing system (Illumina, San Diego, California). We successfully sequenced 97.6% (9825 of 10 067) of the targeted exons to obtain a minimum coverage of 20× at all bases. We demonstrated 100% concordance in detecting 19 pathogenic single-nucleotide variations and 11 pathogenic insertion-deletion mutations ranging in size from 1 to 18 base pairs across 18 samples that were previously characterized by Sanger sequencing. Using 4 pairs of blinded, duplicate samples, we demonstrated a high degree of concordance (>99%) among the blinded, duplicate pairs. We have successfully demonstrated the feasibility of using the NGS platform to multiplex genetic tests for several rare diseases and the use of cloud computing for bioinformatics analysis as a relatively low-cost solution for implementing NGS in clinical laboratories.

  4. Effect of Maixuekang capsule therapy on optic nerve function, blood coagulation function and cytokines in diabetic optic neuropathy

    Directory of Open Access Journals (Sweden)

    Ya-Li Hao


    Full Text Available Objective: To analyze the effect of Maixuekang capsule therapy on optic nerve function, blood coagulation function and cytokines in diabetic optic neuropathy. Methods: A total of 55 patients (82 eyes with diabetic optic neuropathy treated in our hospital between December 2013 and December 2015 were selected, and according to different therapeutic methods, they were divided into observation group (n=38 (49 eyes who received Maixuekang therapy and control group (n=17 (33 eyes who received compound vitamin therapy. Differences in optic nerve function, blood coagulation function and cytokine content were compared between two groups after 3 months of treatment. Results: After 3 months of treatment, optic nerve function indexes MS, RNFL thickness and AP100 levels of observation group were higher than those of control group while MD and LP100 levels were lower than those of control group; blood coagulation indexes WBV, PV and FBG levels were lower than those of control group while TT, PT and APTT levels were higher than those of control group; thrombelastogram parameters R value and K value levels were higher than those of control group while α angle, MA and CI levels were lower than those of control group; oxidative stress indexes ROS, MDA and CAT content in serum were lower than those of control group while SOD content was higher than that of control group. Conclusions: Maixuekang capsule can significantly optimize the optic nerve function in patients with DON, which is specifically directly related to its anticoagulation and anti-oxidative stress effect.

  5. Establishment of the 2nd Korean national biological reference standard for blood coagulation factor VIII:C concentrate. (United States)

    Lee, Naery; Seo, Ji Suk; Kim, Jae Ok; Ban, Sang Ja


    Since the 1st Korean national biological reference standard for factor (F)VIII concentrate, established in 2001, has shown declining potency, we conducted this study to replace this standard with a 2nd Korean national biological reference standard for blood coagulation FVIII concentrate. The candidate materials for the 2nd standard were prepared in 8000 vials with 10 IU/ml of target potency, according to the approved manufacturing process of blood coagulation Factor VIII:C Monoclonal Antibody-purified, Freeze-dried Human Blood Coagulation Factor VIII:C. Potency was evaluated by one-stage clotting and chromogenic methods and the stability was confirmed to meet the specifications during a period of 73 months. Since the potencies obtained by the two methods differed significantly (P < 0.015), the values were determined separately according to the geometric means (8.9 and 7.4 IU/vial, respectively). The geometric coefficients of interlaboratory variability were 3.4% and 7.6% by the one-stage clotting and chromogenic assays, respectively. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  6. Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies. (United States)

    Fornaguera, Cristina; Calderó, Gabriela; Mitjans, Montserrat; Vinardell, Maria Pilar; Solans, Conxita; Vauthier, Christine


    The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising alternative for delivery of drugs to specific cells. However, studies on their interaction with diverse blood components using different techniques are still lacking. Therefore, in the present work, the interaction of PLGA nanoparticles with blood components was described using different complementary techniques. The influence of different encapsulated compounds/functionalizing agents on these interactions was also reported. It is worth noting that all these techniques can be simply performed, without the need for highly sophisticated apparatus or skills. Moreover, their transference to industries and application of quality control could be easily performed. Serum albumin was adsorbed onto all types of tested nanoparticles. The saturation concentration was dependent on the nanoparticle size. In contrast, fibrinogen aggregation was dependent on nanoparticle surface charge. The complement activation was also influenced by the nanoparticle functionalization; the presence of a functionalizing agent increased complement activation, while the addition of an encapsulated compound only caused a slight increase. None of the nanoparticles influenced the coagulation cascade at low concentrations. However, at high concentrations, cationized nanoparticles did activate the coagulation cascade. Interactions of nanoparticles with erythrocytes did not reveal any hemolysis. Interactions of PLGA nanoparticles with blood proteins depended both on the nanoparticle properties and the protein studied. Independent of their loading/surface functionalization, PLGA nanoparticles did not influence the coagulation cascade and did not induce hemolysis of erythrocytes; they could be defined as safe concerning induction of embolization and cell lysis.

  7. Effects of Blood Coagulate Removal Method on Aedes albopictus (Diptera: Culicidae) Life Table Characteristics and Vector Competence for Dengue Virus. (United States)

    van Dodewaard, Caitlin A M; Richards, Stephanie L; Harris, Jonathan W


    Commercially available blood can be used as an alternative to live animals to maintain mosquito colonies and deliver infectious bloodmeals during research studies. We analyzed the extent to which two methods for blood coagulate removal (defibrination or addition of sodium citrate) affected life table characteristics (i.e., fecundity, fertility, hatch rate, and adult survival) and vector competence (infection, dissemination, and transmission) of Aedes albopictus (Skuse) for dengue virus (DENV). Two types of bovine blood were tested at two extrinsic incubation temperatures (27 or 30°C) for DENV-infected and uninfected mosquitoes. Fully engorged mosquitoes were transferred to individual cages containing an oviposition cup and a substrate. Eggs (fecundity) and hatched larvae (fertility) were counted. At 14 and 21 d post feeding on a DENV-infected bloodmeal, 15 mosquitoes were sampled from each group, and vector competence was analyzed (bodies [infection], legs [dissemination], and saliva [transmission]). Differences in life table characteristics and vector competence were analyzed for mosquitoes fed blood processed using different methods for removal of coagulates. The method for removal of coagulates significantly impacted fecundity, fertility, and hatch time in the uninfected group, but not DENV-infected group. Infected mosquitoes showed significantly higher fecundity and faster hatch time than uninfected mosquitoes. We show no significant differences in infection or dissemination rates between groups; however, horizontal transmission rate was significantly higher in mosquitoes fed DENV-infected citrated compared with defibrinated blood. We expect the findings of this study to inform research using artificial blood delivery methods to assess vector competence. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email:

  8. Interaction of blood coagulation factor Va with phospholipid vesicles examined by using lipophilic photoreagents

    International Nuclear Information System (INIS)

    Krieg, U.C.; Isaacs, B.S.; Yemul, S.S.; Esmon, C.T.; Bayley, H.; Johnson, A.E.


    Two different lipophilic photoreagents, [ 3 H]adamantane diazirine and 3-(trifluoromethyl)-3-(m-[ 125 I]iodophenyl)diazirine (TID), have been utilized to examine the interactions of blood coagulation factor Va with calcium, prothrombin, factor Xa, and, in particular, phospholipid vesicles. With each of these structurally dissimilar reagents, the extent of photolabeling of factor Va was greater when the protein was bound to a membrane surface than when it was free in solution. Specifically, the covalent photoreaction with Vl, the smaller subunit of factor Va, was 2-fold higher in the presence of phosphatidylcholine/phosphatidylserine (PC/PS, 3:1) vesicles, to which factor Va binds, than in the presence of 100% PC vesicles, to which the protein does not bind. However, the magnitude of the PC/PS-dependent photolabeling was much less than has been observed previously with integral membrane proteins. It therefore appears that the binding of factor Va to the membrane surface exposes Vl to the lipid core of the bilayer, but that only a small portion of the Vl polypeptide is exposed to, or embedded in, the bilayer core. Addition of either prothrombin or active-site-blocked factor Xa to PC/PS-bound factor Va had little effect on the photolabeling of Vl with TID, but reduced substantially the covalent labeling of Vh, the larger subunit of factor Va. This indicates that prothrombin and factor Xa each cover nonpolar surfaces on Vh when the macromolecules associate on the PC/PS surface. It therefore seems likely that the formation of the prothrombinase complex involves a direct interaction between Vh and factor Xa and between Vh and prothrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Novel aspects of blood coagulation factor XIII. I. Structure, distribution, activation, and function

    Energy Technology Data Exchange (ETDEWEB)

    Muszbek, L.; Adany, R. [Univ. Medical School of Debrecen (Hungary); Mikkola, H. [Univ. of Helsinki (Finland)


    Blood coagulation factor XIII (FXIII) is a protransglutaminase that becomes activated by the concerted action of thrombin and Ca{sup 2+} in the final stage of the clotting cascade. In addition to plasma, FXIII also occurs in platelets, monocytes, and monocyte-derived macrophages. While the plasma factor is a heterotetramer consisting of paired A and B subunits (A{sub 2}B{sub 2}), its cellular counterpart lacks the B subunits and is a homodimer of potentially active A subunits (A{sub 2}). The gene coding for the A and B subunits has been localized to chromosomes 6p24-25 and 1q31-32.1, respectively. The genomic as well as the primary protein structure of both subunits has been established. Plasma FXIII circulates in association with its substrate precursor, fibrinogen. Fibrin(ogen) has an important regulatory role in the activation of plasma FXIII, for instance the proteolytic removal of activation peptide by thrombin, the dissociation of subunits A and B, and the exposure of the originally buried active site on the free A subunits. The end result of this process is the formation of an active transglutaminase, which crosslinks peptide chains through {epsilon}({gamma}-glutamyl)lysyl isopeptide bonds. The protein substrates of activated FXIII include components of the clotting-fibrinolytic system, adhesive and contractile proteins. The main physiological function of plasma FXIII is to cross-link fibrin and protect it from the fibrinolytic enzyme plasmin. The latter effect is achieved mainly by covalently linking {alpha}{sub 2} antiplasmin, the most potent physiological inhibitor of plasmin, to fibrin. Plasma FXIII seems to be involved in wound healing and tissue repair, and it is essential to maintaining pregnancy. Cellular FXIII, if exposed to the surface of the cells, might support or perhaps take over the hemostatic functions of plasma FXIII; however, its intracellular role has remained mostly unexplored. 328 refs., 4 figs.

  10. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. (United States)

    Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A


    Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM ( is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

  11. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik


    ) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation......Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD...... stability of activation loop 3. Altogether, our findings strongly support an allosteric activation mechanism initiated by the stabilization of the Leu305{163}/Phe374{225} pair, which, in turn, stabilizes activation loop 3 and the S(1) and S(3) substrate pockets, the activation pocket, and N...

  12. Evaluation of optical coherence tomography for the measurement of the effects of activators and anticoagulants on the blood coagulation in vitro. (United States)

    Xu, Xiangqun; Geng, Jinhai; Liu, Gangjun; Chen, Zhongping


    Optical properties of human blood during coagulation were studied using optical coherence tomography (OCT) and the parameter of clotting time derived from the 1/e light penetration depth (d(1/e)) versus time was developed in our previous work. In this study, in order to know if a new OCT test can characterize the blood-coagulation process under different treatments in vitro, the effects of two different activators (calcium ions and thrombin) and anticoagulants, i.e., acetylsalicylic acid (ASA, a well-known drug aspirin) and melagatran (a direct thrombin inhibitor), at various concentrations are evaluated. A swept-source OCT system with a 1300 nm center wavelength is used for detecting the blood-coagulation process in vitro under a static condition. A dynamic study of d1/e reveals a typical behavior due to coagulation induced by both calcium ions and thrombin, and the clotting time is concentration-dependent. Dose-dependent ASA and melagatran prolong the clotting times. ASA and melagatran have different effects on blood coagulation. As expected, melagatran is much more effective than ASA in anticoagulation by the OCT measurements. The OCT assay appears to be a simple method for the measurement of blood coagulation to assess the effects of activators and anticoagulants, which can be used for activator and anticoagulant screening.

  13. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

    DEFF Research Database (Denmark)

    Højlund, Kurt


    . These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance...

  14. Evaluation of resuscitation fluids on endothelial glycocalyx, venular blood flow, and coagulation function after hemorrhagic shock in rats. (United States)

    Torres, Luciana N; Sondeen, Jill L; Ji, Lisa; Dubick, Michael A; Torres Filho, Ivo


    Endothelial glycocalyx (EG) plays an essential role in endothelium integrity and may be compromised by hemorrhagic shock. The effects of currently available resuscitation fluids such as Hextend (HEX) or lactated Ringer's solution (LR) on vascular function and coagulation are not well understood. The aim of the present study was to compare the effects of fresh frozen plasma (FFP) with HEX or LR in their ability to repair EG structure, promote volume expansion, increase blood flow, and prevent coagulopathy. A total of 121 microvessels from cremaster muscle were studied in 32 anesthetized instrumented rats. After baseline systemic and microvascular measurements, 40% hemorrhage followed by resuscitation was performed, and measurements were repeated. Coagulation was evaluated using ROTEM to assay clot formation time, clotting time, firmness, strength, and lysis. Velocity and "platelet component" of strength were calculated. Fluorescein isothiocyanate or Texas Red bound to Dextrans was injected to estimate EG thickness in vivo. Respiratory rate, blood pH, base excess, and lactate returned to near-baseline levels in all treatments. Hemodilution caused by LR and HEX decreased firmness, prolonged clotting time, and lowered platelet counts. EG thickness in HEX- and LR-treated rats was 50% lower, and plasma syndecan 1 was 50% higher than sham and FFP groups. Blood flow and shear rate were restored in the HEX group. Resuscitation with FFP improved coagulation and blood flow. Our findings support the concept of cardiovascular and microvascular stabilization by infused FFP, in which the increase in microvascular perfusion associated with restored EG is essential for an optimal resuscitation strategy.

  15. Monitoring of home safety issues in children on enteral feeds with inherited metabolic disorders. (United States)

    Evans, S; Shelton, F; Holden, C; Daly, A; Hopkins, V; MacDonald, A


    To assess the safety aspects of carers' enteral feeding technique when home enteral tube feeding children with inherited metabolic disorders (IMD). 40 patients (median age, 5.1 years; range, 0.3-13.6 years) with IMD requiring pump tube feeding were recruited. 12 patients had glycogen storage disease, 11 organic acidemias, 8 fatty acid oxidation disorders, 4 urea cycle disorders, and 5 had other conditions. 50% of the patients were fed by gastrostomy and 50% nasogastric tube. A questionnaire and practical assessment of feeding process was completed with carers by a dietician and nurse in the child's home. Areas investigated included carer hygiene, feed preparation, tube care, tube changing, use of feeding pumps and equipment, and storage of enteral feeding equipment. The main issues identified were poor hygiene practices (78% unclean work surfaces; 25% no hand washing); inaccurate ingredient measuring (40%); irregular checking of tube position (40%); inadequate tube flushing (50%); poor knowledge of how to clear tube blockages (80%); incorrect priming of pump sets (50%); incorrect position of child for night feeding (63%); untrained secondary carers (43%); and poor knowledge of pump alarms, battery life, and charging time. Children commonly slept in parent's room as a safety precaution (58%). Long term follow-up of children with IMD on home enteral tube feeding suggests that regular updates on knowledge and technique for carers may be necessary to reduce risk.

  16. Getting priorities straight: risk assessment and decision-making in the improvement of inherited disorders in pedigree dogs. (United States)

    Collins, Lisa M; Asher, Lucy; Summers, Jennifer; McGreevy, Paul


    The issue of inherited disorders in pedigree dogs is not a recent phenomenon and reports of suspected genetic defects associated with breeding practices date back to Charles Darwin's time. In recent years, much information on the array of inherited defects has been assimilated and the true extent of the problem has come to light. Historically, the direction of research funding in the field of canine genetic disease has been largely influenced by the potential transferability of findings to human medicine, economic benefit and importance of dogs for working purposes. More recently, the argument for a more canine welfare-orientated approach has been made, targeting research efforts at the alleviation of the most suffering in the greatest number of animals. A method of welfare risk assessment was initially developed as a means of objectively comparing, and thus setting priorities for, different welfare problems. The method has been applied to inherited disorders in pedigree dogs to investigate which disorders have the greatest welfare impact and which breeds are most affected. Work in this field has identified 396 inherited disorders in the top 50 most popular breeds in the UK. This article discusses how the results of welfare risk assessment for inherited disorders can be used to develop strategies for improving the health and welfare of dogs in the long term. A new risk assessment criterion, the Breed-Disorder Welfare Impact Score (BDWIS), which takes into account the proportion of life affected by a disorder, is introduced. A set of health and welfare goals is proposed and strategies for achieving these goals are highlighted, along with potential rate-determining factors at each step. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Newborn screening of inherited metabolic disorders by tandem mass spectrometry: past, present and future

    Directory of Open Access Journals (Sweden)

    G. Scaturro


    Full Text Available Inborn errors of metabolism are inherited biochemical disorders caused by lack of a functional enzyme, transmembrane transporter, or similar protein, which then results in blockage of the corresponding metabolic pathway. Taken individually, inborn errors of metabolism are rare. However, as a group these diseases are relatively frequent and they may account for most of neonatal mortality and need of health resources. The detection of genetic metabolic disorders should occur in a pre-symptomatic phase. Recently, the introduction of the tandem mass spectrometric methods for metabolite analysis has changed our ability to detect intermediates of metabolism in smaller samples and provides the means to detect a large number of metabolic disorders in a single analytical run. Screening panels now include a large number of disorders that may not meet all the criteria that have been used as a reference for years. The rationale behind inclusion or exclusion of a respective disorder is difficult to understand in most cases and it may impose an ethical dilemma. The current organization is an important tool of secondary preventive medicine, essential for children’s healthcare, but the strong inhomogeneity of the regional models of screening applied today create in the Italian neonatal population macroscopic differences with regards to healthcare, which is in effect mainly diversified by the newborn’s place of birth, in possible violation of the universal criterion of the equality of all citizens. Carefully weighed arguments are urgently needed since patient organizations, opinion leaders and politicians are pressing to proceed with expansion of neonatal population screening.

  18. Coagulation management. (United States)

    Grottke, Oliver


    Trauma-induced coagulopathy is a frequent complication in severely injured patients. To correct coagulopathy and restore haemostasis, these patients have traditionally been treated with fresh frozen plasma, but in the last decade, there has been a shift from empirical therapy to targeted therapy with coagulation factor concentrates and other haemostatic agents. This review highlights emerging therapeutic options and controversial topics. Early administration of the antifibrinolytic medication tranexamic acid was shown in the multicentre CRASH-2 trial to be an effective and inexpensive means of decreasing blood loss. Numerous retrospective and experimental studies have shown that the use of coagulation factor concentrates decreases blood loss and may be useful in reducing the need for transfusion of allogeneic blood products. In particular, early use of fibrinogen concentrate and thrombin generators has a positive impact on haemostasis. However, the use of prothrombin complex concentrate to correct trauma-induced coagulopathy has also been associated with a potential risk of serious adverse events. Current evidence in trauma resuscitation indicates a potential role for coagulation factor concentrates and other haemostatic agents in correcting trauma-induced coagulopathy. Despite a shift towards such transfusion strategy, there remains a shortage of data to support this approach.

  19. Contribution of a portable air plasma torch to rapid blood coagulation as a method of preventing bleeding

    International Nuclear Information System (INIS)

    Kuo, S P; Chen, C Y; Fan, H W; Tarasenko, O; Scott, A; Lahiani, M; Alusta, P; Chang, J; Popovic, S; Drake, J D; Nikolic, M


    The effectiveness and mechanism of a low temperature air plasma torch in clotting blood are explored. Both blood droplets and smeared blood samples were used in the tests. The treated droplet samples reveal how blood clotting depends on the distance at which the torch operated, and for how long the droplets have been exposed to the torch. Microscopy and cell count of smeared blood samples shed light on dependencies of erythrocyte and platelet counts on torch distance and exposure time. With an increase of torch distance, the platelet count of treated blood samples increases but is less than that of the control. The flux of reactive atomic oxygen (RAO) and the degree of blood clotting decreased. With an increase of exposure time, platelet count of treated samples decreased, while the degree of clot increased. The correlation among these dependencies and published data support a blood clotting mechanism that RAO as well as other likely reactive oxygen species generated by the plasma torch activate erythrocyte-platelets interactions and induces blood coagulation.

  20. Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII

    NARCIS (Netherlands)

    van Haren, Simon D.; Wroblewska, Aleksandra; Herczenik, Eszter; Kaijen, Paul H.; Ruminska, Aleksandra; ten Brinke, Anja; Meijer, Alexander B.; Voorberg, Jan


    The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII) is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+) T cell-dependent process. Activation of FVIII-specific CD4(+) T cells is dependent on the

  1. Modification of the functional state of neutrophilic granulocytes of blood due to coagulation and shear stress in patients with coronary heart disease: General cytochemical phenomena (United States)

    Teplyakov, A. I.; Kruchinskii, N. G.


    A comparative study is made of the influence of a viscosimetric trauma and a coagulation process on the functional state of neutrophilic granulocytes of blood (NGB) in 25 patients with coronary heart disease (CHD). It is shown that different mechanisms of cell activation exist in CHD patients with a stable and unstable course of the disease caused by the viscosimetric trauma effect, which have common features with the NGB activation due to coagulation.

  2. Effects of the coadministration of Huatuo Zaizao pills and aspirin on hemorrheology and blood coagulation in rabbits




    Huatuo Zaizao pills (HT) is a compound used in Chinese medicine for the treatment of cerebrovascular diseases. The present study aimed to investigate the effects of the coadministration of HT and aspirin on hemorrheology and blood coagulation in rabbits. Rabbits were randomly divided into the control, HT, aspirin and HT plus aspirin groups (n=5 animals per group). The rabbits were treated with HT at a dose of 1 g/kg, aspirin at a dose of 5 mg/kg or HT (1 g/kg) plus aspirin (5 mg/kg) administe...

  3. A catalog for the transcripts from the venomous structures of the caterpillar Lonomia obliqua: identification of the proteins potentially involved in the coagulation disorder and hemorrhagic syndrome (United States)

    Veiga, Ana B. G.; Ribeiro, José M. C.; Guimarães, Jorge A.; Francischetti, Ivo M.B.


    Accidents with the caterpillar Lonomia obliqua are often associated with a coagulation disorder and hemorrhagic syndrome in humans. In the present study, we have constructed cDNA libraries from two venomous structures of the caterpillar, namely the tegument and the bristle. High-throughput sequencing and bioinformatics analyses were performed in parallel. Over one thousand cDNAs were obtained and clustered to produce a database of 538 contigs and singletons (clusters) for the tegument library and 368 for the bristle library. We have thus identified dozens of full-length cDNAs coding for proteins with sequence homology to snake venom prothrombin activator, trypsin-like enzymes, blood coagulation factors and prophenoloxidase cascade activators. We also report cDNA coding for cysteine proteases, Group III phospholipase A2, C-type lectins, lipocalins, in addition to protease inhibitors including serpins, Kazal-type inhibitors, cystatins and trypsin inhibitor-like molecules. Antibacterial proteins and housekeeping genes are also described. A significant number of sequences were devoid of database matches, suggesting that their biologic function remains to be defined. We also report the N-terminus of the most abundant proteins present in the bristle, tegument, hemolymph, and "cryosecretion". Thus, we have created a catalog that contains the predicted molecular weight, isoelectric point, accession number, and putative function for each selected molecule from the venomous structures of L. obliqua. The role of these molecules in the coagulation disorder and hemorrhagic syndrome caused by envenomation with this caterpillar is discussed. All sequence information and the Supplemental Data, including Figures and Tables with hyperlinks to FASTA-formatted files for each contig and the best match to the Databases, are available at PMID:16023793

  4. Synergistic effect of a factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats. (United States)

    Konishi, Noriko; Hiroe, Katsuhiko; Kawamura, Masaki


    Activated platelets facilitate blood coagulation by providing factor V and a procoagulant surface for prothrombinase. Here, we investigated the potential synergy of a potent factor Xa/prothrombinase inhibitor, TAK-442, plus aspirin or clopidogrel in preventing arterial thrombosis and whole blood coagulation. Thrombus formation was initiated by FeCl(3)-induced rat carotid injury. Bleeding time was evaluated with the rat tail transection model. Whole blood coagulation was assessed by thromboelastographic examination (TEG) for which blood obtained from control, aspirin-, or clopidogrel-treated rats was transferred to a TEG analyzer containing, collagen or adenosine diphosphate (ADP), and TAK-442 or vehicle. TAK-442 (3mg/kg, po), aspirin (100mg/kg, po) or clopidogrel (3mg/kg, po) alone had no significant effect on thrombus formation, whereas the combination of TAK-442 with aspirin and clopidogrel remarkably prolonged the time to thrombus formation without additional significant prolongation of bleeding time. TEG demonstrated that the onset of collagen-induced blood coagulation were slightly longer in aspirin-treated rats than control; however, when the blood from aspirin-treated rats was subsequently treated in vitro with 100 nM TAK-442, the onset of clotting was significantly prolonged. In contrast, only marginal prolongation was observed with TAK-442 treatment of blood from control animals. The onset time of ADP-induced blood coagulation was slightly longer in clopidogrel-treated rats compared with control, and it was further extended by TAK-442 treatment. These results demonstrate that blood coagulation can be markedly delayed by the addition of TAK-442 to antiplatelets treatment which could contribute to synergistic antithrombotic efficacy in these settings. (c) 2010 Elsevier Ltd. All rights reserved.

  5. Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders. (United States)

    Ochoa-Ruiz, Estefanía; Díaz-Ruiz, Rodrigo; Hernández-Vázquez, Alaín de J; Ibarra-González, Isabel; Ortiz-Plata, Alma; Rembao, Daniel; Ortega-Cuéllar, Daniel; Viollet, Benoit; Uribe-Carvajal, Salvador; Corella, José Ahmed; Velázquez-Arellano, Antonio


    Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases.Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders.

  6. Clinical investigation of oral findings in inherited disorders of platelet function

    Directory of Open Access Journals (Sweden)

    Müjgan Güngör Hatipoğlu


    Full Text Available Objective: Bleeding disorders are a very important health problem due to the associated high risk of hemorrhage during dental procedures. The present study aimed to investigate oral manifestations of inherited disorders of platelet function (IDPF. Materials and Methods: The study included 20 IDPF patients (mean age: 31.90±10.71 years and 40 healthy controls (mean age: 31.63±9.07 years. Tooth brushing habits, level of education, and clinical index scores (Simplified Oral Hygiene Index [OHI-S], Decayed Missing Filled Teeth Index [DMFT] index, probing depth [PD] index, Gingival Bleeding Index [GBI], and Community Periodontal Index [CPI] were recorded. Results: There weren’t any significant differences between the 2 groups with respect to tooth brushing habit, level of education level, OHI-S, DMFT index, or CPI (p>0.05, whereas significant differences in PD index and GBI were observed between the groups (p<0.05.Conclusion: The present study’s findings show that IDPF has a negative effect on periodontal tissues.

  7. Characterization and blood coagulation evaluation of the water-soluble chitooligosaccharides prepared by a facile fractionation method. (United States)

    Lin, Chia-Wen; Lin, Jui-Che


    Water-soluble chitooligosaccharides have been reported to have specific biological activities. In this study, the chitosan samples with different degree of acetylation were used separately to prepare chitooligosaccharide (COS) and highly deacetylated chitooligosaccharide (HDCOS) through the nitrous acid depolymerization. Rather than using the conventional fractionation schemes commonly employed, such as dialysis and ultrafiltration which require a large amount of deionized water as well as a fair long dwell time, an unique fractionation scheme is explored to recover and desalt these nitrous-acid depolymerized chitosan with different molecular weights. This fractionation scheme is based on the differential solubility variation of depolymerized products within the aqueous solutions that contain various ratios of methanol. It was noted that chitosan with different molecular weight can be successfully recovered and fractionated with methanol added sequentially up to a volume of four times of original depolmerized product. In addition, chemical characterization of the fractionated water-soluble COS and HDCOS by 1H NMR spectroscopy and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) indicated that the chitosan depolymerization reaction is greatly influenced by the degree of acetylation of the parental chitosan reactant. Moreover, the modified whole blood clotting time assay and the platelet coagulation test suggested that the 1:2 fractionated water-soluble COS and HDCOS obtained are much less procoagulant than their parental chitosan compound and can be of use in biomedical applications in which blood coagulation is not desired.

  8. The pro-coagulant fibrinogenolytic serine protease isoenzymes purified from Daboia russelii russelii venom coagulate the blood through factor V activation: role of glycosylation on enzymatic activity.

    Directory of Open Access Journals (Sweden)

    Ashis K Mukherjee

    Full Text Available Proteases from Russell's viper venom (RVV induce a variety of toxic effects in victim. Therefore, four new RVV protease isoenzymes of molecular mass 32901.044 Da, 333631.179 Da, 333571.472 Da, and 34594.776 Da, were characterized in this study. The first 10 N-terminal residues of these serine protease isoenzymes showed significant sequence homology with N-terminal sequences of snake venom thrombin-like and factor V-activating serine proteases, which was reconfirmed by peptide mass fingerprinting analysis. These proteases were found to be different from previously reported factor V activators isolated from snake venoms. These proteases showed significantly different fibrinogenolytic, BAEE-esterase and plasma clotting activities but no fibrinolytic, TAME-esterase or amidolytic activity against the chromogenic substrate for trypsin, thrombin, plasmin and factor Xa. Their Km and Vmax values towards fibrinogen were determined in the range of 6.6 to 10.5 µM and 111.0 to 125.5 units/mg protein, respectively. On the basis of fibrinogen degradation pattern, they may be classified as A/B serine proteases isolated from snake venom. These proteases contain ∼ 42% to 44% of N-linked carbohydrates by mass whereas partially deglycosylated enzymes showed significantly less catalytic activity as compared to native enzymes. In vitro these protease isoenzymes induce blood coagulation through factor V activation, whereas in vivo they provoke dose-dependent defibrinogenation and anticoagulant activity in the mouse model. At a dose of 5 mg/kg, none of these protease isoenzymes were found to be lethal in mice or house geckos, suggesting therapeutic application of these anticoagulant peptides for the prevention of thrombosis.

  9. The importance of studying inherited hematological disorders in ancient Anatolian populations

    Directory of Open Access Journals (Sweden)

    Yeşim Doğan Alakoç


    Full Text Available Before analysis of DNA from ancient remains was possible, anthropologists studied evolution and migration patterns using data obtained from population genetic studies on modern populations combined with data obtained from morphological evaluations of ancient remains. Currently, DNA analysis of ancient populations is making a valuable contribution to these efforts. Researchers that perform ancient DNA analysis prefer to study polymorphisms on the Y chromosome or mitochondrial DNA because the results are easier to statistically evaluate. To evaluate polymorphisms on diploid genomes, which are more informative, only mutations that have been extensively examined in modern populations should be chosen. The most extensively evaluated mutations are those related to prevalent inherited disorders. As such, beta-thalassemia, sickle cell anemia, FVL mutation of globin and the factor V genes are good candidates for DNA studies in ancient populations. These mutations are common in Anatolia, host to many civilizations since the Paleolithic period. This history makes Anatolia a good place for conducting research that could enhance our understanding of human evolution and migration patterns.

  10. Renal phosphate handling and inherited disorders of phosphate reabsorption: an update. (United States)

    Wagner, Carsten A; Rubio-Aliaga, Isabel; Hernando, Nati


    Renal phosphate handling critically determines plasma phosphate and whole body phosphate levels. Filtered phosphate is mostly reabsorbed by Na + -dependent phosphate transporters located in the brush border membrane of the proximal tubule: NaPi-IIa (SLC34A1), NaPi-IIc (SLC34A3), and Pit-2 (SLC20A2). Here we review new evidence for the role and relevance of these transporters in inherited disorders of renal phosphate handling. The importance of NaPi-IIa and NaPi-IIc for renal phosphate reabsorption and mineral homeostasis has been highlighted by the identification of mutations in these transporters in a subset of patients with infantile idiopathic hypercalcemia and patients with hereditary hypophosphatemic rickets with hypercalciuria. Both diseases are characterized by disturbed calcium homeostasis secondary to elevated 1,25-(OH) 2 vitamin D 3 as a consequence of hypophosphatemia. In vitro analysis of mutated NaPi-IIa or NaPi-IIc transporters suggests defective trafficking underlying disease in most cases. Monoallelic pathogenic mutations in both SLC34A1 and SLC34A3 appear to be very frequent in the general population and have been associated with kidney stones. Consistent with these findings, results from genome-wide association studies indicate that variants in SLC34A1 are associated with a higher risk to develop kidney stones and chronic kidney disease, but underlying mechanisms have not been addressed to date.

  11. The Analysis of Genetic Aberrations in Children with Inherited Neurometabolic and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Krystyna Szymańska


    Full Text Available Inherited encephalopathies include a broad spectrum of heterogeneous disorders. To provide a correct diagnosis, an integrated approach including genetic testing is warranted. We report seven patients with difficult to diagnose inborn paediatric encephalopathies. The diagnosis could not be attained only by means of clinical and laboratory investigations and MRI. Additional genetic testing was required. Cytogenetics, PCR based tests, and array-based comparative genome hybridization were performed. In 4 patients with impaired language abilities we found the presence of microduplication in the region 16q23.1 affecting two dose-sensitive genes: WWOX (OMIM 605131 and MAF (OMIM 177075 (1 case, an interstitial deletion of the 17p11.2 region (2 patients further diagnosed as Smith-Magenis syndrome, and deletion encompassing first three exons of Myocyte Enhancer Factor gene 2MEF2C (1 case. The two other cases represented progressing dystonia. Characteristic GAG deletion in DYT1 consistently with the diagnosis of torsion dystonia was confirmed in 1 case. Last enrolled patient presented with clinical picture consistent with Krabbe disease confirmed by finding of two pathogenic variants of GALC gene and the absence of mutations in PSAP. The integrated diagnostic approach including genetic testing in selected examples of complicated hereditary diseases of the brain is largely discussed in this paper.

  12. Diagnosis of rare inherited glyoxalate metabolic disorders through in-situ analysis of renal stones (United States)

    Jacob, D. E.; Grohe, B.; Hoppe, B.; Beck, B. B.; Tessadri, R.


    The primary hyperoxalurias type I - III constitute rare autosomal-recessive inherited disorders of the human glyoxylate metabolism. By mechanisms that are ill understood progressive nephrocalcinosis and recurrent urolithiasis (kidney stone formation) often starting in early childhood, along with their secondary complications results in loss of nephron mass which progresses to end-stage renal failure over time. In the most frequent form, end-stage renal failure (ESRF) is the rule and combined liver/kidney transplantation respectively pre-emptive liver transplantation are the only causative treatment today. Hence, this contributes significantly to healthcare costs and early diagnosis is extremely important for a positive outcome for the patient. We are developing a stone-based diagnostic method by in-detail multi-methods investigation of the crystalline moiety in concert with urine and stone proteomics. Stone analysis will allow faster analysis at low-impact for the patients in the early stages of the disease. First results from combined spectroscopic (Raman, FTIR)and geochemical micro-analyses (Electron Microprobe and Laser Ablation ICP-MS) are presented here that show significant differences between stones from hyperoxaluria patients and those formed by patients without this disorder (idiopathic stones). Major differences exist in chemistry as well as in morphology and phase composition of the stones. Ca/P ratios and Mg contents differentiate between oxalate-stones from hyperoxaluria patients and idiopathic stones. Results show that also within the different subtypes of primary hyperoxaluria significant differences can be found in stone composition. These imply differences in stone formation which could be exploited for new therapeutic pathways. Furthermore, the results provide important feedback for suspected but yet unconfirmed cases of primary hyperoxaluria when used in concert with the genetic methods routinely applied.

  13. Accuracy of home enteral feed preparation for children with inherited metabolic disorders. (United States)

    Evans, S; Preston, F; Daly, A; Neville, C; MacDonald, A


    Many children with rare chronic disorders require home enteral tube feeds (HETF) consisting of multiple modular ingredients. Feeds are often complex and the risk of errors during their preparation is high. The consequences of over- or under-concentration can be critical. The aim of the present prospective observation study was to assess the accuracy, skills and technique of caregivers when preparing and administering HETF. Fifty-two HETF patients (median age 7.5 years, range 0.7-18.0 years) with inherited metabolic disorders (IMD) requiring special feeds were recruited. Using observation and a structured questionnaire, a practical assessment of feed preparation and storage by the main caregiver was undertaken by an independent dietitian and nurse in the child's home, including hygiene practices, accuracy of measuring recipe ingredients, and storage of both ingredients and prepared feeds. The majority (85%; n = 44) of feeds were based on >1 ingredient (median 3; range 1-6). Almost half (48%; n = 25) of caregivers measured feed ingredients inaccurately. Of the 31% (n = 16) using scoops, 31% used incorrect measuring spoons and 25% did not level scoops appropriately. Some 45% (n = 20/44) of carers measured liquid ingredients inaccurately. Hygiene practices during feed preparation were poor, including a lack of hand washing (31%: n = 16) and incorrect storage procedures for unused feed ingredients (56%; n = 29). Practices in the preparation of modular HETF for children with IMD were not ideal. A combination of inaccuracy, poor hygiene, inappropriate storage, and long feed hanging times increases both metabolic and microbial risk. Better education, regular monitoring and the development of ready-to-use or preweighed ingredients would be beneficial. © 2010 The Authors. Journal compilation © 2010 The British Dietetic Association Ltd.

  14. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    International Nuclear Information System (INIS)

    Tormoen, Garth W; Khader, Ayesha; Gruber, András; McCarty, Owen J T


    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis. (paper)

  15. Algorithmic and consultative integration of transfusion medicine and coagulation: a personalized medicine approach with reduced blood component utilization. (United States)

    Brown, Robert E; Dorion, R Patrick; Trowbridge, Cody; Stammers, Alfred H; Fitt, Walter; Davis, Jerry


    Therapy customized for the individual patient defines personalized medicine. Current transfusion therapy is performed primarily using general guidelines such as keeping the platelet count at >100,000/μL, the INR at ≤ 1.7 and fibrinogen at >100mg/dL for patients undergoing surgery. The purpose of this report is to provide an algorithmic and consultative approach for the delivery of personalized and targeted blood component, blood derivative, and recombinant therapies in order to minimize unnecessary exposure to such therapies and to deliver an optimal risk-benefit ratio for a particular patient. The initiative involved a step-wise process that included: 1. establishing "triggers" to alert and permit the clinical pathologist to intervene in the utilization of blood components for a given patient in the context of the blood bank inventory; 2. developing algorithms for the assessment of the patient's procoagulant/anticoagulant status so that appropriate blood component, derivative, and/or recombinant therapies could be instituted while minimizing the risk of thrombophilia; 3. a real time assessment and interpretation of the coagulation data so that dialogue between the pathologist and the patient's clinical team could be effected 24 hours a day, 7 days a week; and 4. monitoring the outcome of these efforts by comparing blood component utilization prior to or during development, early implementation and following full implementation of the program. "Triggers" (i.e., administration of six units of fresh frozen plasma [FFP] or ten units of cryoprecipitate or two single donor [apheresis] platelets in a 24-hour period) were approved. A diagnostic and therapeutic algorithm was constructed, with multidisciplinary input to assist in defining the coagulopathy contributing to the patient's microvascular bleeding in the adult cardiac surgery/cardiac intensive care unit (CICU) and the adult intensive care unit (AICU). Monitoring of utilization, prior to or during development

  16. Network-Based Biomarkers for Cold Coagulation Blood Stasis Syndrome and the Therapeutic Effects of Shaofu Zhuyu Decoction in Rats

    Directory of Open Access Journals (Sweden)

    Shulan Su


    Full Text Available In this study, the reverse docking methodology was applied to predict the action targets and pathways of Shaofu Zhuyu decoction (SFZYD bioactive ingredients. Furthermore, Traditional Chinese Medicine (TCM cold coagulation blood stasis (CCBS syndrome was induced in female Sprague-Dawley rats with an ice-water bath and epinephrine, and SFZYD was used to treat CCBS syndrome. A metabolomic approach was used to evaluate changes in the metabolic profiles and to analyze the pharmacological mechanism of SFZYD actions. Twenty-three potential protein targets and 15 pathways were discovered, respectively; among these, pathways are associated with inflammation and immunological stress, hormone metabolism, coagulation function, and glycometabolism. There were also changes in the levels of endogenous metabolites of LysoPCs and glucuronides. Twenty endogenous metabolites were identified. Furthermore, the relative quantities of 6 endogenous metabolites in the plasma and 5 in the urine were significantly affected by SFZYD (P<0.05. The pharmacological mechanism of SFZYD was partially associated with glycerophospholipid metabolism and pentose and glucuronate interconversions. In conclusion, our findings demonstrated that TCM CCBS pattern induced by ice water and epinephrine was complex and related to multiple metabolic pathways. SFZYD did regulate the TCM CCBS by multitargets, and biomarkers and SFZYD should be used for the clinical treatment of CCBS syndrome.

  17. A cross-sectional study of complementary and alternative medicine use in patients with coagulation disorders in Southern Iran. (United States)

    Bordbar, Mohammadreza; Pasalar, Mehdi; Aresehiri, Rezvan; Haghpanah, Sezaneh; Zareifar, Soheila; Amirmoezi, Fatemeh


    Complementary and alternative medicine (CAM) use has an increasing trend around the world. Despite the wild application of CAM in patients with coagulation disorders, its efficacy is still questioned by many studies. The aim of this study was to determine the frequency and types of CAM usage, and the factors affecting CAM use among patients with bleeding disorders. This cross-sectional study investigated the usage of CAM with a standard validated questionnaire in coagulopathic patients who were referred to Dastgheib Hospital, an educational therapeutic center affiliated to the Shiraz University of Medical Sciences in Shiraz, Southern Iran. Between December 2015 and May 2016, 75 patients were included in this survey. Severe hemophilia A and rare bleeding disorders were the most frequent among our participants. Overall, nearly half of the studied population (49.3%) used at least one CAM product or practices. The most common products were multivitamin (29.3%), followed by folic acid (21.3%) and chamomile (12%). 32% of the patients resorted to faith healing. The main reasons of using CAM were reported to be increased general health, correction of anemia and thrombocytopenia and control of bleeding tendency. CAM is being used frequently in patients with coagulation disorders like many other chronic illnesses all around the world. Due to emerging concern regarding the safety and possible interaction with the conventional medicine, it is necessary to develop basic data about the hematologic effects of these methods in order to use them more safely.

