DOCSLIB.ORG

Neonatal Hematology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Neonatal Hematology Neonatal Hematology Tung Wynn, MD April 28, 2016 Disclosures • I am site principal investigator for Baxalta, Novonordisk, Bayer, and AstraZeneca studies Hemophilia Factor VIII Def Protein C Def Factor IX Def Protein S Def Rare factor deficiencies Antithrombin III Def Factor XIII Factor V Leiden Mut Factor VII Prothrombin Mut Von Willebrands AntiPhospholipids Antibodies Thrombocytopenia Hyperhomocysteinemia Platelet dysfunctions MTHFR mutations Liver Disease Factor VIII elevation Vitamin K deficiency Liver Disease Afibrinogenemia Vitamin K deficiency Dysfibrinogenemia Dysfibrinogenemia Alpha-2 antiplasmin Def Plasminogen activator inhibitor-1 mut Plasminogen activator Inhibitor-1 Def Coagulation Anti-Coagulation Overview • Three phases of Coagulation – Vascular phase – Platelet phase • Platelet adhesion • Platelet aggregation – Coagulation phase • Intrinsic pathway • Extrinsic pathway • Clot contraction • Activation of coagulation also initiates the process of fibrinolysis Neonatal Hemostatic System Differences Coagulation Anticoagulation – Factor II – Plasminogen – Factor VII – Antithrombin III – Factor IX – Protein C – Factor X – Protein S – Factor XI – Factor XIII – Platelet levels are normal, but have wider variability Physiologic “deficiencies” of both coagulation and anticoagulation “balance” each other out in the neonate. General Approach to Neonatal bleeding • History – Fever – PPROM – Chorioamnonitis – Fetal Distress – Birth Trauma – Maternal infection – Maternal CBC – Family history autoimmune disease, coagulation disorder, low platelets – Vitamin K administration • Physical – Well or Sick Infant – Confounding medical conditions (Trisomy 21) – Signs of birth trauma – Bruises – Petechiae – Flank Masses – Hepatosplenomegaly Platelets • By 11 weeks, platelets can be recovered • Platelet reference ranges are similar in premature and term newborns to adults, but may vary more widely • Lifespan 7-10 days • Removed in the RES by macrophages • 25-35% of platelet located in the spleen Bozza FA, Shah AM, Weyrich AS, Zimmerman GA.Amicus or Adversary : Platelets in Lung Biology, Acute Injury, and Inflammation, Volume 40, Issue 2, American Journal of Respiratory Cell and Molecular Biology Platelets • Cellular fragments formed in bone marrow from megakaryocytes regulated primarily by thrombopoietin • Discoid in circulation, but once activated they release their granules and form multiple pseudopodia and become spherical • Platelet problems present either as quantitative deficiency or bleeding complication Thrombocytopenia • Infections – TORCH – HIV – DIC – Bacterial Sepsis • Drug exposure – Salicylates – Quinine – Hydralizine – Tolbutamide – Thiazide diuretics Thrombocytopenia • Immune Mediated Treatment may be with IVIg, Steroids, and/or transfusions – NAIT • Severely affects platelet function because antibodies blocks GPIIb/IIIa (VWF receptor); keep platelets >50K • Transfusions should be with HPA- (PLA-) negative or with maternal pheresis product • Random donor platelets can be given with IVIg, but steroids are not as helpful • More severe upon second exposure/pregnancies • Manage future pregnancies with maternal weekly IVIg or daily corticosteroids or fetal platelet transfusions – Isoimmune thrombocytopenia (maternal ITP) • Does not affect platelet function; platelets may be >30K – Autoimmune thrombocytopenia (ITP) • Very rare in the neonate Thrombocytopenia • Syndromes – Trisomy 21 • Transient myeloproliferative disorder or – Spontaneously resolves in 3-6 months – 20% will recur as AML • AML – GATA1 mutations help to distinguish – Trisomy 13, 18 • Jacobsen Syndrome – Paris-Trousseau Syndrome – 11q23 deletion – Large platelets, thrombocytopenia, cardiac defect, mental retardation characteristic facial feature Thrombocytopenia • TAR Syndrome (Thrombocytopenia, Absent Radii) – Severe thrombocytopenia that improves spontaneously as babies become older – Platelet transfusions recommended if bleeding; but high risk of alloimmunization • MYH9 related disorders – May-Hegglin Anomaly (large platelets with Döhle bodies) – Sebastian syndrome (cataracts, deafness) – Fechtner’s syndrome (nephritis, cataracts, deafness) – Epstein’s syndrome (deafness, nephritis, no döhle bodies) Thrombocytopenia • Wiskott Aldrich Syndrome (WAS) – Triad: small platelets, immune deficiency, eczematous rash – X-linked disorder – WASP gene mutation – HSCT may be curative • Congenital AMegakaryocytic Thrombocytopenia (CAMT) – Mutation of TPO receptor (c-mpl) – High risk of developing bone marrow failure – HSCT may be curative Miscellaneous Causes of Thrombocytopenia • Kasabach-Merritt Phenomenon – Consumptive coagulopathy associated with hemangiomas • ECMO – Heparin – Chronic platelet activation – Factor deficiencies – hypoxia Pseudo-thrombocytopenia Platelet Dysfunctions • Bernard-Soulier Syndrome – Large platelets with mild thrombocytopenia caused by deficiency of GP 1b/IX/V complex – Absent aggregation with ristocetin – High risk of alloantibody due to platelet transfusion – Responsive to DDAVP • Glanzmann’s Thrombasthenia – Rarely seen in neonates – Most commonly present with GI bleeding or menorrhagia – Respond well to Factor VIIa – High risk of alloantibody with frequent platelet transfusions Platelet Dysfunctions • Hermansky-Pudlak Syndrome – oculocutaneous albinism – mild/mod bleeding tendency – Colitis, pulmonary fibrosis in 2nd-3rd decade – Most common form of albinism in Puerto Rico – May respond to DDAVP, F VIIa, plasma, platelets • Chediak-Higashi Sydrome – Partial albinism – Immune deficiency – Neurologic deterioration – Autosomal recessive – Lymphoproliferation/lymphoma often fatal in 1st decade – intracellular disorder of organelle transport and synthesis – HSCT is curative Coagulation Coagulation • Coagulation proteins are not likely to cross placenta • Levels are 10-30% of adults • At 32 weeks, Fibrinogen, Factors V, VIII, XIII, and VWF are similar to adults • II, VII, IX, X and XI and XIII remain low Coagulopathy • PT, aPTT – PT: 16 sec (13-20) – aPTT: 55 sec (+/- 10) – Factors primarily made in liver, except VWF • Factor V – Megakaryocytes • Factor VIII – Endothelial Cells • Factor XIII – Macrophages – VWF made in endothelial cells and megakaryocytes Coagulopathy • Hemorrhagic Disease of the Newborn – Hemorrhaging that occurs in first 1-5 days of life in an otherwise healthy infant – Caused by Vitamin K deficiency, and increased sensitivity because of lowered Vit K dependent factor levels (II, VII, IX, X and Prot C, Prot S) – Without prophylactic Vit K, 0.25-1.7% incidence – Vit K 0.5-1 mg IM or 2-4 mg PO – Takes 12-24 hours for correction – Emergencies (ICH) should be treated with PCC or aPCC (FEIBA or K- centra) Coagulopathy • Disseminate Intravascular Coagulation (DIC) – Consumptive coagulopathy secondary to a variety of conditions, most often sepsis, malignancy, major trauma, obstetric complication – Can manifest with bleeding, thrombosis, or both – Labs: • Increased D-dimer, FDP, schistocytes, PT, aPTT, TT • Decreased factors, platelets, fibrinogen – Treatment: • Manage primary condition • Supportive management. – Replacement if bleeding – Anticoagulation if thrombotic Hemophilia • X-linked diseases • Cord blood may be used for initial factor determination if there is a family history • Avoid fetal scalp blood sampling and electrodes, prolonged labor, delivery with forceps or vacuum. • Carriers may be in the moderate or severe range due to extreme lyonization. • Mother may need peripartum factor replacement. • Circumcision bleeding most frequent presentation – Cephalohematoma, Vit K injection, Heel stick, immunization • FFP if unknown factor deficiency • Factor product if deficiency is known Hemophilia • Incidence: 20-25 per 100,000 males • Factor VIII deficiency accounts for about 85% of the cases Hemophilia B Hemophilia A 15% 85% • Approx. 30% of the cases are due to spontaneous mutations with no family history. Hemophilia: Laboratories • Prolonged aPTT, Normal PT, Normal Platelet counts • Mixing Studies correct • Specific Factor Assays (antigen-quantitative, activity-qualitative – Hemophilia A (Classic) • Factor VIII is linked through non-covalent bonds with vWF in plasma and this may cause confusion for the diagnosis of VWD (type 2 N) – Hemophilia B (Christmas) – Hemophilia C • Factor XI deficiency is sometimes known as this • Gene profiling is available – Deletions are associated with more severe diseases while point mutations are associated with milder disease – Consider gene testing if clinical state does not match up with the Factor activity assay, in a child you are considering VWD, or if you are asked to assess a carrier