The Bleeding Child; Is It NAI? a E Thomas
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MONONINE (“Difficulty ® Monoclonal Antibody Purified in Concentrating”; Subject Recovered)
CSL Behring IU/kg (n=38), 0.98 ± 0.45 K at doses >95-115 IU/kg (n=21), 0.70 ± 0.38 K at doses >115-135 IU/kg (n=2), 0.67 K at doses >135-155 IU/kg (n=1), and 0.73 ± 0.34 K at doses >155 IU/kg (n=5). Among the 36 subjects who received these high doses, only one (2.8%) Coagulation Factor IX (Human) reported an adverse experience with a possible relationship to MONONINE (“difficulty ® Monoclonal Antibody Purified in concentrating”; subject recovered). In no subjects were thrombo genic complications MONONINE observed or reported.4 only The manufacturing procedure for MONONINE includes multiple processing steps that DESCRIPTION have been designed to reduce the risk of virus transmission. Validation studies of the Coagulation Factor IX (Human), MONONINE® is a sterile, stable, lyophilized concentrate monoclonal antibody (MAb) immunoaffinity chromatography/chemical treatment step and of Factor IX prepared from pooled human plasma and is intended for use in therapy nanofiltration step used in the production of MONONINE doc ument the virus reduction of Factor IX deficiency, known as Hemophilia B or Christmas disease. MONONINE is capacity of the processes employed. These studies were conducted using the rel evant purified of extraneous plasma-derived proteins, including Factors II, VII and X, by use of enveloped and non-enveloped viruses. The results of these virus validation studies utilizing immunoaffinity chromatography. A murine monoclonal antibody to Factor IX is used as an a wide range of viruses with different physicochemical properties are summarized in Table affinity ligand to isolate Factor IX from the source material. -
Genetic and Epigenetic Determinants of Thrombin Generation Potential : an Epidemiological Approach Maria-Ares Rocanin-Arjo
Genetic and Epigenetic Determinants of Thrombin Generation Potential : an epidemiological approach Maria-Ares Rocanin-Arjo To cite this version: Maria-Ares Rocanin-Arjo. Genetic and Epigenetic Determinants of Thrombin Generation Potential : an epidemiological approach. Génétique humaine. Université Paris Sud - Paris XI, 2014. Français. NNT : 2014PA11T067. tel-01231859 HAL Id: tel-01231859 https://tel.archives-ouvertes.fr/tel-01231859 Submitted on 21 Nov 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ PARIS-SUD ÉCOLE DOCTORALE 420 : SANTÉ PUBLIQUE PARIS SUD 11, PARIS DESCARTES Laboratoire : Equip 1 de Unité INSERM UMR_S1166 Genomics & Pathophysiology of Cardiovascular Diseases THÈSE DE DOCTORAT SANTÉ PUBLIQUE - GÉNÉTIQUE STATISTIQUE par Ares ROCAÑIN ARJO Genetic and Epigenetic Determinants of Thrombin Generation Potential: an epidemiological approach. Date de soutenance : 20/11/2014 Composition du jury : Directeur de thèse : David Alexandre TREGOUET DR, INSERM U1166, Université Paris 6, Jussieu Rapporteurs : Guy MEYER PU_PH, Service de pneumologie. Hôpital européen Georges Pompidou Richard REDON DR, Institut thorax, UMR 1087 / CNRS UMR 6291 , Université de Nantes Examinateurs : Laurent ABEL DR, INSERM U980, Institut Imagine Marie Aline CHARLES DR, INSERM U1018, CESP Al meu pare (to my father /à mon père) Your genetics load the gun. -
Haemostatic Effects of Recombinant Coagulation Factor Viia
Haemostatic effects of recombinant coagulation factor VIIa Ton Lisman Lay-out: Pre Press, Baarn Cover illustration by Janine Marie¨n Inside illustrations by Geert Donker ISBN: 90-393-3192-8 Haemostatic effects of recombinant coagulation factor VIIa Bloedstelping door recombinant stollingsfactor VIIa (Met een samenvatting in het Nederlands) PROEFSCHIFT Ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de Rector Magnificus, Prof. Dr. W.H. Gispen, in gevolge het besluit van het College voor Promoties in het openbaar te verdedigen op dinsdag 17 december 2002 des ochtends te 10.30 uur. door Johannes Antonius Lisman Geboren op 10 Maart 1976, te Arnhem Promotor: Prof. Dr. Ph.G. de Groot Faculteit geneeskunde, Universiteit Utrecht Co-Promotor: Dr. H.K. Nieuwenhuis Faculteit geneeskunde, Universiteit Utrecht The studies described in this thesis were supported in part by an unrestricted educational grant from Novo Nordisk. Financial support by Novo Nordisk for the publication of this thesis is gratefully acknowledged. I’ve got a pen in my pocket does that make me a writer Standing on the mountain doesn’t make me no higher Putting on gloves don’t make you a fighter And all the study in the world Doesn’t make it science Paul Weller Contents Chapter 1. General Introduction 9 Haemophilia Chapter 2. Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe haemophilia A 41 Appendix to chapter 2. Enhanced procoagulant and antifibrinolytic potential of superactive variants of recombinant factor VIIa in plasma from patients with severe haemophilia A 55 Cirrhosis and liver transplantation Chapter 3. -
Duchenne Muscular Dystrophy in a Female Patient with a Karyotype of 46,X,I(X)(Q10)
Tohoku J. Exp. Med., 2010, 222, 149-153Karyotype Analysis of a Female Patient with DMD 149 Duchenne Muscular Dystrophy in a Female Patient with a Karyotype of 46,X,i(X)(q10) Zhanhui Ou,1 Shaoying Li,1 Qing Li,1 Xiaolin Chen,1 Weiqiang Liu1 and Xiaofang Sun1 1Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical College, Duobao Road, Guangzhou, China Duchenne muscular dystrophy (DMD) is a severe recessive X-linked form of muscular dystrophy caused by mutations in the dystrophin gene and it affects males predominantly. Here we report a 4-year-old girl with DMD from a healthy family, in which her parents and sister have no DMD genotype. A PCR-based method of multiple ligation-dependent probe amplification (MLPA) analysis showed the deletion of exons 46 and 47 in the dystrophin gene, which led to loss of dystrophin function. No obvious phenotype of Turner syndrome was observed in this patient and cytogenetic analysis revealed that her karyotype is 46,X,i(X)(q10). In conclusion, we describe the first female patient with DMD who carries a de novo mutation of the dystrophin gene in one chromosome and isochromosome Xq, i(Xq), in another chromosome. Keywords: Duchenne Muscular Dystrophy; de novo mutation; isochromosome Xq; karyotype; Turner syndrome Tohoku J. Exp. Med., 2010, 222 (2), 149-153. © 2010 Tohoku University Medical Press Duchenne muscular dystrophy (DMD) is a severe an uneventful pregnancy. At birth, her growth parameters recessive X-linked form of muscular dystrophy which is were normal. Her motor development was delayed: she characterized by rapid progression of muscle degeneration, could sit at 10 months and walk at 15 months, but fell down eventually leading to loss of ambulation and death. -
Haematology: Non-Malignant
Haematology: Non-Malignant Mr En Lin Goh, BSc (Hons), MBBS (Dist.), MRCS 25th February 2021 Introduction • ICSM Class of 2018 • Distinction in Clinical Sciences • Pathology = 94% • Wallace Prize for Pathology • Jasmine Anadarajah Prize for Immunology • Abrahams Prize for Histopathology Content 1. Anaemia 2. Haemoglobinopathies 3. Haemostasis and thrombosis 4. Obstetric haematology 5. Transfusion medicine Anaemia Background • Hb <135 g/L in males and <115 g/L in females • Causes: decreased production, increased destruction, dilution • Classified based on MCV: microcytic (<80 fL), normocytic (80-100 fL), macrocytic (>100 fL) • Arise from disease processes affecting synthesis of haem, globin or porphyrin Microcytic anaemia work-up • Key differentials • Iron deficiency anaemia • Thalassaemia • Sideroblastic anaemia • Key investigations • Peripheral blood smear • Iron studies Iron deficiency anaemia • Commonest cause is blood loss • Key features • Peripheral blood smear – pencil cells • Iron studies – ↓iron, ↓ferritin, ↑transferrin, ↑TIBC • FBC – reactive thrombocytosis • Management – investigate underlying cause, iron supplementation Thalassaemia • α-thalassaemia, β-thalassaemia, thalassaemia trait • Key features • Peripheral blood smear – basophilic stippling, target cells • Iron studies – all normal • Management – iron supplementation, regular transfusions, iron chelation Sideroblastic anaemia • Congenital or acquired • Key features • Peripheral blood smear – basophilic stippling • Iron studies – ↑iron, ↑ferritin, ↓transferrin, ↓TIBC • Bone -
Molecular Basis of Fibrinogen Naples Associated with Defective Thrombin Binding and Thrombophilia