  18. Dynamics of changes in the activation of blood coagulation tests at different variants of thromboprophylaxis

    Directory of Open Access Journals (Sweden)

    Олена Миколаївна Клигуненко


    Full Text Available Aim: To study an influence of the different variants of thromboprophylaxis on activation of blood coagulation test on the background of surgical aggression. D-dimer concentration in serum is in direct proportion to fibrinolysis activity and to an amount of lysed fibrin. At the same time fibrinolysis activation is followed with an increase of formation of products of fibrin degradation (PFD that interact with fibrin-monomers and increase the number of SFMC.Materials and methods: After informed consent 200 patients were prospectively divided into groups depending on preparation and regimen of thromboprophylaxis. 1 group (n=30 – ungraded heparin (UGH (5000 ОD for 2 hours before surgery 2 times during 7 days after it. 2 group(n=30 nadraparin calcium 9500 anti-Ха МO (0,3 ml for 2 hours before surgery 2500 МО 1 time for a day 7 days after surgery; 3 group(n=48 – endoxaparin sodium(0,2 ml for 2 hours before surgery 1 time a day 7 days; 4 group(n=29 endoxaparin sodium(0,2ml for 8 hours before surgery, 0,2 ml 1 time a day 7 days; 5 group(n=34 – bemiparin sodium(0,2 ml for 2 hours before surgery 0,2 ml 1 time a day 7 days; 6 group(n=29 bemiparin sodium(0,2ml in 6 hours after surgery 1 time a day 7 days. Patients were comparable on sex, concomitant pathology, class АSA (1-2 and type of surgical intervention. There were studied the number of thrombocytes, prothrombin time (PT, INR AFTT, fibrinogen, Х-а factor activity, antithrombin, 111 (AT111, protein C, SFMC, d-dimer before surgery, on 1,5 and 7 day after it.Results and discussions: On the 1 day of postsurgical period the most influence on D-dimer level had presurgical thromboprophylaxis (TPP with UGH and nadroparin calcium. So the D-dimer level exceeded norm respectively by 67 % (р=0,017 and 65,9 % (р<0,05. In patients of 3 and 4 groups D-dimer level was the lowest that formed deficiency by 56 % (р<0,05 and 52,7 % (р<0,05 from the norm respectively. At the same time an analysis of

  19. Novel two-step derivation method for the synchronous analysis of inherited metabolic disorders using urine. (United States)

    Sheng, Xiao-Qi; Wang, Yi-Chao


    The aim of the present study was to conduct preliminary clinical screening and monitoring using a novel two-step derivatization process of urine in five categories of inherited metabolic disease (IMD). Urine samples (100 µl, containing 2.5 mmol/l creatinine) were taken from patients with IMDs. The collected urine was then treated using a two-step derivatization method (with oximation and silylation at room temperature), where urea and protein were removed. In the first step of the derivatization, α-ketoacids and α-aldehyde acids were prepared by oximation using novel oximation reagents. The second-step of the derivatization was that residues were silylated for analysis. Urine samples were examined using gas chromatography/mass spectrometry (GC/MS) and a retention time-locking technique. The simultaneous analysis and identification of >400 metabolites in >130 types of IMD was possible from the GC/MS results, where the IMDs included phenylketonuria, ornithine transcarbamylase deficiency, neonatal intrahepatic cholestasis caused by citrin deficiency, β-ureidopropionase deficiency and mitochondrial metabolic disorders. This method was demonstrated to have good repeatability. Considering α-ketoglutarate (α-KG) as an example, the relative standard deviations (RSDs) of the α-KG retention time and peak area were 0.8 and 3.9%, respectively, the blank spiked recovery rate was between 89.6 and 99.8%, and the RSD was ≤7.5% (n=5). The method facilitates the analysis of thermally non-stable and semi-volatile metabolites in urine, and greatly expands the range of materials that can be synchronously screened by GC/MS. Furthermore, it provides a comprehensive, effective and reliable biochemical analysis platform for the pathological research of IMDs.

  20. Feeding difficulties in children with inherited metabolic disorders: a pilot study. (United States)

    Evans, S; Alroqaiba, N; Daly, A; Neville, C; Davies, P; Macdonald, A


    In children with inherited metabolic disorders (IMD), feeding difficulties are often assumed to be inherent, although there is little evidence describing their frequency or severity. The present study aimed to describe feeding patterns/difficulties among children with IMD on protein-restricted diets from one centre. Data from an observational, pilot study of 20 IMD children, nine females (median age, 2.7 years; range, 1-6 years) were compared with data obtained from a retrospective historical group of 15 healthy children (HC), 12 females, aged 1-5 years (median 3.0 years). Caregivers completed a feeding assessment questionnaire, and three separate video recordings were taken of each child eating at home. The main feeding problems identified by the caregivers' questionnaire in the IMD group (compared to HC) were: poor appetite (55% versus 7%; P = 0.004), limited food variety (55% versus 27%; P = 0.04) and lengthy mealtimes (70% versus 20%; P = 0.006). During mealtimes, children from the IMD group were more likely to vomit, exhibit negative behaviour, get distracted and self-feed less often. From video recordings of meals, although the median meal duration was similar for the two groups (18 min IMD versus 16 min HC), the HC ate twice the quantity of food (3.4 mouthfuls min(-1) versus 1.5 mouthfuls min(-1) ; P children (median parent to child communications: IMD group, seven in 10 min; HC, 17 in 10 min). Eighty-three percent of IMD children regularly ate alone. In children with IMD on protein restrictions, severe feeding difficulties were common. Caregivers need to focus more attention on the social aspects of feeding. Further larger scale studies are required. © 2012 The Authors. Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.

  1. Thrombin generation and fibrin clot formation under hypothermic conditions: an in vitro evaluation of tissue factor initiated whole blood coagulation. (United States)

    Whelihan, Matthew F; Kiankhooy, Armin; Brummel-Ziedins, Kathleen E


    Despite trauma-induced hypothermic coagulopathy being familiar in the clinical setting, empirical experimentation concerning this phenomenon is lacking. In this study, we investigated the effects of hypothermia on thrombin generation, clot formation, and global hemostatic functions in an in vitro environment using a whole blood model and thromboelastography, which can recapitulate hypothermia. Blood was collected from healthy individuals through venipuncture and treated with corn trypsin inhibitor, to block the contact pathway. Coagulation was initiated with 5pM tissue factor at temperatures 37°C, 32°C, and 27°C. Reactions were quenched over time, with soluble and insoluble components analyzed for thrombin generation, fibrinogen consumption, factor (f)XIII activation, and fibrin deposition. Global coagulation potential was evaluated through thromboelastography. Data showed that thrombin generation in samples at 37°C and 32°C had comparable rates, whereas 27°C had a much lower rate (39.2 ± 1.1 and 43 ± 2.4 nM/min vs 28.6 ± 4.4 nM/min, respectively). Fibrinogen consumption and fXIII activation were highest at 37°C, followed by 32°C and 27°C. Fibrin formation as seen through clot weights also followed this trend. Thromboelastography data showed that clot formation was fastest in samples at 37°C and lowest at 27°C. Maximum clot strength was similar for each temperature. Also, percent lysis of clots was highest at 37°C followed by 32°C and then 27°C. Induced hypothermic conditions directly affect the rate of thrombin generation and clot formation, whereas global clot stability remains intact. © 2013.

  2. Methodical aspects of blood coagulation measurements in birds applying commercial reagents--a pilot study. (United States)

    Guddorf, Vanessa; Kummerfeld, Norbert; Mischke, Reinhard


    The aim of this study was to examine the suitability of commercially available reagents for measurements of coagulation parameters in citrated plasma from birds. Therefore, plasma samples of 17 healthy donor birds of different species were used to determine prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT) applying various commercial reagents which are routinely used in coagulation diagnostics in humans and mammals. A PT reagent based on human placental thromboplastin yielded not only shorter clotting times than a reagent containing recombinant human tissue factor (median 49 vs. 84 s), but also showed a minor range of distribution of values (43-55 s vs. 30-147 s, minimum-maximum, n = 5 turkeys). An aPTT reagent containing kaolin and phospholipids of animal origin delivered the shortest clotting times and the lowest range of variation in comparison to three other reagents of different composition. However, even when this reagent was used, aPTTs were partially extremely long (> 200 s). Thrombin time was 38 s (28-57 s, n = 5 chicken) when measured with bovine thrombin at a final concentration of 2 IU thrombin/ ml. Coefficients of variation for within-run precision analysis (20 repetitions) of PT was 8.0% and 4.7% for aPTT measurements using selected reagents of mammalian origin. In conclusion, of the commercially available reagents tested, a PT reagent based on human placental thromboplastin and an aPTT reagent including rabbit brain phospholipid and kaolin, show some promise for potential use in birds.

  3. Effect of Taohongsiwu decoction after total hip replacement on blood coagulation function, pain degree as well as RANKL and OPG content

    Directory of Open Access Journals (Sweden)

    Zhao-Xia Lu


    Full Text Available Objective: To analyze the effect of Taohongsiwu decoction after total hip replacement on blood coagulation function, pain degree as well as RANKL and OPG content. Methods: A total of 118 patients who underwent total hip replacement were divided into observation group and control group, and serum blood coagulation indexes, fibrinolysis indexes, pain mediators and inflammatory mediators as well as RANKL and OPG content were compared between two groups of patients 12 d after operation. Results: Blood coagulation indexes PT, APTT and TT levels of observation group 12 d after operation were greater than those of control group while D-D content was lower than that of control group; fibrinolysis indexes FIB, FDP, PAI-1 and t-PA content in serum were lower than those of control group while Plg and u-PA content were higher than those of control group; pain mediators β-EP, NO, CGRP, SP and PGE2 content in serum were lower than those of control group; inflammatory mediators hs-CRP, IL-6, TNF-α, IL-17, IL-33 and TREM-1 content in serum were lower than those of control group; RANKL and OPG content in serum were lower than those of control group. Conclusions: Taohongsiwu decoction can optimize patients’ blood coagulation function and reduce the perception of pain after total hip replacement, and is also of positive significance in promoting patients’ long-term fracture healing.

  4. Associations between blood coagulation markers, NT-proBNP and risk of incident heart failure in older men: The British Regional Heart Study. (United States)

    Wannamethee, S Goya; Whincup, Peter H; Papacosta, Olia; Lennon, Lucy; Lowe, Gordon D


    Chronic heart failure (HF) is associated with activation of blood coagulation but there is a lack of prospective studies on the association between coagulation markers and incident HF in general populations. We have examined the association between the coagulation markers fibrinogen, von Willebrand Factor (VWF), Factors VII, VIII and IX, D-dimer, activated protein C (APC) and activated partial thromboplastin time (aPPT) with NT-proBNP and incident HF. Prospective study of 3366 men aged 60-79years with no prevalent HF, myocardial infarction or venous thrombosis and who were not on warfarin, followed up for a mean period of 13years, in whom there were 203 incident HF cases. D-dimer and vWF were significantly and positively associated with NT-proBNP (a marker of neurohormonal activation and left ventricular wall stress) even after adjustment for age, lifestyle characteristics, renal dysfunction, atrial fibrillation (AF) and inflammation (C-reactive protein). By contrast Factor VII related inversely to AF and NT-proBNP even after adjustment. No association was seen however between the coagulation markers VWF, Factor VII, Factor VIII, Factor IX, D-dimer, APC resistance or aPPT with incident HF in age-adjusted analyses. Fibrinogen was associated with incident HF but this was abolished after adjustment for HF risk factors. Coagulation activity is not associated with the development of HF. However D-dimer and vWF were significantly associated with NT-proBNP, suggesting that increased coagulation activity is related to cardiac stress; and the increased coagulation seen in HF patients may in part be a consequence of neurohormonal activation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Transmission of Neurodegenerative Disorders Through Blood Transfusion

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Hjalgrim, Henrik; Rostgaard, Klaus


    : Multivariable Cox regression models were used to estimate hazard ratios for dementia of any type, Alzheimer disease, and Parkinson disease in patients receiving blood transfusions from donors who were later diagnosed with any of these diseases versus patients who received blood from healthy donors. Whether.......9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy......BACKGROUND: The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health...

  6. Effect of hyperbilirubunemia on coagulation system of blood in patients with obstructive jaundice

    Directory of Open Access Journals (Sweden)

    Sarkisian Z.O.


    Full Text Available Objective of the study: determination of the degree of influence of bilirubin in the blood during obstructive jaundice, on blood clotting. Methods. A retrospective study of case histories of patients with obstructive jaundice who have been treated at the Regional Hospital of Saratov in the period from 2000 to 2010. Results. The results confirm the assumption that the causes of bleeding in obstructive jaundice is hepatic failure. Conclusion. Absence of bile in the small intestine in obstructive jaundice is not the cause of bleeding. Bile acids are not involved in metabolizing fat-soluble vitamin K1

  7. Plasma fractionation for blood products: isolation and purification of coagulating factors, albumin and immunoglobulin

    International Nuclear Information System (INIS)

    Siti Najila Mohd Janib; Shaharuddin Mohd; Wan Hamirul Bahrin Wan Kamal


    Approximately 12 million liters of human plasma are fractionated world-wide annually. However, with the market for clotting factors and other haemoderivatives steadily increasing from year to year, the amount processed will also increase correspondingly to keep up with the demand. In Malaysia, part of the need for the blood products are obtained commercially but a major portion of the requirement involves sending the plasma collected by the National Blood Centre to Australia for processing. Following purification and isolation of the blood products, they are sent back to Malaysia for local consumption. As yet there are no plasma fractionation plants in the South East Asia region, it would be advantageous to establish a local fractionation plant as it would be able to cater for local demands of the haemoderivatives and thus reduces the cost of importing these products. Besides, this facility will be able to provide contract fractionation services to the surrounding region. Early work in MINT has started in trying to purify plasma obtained from rats. Purification of the plasma was performed by using Sephadex G-25 column. Short term objective of this project is to develop the technique of extraction, fractionation and purification of blood products such as albumin, globulin and clotting factors (Factor VIII and Factor IX). The long term emphasis will be to scale up the production facility to a pilot plant stage and eventually to a national fractionation and purification plant. (Author)

  8. Hemodynamics and Blood Coagulation System in Patients Operated Following Ulcer Disease Hemorrhagia

    Directory of Open Access Journals (Sweden)

    V. V. Filatov


    Full Text Available Objective: to evaluate the clinical efficacy of hypoxen and nutrients used in the combination therapy of patients operated for bleeding gastroduodenal ulcer. Subjects and methods. Seventy-four patients were examined and treated. All the patients were divided into 3 groups: 1 standard therapy + hypoxen in a daily dose of 1 g for a week; 2 standard therapy + hypox-en and nutrients; 3 standard therapy only. Hypoxen and nutrients were administered on postoperative day 1 via an enter-al feeding tube. Systemic hemodynamic and hemostatic parameters were determined using MICAR-RHEO hardware-software rheographic unit APG2-01 analyzer, respectively. Results. It was established that the hyper- and eukinetic hemodynamic types were predominant before surgery and the eukinetic type was prevalent in the early postoperative period. Hypoxen and nutrients were observed to positively affect central hemodynamic parameters, such as blood pressure, cardiac output, circulating blood volume, and heart rate. Hypercoagulation changes (shorter blood clotting time in a study group and elevated serum fibrinogen levels in a comparison group on postoperative day 10 suggest that the hemostatic parameters should be monitored and corrected as soon as possible. Key words: ulcer disease, hypoxen, nutritional support, blood circulation, hemostatic system.

  9. QCM-D surpassing clinical standard for the dose administration of new oral anticoagulant in the patient of coagulation disorders. (United States)

    Hussain, Munawar; Wendel, Hans Peter; Schmidt, Katrin; Langer, Elisabeth; Körber, Mareike Kristina; Faul, Oksana; Northoff, Hinnak; von Heymann, Christian; Gehring, Frank K


    The study focuses the dose administration of dabigatran to avoid the deaths due to hemorrhagic complications and thromboembolic stroke in clinics worldwide. To target the issue, a novel emerging acoustic technology, namely ''Quartz Crystal Microbalance with Dissipation'' (QCM-D) has been applied, while the acoustic assays namely ''activated Partial Thromboplastin Time'' (aPTT) and ''Prothrombinase complex-induced Clotting Test'' (PiCT) have been compared with the standard methods in parallel. Both techniques have been applied to 300 samples, including 220 plasma samples of patients suffering coagulation disorders and 80 plasma samples of non-patients. In comparison, the coagulation times of the acoustic aPTT and PiCT yielded an excellent correlation with the standard methods with in analytical standard deviation limits. Finally, the acoustic aPTT assay is the ''gold standard'' for a dose administration of the new oral anticoagulant, where the Δf/ΔΓ ratio of the acoustic assay demonstrates that dabigatran with FEIBA 50 combination could be a safe remedy to avoid the deaths in clinics. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effects of Thermal Status on Markers of Blood Coagulation During Simulated Hemorrhage (United States)


    reduction in central blood volume to near syncope. Aviat Space Environ Med 80, 1012–1017. Conway C (1975). Haemodynamic effects of pulmonary ventilation ...influences of passive heat stress and exercise in altering vascular control via unique mechanisms , we expected an additive effect resulting in lower tolerance...hemorrhage. Currently, warming a bleeding victim is the standard of care due to the adverse effects of combined hemorrhage and hypothermia on survival. We

  11. 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.


    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

  12. In-vitro effects of tri-iodinated X-ray contrast media on blood coagulation, fibrinolysis and complement system

    International Nuclear Information System (INIS)

    Blanke, D.


    In-vitro experiments with Jodipamid, Jothalamat and Diatrizoat served the purpose of determining influences of contrast media on blood coagulation, fibrinolysis and the complement system. For all three contrast media investigated the effect noted was dose-dependent and was only brought about by concentrations higher than physiological ones. Liver-pathway Jodipamid was seen to have a much stronger effect than the two renal-pathway contrast media Jothalamat and Diatrizoat, which is probably due to the different protein binding capacities. In detail, the results with Jodipamid were as follows: a sharp fall in thrombinogen, a distinct decrease in fibrinogen both in the immunological and functional test, but only delayed decrease in complement factor C 4. Fibrinolytic fission products were found after applying the dose of 30 mM, as compared to 400 mM for the renal-pathway contrast media. Furthermore the functional tests (F I and F II) with Jothalamat and Diatrizoat showed only slight effects, the immunological ones (F I and C 4) none at all. The influence of the contrast media on factors I and II is interpreted by the author as an inhibition of fibrin polymerization. What seems to be the verification of fibrinolytic fission products is explained by a non-specific agglutination reaction, the decrease in C 4 by contrast-medium-induced protein denaturation. (orig./MG) [de

  13. Impact of Inherited Prothrombotic Disorders on the Long-Term Clinical Outcome of Percutaneous Transluminal Angioplasty in Patients with Diabetes

    Directory of Open Access Journals (Sweden)

    Michal Dubský


    Full Text Available The aim of our study was to analyse inherited thrombotic disorders that influence the long-term outcome of PTA. Methods. Diabetic patients with peripheral arterial disease (PAD treated by PTA in our centre between 2008 and 2011 were included in the study. Patients were divided into unsuccessful PTA group (75 patients, successful PTA group (58 patients, and control group (65 patients, with diabetes but no PAD. Diagnosis of inherited thrombotic disorders included mutation in factor V (Leiden, factor II (prothrombin, and mutation in genes for methylenetetrahydrofolate reductase—MTHFR (C677T and A1298C. Results. The genotypic frequency of Leiden allele G1691A was significantly associated with a risk of unsuccessful PTA in comparison with successful PTA group and control group (OR 8.8 (1.1–70.6, p=0.041, and OR 9.8 (1.2–79.2, p=0.032, resp.. However, we only observed a trend for the association of the prothrombin allele G20210A and risk of PTA failure. The frequencies of alleles of MTHFR 677 or 1298 did not differ significantly among the groups. Conclusion. Our study showed higher frequency of heterozygous form of Leiden mutation in diabetic patients with unsuccessful outcome of PTA in comparison with patients with successful PTA and diabetic patients without PAD.

  14. Effects of dietary fat quality and quantity on postprandial activation of blood coagulation factor VII

    DEFF Research Database (Denmark)

    Larsen, L F; Bladbjerg, E-M; Jespersen, J


    , palm oil, or butter (42% of energy from fat) or isoenergetic low-fat meals (6% of energy from fat). Fasting and series of nonfasting blood samples (the last at time 8 1/2 hours) were collected. Plasma triglycerides, FVIIc, FVIIa, and free fatty acids were analyzed. There were marked effects of the fat......, monounsaturated, or polyunsaturated fats differed regarding postprandial activation of FVII. Eighteen healthy young men participated in the study. On 6 separate days each participant consumed two meals (times, 0 and 1 3/4 hours) enriched with 70 g (15 and 55 g) of either rapeseed oil, olive oil, sunflower oil...

  15. Plasma concentrations of blood coagulation factor VII measured by immunochemical and amidolytic methods

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Gram, J; Jespersen, J


    :Ag) or estimated with an amidolytic method (FVII:Am). We have investigated whether FVII:Am is a valuable alternative to FVII:Ag. FVII:Ag and FVII:Am were measured in 147 plasma samples from blood donors, patients on oral anticoagulant therapy, postmenopausal women on hormone replacement therapy, in postprandial...... omitting the data from patients on oral anticoagulant therapy, with mean values of 113 U/ml for FVII:Ag and 110 U/ml for FVII:Am (p regression analysis, the intercept (alpha=-21.50) was different from zero (p

  16. Lactadherin inhibits enzyme complexes of blood coagulation by competing for phospholipid-binding sites. (United States)

    Shi, Jialan; Gilbert, Gary E


    Lactadherin, a glycoprotein of the milk-fat globule membrane, contains tandem C domains with homology to discoidin-type lectins and to membrane-binding domains of blood-clotting factors V and VIII. We asked whether the structural homology confers the capacity to compete for the membrane-binding sites of factor VIII and factor V and to function as an anticoagulant. Our results indicate that lactadherin competes efficiently with factor VIII and factor V for binding sites on synthetic phosphatidylserine-containing membranes with half-maximal displacement at lactadherin concentrations of 1 to 4 nM. Binding competition correlated to functional inhibition of factor VIIIa-factor IXa (factor Xase) enzyme complex. In contrast to annexin V, lactadherin was an efficient inhibitor of the prothrombinase and the factor Xase complexes regardless of the degree of membrane curvature and the phosphatidylserine content. Lactadherin also inhibited the factor VIIa-tissue factor complex efficiently whereas annexin V was less effective. Because the inhibitory concentration of lactadherin was proportional to the phospholipid concentration, and because lactadherin was not an efficient inhibitor in the absence of phospholipid, the major inhibitory effect of lactadherin relates to blocking phospholipid sites rather than forming inhibitory protein-protein complexes. Lactadherin was also an effective inhibitor of a modified whole blood prothrombin time assay in which clotting was initiated by dilute tissue factor; 60 nM lactadherin prolonged the prothrombin time 150% versus 20% for 60 nM annexin V. These results indicate that lactadherin can function as a potent phospholipid-blocking anticoagulant.

  17. Hepatitis A and B immunization for individuals with inherited bleeding disorders. (United States)

    Steele, M; Cochrane, A; Wakefield, C; Stain, A-M; Ling, S; Blanchette, V; Gold, R; Ford-Jones, L


    Hepatitis A and B vaccines are highly effective tools that can greatly reduce infection risk in the bleeding disorder population. Although hepatitis A and B immunization for individuals with bleeding disorders is universally recommended, various advisory bodies often differ with respect to many practical aspects of vaccination. To review the published literature and guidelines and form a practical, comprehensive and consistent approach to hepatitis A and B immunization for individuals with bleeding disorders. We reviewed published immunization guidelines from North American immunization advisory bodies and published statements from North American and international haemophilia advisory bodies. A search of the MEDLINE database was performed to find original published literature pertaining to hepatitis A or B immunization of patients with haemophilia or bleeding disorder patients that provided supporting or refuting evidence for advisory body guidelines. Various advisory bodies' immunization guidelines regarding individuals with bleeding disorders have contradictory statements and often did not clarify issues (e.g. post vaccination surveillance). Published literature addressing immunization in bleeding disorder patients is sparse and mostly examines route of vaccine administration, complications and corresponding antibody response. Although the risk of hepatitis A and B infection is low, the use of simple measures such as vaccination is reasonable and advocated by haemophilia advisory bodies. Following our review of the available literature and North American guidelines, we have developed comprehensive and practical recommendations addressing hepatitis A and B immunization for the bleeding disorder population that may be applicable in Bleeding Disorder clinics.

  18. Whole blood coagulation assays ROTEM and T-TAS to monitor dabigatran treatment. (United States)

    Taune, Viktor; Wallén, Håkan; Ågren, Anna; Gryfelt, Gunilla; Sjövik, Carolina; Wintler, Anna M; Malmström, Rickard E; Wikman, Agneta; Skeppholm, Mika


    A rapid and reliable assessment of the dabigatran effect is desirable in dabigatran treated patients with uncontrolled bleeding or before acute surgery. To evaluate how the viscoelastic point-of-care test Rotational thromboelastometry (ROTEM) and Total Thrombus-formation system (T-TAS), which studies thrombus formation under flowing conditions, correlate with dabigatran concentrations in patients with atrial fibrillation (AF). ROTEM using the reagents In-tem, Ex-tem, Fib-tem or low tissue factor concentration (TF), and T-TAS with the AR-chip (shear rate 600s -1 , representing flow in large arteries) were investigated in whole blood samples. Plasma concentrations were determined by mass spectrometry (LC-MS/MS) at trough and post-dose in 30 patients on dabigatran 150mg BID. Median plasma dabigatran concentrations at trough were 86ng/mL (29-150) and post-dose (2.8h after ingestion) 175ng/mL (67-490). The ROTEM clotting time (CT) correlated strongly with dabigatran concentrations when activated with the reagents Ex-tem (r=0.92, p<0.01) and Fib-tem (r=0.93, p<0.01), while with In-tem and low TF the correlation was weaker (r=0.72 and r=0.36, p<0.01). There were significant but weaker correlations also between dabigatran concentrations and T-TAS variables (r-values 0.39-0.41, p<0.01), aPTT (r=0.70, p<0.01) and PT-INR (r=0.43, p<0.01) respectively. ROTEM Ex-tem and Fib-tem CT shows a strong correlation with dabigatran concentrations in real-life AF-patients, and results are obtained within minutes. This could make ROTEM useful in acute situations. T-TAS detect differences in hemostasis caused by dabigatran, but the relationships to plasma concentrations of dabigatran are weaker than for ROTEM CT with the settings used in this study. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation

    International Nuclear Information System (INIS)

    O'Hara, P.J.; Grant, F.J.; Haldeman, B.A.; Gray, C.L.; Insley, M.Y.; Hagen, F.S.; Murray, M.J.


    Activated factor VII (factor VIIa) is a vitamin K-dependent plasma serine protease that participates in a cascade of reactions leading to the coagulation of blood. Two overlapping genomic clones containing sequences encoding human factor VII were isolated and characterized. The complete sequence of the gene was determined and found to span about 12.8 kilobases. The mRNA for factor VII as demonstrated by cDNA cloning is polyadenylylated at multiple sites but contains only one AAUAAA poly(A) signal sequence. The mRNA can undergo alternative splicing, forming one transcript containing eight segments as exons and another with an additional exon that encodes a larger prepro leader sequence. The latter transcript has no known counterpart in the other vitamin K-dependent proteins. The positions of the introns with respect to the amino acid sequence encoded by the eight essential exons of factor VII are the same as those present in factor IX, factor X, protein C, and the first three exons of prothrombin. These exons code for domains generally conserved among members of this gene family. The comparable introns in these genes, however, are dissimilar with respect to size and sequence, with the exception of intron C in factor VII and protein C. The gene for factor VII also contains five regions made up of tandem repeats of oligonucleotide monomer elements. More than a quarter of the intron sequences and more than a third of the 3' untranslated portion of the mRNA transcript consist of these minisatellite tandem repeats

  20. Factors affecting the lung perfused blood volume in patients with intrapulmonary clots after anti-coagulation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Munemasa, E-mail: [Department of Radiology, Yamaguchi University Graduate School of Medicine 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Masuda, Yu [4th Grade of 6-year Medicine Doctor Program, Department of Medicine, Yamaguchi University Faculty of Medicine and Health Sciences 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Nakashima, Yoshiteru [Department of Radiology, Yamaguchi Grand Medical Center, Oosaki 77, Hofu, Yamaguchi 747-8511 (Japan); Nomura, Takafumi; Nakao, Sei [Department of Radiology, Yamaguchi University Graduate School of Medicine 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Suga, Kazuyoshi [Department of Radiology, St Hills Hospital, Imamurakita 3-7-18, Ube, Yamaguchi 755-0155 (Japan); Kido, Shoji [Computer-aided Diagnosis and Biomedical Imaging Research Biomedical Engineering, Applied Medical Engineering Science Graduate School of Medicine, Yamaguchi University, Tokiwadai 2-16-1, Ube, Yamaguchi 755-8611 (Japan); Matsunaga, Naofumi [Department of Radiology, Yamaguchi University Graduate School of Medicine 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan)


    Highlights: • Dual-energy CT can provide morphological and functional lung images in the same examination. • The subsequent dual-energy CT demonstrates the increased whole lung perfused blood volume (V{sub 120}) despite the residual intrapulmonary clots after treatment in one examination. • The increased whole lung perfusion (V{sub 120}) and a decreased low perfusion volume (V{sub 5}) result in the improvement in the low perfusion rate (%V{sub 5}) in the patients with acute pulmonary embolism after treatment. - Abstract: Objectives: Factors affecting the improvement in the lung perfused blood volume (LPBV) were evaluated based on the presence of intrapulmonary clots (IPCs) after anti-coagulation therapy using 64-slice dual-energy CT. Materials and methods: 96 patients exhibiting venous thromboembolism underwent initial and repeated LPBV examinations between December 2008 and July 2014. Fifteen patients were excluded due to pulmonary comorbidities, and a total of 81 patients were included in this study. Acute pulmonary embolism (PE) was diagnosed in 46 of the patients (56.7%). LPBV images were three-dimensionally reconstructed with two threshold ranges: 1–120 HU (V{sub 120}) and 1–5 HU (V{sub 5}), and the relative value of V{sub 5} per V{sub 120} expressed as %V{sub 5}. These values were subsequently compared with indicators of the severity of PE, such as the D-dimer level, heart rate and CT measurements. This study was approved by the local ethics committee. Results: In patients with IPCs, the D-dimer, V{sub 5} and %V{sub 5}values were significantly larger (p ≤ 0.01) in the initial LPBV, although these differences disappeared in subsequent LPBV after treatment. The right ventricular (RV) diameter, RV/left ventricular (RV/LV) diameter ratio and %V{sub 5} values were also significantly reduced, whereas the V{sub 5} value did not significantly decrease (p = 0.07), but V{sub 120} value significantly increased (p < 0.001) after treatment. However, in

  1. Adherence issues in inherited metabolic disorders treated by low natural protein diets

    DEFF Research Database (Denmark)

    MaCdonald, A; van Rijn, M; Feillet, F


    Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor-free or esse......Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor...... usually shadowed that of PKU. There remains much work to be done in refining dietary treatments for all conditions and gaining acceptable dietary adherence and concordance, which is crucial for an optimal outcome....

  2. Bleeding Episodes Among Patients with Congenital Fibrinogen Disorders, a Study On 12 New Iranian Patients

    Directory of Open Access Journals (Sweden)

    Majid Naderi


    Full Text Available Background: Congenital fibrinogen disorders (CFDs comprise about 10% of rare bleeding disorders (RBDs. CFDs are divided into two groups of quantitative (afibrinogenemia and hypofibrinogenemia with autosomal recessive inheritance pattern, and qualitative (dysfibrinogenemia, hypodysfibrogenemia disorders, mainly with autosomal dominant inheritance pattern. Sistan and Baluchestan Province in Iran, with its high rate of consanguineous marriages, has a high incidence of RBDs including CFD. In the current study, we report clinical manifestations of patients with CFDs.Methods: Twelve new Iranian patients from Sistan and Baluchestan Province with different types of CFDs were selected for this study. Diagnosis of CFDs was based on clinical features and familial history followed by laboratory assessment by routine and specific coagulation tests including prothrombin time (PT and activated partial time tests (APTT, as well as FI activity assay by Clauss method.Results: Out of 12 patients, 3(25% had afibrinogenemia, 7(58.3% had hypofibrinogenemia while 2(16/7% were suspected of having dysfibrinogenemia. Although umbilical cord bleeding (UCB 9(75% was the most common clinical presentation among the study population, this feature was not observed among patients with dysfibrinogenemia. Hematoma (100% was the most common presentation of patients with dysfibrinogenemia.  Conclusion: Results of this study revealed that some clinical presentations are the diagnostic features of CFDs and can be used for precise and in-time diagnosis CFDs in conjunction with family history and laboratory findings.Keywords: Fibrinogen Deficiency; Congenital Afibrinogenemia; Blood Coagulation Disorder; Afibrinogenemia

  3. Dynamics of change of lipid and monoamine metabolisms and the blood coagulation system during experimental atherosclerosis caused by restriction of movement (United States)

    Gvishiani, G. S.; Kobakhidze, N. G.


    Shifts in lipid, catecholamine, and blood coagulation systems following various periods (1, 2, 3, and 4 months) of experimentally induced atherosclerosis were studied. The same indices were studied in the tissues of the myocardium, liver, and brain stem-reticular formation after decapitation of the animals at the end of the experiment. Periodic motion restriction caused an increase in blood beta-lipoproteins in the rabbits at the beginning of the experiment. An increase in general cholesterol content and a decrease in the lecithincholesterol index were established at the end of the experiment. Myocardial beta-lipoprotein and brain stem reticular formation general cholesterol contents were elevated; catecholamine content was increased at the end of the experiment. In the initial months, free adrenaline basically increased, while in later months blood adrenaline decreased and blood noradrenaline increased.

  4. The interplay between platelets and coagulation

    NARCIS (Netherlands)

    Weeterings, C.


    Platelet activation and blood coagulation are two processes often studied separately, but which cannot be seen independently from each other. Platelets play a pivotal role in coagulation, not only by providing negatively charged phospholipids, but also in localizing the coagulation process from a

  5. Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism (United States)


    Very Long-chain acylCoA Dehydrogenase (VLCAD) Deficiency; Carnitine Palmitoyltransferase Deficiencies (CPT1, CPT2); Mitochondrial Trifunctional Protein Deficiency; Long-chain Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogen Storage Disorders; Pyruvate Carboxylase Deficiency Disease; ACYL-CoA DEHYDROGENASE FAMILY, MEMBER 9, DEFICIENCY of; Barth Syndrome

  6. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

    NARCIS (Netherlands)

    Chrast, R.; Saher, G.; Nave, K.A.; Verheijen, M.H.G.


    The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid

  7. The protein concentration of blood coagulation factor VII can be measured equally well in plasma and serum

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Overgaard, K; Gram, J


    In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation...

  8. The prospects of application of natural antioxidants in correction of blood coagulation in patients with breast cancer during radiation therapy

    International Nuclear Information System (INIS)

    Syimonova, L.Yi.; Byilogurova, L.V.; Gertman, V.Z.; Pushkar, S.M.; Muzikant, P.M.; Nesterenko, G.Yi.


    As an accompanying therapy of the patients with BC Bipolan produced positive effect on coagulation homeostasis. By the end of the course of treatment the indices of homeostasis normalized in the experimental group of the patients; manifestations of DIC syndrome and thromboembolic complications were controlled


    Uwamungu, S; Nyamache, A K; Masaisa, F; Njoki, S K; Abdalah, F; Saibu, K; Ndahiriwe, O; Agwata, D


    Objectives: To determine the level of coagulation factors and inherited inhibitors in Fresh Frozen Plasma (FFP) and to evaluate Prothrombin Time and activated partial thrombin time in fresh frozen plasma. Cross-sectional study. Jomo Kenyatta University of Agriculture and Technology in Medical Laboratory Sciences. Eighteen blood bags collected from voluntary blood donors. Coagulation factors and inhibitors levels, Prothrombin Time (PT) and Activated Partial thrombin Time (APTT) remained within the reference range requested by quality assurance regulations after three months of storage. APTT and PT show an increase from baseline to one month then remain constant up to three months, while, Fibrinogen, Factor II, Factor V, Factor VII, Factor X, Von Willbrand Factor, Protein C and Antithrombin decreased from baseline up to three months and then Factor VIII, Factor IX, Factor XI, Factor XII and Protein S, remained constant from baseline up to one month and decreased up to three months. There is good retention of all coagulation factors and inhibitors in plasma produced from whole blood within eight hours of collection, stored at minus 18 degrees C for three months.


    Directory of Open Access Journals (Sweden)

    Youssef Al Tonbary


    The study included 72 children with hematological disorders registered from 2000 to 2008 in MUCH. The hemophilic patient was defined as a person with physician-diagnosed hemophilia A or B and a measured factor VIII or IX activity level of 30% or less. Persons with acquired inhibitors of FVIII or FIX excluded. Severity level was categorized as mild if the factor activity level was 6–30%, moderate if 1–5% and severe if

  11. Pandora's box: ethics of PGD for inherited risk of late-onset disorders. (United States)

    Noble, Ray; Bahadur, Gulam; Iqbal, Mohammad; Sanyal, Arnab


    Until recently, the primary use of preimplantation genetic diagnosis (PGD) has been the selection of embryos to avoid lethal or debilitating gene mutations or abnormal chromosome complement. PGD can be used to reduce the risk of transferring to the uterus an embryo with Down syndrome, and parents who are carriers of severe genetic diseases may choose to avoid having children with these debilitating genetic conditions. The use of PGD is now being extended to include gene mutations that increase the risk of late-onset disorders such as breast and ovarian cancer. This paper argues for caution in advocating reproductive methods that are costly, have a limited chance of success, and for which the long-term outcome is unknown. Counselling should allow women a true choice of declining the option of PGD without recrimination, feelings of guilt or social pressure. There is concern that the Human Fertilisation and Embryology Authority has approved extension of PGD to late-onset multifactorial diseases without clear guidelines for its use. Guidelines for embryo selection should be revised to deal with potential conflict between reproductive success and genetic screening for disorders that do not profoundly affect the embryo or the children.

  12. Comparison of the in vitro effects of saline, hypertonic hydroxyethyl starch, hypertonic saline, and two forms of hydroxyethyl starch on whole blood coagulation and platelet function in dogs. (United States)

    Wurlod, Virginie A; Howard, Judith; Francey, Thierry; Schweighauser, Ariane; Adamik, Katja N


    To compare the in vitro effects of hypertonic solutions and colloids to saline on coagulation in dogs. In vitro experimental study. Veterinary teaching hospital. Twenty-one adult dogs. Blood samples were diluted with saline, 7.2% hypertonic saline solution with 6% hydroxyethylstarch with an average molecular weight of 200 kDa and a molar substitution of 0.4 (HH), 7.2% hypertonic saline (HTS), hydroxyethyl starch (HES) 130/0.4 or hydroxyethyl starch 600/0.75 at ratios of 1:22 and 1:9, and with saline and HES at a ratio of 1:3. Whole blood coagulation was analyzed using rotational thromboelastometry (extrinsic thromboelastometry-cloting time (ExTEM-CT), maximal clot firmness (MCF) and clot formation time (CFT) and fibrinogen function TEM-CT (FibTEM-CT) and MCF) and platelet function was analyzed using a platelet function analyzer (closure time, CTPFA ). All parameters measured were impaired by saline dilution. The CTPFA was prolonged by 7.2% hypertonic saline solution with 6% hydroxyethylstarch with an average molecular weight of 200 kDa and a molar substitution of 0.4 (HH) and HTS but not by HES solutions. At clinical dilutions equivalent to those generally administered for shock (saline 1:3, HES 1:9, and hypertonic solutions 1:22), CTPFA was more prolonged by HH and HTS than other solutions but more by saline than HES. No difference was found between the HES solutions or the hypertonic solutions. ExTEM-CFT and MCF were impaired by HH and HTS but only mildly by HES solutions. At clinically relevant dilutions, no difference was found in ExTEM-CFT between HTS and saline or in ExTEM-MCF between HH and saline. No consistent difference was found between the 2 HES solutions but HH impaired ExTEM-CFT and MCF more than HTS. At high dilutions, FibTEM-CT and -MCF and ExTEM-CT were impaired by HES. Hypertonic solutions affect platelet function and whole blood coagulation to a greater extent than saline and HES. At clinically relevant dilutions, only CTPFA was markedly more

  13. [Inherited aplastic anemias]. (United States)

    Esteves, A C; Freitas, O; Almeida, T; Rosado, L


    The inherited aplastic anaemias are a heterogeneous group of disorders characterized by bone marrow failure, frequent association with one or more somatic anomalies and increased risk of cancer. They are rare disorders, usually diagnosed at paediatric age, and have significant premature mortality. The authors report 11 cases of inherited aplastic anaemias, 8 of Fanconi's anaemia and 3 of Dyskeratosis congenita. These cases were diagnosed in the last 14 years in the Dona Estefânia Hospital. 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  14. Tracheostomy: current practice on timing, correction of coagulation disorders and peri-operative management - a postal survey in the Netherlands

    NARCIS (Netherlands)

    Veelo, D. P.; Dongelmans, D. A.; Phoa, K. N.; Spronk, P. E.; Schultz, M. J.


    BACKGROUND: Several factors may delay tracheostomy. As many critically ill patients either suffer from coagulation abnormalities or are being treated with anticoagulants, fear of bleeding complications during the procedure may also delay tracheostomy. It is unknown whether such (usually mild)

  15. A Web Site to Improve Management of Patients with Inherited Bleeding Disorders in the Emergency Department: Results at 2 Years. (United States)

    Tagliaferri, Annarita; Di Perna, Caterina; Biasoli, Chiara; Rivolta, Gianna Franca; Quintavalle, Gabriele; Cervellin, Gianfranco; Barozzi, Marco; Benedettini, Laura; Pattacini, Corrado


    Treatment of patients with inherited bleeding disorders (PWIBD) in the emergency department (ED) is challenging. In 2010, a project was started involving all eight hemophilia centers (HC) and all 44 EDs of the Region of Emilia-Romagna (Italy) to improve emergency care for PWIBD. The project incorporates guidelines for emergency treatment, education for ED staff, and a dedicated Web site providing extensive information, proposing treatments, and sharing data with patients' electronic clinical records. A Web algorithm, accessible to PWIBD as well as ED and HC staff, suggests the first dose of concentrate for each type and severity of bleed or trauma. Following training courses in each ED, the network was activated. During 2012 and 2013, the site was visited 14,000 times, the EDs accessed the Web site 1,739 times, and used the algorithms 206 times. In two reference EDs, triage-assessment and triage-treatment times were reduced in 2013 and 2012 (27/20 and 110/71.5 minutes, respectively) and medical advice from the HC increased (54 vs. 24% cases). The main advantages of this system are better management of patients in ED (shorter triage-to-treatment times) and improved collaboration between HCs and EDs. The most critical point remaining is staff turnover in EDs, necessitating continual training. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. (United States)

    Shafqat, Naeem; Turnbull, Andrew; Zschocke, Johannes; Oppermann, Udo; Yue, Wyatt W


    3-Hydroxy-3-methylglutaryl coenzyme A (CoA) synthase (HMGCS) catalyzes the condensation of acetyl-CoA and acetoacetyl-CoA into 3-hydroxy-3-methylglutaryl CoA. It is ubiquitous across the phylogenetic tree and is broadly classified into three classes. The prokaryotic isoform is essential in Gram-positive bacteria for isoprenoid synthesis via the mevalonate pathway. The eukaryotic cytosolic isoform also participates in the mevalonate pathway but its end product is cholesterol. Mammals also contain a mitochondrial isoform; its deficiency results in an inherited disorder of ketone body formation. Here, we report high-resolution crystal structures of the human cytosolic (hHMGCS1) and mitochondrial (hHMGCS2) isoforms in binary product complexes. Our data represent the first structures solved for human HMGCS and the mitochondrial isoform, allowing for the first time structural comparison among the three isoforms. This serves as a starting point for the development of isoform-specific inhibitors that have potential cholesterol-reducing and antibiotic applications. In addition, missense mutations that cause mitochondrial HMGCS deficiency have been mapped onto the hHMGCS2 structure to rationalize the structural basis for the disease pathology. (c) 2010 Elsevier Ltd. All rights reserved.

  17. Cerebrovascular requirement for sealant, anti-coagulant and remodeling molecules that allow for the maintenance of vascular integrity and blood supply. (United States)

    Atwood, Craig S; Bowen, Richard L; Smith, Mark A; Perry, George


    The integrity of the vasculature and the maintenance of the blood supply to the brain are crucial for the survival of higher vertebrates. However, peripheral mechanisms of sealing the vasculature that rely on the clotting of blood and platelet aggregation around the site of a 'leak' would lead to decreased cerebral perfusion and compromise the viability of terminally differentiated and irreplaceable neurons. Therefore, in higher organisms it is likely that a sealant/anti-coagulant system that maintains vascular supply has evolved as a necessity to life. We propose that one such system involves the amyloid-beta precursor protein (AbetaPP) and its cleavage product Abeta since (1) both AbetaPP/Abeta are known to deposit in the media of the cerebrovasculature wall following localized injury, (2) Abeta is generated from AbetaPP, a known acute phase reactant, (3) Abeta's physiochemical properties allow it to span between the extracellular matrix and the (endothelial) cell membrane and under inflammatory conditions aggregate to form an intracranial 'scab', thereby maintaining structural integrity of the blood brain barrier, (4) AbetaPP/Abeta together act as an anti-coagulant, (5) Abeta promotes vascular/neuronal remodeling, and (6) Abeta deposits resolve after injury. These properties are consistent with the acute phase generation and rapid cortical deposition of AbetaPP/Abeta following injury (either sustained by trauma or stresses associated with aging) that would be an important compensatory response aimed at limiting the loss of terminally differentiated neurons. Such a system would allow the maintenance of blood supply to the brain by sealing vascular lesions, preventing hemorrhagic stroke while at the same time inhibiting the coagulation cascade from blocking capillaries. Obviously, strategies to remove Abeta would have serious consequences for the integrity of the blood-brain barrier. Indeed, recent in vivo evidence demonstrates that the removal of deposited Abeta

  18. To inherit heritage or to inherit inheritance?

    Directory of Open Access Journals (Sweden)

    Vladimir Krivošejev


    Full Text Available The Republic of Serbia is one of the few, if not the only country in the world that, at ratification and translation of the term „baština“– heritage which appears in two significant and related international conventions of UNESCO, used different terms: „baština“– „heritage“, with regard to the Convention Concerning the Protection of the World Cultural and Natural Heritage, and „nasledje“ –inheritance in the Convention for the Safeguarding of the Intangible Cultural Heritage. One of the reasons for the subsequent rejection of the term heritage could lay in the opinion that it was the case of (end of 20th and beginning of the 21st century political bureaucratic introduction of an old, forgotten word, which also contains the notion of gender incorrectness based on pointing out the inheritance through the male line, which could be in conflict with international law. The views expressed in this paper suggest the unsustainability of these claims, as well as greater suitability of the term „baština“– heritage. Namely, the ratification of the Convention Concerning the Protection of the World Cultural and Natural Heritage was done as early as in 1974, and since then the term „baština“– heritage was used, its new introduction into use on the basis of recent daily political aspirations cannot be the case. At the same time inheritance through the male line is encountered with the use of the Latin word „patrimonium“, which is the basis for the terms used in the official translation of the UNESCO-listed conventions in French and Spanish: „patrimoine“ and „patrimonio“ (and other Roman languages so that the use of the term „baština“ –heritage cannot be a violation of international legal norms. Finally, bearing in mind the fact that, in general, use of languages is impossible to achieve complete gender purism, it is necessary to emphasize that in contrast to the term „nasledje“ – inheritance, the

  19. Application of whole-exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia

    DEFF Research Database (Denmark)

    Leinøe, Eva; Zetterberg, Eva; Kinalis, Savvas


    Rare inherited bleeding disorders (IBD) are a common cause of bleeding tendency. To ensure a correct diagnosis, specialized laboratory analyses are necessary. This study reports the results of an upfront diagnostic strategy using targeted whole exome sequencing. In total, 156 patients with a sign......Rare inherited bleeding disorders (IBD) are a common cause of bleeding tendency. To ensure a correct diagnosis, specialized laboratory analyses are necessary. This study reports the results of an upfront diagnostic strategy using targeted whole exome sequencing. In total, 156 patients....... The genetic investigations detailed here extricated our patients from a diagnostic conundrum, thus demonstrating that continuous optimization of the diagnostic work-up of IBD is of great benefit....

  20. Drawings of Blood Cells Reveal People's Perception of Their Blood Disorder: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Steven Ramondt

    Full Text Available Sickle cell disease (SCD and thalassemia are rare but chronic blood disorders. Recent literature showed impaired quality of life (QOL in people with these blood disorders. Assessing one of the determinants of QOL (i.e. illness perceptions therefore, is an important next research area.We aimed to explore illness perceptions of people with a blood disorder with drawings in addition to the Brief Illness Perception Questionnaire (Brief IPQ. Drawings are a novel method to assess illness perceptions and the free-range answers drawings offer can add additional insight into how people perceive their illness.We conducted a cross-sectional study including 17 participants with a blood disorder. Participants' illness perceptions were assessed by the Brief IPQ and drawings. Brief IPQ scores were compared with reference groups from the literature (i.e. people with asthma or lupus erythematosus.Participants with SCD or thalassemia perceived their blood disorder as being more chronic and reported more severe symptoms than people with either asthma or lupus erythematosus. In the drawings of these participants with a blood disorder, a greater number of blood cells drawn was negatively correlated with perceived personal control (P<0.05, indicating that a greater quantity in the drawing is associated with more negative or distressing beliefs.Participants with a blood disorder perceive their disease as fairly threatening compared with people with other chronic illnesses. Drawings can add additional insight into how people perceive their illness by offering free-range answers.

  1. Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and Ringer's lactate on blood loss and coagulation after cardiac surgery. (United States)

    Skhirtladze, K; Base, E M; Lassnigg, A; Kaider, A; Linke, S; Dworschak, M; Hiesmayr, M J


    Infusion of 5% human albumin (HA) and 6% hydroxyethyl starch 130/0.4 (HES) during cardiac surgery expand circulating volume to a greater extent than crystalloids and would be suitable for a restrictive fluid therapy regimen. However, HA and HES may affect blood coagulation and could contribute to increased transfusion requirements. We randomly assigned 240 patients undergoing elective cardiac surgery to receive up to 50 ml kg(-1) day(-1) of either HA, HES, or Ringer's lactate (RL) as the main infusion fluid perioperatively. Study solutions were supplied in identical bottles dressed in opaque covers. The primary outcome was chest tube drainage over 24 h. Blood transfusions, thromboelastometry variables, perioperative fluid balance, renal function, mortality, intensive care unit, and hospital stay were also assessed. The median cumulative blood loss was not different between the groups (HA: 835, HES: 700, and RL: 670 ml). However, 35% of RL patients required blood products, compared with 62% (HA) and 64% (HES group; P=0.0003). Significantly, more study solution had to be administered in the RL group compared with the colloid groups. Total perioperative fluid balance was least positive in the HA group [6.2 (2.5) litre] compared with the HES [7.4 (3.0) litre] and RL [8.3 (2.8) litre] groups (Pcoagulation and produced greater haemodilution, which was associated with more transfusion of blood products compared with crystalloid use only.

  2. [Detection of lupus anticoagulants in the routine blood coagulation laboratory exemplified by 36 patients with systemic lupus erythematosus]. (United States)

    Halbmayer, W M; Haushofer, A; Schratzberger, W; Petera, P; Duschet, P; Fischer, M


    36 patients suffering from systemic lupus erythematosus (SLE) were subjected to various screening and confirmation tests for the presence of lupus anticoagulants (LA) which are a risk for thrombosis. In five out of the 36 patients (14%) lupus anticoagulants could be found. Five out of the 36 patients (14%) showed increased antiphospholipid antibody (APA) levels whereby only two of these patients were at the same time LA-positive. The specificity, sensitivity and effectiveness of various tests in respect of LA-demonstrability have been assessed and the results taken as the basis for proposal of a largely automated stepwise diagnostic procedure for LA-determination within the routine coagulation laboratory.

  3. Thromboelastometry versus standard coagulation tests versus restrictive protocol to guide blood transfusion prior to central venous catheterization in cirrhosis: study protocol for a randomized controlled trial. (United States)

    Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Neto, Ary Serpa; do Prado, Rogerio Ruscitto; Silva, Eliezer; de Almeida, Marcio Dias; Correa, Thiago Domingos


    Liver failure patients have traditionally been empirically transfused prior to invasive procedures. Blood transfusion is associated with immunologic and nonimmunologic reactions, increased risk of adverse outcomes and high costs. Scientific evidence supporting empirical transfusion is lacking, and the best approach for blood transfusion prior to invasive procedures in cirrhotic patients has not been established so far. The aim of this study is to compare three transfusion strategies (routine coagulation test-guided - ordinary or restrictive, or thromboelastometry-guided) prior to central venous catheterization in critically ill patients with cirrhosis. Design and setting: a double-blinded, parallel-group, single-center, randomized controlled clinical trial in a tertiary private hospital in São Paulo, Brazil. adults (aged 18 years or older) admitted to the intensive care unit with cirrhosis and an indication for central venous line insertion. Patients will be randomly assigned to three groups for blood transfusion strategy prior to central venous catheterization: standard coagulation tests-based, thromboelastometry-based, or restrictive. The primary efficacy endpoint will be the proportion of patients transfused with any blood product prior to central venous catheterization. The primary safety endpoint will be the incidence of major bleeding. Secondary endpoints will be the proportion of transfusion of fresh frozen plasma, platelets and cryoprecipitate; infused volume of blood products; hemoglobin and hematocrit before and after the procedure; intensive care unit and hospital length of stay; 28-day and hospital mortality; incidence of minor bleeding; transfusion-related adverse reactions; and cost analysis. This study will evaluate three strategies to guide blood transfusion prior to central venous line placement in severely ill patients with cirrhosis. We hypothesized that thromboelastometry-based and/or restrictive protocols are safe and would significantly

  4. Hemophilia as a defect of the tissue factor pathway of blood coagulation: Effect of factors VIII and IX on factor X activation in a continuous-flow reactor

    International Nuclear Information System (INIS)

    Repke, D.; Gemmell, C.H.; Guha, A.; Turitto, V.T.; Nemerson, Y.; Broze, G.J. Jr.


    The effect of factors VIII and IX on the ability of the tissue factor-factor VIIa complex to activate factor X was studied in a continuous-flow tubular enzyme reactor. Tissue factor immobilized in a phospholipid bilayer on the inner surface of the tube was exposed to a perfusate containing factors VIIa, VIII, IX, and X flowing at a wall shear rate of 57, 300, or 1130 sec -1 . The addition of factors VIII and IX at their respective plasma concentrations resulted in a further 2 endash-to 3 endash fold increase. The direct activation of factor X by tissue factor-factor VIIa could be virtually eliminated by the lipoprotein-associated coagulation inhibitor. These results suggest that the tissue factor pathway, mediated through factors VIII and IX, produces significant levels of factor Xa even in the presence of an inhibitor of the tissue factor-factor VIIa complex; moreover, the activation is dependent on local shear conditions. These findings are consistent both with a model of blood coagulation in which initiation of the system results from tissue factor and with the bleeding observed in hemophilia

  5. Home enteral tube feeding in children with inherited metabolic disorders: a review of long-term carer knowledge and technique. (United States)

    Evans, S; Preston, F; Daly, A; Ashmore, C; Holden, C; MacDonald, A


    Home enteral tube feeding (HETF) is commonly used in children with inherited metabolic disorders (IMD). It is unclear how caregiver knowledge and their safety in using tube feeding techniques changes over time. Caregivers of children with IMD on HETF from one UK IMD centre had annual interviews over 3 years using a structured questionnaire and observation to assess HETF knowledge and safety techniques. Thirty-two caregivers of IMD children (median age 5.3 years; range 0.3-13.6 years) were studied. Seventy-eight percent (n = 25) of subjects had been on HETF for >5 years. Over 3 years, many caregivers' HETF techniques deteriorated: accurate feed ingredient measurement decreased from 36% to 11%; correct flushing of tubes decreased from 56% to 44%; checking tube position as recommended decreased from 72% to 56%; and correct hand washing decreased from 38% to 25%. Despite improvements, knowledge of some aspects remained poorly understood: dangers of incorrect tube placement increased from 41% to 56%; correct position for night feeding increased from 38% to 56%; and feed ingredient storage decreased from 87% to 38%. The HETF techniques of caregivers of children with IMD declined over time. Caregivers need to understand that HETF, particularly in IMD, is a serious procedure associated with life-threatening risks. Poor HETF practices may cause feed contamination, incorrect feed concentration, feed intolerance, aspiration, peritonitis and even metabolic decompensation. HETF skills should be reassessed annually, with compulsory retraining if basic 'core' HETF competencies are not demonstrated. © 2012 The Authors. Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.

  6. Mechanisms Linking Red Blood Cell Disorders and Cardiovascular Diseases


    Mozos, Ioana


    The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular dise...

  7. Inherited bleeding disorders

    African Journals Online (AJOL)


    Jan 10, 2018 ... The incidence is 1 in 10 000 live births in haemophilia A and 1 in 25 000 live births ... heparin, lupus anticoagulant or antifactor inhibitor. Table 1. Expected results of laboratory tests for various .... vWD, as factor VIII/vWF levels correct at the end of pregnancy in mild type 1 cases. Patients with vWD types 2A, ...

  8. Impact of different storage times at room temperature of unspun citrated blood samples on routine coagulation tests results. Results of a bicenter study and review of the literature. (United States)

    Toulon, P; Metge, S; Hangard, M; Zwahlen, S; Piaulenne, S; Besson, V


    A maximum delay between blood collection and coagulation testing of 4 hours is recommended by most guidelines. As information on optimal storage times is limited, we investigated the potential effect of different storage times of unspun tubes, that is, ≤2, 4, 6, and 8 hours, on routine coagulation test results. Four evacuated polymer tubes containing 0.109 mol/L tri-Na citrate were drawn from 144 patients, including 39 patients on vitamin K-antagonists. Except for storage time, all tubes underwent the same preanalytical process. Prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, factor V (FV), FVIII, and D-dimer were evaluated in two centers using the same technical conditions. Analytical comparison of aPTT, fibrinogen, FV, and FVIII results evaluated after prolonged storage times vs a <2-hours storage demonstrated significant difference, whereas PT/INR and D-dimer remained unchanged up to 8 hours. Mean bias between test results obtained after prolonged storage times remained below the desirable values for all studied parameters except for FVIII evaluated after 6- and 8-hours storages, but only in patients with FVIII above 100 IU/dL. Even though the corresponding bias of -5.2% and -8.5%, respectively, remained within the GEHT recommended limits of variation, its evaluation after an 8-hours storage could lead to significant underestimation of FVIII. These results suggest that, in the studied technical conditions, PT/INR, aPTT, fibrinogen, FV, and D-dimer can be reliably evaluated in tubes stored unspun at room temperature for up to 8 hours after blood collection. That optimal delay should be of 6 hours for FVIII. © 2017 The Authors. International Journal of Laboratory Hematology Published by John Wiley & Sons Ltd.

  9. Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Skouby, S O.; Andersen, L F


    BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen...... after progestin intake. The integrated response, AUC, for TFPI was significantly lower in the HRT groups compared with the reference group. CONCLUSION: The observed changes may increase the early thrombotic risk associated with HRT use. Udgivelsesdato: 2002-Dec...

  10. Neutralisation of the anti-coagulant effects of heparin by histones in blood plasma and purified systems. (United States)

    Longstaff, Colin; Hogwood, John; Gray, Elaine; Komorowicz, Erzsebet; Varjú, Imre; Varga, Zoltán; Kolev, Krasimir


    Neutrophil extracellular traps (NETs) composed primarily of DNA and histones are a link between infection, inflammation and coagulation. NETs promote coagulation and approaches to destabilise NETs have been explored to reduce thrombosis and treat sepsis. Heparinoids bind histones and we report quantitative studies in plasma and purified systems to better understand physiological consequences. Unfractionated heparin (UFH) was investigated by activated partial thromboplastin time (APTT) and alongside low-molecular-weight heparins (LMWH) in purified systems with thrombin or factor Xa (FXa) and antithrombin (AT) to measure the sensitivity of UFH or LMWH to histones. A method was developed to assess the effectiveness of DNA and non-anticoagulant heparinoids as anti-histones. Histones effectively neutralised UFH, the IC50 value for neutralisation of 0.2 IU/ml UFH was 1.8 µg/ml histones in APTT and 4.6 µg/ml against 0.6 IU/ml UFH in a purified system. Histones also inhibited the activities of LMWHs with thrombin (IC50 6.1 and 11.0 µg/ml histones, for different LMWHs) or FXa (IC50 7.8 and 7.0 µg/ml histones). Direct interactions of UFH and LMWH with DNA and histones were explored by surface plasmon resonance, while rheology studies showed complex effects of histones, UFH and LMWH on clot resilience. A conclusion from these studies is that anticoagulation by UFH and LMWH will be compromised by high affinity binding to circulating histones even in the presence of DNA. A complete understanding of the effects of histones, DNA and heparins on the haemostatic system must include an appreciation of direct effects on fibrin and clot structure.

  11. Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: a congenital disorder of glycosylation mimicking glycogen storage disease. (United States)

    Choi, Rihwa; Woo, Hye In; Choe, Byung-Ho; Park, Seungman; Yoon, Yeomin; Ki, Chang-Seok; Lee, Soo-Youn; Kim, Jong-Won; Song, Junghan; Kim, Dong Sub; Kwon, Soonhak; Park, Hyung-Doo


    Rare inherited metabolic diseases with neurological and gastrointestinal manifestations can be misdiagnosed as other diseases or remain as disorders with indeterminate etiologies. This study aims to provide evidence to recommend the utility of whole exome sequencing in clinical diagnosis of a rare inherited metabolic disease. A 4-month-old female baby visited an outpatient clinic due to poor weight gain, repeated seizure-like episodes, developmental delay, and unexplained hepatomegaly with abnormal liver function test results. Although liver biopsy revealed moderate fibrosis with a suggested diagnosis of glycogen storage disease (GSD), no mutations were identified either by single gene approach for GSD (G6PC and GAA) or by next generation sequencing panels for GSD (including 21 genes). Whole exome sequencing of the patient revealed compound heterozygous mutations of PMM2: c.580C>T (p.Arg194*) and c.713G>C (p.Arg238Pro) which mutations were associated with congenital disorder of glycosylation Ia (CDG-Ia: PMM2-CDG). We successfully applied exome sequencing to diagnose the first reported Korean patient with CDG-Ia, which was misdiagnosed as GSD. Whole exome sequencing may prove to be the preferred strategy for analysis of clinical features that do not readily suggest a specific diagnosis, such as those observed in inherited metabolic diseases, including CDG. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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


    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.

  13. Chapter 3. Biological properties of ethynyl-piperidol polymers. 3.1. Activating effect of quaternized linear and graft-polymers of ethynyl-piperidol on blood coagulation system

    International Nuclear Information System (INIS)

    Khalikov, D.Kh.


    This article is devoted to activating effect of quaternized linear and graft-polymers of ethynyl-piperidol on blood coagulation system. The indexes of blood clotting at intraperitoneal injection of polymers were considered. The anti heparin activity of methiodide of poly-isopropenyl trimethyl ethynyl piperidol was considered as well. The influence of molecular weight on styptic activity and toxicity of methiodide of poly-isopropenyl trimethyl ethynyl piperidol was studied. The styptic activity of grafted polymers of ethynyl piperidol was defined.

  14. ABO blood groups and psychiatric disorders: a Croatian study. (United States)

    Pisk, Sandra Vuk; Vuk, Tomislav; Ivezić, Ena; Jukić, Irena; Bingulac-Popović, Jasna; Filipčić, Igor


    The prevalence of ABO alleles is different in different populations, and many studies have shown a correlation between the occurrences of some diseases and different genotypes of ABO blood groups. The aim of this study was to determine whether there is a significant association between psychiatric syndromes and ABO blood groups. This case-control study involved 156 psychiatric patients and 303 healthy, unrelated, voluntary blood donors. Genomic DNA was isolated from blood on a QIAcube device using a QIAamp DNA Blood mini QIAcube kit. ABO genotyping on five basic ABO alleles was performed using allele-specific polymerase chain reaction analysis. Compared with healthy subjects, a significantly higher proportion of psychiatric patients had AB blood group (χ 2 =9.359, df=3, p=0.025) and, accordingly, a significantly higher incidence of A1B genotype (χ 2 =8.226, df=3, p=0.042). The odds ratio showed that psychiatric disorders occur almost three times more frequently in carriers of AB group compared to other blood groups. However, no statistically significant difference was found in the distribution of ABO blood groups among patients with different psychiatric diagnoses. Likewise, no correlations were found between ABO blood groups and other characteristics of the psychiatric patients (sex, psychiatric heredity, somatic comorbidity, suicidality). The results of this study support the hypothesis of an association between psychiatric disorders and ABO blood groups. The probability is that psychiatric disorders will occur almost three times more frequently in carriers of AB group compared to other ABO blood groups in the Croatian population.

  15. The relationship of HIV status, type of coagulation disorder, and school absenteeism to cognition, educational performance, mood, and behavior of boys with hemophilia. (United States)

    Mayes, S D; Handford, H A; Schaefer, J H; Scogno, C A; Neagley, S R; Michael-Good, L; Pelco, L E


    Psychological and educational data were analyzed for all school-aged males with hemophilia at the Hemophilia Center of Central Pennsylvania (N = 66). Mean IQ (113.5) was higher than normal, and 2.4 times as many boys with hemophilia were enrolled in gifted programming than is the state average for boys. However, there was a disproportionately high prevalence of attention-deficit/hyperactivity disorder (ADHD; 28.3%), learning disability (LD; 15.8%), and graphomotor weakness. These were not significantly associated with HIV status or type and severity of coagulation disorder. School absenteeism was high but was not significantly related to academic achievement, IQ/achievement discrepancy, need for educational intervention, or diagnosis of ADHD or LD.

  16. Inflammation and coagulation

    NARCIS (Netherlands)

    Levi, Marcel; van der Poll, Tom


    In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation leads to activation of coagulation, and coagulation also considerably affects inflammatory activity. Molecular

  17. Coagulation and fibrinolysis during laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Rahr, H B; Fabrin, K; Larsen, J F


    Laparoscopic surgery appears to be less traumatic to the patient than open surgery, but its influence upon coagulation and fibrinolysis is incompletely elucidated. Our aim was to measure markers of coagulation and fibrinolysis before, during. and after laparoscopic cholecystectomy (LC). Blood...

  18. Blood and Brain Glutamate Levels in Children with Autistic Disorder (United States)

    Hassan, Tamer H.; Abdelrahman, Hadeel M.; Fattah, Nelly R. Abdel; El-Masry, Nagda M.; Hashim, Haitham M.; El-Gerby, Khaled M.; Fattah, Nermin R. Abdel


    Despite of the great efforts that move forward to clarify the pathophysiologic mechanisms in autism, the cause of this disorder, however, remains largely unknown. There is an increasing body of literature concerning neurochemical contributions to the pathophysiology of autism. We aimed to determine blood and brain levels of glutamate in children…

  19. Peripheral blood brain-derived neurotrophic factor in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, K; Vinberg, M; Kessing, L V


    subjects and between affective states in bipolar disorder patients, including assessment of the effect of treatment of acute episodes on BDNF levels. A systematic review of English language studies without considering publication status was conducted in PubMed (January 1950-November 2014), Embase (1974......Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in bipolar disorder, speculated to mirror alterations in brain expression of BDNF. The research area is rapidly evolving; however, recent...... investigations have yielded conflicting results with substantial variation in outcomes, highlighting the need to critically assess the state of current evidence. The aims of the study were to investigate differences in peripheral blood BDNF concentrations between bipolar disorder patients and healthy control...

  20. A case of maternal vitamin K deficiency associated with hyperemesis gravidarum: its potential impact on fetal blood coagulability. (United States)

    Shigemi, Daisuke; Nakanishi, Kazuho; Miyazaki, Miwa; Shibata, Yoshie; Suzuki, Shunji


    Vitamin K deficiency is associated with malnutrition in some complications, such as hyperemesis gravidarum, active gastrointestinal diseases, and psychological disorders. Maternal vitamin K deficiency can cause fetal bleeding, in particular, fetal intracranial hemorrhage. Although fetal hemorrhage is uncommon, severe damage to the fetus may be inevitable. We describe a pregnant woman with vitamin K deficiency possibly due to hyperemesis gravidarum. The patient was treated for the deficiency, and no fetal or neonatal hemorrhagic diseases were manifested.

  1. The Role of Yeast Beta Glucan on Blood Coagulation in Streptozotocin-Induced Diabetes and Irradiated Rats

    International Nuclear Information System (INIS)

    El-Kashoury, M.M.A.; Abdel Fattah, S.M.; Ramadan, L.A.; El-Denshary, E.S.


    Clotting abnormalities are observed after exposure to ionizing radiation as well as in diabetes melittus. The objective of this study is to elucidate the role of yeast beta glucan (YBG) in the modulation of some biochemical variations observed in γ-irradiated, diabetic and diabeticγγ-irradiated rats. Gamma-irradiation was performed through the whole body exposure of rats to 6 Gy administered in four fractions of 1.5 Gy two times per week for two weeks. Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg body weight). YBG was given orally to male albino rats (1 g/kg body weight) for two weeks post irradiation and/or induction of diabetes. Animals were divided into 4 main groups: 1- control, 2- γ-irradiated, 3- diabetic and 4- diabetic-γ-irradiated rats. Each group was subdivided into 2 subgroups (a) untreated and (b) treated. The 3rd and 14th day, after the last dose of radiation in the irradiated groups and after the induction of diabetes in diabetic groups, were chosen to evaluate the effect of oral YBG in irradiated and/or diabetic rats. The results revealed that the body weight decreased significantly in irradiated, diabetic and diabetic–irradiated rats. The loss of weight was accompanied by a reduction in the pancreas weight. Glucose concentration was significantly increased in diabetic group at the two time intervals. It is worth noting that, radiation ameliorated blood glucose level in diabetic-γ-irradiated group. Radiation exposure and/or diabetes caused an oxidative stress manifested by a significant increase of malondialdhyde (MDA) accompanied by a significant decrease in glutathione (GSH) level. This oxidative stress caused disturbances in the measured clotting parameters by enhancing platelet aggregation (PA) induced by arachidonic acid and increased thrombin level as concluded from the significant shortening of prothrombin time (PT) and activated partial thromboplastin time (APTT). Also, exposure to radiation

  2. Targeted massively parallel sequencing and histological assessment of skeletal muscles for the molecular diagnosis of inherited muscle disorders. (United States)

    Nishikawa, Atsuko; Mitsuhashi, Satomi; Miyata, Naomasa; Nishino, Ichizo


    Inherited skeletal muscle diseases are genetically heterogeneous diseases caused by mutations in more than 150 genes. This has made it challenging to establish a high-throughput screening method for identifying causative gene mutations in clinical practice. In the present study, we developed a useful method for screening gene mutations associated with the pathogenesis of skeletal muscle diseases. We established four target gene panels, each covering all exonic and flanking regions of genes involved in the pathogenesis of the following muscle diseases: (1) muscular dystrophy (MD), (2) congenital myopathy/congenital myasthenic syndrome, (3) metabolic myopathy and (4) myopathy with protein aggregations/rimmed vacuoles. We assigned one panel to each patient based on the results of clinical and histological analyses of biopsied muscle samples and performed high-throughput sequencing by using Ion PGM next-generation sequencer. We also performed protein analysis to confirm defective proteins in patients with major muscular dystrophies. Further, we performed muscle-derived cDNA analysis to identify splice-site mutations. We identified possible causative gene mutations in 33% of patients (62/188) included in this study. Our results showed that the MD panel was the most useful, with a diagnostic rate of 46.2%. Thus, we developed a high-throughput sequencing technique for diagnosing inherited muscle diseases. The use of this technique along with histological and protein analyses may be useful and cost-effective for screening mutations in patients with inherited skeletal muscle diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  3. Networks of enzymatically oxidized membrane lipids support calcium-dependent coagulation factor binding to maintain hemostasis

    NARCIS (Netherlands)

    Lauder, Sarah N; Allen-Redpath, Keith; Slatter, David A; Aldrovandi, Maceler; O'Connor, Anne; Farewell, Daniel; Percy, Charles L; Molhoek, Jessica E; Rannikko, Sirpa; Tyrrell, Victoria J; Ferla, Salvatore; Milne, Ginger L; Poole, Alastair W; Thomas, Christopher P; Obaji, Samya; Taylor, Philip R; Jones, Simon A.; de Groot, Phillip G; Urbanus, Rolf T; Hörkkö, Sohvi; Uderhardt, Stefan; Ackermann, Jochen; Vince Jenkins, P; Brancale, Andrea; Krönke, Gerhard; Collins, Peter W; O'Donnell, Valerie B


    Blood coagulation functions as part of the innate immune system by preventing bacterial invasion, and it is critical to stopping blood loss (hemostasis). Coagulation involves the external membrane surface of activated platelets and leukocytes. Using lipidomic, genetic, biochemical, and mathematical

  4. Daclatasvir and Asunaprevir Combination Therapy-induced Hepatitis and Cholecystitis with Coagulation Disorder due to Hypersensitivity Reactions (United States)

    Miyashima, Yuichi; Honma, Yuichi; Miyagawa, Koichiro; Oe, Shinji; Senju, Michio; Shibata, Michihiko; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru


    A 70-year-old woman with chronic hepatitis C was admitted to our hospital due to liver injury, cholecystitis, and disseminated intravascular coagulation with a fever and skin rash. She had been on a combination regimen of daclatasvir and asunaprevir for 2 weeks of a 24-week regimen. Because of the symptoms, laboratory findings, results of a drug-induced lymphocyte stimulation test, and pathological findings of liver biopsy, we diagnosed her with drug-induced liver injury. Although daclatasvir and asunaprevir combination therapy is generally well-tolerated, some serious adverse effects have been reported. Our findings indicate that immunoallergic mechanisms were associated with daclatasvir and asunaprevir-induced liver injury. PMID:27980259

  5. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    DEFF Research Database (Denmark)

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie


    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples...... by monocytes, factor XII or insulin in postprandial FVII activation was observed. Tissue factor pathway inhibitor and prothrombin fragment 1+2, a marker of thrombin generation, were not affected postprandially after either the high-fat or the low-fat meals. Our findings indicate that triglyceride......-rich lipoproteins activate prokallikrein postprandially, which might form an important initial event in FVII activation after consumption of high-fat meals....

  6. [Stability of blood coagulation factors in deep frozen fresh plasma by storage at -20 degrees C and -40 degrees C]. (United States)

    Koerner, K; Stampe, D


    Fresh frozen plasma (FFP), was shock-frozen to -25 degrees C within six hours after blood donation. The platelet count was reduced to 20 000/mm3. Aliquots were stored at -20 degrees C and -40 degrees C up to 24 months. Quick, PTT, factor V, VIII, IX, thrombin, antithrombin III, plasminogen, plasma-prekallikrein and kallikrein were determined monthly. With respect to the parameters investigated there was no significant difference between storage at -20 degrees C and -40 degrees C. Factor VIII loss was 10% after 12 months of storage. The activity of factor IX and V remained unchanged during 12 months, then factor V increased during storage. The other parameters did not change. Our study indicates quality of FFP seems not primarily depend on storage temperature, but an optimal preparation technique is much more important.

  7. Coagulation assays and anticoagulant monitoring. (United States)

    Funk, Dorothy M Adcock


    Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.

  8. The treatment of neurodegenerative disorders using umbilical cord blood and menstrual blood-derived stem cells. (United States)

    Sanberg, Paul R; Eve, David J; Willing, Alison E; Garbuzova-Davis, Svitlana; Tan, Jun; Sanberg, Cyndy D; Allickson, Julie G; Cruz, L Eduardo; Borlongan, Cesar V


    Stem cell transplantation is a potentially important means of treatment for a number of disorders. Two different stem cell populations of interest are mononuclear umbilical cord blood cells and menstrual blood-derived stem cells. These cells are relatively easy to obtain, appear to be pluripotent, and are immunologically immature. These cells, particularly umbilical cord blood cells, have been studied as either single or multiple injections in a number of animal models of neurodegenerative disorders with some degree of success, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Sanfilippo syndrome type B. Evidence of anti-inflammatory effects and secretion of specific cytokines and growth factors that promote cell survival, rather than cell replacement, have been detected in both transplanted cells.

  9. Cell and gene therapy for genetic diseases: inherited disorders affecting the lung and those mimicking sudden infant death syndrome. (United States)

    Keeler, Allison M; Flotte, Terence R


    Some of the first human gene therapy trials targeted diseases of the lung and provided important information that will continue to help shape future trials. Here we describe both cell and gene therapies for lung diseases such as cystic fibrosis and alpha-1 antitrypsin disorder as well as fatty acid oxidation disorders that mimic sudden infant death syndrome (SIDS). Human clinical gene therapy trials for cystic fibrosis and alpha-1 antitrypsin have been performed using a variety of vectors including adenovirus, adeno-associated virus, and nonviral vectors. No human clinical gene therapy trials have been performed for disorders of fatty acid oxidation; however, important proof-of-principle studies have been completed for multiple fatty acid oxidation disorders. Important achievements have been made and have yet to come for cell and gene therapies for disorders of the lung and those mimicking SIDS.

  10. The susceptibility of plasma coagulation factor XI to nitration and peroxynitrite action. (United States)

    Ponczek, Michał Błażej


    Coagulation factor XI is present in blood plasma as the zymogen, like other serine proteases of hemostatic system, but as the only coagulation factor forms 140-160kDa homodimers. Its activation is induced by thrombin, and a positive feedback increases the generation of the extra thrombin. Experimental and clinical observations confirm protective roles of factor XI deficiencies in certain types of thromboembolic disorders. Thromboembolism still causes serious problems for modern civilization. Diseases associated with the blood coagulation system are often associated with inflammation and oxidative stress. Peroxynitrite is produced from nitric oxide and superoxide in inflammatory diseases. The aim of the current study is to evaluate effects of nitrative stress triggered by peroxynitrite on coagulation factor XI in human plasma employing biochemical and bioinformatic methods. The amidolytic assay shows increase in factor XI activity triggered by peroxynitrite. Peroxynitrite interferes factor XI by nitration and fragmentation, which is demonstrated by immunoprecipitation followed by western blotting. Nitrated factor XI is even present in control blood plasma. The results suggest possible modifications of factor XI on the molecular level. Computer simulations show tyrosine residues as targets of peroxynitrite action. The modifications induced by peroxynitrite in factor XI might be important in thrombotic disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Blood markers of inflammation and coagulation and exposure to airborne particles in employees in the Stockholm underground. (United States)

    Bigert, C; Alderling, M; Svartengren, M; Plato, N; de Faire, U; Gustavsson, P


    Although associations have been found between levels of ambient airborne particles and cardiovascular disease (CVD) in the general population, little is known about possible cardiovascular effects from high exposure to particles in underground railway systems. This study investigates risk markers for CVD in employees exposed to particles in the Stockholm underground system. 79 workers (54 men and 25 women) in the Stockholm underground were investigated between November 2004 and March 2005. All were non-smokers aged 25-50 years. Three exposure groups were delineated: 29 platform workers with high exposure to particles, 29 train drivers with medium exposure and 21 ticket sellers with low exposure (control group). A baseline blood sample was taken after 2 non-working days, and a second sample after 2 working days, for analysis of levels of plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hs-CRP), interleukin-6, fibrinogen, von Willebrand factor and factor VII. The study investigated changes in plasma concentrations between sample 1 and sample 2, and differences in average concentrations between the groups. No changes between sample 1 and 2 were found that could be attributed to particle exposure. However, the highly exposed platform workers were found to have higher plasma concentrations of PAI-1 and hs-CRP than the ticket sellers and train drivers. This suggests that particle exposure could have a long-term inflammatory effect. These differences remained for PAI-1 in the comparison between platform workers and ticket sellers after adjusting for body mass index. Employees who were highly exposed to airborne particles in the Stockholm underground tended to have elevated levels of risk markers for CVD relative to employees with low exposure. However, the differences observed cannot definitely be linked to particle exposure as such.

  12. Effects of two oral contraceptives, containing 30 or 20 microg of ethinyl estradiol in combination with gestodene, on blood coagulation and fibrinolysis in Brazilian women. (United States)

    Ferreira, A C; Montes, M B; Franceschini, S A; Toloi, M R


    Blood coagulation and fibrinolytic variables were evaluated in 46 Brazilian women treated with either of two monophasic oral contraceptives (OC), containing 30 or 20 microg of ethinyl estradiol, and 75 microg of gestodene. The effects on procoagulants, anticoagulants, pro-fibrinolytics and antifibrinolytics and fibrin turnover were evaluated after treatment for six consecutive cycles, the impact of reduction of ethinyl estradiol dosage on these effects being assessed. The OC containing 30 microg of ethinyl estradiol significantly increased the activities of factors VIII and X, whereas the one containing 20 microg of ethinyl estradiol caused no changes in clotting factors. Neither treatment altered fibrinogen levels or factor VII, IX or XII activity. There were no changes in antithrombin levels, but treatment with 30 microg ethinyl estradiol increased protein C levels and treatment with 20 microg decreased total protein S levels. Concerning the fibrinolytic parameters, both OCs increased plasminogen activity, whereas no changes in PAI-1, t-PA, alpha-2-antiplasmin or fibrin degradation products were observed. The reduction in ethinyl estradiol dosage from 30 microg to 20 microg eliminated the effects on factors VIII and X. The results show that the OC studied did not cause sufficient changes to indicate that there may be a correlation between these laboratory alterations and clinical results. The lack of reports concerning the hemostatic effects of OCs on Brazilian women hinders comparison of the present data with those obtained for other ethnic groups, at different geographical locations, and emphasizes the importance of such a study for future epidemiological investigation of the prothrombotic effects of OCs in Brazilian women.

  13. Fat high in stearic acid favorably affects blood lipids and factor VII coagulant activity in comparison with fats high in palmitic acid or high in myristic and lauric acids. (United States)

    Tholstrup, T; Marckmann, P; Jespersen, J; Sandström, B


    The effect of fats high in individual, prevalent saturated dietary fatty acids on lipoproteins and hemostatic variables in young healthy subjects was evaluated in a randomized strictly controlled metabolic feeding study. Three experimental diets: shea butter (S; 42% stearic acid), palm oil (P; 43% palmitic palmitic acid), and palm-kernel oil with high-oleic sunflower oil (ML; 10% myristic acid, 30% lauric acid) were served to 15 men for 3 wk each, separated by washout periods. Diet S compared with diet P resulted in significant reduction in plasma cholesterol (22%) LDL cholesterol (26%), apolipoprotein B (18%), HDL cholesterol (12%), apolipoprotein A-I (13%), and a 13% lower factor VII coagulant activity (P = 0.001). Similar differences were observed between diets S and ML. In conclusion, intake of shea butter high in stearic acid favorably affects blood lipids and factor VII coagulant activity in young men, compared with fats high in saturated fatty acids with 12-16 carbons.

  14. Coagulation defects in experimental hepatic injury in the dog. (United States)

    Osbaldiston, G W; Hoffman, M W


    Alteration in activity of blood coagulation factors in dogs with acute hepatic injury caused by oral carbon tetrachloride dosing was studied. Coagulation Factors II, VII and IX were dramatically reduced within 48 hours but recovered to normal in the next five days. Because surgery is rarely performed on dogs with hepatic necrosis, the use of fresh whole blood tranfusion to improve the coagulation defect in hepatic injury was also studied. Transfusion was found to have only a temporary beneficial effect.

  15. Interplay of co-inherited diseases can turn benign syndromes in a deadly combination : haemoglobinopathy and bilirubin transport disorder

    NARCIS (Netherlands)

    Stolmeijer, T. M.; van den Berg, A. P.; Koeze, J.; Gouw, A. S. H.; Croles, F. N.; Sieders, E.; Zijlstra, J. G.

    We present a case about a 25-year-old male patient suffering from a rare genetic disorder called Mizuho haemoglobin. He was admitted to the Intensive Care Unit with acute liver and renal failure. During admission he also developed a cardiac tamponade twice. Finally he received a liver

  16. Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance

    DEFF Research Database (Denmark)

    Dibbens, Leanne M; Mullen, Saul; Helbig, Ingo


    Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.3 deletions and IGE. We th...

  17. Effects of nucleotides and nucleosides on coagulation

    DEFF Research Database (Denmark)

    Bune, Laurids; Thaning, Pia; Johansson, Pär I


    Nucleotides, including ADP, ATP and uridine triphosphate (UTP), are discharged profusely in the circulation during many pathological conditions including sepsis. Sepsis can cause hypotension and systemic activation of the coagulation and fibrinolytic systems in humans, which may cause disseminated...... intravascular coagulation. We investigated whether nucleotide-induced cardiovascular collapse as provoked by systemic infusion of adenosine, ADP, ATP, UTP and nitric oxide affected the haemostatic system as assessed by whole blood thromboelastography (TEG) analysis. Ten pigs received a randomized infusion...

  18. Review and evaluation of the methodological quality of the existing guidelines and recommendations for inherited neurometabolic disorders

    DEFF Research Database (Denmark)

    Cassis, Linda; Cortès-Saladelafont, Elisenda; Molero-Luis, Marta


    of existing guidelines and recommendations for iNMDs. METHODS: We performed a systematic search on PubMed, the National Guideline Clearinghouse (NGC), the Guidelines International Network (G-I-N), the Scottish Intercollegiate Guideline Network (SIGN) and the National Institute for Health and Care Excellence...... and timely treatments are often pivotal for the favorable course of the disease. Thus, the elaboration of new evidence-based recommendations for iNMD diagnosis and management is increasingly requested by health care professionals and patients, even though the methodological quality of existing guidelines...... is largely unclear. InNerMeD-I-Network is the first European network on iNMDs that was created with the aim of sharing and increasing validated information about diagnosis and management of neurometabolic disorders. One of the goals of the project was to determine the number and the methodological quality...

  19. Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on whole blood coagulation and platelet function in dogs with suspected intracranial hypertension - a pilot study. (United States)

    Yozova, Ivayla D; Howard, Judith; Henke, Diana; Dirkmann, Daniel; Adamik, Katja N


    Hyperosmolar therapy with either mannitol or hypertonic saline (HTS) is commonly used in the treatment of intracranial hypertension (ICH). In vitro data indicate that both mannitol and HTS affect coagulation and platelet function in dogs. The aim of this study was to compare the effects of 20% mannitol and 7.2% HTS on whole blood coagulation using rotational thromboelastometry (ROTEM®) and platelet function using a platelet function analyzer (PFA®) in dogs with suspected ICH. Thirty client-owned dogs with suspected ICH needing osmotherapy were randomized to receive either 20% mannitol (5 ml/kg IV over 15 min) or 7.2% HTS (4 ml/kg IV over 5 min). ROTEM® (EXTEM® and FIBTEM® assays) and PFA® analyses (collagen/ADP cartridges) were performed before (T 0 ), as well as 5 (T 5 ), 60 (T 60 ) and 120 (T 120 ) minutes after administration of HTS or mannitol. Data at T 5 , T 60 and T 120 were analyzed as a percentage of values at T 0 for comparison between groups, and as absolute values for comparison between time points, respectively. No significant difference was found between the groups for the percentage change of any parameter at any time point except for FIBTEM® clotting time. Within each group, no significant difference was found between time points for any parameter except for FIBTEM® clotting time in the HTS group, and EXTEM® and FIBTEM® maximum clot firmness in the mannitol group. Median ROTEM® values lay within institutional reference intervals in both groups at all time points, whereas median PFA® values were above the reference intervals at T 5 (both groups) and T 60 (HTS group). Using currently recommended doses, mannitol and HTS do not differ in their effects on whole blood coagulation and platelet function in dogs with suspected ICH. Moreover, no relevant impairment of whole blood coagulation was found following treatment with either solution, whereas a short-lived impairment of platelet function was found after both solutions.