Molecular basis of fibrinogen Naples associated with defective thrombin binding and thrombophilia. Homozygous substitution of B beta 68 Ala----Thr. J Koopman, … , J Grimbergen, P M Mannucci J Clin Invest. 1992;90(1):238-244. https://doi.org/10.1172/JCI115841. Research Article In an abnormal fibrinogen (fibrinogen Naples) associated with congenital thrombophilia we have identified a single base substitution (G----A) in the B beta chain gene that results in an amino acid substitution of alanine by threonine at position 68 in the B beta chain of fibrinogen. The propositus and two siblings were found to be homozygous for the mutation, whereas the parents and another sibling were found to be heterozygous. Individuals homozygous for the defect had a severe history of both arterial and venous thrombosis; heterozygous individuals had no clinical symptoms. The three homozygotes had a prolonged thrombin clotting time in plasma, whereas the heterozygotes had a normal thrombin clotting time. Fibrinopeptide A and B (FpA and FpB) release from purified fibrinogen by human alpha-thrombin was delayed in both the homozygous propositus and a heterozygous family member. Release of FpA from the normal and abnormal amino-terminal disulfide knot (NDSK) corresponded to that found with the intact fibrinogens, indicating a decreased interaction of thrombin with the NDSK part of fibrinogen Naples. Binding studies showed that fibrin from homozygous abnormal fibrinogen bound less than 10% of active site inhibited alpha-thrombin as compared with normal fibrin, while fibrin formed from heterozygous abnormal fibrinogen bound approximately 50% of alpha-thrombin. These results suggest that the mutation of B beta Ala 68----Thr affects the binding of alpha-thrombin […] Find the latest version: https://jci.me/115841/pdf Molecular Basis of Fibrinogen Naples Associated with Defective Thrombin Binding and Thrombophilia Homozygous Substitution of BB 68 Ala -- Thr Jaap Koopman,** Frits Haverkate,t Susan T. -
MGH Clinical Laboratories
MGH Laboratory Handbook Online Lab Handbook: http://mghlabtest.partners.org Reference Intervals - MGH Clinical Laboratories MGH Department of Pathology 55 Fruit Street, GRJ 220 Boston, MA 02114-2696 Report generated: August 19, 2009 Test name Reference Interval Laboratory 1-25-OH Vitamin D Core lab (Sendouts) 1-3-Beta D glucan assay Core lab (Sendouts) 17-OH Progesterone Core lab (Sendouts) 25-OH Vitamin D Desired: > 32 ng/mL Core 3-Methylhistidine, urine Age matched reference range and interpretation Neurochemistry provided 5-Nucleotidase Core lab (Sendouts) A1AT deficiency profile Core lab (Sendouts) ABO/Rh Type Blood Transfusion Service Acetaminophen Negative Core Acetone Negative Core Acetylaspartate, urine Interpretation provided Neurochemistry ACTH 6-76 pg/ml Core Acylcarnitines (plasma) Core lab (Sendouts) ADAMTS13 activity/inhibitor Core lab (Sendouts) Adenosine deaminase (fluid--NOT CSF) Core lab (Sendouts) Adenovirus antibody Reported with results Microbiology Adenovirus antigen Negative Microbiology Adenylosuccinase deficiency, screen Interpretation provided Neurochemistry AFP (non-maternal specimens) Core Alanine, CSF Interpretation and age-matched reference ranges Neurochemistry provided. Wednesday, August 19, 2009 Page 1 of 26 Test name Reference Interval Laboratory Alanine, plasma Interpretation and age-matched reference ranges Neurochemistry provided. Albumin 3.1-4.3 g/dl Chelsea Healthcenter Albumin 3.3-5.0 g/dl Core Albumin (fluid--NOT CSF) Core Alcohols (ethanol, MeOH, isoprop) Negative Core Aldolase Core lab (Sendouts) -
5.1.1 OCR Exambuilder