  20. Chronic Disseminated Intravascular Coagulation: A Case Report

    Directory of Open Access Journals (Sweden)

    Md Abul Kalam Azad


    Full Text Available In health there is a balance between the coagulation and anti-coagulation systems, but in disseminated intravascular coagulation (DIC the coagulation mechanism is activated inappropriately and in a diffuse way. This may lead to thrombosis, but more often haemorrhage occurs when the clotting factors are exhausted. DIC may present as acute, subacute, and rarely chronic form. Here we present a case of chronic DIC following pelvic inflammatory disease (PID as a consequence of repeated menstruation regulation (MR. We treated her with fresh frozen plasma, fresh blood, doxycycline with significant clinical improvement.DOI: 10.3329/bsmmuj.v1i1.3696 BSMMU J 2008; 1(1: 33-34

  1. Development of newborn screening connect (NBS connect): a self-reported patient registry and its role in improvement of care for patients with inherited metabolic disorders. (United States)

    Osara, Yetsa; Coakley, Kathryn; Devarajan, Aishwarya; Singh, Rani H


    Newborn Screening Connect (NBS Connect) is a web-based self-reported patient registry and resource for individuals and families affected by disorders included in the newborn screening panel. NBS Connect was launched in 2012 by Emory University after years of planning and grassroots work by professionals, consumers, and industry. Individuals with phenylketonuria (PKU), maple syrup urine disease (MSUD) or tyrosinemia (TYR) have been recruited through distribution of outreach materials, presentations at parent organization meetings and direct recruitment at clinic appointments. Participants complete online profiles generating data on diagnosis, treatment, symptoms, outcomes, barriers to care, and quality of life. Resources such as education materials, information on the latest research and clinical trials, recipes, interactive health tracking systems, and professional support tools are described. In addition, to examine the ability of NBS Connect to generate data that guides hypothesis-driven research, data pertaining to age at diagnosis, bone health, and skin conditions in individuals with PKU were assessed. The objective of this paper is to describe the development of NBS Connect and highlight its data, resources and research contributions. In September 2016, NBS Connect had 442 registered participants: 314 (71%) individuals with PKU, 68 (15%) with MSUD, 20 (5%) with TYR, and 40 (9%) with other disorders on the NBS panel. Age at diagnosis was less than 4 weeks in 285 (89%) of 319 respondents to this question and between 1 month and 14 years in 29 (9%) individuals. Of 216 respondents with PKU, 33 (15%) had a DXA scan in the past year. Of 217 respondents with PKU, 99 (46%) reported at least one skin condition. NBS Connect was built and refined with feedback from all stakeholders, including individuals with inherited metabolic disorders. Based on patient-reported data, future studies can be initiated to test hypotheses such as the relationship between PKU and skin

  2. Networks of enzymatically oxidized membrane lipids support calcium-dependent coagulation factor binding to maintain hemostasis. (United States)

    Lauder, Sarah N; Allen-Redpath, Keith; Slatter, David A; Aldrovandi, Maceler; O'Connor, Anne; Farewell, Daniel; Percy, Charles L; Molhoek, Jessica E; Rannikko, Sirpa; Tyrrell, Victoria J; Ferla, Salvatore; Milne, Ginger L; Poole, Alastair W; Thomas, Christopher P; Obaji, Samya; Taylor, Philip R; Jones, Simon A; de Groot, Phillip G; Urbanus, Rolf T; Hörkkö, Sohvi; Uderhardt, Stefan; Ackermann, Jochen; Vince Jenkins, P; Brancale, Andrea; Krönke, Gerhard; Collins, Peter W; O'Donnell, Valerie B


    Blood coagulation functions as part of the innate immune system by preventing bacterial invasion, and it is critical to stopping blood loss (hemostasis). Coagulation involves the external membrane surface of activated platelets and leukocytes. Using lipidomic, genetic, biochemical, and mathematical modeling approaches, we found that enzymatically oxidized phospholipids (eoxPLs) generated by the activity of leukocyte or platelet lipoxygenases (LOXs) were required for normal hemostasis and promoted coagulation factor activities in a Ca 2+ - and phosphatidylserine (PS)-dependent manner. In wild-type mice, hydroxyeicosatetraenoic acid-phospholipids (HETE-PLs) enhanced coagulation and restored normal hemostasis in clotting-deficient animals genetically lacking p12-LOX or 12/15-LOX activity. Murine platelets generated 22 eoxPL species, all of which were missing in the absence of p12-LOX. Humans with the thrombotic disorder antiphospholipid syndrome (APS) had statistically significantly increased HETE-PLs in platelets and leukocytes, as well as greater HETE-PL immunoreactivity, than healthy controls. HETE-PLs enhanced membrane binding of the serum protein β2GP1 (β2-glycoprotein 1), an event considered central to the autoimmune reactivity responsible for APS symptoms. Correlation network analysis of 47 platelet eoxPL species in platelets from APS and control subjects identified their enzymatic origin and revealed a complex network of regulation, with the abundance of 31 p12-LOX-derived eoxPL molecules substantially increased in APS. In summary, circulating blood cells generate networks of eoxPL molecules, including HETE-PLs, which change membrane properties to enhance blood coagulation and contribute to the excessive clotting and immunoreactivity of patients with APS. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  3. Disseminated intravascular coagulation in sepsis

    NARCIS (Netherlands)

    Zeerleder, Sacha; Hack, C. Erik; Wuillemin, Walter A.


    Disseminated intravascular coagulation is a frequent complication of sepsis. Coagulation activation, inhibition of fibrinolysis, and consumption of coagulation inhibitors lead to a procoagulant state resulting in inadequate fibrin removal and fibrin deposition in the microvasculature. As a

  4. Components of an effective large scale program for the prevention of inherited hemoglobin disorders; the paradigm of Greece

    Directory of Open Access Journals (Sweden)

    D. Loukopoulos


    Full Text Available Large scale prevention programs for Thalassemia major or Sickle cell disease have already been set up in several places with high frequency of the deleterious genes. The Greek health authorities realized the magnitude of the problem and allowed the creation of a National Thalassemia Center in 1972. The incidence of thalassemia in Greece varies from 1-2 per cent up to 15%, the mean being around 8 per cent. With an annual number of births around 100,000, if no prevention measures are taken, the expected yearly number of newborns with thalassemia major in Greece should be of the order of 100-120. To these one should add a few decades of sickle cell patients, homozygotes or compound HbS/β-thalassemia heterozygotes. The total number of patients with thalassemia major now surviving is estimated at 4,000 plus another 600-800 patients with sickle cell disease. The National Thalassemia Center Center defined a network of peripheral Thalassemia Units in the major regional hospitals of the country, let them provide free carrier identification to couples requesting the test. When both partners were identified as carriers, they were given preliminary information locally and were referred to the Central Laboratory in Athens for further genetic counselling and, if so decided, prenatal diagnosis. Prenatal diagnosis was provided initially by fetoscopy and fetal blood biosynthesis; this approach was soon replaced by chorionic villi sampling and molecular techniques. The number of prenatal diagnoses carried out yearly over the last decade appears to cover the needs; the number of positive diagnoses is very close to the expected 25%, which also excludes overdiagnosis. The overall evaluation of the the program is reflected in the number of infants who were admitted to the pediatric clinics of the country in need of transfusion over the years the program was functioning. In fact, over the past years this number has steadily decreased to approximately 10 missed

  5. Could light meal jeopardize laboratory coagulation tests? (United States)

    Lima-Oliveira, Gabriel; Salvagno, Gian Luca; Lippi, Giuseppe; Danese, Elisa; Gelati, Matteo; Montagnana, Martina; Picheth, Geraldo; Guidi, Gian Cesare


    Presently the necessity of fasting time for coagulation tests is not standardized. Our hypothesis is that this can harm patient safety. This study is aimed at evaluating whether a light meal (i.e. breakfast) can jeopardize laboratory coagulation tests. A blood sample was firstly collected from 17 fasting volunteers (12 h). Immediately after blood collection, the volunteers consumed a light meal. Then samples were collected at 1, 2 and 4 h after the meal. Coagulation tests included: activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fbg), antithrombin III (AT), protein C (PC) and protein S (PS). Differences between samples were assessed by Wilcoxon ranked-pairs test. The level of statistical significance was set at P coagulation tests had significant variation after comparison with RCV. A light meal does not influence the laboratory coagulation tests we assessed, but we suggest that the laboratory quality managers standardize the fasting time for all blood tests at 12 hours, to completely metabolize the lipids intake.

  6. Microelements and inherited metabolic diseases. (United States)

    Marklová, Eliska


    In addition to the main groups of inherited metabolic diseases, including mitochondrial, peroxisomal and lysosomal defects, organic acidurias, porphyrias, defects of amino acids, saccharides and fatty acids metabolism, disorders of transport and utilisation of microelements have also been recognized. Recent findings concerning hereditary hemochromatosis (iron), Wilson and Menkes diseases (copper), molybdenum cofactor deficiency (molybdenum), defects of cobalamine synthesis (cobalt) and acrodermatitis enteropathica (zinc) are reviewed.

  7. The Study of Hemolysis Effects on Coagulation Parameters

    African Journals Online (AJOL)

    In coagulation assays rejection of hemolyzed samples is ... Background: Rejecting hemolyzed specimens received for coagulation studies is advised ... with the first group. The approval from ethics committee was taken for drawing blood samples from volunteers. Statistical evaluation. GraphPad Prism 5 was the software ...

  8. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

    DEFF Research Database (Denmark)

    Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H


    Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics...

  9. Stimulated Gene Expression Profiles as a Blood Marker of Major Depressive Disorder

    NARCIS (Netherlands)

    Spijker, Sabine; Van Zanten, Jeroen S.; De Jong, Simone; Penninx, Brenda; van Dyck, Richard; Zitman, Frans G.; Smit, Jan H.; Ylstra, Bauke; Smit, August B.; Hoogendijk, Witte J. G.


    Background: Major depressive disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of unmedicated

  10. Distúrbios de coagulação em pacientes com osteonecrose da cabeça femoral Coagulation disorders in patients with femoral head osteonecrosis

    Directory of Open Access Journals (Sweden)

    Flávio Luís Garcia


    compared the results using the odds ratio statistics for the thrombophilic disorders between the two groups. RESULTS: The odds ratio for the protein S deficiency and protein C deficiency between the idiopathic and secondary groups were 5 and 2.14, respectively. Thus, an individual with idiopathic osteonecrosis has 5 times more chance of presenting protein S deficiency and 2.14 times more chance of presenting protein C deficiency than an individual with secondary osteonecrosis. CONCLUSION: Patients with idiopathic osteonecrosis have more chances of presenting thrombophilias than those with secondary osteonecrosis, suggesting these coagulation disorders can play an important role in the pathogenesis of the osteonecrosis in cases where there was no initial risk factor recognized. Level of Evidence III, Case-Control Study.

  11. Characterization of core/shell Cu/Ag nanopowders synthesized by electrochemistry and assessment of their impact on hemolysis, platelet aggregation, and coagulation on human blood for potential wound dressing use (United States)

    Laloy, Julie; Haguet, Hélène; Alpan, Lutfiye; Mancier, Valérie; Mejia, Jorge; Levi, Samuel; Dogné, Jean-Michel; Lucas, Stéphane; Rousse, Céline; Fricoteaux, Patrick


    Copper/silver core/shell nanopowders with different metal ratio have been elaborated by electrochemistry (ultrasound-assisted electrolysis followed by a displacement reaction). Characterization was performed by several methods (X-ray diffraction, scanning electron microscope, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, centrifugal liquid sedimentation, and zeta potential measurements). The mean diameter of all nanoparticles is around 10 nm. The impact of each nanopowder on hemolysis, platelet aggregation, and coagulation has been studied on whole human blood. Hemolysis assays were performed with spectrophotometric measurement and platelet aggregation, with light transmission aggregometry and was compared to Cu/Pt core/shell nanoparticles with similar size as negative control. Calibrated thrombin generation test has been used for a coagulation study. They neither impact platelet aggregation nor hemolysis and have a procoagulant effect whatever their composition (i.e., metal ratio). These results highlight that such nanopowders have a potential use in medical applications (e.g., wound dressing).

  12. Dust coagulation in ISM (United States)

    Chokshi, Arati; Tielens, Alexander G. G. M.; Hollenbach, David


    Coagulation is an important mechanism in the growth of interstellar and interplanetary dust particles. The microphysics of the coagulation process was theoretically analyzed as a function of the physical properties of the coagulating grains, i.e., their size, relative velocities, temperature, elastic properties, and the van der Waal interaction. Numerical calculations of collisions between linear chains provide the wave energy in individual particles and the spectrum of the mechanical vibrations set up in colliding particles. Sticking probabilities are then calculated using simple estimates for elastic deformation energies and for the attenuation of the wave energy due to absorption and scattering processes.

  13. Genetic Blood Disorders Survey in the Sultanate of Oman. (United States)

    Al-Riyami, Asya; Ebrahim, G J


    The Genetic Blood Disorders Survey is the first community-based survey in the Arabic world and the Middle East to determine the prevalence of the most common genetic blood disorders. The objective of the survey was to determine the prevalence of the most common genetic blood disorders reported among Omani children under 5 years of age in order to provide the planners and policy-makers with reliable information suitable for formulating health policies, planning, and evaluation. The survey was designed, executed, and financed by the Ministry of Health of the Sultanate of Oman. To reduce costs and save effort and time, data collection for the survey was implemented with the Gulf Family Health Survey (GFHS). The GFHS in the Sultanate of Oman is a research project undertaken by the Council of Health Ministers of the Gulf Co-operation Council States. The six member countries have participated in this GFHS project. A total of 6103 households were interviewed. From these households 6342 children under 5 years of age were taken by their parents to neighbourhood hospitals or health centres for blood collection. Fifty-one per cent of the sample were male and 49 per cent were female. Among the child respondents, 17.9 per cent were in the age group 0 to education, 20 per cent had completed primary school, 9 per cent had attended preparatory school, 5 per cent had attended secondary school, 1 per cent had had intermediate education, while 0.6 per cent had completed university or higher education. The results of this survey revealed that haemoglobinopathies are prevalent in Oman; the prevalence of sickle cell trait was 6 per cent, and of beta-thalassaemia 2 per cent. The prevalence of sickle cell and homozygous beta-thalassaemia were 0.2 and 0.07 per cent, respectively. Other abnormal haemoglobins (Hb) have been detected in this survey; HbD (0.6 per cent), HbE (0.3 per cent), HbC (0.02 per cent). Combination of sickle cell with other abnormal Hb was also detected at low

  14. In vitro study of uptake and synthesis of creatine and its precursors by cerebellar granule cells and astrocytes suggests some hypotheses on the physiopathology of the inherited disorders of creatine metabolism

    Directory of Open Access Journals (Sweden)

    Carducci Claudia


    Full Text Available Abstract Background The discovery of the inherited disorders of creatine (Cr synthesis and transport in the last few years disclosed the importance of blood Cr supply for the normal functioning of the brain. These putatively rare diseases share a common pathogenetic mechanism (the depletion of brain Cr and similar phenotypes characterized by mental retardation, language disturbances, seizures and movement disorders. In the effort to improve our knowledge on the mechanisms regulating Cr pool inside the nervous tissue, Cr transport and synthesis and related gene transcripts were explored in primary cultures of rat cerebellar granule cells and astrocytes. Methods Cr uptake and synthesis were explored in vitro by incubating monotypic primary cultures of rat type I astrocytes and cerebellar granule cells with: a D3-Creatine (D3Cr and D3Cr plus β-guanidinopropionate (GPA, an inhibitor of Cr transporter, and b labelled precursors of Guanidinoacetate (GAA and Cr (Arginine, Arg; Glycine, Gly. Intracellular D3Cr and labelled GAA and Cr were assessed by ESI-MS/MS. Creatine transporter (CT1, L-arginine:glycine amidinotransferase (AGAT, and S-adenosylmethionine:guanidinoacetate N-methyltransferase (GAMT gene expression was assessed in the same cells by real time PCR. Results D3Cr signal was extremely high in cells incubated with this isotope (labelled/unlabelled Cr ratio reached about 10 and 122, respectively in cerebellar granule cells and astrocytes and was reduced by GPA. Labelled Arg and Gly were taken up by the cells and incorporated in GAA, whose concentration paralleled that of these precursors both in the extracellular medium and inside the cells (astrocytes. In contrast, the increase of labelled Cr was relatively much more limited since labelled Cr after precursors' supplementation did not exceed 2,7% (cerebellar granule cells and 21% (astrocytes of unlabelled Cr. Finally, AGAT, GAMT and SLC6A8 were expressed in both kind of cells. Conclusions Our

  15. Inherited epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Fine Jo-David


    Full Text Available Abstract Inherited epidermolysis bullosa (EB encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient.

  16. Towards a blood-based diagnostic panel for bipolar disorder

    NARCIS (Netherlands)

    F. Haenisch (Frieder); J.D. Cooper (Jason); A. Reif (Andreas); S. Kittel-Schneider (Sarah); J. Steiner (Johann); F.M. Leweke (Marcus); M. Rothermundt (Matthias); N.J.M. van Beveren (Nico); B. Crespo-Facorro (Benedicto); D. Niebuhr (David); D. Cowan (David); N. Weber (Natalya); R.H. Yolken (Robert); B.W.J.H. Penninx (Brenda W.J.H.); S. Bahn (Sabine)


    markdownabstract_Background:_ Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic

  17. Inheritance versus parameterization

    DEFF Research Database (Denmark)

    Ernst, Erik


    This position paper argues that inheritance and parameterization differ in their fundamental structure, even though they may emulate each other in many ways. Based on this, we claim that certain mechanisms, e.g., final classes, are in conflict with the nature of inheritance, and hence causes...

  18. A loop of coagulation factor VIIa influencing macromolecular substrate specificity

    DEFF Research Database (Denmark)

    Bjelke, Jais R; Persson, Egon; Rasmussen, Hanne B


    Coagulation factor VIIa (FVIIa) belongs to a family of proteases being part of the stepwise, self-amplifying blood coagulation cascade. To investigate the impact of the mutation Met(298{156})Lys in FVIIa, we replaced the Gly(283{140})-Met(298{156}) loop with the corresponding loop of factor Xa....../Met(298{156})Lys-FVIIa with almost the same activity and specificity profile. We conclude that a lysine residue in position 298{156} of FVIIa requires a hydrophilic environment to be fully accommodated. This position appears critical for substrate specificity among the proteases of the blood coagulation...

  19. Usefulness of human coagulation and fibrinolysis assays in domestic pigs

    DEFF Research Database (Denmark)

    Münster, Anna-Marie Bloch; Olsen, Aage Kristian; Bladbjerg, Else-Marie


    Pigs are often used as animal models in research on blood coagulation and fibrinolysis. The usefulness of the assays applied within this field, and the knowledge of reference intervals are therefore essential and of utmost importance. In the study reported here, we investigated the applicability...... of commercial human coagulation and fibrinolysis assays for use with porcine plasma. In total, 22 functional and immunologic assays were applied to plasma obtained from domestic pigs, and the following blood coagulation and fibrinolysis variables were measured: prothrombin time, activated partial thromboplastin...

  20. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin or 2,2',4,4',5,5'-hexachlorobiphenyl on vitamin K-dependent blood coagulation in male and female WAG/Rij-rats. (United States)

    Bouwman, C A; Van Dam, E; Fase, K M; Koppe, J G; Seinen, W; Thijssen, H H; Vermeer, C; Van den Berg, M


    Newborns are susceptible to hemorrhages (hemorrhagic disease of the newborn or HDN) due to vitamin K deficiency. Induction of cytochrome P450 in the fetal liver by maternal anticonvulsant therapy such as phenobarbital or phenytoin is considered to be a major cause. An observed increase in late hemorrhagic disease (LHD) in breast fed neonates gave rise to the hypothesis that PCBs and dioxins, P450-inducing contaminants present in human milk, might effect vitamin K-dependent blood coagulation. This hypothesis was studied in rats. Administration of a single oral dose of 0.003, 0.03, 0.3, 3 or 30 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) per kg bodyweight or 0.75, 4, 20, 100 or 500 micromol 2,2',4,4',5,5'-hexachlorobiphenyl/kg bw (HxCB) to female and male rats resulted in dose-related reductions of the vitamin K-dependent coagulation factor VII. The highest factor VII reduction in female rats was 44%, observed after TCDD exposure. The Lowest Observed Adverse Effect Level (LOAEL) of TCDD on female factor VII levels was 0.3 nmol/kg bw (96 ng/kg). There was a significant inverse correlation between Factor VII levels and induction of hepatic ethoxyresorufin O-deethylating (EROD) activity, reflecting CYP1A1, and total P450 content. HxCB had no effect on female coagulation factors. In contrast, in male rats only exposure to HxCB, which induces mainly CYP2B1 and 2B2, decreased both coagulation factors dramatically up to 88%. The LOAEL of HxCB on factor VII in male rats was 100 micromol/kg bw (36 mg/kg). In general, effects on coagulation factors in male rats exceeded those in females. In addition, sex-dependent differences of TCDD and HxCB were observed on the hepatic vitamin K cycle enzyme activities in female and male rats. Vitamin K-dependent (gamma-glutamyl carboxylase activity was mainly induced in female rats; 2.3-fold in the highest dose group of TCDD. In male rats only vitamin K 2,3-epoxide reductase (KO-reductase) activity was induced 1.7-fold by the highest

  1. Monitoring Oral Anticoagulant Therapy: Measuring Coagulant Activity

    DEFF Research Database (Denmark)

    Attermann, Jorn

    daily anticoagulant therapy. The therapy necessitates close monitoring of coagulant activity, since excess doses of anticoagulant medicine may lead to life-threatening bleedings. Traditionally, patients on OAT are required to pay regular visits to a physician, who decides on drug dosage adjustments....... There is general agreement that the quality of the therapy is too low, and often unexpected fluctuations in the coagulant activity are seen. Recently, OAT based on patient self-management has become a realistic alternative by the availability of small portable whole blood coagulometers. An important part...... of the new concept is the training and continuous support and monitoring of the patients, and a center with these purposes has been established at Skejby Sygehus. The main instrument for monitoring the coagulant activity is the prothrombin time (PT). This is the time until clotting can be observed...

  2. Coagulation management in patients undergoing neurosurgical procedures. (United States)

    Robba, Chiara; Bertuetti, Rita; Rasulo, Frank; Bertuccio, Alessando; Matta, Basil


    Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

  3. Coagulation profile in open and video-assisted thoracoscopic lobectomies

    DEFF Research Database (Denmark)

    Christensen, Thomas Decker; Vad, Henrik; Pedersen, Søren


    OBJECTIVES: Lung cancer patients are perceived to have a relatively high risk of venous thromboembolic events due to an activation of the coagulation system. In terms of activation of the coagulation system, the difference between video-assisted thoracoscopic surgery (VATS) and open lobectomies...... for primary lung cancer has not been investigated. The aim of this study was to compare the impact on the coagulation system in patients undergoing curative surgery for primary lung cancer by either VATS or open lobectomies. METHODS: In total, 62 patients diagnosed with primary lung cancer were allocated...... to either VATS (n = 32) or open lobectomies (n = 30). All patients received subcutaneous injections with dalteparin (Fragmin®) 5000 IE once daily. The coagulation was assessed pre- and intraoperatively, and the first 2 days postoperatively by standard coagulation blood tests, thromboelastometry (ROTEM...

  4. Molecular autopsy in victims of inherited arrhythmias

    Directory of Open Access Journals (Sweden)

    Christopher Semsarian, MBBS, PhD, MPH


    Full Text Available Sudden cardiac death (SCD is a rare but devastating complication of a number of underlying cardiovascular diseases. While coronary artery disease and acute myocardial infarction are the most common causes of SCD in older populations, inherited cardiac disorders comprise a substantial proportion of SCD cases aged less than 40 years. Inherited cardiac disorders include primary inherited arrhythmogenic disorders such as familial long QT syndrome (LQTS, Brugada syndrome (BrS, catecholaminergic polymorphic ventricular tachycardia (CPVT, and inherited cardiomyopathies, most commonly hypertrophic cardiomyopathy (HCM. In up to 40% of young SCD victims (defined as 1–40 years old, excluding sudden unexplained death in infancy from 0 to 1 years, referred to as SIDS, no cause of death is identified at postmortem [so-called “autopsy negative” or “sudden arrhythmic death syndrome” (SADS]. Management of families following a SCD includes the identification of the cause of death, based either on premorbid clinical details or the pathological findings at the postmortem. When no cause of death is identified, genetic testing of DNA extracted from postmortem tissue (the molecular autopsy may identify a cause of death in up to 30% of SADS cases. Targeted clinical testing in a specialized multidisciplinary clinic in surviving family members combined with the results from genetic testing, provide the optimal setting for the identification of relatives who may be at risk of having the same inherited heart disease and are therefore also predisposed to an increased risk of SCD.

  5. Coagulation of sheep intestinal and prefemoral lymph. (United States)

    Hanley, C A; Johnston, M G; Nelson, W


    We have determined the most suitable method for the automated analysis of the clotting parameters in sheep intestinal and prefemoral lymph as defined by the Activated Partial Thromboplastin Times (APTT; measure of intrinsic coagulation pathway) and the Prothrombin Times (PT; measure of extrinsic coagulation pathway). As opposed to optical density systems, the use of a Fibro-System Fibrometer was found to provide the most consistent assessment of coagulation with the endpoint being the time to fibrin strand formation. We measured APTT in sheep intestinal and prefemoral lymph of 59.78 +/- 7.69 seconds and 51.03 +/- 10.49 seconds respectively. These values were more prolonged than those obtained from sheep blood plasma but only in the case of intestinal lymph were the differences significant (p less than 0.025). Human blood APTT values were significantly less than both sheep blood (p less than 0.05) and sheep intestinal (p less than 0.001) and prefemoral lymph (p less than 0.01). PT values were found to be 21.56 +/- 1.14 seconds in intestinal and 22.00 +/- 1.88 seconds in prefemoral lymph. These values were also significantly greater than those obtained from sheep blood (both p less than 0.001). Human blood PTs were significantly less than both sheep blood (p less than 0.001) and intestinal and prefemoral lymph (both p less than 0.001). Measurement of APTT and PT values in intestinal lymph and PT determinations in prefemoral lymph were not affected by storage in the refrigerator or freezer. There was some indication that APTT values in prefemoral samples were susceptible to storage artifacts; however, the differences in coagulation times were not significant.

  6. Inheriting geodesic flows

    Indian Academy of Sciences (India)

    times possessing a high degree of symmetry. In this paper we impose the ... The geometric and dynamic features, with perfect fluid and anisotropic matter tensors, ... so that the inheriting vector X is a conformal motion of the projection tensor.

  7. Moojenactivase, a novel pro-coagulant PIIId metalloprotease isolated from Bothrops moojeni snake venom, activates coagulation factors II and X and induces tissue factor up-regulation in leukocytes. (United States)

    Sartim, Marco A; Costa, Tassia R; Laure, Helen J; Espíndola, Milena S; Frantz, Fabiani G; Sorgi, Carlos A; Cintra, Adélia C O; Arantes, Eliane C; Faccioli, Lucia H; Rosa, José C; Sampaio, Suely V


    Coagulopathies following snakebite are triggered by pro-coagulant venom toxins, in which metalloproteases play a major role in envenomation-induced coagulation disorders by acting on coagulation cascade, platelet function and fibrinolysis. Considering this relevance, here we describe the isolation and biochemical characterization of moojenactivase (MooA), a metalloprotease from Bothrops moojeni snake venom, and investigate its involvement in hemostasis in vitro. MooA is a glycoprotein of 85,746.22 Da, member of the PIIId group of snake venom metalloproteases, composed of three linked disulfide-bonded chains: an N-glycosylated heavy chain, and two light chains. The venom protease induced human plasma clotting in vitro by activating on both blood coagulation factors II (prothrombin) and X, which in turn generated α-thrombin and factor Xa, respectively. Additionally, MooA induced expression of tissue factor (TF) on the membrane surface of peripheral blood mononuclear cells (PBMC), which led these cells to adopt pro-coagulant characteristics. MooA was also shown to be involved with production of the inflammatory mediators TNF-α, IL-8 and MCP-1, suggesting an association between MooA pro-inflammatory stimulation of PBMC and TF up-regulation. We also observed aggregation of washed platelets when in presence of MooA; however, the protease had no effect on fibrinolysis. Our findings show that MooA is a novel hemostatically active metalloprotease, which may lead to the development of coagulopathies during B. moojeni envenomation. Moreover, the metalloprotease may contribute to the development of new diagnostic tools and pharmacological approaches applied to hemostatic disorders.

  8. Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry. (United States)

    Han, Lianshu; Han, Feng; Ye, Jun; Qiu, Wenjuan; Zhang, Huiwen; Gao, Xiaolan; Wang, Yu; Ji, Wenjun; Gu, Xuefan


    Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients. Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests. Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years. In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants. © 2014 Wiley Periodicals, Inc.

  9. Anaesthesia in children with inherited neuromuscular diseases


    Simić Dušica; Bogićević Dragana; Milojević Irina; Budić Ivana; Marković Marija


    Children with inherited neuromuscular diseases often require anaesthesia for diagnostic or therapy procedures. These patients have an increased risk of perioperative complications due to the nature of the disease and medications administered during anaesthesia. Many anaesthetics and muscle relaxants can aggravate the underlying disease and trigger life-threatening reactions (cardiorespiratory complications, malignant hyperthermia). Besides, the neuromuscular disorders are associated wit...

  10. Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers


    Nahar, Risha; Saxena, Renu; Deb, Roumi; Verma, Ishwar C.


    Context: Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of coumarin response profile in such thrombophilic population. Aims: The current pilot study aims to estimate coumarin sensitivity in an Indian cohort with an inherited thrombophilia risk factor (Factor V Leiden mutation carriers) based on the observed frequency of CYP2C9 FNx01...

  11. Anxiety and depression in patients three months after myocardial infarction: Association with markers of coagulation and the relevance of age. (United States)

    Geiser, Franziska; Urbach, Anne Sarah; Harbrecht, Ursula; Conrad, Rupert; Pötzsch, Bernd; Amann, Nele; Kiesewetter, Katharina; Sieke, Alexandra; Wolffs, Kyra; Skowasch, Dirk


    Anxiety and depression are associated with an activation of coagulation and an impairment of fibrinolysis, which may contribute to the increased cardiovascular risk associated with the two disorders. However, very few studies have examined the impact of psychological distress on coagulation factors in coronary artery disease patients. The aim of this study was to assess the correlation between anxiety/depression and factors of coagulation and fibrinolysis in patients who had suffered an acute MI three months prior. In 148 patients, anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS) shortly after MI and three months later. At the second time of assessment, plasma levels of fibrinogen, factor VII, factor VIII, von Willebrand factor, prothrombin-fragment 1 and 2, tissue-plasminogen-activator, plasminogen activator inhibitor-1, D-dimer, and homocysteine were measured. In 32% of the patients, elevated levels of anxiety and depression were found three months after a MI. Multiple regression analyses showed that coagulation and fibrinolysis markers were not significantly associated with HADS anxiety and depression scores. We found that age, gender, BMI, and smoking status were significant predictors for haemostasis factors. A higher age was associated with a higher coagulability but lower anxiety levels. We measured parameters of coagulation and fibrinolysis in patients three months after MI and found no predictive value of HADS anxiety and depression scores shortly after MI or at the time of blood sampling. The effects of age on the relationship between anxiety and haemostasis should be further investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Inheritance is Specialisation

    DEFF Research Database (Denmark)

    Torgersen, Mads


    of Smalltalk there has been a strong tension in the object-oriented community between two opposing views of the role of inheritance: as an incremental modification mechanism or as a vehicle for conceptual modelling. Madsen [5] and many others characterise the two approaches as the “American ” and “Scandinavian......How can we get a simpler but much more general subclass construct? This position paper takes a "specialisationist" approach to inheritance. Old SIMULA virtues are restored to prominence, but boiled with new unificational ingredients to obtain a substrate of specialisation. Ever since the advent...

  13. Safe Dynamic Multiple Inheritance

    DEFF Research Database (Denmark)

    Ernst, Erik


    Multiple inheritance and similar mechanisms are usually only supported at compile time in statically typed languages. Nevertheless, dynamic multiple inheritance would be very useful in the development of complex systems, because it allows the creation of many related classes without an explosion ...... of operands the '&' operator fails; as a result, dynamic creation of new classes and methods was considered a dangerous operation in all cases. This paper presents a large and useful category of combinations, and proves that combinations in this category will always succeed....

  14. Establishing reference intervals in the coagulation laboratory. (United States)

    Castellone, D D


    Obtaining a reference interval (RI) is a challenge for any laboratory and becomes more complicated in the coagulation laboratory due to testing on samples with limited stability on reagents that are poorly standardized. Reference intervals are required to be able to evaluate results in relation to a patients' hemostatic disorder. This becomes one of the most important tasks conducted in the coagulation laboratory. However, many laboratories lack the time, finances and in many cases the expertise to conduct this study. Many RI are obtained from package inserts, or from publications written by experts in lieu of laboratories conducting their own studies. An overview of validating reference intervals and options for verifying or transference of reference intervals is discussed. Based on the confidence interval and the acceptability of risk laboratories are willing to accept, coagulation laboratories have options to conduct robust studies for their RI. Data mining or global reference studies may help to provide data for age specific ranges. Pre-analytical variables and selection of healthy subjects have the largest impact on coagulation testing outcomes and need to be well controlled during the establishment of reference intervals. Laboratories have options in lieu of conducting a full validation on how to verify RI based on smaller RI studies or transference of RI after determining compatibility of the original RI study. © 2017 John Wiley & Sons Ltd.

  15. Electromagnetic induction sensor for dynamic testing of coagulation process. (United States)

    Wang, Zhe; Yu, Yuanhua; Yu, Zhanjiang; Chen, Qimeng


    With the increasing demand for coagulation POCT for patients in the surgery department or the ICU, rapid coagulation testing techniques and methods have drawn widespread attention from scholars and businessmen. This paper proposes the use of electromagnetic induction sensor probe for detection of dynamic process causing changes in the blood viscosity and density before and after coagulation based on the damped vibration principle, in order to evaluate the coagulation status. Utilizing the dynamic principle, the differential equation of vibration system comprising elastic support and electromagnetic induction device is established through sensor dynamic modeling. The structural parameters of elastic support are optimized, and the circular sheet spring is designed. Furthermore, harmonic response analysis and vibration fatigue coupling analysis are performed on the elastic support of the sensor by considering the natural frequency of the system, and the electromagnetic induction sensor testing device is set up. Using the device and coagulation reagent, the standard curve for coagulation POCT is plotted, and the blood sample application in clinical patients is established, which are methodologically compared with the imported POCT coagulation analyzer. The results show that the sensor designed in this paper has a first-order natural frequency of 11.368 Hz, which can withstand 5.295 × 10 2 million times of compressions and rebounds. Its correlation with the results of SONOCLOT analyzer reaches 0.996, and the reproducibility 0.002. The electromagnetic induction coagulation testing sensor designed has good elasticity and anti-fatigue, which can meet the accuracy requirement of clinical detection. This study provides the core technology for developing the electromagnetic induction POCT instrument for dynamic testing of coagulation process.

  16. Coagulation factor XII in thrombosis and inflammation. (United States)

    Maas, Coen; Renné, Thomas


    Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. The factor XII-driven-contact system starts coagulation and inflammatory mechanisms via the intrinsic pathway of coagulation and the bradykinin-producing kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood, however its in vivo functions are just beginning to emerge. Challenging the concept of the coagulation balance, targeting factor XII or its activator polyphosphate provides protection from thromboembolic diseases without interfering with hemostasis. This suggests that the polyphosphate/factor XII axis contributes to thrombus formation while being dispensable for hemostatic processes. In contrast to deficiency in factor XII providing safe thromboprotection, excessive FXII activity is associated with the life-threatening inflammatory disorder hereditary angioedema. The current review summarizes recent finding of the polyphosphate/factor XII-driven contact system at the intersection of procoagulant and proinflammatory disease states. Elucidating the contact system offers the exciting opportunity to develop strategies for safe interference with both thrombotic and inflammatory disorders. Copyright © 2018 American Society of Hematology.

  17. Effect of delivery modalities on the physiologic inhibition system of coagulation of the neonate. (United States)

    Franzoi, Malida; Simioni, Paolo; Luni, Sonia; Zerbinati, Patrizia; Girolami, Antonio; Zanardo, Vincenzo


    The perinatal period is associated with an increased incidence of thromboembolic complications, which may occur in both the maternal and fetal circulation in otherwise normal and healthy adults and fetuses, and this may be related to the activation of the coagulation system at the time of parturition. The risk of these complications is generally much higher in neonates, who have decreased activity of the physiologic inhibition system of coagulation (PISC), including protein C, protein S and antithrombin, in comparison with adults. Therefore, any additional obstetric iatrogenic factors could predispose the neonate to an increased risk of thromboembolic complications. The aim of this study was to evaluate the influence of modality of delivery (spontaneous vaginal delivery vs. elective caesarian section) on the neonatal PISC factor (protein C, protein S and antithrombin) levels and the fibrinolytic system (plasminogen and fibrinogen levels). We studied 41 consecutive healthy newborns, 18 delivered vaginally (mean gestational age 39.7 +/- 0.8) and 23 by elective caesarian section (mean gestational age 38.5 +/- 0.7). Plasma samples were collected from the umbilical cord at birth. AT activity, protein C antigen and activity, total and free protein S antigen, fibrinogen concentration and plasminogen activity were tested. Among PISC factors studied in cord blood of infants born after vaginal delivery, protein C antigen levels and antithrombin activity were statistically higher (41.3 +/- 9.4 vs. 33.9 +/- 7.2 and 58.5 +/- 10.0 vs. 48.4 +/- 12.7, respectively; Plabor stress of vaginal delivery may play a role in influencing the levels of some PISC factors in the cord blood of full-term neonates. In newborns with coagulation disorders, separate reference ranges in coagulation screening tests should be possibly needed depending on the delivery modality.

  18. [The association between blood pressure variability and sleep stability in essential hypertensive patients with sleep disorder]. (United States)

    Zhu, Y Q; Long, Q; Xiao, Q F; Zhang, M; Wei, Y L; Jiang, H; Tang, B


    Objective: To investigate the association of blood pressure variability and sleep stability in essential hypertensive patients with sleep disorder by cardiopulmonary coupling. Methods: Performed according to strict inclusion and exclusion criteria, 88 new cases of essential hypertension who came from the international department and the cardiology department of china-japan friendship hospital were enrolled. Sleep stability and 24 h ambulatory blood pressure data were collected by the portable sleep monitor based on cardiopulmonary coupling technique and 24 h ambulatory blood pressure monitor. Analysis the correlation of blood pressure variability and sleep stability. Results: In the nighttime, systolic blood pressure standard deviation, systolic blood pressure variation coefficient, the ratio of the systolic blood pressure minimum to the maximum, diastolic blood pressure standard deviation, diastolic blood pressure variation coefficient were positively correlated with unstable sleep duration ( r =0.185, 0.24, 0.237, 0.43, 0.276, P Blood pressure variability is associated with sleep stability, especially at night, the longer the unstable sleep duration, the greater the variability in night blood pressure.

  19. Whole blood BDNF levels in healthy twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Vinberg, Maj; Aznar, Susana


    and protected against affective disorder. Whole blood assessed for BDNF concentrations and correlated to risk status, neuroticism, and number of stressful life events. RESULTS: Between the groups, we found no significant difference in whole blood BDNF levels. Women at high-risk for depression who had......BACKGROUND: Depression has been associated with decreased blood BDNF concentrations; but it is unclear if low blood BDNF levels are a state or a trait marker of depression. METHODS: We investigated blood BDNF concentrations in a twin population including both subjects highly predisposed...... experienced three or more recent stressful events (n=26) had decreased whole blood BDNF levels compared to high-risk women with two or less recent stressful events (n=35), 21.6+/-7.0 vs. 18.5+/-4.1 ng/ml, respectively, (p

  20. Genetics Home Reference: inherited thyroxine-binding globulin deficiency (United States)

    ... problems, it can be mistaken for more serious thyroid disorders (such as hypothyroidism). Therefore, it is important to ... TBG Level Health Topic: Newborn Screening Health Topic: Thyroid Diseases Educational Resources (1 link) MalaCards: inherited thyroxine-binding ...

  1. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder


    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy


    Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen...

  2. The study of SPECT cerebral blood flow and neuroreceptor imaging in depressive disorders

    International Nuclear Information System (INIS)

    Yuan Ling; Liu Jianzhong; Wu Zhifang


    The imaging methods of depressive disorders include structural imaging and functional imaging, the abnormal of cerebral structure in CT and MRI is neither significant nor specific, while the use of PET and SPECT provides depression study in-vivo about regional cerebral blood flow and central neurotransmitter and receptor's structure and function, which further have advanced research on aetiology, pathogenesis and therapy of' depressive disorders. (authors)

  3. Alterations of Regional Cerebral Blood Flow in Major Depressive Disorder

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won Hyoung; Chung, Yong An; Seo, Ye Young; Yoo, Ik Dong; Na, Sae Jung; Jung, Hyun Suk; Kim, Ki Jun [College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)


    The authors analyzed how the regional cerebral blood flow (rCBF) findings of patients with major depression differ from the normal control, and our results were compared to previous reports. Twelve patients fulfilling DSM-IV criteria for major depression who were off all psychotropic medications for > 4 weeks (male: 7, female: 5, age range: 19approx52 years, average age: 29.3+-9.9 years) and 14 normal volunteers (male: 8, female: 6, age range: 19approx53 years, average age: 31.4+-9.2 years) were recruited. Images of brain perfusion SPECT were obtained using Tc-99m ECD and patterns of the rCBF were compared between patients with major depression and the healthy control subjects. The patients with major depression showed increase of the r-CBF in right lingual gyrus, right fusiform gyrus, left lingual gyrus, left precuneus, and left superior temporal gyrus, and showed decrease of r-CBF in right pons, left medial frontal gyrus, cingulate gyrus of left limbic lobe, cingulate gyrus of right frontal lobe, and cingulate gyrus of right limbic lobe compared to the normal control. The Tc-99m ECD brain perfusion SPECT findings in our study did not differ from the previously reported regional cerebral blood flow pattern of patients with major depression. Especially, decreased rCBF pattern typical to major depression patients in the right pons, left medial frontal gyrus, and cingulate regions was clearly demonstrated

  4. Alterations of Regional Cerebral Blood Flow in Major Depressive Disorder

    International Nuclear Information System (INIS)

    Lee, Won Hyoung; Chung, Yong An; Seo, Ye Young; Yoo, Ik Dong; Na, Sae Jung; Jung, Hyun Suk; Kim, Ki Jun


    The authors analyzed how the regional cerebral blood flow (rCBF) findings of patients with major depression differ from the normal control, and our results were compared to previous reports. Twelve patients fulfilling DSM-IV criteria for major depression who were off all psychotropic medications for > 4 weeks (male: 7, female: 5, age range: 19∼52 years, average age: 29.3±9.9 years) and 14 normal volunteers (male: 8, female: 6, age range: 19∼53 years, average age: 31.4±9.2 years) were recruited. Images of brain perfusion SPECT were obtained using Tc-99m ECD and patterns of the rCBF were compared between patients with major depression and the healthy control subjects. The patients with major depression showed increase of the r-CBF in right lingual gyrus, right fusiform gyrus, left lingual gyrus, left precuneus, and left superior temporal gyrus, and showed decrease of r-CBF in right pons, left medial frontal gyrus, cingulate gyrus of left limbic lobe, cingulate gyrus of right frontal lobe, and cingulate gyrus of right limbic lobe compared to the normal control. The Tc-99m ECD brain perfusion SPECT findings in our study did not differ from the previously reported regional cerebral blood flow pattern of patients with major depression. Especially, decreased rCBF pattern typical to major depression patients in the right pons, left medial frontal gyrus, and cingulate regions was clearly demonstrated

  5. Hypothesis: Disseminated Intravascular Inflammation as the Inflammatory Counterpart to Disseminated Intravascular Coagulation (United States)

    Bull, Brian S.; Bull, Maureen H.


    We have identified a leukocyte activation syndrome that is occasionally associated with the transfusion of intraoperatively recovered erythrocytes. This syndrome appears to result from intravascular damage caused by leukocytes activated during the erythrocyte salvage process. We hypothesize that this syndrome is part of a larger disease grouping: disseminated intravascular inflammation (DII). DII is the analog of the coagulation disorder disseminated intravascular coagulation. In disseminated intravascular coagulation, the organ damage results from uncontrolled activation of the clotting pathway; in DII the damage is caused by leukocytes that have become activated by direct contact with bacteria or in rare instances-such as erythrocyte salvage-in the absence of bacteria and bacterial products. Recent studies of the hazards associated with intraoperative blood salvage indicate that activation of leukocytes can be achieved by exposure to activated platelets alone. If such activated leukocytes are reinfused along with the washed erythrocytes, widespread organ damage may result. The lung is the organ most severely affected by activated leukocytes. Adult respiratory distress syndrome is one outcome. It is likely that DII is a presently unrecognized pathophysiological process that complicates a variety of primary disease states and increases their lethality.

  6. Genetic Disorders (United States)

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  7. Coagulation Management in Jersey Calves: An ex vivo Study. (United States)

    Gröning, Sabine; Maas, Judith; van Geul, Svenja; Rossaint, Rolf; Steinseifer, Ulrich; Grottke, Oliver


    Jersey calves are frequently used as an experimental animal model for in vivo testing of cardiac assist devices or orthopedic implants. In this ex vivo study, we analyzed the coagulation system of the Jersey calves and the potential of human-based coagulation management to circumvent perioperative bleeding complications during surgery. Experimental Procedure: Blood from 7 Jersey calves was subjected to standard laboratory tests and thromboelastometry analysis. An ex vivo model of dilutional coagulopathy was used to study the effects of fibrinogen or prothrombin complex concentrate supplementation. Fibrinolysis was induced with tissue plasminogen activator to identify potential therapeutic strategies involving tranexamic acid or aprotinin. Furthermore, anticoagulation strategies were evaluated by incubating the blood samples with dabigatran or rivaroxaban. Baseline values for thromboelastometry and standard laboratory parameters, including prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers, were established. Fifty percent diluted blood showed a statistically significant impairment of hemostasis. The parameters significantly improved after the administration of fibrinogen or prothrombin complex concentrate. Tranexamic acid and aprotinin ameliorated tissue plasminogen activator-induced fibrinolysis. Both dabigatran and rivaroxaban significantly prolonged the coagulation parameters. In this ex vivo study, coagulation factors, factor concentrate, antifibrinolytic reagents, and anticoagulants regularly used in the clinic positively impacted coagulation parameters in Jersey calf blood. © 2017 S. Karger AG, Basel.

  8. A C-type lectin isolated from the skin of Japanese bullhead shark (Heterodontus japonicus) binds a remarkably broad range of sugars and induces blood coagulation. (United States)

    Tsutsui, Shigeyuki; Dotsuta, Yuma; Ono, Ayaka; Suzuki, Masanari; Tateno, Hiroaki; Hirabayashi, Jun; Nakamura, Osamu


    The aim of this study was to determine the physiological role of skin lectins of the Japanese bullhead shark (Heterodontus japonicus). A skin extract was subjected to affinity chromatography using seven different sugars as ligands. Molecular mass and N-terminal amino acid sequence analyses indicated elution of the same protein by each of the seven respective cognate ligands from sugar affinity columns. The predicted amino acid sequence encoded by the cDNA of this protein [designated as H. japonicus C-type-lectin (HjCL)] identified it as a novel fish subgroup VII C-type lectin evolutionarily related to snake venom lectins. HjCL was predicted to bind to mannose because of the presence of a Glu-Pro-Asn (EPN) motif; however, haemagglutination inhibition assays and glycoconjugate microarray analysis demonstrated its binding to numerous structurally diverse sugars. Competitive sugar-binding assays using affinity chromatography indicated that HjCL bound multiple sugars via a common carbohydrate-recognition domain. The mRNA encoding HjCL was specifically detected in the skin, and immunohistochemical analysis detected its expression in uncharacterized large cells in the epidermis. HjCL agglutinated the bacterial pathogen Edwardsiella tarda and promoted immediate clotting of shark blood, indicating that HjCL is involved in host defence on the skin surface especially when the shark is injured and bleeds. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  9. Coagulation profile in patients undergoing video-assisted thoracoscopic lobectomy

    DEFF Research Database (Denmark)

    Christensen, Thomas Decker; Vad, Henrik; Pedersen, Søren


    Background: Knowledge about the impact of Low-Molecular-Weight Heparin (LMWH) on the coagulation system in patients undergoing minimal invasive lung cancer surgery is sparse. The aim of this study was to assess the effect of LMWH on the coagulation system in patients undergoing Video......-Assisted Thoracoscopic Surgery (VATS) lobectomy for primary lung cancer. Methods: Sixty-three patients diagnosed with primary lung cancer undergoing VATS lobectomy were randomized to either subcutaneous injection with dalteparin (Fragmin®) 5000 IE once daily or no intervention. Coagulation was assessed pre-, peri......-, and the first two days postoperatively by standard coagulation blood test, thromboelastometry (ROTEM®) and thrombin generation. Results: Patients undergoing potential curative surgery for lung cancer were not hypercoagulable preoperatively. There was no statistically significant difference in the majority...

  10. Valproic acid modulates platelet and coagulation function ex vivo

    DEFF Research Database (Denmark)

    Bambakidis, Ted; Dekker, Simone E; Halaweish, Ihab


    of coagulopathy, it remains unknown whether this is a direct effect of the drug, or the establishment of an overall prosurvival phenotype. We thus conducted an ex-vivo experiment to determine if VPA has an effect on coagulation and platelet function. Ten swine were subjected to traumatic brain injury (TBI......) and hemorrhagic shock (HS). Blood samples were drawn prior to TBI+HS insult (Healthy group) and 2 h following TBI+HS (Shock group). Samples were incubated with VPA or vehicle controls for 1 h. Platelet aggregation was analyzed via impedance aggregometry and coagulation was measured using thromboelastography....... Addition of VPA to the healthy blood did not affect platelet aggregation or coagulation parameters. In shock blood, incubation with VPA significantly reduced collagen-(P = 0.050), arachidonic acid-(P = 0.005), and adenosine diphosphate-(P = 0.023) induced platelet aggregation. VPA also significantly...

  11. Non-traditional inheritance

    International Nuclear Information System (INIS)

    Hall, J.G.


    In the last few years, several non-traditional forms of inheritance have been recognized. These include mosaicism, cytoplasmic inheritance, uniparental disomy, imprinting, amplification/anticipation, and somatic recombination. Genomic imprinting (GI) is the dependence of the phenotype on the sex of the transmitting parent. GI in humans seems to involve growth, behaviour, and survival in utero. The detailed mechanism of genomic imprinting is not known, but it seems that some process is involved in turning a gene off; this probably involves two genes, one of which produces a product that turns a gene off, and the gene that is itself turned off. The process of imprinting (turning off) may be associated with methylation. Erasure of imprinting can occur, and seems to be associated with meiosis. 10 refs

  12. Lipedema: an inherited condition. (United States)

    Child, Anne H; Gordon, Kristiana D; Sharpe, Pip; Brice, Glen; Ostergaard, Pia; Jeffery, Steve; Mortimer, Peter S


    Lipedema is a condition characterized by swelling and enlargement of the lower limbs due to abnormal deposition of subcutaneous fat. Lipedema is an under-recognized condition, often misdiagnosed as lymphedema or dismissed as simple obesity. We present a series of pedigrees and propose that lipedema is a genetic condition with either X-linked dominant inheritance or more likely, autosomal dominant inheritance with sex limitation. Lipedema appears to be a condition almost exclusively affecting females, presumably estrogen-requiring as it usually manifests at puberty. Lipedema is an entity distinct from obesity, but may be wrongly diagnosed as primary obesity, due to clinical overlap. The phenotype suggests a condition distinct from obesity and associated with pain, tenderness, and easy bruising in affected areas. (c) 2010 Wiley-Liss, Inc.

  13. Coagulation Factors Test (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  14. Comparative serological investigation between cat and tiger blood for transfusion. (United States)

    Thengchaisri, Naris; Sinthusingha, Chayakrit; Arthitwong, Surapong; Sattasathuchana, Panpicha


    Evidence suggests that non-domesticated felids inherited the same AB-erythrocyte antigens as domestic cats. To study the possible compatibility of tiger blood with that of other endangered felidae, blood samples from captive tigers and domestic cats were subjected to an in vitro study. The objectives of this study were to (1) identify whether the captive tigers had blood type AB and (2) determine the compatibility between the blood of captive tigers and that of domestic cats with a similar blood type. The anti-coagulated blood with ethylenediaminetetraacetic acid of 30 tigers was examined to determine blood type, and a crossmatching test was performed between tiger and cat blood. All 30 tigers had blood type A. Tube agglutination tests using tiger plasma with cat erythrocytes resulted in 100% agglutination (n=30) with type B cat erythrocytes and 76.7% agglutination (n=23) with type A cat erythrocytes. The 80% of major and 60% of minor compatibilities between blood from 10 tigers and 10 domestic cats with blood type A were found to pass compatibility tests. Interestingly, 3/10 of the tigers' red blood cell samples were fully compatible with all cat plasmas, and 1/10 of the tiger plasma samples were fully compatible with the type A red cells of domestic cats. Although the result of present findings revealed type-A blood group in the surveyed tigers, the reaction of tiger plasma with Type-A red cell from cats suggested a possibility of other blood type in tigers.

  15. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder (United States)

    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy


    Elevated whole blood serotonin levels are observed in more than 25% of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD,…

  16. Disruption of the leptomeningeal blood barrier in neuromyelitis optica spectrum disorder

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Flanagan, Eoin P.; Fujihara, Kazuo


    Objective: To describe leptomeningeal blood-barrier impairment reflected by MRI gadoliniumenhanced lesions in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD). Methods: A retrospective case series of 11 AQP4-IgG-positive NMOSD patients ...

  17. [Inheritance of human fingerprints]. (United States)

    Voĭtenko, V P; Poliukhov, A M; Kolodchenko, V P


    Polygenic threshold model of finger dermatoglyphics inheritance is worked out on the basis of family and population data. According to the model, ulnar loops are subthreshold patterns, which transforms into whorl or arch under the control of SU and SR gene complexes. Epistasis-hypostasis interactions take place between genes of SU and SR complexes. Classification of phenotypes for finger dermatoglyphics is offered and the frequency of these phenotypes in three populational samples of Kiev is studied.

  18. A Rare Case of Inherited Factor‑II Deficiency Causing Life ...

    African Journals Online (AJOL)

    Careful history taking and clinical suspicion for an underlying bleeding ... disorders. Menorrhagia may be the only clinical manifestation of an inherited bleeding disorder. We report a case of inherited hypoprothrombinemia (factor II deficiency), a rare bleeding ... Bleeding disorder as a cause of life threatening menorrhagia.

  19. Inheritance of cancer. (United States)

    Frank, Steven A


    Extract: A single inherited mutant gene may be enough to cause a very high cancer risk. Single-mutation cases have provided much insight into the genetic basis of carcinogenesis, but they are relatively rare and account for only a small fraction of all cancers. Examples include mutation to the APC gene, causing early onset colon cancer in the syndrome familial adenomatous polyposis (tumorous polyp-tissue in the colon); mutation to either the BRCA1 or BRCA2 genes, causing an increased risk of breast cancer; and mutation to the TP53 gene, causing Li-Fraumeni syndrome with various early onset cancers such as bone or soft tissue sarcoma. Cancers sometimes cluster in families, but do not follow the rigid inheritance pattern characteristic of a mutation to a single gene. Males with a brother or father who has suffered prostate cancer are more likely to develop the disease. Similarly, females with a sister or mother who has suffered breast cancer are more likely to get a breast tumor. Some of the clustering may arise from the common diet and environment shared by families. Recently, however, researchers have begun to assign a significant fraction of cancer risk to the particular genetic variants that individuals inherit.

  20. Raman Tweezers as a Diagnostic Tool of Hemoglobin-Related Blood Disorders

    Directory of Open Access Journals (Sweden)

    Giulia Rusciano


    Full Text Available This review presents the development of a Raman Tweezers system for detecting hemoglobin-related blood disorders at a single cell level. The study demonstrates that the molecular fingerprint insight provided by Raman analysis holds great promise for distinguishing between healthy and diseased cells in the field of biomedicine. Herein a Raman Tweezers system has been applied to investigate the effects of thalassemia, a blood disease quite diffuse in the Mediterranean Sea region. By resonant excitation of hemoglobin Raman bands, we examined the oxygenation capability of normal, alpha- and beta-thalassemic erythrocytes. A reduction of this fundamental red blood cell function, particularly severe for beta-thalassemia, has been found. Raman spectroscopy was also used to draw hemoglobin distribution inside single erythrocytes; the results confirmed the characteristic anomaly (target shape, occurring in thalassemia and some other blood disorders. The success of resonance Raman spectroscopy for thalassemia detection reported in this review provide an interesting starting point to explore the application of a Raman Tweezers system in the analysis of several blood disorders.

  1. Umbilical cord blood stem cells: clinical trials in non-hematological disorders. (United States)

    Ilic, Dusko; Miere, Cristian; Lazic, Emilija


    Umbilical cord blood (UCB) has become the second most common source of stem cells for cell therapy. The recent boom in stem cell research and public fascination with promises of stem cell-based therapies, fueled by the media, have led researchers to explore the potential of UCB stem cells in therapy for non-hematological disorders. database searched with key words 'cord blood stem cells' on December 28, 2011. As a rich source of the most primitive hematopoietic stem cells, UCB has a strong regenerative potential in stem cell-based-therapy for hematological disorders. Potential of UCB stem cells in therapy for non-hematological disorders. Increasing number of clinical trials with UCB stem cell-based therapy for a variety of diseases. A need for standardization of criteria for selection of UCB units for stem cell-based therapy, outcome measures and long-term follow-up.

  2. Regional cerebral blood flow and P300 in neurosurgical disorders

    Energy Technology Data Exchange (ETDEWEB)

    Funahashi, Kazuyoshi; Hyoutani, Genhachi; Maeshima, Shinichirou; Miyamoto, Kazuki; Kuwata, Toshikazu; Terada, Tomoaki; Komai, Norihiko (Wakayama Medical Coll. (Japan))


    Changes in regional cerebral blood flow (rCBF), P300 and higher brain function were studied in neurosurgical patients with localized lesions on computed tomography (CT). Twenty-five patients ranging in age from 30 to 81 were studied. Nineteen of these suffered from cerebrovascular disease and six had tumors. Using the oddball paradigm, P300 components were elicited by rate tones (2 KHz) and recorded at Cz and Pz referred to linked ear-lobe electorodes. The P300 latencies of the patients were statistically compared with those of 27 normal subjects. Higher brain function was evaluated with the following psychological tests: a rating scale for psychological function (Sano and Tanemura), Mini-Mental State (MMS), Hasegawa's Dementia Scale (HDS) and the 'Kanahiroi' test. Regional CBF was measured in the bilateral cerebral cortices (the frontal, temporal and occipital lobes), thalamus and basal ganglia by means of a cold xenon CT method. The laterality indices of rCBF (Rt. rCBF/Lt. rCBF) in the bilateral symmetrical areas of the patients were compared to those of 8 normal subjects. Of the 25 patients, 12 revealed prolongation of P300 latency. Ten (86%) of the 12 with prolonged P300 latency showed reduction of rCBF in the right cerebral hemisphere (rt. frontal lobe, rt. thalamus and rt. basal ganglia). Significant correlations (P<0.025) were recognized between the P300 latencies and the laterality indices of rCBF in the frontal lobe and thalamus. There was a significant correlation (P<0.05) between the scores of MMS and HDS and the laterality indicies of rCBF in the frontal lobe only. In the 13 patients with normal P300 latency, 6 (46%) displayed no reduction in rCBF. The remaining 7 patients with normal P300 showed reduction of rCBF in the left hemisphere. Both right frontal lobe and right thalamus have an important role affecting the prolongation of P300 latency and disturbance of cognitive functions. (author).

  3. Regional cerebral blood flow and P300 in neurosurgical disorders

    International Nuclear Information System (INIS)

    Funahashi, Kazuyoshi; Hyoutani, Genhachi; Maeshima, Shinichirou; Miyamoto, Kazuki; Kuwata, Toshikazu; Terada, Tomoaki; Komai, Norihiko


    Changes in regional cerebral blood flow (rCBF), P300 and higher brain function were studied in neurosurgical patients with localized lesions on computed tomography (CT). Twenty-five patients ranging in age from 30 to 81 were studied. Nineteen of these suffered from cerebrovascular disease and six had tumors. Using the oddball paradigm, P300 components were elicited by rate tones (2 KHz) and recorded at Cz and Pz referred to linked ear-lobe electorodes. The P300 latencies of the patients were statistically compared with those of 27 normal subjects. Higher brain function was evaluated with the following psychological tests: a rating scale for psychological function (Sano and Tanemura), Mini-Mental State (MMS), Hasegawa's Dementia Scale (HDS) and the 'Kanahiroi' test. Regional CBF was measured in the bilateral cerebral cortices (the frontal, temporal and occipital lobes), thalamus and basal ganglia by means of a cold xenon CT method. The laterality indices of rCBF (Rt. rCBF/Lt. rCBF) in the bilateral symmetrical areas of the patients were compared to those of 8 normal subjects. Of the 25 patients, 12 revealed prolongation of P300 latency. Ten (86%) of the 12 with prolonged P300 latency showed reduction of rCBF in the right cerebral hemisphere (rt. frontal lobe, rt. thalamus and rt. basal ganglia). Significant correlations (P<0.025) were recognized between the P300 latencies and the laterality indices of rCBF in the frontal lobe and thalamus. There was a significant correlation (P<0.05) between the scores of MMS and HDS and the laterality indicies of rCBF in the frontal lobe only. In the 13 patients with normal P300 latency, 6 (46%) displayed no reduction in rCBF. The remaining 7 patients with normal P300 showed reduction of rCBF in the left hemisphere. Both right frontal lobe and right thalamus have an important role affecting the prolongation of P300 latency and disturbance of cognitive functions. (author)

  4. Blood group AB and factor V Leiden as risk factors for pre-eclampsia: a population-based nested case-control study. (United States)

    Hiltunen, Leena M; Laivuori, Hannele; Rautanen, Anna; Kaaja, Risto; Kere, Juha; Krusius, Tom; Paunio, Mikko; Rasi, Vesa


    Pre-eclampsia is an important cause of maternal morbidity and mortality. Its etiology is still unknown. Clinical symptoms correlate with activation of coagulation and inherited thrombophilia has been associated with pre-eclampsia. ABO blood group has been associated with thrombotic disorders and pre-eclampsia. We assessed ABO blood group, seven thrombophilia associated polymorphisms, and anti-beta2-glycoprotein I antibodies as risk factors for pre-eclampsia. We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers and medical records were reviewed. We studied 248 cases fulfilling strict criteria for pre-eclampsia and 679 controls. Severe pre-eclampsia, early pre-eclampsia, and pre-eclampsia with intra-uterine growth restriction (IUGR) were analyzed separately. Blood group AB increased the risk for pre-eclampsia as a whole (OR 2.1, 95% CI 1.3-3.5), and in the three subgroups (OR 2.3, 3.8, 3.4; 95% CI 1.3-3.9, 2.0-7.1, 1.6-7.1). FV Leiden increased the risk as a whole (OR 1.7, 95% CI 0.8-3.9), and in the three subgroups, although not statistically significantly. Anti-beta2-glycoprotein I antibodies were not associated with pre-eclampsia. High body mass index, diabetes, first pregnancy, and twin pregnancy increased the risk from 1.5-fold to 8.2-fold. Our results confirm and extend the prior observation of blood group AB being a risk factor for pre-eclampsia. ABO blood group is known from all pregnant women. The value of blood group as risk factor for pre-eclampsia should be further assessed in prospective studies. In this study, FV Leiden was not statistically significant risk factor.

  5. Blood Product Administration in the Critical Care and Perioperative Settings. (United States)

    Rygård, Sofie Louise; Holst, Lars Broksø; Perner, Anders


    The critical care and perioperative settings are high consumers of blood products, with multiple units and different products often given to an individual patient. The recommendation of this review is always to consider the risks and benefits for a specific blood product for a specific patient in a specific clinical setting. Optimize patient status by treating anemia and preventing the need for red blood cell transfusion. Consider other options for correction of anemia and coagulation disorders and use an imperative non-overtransfusion policy for all blood products. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Peijs, L; Vinberg, M


    as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6-12-month period and in 40 age......- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with healthy control...... subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver...

  7. Alginate microbeads are coagulation compatible, while alginate microcapsules activate coagulation secondary to complement or directly through FXII. (United States)

    Gravastrand, Caroline; Hamad, Shamal; Fure, Hilde; Steinkjer, Bjørg; Ryan, Liv; Oberholzer, Josè; Lambris, John D; Lacík, Igor; Mollnes, Tom Eirik; Espevik, Terje; Brekke, Ole-Lars; Rokstad, Anne Mari


    Alginate microspheres are presently under evaluation for future cell-based therapy. Their ability to induce harmful host reactions needs to be identified for developing the most suitable devices and efficient prevention strategies. We used a lepirudin based human whole blood model to investigate the coagulation potentials of alginate-based microspheres: alginate microbeads (Ca/Ba Beads), alginate poly-l-lysine microcapsules (APA and AP microcapsules) and sodium alginate-sodium cellulose sulfate-poly(methylene-co-cyanoguanidine) microcapsules (PMCG microcapsules). Coagulation activation measured by prothrombin fragments 1+2 (PTF1.2) was rapidly and markedly induced by the PMCG microcapsules, delayed and lower induced by the APA and AP microcapsules, and not induced by the Ca/Ba Beads. Monocytes tissue factor (TF) expression was similarly activated by the microcapsules, whereas not by the Ca/Ba Beads. PMCG microcapsules-induced PTF1.2 was abolished by FXII inhibition (corn trypsin inhibitor), thus pointing to activation through the contact pathway. PTF1.2 induced by the AP and APA microcapsules was inhibited by anti-TF antibody, pointing to a TF driven coagulation. The TF induced coagulation was inhibited by the complement inhibitors compstatin (C3 inhibition) and eculizumab (C5 inhibition), revealing a complement-coagulation cross-talk. This is the first study on the coagulation potentials of alginate microspheres, and identifies differences in activation potential, pathways and possible intervention points. Alginate microcapsules are prospective candidate materials for cell encapsulation therapy. The material surface must be free of host cell adhesion to ensure free diffusion of nutrition and oxygen to the encapsulated cells. Coagulation activation is one gateway to cellular overgrowth through deposition of fibrin. Herein we used a physiologically relevant whole blood model to investigate the coagulation potential of alginate microcapsules and microbeads. The

  8. Disseminated intravascular coagulation in solid tumors

    International Nuclear Information System (INIS)

    Terzieff, V.; Alonso, I.; Vázquez, A.


    It is estimated that 20-25% of cases of disseminated intravascular coagulation (DIC) relate to an underlying neoplasia primarily hematologic. It is estimated that about 5% of patients with solid tumors have CID clinic, although the incidence of subclinical alterations is much higher. The CID is not limited to the activation of the coagulation cascade, which leads to bleeding micro thrombosis and consumption of coagulation factors. Solid tumors are frequently associated adenocarcinomas producers mucin (especially gastric), usually in the context of a disseminated disease. The mucin may act as a promoter of the cascade, but probably it is a multi-event. High levels of TNF to produced by the tumor mass and chemotherapy-induced cell lysis have Also linked. Although the bleeding is usually oriented diagnosis, the most frequent cause of death is thrombosis. There are no specific tests for diagnosis. Elevated levels of D-dimer and products oriented fibrinogen degradation diagnosis. No reduction fibrinogen and almost always, one thrombocytopenia consumption. Treatment is complex and there is no consensus on many points. To recover the lost factors for consumption, it is recommended to use fresh frozen plasma and / or washed red blood cells. the heparin anticoagulation low dose is indicated since the disease causal can not be controlled quickly, but should not be initiated if there thrombocytopenia 50.000.El under profuse bleeding can require the use of tranexamic acid or EACA. Acute DIC, the case of our patient, is rare and very serious


    Directory of Open Access Journals (Sweden)

    Jaroslav Kováčik


    Full Text Available The aim of this work was to monitor the relations between selected indicators of technological properties of milk and blood biochemical parameters of dairy cows with metabolic disorders. Thirty-two cows were chosen, which were divided into 3 groups: first group - cows with metabolic problems of acidosis, second group - cows with metabolic problems of alkalosis, third group - healthy cows. Blood, urine and milk samples were collected. Urea, total lipids, total proteins, glucose and calcium was determined in the blood serum. Pure acidobasic forms, pH and density of urine were determined. Proteins, lactose, non-fat-solids, somatic cells count, calcium, urea, titratable acidity, fermentability, rennetability and thermostability were determined in samples of milk. Significant negative dependences were observed in the group of cows with metabolic problems of acidosis between urea in blood and in milk (r = -0.694, P <0.05, between calcium in blood and in milk (r = -0.653, P <0, 05, and between calcium in milk and glucose in blood (r = -0.648, P <0.05. In the group of cows with alkalosis, statistically significant correlation between total lipids in blood and fat in milk was found (r = -0.879, P <0.05.

  10. [Evoked potentials and regional cerebral blood flow changes in conversion disorder: a case report and review]. (United States)

    Gürses, Nadide; Temuçin, Cağri Mesut; Lay Ergün, Eser; Ertuğrul, Aygün; Ozer, Suzan; Demir, Başaran


    Conversion disorder is defined as the presence of functional impairment in motor, sensory or neurovegetative systems which cannot be explained by a general medical condition. Although the diagnostic systems emphasize the absence of an organic basis for the dysfunction in conversion disorder, there has been a growing interest in the specific functional brain correlates of conversion symptoms in recent years, particularly by examining neuroimaging and neurophysiological measures. In this case report, regional cerebral blood flow changes and evoked potentials of a patient with conversion symptoms are presented. Somatosensory evoked potentials (SEP) of this patient with conversion disorder who had signs of movement disorder revealed that the latency to N20, P 25 waves were in normal limits while the amplitudes of the P25 and N33 components were extremely high (giant SEP). Regional cerebral blood flow assessment revealed hypoperfusion in the left parietal and temporal lobes of the brain. Three months after the first assessment, the control scans showed that the left parietal hypoperfusion disappeared while the left temporal hypoperfusion was still present. The following SEP evaluations which were repeated twice in three months intervals after the initial recordings, showed the persistence of the abnormalities in somatosensorial measures. The neurophysiological and neuroimaging findings in conversion disorder were reviewed and the results of the evaluations of this case were discussed in this article.

  11. Learning disorder and blood concentration of heavy metals in the United Arab Emirates. (United States)

    Yousef, Said; Eapen, Valsamma; Zoubeidi, Taoufik; Kosanovic, Melita; Mabrouk, Abdel Azim; Adem, Abdu


    Children are frequently exposed to toxic metals in the environment, and their developing central nervous system is particularly vulnerable to their effects. This study examined the blood level of heavy metals in children with learning disorder (LD) as compared to children without LD in the United Arab Emirates (UAE). Significantly high blood concentrations of seven heavy metals were found in children with LD. Further analysis using forward stepwise logistic regression showed that molybdenum levels and family history of developmental problems were the best predictors of LD. Our findings suggest the need for monitoring for toxic metals in the environment. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Coagulation Function of Stored Whole Blood is Preserved for 14 Days in Austere Conditions: A ROTEM Feasibility Study During a Norwegian Antipiracy Mission and Comparison to Equal Ratio Reconstituted Blood (United States)


    donors.11 Of 143 volunteers, none tested positive for TTDs in two separate samples, and screening for irregular blood type antibodies was weakly posi...titers, and for infectious disease screening. Group O do- nors were categorized as high-titer (anti-A/B Q 100 IgMor400 IgG antibody titers) or low-titer

  13. Blood coagulation factor VIII: An overview

    Indian Academy of Sciences (India)


    Solvent, detergent and heat treatment. Hemofil-M. Baxter. Pooled human venous plasma. Immunoaffinity chromatography using murine monoclonal anti- body. Solvent and detergent. Monarc-M. American. Red Cross. Pooled human venous plasma. Immunoaffinity chromatography using murine monoclonal antibody.

  14. Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection. (United States)

    Jabado, N; Le Deist, F; Cant, A; De Graeff-Meeders, E R; Fasth, A; Morgan, G; Vellodi, A; Hale, G; Bujan, W; Thomas, C; Cavazzana-Calvo, M; Wijdenes, J; Fischer, A


    For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study. Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and

  15. BMC Blood Disorders becomes BMC Hematology: evolving along with the hematology field


    Chap, Christna


    This Editorial marks the launch of BMC Hematology, formerly known as BMC Blood Disorders, within the BMC series of journals published by BioMed Central. The scope of BMC Hematology encompasses basic, experimental and clinical research related to hematology. In this Editorial we will discuss the rationale behind this relaunch and how, as an open access journal providing unrestricted and free access to scientific and scholarly work, BMC Hematology will help disseminate research in the hematolog...

  16. Coagulation tests show significant differences in patients with breast cancer. (United States)

    Tas, Faruk; Kilic, Leyla; Duranyildiz, Derya


    Activated coagulation and fibrinolytic system in cancer patients is associated with tumor stroma formation and metastasis in different cancer types. The aim of this study is to explore the correlation of blood coagulation assays for various clinicopathologic factors in breast cancer patients. A total of 123 female breast cancer patients were enrolled into the study. All the patients were treatment naïve. Pretreatment blood coagulation tests including PT, APTT, PTA, INR, D-dimer, fibrinogen levels, and platelet counts were evaluated. Median age of diagnosis was 51 years old (range 26-82). Twenty-two percent of the group consisted of metastatic breast cancer patients. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group except for PT (p50 years) was associated with higher D-dimer levels (p=0.003). Metastatic patients exhibited significantly higher D-dimer values when compared with early breast cancer patients (p=0.049). Advanced tumor stage (T3 and T4) was associated with higher INR (p=0.05) and lower PTA (p=0.025). In conclusion, coagulation tests show significant differences in patients with breast cancer.

  17. Blood serum concentrations of kynurenic acid in patients diagnosed with recurrent depressive disorder, depression in bipolar disorder, and schizoaffective disorder treated with electroconvulsive therapy. (United States)

    Olajossy, Marcin; Olajossy, Bartosz; Wnuk, Sebastian; Potembska, Emilia; Urbańska, Ewa


    The aim of the present study was to compare blood serum kynurenic acid (KYNA) concentrations measured before ECT and after 1, 6 and 12 electroconvulsive treatment (ECT) sessions in patients with diagnoses of recurrent depressive disorder (RDD), depression in bipolar disorder (DBD) and schizoaffective disorder (SAD). The study group comprised of 50 patients with ICD-10 diagnoses of RDD, DBD and SAD. Blood serum KYNA concentrations were determined and clinical assessment was performed using the MADRS and the GAF scale. Significant differences were found in blood serum KYNA levels between RDD, DBD and SAD patients treated with electroconvulsive therapy and healthy controls: 1) KYNA concentrations in DBD patients measured before ECT and after 12 ECT sessions were significantly lower than in the control group; 2) KYNA concentrations in the serum of RDD patients measured before ECT and after one and 12 ECT sessions were significantly lower than in the control group, while those measured after 6 ECT session did not differ significantly from KYNA concentrations in healthy controls; 3) higher pre-treatment blood serum concentrations of KYNA in DBD patients correlated with a higher number of illness phases and poorer general functioning before treatment; 4) significant relationships were found between higher blood serum concentrations of KYNA in RDD patients after 1 ECT session and male gender, and between higher KYNA concentrations after 6 ECT sessions and increased depression and poorer functioning before treatment in those patients. Results show that KYNA concentrations in all diagnostic groups were lower before ECT (not statistically significant for the SAD group) and that there were no significant changes in those concentrations (compared with the baseline) during ECT.

  18. Association between sleep disorders and morning blood pressure in hypertensive patients. (United States)

    Li, Xinran; Li, Jiangbo; Liu, Kai; Gong, Shenzhen; Shi, Rufeng; Pan, Pei; Yang, Yujie; Chen, Xiaoping


    Sleep disorders are known to increase the risk of hypertension, yet few studies have investigated the relation between sleep disorders and morning blood pressure (BP). This study aimed to determine, whether the morning BP is associated with sleep quality and sleep-disordered breathing. A total of 144 hypertensive patients were included in this cross-sectional study. Each subject underwent anthropometric measurements, biochemical testing, 24-h ambulatory BP monitoring, and polysomnography (PSG). Sleep quality and sleep-disordered breathing were determined by PSG parameters of sleep architecture and sleep respiratory. There were no significant differences between subjects with and without morning hypertension in the parameters of sleep architecture and sleep respiratory. In multiple regression analysis, morning BP was independently associated with night-time BP and morning BP surge, but not with the parameters of sleep architecture and sleep respiratory. Further analysis showed that both night-time BP and morning BP surge were independently associated with the sleep respiratory parameters. In conclusion, sleep-disordered breathing might indirectly affect the morning BP by elevated night-time BP, yet neither poor sleep quality nor sleep-disordered breathing was major determinants of elevated morning BP in hypertensive patients.

  19. coagulation factors level in fresh frozen plasma in rwanda

    African Journals Online (AJOL)


    Feb 2, 2014 ... National Centre for Blood Transfusion Division/Kigali-Rwanda, D. Agwata, BSc, MSc, Medical Laboratory Sciences,. Jomo Kenyatta University Of Agriculture and Technology. COAGULATION FACTORS LEVEL IN FRESH FROZEN PLASMA IN RWANDA. S. UWAMUNGU, A. K. NYAMACHE, F. MASAISA, ...

  20. Coagulation for the clinician | Rutmann | South African Journal of ...

    African Journals Online (AJOL)

    The integrity of the circulation is maintained through the provision of a rapid, potent, but tightly localised coagulation response to vascular damage. There is, however, one extraordinary problem in the regulation of haemostasis – blood flows. Normal haemostasis is the ability of the haemostatic system to control activation of ...

  1. 21 CFR 864.5400 - Coagulation instrument. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Coagulation instrument. 864.5400 Section 864.5400....5400 Coagulation instrument. (a) Identification. A coagulation instrument is an automated or semiautomated device used to determine the onset of clot formation for in vitro coagulation studies. (b...

  2. Inherited ichthyosis: Non-syndromic forms. (United States)

    Takeichi, Takuya; Akiyama, Masashi


    Inherited ichthyoses are a group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, and often associated with erythroderma. These manifestations are due to mutations in genes mostly involved in skin barrier formation. Inherited ichthyoses consist of non-syndromic ichthyoses and ichthyosis syndromes. Non-syndromic ichthyoses are characterized by the phenotypic expression of the disorder being seen only in the skin. Non-syndromic ichthyoses include ichthyosis vulgaris, recessive X-linked ichthyosis, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis and other forms. This review focuses on updates for each type of non-syndromic ichthyosis, highlighting molecular mechanisms and phenotype/genotype correlations. Included in autosomal recessive congenital ichthyosis are three of the major phenotypes (harlequin ichthyosis, lamellar ichthyosis and congenital ichthyosiform erythroderma) and three of the minor subtypes (self-healing collodion baby, acral self-healing collodion baby and bathing suit ichthyosis). Keratinopathic ichthyosis is proposed as an umbrella term for ichthyoses caused by mutations in keratin genes. Next-generation sequencing technologies have become powerful tools for the diagnosis of inherited ichthyoses and the discovery of their genetic causes. This article reviews the current understanding of molecular pathomechanisms for non-syndromic ichthyoses and explores future perspectives. © 2016 Japanese Dermatological Association.

  3. Coagulability in Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Christina Liak


    Full Text Available BACKGROUND: Obstructive sleep apnea (OSA is a common disorder that affects both quality of life and cardiovascular health. The causal link between OSA and cardiovascular morbidity/mortality remains elusive. One possible explanation is that repeated episodes of nocturnal hypoxia lead to a hypercoagulable state that predisposes patients to thrombotic events. There is evidence supporting a wide array of hematological changes that affect hemostasis (eg, increased hematocrit, blood viscosity, platelet activation, clotting factors and decreased fibrinolytic activity.

  4. Blood Clotting and Pregnancy

    Medline Plus

    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 ...

  5. Acute heat stroke. Epidemiologic, biochemical, renal, and coagulation studies. (United States)

    O'Donnell, T F


    Fifteen Marine recruits with acute heat stroke were examined for (1) predisposing factors, (2) blood coagulation disturbances, (3) renal function abnormalities, and (4) blood composition alterations. Epidemiologic data identified the following risk factors; previous residence in a temperate climate, first phase of training, fatigue, and strenuous exercise in hot, humid conditions. Results of blood coagulation studies disclosed an increase in prothrombin and partial thromboplastin times, with a decrease in platelet count, probably indicating a transient, low-grade consumptive process. Blood urea nitrogen and creatinine levels and creatinine clearance were normal. Only mild elevations of SGOT, SGPT, and lactic dehydrogenase levels were noted, and in combination with clinical observations, they argued against significant muscle damage. No deaths or instances of renal failure occurred.

  6. Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice. (United States)

    Gansevoort, Ron T; Arici, Mustafa; Benzing, Thomas; Birn, Henrik; Capasso, Giovambattista; Covic, Adrian; Devuyst, Olivier; Drechsler, Christiane; Eckardt, Kai-Uwe; Emma, Francesco; Knebelmann, Bertrand; Le Meur, Yannick; Massy, Ziad A; Ong, Albert C M; Ortiz, Alberto; Schaefer, Franz; Torra, Roser; Vanholder, Raymond; Więcek, Andrzej; Zoccali, Carmine; Van Biesen, Wim


    Recently, the European Medicines Agency approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease. In this paper, on behalf of the ERA-EDTA Working Groups of Inherited Kidney Disorders and European Renal Best Practice, we aim to provide guidance for making the decision as to which ADPKD patients to treat with tolvaptan. The present position statement includes a series of recommendations resulting in a hierarchical decision algorithm that encompasses a sequence of risk-factor assessments in a descending order of reliability. By examining the best-validated markers first, we aim to identify ADPKD patients who have documented rapid disease progression or are likely to have rapid disease progression. We believe that this procedure offers the best opportunity to select patients who are most likely to benefit from tolvaptan, thus improving the benefit-to-risk ratio and cost-effectiveness of this treatment. It is important to emphasize that the decision to initiate treatment requires the consideration of many factors besides eligibility, such as contraindications, potential adverse events, as well as patient motivation and lifestyle factors, and requires shared decision-making with the patient. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

  7. Coagulation Testing in the Core Laboratory. (United States)

    Winter, William E; Flax, Sherri D; Harris, Neil S


    Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors.In vitro the intrinsic pathway is initiated when fresh whole blood is placed in a glass tube. The negative charge of the glass initiates the "contact pathway" where FXII is activated and then FXIa cleaves FIX to FIXa. The extrinsic pathway is triggered when tissue factor, phospholipid and calcium are added to plasma anticoagulated with citrate. In vitro, FVII is activated to FVIIa, and TF-FVIIa preferentially converts FX to FXa activating the common pathway.The prothrombin time is commonly used to monitor warfarin anticoagulant therapy. To correct for differences in reagent and instrument, the international normalized ratio was developed to improve standardization of PT reporting globally. The activated partial thromboplastin time (aPTT) is used to evaluate the intrinsic and common pathways of coagulation. The aPTT is useful clinically as a screening test for inherited and acquired factor deficiencies as well as to monitor unfractionated heparin therapy although the anti-Xa assay is now the preferred measure of the effects of unfractionated heparin. The Clauss assay is the most commonly performed fibrinogen assay and uses diluted plasma where clotting is initiated with a high concentration of reagent thrombin.The mixing study assists in the assessment of an abnormally prolonged PT or aPTT. An equal volume of citrated patient plasma is mixed with normal pooled plasma

  8. Reincarnation of ancient links between coagulation and complement. (United States)

    Conway, E M


    Throughout evolution, organisms have developed means to contain wounds by simultaneously limiting bleeding and eliminating pathogens and damaged host cells via the recruitment of innate defense mechanisms. Disease emerges when there is unchecked activation of innate immune and/or coagulation responses. A key component of innate immunity is the complement system. Concurrent excess activation of coagulation and complement - two major blood-borne proteolytic pathways - is evident in numerous diseases, including atherosclerosis, diabetes, venous thromboembolic disease, thrombotic microangiopathies, arthritis, cancer, and infectious diseases. Delineating the cross-talk between these two cascades will uncover novel therapeutic insights. © 2015 International Society on Thrombosis and Haemostasis.

  9. Psychological stress and psychosomatic treatment: major impact on serious blood disorders? (United States)

    Gramotnev, Dmitri K; Gramotnev, Galina


    To demonstrate evidence of possible major impacts of psychological stress and psychosomatic interventions on myeloproliferative blood disorders and develop new approaches for the unification and quantified analysis of stress and psychosomatic treatments. This 3.5- year longitudinal study was based upon the regular blood tests of a person with myelofibrosis who experienced severe and repeated work-related psychological stress and was subjected to psychosomatic treatment in the form of regular (approximately 4 h per day) self-hypnosis sessions. Statistical data analysis was conducted on the basis of an introduced concept of generalized stress that mathematically unifies psychological stress and psychosomatic treatment. Severe stress and psychosomatic treatment were statistically shown to have a major (dominant) impact on blood platelet counts well described by an exponential dependence on cumulative levels of generalized stress. The typical relaxation time for the impacts of both stress and treatment was shown to be approximately 2 months. Only approximately 12% of the total variation in platelet counts could be attributed to factors other than psychological stress and psychosomatic treatment. The psychosomatic intervention resulted in a consistent reduction of high platelet counts from approximately 1,400 x 10⁹ l⁻¹ to approximately the middle of the normal range, with other blood parameters being either approximately stable or showing indications of a strengthening immune system. Our findings give hope for a possible development of psychosomatic treatments of at least some blood disorders. They also indicate a highly instrumental role of platelets in the quantified analysis of stress, psychosomatic interventions, and their neuroimmunological pathways. 2011 S. Karger AG, Basel.

  10. Systemic coagulation parameters in mice after treatment with vascular targeting agents

    Directory of Open Access Journals (Sweden)

    Gottstein Claudia


    Full Text Available Abstract Background Vascular targeting of malignant tumors has become a clinically validated new treatment approach with clear patient benefit. However clinical studies have also revealed that some types of vascular targeting agents (VTAs are prone to coagulation system side effects. It is therefore essential to predetermine coagulation parameters in preclinical studies. As of to date, this has rarely been done, predominantly due to technical issues. The goal of this study was to establish and apply a standardized process, whereby systemic coagulation activation can be routinely measured in mice. Results We have evaluated a number of sampling techniques and coagulation tests regarding their suitability for this purpose. We were able to adapt two assays measuring soluble fibrin, a marker for a prethrombotic status. Thus, soluble fibrin could be measured for the first time in mice. All assays were validated in a positive control model for systemic coagulation activation, i.e. lipopolysaccharide-induced endotoxemia. Based on our results, we selected a panel of coagulation tests, which are both feasable and informative for preclinical testing of VTAs: soluble fibrin, thrombin-antithrombin complexes, free antithrombin III, white blood cell counts and platelet counts. The effect of tumor transplants on coagulation parameters was evaluated using this panel. We then applied this set of assays in treatment studies with a VTA developed in our laboratory to investigate a potential systemic coagulation activation. Conclusion We have established a standardized panel of assays that can be used to test murine blood samples for coagulation activation in preclinical studies. All tests are feasible to perform in any research laboratory without specialized equipment. In addition, this is the first report to measure soluble fibrin, an early marker of systemic coagulation activation, in mice. The panel was applied on tumor bearing mice and mice treated with a VTA

  11. Action of Nanoparticles on Platelet Activation and Plasmatic Coagulation (United States)

    Fröhlich, Eleonore


    Nanomaterials can get into the blood circulation after injection or by release from implants but also by permeation of the epithelium after oral, respiratory or dermal exposure. Once in the blood, they can affect hemostasis, which is usually not intended. This review addresses effects of biological particles and engineered nanomaterials on hemostasis. The role of platelets and coagulation in normal clotting and the interaction with the immune system are described. Methods to identify effects of nanomaterials on clotting and results from in vitro and in vivo studies are summarized and the role of particle size and surface properties discussed. The literature overview showed that mainly pro-coagulative effects of nanomaterials have been described. In vitro studies suggested stronger effects of smaller than of larger NPs on coagulation and a greater importance of material than of surface charge. For instance, carbon nanotubes, polystyrene particles, and dendrimers inferred with clotting independent from their surface charge. Coating of particles with polyethylene glycol was able to prevent interaction with clotting by some particles, while it had no effect on others and the more recently developed bio-inspired surfaces might help to design coatings for more biocompatible particles. The mainly pro-coagulative action of nanoparticles could present a particular risk for individuals affected by common diseases such as diabetes, cancer, and cardiovascular diseases. Under standardized conditions, in vitro assays using human blood appear to be a suitable tool to study mechanisms of interference with hemostasis and to optimize hemocompatibility of nanomaterials. PMID:26063498

  12. Coagulation parameters as a guide for fresh frozen plasma transfusion practice: A tertiary hospital experience

    Directory of Open Access Journals (Sweden)

    Wan Haslindawani W


    Full Text Available Introduction: The appropriate use of blood and blood products means the transfusion of safe blood products only to treat a condition leading to significant morbidity or mortality, which cannot be prevented or managed effectively by other means. The safety and effectiveness of transfusion depend on the appropriate clinical use of blood and blood products. This study was conducted to review the practice of fresh frozen plasma usage (FFP for transfusion, based on the coagulation profile, requested by various departments in the Hospital Universiti Sains Malaysia (HUSM. Methodology: A retrospective review of blood bank records and coagulation profile results of the patients given FFP from October to December 2006, in Hospital USM was undertaken. The criteria set by the College of American Pathologists in 1994, were used as the guidelines. Results: One thousand six hundred and ninety-eight units of FFP were used during this study period. Only 806 (47.47% FFP units were deemed appropriate. 20.38% were based on studies without any coagulation tests prior to transfusion and 21.13% were transfused for mild prolongation of coagulation test results. About 6.41% requested FFP in the setting of normal coagulation results. Conclusion: Our results showed that a significant proportion of the FFP transfusion was not guided by the coagulation profile. We recommend that a continuous education on FFP transfusion may help to guide the appropriate request for FFP.