1. Thirty-three human blood group systems are known to exist. Two of these are the ABO blood group system and the Hh blood group system. Explain why a person whose blood group is AB expresses both A and B antigens on the surface of their red blood cells. [2] © OCR 2019. 1 of 42 PhysicsAndMathsTutor.com 2. Some varieties of maize plants have smooth kernels (seeds), whereas others have wrinkled kernels. This is a genetic trait. Varieties with smooth kernels are rich in starch and useful for making flour. A farmer has been given some smooth seeds all of the same unknown genotype. The farmer carries out a cross- breeding experiment using these seeds and some known to be heterozygous for this trait. The results are shown in Table 4.1. F1 phenotype Observed results Expected results Smooth 547 Wrinkled 185 Total 732 Table 4.1 The χ2 statistic is calculated in the following way: (i) Calculate the value of χ2 for the above data. Show your working. Answer _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ [2] (ii) Table 4.2 shows a critical values table. Degrees of freedom probability, p 0.90 0.50 0.10 0.05 1 0.016 0.455 2.71 3.84 2 0.211 1.386 4.61 5.99 3 0.584 2.366 6.25 7.81 4 1.064 3.357 7.78 9.49 Table 4.2 Using your calculated value of χ2 and Table 4.2 what conclusions should you make about the significance of © OCR 2019. -
The Role of the Laboratory in Treatment with New Oral Anticoagulants
Journal of Thrombosis and Haemostasis, 11 (Suppl. 1): 122–128 DOI: 10.1111/jth.12227 INVITED REVIEW The role of the laboratory in treatment with new oral anticoagulants T. BAGLIN Department of Haematology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK To cite this article: Baglin T. The role of the laboratory in treatment with new oral anticoagulants. J Thromb Haemost 2013; 11 (Suppl. 1): 122–8. tion of thromboembolism in patients with atrial fibrilla- Summary. Orally active small molecules that selectively tion. For some patients, these drugs offer substantial and specifically inhibit coagulation serine proteases have benefits over oral vitamin K antagonists (VKAs). For the been developed for clinical use. Dabigatran etexilate, majority of patients, these drugs are prescribed at fixed rivaroxaban and apixaban are given at fixed doses and doses without the need for monitoring or dose adjustment. do not require monitoring. In most circumstances, these There are no food interactions and very limited drug inter- drugs have predictable bioavailability, pharmacokinetic actions. The rapid onset of anticoagulation and short half- effects, and pharmacodynamic effects. However, there life make the initiation and interruption of anticoagulant will be clinical circumstances when assessment of the therapy considerably easier than with VKAs. As with all anticoagulant effect of these drugs will be required. The anticoagulants produced so far, there is a correlation effect of these drugs on laboratory tests has been deter- between intensity of anticoagulation and bleeding. Conse- mined in vitro by spiking normal samples with a known quently, the need to consider the balance of benefit and risk concentration of active compound, or ex vivo by using in each individual patient is no less important than with plasma samples from volunteers and patients. -
Approach to Coagulopathy in the Icu Dic and Thrombotic Emergencies
APPROACH TO COAGULOPATHY IN THE ICU DIC AND THROMBOTIC EMERGENCIES NEIL KUMAR, MD UNIVERSITY OF ROCHESTER MEDICAL CENTER Disclosures u I have no financial disclosures u I am NOT A HEMATOLOGIST Outline u Review of hemostasis and coagulopathy u Discuss laboratory markers for coagulopathy u Discuss an approach to a few specific coagulopathies and thrombotic emergencies Outline u Review of hemostasis and coagulopathy u Discuss laboratory markers for coagulopathy u Discuss an approach to a few specific coagulopathies and thrombotic emergencies Coagulation u Coagulation is the process in which blood clots u Fibrinolysis is the process in which clot dissolves u Hemostasis is the stopping of bleeding or hemorrhage. u Ideally, hemostasis is a balance between coagulation and fibrinolysis Coagulation (classic pathways) Michael G. Crooks Simon P. Hart Eur Respir Rev 2015;24:392-399 Coagulation (another view) Gando, S. et al. (2016) Disseminated intravascular coagulation Nat. Rev. Dis. Primers doi:10.1038/nrdp.2016.37 Coagulation (yet another view) u Inflammation and coagulation intersect with platelets in the middle u An example of this is Disseminated Intravascular Coagulation. Gando, S. et al. (2016) Disseminated intravascular coagulation Nat. Rev. Dis. Primers doi:10.1038/nrdp.2016.37 Outline u Review of hemostasis and coagulopathy u Discuss laboratory markers for coagulopathy u Discuss an approach to a few specific coagulopathies and thrombotic emergencies PT / INR u Prothrombin Time u Test of Extrinsic Pathway u Take plasma (blood without cells) and re-add calcium u Calcium was removed with citrate in tube u Add tissue factor u See how long it takes to clot and normalize PT to get INR Coagulation (classic pathways) Michael G. -