  13. Blood Lead Concentrations in Jamaican Children with and without Autism Spectrum Disorder (United States)

    Rahbar, Mohammad H.; Samms-Vaughan, Maureen; Dickerson, Aisha S.; Loveland, Katherine A.; Ardjomand-Hessabi, Manouchehr; Bressler, Jan; Shakespeare-Pellington, Sydonnie; Grove, Megan L.; Pearson, Deborah A.; Boerwinkle, Eric


    Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting by early childhood. Lead is a toxic metal shown to cause neurodevelopmental disorders in children. Several studies have investigated the possible association between exposure to lead and ASD, but their findings are conflicting. Using data from 100 ASD cases (2–8 years of age) and their age- and sex-matched typically developing controls, we investigated the association between blood lead concentrations (BLC) and ASD in Jamaican children. We administered a questionnaire to assess demographic and socioeconomic information as well as exposure to potential lead sources. We used General Linear Models (GLM) to assess the association of BLC with ASD status as well as with sources of exposure to lead. In univariable GLM, we found a significant difference between geometric mean blood lead concentrations of ASD cases and controls (2.25 μg/dL cases vs. 2.73 μg/dL controls, p lead concentrations of ASD cases and controls (2.55 μg/dL vs. 2.72 μg/dL, p = 0.64). Our results do not support an association between BLC and ASD in Jamaican children. We have identified significant confounders when assessing an association between ASD and BLC. PMID:25546274

  14. Compiler generation based on grammar inheritance

    NARCIS (Netherlands)

    Aksit, Mehmet; Mostert, Rene; Haverkort, Boudewijn R.H.M.


    The concept of grammar inheritance is introduced. Grammar inheritance is a structural organization of grammar rules by which a grammar inherits rules from ancestor grammars or may have its own rules inherited by descendant grammars. Grammar inheritance supports reusability and extensibility of

  15. Disseminated intravascular coagulation (DIC) (United States)

    ... certain types of leukemia Inflammation of the pancreas (pancreatitis) Infection in the blood, especially by bacteria or fungus Liver disease Pregnancy complications (such as placenta that is left behind ...

  16. Congenital and inherited renal disease of small animals. (United States)

    Greco, D S


    Congenital renal diseases are present at birth and may be determined genetically; familial renal disorders occur in related animals with a higher frequency than would be expected by chance, and frequently are inherited. The most common familial disorders in cats and dogs include renal amyloidosis, renal dysplasia, polycystic kidneys, basement membrane disorders, and tubular dysfunction (Fanconi's syndrome). This article alerts the veterinarian to commonly observed congenital and hereditary conditions of the kidneys in small animals.

  17. ABO and RhD blood groups and gestational hypertensive disorders: a population-based cohort study. (United States)

    Lee, B K; Zhang, Z; Wikman, A; Lindqvist, P G; Reilly, M


    To examine the association between ABO and RhD blood groups and gestational hypertensive disorders in a large population-based cohort. Cohort study. Risks of gestational hypertensive disorders, pre-eclampsia, and severe pre-eclampsia, estimated by odds ratios for maternal ABO blood group and RhD status. National health registers of Sweden. All singleton deliveries in Sweden born to first-time mothers during the period 1987-2002 [total n = 641 926; any gestational hypertensive disorders, n = 39 011 (6.1%); pre-eclampsia cases, n = 29 337 (4.6%); severe pre-eclampsia cases, n = 8477 (1.3%)]. Using blood group O as a reference, odds ratios of gestational hypertensive disorders, pre-eclampsia, and severe pre-eclampsia were obtained from logistic regression models adjusted for potential confounding factors. Gestational hypertensive disorders, pre-eclampsia, and severe pre-eclampsia. Compared with blood group O, all non-O blood groups had modest but statistically significantly higher odds of pre-eclampsia. Blood group AB had the highest risk for pre-eclampsia (OR = 1.10, 95% CI 1.04-1.16) and severe pre-eclampsia (OR = 1.18, 95% CI 1.07-1.30). RhD-positive mothers had a small increased risk for pre-eclampsia (OR = 1.07, 95% CI 1.03-1.10). In the largest study on this topic to date, women with AB blood group have the highest risks of gestational hypertensive disorders, pre-eclampsia, and severe pre-eclampsia, whereas women with O blood group have the lowest risks of developing these disorders. Although the magnitude of increased risk is small, this finding may help improve our understanding of the etiology of pre-eclampsia. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

  18. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III (United States)

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M.; Drouet, Christian; Braley, Hal; Nolte, Marc W.; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas


    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  19. Regional cerebral blood flow distribution in newly diagnosed schizophrenia and schizophreniform disorder

    DEFF Research Database (Denmark)

    Rubin, P; Holm, S; Madsen, P L


    Regional cerebral blood flow distribution (rCBF) in 24 first admissions with schizophrenia or schizophreniform disorder and in 17 healthy volunteers was examined. Single photon emission computed tomography with a brain-retained tracer, technetium-99m-d,l-hexamethyl-propylene amine oxime, was used...... to study subjects under resting conditions and during performance of the Wisconsin Card Sorting Test. The study is a replication of a previous investigation in an independent series of patients and healthy volunteers. The patients had significantly lower relative blood flow in prefrontal regions during...... activation than did the healthy volunteers. An earlier series of 19 patients and 7 healthy volunteers was studied using exactly the same procedure. Analyses of the combined samples from the two studies (43 patients and 24 healthy volunteers) showed the patients to have significantly lower relative flow...

  20. Coagulation competence for predicting perioperative hemorrhage in patients treated with lactated Ringer's vs. Dextran

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten C; Højskov, Michael; Johansson, Per Ingemar


    BACKGROUND: Perioperative hemorrhage may depend on coagulation competence and this study evaluated the influence of coagulation competence on blood loss during cystectomy due to bladder cancer. METHODS: Forty patients undergoing radical cystectomy were included in a randomized controlled trial...... to receive either lactated Ringer's solution or Dextran 70 (Macrodex ®) that affects coagulation competence. RESULTS: By thrombelastography evaluated coagulation competence, Dextran 70 reduced "maximal amplitude" (MA) by 25 % versus a 1 % reduction with the administration of lactated Ringer's solution (P ....001). Blinded evaluation of the blood loss was similar in the two groups of patients - 2339 ml with the use of Dextran 70 and 1822 ml in the lactated Ringer's group (P = 0.27). Yet, the blood loss was related to the reduction in MA (r = -0.427, P = 0.008) and by multiple regression analysis independently...

  1. Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy. (United States)

    Redei, E E; Andrus, B M; Kwasny, M J; Seok, J; Cai, X; Ho, J; Mohr, D C


    An objective, laboratory-based diagnostic tool could increase the diagnostic accuracy of major depressive disorders (MDDs), identify factors that characterize patients and promote individualized therapy. The goal of this study was to assess a blood-based biomarker panel, which showed promise in adolescents with MDD, in adult primary care patients with MDD and age-, gender- and race-matched nondepressed (ND) controls. Patients with MDD received cognitive behavioral therapy (CBT) and clinical assessment using self-reported depression with the Patient Health Questionnaire-9 (PHQ-9). The measures, including blood RNA collection, were obtained before and after 18 weeks of CBT. Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1 and TLR7, differed significantly between participants with MDD (N=32) and ND controls (N=32) at baseline (qdepressed. Thus, blood levels of different transcript panels may identify the depressed from the nondepressed among primary care patients, during a depressive episode or in remission, or follow and predict response to CBT in depressed individuals.

  2. A study on regional cerebral blood flow at rest and stress state in anxiety disorder patients

    International Nuclear Information System (INIS)

    Wan Li; Liu Jian


    Objective: To investigate he characteristics of rest and stress regional cerebral blood flow (rCBF) in naive anxiety disorder patients. Methods: Twenty naive anxiety disorder patients were enrolled in the study with twenty healthy volunteers as controls. The rest and stress 99 Tc m -ethylene cystein dimer (ECD) SPECT were performed separately at 2 consecutive days, Raven reasoning test was used as a stressor. Results: 1) Compared to the healthy controls, the patients' rest rCBF of the frontal lobe, temporal lobe, thalamus and basal ganglia were significantly lower (P<0.05 and 0.01). 2)The patients' stress rCBF of the frontal lobe, temporal lobe, part occipital lobe, part parietal lobe, thalamus and basal ganglia were significantly lower compared to the healthy controls' (P<0.05 and 0.01). 3) Opposite to the healthy controls, the rCBF of patients increased significantly after stressor simulating. Conclusions: The hypofunction of frontal lobe, temporal lobe, thalamus and basal ganglia may exist in naive anxiety disorder patients. The abnormal rCBF of patients after simulating may be one of the characteristics of anxiety disorder

  3. Single-step blood direct PCR: A robust and rapid method to diagnose triplet repeat disorders. (United States)

    Singh, Inder; Swarup, Vishnu; Shakya, Sunil; Goyal, Vinay; Faruq, Mohammed; Srivastava, Achal Kumar


    DNA extraction prior to polymerase chain reaction (PCR) amplification in genetic diagnoses of triplet repeat disorders (TRDs) is tedious and labour-intensive and has the limitations of sample contamination with foreign DNA, including that from preceding samples. Therefore, we aimed to develop a rapid, robust, and cost-effective method for expeditious genetic investigation of TRDs from whole blood as a DNA template. Peripheral blood samples were collected from 70 clinically suspected patients of progressive ataxia. The conventional method using genomic DNA and single-step Blood-Direct PCR (BD-PCR) method with just 2μl of whole blood sample were tested to amplify triplet repeat expansion in genes related to spinocerebellar ataxia (SCA) types 1, 2, 3, 12 and Friedreich's ataxia (FRDA). Post-PCR, the allele sizes were mapped and repeat numbers were calculated using GeneMapper and macros run in Microsoft Excel programmes. Successful amplification of target regions was achieved in all samples by both methods. The frequency of the normal and mutated allele was concordant between both methods, diagnosing 37% positive for a mutation in either of the candidate genes. The BD-PCR resulted in higher intensities of product peaks of normal and pathogenic alleles. The nearly-accurate sizing of the normal and expanded allele was achieved in a shorter time (4-5h), without DNA extraction and any risk of cross contamination, which suggests the BD-PCR to be a reliable, inexpensive, and rapid method to confirm TRDs. This technique can be introduced in routine diagnostic procedures of other tandem repeat disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Biological and analytical variations of 16 parameters related to coagulation screening tests and the activity of coagulation factors. (United States)

    Chen, Qian; Shou, Weiling; Wu, Wei; Guo, Ye; Zhang, Yujuan; Huang, Chunmei; Cui, Wei


    To accurately estimate longitudinal changes in individuals, it is important to take into consideration the biological variability of the measurement. The few studies available on the biological variations of coagulation parameters are mostly outdated. We confirmed the published results using modern, fully automated methods. Furthermore, we added data for additional coagulation parameters. At 8:00 am, 12:00 pm, and 4:00 pm on days 1, 3, and 5, venous blood was collected from 31 healthy volunteers. A total of 16 parameters related to coagulation screening tests as well as the activity of coagulation factors were analyzed; these included prothrombin time, fibrinogen (Fbg), activated partial thromboplastin time, thrombin time, international normalized ratio, prothrombin time activity, activated partial thromboplastin time ratio, fibrin(-ogen) degradation products, as well as the activity of factor II, factor V, factor VII, factor VIII, factor IX, and factor X. All intraindividual coefficients of variation (CVI) values for the parameters of the screening tests (except Fbg) were less than 5%. Conversely, the CVI values for the activity of coagulation factors were all greater than 5%. In addition, we calculated the reference change value to determine whether a significant difference exists between two test results from the same individual. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Dominantly inherited cystoid macular edema. (United States)

    Fishman, G A; Goldberg, M F; Trautmann, J C


    Four patients of Greek ancestry had dominantly inherited cystoid macular edema. Characteristics of this syndrome include the following: an early onset and prolonged course of cystoid changes in the macula, followed by atrophy of the macula in later stages. Some patients also show leakage of fluorescein from the optic disc capillaries, subnormal EOG Lp/Dt ratios, elevated rod dark adaptation thresholds, red-green and blue-yellow color deficiencies, normal ERG findings, hyperopia, peripheral pigmentary retinopathy, and vitreous opacities. Dominantly inherited cystoid macular edema is a distinct genetic trait among the dominantly inherited macular dystrophies.

  6. Hydrolysis of polyaluminum chloride prior to coagulation: Effects on coagulation behavior and implications for improving coagulation performance. (United States)

    Zhang, Zhongguo; Wang, Jun; Liu, Dan; Li, Jiuyi; Wang, Xiaolin; Song, Boyu; Yue, Bing; Zhao, Kehui; Song, Yun


    The effects of polyaluminum chloride (PACl) hydrolysis prior to coagulation on both the coagulation zone and coagulation performance of a kaolin suspension were investigated by a novel jar test named the "reversed coagulation test". The tests showed that PACl hydrolysis prior to coagulation decreased the performance of charge neutralization coagulation in the case of short-time slow mixing (10min; G=15sec -1 ) and increased the optimal dosage for charge neutralization and sweep coagulation. Moreover, the hydrolysis time had insignificant effects on the size and zeta potential of PACl precipitates and the residual turbidity of the raw water. However, PACl hydrolysis prior to coagulation and the size of PACl precipitates had a negligible effect on the performance of sweep coagulation. The results imply that, in practice, preparing a PACl solution with deionized water, rather than tap water or the outlet water from a wastewater treatment unit, can significantly save PACl consumption and improve the performance of charge neutralization coagulation, while preparing the PACl solution with tap or outlet water would not affect the performance of sweep coagulation. In addition, the optimal rapid mixing intensity appears to be determined by a balance between the degree of coagulant hydrolysis before contacting the primary particles and the average size of flocs in the rapid mixing period. These results provide new insights into the role of PACl hydrolysis and will be useful for improving coagulation efficiency. Copyright © 2016. Published by Elsevier B.V.

  7. Ultrasonic measurement of milk coagulation time (United States)

    Bakkali, F.; Moudden, A.; Faiz, B.; Amghar, A.; Maze, G.; Montero de Espinosa, F.; Akhnak, M.


    Using a pulse reflection technique an ultrasonic system has been developed to monitor in situ the coagulation process of rennetted milk. The velocity and attenuation of ultrasonic waves through coagulating milk were continuously monitored. The observed changes in ultrasonic velocity during coagulation were used to predict the coagulation time. The coagulation time is indicative of the transition from the enzymatic phase to the physicochemical phase. The determination of coagulation time has a decisive role in determining the qualities of the end product in cheesemaking.

  8. Blood (For Parents) (United States)

    ... disease among people of African, Mediterranean, and Southeast Asian descent. Hereditary spherocytosis is an inherited condition in ... on this topic for: Parents Kids Teens Blood Culture Leukemia Iron-Deficiency Anemia Menstrual Problems Blood Transfusions ...

  9. ABO blood group and thrombotic vascular disease. (United States)

    Franchini, M; Mannucci, P M


    ABO blood group antigens are complex carbohydrate molecules expressed on red blood cells and a variety of tissues. The ABO blood type is implicated in the development of a number of human diseases and there is increasing evidence regarding its involvement in the pathogenesis of cardiovascular disorders, mainly through its effect on von Willebrand factor levels. In this review, after a brief analysis of the potential molecular mechanisms by which the blood group influences haemostasis, we focus on the clinical implications of such interaction. Overall, the literature data document the close relationship between venous thromboembolism (VTE) and non-O blood type, which is associated with an approximately two-fold increased risk of venous thrombosis. A supra-additive effect on VTE risk is observed when an inherited thrombophilic condition is associated with non-O blood group. A weaker association exists between non-O blood type and arterial thrombosis, which needs to be further investigated.

  10. Epigenetic inheritance, prions and evolution

    Indian Academy of Sciences (India)

    Johannes Manjrekar


    classical' TEI phenomena and their possible implications for evolution. The review then focusses on a less-discussed, unique kind of protein-only epigenetic inheritance mediated by prions. Much remains to be learnt about the ...

  11. Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population. (United States)

    Barillari, Giovanni; Fabbro, Elisabetta; Pasca, Samantha; Bigotto, Enrico


    Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by relative insulin deficiency, insulin resistance and hyperglycemia. DM2 improperly managed can cause severe complications such as renal failure, blindness or arterial disease. In addition to serious complications due to DM2, in the past 20 years, several studies have demonstrated the association between DM2, insulin resistance and prothrombotic risk. In our study, we wanted to evaluate the correlation between coagulation factor levels, oxidative plasmatic levels and DM2. We considered 20 DM2 patients (65% women and 35% men), 40-65 years of age, who had a BMI between 25 and 40 kg/m2 and followed a diet with or without oral antidiabetic treatment and 20 controls, blood donors, 15 men (75%) and five women (25%), who had a BMI between 25 and 40 kg/m2 and their age was between 40 and 65 years. Plasmatic levels of oxidative stress markers (tumor necrosis factor-alpha, nitrotyrosine, oxidized low-density lipoprotein) and coagulation markers (factors VII, VIII, IX, XI, XII, antithrombin III and fibrinogen) of both populations were analyzed following statistic criteria. The analyzed data of this study related to oxidative stress and coagulation factors proved that the differences observed between diabetic patients and controls were not statistically significant (P DM2, factor VIII increased from 79 to 103%, factor IX from 88 to 103%, factor XII from 87 to 105% and finally, antithrombin III from 81 to 103%. Different results between literature and our study could be due to fact that the patients considered were in the early stage of diabetes when endothelial damage is absent and vascular complications are not clinically expressed. In this study, it is still shown that DM2 is a multifactor disease and its physiopathologic mechanisms are not completely known today.

  12. Evaluation the Effects of Copper, Zinc and Aluminum on Plasma Coagulation and Fibrinolysis Indices

    Directory of Open Access Journals (Sweden)

    A Absalan


    Full Text Available Introduction: Myocardial infarction as a leading cause of death in most populations is associated with blood clot formation in coronary artery, and rapid clot lysis is important for patient treatment. Some reports have indicated the effects of some trace elements on blood coagulation and clot lysis. The aim of this study was to evaluate the effects of zinc, copper and aluminum on in-vitro coagulation and clot lysis by streptokinase. Methods: The citrated fasting fresh-pooled plasma prepared from healthy individuals was divided to zinc, copper, aluminum and control groups. Calcium chloride and streptokinase were used for induction of plasma coagulation and Fibrinolysis, respectively. Clot formation and lysis were monitored turbidimetrically, and quantitative parameters including lag time for coagulation, clot lysis, time of coagulation and time for half lysis were calculated after plotting a kinetic curve of time versus absorbance. SPSS software and independent t-test were used for statistical analysis. Results: In comparison with control, addition of zinc reduced lag time of coagulation(216.8±4.4 vs 229.2±2.6 sec, P= 0.001 and copper reduced coagulation time(194.4±3.7 vs 280±3.5 sec, P= 0.001. Addition of aluminum increased lag time for coagulation(563.6±8.8 Sec, P= 0.001, lag time for clot lysis(194±3.6 sec, P= 0.001, coagulation time(484±7 sec, P= 0.001, and time for half lysis of clot (328.4±6.1 sec, P=0.001. Conclusion: Results indicated that essential trace elements including zinc and copper at low levels do not have important effects on coagulation and fibrinolysis, but aluminum as a toxic element affects these processes and partially inhibits them even at very low levels.

  13. Estudo farmacognóstico e atividade in vitro sobre a coagulação sanguínea e agregação plaquetária das folhas de Passiflora nitida Kunth (Passifloraceae Pharmacognostic study and in vitro activity on blood coagulation and platelet aggregation of leaves of Passiflora nitida Kunth (Passifloraceae

    Directory of Open Access Journals (Sweden)

    Maria José de Carvalho


    fruits of this species by the local population for gastrointestinal disorders. Considering the pharmacological potential of the genus, this work aimed to carry out study of phytochemical characterization of this species and study the effects of the aqueous (AE, ethanol (EE and hexane (HE extracts from its leaves on blood coagulation and platelet aggregation. Thin-layer chromatography and nuclear magnetic resonance were carried out for the phytochemical characterization. The effect of the extracts on the coagulation was evaluated by prothrombin time (PT and activated partial thromboplastin time (aPTT tests. The effect on the platelet aggregation was evaluated in platelet-rich plasma by spectrophotometric method, using adenosine diphosphate (ADP and adrenaline (ADR as inducers of aggregation. The AE, EE and HE extracts showed coagulant activity by the PT test, and the EE showed anticoagulant activity by the aPTT. When induced by ADP, the AE, EE and HE extracts showed 50% inhibitory concentration values (IC50, µg/mL of 450.5 ± 50.7, 511.2 ± 35.5 and 394.4 ± 8.9, respectively, and when induced by ADR showed values of 438.7 ± 5.2, 21.0 ± 1.9 and 546.9 ± 49.9, respectively. The EE showed inhibitory effect on the aggregation. The phytochemical characterization was suggestive of the presence of flavonoids and coumarins, which can be attributed in part to the biological effects studied.

  14. Inherited knee disorders in the Medici family. (United States)

    Lippi, Donatella; Matucci-Cerinic, Marco; Alburyc, W R; Weisz, George M


    Reconstructing a medical condition which was existent centuries ago is limited by the lack of contemporaneous evidence-based descriptions in the accounts given by physicians and other observers. Despite these limitations modern paleopathological evidence, supplemented by techniques of historical investigation, have led to the conclusion that males in the Medici family typically suffered from a complex clinical entity with a triple pathology of stenotic spinal ankylosis, recurrent peripheral joint disease and erythematous skin disease; the Medici Syndrome. Examination of the knee joint is illustrative of recurrent joint disease both in the primary and secondary lines of the family. Pictorial and sculptural representations, if used cautiously, can assist in this retrospective process. The six cases presented here illustrate the involvement of the knee joint where the joint destruction ultimately led to an ankylosis. Copyright © 2013. Published by Elsevier B.V.

  15. Coagulation Status in Hidradenitis Suppurativa

    DEFF Research Database (Denmark)

    Miller, Iben Marie; Johansen, Maria Egede; Mogensen, Ulla B


    performed a hospital- and population-based cross-sectional study investigating the coagulation status (thrombocytes, mean platelet volume [MPV], international normalized ratio [INR] and activated partial thromboplastin time [APTT]). RESULTS: 32 hospital HS subjects, 430 population HS subjects and 20.......3432). CONCLUSION: We did not find an association between HS and prothrombotic/hypercoagulable status. Thus, thrombocytes may not be activated in HS. Furthermore, INR may not be affected in HS, suggesting that intrinsic and vitamin K-dependent coagulation factors appear unaffected....

  16. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... America Asia-Pacific Latin America Meeting on Hematologic Malignancies Gain knowledge, through “How I Treat” presentations, that ... Blood Basics Blood Disorders Anemia Bleeding Disorders Blood Cancers Blood Clots Blood Clotting and Pregnancy Clots and ...

  17. Blood Clotting and Pregnancy

    Medline Plus

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

  18. Changes in Regional Cerebral Blood Flow with Cognitive Behavioral Therapy in the Treatment of Panic Disorder

    Energy Technology Data Exchange (ETDEWEB)

    Won, K. S.; Jun, S. K.; Kim, J. B.; Jang, E. J. [College of Medicine, Univ. of Kyemyoung, Taegu (Korea, Republic of)


    This study attempted to prospectively investigate changes in regional cerebral blood flow (rCBF) on SPECT and clinical response to cognitive behavioral therapy (CBT) in patients with panic disorder with (PDA) and without (PD) agoraphobia. Using 99mTc-ECD brain SPECT, we assessed brain perfusion in 5 out patients at rest before and after CBT. The subjects received 12 weekly sessions of CBT. Subjects were assessed by Agoraphobic Cognitions Questionnaire, Body Sensations Questionnaire, Beck Anxiety Inventory, Anxiety Sensitivity Index, Beck Depression Inventory-II, Panic Disorder Severity Scale (PDSS) and clinical global improvement (CGI) scale measurement were used as outcome measures. Patients were considered responders to CBT if they are much or very much improved on CGI scale and have a PDSS score at least 30% below their baseline. The scans were statistically analyzed by using statistical parametric mapping (SPM99). The baseline scans were compared to the post-CBT scans by using the statistics option multi subject, different conditions. Of 5 subjects 4 were male, 3 diagnosed PDA, and 4 on anti-anxiety medication. All of the subjects were classified as CBT responders. Their mean pretreatment and posttreatment PDSS were 17.4 (SD=8.2) and 4.2 (SD=3.1), respectively. The results of SPM analysis showed a significant decrease in blood flow after CBT in the thalamus bilaterally and right middle frontal gyrus (Brodmann's area 6). All results were thresholded at an uncorrected p<0.001 (for voxel height) and a corrected p<0.04 (for spatial extent). These preliminary data suggest that SPM analysis of 99mTc-ECD brain SPECT can reveal the change of rCBF in patient with panic disorder before and after CBT and the CBT effect may be associated with limbic and thalamic networks. However this study was a short trial with small number of subjects. Further studies with larger patient cohorts are needed.

  19. Changes in Regional Cerebral Blood Flow with Cognitive Behavioral Therapy in the Treatment of Panic Disorder

    International Nuclear Information System (INIS)

    Won, K. S.; Jun, S. K.; Kim, J. B.; Jang, E. J.


    This study attempted to prospectively investigate changes in regional cerebral blood flow (rCBF) on SPECT and clinical response to cognitive behavioral therapy (CBT) in patients with panic disorder with (PDA) and without (PD) agoraphobia. Using 99mTc-ECD brain SPECT, we assessed brain perfusion in 5 out patients at rest before and after CBT. The subjects received 12 weekly sessions of CBT. Subjects were assessed by Agoraphobic Cognitions Questionnaire, Body Sensations Questionnaire, Beck Anxiety Inventory, Anxiety Sensitivity Index, Beck Depression Inventory-II, Panic Disorder Severity Scale (PDSS) and clinical global improvement (CGI) scale measurement were used as outcome measures. Patients were considered responders to CBT if they are much or very much improved on CGI scale and have a PDSS score at least 30% below their baseline. The scans were statistically analyzed by using statistical parametric mapping (SPM99). The baseline scans were compared to the post-CBT scans by using the statistics option multi subject, different conditions. Of 5 subjects 4 were male, 3 diagnosed PDA, and 4 on anti-anxiety medication. All of the subjects were classified as CBT responders. Their mean pretreatment and posttreatment PDSS were 17.4 (SD=8.2) and 4.2 (SD=3.1), respectively. The results of SPM analysis showed a significant decrease in blood flow after CBT in the thalamus bilaterally and right middle frontal gyrus (Brodmann's area 6). All results were thresholded at an uncorrected p<0.001 (for voxel height) and a corrected p<0.04 (for spatial extent). These preliminary data suggest that SPM analysis of 99mTc-ECD brain SPECT can reveal the change of rCBF in patient with panic disorder before and after CBT and the CBT effect may be associated with limbic and thalamic networks. However this study was a short trial with small number of subjects. Further studies with larger patient cohorts are needed

  20. [Secular trends in blood lipid disorders among adolescents: population study in Novosibirsk (1989-2003)]. (United States)

    Denisova, D V; Nikitin, Iu P; Zav'ialova, L G; Burakova, S V; Ivanova, M V


    Hyperlipidemia is a known risk factor of coronary artery disease. The reduction of elevated serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in childhood may reduce cardiovascular morbidity and mortality in adulthood. Aim of the study was to assess prevalence and trends in lipid profile and lipid disorders in adolescent population in Novosibirsk (1989-2003). Four cross-sectional surveys of school children aged 14-17 years in 1989 (n=656), in 1994 (n=620), in 1999 (n=626) and in 2003 (n=667) were carried out. Total sample was 2569 (1214 males and 1355 females). Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) were measured by enzymatic methods. LDL-C was calculated with Friedwald's formula. Associations of blood lipids with age, sex, year of study, body mass index (kg/m2), blood pressure and main nutrients of diet were measured by GLM method. Prevalence of dyslipidemia was evaluated with NCEP-peds criteria. Diet was estimated using 24-hour dietary recall. During the 15-year period (1989-2003) mean serum TC decreased from 175 to 162 mg/dl in males and from 191 to 175 mg/dl in females (p dislipidemias in adolescents of Novosibirsk significantly changed following the changes of body mass index and diet.

  1. Impact of Albumin on Coagulation Competence and Hemorrhage During Major Surgery

    DEFF Research Database (Denmark)

    Rasmussen, Kirsten C; Højskov, Michael; Johansson, Pär I.


    trial evaluates whether administration of 5% human albumin (HA) or lactated Ringer solution (LR) affects coagulation competence and in turn blood loss during cystectomy due to bladder cancer. Forty patients undergoing radical cystectomy were included to receive either 5% HA (n = 20) or LR (n = 20...... (TEG) evaluated coagulation competence, albumin affected clot growth (TEG-angle 69 ± 5 vs 74° ± 3°, P ...For patients exposed to a massive blood loss during surgery, maintained coagulation competence is important. It is less obvious whether coagulation competence influences bleeding during elective surgery where patients are exposed to infusion of a crystalloid or a colloid. This randomized controlled...

  2. The pattern of inherited microcephaly and role of the ...

    African Journals Online (AJOL)


    recessive pattern inherited disorder who attended the centers of Khuzestan state welfare organization, southwestern. Iran during 2011 to ... environmental factors affect mental health response, these factors are believed play crucial role in reducing the incidence of .... microcephaly in a family with a history of disability was.

  3. Elucidation of the molecular genetic basis of inherited hearing impairment

    NARCIS (Netherlands)

    Luijendijk, Mirjam Wilhelmina Johanna


    Hearing loss is the most common sensory disorder in the human population. It affects 0.1% of all young children and by the age of 70, 30% of the population suffers from hearing loss greater than 40 dB. When early onset hearing loss is inherited, 70% is classified as nonsyndromic and 30% as

  4. Challenges identified in the management of patients with inherited ...

    African Journals Online (AJOL)

    Background: Pakistan is the sixth most populous country in the World. High rates of consanguinity and inter caste marriages have resulted in a substantial burden of inherited metabolic disorders (IMDs). Despite this load, there is a dearth of both medical genetic and clinical metabolic services in Pakistan. There are ...

  5. Rare inherited kidney diseases: challenges, opportunities, and perspectives.

    NARCIS (Netherlands)

    Devuyst, O.; Knoers, N.V.A.M.; Remuzzi, G.; Schaefer, F.; Bindels, R.J.; et al.,


    At least 10% of adults and nearly all children who receive renal-replacement therapy have an inherited kidney disease. These patients rarely die when their disease progresses and can remain alive for many years because of advances in organ-replacement therapy. However, these disorders substantially

  6. Whole blood BDNF levels in healthy twins discordant for affective disorder: association to life events and neuroticism

    DEFF Research Database (Denmark)

    Trajkovska, V.; Vinberg, M.; Aznar, S.


    and protected against affective disorder. Whole blood assessed for BDNF concentrations and correlated to risk status, neuroticism, and number of stressful life events. RESULTS: Between the groups, we found no significant difference in whole blood BDNF levels. Women at high-risk for depression who had......BACKGROUND: Depression has been associated with decreased blood BDNF concentrations; but it is unclear if low blood BDNF levels are a state or a trait marker of depression. METHODS: We investigated blood BDNF concentrations in a twin population including both subjects highly predisposed...... experienced three or more recent stressful events (n=26) had decreased whole blood BDNF levels compared to high-risk women with two or less recent stressful events (n=35), 21.6+/-7.0 vs. 18.5+/-4.1 ng/ml, respectively, (p

  7. Impact of Silver Nanoparticles on Haemolysis, Platelet Function and Coagulation

    Directory of Open Access Journals (Sweden)

    Julie Laloy


    Full Text Available Silver nanoparticles (Ag NPs are increasingly used in biomedical applications because of their large antimicrobial spectrum. Data in the literature on the ability of Ag NPs to perform their desired function without eliciting undesirable effects on blood elements are very limited and contradictory. We studied the impact of Ag NPs on erythrocyte integrity, platelet function and blood coagulation. Erythrocyte integrity was assessed by spectrophotometric measurement of haemoglobin release. Platelet adhesion and aggregation was determined by light transmission aggregometry and scanning electron microscopy. The calibrated thrombin generation test was used to study the impact on coagulation cascade. We demonstrated that Ag NPs induced haemolysis. They also increase platelet adhesion without having any impact on platelet aggregation. Finally, they also had procoagulant potential. Bringing all data from these tests together, the no observed effect concentration is 5 μg/mL.

  8. Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis

    DEFF Research Database (Denmark)

    Tommiska, Johanna; Känsäkoski, Johanna; Skibsbye, Lasse


    Familial growth hormone deficiency provides an opportunity to identify new genetic causes of short stature. Here we combine linkage analysis with whole-genome resequencing in patients with growth hormone deficiency and maternally inherited gingival fibromatosis. We report that patients from three...... associated with maternally inherited gingival fibromatosis is an allelic disorder with cardiac arrhythmia syndromes caused by KCNQ1 mutations....

  9. Regional cerebral blood flow and cognitive function in patients with obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Huirong Guo


    Full Text Available Objective: To explore the relationship between regional cerebral blood flow (CBF and cognitive function in obsessive-compulsive disorder (OCD. Method: Single-photon emission computed tomography (SPECT was performed for 139 OCD patients and 139 controls, and the radioactivity rate (RAR was calculated. Cognitive function was assessed by the Wisconsin Card Sorting Test (WCST. Results: The RARs of the prefrontal, anterior temporal, and right occipital lobes were higher in patients than controls. For the WCST, correct and classification numbers were significantly lower, and errors and persistent errors were significantly higher in OCD patients. Right prefrontal lobe RAR was negatively correlated with correct numbers, right anterior temporal lobe RAR was positively correlated with errors, and the RARs of the right prefrontal lobe and left thalamus were positively correlated with persistent errors. Conclusion: OCD patients showed higher CBF in the prefrontal and anterior temporal lobes, suggesting that these areas may be related with cognitive impairment.

  10. Evaluation of a whole blood remote platelet function test for the diagnosis of mild bleeding disorders. (United States)

    Dovlatova, N; Lordkipanidzé, M; Lowe, G C; Dawood, B; May, J; Heptinstall, S; Watson, S P; Fox, S C


    Mild platelet function disorders (PFDs) are complex and difficult to diagnose. The current gold standard test, light transmission aggregometry (LTA), including lumi-aggregometry, is time and labour intensive and blood samples must be processed within a limited time after venepuncture. Furthermore, many subjects with suspected PFDs do not show a platelet abnormality on LTA. To assess the diagnostic potential of an easy-to-use remote platelet function test (RPFT) as a diagnostic pre-test for suspected PFDs. A remote platelet function test was compared with lumi-aggregometry in participants recruited to the Genotyping and Phenotyping of Platelets Study (GAPP, ISRCTN 77951167). For the RPFT, whole blood was stimulated with platelet agonists, stabilized with PAMFix and returned to the central laboratory for analysis of P-selectin and CD63 by flow cytometry. For the 61 study participants (42 index cases and 19 relatives) there was a good agreement between lumi-aggregometry and the RPFT, with diagnosis being concordant in 84% of cases (κ = 0.668, P < 0.0001). According to both tests, 29 participants were identified to have a deficiency in platelet function and 22 participants appeared normal. There were four participants where lumi-aggregometry revealed a defect but the RPFT did not, and six participants where the RPFT detected an abnormal platelet response that was not identified by lumi-aggregometry. This study suggests that the RPFT could be an easy-to-use pre-test to select which participants with bleeding disorders would benefit from extensive platelet phenotyping. Further development and evaluation of the test are warranted in a wider population of patients with excessive bleeding and could provide informative screening tests for PFDs. © 2014 International Society on Thrombosis and Haemostasis.

  11. Application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in screening of high risk children with inherited metabolic diseases in northern China. (United States)

    Tu, Wenjun; Song, Xiaotao; Dai, Fang; Ho, James Jian


    To investigate the morbidity and distribution of 35 inherited metabolic diseases in high risk children by LC-MS/MS in northern China. The dry blood on filter papers, collected from 2760 children clinically suspected to have inherited metabolic diseases from more than sixty hospitals in north China, was tested by LC-MS/MS. The specimen was extracted out of the dry blood on filter paper, derivatized before being injected into LCMS/MS. The LC-MS/MS methodology used in the study was transferred from Pediatrix Medical Group (1301 Concord Terrace, Sunrise, FL 33323), validated in our lab and further compared with United States CDC standard. The positive results were further confirmed by gas chromatography-mass, other laboratory tests and clinical symptoms. 249 of the 2760 children (9%) were diagnosed with one or more of twenty-one disorders. Out of 249 patients, there are 41 (16.5%) fatty acid disorders, 71 (28.5%) amino acid diseases, and 137 (55%) organic acidemias. 48 of the 249 patients (19.3%) were neonates, including 11 (22.9%) with fatty acid disorders, 15 (31.3%) with amino acid diseases, and 22 (45.8%) with organic acidemias. 201 of the 249 patients were elder than 28 days, and was composed of 30 (14.9%) with fatty acid disorders, 56 (27.9%) with amino acid diseases, 115 (57.2%) with organic acidemias. The LC-MS/MS technology can be used to detect over 30 inherited metabolic disorders for Chinese pediatric clinic in a single collection of blood. The morbidity of IMD (9%) is relatively high among high risk children, thus we highly suggest that we shall provide initial screening of over 30 IMDs for the high risk children in China using the technology of LC-MS/MS.

  12. Blood (United States)

    ... production of red blood cells, including: Iron deficiency anemia. Iron deficiency anemia is the most common type of anemia and ... inflammatory bowel disease are especially likely to have iron deficiency anemia. Anemia due to chronic disease. People with chronic ...

  13. The inheritance of groin hernia

    DEFF Research Database (Denmark)

    Burcharth, J; Pommergaard, H C; Rosenberg, Jacob


    Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias.......Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias....

  14. Laparoscopic off-clamp partial nephrectomy using soft coagulation. (United States)

    Hongo, Fumiya; Kawauchi, Akihiro; Ueda, Takashi; Fujihara-Iwata, Atsuko; Nakamura, Terukazu; Naya, Yoshio; Kamoi, Kazumi; Okihara, Koji; Miki, Tsuneharu


    To assess the effectiveness of soft coagulation in off-clamp laparoscopic partial nephrectomy. A total of 32 patients with renal tumors underwent laparoscopic partial nephrectomy with off-clamp using soft coagulation between May 2012 and September 2013. Tumor resection was carried out using a combination of bipolar forceps and a ball electrode using the soft coagulation system without hilar clamping. The outcomes of these patients were compared with those of 30 patients treated with hilar clamping. This off-clamp procedure was successfully completed in 31 cases. No significant differences were observed in the mean age (60 vs 61 years), sex (male/female; 25/7 vs 20/10), mean RENAL nephrometry score (5.7 vs 5.8), mean body mass index (24.4 vs 23) or tumor size (15 mm vs 16 mm) between the two groups. No significant differences were noted in positive surgical margins (0 vs 0) or blood loss (104 vs 115 cc) as well. In contrast, a significant difference was noted in the total operative time (278 vs 238 min). Serum creatinine percentage changes at 3 months were 6.4 versus 7.3% in the off-clamp and hilum-clamp groups, respectively, which were not significantly different. Off-clamp laparoscopic partial nephrectomy can be safely carried out by using a soft coagulation technique. © 2015 The Japanese Urological Association.

  15. The effects of ropivacaine hydrochloride on coagulation and fibrinolysis. An assessment using thromboelastography.

    LENUS (Irish Health Repository)

    Porter, J M


    Amide local anaesthetics impair coagulation by inhibition of platelet function and enhanced fibrinolysis. The potential therefore exists that the presence of amide local anaesthetics in the epidural space could contribute to the therapeutic failure of an epidural autologous blood patch. Ropivacaine is an aminoamide local anaesthetic increasingly used for epidural analgesia and anaesthesia, particularly in obstetric practice. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur clinically in the epidural space, alter coagulation or fibrinolysis. Thromboelastography was used to assess clotting and fibrinolysis of blood to which ropivacaine had been added. Although modest alterations in maximum amplitude, coagulation time and alpha angle were observed, the effect of ropivacaine on clotting and fibrinolysis was not clinically significant. We conclude that it is unlikely that the presence of ropivacaine in the epidural space would reduce the efficacy of an early or prophylactic epidural blood patch.

  16. Elucidating nature's solutions to heart, lung, and blood diseases and sleep disorders. (United States)

    Carey, Hannah V; Martin, Sandra L; Horwitz, Barbara A; Yan, Lin; Bailey, Shannon M; Podrabsky, Jason; Storz, Jay F; Ortiz, Rudy M; Wong, Renee P; Lathrop, David A


    Evolution has provided a number of animal species with extraordinary phenotypes. Several of these phenotypes allow species to survive and thrive in environmental conditions that mimic disease states in humans. The study of evolved mechanisms responsible for these phenotypes may provide insights into the basis of human disease and guide the design of new therapeutic approaches. Examples include species that tolerate acute or chronic hypoxemia like deep-diving mammals and high-altitude inhabitants, as well as those that hibernate and interrupt their development when exposed to adverse environments. The evolved traits exhibited by these animal species involve modifications of common biological pathways that affect metabolic regulation, organ function, antioxidant defenses, and oxygen transport. In 2006, the National Heart, Lung, and Blood Institute released a funding opportunity announcement to support studies that were designed to elucidate the natural molecular and cellular mechanisms of adaptation in species that tolerate extreme environmental conditions. The rationale for this funding opportunity is detailed in this article, and the specific evolved mechanisms examined in the supported research are described. Also highlighted are past medical advances achieved through the study of animal species that have evolved extraordinary phenotypes as well as the expectations for new understanding of nature's solutions to heart, lung, blood, and sleep disorders through future research in this area.

  17. Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder. (United States)

    Tărlungeanu, Dora C; Deliu, Elena; Dotter, Christoph P; Kara, Majdi; Janiesch, Philipp Christoph; Scalise, Mariafrancesca; Galluccio, Michele; Tesulov, Mateja; Morelli, Emanuela; Sonmez, Fatma Mujgan; Bilguvar, Kaya; Ohgaki, Ryuichi; Kanai, Yoshikatsu; Johansen, Anide; Esharif, Seham; Ben-Omran, Tawfeg; Topcu, Meral; Schlessinger, Avner; Indiveri, Cesare; Duncan, Kent E; Caglayan, Ahmet Okay; Gunel, Murat; Gleeson, Joseph G; Novarino, Gaia


    Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment. (United States)

    Zetterberg, Henrik; Jakobsson, Joel; Redsäter, Mikael; Andreasson, Ulf; Pålsson, Erik; Ekman, Carl Johan; Sellgren, Carl; Johansson, Anette Gm; Blennow, Kaj; Landén, Mikael


    Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Blood Pressure Responses to Endovascular Stimulation: A Potential Therapy for Autonomic Disorders With Vasodilatation. (United States)

    Naksuk, Niyada; Killu, Ammar M; Yogeswaran, Vidhushei; Desimone, Christopher V; Suddendorf, Scott H; Ladewig, Dorothy J; Powers, Joanne M; Weber, Sarah; Madhavan, Malini; Cha, Yong-Mei; Kapa, Suraj; Asirvatham, Samuel J


    We have previously shown that sympathetic ganglia stimulation via the renal vein rapidly increases blood pressure. This study further investigated the optimal target sites and effective energy levels for stimulation of the renal vasculatures and nearby sympathetic ganglia for rapid increase in blood pressure. The pre-study protocol for endovascular stimulations included 2 minutes of stimulation (1-150 V and 10 pulses per second) and at least 2 minutes of rest during poststimulation. If blood pressure and/or heart rate were changed during the stimulation, time to return to baseline was allowed prior to the next stimulation. In 11 acute canine studies, we performed 85 renal artery, 30 renal vein, and 8 hepatic vasculature stimulations. The mean arterial pressure (MAP) rapidly increased during stimulation of renal artery (95 ± 18 mmHg vs. 103 ± 15 mmHg; P vein (90 ± 16 mmHg vs. 102 ± 20 mmHg; P = 0.001), and hepatic vasculatures (74 ± 8 mmHg vs. 82 ± 11 mmHg; P = 0.04). Predictors of a significant increase in MAP were energy >10 V focused on the left renal artery, bilateral renal arteries, and bilateral renal veins (especially the mid segment). Overall, heart rate was unchanged, but muscle fasciculation was observed in 22.0% with an output >10 V (range 15-150 V). Analysis after excluding the stimulations that resulted in fasciculation yielded similar results to the main findings. Stimulation of intra-abdominal vasculatures promptly increased the MAP and thus may be a potential treatment option for hypotension in autonomic disorders. Predictors of optimal stimulation include energy delivery and the site of stimulation (for the renal vasculatures), which informs the design of subsequent research. © 2016 Wiley Periodicals, Inc.

  20. Hemomath the mathematics of blood

    CERN Document Server

    Fasano, Antonio


    This book illustrates applications of mathematics to various processes (physiological or artificial) involving flowing blood, including hemorheology, microcirculation, coagulation, kidney filtration and dialysis, offering a historical overview of each topic. Mathematical models are used to simulate processes normally occurring in flowing blood and to predict the effects of dysfunctions (e.g. bleeding disorders, renal failure), as well as the effects of therapies with an eye to improving treatments. Most of the models have a completely new approach that makes patient-specific simulations possible. The book is mainly intended for mathematicians interested in medical applications, but it is also useful for clinicians such as hematologists, nephrologists, cardio-surgeons, and bioengineers. Some parts require no specific knowledge of mathematics. The book is a valuable addition to mathematics, medical, biology, and bioengineering libraries.

  1. The association of early blood oxygenation with child development in preterm infants with acute respiratory disorders. (United States)

    Smith, Karen E; Keeney, Susan; Zhang, Lifang; Perez-Polo, J Regino; Rassin, David K


    The potential negative impact of early blood oxygenation on development of specific cognitive and motor outcomes in children born at very low birth weight (VLBW; 1000-1500g) has not been examined even though these infants are exposed to varying durations and amounts of oxygen as part of their neonatal care. While this is the largest group of preterm infants, they receive much less research attention than extremely low birth weight infants (ELBW<1000g). Although neonatologists are questioning the routine use of oxygen therapy for all neonates, research has focused primarily on the more medically fragile ELBW infants. To date there are no systematic studies available to guide decision making for oxygen supplementation for a large segment of the preterm infant population. The aim of the present study was to determine if there is an association between blood oxygenation in the first 4h of life and specific cognitive and motor skills in preterm infants with acute respiratory disorders but no severe intracranial insult using a selected cohort from a longitudinal study children recruited in 1991 and 1992 designed to examine the role of biological immaturity as defined by gestational age and parenting in development. From this cohort, 55 children had acute respiratory disorders without severe intracranial insult. Of these, 35 children had at least one partial pressure of oxygen obtained from arterial blood (PaO2) during the first 4h of life as part of their clinical care. Higher early PaO2 values were associated with lower impulse control and attention skills in the elementary school age period. Models that were examined for relations between PaO2 values that also included birth weight and parenting quality across the first year of life revealed that higher PaO2 remained associated with impulse control but not attention skills. Birth weight was not associated with any outcomes. These results suggest that hyperoxia may be a risk factor for developmental problems that are

  2. Assessment of ABO blood grouping and secretor status in the saliva of the patients with oral potentially malignant disorders. (United States)

    Rai, Pragati; Acharya, Swetha; Hallikeri, Kaveri


    Secretor status may possibly be one of the factors in the etiopathogenesis of oral precancerous lesions and subsequently cancer. Studies have shown the relationship between the pathogenesis of disease and secretor status. They have made known that secretor status is a possible factor influencing disease status. Studies have revealed the association between blood groups and specific diseases. To assess any association of ABO blood grouping with oral potentially malignant disorders (OPMDs) and to examine whether there is any difference in the saliva secretor status in the patients with OPMDs and healthy controls. The study consisted of 90 subjects, with 45 patients assigned to two groups (a) Patients with potentially malignant disorders and (b) healthy controls. ABO blood grouping was done and 1 ml of unstimulated saliva was collected in a sterile test tube. The Wiener agglutination test was performed to analyze the secretor status in both the groups. Chi-square test and odd ratio were used to assess the relationship between ABO blood group and OPMDs. Chi-square test was performed to assess the relationship between secretor status and OPMDs. Probability level was fixed at ABO blood groups and OPMDs (P > 0.05). The study confirms the inability to secrete blood group antigens in the saliva of patients with OPMDs which could be regarded as a host risk factor. Results could not propose a relationship between ABO blood group and OPMDs.

  3. Epigenetic inheritance, prions and evolution

    Indian Academy of Sciences (India)

    Such transgenerational epigenetic inheritance (TEI) raises obvious questions about a possible evolutionary role for epigenetic 'Lamarckian' mechanisms in evolution, particularly when epigenetic modifications are induced by environmental cues. In this review I attempt a brief overview of the periodically reviewed and ...

  4. Tragedy and the Epic Inheritance

    African Journals Online (AJOL)

    Tragedy and the Epic Inheritance. Chaos, says Hesiod in the Theogony, came into being .... fifth century) offered a cosmology which was in effect a remythologization of ideas of the origins of the world ... Unlike Euripides and Aristophanes, Empedocles was not concerned with the personalities and effects which could be.

  5. Biology of Blood (United States)

    ... switch to the Professional version Home Blood Disorders Biology of Blood Overview of Blood Resources In This ... Version. DOCTORS: Click here for the Professional Version Biology of Blood Overview of Blood Components of Blood ...

  6. Disorders of oxidation homeostasis in the blood and organs of rats under the influence of external x-ray exposure

    International Nuclear Information System (INIS)

    Uzlenkova, N.Je.


    The study was performed in the blood and organs (lungs and skin) of male rats weighing 160-180 g. Single external x-ray exposure to minimal and medial lethal doses causes stable disorders in oxidation homeostasis resulting in peroxidation state and development of chronic oxidative stress in the organism of the exposed rats.

  7. The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro (United States)

    Golderman, Valery; Shavit-Stein, Efrat; Tamarin, Ilia; Rosman, Yossi; Shrot, Shai; Rosenberg, Nurit


    Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain. PMID:27689805

  8. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... scientific research View all publications For Patients Blood Basics Blood Disorders Anemia Bleeding Disorders Blood Cancers Blood ... that provide information. back to top ASH Foundation Support the mission of ASH and help move hematology ...

  9. Evaluation of coagulation factors in fresh frozen plasma treated with riboflavin and ultraviolet light

    Directory of Open Access Journals (Sweden)

    Antić Ana


    Full Text Available Background/Aim. Pathogen inactivation in blood products using riboflavin and ultraviolet (UV light represents a proactive approach to blood safety, not only for known infectious agents but also for new ones or not yet recognized as threats to the blood supply. This method inactivates a virus, bacteria, fungus, or protozoan pathogen from the blood product without damaging its function or shelf-life. The aim of the study was to study the influence of photoinactivation using riboflavin on the concentration of coagulation factors and coagulation inhibitors in plasma that was treated before freezing. Methods. The examination included 30 units of plasma, separated from whole blood donated by voluntary blood donors around 6 h from the moment of collection. They were treated by riboflavin (35 mL and UV rays (6.24 J/mL, 265-370 nm on Mirasol aparature (Caridian BCT Biotechnologies, USA in approximate duration of 6 min. The samples for examining were taken before (K - control units and after illumination (I - illuminated units. Results. Comparing the middle values of coagulation factors in the control and illuminated units we noticed their statistically significant decrease in illuminated units (p < 0.001, but the activity of coagulation ones was still in the reference range. The most sensitive coagulation factors to photoinactivation were FVIII, FIX and FXI (21.99%, 20.54% and 17.26% loss, respectively. Anticoagulant factors were better preseved than coagulation factors. Conclusion. Plasma separated from whole blood donation within 6 h, treated with riboflavin and UV light within 6 h from separation and frozen at temperature below -30ºC within 24 h, shows good retention of pro- and anticoagulation activity.

  10. Inherited renal tubular defects with hypokalemia

    Directory of Open Access Journals (Sweden)

    Muthukrishnan J


    Full Text Available Bartter′s and Gitelman′s syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter′s syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman′s syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.

  11. Gene expression in blood of children and adolescents: Mediation between childhood maltreatment and major depressive disorder. (United States)

    Spindola, Leticia Maria; Pan, Pedro Mario; Moretti, Patricia Natalia; Ota, Vanessa Kiyomi; Santoro, Marcos Leite; Cogo-Moreira, Hugo; Gadelha, Ary; Salum, Giovanni; Manfro, Gisele Gus; Mari, Jair Jesus; Brentani, Helena; Grassi-Oliveira, Rodrigo; Brietzke, Elisa; Miguel, Euripedes Constantino; Rohde, Luis Augusto; Sato, João Ricardo; Bressan, Rodrigo Affonseca; Belangero, Sintia Iole


    Investigating major depressive disorder (MDD) in childhood and adolescence can help reveal the relative contributions of genetic and environmental factors to MDD, since early stages of disease have less influence of illness exposure. Thus, we investigated the mRNA expression of 12 genes related to the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, neurodevelopment and neurotransmission in the blood of children and adolescents with MDD and tested whether a history of childhood maltreatment (CM) affects MDD through gene expression. Whole-blood mRNA levels of 12 genes were compared among 20 children and adolescents with MDD diagnosis (MDD group), 49 participants without MDD diagnosis but with high levels of depressive symptoms (DS group), and 61 healthy controls (HC group). The differentially expressed genes were inserted in a mediation model in which CM, MDD, and gene expression were, respectively, the independent variable, outcome, and intermediary variable. NR3C1, TNF, TNFR1 and IL1B were expressed at significantly lower levels in the MDD group than in the other groups. CM history did not exert a significant direct effect on MDD. However, an indirect effect of the aggregate expression of the 4 genes mediated the relationship between CM and MDD. In the largest study investigating gene expression in children with MDD, we demonstrated that NR3C1, TNF, TNFR1 and IL1B expression levels are related to MDD and conjunctly mediate the effect of CM history on the risk of developing MDD. This supports a role of glucocorticoids and inflammation as potential effectors of environmental stress in MDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Increased cerebral blood flow velocity in children with mild sleep-disordered breathing: a possible association with abnormal neuropsychological function. (United States)

    Hill, Catherine M; Hogan, Alexandra M; Onugha, Nwanneka; Harrison, Dawn; Cooper, Sara; McGrigor, Victoria J; Datta, Avijit; Kirkham, Fenella J


    Sleep-disordered breathing describes a spectrum of upper airway obstruction in sleep from simple primary snoring, estimated to affect 10% of preschool children, to the syndrome of obstructive sleep apnea. Emerging evidence has challenged previous assumptions that primary snoring is benign. A recent report identified reduced attention and higher levels of social problems and anxiety/depressive symptoms in snoring children compared with controls. Uncertainty persists regarding clinical thresholds for medical or surgical intervention in sleep-disordered breathing, underlining the need to better understand the pathophysiology of this condition. Adults with sleep-disordered breathing have an increased risk of cerebrovascular disease independent of atherosclerotic risk factors. There has been little focus on cerebrovascular function in children with sleep-disordered breathing, although this would seem an important line of investigation, because studies have identified abnormalities of the systemic vasculature. Raised cerebral blood flow velocities on transcranial Doppler, compatible with raised blood flow and/or vascular narrowing, are associated with neuropsychological deficits in children with sickle cell disease, a condition in which sleep-disordered breathing is common. We hypothesized that there would be cerebral blood flow velocity differences in sleep-disordered breathing children without sickle cell disease that might contribute to the association with neuropsychological deficits. Thirty-one snoring children aged 3 to 7 years were recruited from adenotonsillectomy waiting lists, and 17 control children were identified through a local Sunday school or as siblings of cases. Children with craniofacial abnormalities, neuromuscular disorders, moderate or severe learning disabilities, chronic respiratory/cardiac conditions, or allergic rhinitis were excluded. Severity of sleep-disordered breathing in snoring children was categorized by attended polysomnography. Weight

  13. The role of seeing blood in non-suicidal self-injury in female patients with borderline personality disorder. (United States)

    Naoum, Janina; Reitz, Sarah; Krause-Utz, Annegret; Kleindienst, Nikolaus; Willis, Franziska; Kuniss, Sarah; Baumgärtner, Ulf; Mancke, Falk; Treede, Rolf-Detlef; Schmahl, Christian


    Patients with Borderline Personality Disorder (BPD) often engage in non-suicidal self-injury (NSSI), to reduce arousal levels under stress. However, the importance of seeing blood for the effect of NSSI is yet unknown. The present pilot study examined 20 female BPD patients and 20 healthy controls (HC) to assess the role of seeing blood on arousal, pain, urge for NSSI (ratings) and heart rate (continuously measured). Participants completed two sessions consisting of stress induction (forced mental arithmetics with white noise), followed by a seven second non-invasive pain stimulus with a blade to the volar forearm. At one session, only the painful blade stimulus was applied, at the other, artificial blood was added. For arousal, a significantly stronger decrease was revealed in the BPD than in the HC group, however with no significant effects between blood and non-blood conditions. Concerning urge for NSSI, the BPD showed a significantly greater decrease in blood condition over time than the HC group. Interestingly, heart rate decreased stronger over time in the HC group during the blood condition than in BPD. For tension relief by non-damaging mechanical painful stimulus the addition of visible blood showed neither subjective (arousal, urge for NSSI), nor objective (heart rate) advantages. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. [Automation in the modern coagulation laboratory. Exemplified by the integration of the Microanalyser ACL 300]. (United States)

    Haushofer, A; Halbmayer, W M; Fischer, M


    We report on the organisation of our coagulation laboratory which had to meet the requirements of both, the large routine operations and those of a special laboratory for specific blood coagulation problems. A valuable support for the routine activities of our coagulation laboratory was the installation of 2 automated coagulation analysers, type ACL 300. Due to the selective (diagnosis/therapy) patient-related allotment of samples and the establishment of a final diagnosis according to a step-wise method it was possible to integrate the 2 ACL 300 analysers into our existing system and consequently to take full advantage of the savings in staff time. Moreover we report on the evaluation of the 1st ACL 300 (810) analyser and the specific characteristics of the ACL series.

  15. Point-of-Care Coagulation Monitoring in Trauma Patients. (United States)

    Stein, Philipp; Kaserer, Alexander; Spahn, Gabriela H; Spahn, Donat R


    Trauma remains one of the major causes of death and disability all over the world. Uncontrolled blood loss and trauma-induced coagulopathy represent preventable causes of trauma-related morbidity and mortality. Treatment may consist of allogeneic blood product transfusion at a fixed ratio or in an individualized goal-directed way based on point-of-care (POC) and routine laboratory measurements. Viscoelastic POC measurement of the developing clot in whole blood and POC platelet function testing allow rapid and tailored coagulation and transfusion treatment based on goal-directed, factor concentrate-based algorithms. The first studies have been published showing that this concept reduces the need for allogeneic blood transfusion and improves outcome. This review highlights the concept of goal-directed POC coagulation management in trauma patients, introduces a selection of POC devices, and presents algorithms which allow a reduction in allogeneic blood product transfusion and an improvement of trauma patient outcome. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. Evaluation of Disseminated Intravascular Coagulation in the Craniocerebral Traumas

    Directory of Open Access Journals (Sweden)

    Faruk Altinel


    Full Text Available Traumatic injury is one of the most important cause of disseminated intravascular coagulation (DIC. It occurs because of blood loss and hemodilution due to fluid resuscitation. The incidence of trauma associated DIC is mainly higher in the craniocerebral traumas. Even though craniocerebral trauma related DIC is well defined, the pathophysiology has been poorly characterized in the literature. Due to the fact that brain tissue is highly significant for procoagulant molecules, craniocerebral traumas are closely related to DIC. In the current study, 30 patients admitted to emergency room have been considered on the first and fifth day of admission to the hospital for the coagulation tests to evaluate DIC in both two groups. [Cukurova Med J 2014; 39(3.000: 488-495

  17. Light and inherited retinal degeneration


    Paskowitz, D M; LaVail, M M; Duncan, J L


    Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summ...

  18. Epigenetic Inheritance across the Landscape. (United States)

    Whipple, Amy V; Holeski, Liza M


    The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here, we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome-environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype.

  19. Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder. (United States)

    Frick, Andreas; Åhs, Fredrik; Appel, Lieuwe; Jonasson, My; Wahlstedt, Kurt; Bani, Massimo; Merlo Pich, Emilio; Bettica, Paolo; Långström, Bengt; Lubberink, Mark; Fredrikson, Mats; Furmark, Tomas


    Social anxiety disorder (SAD) is associated with increased fear-related neural activity in the amygdala and we recently found enhanced serotonin synthesis rate in the same region. Anxiolytic agents like selective serotonin re-uptake inhibitors (SSRIs) and neurokinin-1 receptor (NK1R) antagonists reduce amygdala activity and may attenuate serotonin formation according to animal studies. Here, we examined the effects of SSRI pharmacotherapy, NK1R antagonism, and placebo on serotonin synthesis rate in relation to neural activity, measured as regional cerebral blood flow (rCBF), and symptom improvement in SAD. Eighteen SAD patients were randomized to receive daily double-blind treatment for six weeks either with the SSRI citalopram (n=6; 40mg), the NK1R antagonist GR205171 (n=6; 5mg; 4 weeks following 2 weeks of placebo), or placebo (n=6). Serotonin synthesis rate at rest and rCBF during stressful public speaking were assessed, before and after treatment, using positron emission tomography with the tracers [ 11 C]5-hydroxytryptophan and [ 15 O]water respectively. The Liebowitz Social Anxiety Scale (LSAS-SR) indexed symptom severity. All groups exhibited attenuated amygdala serotonin synthesis rate after treatment, which was associated with reduced amygdala rCBF during public speaking and accompanied by symptom improvement. These results are consistent with the notion that serotonin in the amygdala exerts an anxiogenic influence and, conversely, that anxiolysis is achieved through decreased serotonin formation in the amygdala. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  20. Cognitive profiles and regional cerebral blood flow changes in individuals with Asperger's disorder and Schizophrenia

    International Nuclear Information System (INIS)

    Kato, Motoichiro; Hayashi, Mika; Nozaki, Syoko


    Described are differences of the profiles and blood flow (CBF) changes in the title between individuals with Asperger's disorder (AD) and Schizophrenia (SZ). Children with AD syndrome have been suggested to have reasoning and fluid intelligence superior to normally developed ones, and to be of cognitive disability for the spatial composition which is thought to reflect the impairment in the right hemisphere. These characteristics are not suggested in SZ. Presented are examinations by authors of 99m ethyl cysteinate dimer (ECD)-single photon emission computed tomography (SPECT) images with Patlak method of 7 AD males (average age 24.4 y), 4 AD females (25.5 y), and 4 males and 2 females with SZ (25.8 y). Image analysis is done by SPM99 (Statistical Parametric Mapping) with standardized brain. Control with the matched age and sex is obtained from database of the normal healthy ones. In AD, clearly lowered CBF is observed in the right lateral and medial parietal lobe and right superior temporal convolution (particularly, in females), and in SZ, in the dorsolateral and dorsomedial regions of frontal lobe of both sides. The finding in the right superior temporal convolution in AD is considered to be important from the aspect of impairment of eye gaze processing. (R.T.)


    Lee, Brendan; Diaz, George A.; Rhead, William; Lichter-Konecki, U.; Feigenbaum, Annette; Berry, Susan A.; Le Mons, C.; Bartley, James A; Longo, Nicola; Nagamani, Sandesh C.; Berquist, William; Gallagher, Renata; Bartholomew, Dennis; Harding, Cary O.; Korson, Mark S.; McCandless, Shawn E.; Smith, Wendy; Cederbaum, Stephen; Wong, Derek; Merritt, J. Lawrence; Schulze, A.; Vockley, Gerard.; Kronn, David; Zori, Roberto; Summar, Marshall; Milikien, D.A.; Marino, M.; Coakley, D.F.; Mokhtarani, M.; Scharschmidt, B.F.


    Purpose To examine predictors of ammonia exposure and hyperammonemic crises (HAC) in patients with urea cycle disorders (UCDs). Methods The relationships between fasting ammonia, daily ammonia exposure, and HACs were analyzed in >100 UCD patients. Results Fasting ammonia correlated strongly with daily ammonia exposure (r=0.764, pammonia levels ammonia value was 87%, 60%, and 39%, respectively, and 10.3%, 14.1%, and 37.0% of these patients experienced ≥1 HAC over 12 months. Time to first HAC was shorter (p=0.008) and relative risk (4.5×; p=0.011) and rate (~5×, p=0.006) of HACs higher in patients with fasting ammonia ≥1.0 ULN vs. ammonia exposure increased the relative risk of a HAC by 50% and >200% (pammonia and HAC risk appeared independent of treatment, age, UCD subtype, dietary protein intake, or blood urea nitrogen. Fasting glutamine correlated weakly with AUC0-24 and was not a significant predictor of HACs. Conclusions Fasting ammonia correlates strongly and positively with daily ammonia exposure and with the risk and rate of HACs, suggesting that UCD patients may benefit from tight ammonia control. PMID:25503497

  2. Study of regional cerebral blood flow in obsessive compulsive disorder patients with SPM and ROI method

    International Nuclear Information System (INIS)

    Li Peiyong; Jiang Xufeng; Zhang Liying; Guo Wanhua; Zhu Chengmo


    Objective: To investigate the alternations in regional cerebral blood flow (rCBF) in obsessive compulsive disorder (OCD) patients using statistical parametric mapping (SPM). Methods: rCBF measurements using 99 Tc m -ethyl cysteinate dimer (ECD) SPECT was performed on 14 OCD patients and 23 age-matched healthy volunteers. The rCBF distribution was compared between these two groups with SPM under the conditions of increased and decreased perfusion, and with regions of interest (ROIs) using cerebral template. P value was set at 0.01 level. Results: SPM analysis showed that rCBF decreased in cerebral areas including bilateral putamen, superior temporal gyrus and precuneus, and right orbital gyrus, superior and middle frontal gyrus, and left temporo-occipital lobule and superior parietal gyrus, and vermis. rCBF was also increased in left inferior frontal gyrus and posterior cingulate gyrus. With ROIs method, rCBF was decreased in right anterior frontal, temporo-parietal lobule and left temporo-occipital lobule. Conclusions: The study supports the viewpoint that rCBF abnormality of fronto-striatal circuits is involved in OCD patients. SPM method is a forceful tool in analyzing cerebral regional characters

  3. Blood diagnostic biomarkers for major depressive disorder using multiplex DNA methylation profiles: discovery and validation. (United States)

    Numata, Shusuke; Ishii, Kazuo; Tajima, Atsushi; Iga, Jun-ichi; Kinoshita, Makoto; Watanabe, Shinya; Umehara, Hidehiro; Fuchikami, Manabu; Okada, Satoshi; Boku, Shuken; Hishimoto, Akitoyo; Shimodera, Shinji; Imoto, Issei; Morinobu, Shigeru; Ohmori, Tetsuro


    Aberrant DNA methylation in the blood of patients with major depressive disorder (MDD) has been reported in several previous studies. However, no comprehensive studies using medication-free subjects with MDD have been conducted. Furthermore, the majority of these previous studies has been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the present study is to identify DNA methylation markers that distinguish patients with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of peripheral leukocytes was conducted in two set of samples, a discovery set (20 medication-free patients with MDD and 19 controls) and a replication set (12 medication-free patients with MDD and 12 controls), using Infinium HumanMethylation450 BeadChips. Significant diagnostic differences in DNA methylation were observed at 363 CpG sites in the discovery set. All of these loci demonstrated lower DNA methylation in patients with MDD than in the controls, and most of them (85.7%) were located in the CGIs in the gene promoter regions. We were able to distinguish patients with MDD from the control subjects with high accuracy in the discriminant analysis using the top DNA methylation markers. We also validated these selected DNA methylation markers in the replication set. Our results indicate that multiplex DNA methylation markers may be useful for distinguishing patients with MDD from non-psychiatric controls.

  4. Reduced Venous Blood Basophil Count and Anxious Depression in Patients with Major Depressive Disorder (United States)

    Baek, Ji Hyun; Kim, Hee-Jin; Fava, Maurizio; Mischoulon, David; Papakostas, George I; Nierenberg, Andrew; Heo, Jung-Yoon


    Objective Anxious depression has a distinct neurobiology, clinical course and treatment response from non-anxious depression. Role of inflammation in anxious depression has not been examined. As an exploratory study to characterize the role of inflammation on a development of anxious depression, we aimed to determine the relationship between white blood cell (WBC) subset counts and anxiety in individuals with major depressive disorder (MDD). Methods A total of 709 patients who were newly diagnosed with MDD were recruited. Anxiety levels of participants were evaluated using the Anxiety/ Somatization subitem of the Hamilton Depression Rating Scale. The association between WBC subset fraction and anxiety was evaluated. Results Basophil and eosinophil sub-fractions showed significant negative correlations with HAM-D anxiety/somatization factor scores (basophils: r=-0.092, p=0.014 and eosinophils: r=-0.075, p=0.046). When an anxiety score (a sum of somatic and psychic anxiety) was entered as a dependent variable, only basophils showed significant negative association with the anxiety scores after adjusting for all other WBC subset counts and demographic factors (t=-2.57, p=0.010). Conclusion This study showed that anxious depression had a decreased basophil subfraction, which might be associated with involvement of inflammation in development of anxious depression. PMID:27247599

  5. Utilizing inheritance in requirements engineering (United States)

    Kaindl, Hermann


    The scope of this paper is the utilization of inheritance for requirements specification, i.e., the tasks of analyzing and modeling the domain, as well as forming and defining requirements. Our approach and the tool supporting it are named RETH (Requirements Engineering Through Hypertext). Actually, RETH uses a combination of various technologies, including object-oriented approaches and artificial intelligence (in particular frames). We do not attempt to exclude or replace formal representations, but try to complement and provide means for gradually developing them. Among others, RETH has been applied in the CERN (Conseil Europeen pour la Rechereche Nucleaire) Cortex project. While it would be impossible to explain this project in detail here, it should be sufficient to know that it deals with a generic distributed control system. Since this project is not finished yet, it is difficult to state its size precisely. In order to give an idea, its final goal is to substitute the many existing similar control systems at CERN by this generic approach. Currently, RETH is also tested using real-world requirements for the Pastel Mission Planning System at ESOC in Darmstadt. First, we outline how hypertext is integrated into a frame system in our approach. Moreover, the usefulness of inheritance is demonstrated as performed by the tool RETH. We then summarize our experiences of utilizing inheritance in the Cortex project. Lastly, RETH will be related to existing work.

  6. Coagulation factor Xa signaling : the link between coagulation and inflammatory bowel disease?

    NARCIS (Netherlands)

    Borensztajn, Keren; Peppelenbosch, Maikel P.; Spek, C. Arnold

    Inflammatory bowel disease (IBD) is characterized by activation of the coagulation cascade and it has long been suspected that coagulation is an essential component of this still largely idiopathic group of diseases. The realization that coagulation factors are not only passive mediators in the

  7. Coagulation factor Xa signaling: the link between coagulation and inflammatory bowel disease?

    NARCIS (Netherlands)

    Borensztajn, Keren; Peppelenbosch, Maikel P.; Spek, C. Arnold


    Inflammatory bowel disease (IBD) is characterized by activation of the coagulation cascade and it has long been suspected that coagulation is an essential component of this still largely idiopathic group of diseases. The realization that coagulation factors are not only passive mediators in the

  8. Childhood Blood Lead Levels and Symptoms of Attention Deficit Hyperactivity Disorder (ADHD): A Cross-Sectional Study of Mexican Children. (United States)

    Huang, Siying; Hu, Howard; Sánchez, Brisa N; Peterson, Karen E; Ettinger, Adrienne S; Lamadrid-Figueroa, Héctor; Schnaas, Lourdes; Mercado-García, Adriana; Wright, Robert O; Basu, Niladri; Cantonwine, David E; Hernández-Avila, Mauricio; Téllez-Rojo, Martha María


    Previous studies suggest that blood lead levels are positively associated with attention deficit/hyperactivity disorder (ADHD) and ADHD-symptoms in children. However, the associations between lead exposure and ADHD subtypes are inconsistent and understudied. The objective of this study was to explore the association of low-level concurrent lead exposure with subtypes of ADHD symptoms in 578 Mexican children 6-13 years of age. We measured concurrent blood lead levels using inductively coupled plasma mass spectrometry (ICPMS). We administered the Conners' Rating Scales-Revised (CRS-R) to mothers to evaluate their children's ADHD symptoms. We used imputation to fill missing values in blood lead levels and used segmented regression models adjusted for relevant covariates to model the nonlinear relationship between blood lead and ADHD symptoms. Mean ± SD blood lead levels were 3.4 ± 2.9 μg/dL. In adjusted models, a 1-μg/dL increase in blood lead was positively associated with Hyperactivity and Restless-Impulsivity scores on the CRS-R scale and Hyperactivity-Impulsivity scores on the CRS-R scale of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, but only in children with blood lead level ≤ 5 μg/dL. Blood lead was not associated with Inattentive symptoms or overall ADHD behavior. In this population of Mexican children, current blood lead level among children with low exposure (≤ 5 μg/dL) was positively associated with hyperactive/impulsive behaviors, but not with inattentiveness. These results add to the existing evidence of lead-associated neurodevelopmental deficits at low levels of exposure. Huang S, Hu H, Sánchez BN, Peterson KE, Ettinger AS, Lamadrid-Figueroa H, Schnaas L, Mercado-García A, Wright RO, Basu N, Cantonwine DE, Hernández-Avila M, Téllez-Rojo MM. 2016. Childhood blood lead levels and symptoms of attention deficit hyperactivity disorder (ADHD): a cross-sectional study of Mexican children. Environ Health Perspect 124

  9. Metabolomic profiling reveals distinct patterns of tricarboxylic acid disorders in blood stasis syndrome associated with coronary heart disease. (United States)

    Wang, Yong; Li, Chun; Chang, Hong; Lu, Ling-Hui; Qiu, Qi; Ouyang, Yu-Lin; Yu, Jun-da; Guo, Shu-Zhen; Han, Jing; Wang, Wei


    To investigate the underlying metabolomic profifiling of coronary heart disease (CHD) with blood stasis syndrome (BSS). CHD model was induced by a nameroid constrictor in Chinese miniature swine. Fifteen miniature swine were randomly divided into a model group (n=9) and a control group (n=6), respectively according to arandom number table. After 4 weeks, plasma hemorheology was detected by automatic hemorheological analyzer, indices including hematocrit, plasma viscosity, blood viscosity, rigidity index and erythrocyte sedimentation rate; cardiac function was assessed by echocardiograph to detect left ventricular end-systolic diameter (LVED), left ventricular end-diastolic diameter (LVEDd), ejection fraction (EF), fractional shortening (FS) and other indicators. Gas chromatography coupled with mass spectrometry (GC-MS) and bioinformatics were applied to analyze spectra of CHD plasma with BSS. The results of hemorheology analysis showed signifificant changes in viscosity, with low shear whole blood viscosity being lower and plasma viscosity higher in the model group compared with the control group. Moreover, whole blood reduction viscosity at high shear rate and whole blood reduction viscosity at low shear rate increased signifificantly (P patterns involved were associated with dysfunction of energy metabolism including glucose and lipid disorders, especially in glycolysis/gluconeogenesis, galactose metabolism and adenosine-triphosphate-binding cassette transporters. Glucose metabolism and lipid metabolism disorders were the major contributors to the syndrome classifification of CHD with BSS.

  10. Dynamic optical absorption characteristics of blood after slow and fast heating. (United States)

    Jia, Hao; Chen, Bin; Li, Dong


    Laser treatment is the most effective therapy in dermatology for vascular skin disorders, such as port-wine stains (PWS). Changes in heat-induced absorbance in blood must be determined for accurate numerical simulation and implementation of multi-pulse laser therapy for treatment of PWS. Thermally induced absorbance changes in hemoglobin in blood were compared in vitro between slow water bath heating and fast heating irradiated by using sub-millisecond Nd:YAG laser. Blood composition at different temperatures was calculated by comparing blood absorption spectra with those of pure HbO 2 , Hb, and metHb at room temperature. Blood absorbance to heat energy were categorized into three stages distinguished by metHb and coagulation points, which are the validity and security thresholds of the optimized therapy, respectively. Rapid laser heating can distinctively enhance blood absorbance by photochemically induced strong instability compared with slow heating at a constant temperature. Slow heating facilitates metHb point at 70 °C and coagulation point at 75 °C as the temperature of the water bath increases. However, the temperature at which metHb or coagulation point shifts to higher than 10 °C when pulses and fluence in laser irradiation change. Laser fluence less than 20 J/cm 2 and more than 50 J/cm 2 is unsuitable for laser treatment because of its low probability to coagulate vascular hyperplasia and high probability to damage normal tissues adjacent to target lesions, respectively. Few bubbles formed after mediate fluence is beneficial to minimize adverse side-effects. Considering blood absorbance, temperature evolution, and bubble formation, we recommend 30-40 J/cm 2 and 2-4 Hz frequency as the optimal laser parameters in sub-millisecond Nd:YAG laser.

  11. Avaliação de anticoagulantes naturais e de fatores da coagulação em pacientes com distúrbios congênitos de glicosilação (DCG tipo I An evaluation of natural anticoagulants and coagulation factors in patients with congenital disorders of glycosylation type I

    Directory of Open Access Journals (Sweden)

    Anna Letícia Soares


    Full Text Available Defeitos na incorporação de N-glicanos nas proteínas humanas ocasionam um grupo de doenças multissistêmicas denominadas coletivamente distúrbios congênitos de glicosilação (DCG. Os DCG manifestam-se na infância com sintomas neurológicos que incluem principalmente atraso psicomotor, ataxia, hipotonia e episódios de acidente vascular cerebral. Várias proteínas do sistema hemostático somente tornam-se biologicamente ativas após a glicosilação. O objetivo deste estudo foi avaliar os anticoagulantes naturais (proteína S livre, proteína C e antitrombina e os fatores da coagulação (VIII, IX e XI em pacientes com DCG tipo I. Foram avaliados 11 pacientes com diagnóstico positivo para DCG tipo I (três do gênero masculino e oito do gênero feminino, idade média de 5,6 anos; e oito pacientes com diagnóstico negativo para DCG(quatro do gênero masculino e quatro do gênero feminino, idade média de 4,5 anos (grupo-controle. O diagnóstico de DCG tipo I foi realizado pela identificação do padrão de hipoglicosilação da transferrina plasmática. Na avaliação dos anticoagulantes naturais pode-se observar redução dos valores de PS livre e PC e uma redução marcante de AT, quando comparados com o grupo controle. Em relação aos fatores de coagulação não houve diferença significativa para os fatores VIII e IX e houve redução marcante do fator XI. Os resultados do presente estudo sugerem que a deficiência combinada de anticoagulantes naturais é responsável pelo estado pró-trombótico observado em pacientes com DCG. Sugerimos também que a análise dos parâmetros hemostáticos seja realizada para pacientes com DCG quando apresentarem sintomas clínicos de alteração do sistema hemostático e antes de procedimentos invasivos.Defects in the biosynthesis of N-linked human protein glycosylation leads to a group of multisystem disorders collectively called congenital disorders of glycosylation (CDG. CDG present in infancy

  12. Maternal eating disorders affect offspring cord blood DNA methylation: a prospective study. (United States)

    Kazmi, Nabila; Gaunt, Tom R; Relton, Caroline; Micali, Nadia


    Eating disorders (ED) are chronic psychiatric disorders, common amongst women of reproductive age. ED in pregnancy are associated with poor nutrition and abnormal intrauterine growth. Increasing evidence also shows offspring of women with ED have adverse developmental and birth outcomes. We sought to carry out the first study investigating DNA methylation in offspring of women with ED. We compared cord blood DNA methylation in offspring of women with active ED ( n  = 21), past ED ( n  = 43) and age- and social class-matched controls ( n  = 126) as part of the Avon Longitudinal Study of Parents and Children. Offspring of women with both active and past ED had lower whole-genome methylation compared to controls (active ED 49.1% (95% confidence intervals 50.5-47.7%), past ED 49.2% (95% CI 50.7-47.7.0%), controls 52.4% (95% CI 53.0%-51.0%)). Amongst offspring of ED women, those born to women with restrictive-type and purging-type ED had lower methylation levels compared to those of controls. Offspring of women with an active restrictive ED in pregnancy had lower whole-genome methylation compared to offspring of women with past restrictive ED. We observed decreased methylation at the DHCR24 locus in offspring of women with active pregnancy ED (effect size (ES) = - 0.124, p  = 6.94 × 10 -8 ) and increased methylation at the LGALS2 locus in offspring of women with past ED (ES = 0.07, p  = 3.74 × 10 -7 ) compared to controls. Maternal active and past ED are associated with differences in offspring whole-genome methylation. Our results show altered DNA methylation in loci relevant to metabolism; these might be biomarkers of disrupted metabolic pathways in offspring of ED mothers. Further work is needed to examine potential mechanisms and functional outcomes of the observed methylation patterns.

  13. Impulsivity is associated with blood pressure and waist circumference among adolescents with bipolar disorder. (United States)

    Naiberg, Melanie R; Newton, Dwight F; Collins, Jordan E; Bowie, Christopher R; Goldstein, Benjamin I


    Cardiovascular risk factors (CVRFs) and impulsivity are common in bipolar disorder (BD), and CVRFs are also linked with impulsivity through a number of mechanisms, both behavioral and biological. This study examines the association between CVRFs and impulsivity in adolescents with BD. Subjects were 34 adolescents with BD and 35 healthy control (HC) adolescents. CVRFs were based on International Diabetes Federation metabolic syndrome criteria (triglycerides, high-density lipoprotein cholesterol, waist circumference, blood pressure (BP) and glucose). Impulsivity was measured using the computerized Cambridge Gambling Task (CGT). Analyses controlled for age, IQ, lifetime attention deficit hyperactivity disorder, and current antipsychotic use. Adolescents with BD had higher diastolic BP (73.36 ± 9.57 mmHg vs. 67.91 ± 8.74 mmHg, U = 401.0, p = 0.03), higher triglycerides (1.13 ± 0.60 mmol/L vs. 0.78 ± 0.38 mmol/L, U = 373.5, p = 0.008), and were more likely to meet high-risk criteria for waist circumference (17.6% vs. 2.9%, p = 0.04) vs. HC. Within the BD group, CGT sub-scores were correlated with CVRFs. For example, overall proportion bet was positively correlated with systolic (r = 0.387, p = 0.026) and diastolic (ρ = 0.404, p = 0.020) BP. Quality of decision-making was negatively correlated with systolic BP (ρ = -0.401, p = 0.021) and waist circumference (ρ = -0.534, p = 0.003). Significant interactions were observed, such that BD diagnosis moderates the relationship between both waist circumference and BP with CGT sub-scores. BP and waist circumference are associated with impulsivity in BD adolescents, but not in HC adolescents. Future studies are warranted to determine temporality and to evaluate whether optimizing CVRFs improves impulsivity among BD adolescents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Syncope in patients with inherited arrhythmias

    Directory of Open Access Journals (Sweden)

    Yukiko Nakano


    Full Text Available Syncope, a common symptom of cerebral ischemia often shows a multifactorial etiopathogenesis. Although inherited arrhythmias causing syncope is uncommon, such an occurrence could be a warning sign preceding cardiac arrest. Long QT syndrome (LQTS is a typical inherited arrhythmia causing syncope in children. Early diagnosis and treatment of LQTS using beta-blockers prevents recurrent syncope in LQTS. Brugada syndrome, another typical inherited arrhythmia causes syncope or sudden cardiac arrest in young individuals. Syncope as a symptom is useful for risk stratification of fatal arrhythmias and in selection of appropriate therapy. Catecholaminergic polymorphic ventricular tachycardia, another rare inherited arrhythmia causing recurrent syncope is associated with poor outcomes without medication. Early detection and therapeutic intervention improve prognosis; thus, correct diagnosis of syncope is imperative in cases of these inherited arrhythmias. We describe syncope associated with three typical inherited arrhythmias and discuss various diagnostic modalities. Keywords: Syncope, Inherited arrhythmia, Long QT syndrome, Brugada syndrome, Catecholaminergic polymorphic ventricular tachycardia

  15. On coagulation process in meteor trails

    International Nuclear Information System (INIS)

    Bergkhanov, M.


    Structure of the meteors processes of collisions of paricles formd after interaction of meteoric matter with the Earth atmosphere are shortly described. Equation describing coagulation in meteor trails is obtained. Primary and secondary particles of meteor nature, representing the source of polydisperse aerosol, exist in meteor zone. Coagulation in meteor trails can be referred to Brownian one

  16. Waardinburg syndrome — inherited deafness with pigmentary involvement

    Directory of Open Access Journals (Sweden)

    M.F. Macrae


    Full Text Available The Waardenburg syndrome was first clearly defined in 1951. The major clinical importance lies in the fact that about 20% of affected individuals are deaf. Furthermore, because the condition is inherited autosomal dominantly, there is a risk of the disorder being handed down from generation to generation. The syndrome consists of six major features which may appear in any combination and to any degree in the affected individual.

  17. Investigation of coagulation activity of natural coagulants from seeds of different leguminose species

    Directory of Open Access Journals (Sweden)

    Šćiban Marina B.


    Full Text Available The ability of seeds of plants: Phaseolus vulgaris, Robinia pseudoacacia Ceratonia siliqua and Amorpha fruticosa, to act as natural coagulants was tested using synthetic turbid water. This water was prepared by adding kaolin into tap water, just before the test. Active components were extracted from ground seeds with distilled water. The coagulation ability of this extract was assessed by the use of standard jar test measurements in water with various initial turbidity. Investigation of these natural coagulants was confirmed their positive coagulation activity. Of all plants that have been examined, the seed extract from Ceratonia siliqua appeared to be one of the most effective coagulants for water treatment. A dose of 20 mg/l of this coagulant resulted in 100% coagulation activity for clarification of water with 17.5 NTU initial turbidity.