Diagnosis of Hemophilia and Other Bleeding Disorders
Diagnosis of Hemophilia and Other Bleeding Disorders A LABORATORY MANUAL Second Edition Steve Kitchen Angus McCraw Marión Echenagucia Published by the World Federation of Hemophilia (WFH) © World Federation of Hemophilia, 2010 The WFH encourages redistribution of its publications for educational purposes by not-for-profit hemophilia organizations. For permission to reproduce or translate this document, please contact the Communications Department at the address below. This publication is accessible from the World Federation of Hemophilia’s website at www.wfh.org. Additional copies are also available from the WFH at: World Federation of Hemophilia 1425 René Lévesque Boulevard West, Suite 1010 Montréal, Québec H3G 1T7 CANADA Tel.: (514) 875-7944 Fax: (514) 875-8916 E-mail: [email protected] Internet: www.wfh.org Diagnosis of Hemophilia and Other Bleeding Disorders A LABORATORY MANUAL Second Edition (2010) Steve Kitchen Angus McCraw Marión Echenagucia WFH Laboratory WFH Laboratory (co-author, Automation) Training Specialist Training Specialist Banco Municipal Sheffield Haemophilia Katharine Dormandy de Sangre del D.C. and Thrombosis Centre Haemophilia Centre Universidad Central Royal Hallamshire and Thrombosis Unit de Venezuela Hospital The Royal Free Hospital Caracas, Venezuela Sheffield, U.K. London, U.K. on behalf of The WFH Laboratory Sciences Committee Chair (2010): Steve Kitchen, Sheffield, U.K. Deputy Chair: Sukesh Nair, Vellore, India This edition was reviewed by the following, who at the time of writing were members of the World Federation of Hemophilia Laboratory Sciences Committee: Mansoor Ahmed Clarence Lam Norma de Bosch Sukesh Nair Ampaiwan Chuansumrit Alison Street Marión Echenagucia Alok Srivastava Andreas Hillarp Some sections were also reviewed by members of the World Federation of Hemophilia von Willebrand Disease and Rare Bleeding Disorders Committee. -
Autosomal Recessive Disorders and X Linked Disorders in Malaysia
Patricia Bowen Library & Knowledge Service Email: [email protected] Website: http://www.library.wmuh.nhs.uk/wp/library/ DISCLAIMER: Results of database and or Internet searches are subject to the limitations of both the database(s) searched, and by your search request. It is the responsibility of the requestor to determine the accuracy, validity and interpretation of the results. Date: 27 January 2020 Sources Searched: Medline, Embase. Autosomal Recessive Disorders and X Linked Disorders in Malaysia See full search strategy 1. International perspectives on the implementation of reproductive carrier screening. Author(s): Delatycki, Martin B; Alkuraya, Fowzan; Archibald, Alison; Castellani, Carlo; Cornel, Martina; Grody, Wayne W; Henneman, Lidewij; Ioannides, Adonis S; Kirk, Edwin; Laing, Nigel; Lucassen, Anneke; Massie, John; Schuurmans, Juliette; Thong, Meow-Keong; van Langen, Irene; Zlotogora, Joël Source: Prenatal diagnosis; Nov 2019 Publication Date: Nov 2019 Publication Type(s): Journal Article Review PubMedID: 31774570 Available at Prenatal diagnosis - from Wiley Online Library Abstract:Reproductive carrier screening started in some countries in the 1970s for hemoglobinopathies and Tay-Sachs disease. Cystic fibrosis carrier screening became possible in the late 1980s and with technical advances, screening of an ever increasing number of genes has become possible. The goal of carrier screening is to inform people about their risk of having children with autosomal recessive and X-linked recessive disorders, to allow for informed decision making about reproductive options. The consequence may be a decrease in the birth prevalence of these conditions, which has occurred in several countries for some conditions. Different programs target different groups (high school, premarital, couples before conception, couples attending fertility clinics, and pregnant women) as does the governance structure (public health initiative and user pays).