  18. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... Toolkit Home For Patients Blood Disorders Blood Clots Blood Clotting & Pregnancy If you are pregnant, or you ... g., cancer, infection) back to top How are Blood Clots in Pregnant Women Treated? Typically, blood clots ...

  19. Blood Clotting and Pregnancy

    Medline Plus

    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 ...

  20. Rapid cycling bipolar affective disorder and recurrent strokes secondary to high blood homocysteine. (United States)

    Awara, Mahmoud A; Zahid, Shazia; Elnenaei, Manal O


    The interface between psychiatric disorders and organicity has been a matter for contentious debate. To report an interesting clinical case of moderate homocystinuria presenting with significant psychiatric and neurological deficits. A case report highlighting the impact of homocystinuria on producing intractable rapid cycling bipolar affective disorder. Homocystinuria is a frequently missed cause for treatment-resistant bipolar affective disorder.

  1. The Use of Tannins from Turkish Acorns (Valonia) in Water Treatment as a Coagulant and Coagulant Aid


    ŞENGİL, Mahmut ÖZACAR and İ. Ayhan


    Coagulants play an important role in the treatment of water and wastewater and in the treatment and disposal of sludge. Aluminum sulfate, alum, is the common chemical coagulant used in the coagulation process. Recently polymers have been utilized in coagulation/flocculation processes for water purification. In this study, a natural indigenous coagulant is suggested as a substitute for alum or as an aid for alum. The coagulant characteristics of the tannins obtained from valonia were examine...

  2. Coagulation profile in patients undergoing video-assisted thoracoscopic lobectomy: A randomized, controlled trial.

    Directory of Open Access Journals (Sweden)

    Thomas Decker Christensen

    Full Text Available Knowledge about the impact of Low-Molecular-Weight Heparin (LMWH on the coagulation system in patients undergoing minimal invasive lung cancer surgery is sparse. The aim of this study was to assess the effect of LMWH on the coagulation system in patients undergoing Video-Assisted Thoracoscopic Surgery (VATS lobectomy for primary lung cancer.Sixty-three patients diagnosed with primary lung cancer undergoing VATS lobectomy were randomized to either subcutaneous injection with dalteparin (Fragmin® 5000 IE once daily or no intervention. Coagulation was assessed pre-, peri-, and the first two days postoperatively by standard coagulation blood test, thromboelastometry (ROTEM® and thrombin generation.Patients undergoing potential curative surgery for lung cancer were not hypercoagulable preoperatively. There was no statistically significant difference in the majority of the assessed coagulation parameters after LMWH, except that the no intervention group had a higher peak thrombin and a shorter INTEM clotting time on the first postoperative day and a lower fibrinogen level on the second postoperative day. A lower level of fibrin d-dimer in the LMWH group was found on the 1. and 2.postoperative day, although not statistical significant. No differences were found between the two groups in the amount of bleeding or number of thromboembolic events.Use of LMWH administered once daily as thromboprophylaxis did not alter the coagulation profile per se. As the present study primarily evaluated biochemical endpoints, further studies using clinical endpoints are needed in regards of an optimized thromboprophylaxis approach.

  3. Rh Factor Blood Test (United States)

    Rh factor blood test Overview Rhesus (Rh) factor is an inherited protein found on the surface of red blood cells. If your ... Rh negative, you might need to have another blood test — an antibody screen — during your first trimester and ...

  4. Disseminated intravascular coagulation and massive obstetric hemorrhage. Management dilemma. (United States)

    Al-Nuaim, Lulu A; Mustafa, Mohamed S; Abdel Gader, Abdel Galil M


    The objective of this retrospective study is to reflect on our experience on an optimal management for major postpartum hemorrhage, which would prevent the occurrence and complications of disseminated intravascular coagulation and minimize maternal mortality and morbidity. Ten cases out of the 30,000 of total deliveries of severe obstetric hemorrhage associated with disseminated intravascular coagulation were studied. This study was carried out over a 7 year period, October 1988 through to September 1995, at the Obstetric Unit, King Khalid University Teaching Hospital, Riyadh, Kingdom of Saudi Arabia. All of the 10 women received packed red blood cells, 8 had fresh frozen plasma, and 6 received platelet transfusion. The 10 cases developed disseminated intravascular coagulation following medical and surgical management, all women needed hysterectomy, 4 subtotal, 6 total, and 5 women had relaparotomy and pelvic packing. Two had bladder injuries. There was no maternal death. An early resort to hysterectomy when conservative measures fail, will minimize maternal morbidity and mortality. In case of continuous bleeding after hysterectomy, pelvic packing proved to be effective.

  5. Effects of Paliperidone Palmitate on Coagulation: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Enver Demirel Yılmaz


    Full Text Available Objective. The aim of the present study was to examine the effects of a new antipsychotic drug paliperidone palmitate on hemogram and coagulation parameters in rats. Materials and Methods. Experiments were performed on 22 female albino Wistar rats (8–12 weeks old. Control group was given drinking water as vehicle (0.3 mL. PAL-1 rats were given 1 mg/kg paliperidone palmitate (in 0.3 mL drinking water by oral gavage once a day for ten days and PAL-3 rats received 3 mg/kg paliperidone palmitate (in 0.3 mL drinking water by oral gavage for ten days. Blood samples were drawn from the heart 24 hours after the last drug dose, and hemogram and coagulation parameters were measured with automated analyzers. Results. Hemogram did not change in the paliperidone treated groups compared to the controls. Factor VIII levels decreased in the PAL-1 and PAL-3 groups; and this decrease was significantly greater in the PAL-3. Factor IX levels decreased in PAL-3 rats, but its levels also increased in PAL-1 rats compared to the control. Discussion. Paliperidone has led to changes in the serum levels of coagulation factors VIII and IX in rats. As a result, paliperidone may be causing thromboembolism or bleeding in a dose-independent manner.

  6. Effects of paliperidone palmitate on coagulation: an experimental study. (United States)

    Yılmaz, Enver Demirel; Motor, Sedat; Sefil, Fatih; Pınar, Neslihan; Kokacya, Hanifi; Kisa, Mustafa; Oktar, Suleyman


    The aim of the present study was to examine the effects of a new antipsychotic drug paliperidone palmitate on hemogram and coagulation parameters in rats. Experiments were performed on 22 female albino Wistar rats (8-12 weeks old). Control group was given drinking water as vehicle (0.3 mL). PAL-1 rats were given 1 mg/kg paliperidone palmitate (in 0.3 mL drinking water) by oral gavage once a day for ten days and PAL-3 rats received 3 mg/kg paliperidone palmitate (in 0.3 mL drinking water) by oral gavage for ten days. Blood samples were drawn from the heart 24 hours after the last drug dose, and hemogram and coagulation parameters were measured with automated analyzers. Hemogram did not change in the paliperidone treated groups compared to the controls. Factor VIII levels decreased in the PAL-1 and PAL-3 groups; and this decrease was significantly greater in the PAL-3. Factor IX levels decreased in PAL-3 rats, but its levels also increased in PAL-1 rats compared to the control. Paliperidone has led to changes in the serum levels of coagulation factors VIII and IX in rats. As a result, paliperidone may be causing thromboembolism or bleeding in a dose-independent manner.

  7. Microwave coagulation therapy and drug injection to treat splenic injury. (United States)

    Zhang, Guoming; Sun, Yuanyuan; Yu, Jie; Dong, Lei; Mu, Nannan; Liu, Xiaohong; Liu, Lanfen; Zhang, Yan; Wang, Xiaofei; Liang, Ping


    The present study compares the efficacy of 915- and 2450-MHz contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave coagulation with that of CEUS-guided thrombin injection for the treatment of trauma-induced spleen hemorrhage. In a canine splenic artery hemorrhage model with two levels of arterial diameter (A, microwaves and drug injection. Therapy efficacy was measured by comparing bleeding rate, hemostatic time, bleeding index, bleeding volume, and pathology. The most efficient technique was CEUS-guided 915-MHz percutaneous microwave coagulation therapy in terms of action time and total blood loss. The success rate of the 915-MHz microwave group was higher than that of the 2450-MHz microwave and the drug injection groups (except A level, P microwave group than those in the 2450-MHz microwave and drug injection groups (P microwave group, but pathologic changes of light injury could be seen in the other groups. The present study provides evidence that microwave coagulation therapy is more efficient than thrombin injection for the treatment of splenic hemorrhage. Furthermore, treatment with 915-MHz microwaves stops bleeding more rapidly and generates a wider cauterization zone than does treatment with 2450-MHz microwaves. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Coagulation and complement system in critically ill patients. (United States)

    Helling, H; Stephan, B; Pindur, G


    Activation of coagulation and inflammatory response including the complement system play a major role in the pathogenesis of critical illness. However, only limited data are available addressing the relationship of both pathways and its assessment of a predictive value for the clinical outcome in intense care medicine. Therefore, parameters of the coagulation and complement system were studied in patients with septicaemia and multiple trauma regarded as being exemplary for critical illness. 34 patients (mean age: 51.38 years (±16.57), 15 females, 19 males) were investigated at day 1 of admittance to the intensive care unit (ICU). Leukocytes, complement factors C3a and C5a were significantly (p complement system as part of the inflammatory response is a significant mechanism in septicaemia, whereas loss and consumption of blood components including parts of the coagulation and complement system is more characteristic for multiple trauma. Protein C in case of severe reduction might be of special concern for surviving in sepsis. Activation of haemostasis was occurring in both diseases, however, overt DIC was not confirmed in this study to be a leading mechanism in critically ill patients. MOF score, lactate, C1-inhibitor and prothrombin time have been the only statistically significant predictors for lethal outcome suggesting that organ function, microcirculation, haemostasis and inflammatory response are essential elements of the pathomechanism and clinical course of diseases among critically ill patients.


    Gerlach, Trevor J; Barratclough, Ashley; Conner, Bobbi


    Veterinarians specializing in nondomestic species are faced with unique challenges regarding research and diagnostic capabilities given the wild and frequently dangerous nature of their patients. Standard diagnostic techniques used in small or large animal practice are not always possible due to anatomical constraints, size, tractability, or the inherent risk of anesthesia in highly valued, rare species. Diagnostic modalities that utilize simple, relatively noninvasive techniques show promise in evaluating nondomestic species and elucidating the pathophysiology behind poorly characterized disease processes in both wild and captive populations. Coagulation profiles, which may include prothrombin time (PT), partial thromboplastin time (PTT), D-dimer concentration, platelet count, and thromboelastography (TEG) are frequently used in domestic species but often overlooked in exotic medicine due to lack of normal reference values and/or availability. Whenever possible, coagulation profiles should be utilized in the evaluation of various disease processes including neoplasia, sepsis, trauma, inflammation, toxin exposure, and envenomation. There are several reports of coagulopathies in both wild and captive species; however, few studies on coagulation profiles have been published on nondomestic species. Clinicians should consider coagulation testing as part of the diagnostic work-up in nondomestic species. A review of available coagulation diagnostic tests is provided here in addition to summarizing the pertinent coagulation disorders currently established in the literature.

  10. Regional cerebral blood flow in mood disorders. I. Comparison of major depressives and normal controls at rest

    International Nuclear Information System (INIS)

    Sackeim, H.A.; Prohovnik, I.; Moeller, J.R.; Brown, R.P.; Apter, S.; Prudic, J.; Devanand, D.P.; Mukherjee, S.


    We measured regional cerebral blood flow with the xenon 133 inhalation technique in 41 patients with major depressive disorder and 40 matched, normal controls during an eyes-closed, resting condition. The depressed group had a marked reduction in global cortical blood flow. To examine topographic abnormalities, traditional multivariate analyses were applied, as well as a new scaled subprofile model developed to identify abnormal functional neural networks in clinical samples. Both approaches indicated that the depressed sample had an abnormality in topographic distribution of blood flow, in addition to the global deficit. The scaled subprofile model identified the topographic abnormality as being due to flow reduction in the depressed patients in selective frontal, central, superior temporal, and anterior parietal regions. This pattern may reflect dysfunction in the parallel distributed cortical network involving frontal and temporoparietal polymodal association areas. The extent of this topographic abnormality, as revealed by the scaled subprofile model, was associated with both patient age and severity of depressive symptoms

  11. Cerebral blood flow patterns using single photon emission computed tomography in patients with dissociative disorders and healthy controls

    International Nuclear Information System (INIS)

    Shah, M.


    To compare the cerebral blood flow (CBF) changes in patients diagnosed to have Dissociative Disorder with healthy controls. This cross sectional comparative study was done at Dept of Psychiatry Military Hospital Rawalpindi in collaboration with nuclear Medical Centre (NMC), at Armed Forces Institute of Pathology (AFIP) which is a tertiary referral center. A sample of 30 patients diagnosed as having Dissociative Disorder was compared with 10 controls for brain perfusion changes using TC-99m HMPAO (Hexamethyl-propylene-amine-oxime) Tc-99m. In group 1 perfusion changes were observed in 27 (90%) cases whereas unremarkable and insignificant changes were noted in 3 (10%) cases but no perfusion were noted in controls (P<0.001) In patients who were suffering from different types of dissociative disorder marked cerebral hypo perfusion was observed in frontal, frontomotor, orbitofrontal and temporal regions whereas hyperperfusion was noted in frontal and orbitofrontal areas in few cases. Conclusion: Cerebral blood flow changes in the fronto parietal brain are associated with symptomotology in dissociative disorders. (author)

  12. False data, positive results in neurobiology: moving beyond the epigenetics of blood and saliva samples in mental disorders. (United States)

    Cariaga-Martinez, A; Alelú-Paz, R


    Many psychiatric diseases are influenced by a set of several genetic and environmental factors that genetics alone cannot explain. Specifically, in schizophrenia and bipolar disorder the absence of consistently replicated genetic effects together with evidence for lasting changes in gene expression after environmental exposures suggest a role of epigenetic mechanisms in its pathophysiological mechanisms. In this field, the presence of positive results could potentially uncover molecular mechanisms of deregulated gene expression in these complex disorders. In this commentary we have reviewed the positive data obtained over the last 5 years from the scientific literature published in PubMed and we have shown that these results are based on peripheral samples (blood, saliva and other fluids) that do not allow us to obtain reliable and/or valid results, under any circumstances. Finally, we highlight the need to employ human brain samples in the epigenetic study of mental disorders.

  13. Commonly Used Dietary Supplements on Coagulation Function during Surgery. (United States)

    Wang, Chong-Zhi; Moss, Jonathan; Yuan, Chun-Su


    Patients who undergo surgery appear to use dietary supplements significantly more frequently than the general population. Because they contain pharmacologically active compounds, dietary supplements may affect coagulation and platelet function during the perioperative period through direct effects, pharmacodynamic interactions, and pharmacokinetic interactions. However, in this regard, limited studies have been conducted that address the pharmacological interactions of dietary supplements. To avoid possible bleeding risks during surgery, information of potential complications of dietary supplements during perioperative management is important for physicians. Through a systematic database search of all available years, articles were identified in this review if they included dietary supplements and coagulation/platelet function, while special attention was paid to studies published after 1990. Safety concerns are reported in commercially available dietary supplements. Effects of the most commonly used natural products on blood coagulation and platelet function are systematically reviewed, including 11 herbal medicines (echinacea, ephedra, garlic, ginger, ginkgo, ginseng, green tea, kava, saw palmetto, St John's wort, and valerian) and 4 other dietary supplements (coenzyme Q 10 , glucosamine and chondroitin sulfate, fish oil, and vitamins). Bleeding risks of garlic, ginkgo, ginseng, green tea, saw palmetto, St John's wort, and fish oil are reported. Cardiovascular instability was observed with ephedra, ginseng, and kava. Pharmacodynamic and pharmacokinetic interactions between dietary supplements and drugs used in the perioperative period are discussed. To prevent potential problems associated with the use of dietary supplements, physicians should be familiar with the perioperative effects of commonly used dietary supplements. Since the effects of dietary supplements on coagulation and platelet function are difficult to predict, it is prudent to advise their

  14. Commonly Used Dietary Supplements on Coagulation Function during Surgery

    Directory of Open Access Journals (Sweden)

    Chong-Zhi Wang


    Full Text Available Background: Patients who undergo surgery appear to use dietary supplements significantly more frequently than the general population. Because they contain pharmacologically active compounds, dietary supplements may affect coagulation and platelet function during the perioperative period through direct effects, pharmacodynamic interactions, and pharmacokinetic interactions. However, in this regard, limited studies have been conducted that address the pharmacological interactions of dietary supplements. To avoid possible bleeding risks during surgery, information about the potential complications of dietary supplements during perioperative management is important for physicians. Methods: Through a systematic database search of all available years, articles were identified in this review if they included dietary supplements and coagulation/platelet function, while special attention was paid to studies published after 1990. Results: Safety concerns are reported in commercially available dietary supplements. Effects of the most commonly used natural products on blood coagulation and platelet function are systematically reviewed, including 11 herbal medicines (echinacea, ephedra, garlic, ginger, ginkgo, ginseng, green tea, kava, saw palmetto, St John’s wort, and valerian and four other dietary supplements (coenzyme Q10, glucosamine and chondroitin sulfate, fish oil, and vitamins. Bleeding risks of garlic, ginkgo, ginseng, green tea, saw palmetto, St John’s wort, and fish oil are reported. Cardiovascular instability was observed with ephedra, ginseng, and kava. Pharmacodynamic and pharmacokinetic interactions between dietary supplements and drugs used in the perioperative period are discussed. Conclusions: To prevent potential problems associated with the use of dietary supplements, physicians should be familiar with the perioperative effects of commonly used dietary supplements. Since the effects of dietary supplements on coagulation and platelet


    Directory of Open Access Journals (Sweden)

    Nicola Semeraro


    Full Text Available Sepsis is almost invariably associated with haemostatic abnormalities ranging from subclinical activation of blood coagulation (hypercoagulability, which may contribute to localized venous thromboembolism, to acute disseminated intravascular coagulation (DIC, characterized by massive thrombin formation and widespread microvascular thrombosis, partly responsible of the multiple organ dysfunction syndrome (MODS, and subsequent consumption of platelets and coagulation proteins causing, in most severe cases, bleeding manifestations. There is general agreement that the key event underlying this life-threatening sepsis complication is the overwhelming inflammatory host response to the infectious agent leading to the overexpression of inflammatory mediators. Mechanistically, the latter, together with the micro-organism and its derivatives, causes DIC by 1 up-regulation of procoagulant molecules, primarily tissue factor (TF, which is produced mainly by stimulated monocytes-macrophages and by specific cells in target tissues; 2 impairment of physiological anticoagulant pathways (antithrombin, protein C pathway, tissue factor pathway inhibitor, which is orchestrated mainly by dysfunctional endothelial cells (ECs; and 3 suppression of fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1 by ECs and likely also to thrombin-mediated  activation of thrombin-activatable fibrinolysis inhibitor (TAFI. Notably, clotting enzymes non only lead to microvascular thrombosis but can also elicit cellular responses that amplify the inflammatory reactions. Inflammatory mediators can also cause, directly or indirectly, cell apoptosis or necrosis and recent evidence indicates that products released from dead cells, such as nuclear proteins (particularly extracellular histones, are able to propagate further inflammation, coagulation, cell death and MODS. These insights into the pathogenetic mechanisms of DIC and MODS may have important implications for the

  16. Bloodcurdling movies and measures of coagulation: Fear Factor crossover trial (United States)

    Nemeth, Banne; Scheres, Luuk J J; Lijfering, Willem M


    Objective To assess whether, as has been hypothesised since medieval times, acute fear can curdle blood. Design Crossover trial. Setting Main meeting room of Leiden University’s Department of Clinical Epidemiology, the Netherlands, converted to a makeshift cinema. Participants 24 healthy volunteers aged ≤30 years recruited among students, alumni, and employees of the Leiden University Medical Center: 14 were assigned to watch a frightening (horror) movie followed by a non-threatening (educational) movie and 10 to watch the movies in reverse order. The movies were viewed more than a week apart at the same time of day and both lasted approximately 90 minutes. Main outcome measures The primary outcome measures were markers, or “fear factors” of coagulation activity: blood coagulant factor VIII, D-dimer, thrombin-antithrombin complexes, and prothrombin fragments 1+2. The secondary outcome was participant reported fear experienced during each movie using a visual analogue fear scale. Results All participants completed the study. The horror movie was perceived to be more frightening than the educational movie on a visual analogue fear scale (mean difference 5.4, 95% confidence interval 4.7 to 6.1). The difference in factor VIII levels before and after watching the movies was higher for the horror movie than for the educational movie (mean difference of differences 11.1 IU/dL (111 IU/L), 95% confidence interval 1.2 to 21.0 IU/dL). The effect of either movie on levels of thrombin-antithrombin complexes, D-dimer, and prothrombin fragments 1+2 did not differ. Conclusion Frightening (in this case, horror) movies are associated with an increase of blood coagulant factor VIII without actual thrombin formation in young and healthy adults. Trial registration NCT02601053. PMID:26673787

  17. Bloodcurdling movies and measures of coagulation: Fear Factor crossover trial. (United States)

    Nemeth, Banne; Scheres, Luuk J J; Lijfering, Willem M; Rosendaal, Frits R


    To assess whether, as has been hypothesised since medieval times, acute fear can curdle blood. Crossover trial. Main meeting room of Leiden University's Department of Clinical Epidemiology, the Netherlands, converted to a makeshift cinema. 24 healthy volunteers aged ≤30 years recruited among students, alumni, and employees of the Leiden University Medical Center: 14 were assigned to watch a frightening (horror) movie followed by a non-threatening (educational) movie and 10 to watch the movies in reverse order. The movies were viewed more than a week apart at the same time of day and both lasted approximately 90 minutes. The primary outcome measures were markers, or "fear factors" of coagulation activity: blood coagulant factor VIII, D-dimer, thrombin-antithrombin complexes, and prothrombin fragments 1+2. The secondary outcome was participant reported fear experienced during each movie using a visual analogue fear scale. All participants completed the study. The horror movie was perceived to be more frightening than the educational movie on a visual analogue fear scale (mean difference 5.4, 95% confidence interval 4.7 to 6.1). The difference in factor VIII levels before and after watching the movies was higher for the horror movie than for the educational movie (mean difference of differences 11.1 IU/dL (111 IU/L), 95% confidence interval 1.2 to 21.0 IU/dL). The effect of either movie on levels of thrombin-antithrombin complexes, D-dimer, and prothrombin fragments 1+2 did not differ. Frightening (in this case, horror) movies are associated with an increase of blood coagulant factor VIII without actual thrombin formation in young and healthy adults. Trial registration NCT02601053. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  18. Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers (United States)

    Nahar, Risha; Saxena, Renu; Deb, Roumi; Verma, Ishwar C.


    CONTEXT: Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of coumarin response profile in such thrombophilic population. AIMS: The current pilot study aims to estimate coumarin sensitivity in an Indian cohort with an inherited thrombophilia risk factor (Factor V Leiden mutation carriers) based on the observed frequency of CYP2C9 *2, *3 and VKORC1-1639G >A genotype combinations. SETTINGS AND DESIGN: A retrospective study carried out in a tertiary health care center in India. MATERIALS AND METHODS: Carriers of FVL mutation were genotyped for CYP2C9 (*2, F*3) and VKORC1 (-1639G >A) variants by PCR-RFLP technique. STATISTICAL ANALYSIS USED: Chi-square test to analyze difference in expected and observed genotype frequency. RESULTS: Sixty-one (n = 61) unrelated carriers of FVL mutation were observed in the 13 years study period. The allele frequency of CYP2C9 *2, CYP2C9 *3, and VKORC1-1639A in this cohort was 0.06, 0.11, and 0.16, respectively. Six (9.7%) individuals had two of the three variant alleles (heterozygous or homozygous), and 28 (45.9%) were heterozygous for at least one polymorphism. CONCLUSIONS: Pre-prescription genotyping for coumarin drugs, if introduced in Indians with inherited thrombophilia (in whom oral anti-coagulant therapy may be necessary), is likely to identify 9.7% (hypersensitive) subjects in whom the optimum anti-coagulation may be achieved with reduced dosages, 44.3% (normal sensitivity) who may require higher dose and also 55.6% (hyper and moderate sensitivity) subjects who are likely to experience bleeding episodes. PMID:23716941

  19. Comparative study of adverse effects of Olanzapine and Risperidone on blood suger, lipid and other side effects in psychotic disorders

    Directory of Open Access Journals (Sweden)

    mitra safa


    Full Text Available Safa M1, Mohammadi MR2, Saki M3, Delfan B4, Tarrahi MJ5, Rouhandeh M6 1. Assistant Professor, Department of psychiatry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran 2. GP, Khorramabad, Iran 3. Instructor, Department of Nursing, Faculty of Nursing and Midwifery, Lorestan University of Medical Sciences, Khorramabad, Iran 4. Associate Professor, Department of Pharmacology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran 5. Instructor, Department of Epidemiology, Faculty of Health, Lorestan University of Medical Sciences, Khorramabad, Iran 6. BSc in Nursing, Khorramabad, Iran Abstract Background: Chronic mental disorders are among the problems in psychiatrics. Atypical anti psychotic drugs are new effective medications to treat these disorders. Unfortunately these drugs lead to side effects such as increase in blood glocuse, weight gain and edema. This study aims to investigate adverse effects of Olanzapine and Rispridone on lipid level and blood glocuse and other complications in patients with psychotic disorders. Materials and methods: This clinical trial-double blinded study, patients with psychotic disorders were randomly categorized into two groups. Group one treated with Olanzapine and other with Rispridone. All the subjects were initially assessed for blood sugar and lipids, and in the case of normal, they were randomly assigned to two groups in a double- blinded method to be treated with Olanzapine or Risperidone. Blood sugar and lipids tests were performed for all subjects at the 1st week and 3 months after initiation of therapy. Other complications were assessed too, then the data were analyzed using SPSS software. Results: The results of the study indicated that the levels of cholesterol, triglycerides and blood suger rose significantly at the 1st week and third month after beginning the treatment. Increase of cholesterol and triglyceride in the Olanzapine and Risperidone

  20. Enhanced coagulation for high alkalinity and micro-polluted water: the third way through coagulant optimization. (United States)

    Yan, Mingquan; Wang, Dongsheng; Qu, Jiuhui; Ni, Jinren; Chow, Christopher W K


    Conventional coagulation is not an effective treatment option to remove natural organic matter (NOM) in water with high alkalinity/pH. For this type of water, enhanced coagulation is currently proposed as one of the available treatment options and is implemented by acidifying the raw water and applying increased doses of hydrolyzing coagulants. Both of these methods have some disadvantages such as increasing the corrosive tendency of water and increasing cost of treatment. In this paper, an improved version of enhanced coagulation through coagulant optimization to treat this kind of water is demonstrated. A novel coagulant, a composite polyaluminum chloride (HPAC), was developed with both the advantages of polyaluminum chloride (PACl) and the additive coagulant aids: PACl contains significant amounts of highly charged and stable polynuclear aluminum hydrolysis products, which is less affected by the pH of the raw water than traditional coagulants (alum and ferric salts); the additives can enhance both the charge neutralization and bridging abilities of PACl. HPAC exhibited 30% more efficiency than alum and ferric salts in dissolved organic carbon (DOC) removal and was very effective in turbidity removal. This result was confirmed by pilot-scale testing, where particles and organic matter were removed synergistically with HPAC as coagulant by sequential water treatment steps including pre-ozonation, coagulation, flotation and sand filtration.

  1. Postpartum Blood Clots (United States)

    ... Kidney Infections Breast Infection Postpartum Blood Clots Postpartum Thyroid Disorders Postpartum Depression The risk of developing blood clots ( ... Kidney Infections Breast Infection Postpartum Blood Clots Postpartum Thyroid Disorders Postpartum Depression NOTE: This is the Consumer Version. ...

  2. Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders

    Directory of Open Access Journals (Sweden)

    Tachikawa Masanori


    Full Text Available Abstract Guanidino compounds (GCs, such as creatine, phosphocreatine, guanidinoacetic acid, creatinine, methylguanidine, guanidinosuccinic acid, γ-guanidinobutyric acid, β-guanidinopropionic acid, guanidinoethane sulfonic acid and α-guanidinoglutaric acid, are present in the mammalian brain. Although creatine and phosphocreatine play important roles in energy homeostasis in the brain, accumulation of GCs may induce epileptic discharges and convulsions. This review focuses on how physiologically important and/or neurotoxic GCs are distributed in the brain under physiological and pathological conditions. Transporters for GCs at the blood-brain barrier (BBB and the blood-cerebrospinal fluid (CSF barrier (BCSFB have emerged as substantial contributors to GCs distribution in the brain. Creatine transporter (CRT/solute carrier (SLC 6A8 expressed at the BBB regulates creatine concentration in the brain, and represents a major pathway for supply of creatine from the circulating blood to the brain. CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6 and organic cation transporter (OCT3/SLC22A3 expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters. Instead, the BCSFB functions as a major cerebral clearance system for GCs. In conclusion, transport of GCs at the BBB and BCSFB appears to be the key determinant of the cerebral levels of GCs, and changes in the transport characteristics may cause the abnormal distribution of GCs in the brain seen

  3. 1-[3-Aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. (United States)

    Pinto, Donald J P; Orwat, Michael J; Quan, Mimi L; Han, Qi; Galemmo, Robert A; Amparo, Eugene; Wells, Brian; Ellis, Christopher; He, Ming Y; Alexander, Richard S; Rossi, Karen A; Smallwood, Angela; Wong, Pancras C; Luettgen, Joseph M; Rendina, Alan R; Knabb, Robert M; Mersinger, Lawrence; Kettner, Charles; Bai, Steven; He, Kan; Wexler, Ruth R; Lam, Patrick Y S


    Attempts to further optimize the pyrazole factor Xa inhibitors centered on masking the aryl aniline P4 moiety. Scaffold optimization resulted in the identification of a novel bicyclic pyrazolo-pyridinone scaffold which retained fXa potency. The novel bicyclic scaffold preserved all binding interactions observed with the monocyclic counterpart and importantly the carboxamido moiety was integrated within the scaffold making it less susceptible to hydrolysis. These efforts led to the identification of 1-[3-aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one 6f (BMS-740808), a highly potent (fXa Ki=30 pM) with a rapid onset of inhibition (2.7x10(7) M-1 s-1) in vitro, selective (>1000-fold over other proteases), efficacious in the AVShunt thrombosis model, and orally bioavailable inhibitor of blood coagulation factor Xa.

  4. Syncope in patients with inherited arrhythmias


    Yukiko Nakano; Shimizu Wataru


    Syncope, a common symptom of cerebral ischemia often shows a multifactorial etiopathogenesis. Although inherited arrhythmias causing syncope is uncommon, such an occurrence could be a warning sign preceding cardiac arrest. Long QT syndrome (LQTS) is a typical inherited arrhythmia causing syncope in children. Early diagnosis and treatment of LQTS using beta-blockers prevents recurrent syncope in LQTS. Brugada syndrome, another typical inherited arrhythmia causes syncope or sudden cardiac arres...

  5. Milk coagulation properties and methods of detection

    Directory of Open Access Journals (Sweden)

    Simone Beux


    Full Text Available ABSTRACT: One of the most crucial steps in cheesemaking is the coagulation process, and knowledge of the parameters involved in the clotting process plays an important technological role in the dairy industry. Milk of different ruminant species vary in terms of their coagulation capacities because they are influenced by the milk composition and mainly by the milk protein genetic variants. The milk coagulation capacity can be measured by means of mechanical and/or optical devices, such as Lactodynamographic Analysis and Near-Infrared and Mid-Infrared Spectroscopy.

  6. Multiorgan dysfunction in a gravid woman with placental abruption and disseminated intravascular coagulation

    Directory of Open Access Journals (Sweden)

    Kezić Aleksandra


    Full Text Available The most frequent obstetrical cause of coagulation disorders as disseminated intravascular coagulation is placental abruption, which can be found in women without any apparent clinical disturbances or in the state of established preeclampsia. Hypertension occurs in 5-8% of all pregnancies and may be complicated by preeclampsia. Preeclampsia is a complex clinical syndrome with insufficiently clear pathophysiology based on the damage of the vascular endothelium. As a result of this, generalized endothelial disruption in preeclampsia, a multiorgan dysfunction, can develop, most frequently reflected in the clinical presentation with hematological and renal disturbances and with a disordered function of the liver and central nervous system. We are presenting a case of a gravid woman with poorly regulated hypertension that resulted from development of preeclampsia, later complicated by placental abruption and disseminated intravascular coagulation (DIC with multi-organ dysfunction. The importance of rapid recognition of coagulation disorder and the attempt at surgical treatment aiming at removal of the triggering mechanisms of DIC was shown, suggesting all the symptomatic therapeutic measures would be ineffective. Although our patient was surgically treated in the phase of generalized disorder characterized by development of coma, acute respiratory distress syndrome and renal insufficiency when mortality was 70%, the recovery of functions of all involved organs was achieved, except for the renal function that required chronic haemodialysis treatment.

  7. Contribution of coagulation factor VII R353Q polymorphism to the ...

    African Journals Online (AJOL)

    Hanan Azzam


    Dec 5, 2016 ... Contribution of coagulation factor VII R353Q polymorphism to the risk of thrombotic disorders development (venous and arterial): A case-control study. Hanan Azzam a, Reham M. El-Farahaty a,*. , Nashwa K. Abousamra a, Hossam Elwakeel b, Sherif Sakr c,. Ayman Helmy c, Eman Khashaba d.

  8. Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Qingying Meng


    Full Text Available The complexity of the traumatic brain injury (TBI pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing, and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.


    Directory of Open Access Journals (Sweden)

    N. R. Telesmanich


    Full Text Available Laboratory parameters of IgE-mediated immunological reaction (total IgE were studied. Subjects with impaired carbohydrate metabolism and persons with diabetes mellitus were classified for blood groups 0(I, A(II, B(III (n = 93. We determined total IgE, glucose levels and percentage of glycosylated hemoglobin (HbA1c in blood serum; as well ABO blood groups. Comparison of these parameters in patient cohorts with 0(I and A(II, B(III blood groups showed different reactogenicity, depending on the degree of carbohydrate metabolism disturbance and ABO group specificity of antigenic determinants of blood glycoproteins. There was a strong direct correlation (r = 0.8 between blood group 0(I antigens, and incidence of type 2 diabetes mellitus (DM. The highest correlation degree was observed between the blood group A(II and type 1 diabetes onset of (r = 1.0. The smallest percentage of DM and the smallest correlation (r = 0.67 were observed in patients, B(III blood group is located. In cases of sufficiently altered carbohydrate metabolism, the blood group 0(I and A(II carriers had total IgE of 43.61±15.12 kIU/L, and 86.2±42.61 kIU/L, respectively, thus being, on average, 4-times lower than in B(III blood group in whom total IgE in type 2 diabetes was 2-fold higher than normal values, being 209.65±52.5 kIU/L.

  10. Graduated Exposure and Compliance Training Intervention for Blood Draw Avoidance and Refusal in a Woman with Intellectual Disability and Schizoaffective Disorder (United States)

    Cromartie, R. Samuel; Flood, William A.; Luiselli, James K.


    This case report concerns a woman with intellectual disability, schizoaffective disorder, and avoidance and refusal of having her blood drawn. She required but refused blood draws to properly monitor the therapeutic dose of a necessary psychotropic medication. During intervention at a community-based habilitation setting and under simulated…

  11. Quantifying interspecific coagulation efficiency of phytoplankton

    DEFF Research Database (Denmark)

    Hansen, J.L.S.; Kiørboe, Thomas


    Non-sticky latex beads and sticky diatoms were used as models to describe mutual coagulation between sticky and non-sticky particles. in mixed suspensions of beads and Thalassiosira nordenskjoeldii, both types of particles coagulated into mixed aggregates at specific rates, from which...... the interspecific coagulation efficiency could be calculated. Stickiness between beads and T. nordenskjoeldii was 50% of that of T. nordenskjoeldii in monospecific suspensions, and this ratio remained constant throughout 12 experiments covering 1 order of magnitude variation in the stickiness level of T....... nordenskjoeldii. Mutual coagulation between Skeletonema costatum and the non-sticky cel:ls of Ditylum brightwellii also proceeded with hall the efficiency of S. costatum alone. The latex beads were suitable to be used as 'standard particles' to quantify the ability of phytoplankton to prime aggregation...

  12. Preimplantation genetic diagnosis of inherited disease. (United States)

    Ao, A


    Research on diagnosis of inherited disease in human embryo before implantation was initiated to help those couples who would prefer to select embryos at this stage rather than during pregnancy. Following in vitro fertilization (IVF), one to two cells were removed from 3 day cleavage stage embryo and cells were analysed for genetic defects. Embryos diagnosed as unaffected were returned to the uterus and thus the resulting pregnancies were assured to be normal. First babies born after the preimplantation diagnosis were using DNA amplification of Y-linked sequences by PCR to avoid X-linked disease. Several pregnancies were obtained by identifying sex of embryos using dual fluorescent in situ hybridization (FISH) with fluorochrome labelled DNA sequences specific for X- and Y-chromosomes to interphase nuclei. Development of single cell PCR for single gene defects led to diagnose several genetic disorders. Preimplantation diagnosis was successfully achieved for predominant delta 508 deletion causing cystic fibrosis, and pregnancies were also diagnosed for Lesch-Nyhan syndrome, Tay-Sachs and Duchenne muscular dystrophy.

  13. A phenomenological model of milk coagulation


    Osintsev, A.; Gromov, E.; Braginsky, V.


    A model of additional stabilization for the milk colloid system by means of the micelle electric charge arising owing to dissociation of micellar calcium caseinate is offered. The model allows comprehending the unique role of calcium in milk clotting and describing some features of coagulation temperature dependence, as well as explaining the nature of rennet, acid, heat-acid and heat-calcium coagulation within uniform concepts.

  14. Removal of silver nanoparticles by coagulation processes

    International Nuclear Information System (INIS)

    Sun, Qian; Li, Yan; Tang, Ting; Yuan, Zhihua; Yu, Chang-Ping


    Highlights: • This study investigated the removal of AgNP suspensions by four regular coagulants. • The optimal removal efficiencies for the four coagulants were achieved at pH 7.5. • The removal efficiency of AgNPs was affected by the natural water characteristics. • TEM and XRD showed that AgNPs or silver-containing NPs were adsorbed onto the flocs. -- Abstract: Commercial use of silver nanoparticles (AgNPs) will lead to a potential route for human exposure via potable water. Coagulation followed by sedimentation, as a conventional technique in the drinking water treatment facilities, may become an important barrier to prevent human from AgNP exposures. This study investigated the removal of AgNP suspensions by four regular coagulants. In the aluminum sulfate and ferric chloride coagulation systems, the water parameters slightly affected the AgNP removal. However, in the poly aluminum chloride and polyferric sulfate coagulation systems, the optimal removal efficiencies were achieved at pH 7.5, while higher or lower of pH could reduce the AgNP removal. Besides, the increasing natural organic matter (NOM) would reduce the AgNP removal, while Ca 2+ and suspended solids concentrations would also affect the AgNP removal. In addition, results from the transmission electron microscopy and X-ray diffraction showed AgNPs or silver-containing nanoparticles were adsorbed onto the flocs. Finally, natural water samples were used to validate AgNP removal by coagulation. This study suggests that in the case of release of AgNPs into the source water, the traditional water treatment process, coagulation/sedimentation, can remove AgNPs and minimize the silver ion concentration under the well-optimized conditions

  15. Cardiopulmonary Bypass and Blood Transfusion (Indications and Problems in Tranfusion of Blood Components as of 1986)


    金沢, 宏; 大関, 一; 矢沢, 正知; 江口, 昭治; Kanazawa, Hiroshi; Oozeki, Hajime; Yazawa, Masatomo; Eguchi, Shoji


    Cardiopulmonary bypass (CPB), functioning as the pumping system and the gas exchange functions, is one of the important instruments in cardiovascular operations. But it has many unfavourable problems such as massive blood transfusion, hemodilution, abnormality of coagulation, etc. In fact, 5 or 6 units of blood are necessary to prime CPB in infant, child, and adult. After CPB, massive blood transfusion is necessary to keep good circulation, and to recover from hemodilution and abnormal coagul...

  16. Disorders of the colloid-osmotic blood condition and methods of their correction during angiography in children

    International Nuclear Information System (INIS)

    Mikhel'son, V.A.; Gudiev, N.D.; Lazarev, V.V.; Polyaev, Yu.A.


    Results of angiography complication frequency reduction via patient preparation for osmotic stress (that is, introduction of radiopaque media bolus) are presented in the paper. Examination of children aged 5 monthes up to 14 years subjected to angiography under general anestesia has shown that during children preparation for angiography the specific infusion therapy corrects initial colloid-osmotic disorder in blood plasma and prevents action of hyperosmolalic radiopaque media. Occurance of critical values of hyperosmolality and hypooncia is not observed in contrast to control experiments, and it prevents development of some complications

  17. Altered coupling of regional cerebral blood flow and brain temperature in schizophrenia compared with bipolar disorder and healthy subjects (United States)

    Ota, Miho; Sato, Noriko; Sakai, Koji; Okazaki, Mitsutoshi; Maikusa, Norihide; Hattori, Kotaro; Hori, Hiroaki; Teraishi, Toshiya; Shimoji, Keigo; Yamada, Kei; Kunugi, Hiroshi


    Previous studies have suggested that schizophrenia patients have dysfunctional thermoregulation. The aim of this study was to examine whether brain temperature (BT) in schizophrenia patients differs from that in patients with bipolar disorder and healthy subjects by using magnetic resonance imaging. We also evaluated the possible relationship between BT and cerebral blood flow (CBF). We analyzed the temperature of lateral ventricles as the mean BT using diffusion-weighted imaging (DWI) thermometry, and evaluated the relationships between the BT and the CBF using pseudo-continuous arterial spin labeling (pCASL) among 3 diagnostic groups, 22 male patients with schizophrenia, 19 male patients with bipolar disorder, and 23 healthy male subjects. There were significant positive correlations between BT in the lateral ventricles and CBF in both the patients with bipolar disorder and healthy subjects. By contrast, there were significant negative correlations in patients with schizophrenia. We could not detect the significant difference in the surrogates of BT among three diagnostic groups. We showed that patients with schizophrenia, but not those with bipolar disorder, have dysfunctional thermoregulation in the brain. Brain temperature is highly dependent on cerebral metabolism and CBF, and thus uncoupling of cerebral metabolism and CBF may occur in schizophrenics. PMID:25182665

  18. Legal Portion in Russian Inheritance Law (United States)

    Inshina, Roza; Murzalimova, Lyudmila


    In this paper the authors describe the right to inherit as one of the basic human rights guaranteed by the Constitution of the Russian Federation. The state has set rules according to which after a person's death, his or her property is inherited by other persons. The Russian civil legislation establishes the institution of legal portions that is…

  19. Inherited thrombophilia and pregnancy complications revisited

    NARCIS (Netherlands)

    Rodger, Marc A.; Paidas, Michael; McLintock, Claire; Claire, McLintock; Middeldorp, Saskia; Kahn, Susan; Martinelli, Ida; Hague, William; Rosene Montella, Karen; Greer, Ian


    Inherited thrombophilias are not yet established as a cause of placenta-mediated pregnancy complications, such as fetal growth restriction, preeclampsia, abruption, and pregnancy loss. An inherited thrombophilia is only one of many factors that lead to development of these diseases and is unlikely

  20. Pathological changes in the structures of the blood-brain barrier in acute cerebral circulatory disorders

    Directory of Open Access Journals (Sweden)

    S.І. Tertyshny


    Full Text Available Morphological changes of the blood-brain barrier were investigated in case of an acute brain disturbed circulation. Autocontrol of vessels with their dilatation and formation of aggregation from formal elements were shown from the onset of the disease. Distructive changes of the endothelium, basement membranes, pericytes, asrtocytosal processes are marked in the microvessels with formation of the perivascular edema. Increase permeability of the blood-brain barrier promotes hemorrhagic transformation and lymphomicrophagical infi ltration of the perivascular zones.