state Laboratories • Lab values change with age Lab Test Newborns Adults Platelets 214 +/- 55 258 +/- 66 PT 13.1 +/- 0.9 11.9 +/- 0.6 aPTT 35 +/- 4.5 28.8 +/- 2.7 Factor VIII 113 +/- 38 92 +/- 21 Factor IX 86 +/- 18 94 +/- 16 Adapted from Nathan and Oski, 7th ed. Factor VIII and IX molecules Factor VIII gene is approximately 180 kb long while Factor IX gene is only 34 kb Current Treatment of Hemophilia • Severe – < 1% Bleeding with minor injuries, spontaneous bleeds – Usually require prophylaxis starting as they are able to ambulate • Moderate – 1-5% Mild to moderate injuries – May or may not need prophylaxis but occasional bleeds • Mild – >5-50% Asymptomatic, bleeding with severe trauma or surgery – Rarely needs factor and may be treated with DDAVP/desmopressin Current Treatment of Hemophilia Type of Bleed Hemophilia A Hemophilia B Epistaxis Pressure, Local Treatments (QR, packing), Pressure, Local Treatments
Load more

Recommended publications
  • Factor XIII and Fibrin Clot Properties in Acute Venous Thromboembolism
    International Journal of Molecular Sciences Review Factor XIII and Fibrin Clot Properties in Acute Venous Thromboembolism Michał Z ˛abczyk 1,2 , Joanna Natorska 1,2 and Anetta Undas 1,2,* 1 John Paul II Hospital, 31-202 Kraków, Poland; [email protected] (M.Z.); [email protected] (J.N.) 2 Institute of Cardiology, Jagiellonian University Medical College, 31-202 Kraków, Poland * Correspondence: [email protected]; Tel.: +48-12-614-30-04; Fax: +48-12-614-21-20 Abstract: Coagulation factor XIII (FXIII) is converted by thrombin into its active form, FXIIIa, which crosslinks fibrin fibers, rendering clots more stable and resistant to degradation. FXIII affects fibrin clot structure and function leading to a more prothrombotic phenotype with denser networks, characterizing patients at risk of venous thromboembolism (VTE). Mechanisms regulating FXIII activation and its impact on fibrin structure in patients with acute VTE encompassing pulmonary embolism (PE) or deep vein thrombosis (DVT) are poorly elucidated. Reduced circulating FXIII levels in acute PE were reported over 20 years ago. Similar observations indicating decreased FXIII plasma activity and antigen levels have been made in acute PE and DVT with their subsequent increase after several weeks since the index event. Plasma fibrin clot proteome analysis confirms that clot-bound FXIII amounts associated with plasma FXIII activity are decreased in acute VTE. Reduced FXIII activity has been associated with impaired clot permeability and hypofibrinolysis in acute PE. The current review presents available studies on the role of FXIII in the modulation of fibrin clot properties during acute PE or DVT and following these events.
    [Show full text]
  • Guideline on Clinical Investigation of Recombinant and Human Plasma-Derived 9 Factor IX Products’ (EMA/CHMP/BPWP/144552/2009 Rev
    1 15 November 2018 2 EMA/CHMP/BPWP/144552/2009 rev. 2 Corr. 1 3 Committee for medicinal products for human use (CHMP) 4 Guideline on clinical investigation of recombinant and 5 human plasma-derived factor IX products 6 Draft Draft Agreed by Blood Products Working Party (BPWP) August 2018 Adopted by Committee for Medicinal Products for Human Use (CHMP) 15 November 2018 Start of public consultation 3 December 2018 End of public consultation 30 June 2019 7 8 This guideline replaces ‘Guideline on clinical investigation of recombinant and human plasma-derived 9 factor IX products’ (EMA/CHMP/BPWP/144552/2009 Rev. 1, Corr. 1) 10 Comments should be provided using this template. The completed comments form should be sent to [email protected] 11 Keywords Recombinant factor IX, plasma-derived factor IX, efficacy, safety, immunogenicity, inhibitor, thrombogenicity, anaphylactic reactions, potency assays 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2019. Reproduction is authorised provided the source is acknowledged. 12 Guideline on the clinical investigation of recombinant and 13 human plasma-derived factor IX products 14 Table of contents 15 Executive summary ..................................................................................... 4 16 1. Introduction (background) .....................................................................
    [Show full text]
  • Protein S Deficiency Presenting with Hemorrhage in a Term Neonate
    : Curre re nt a R C e Ayari et al., Health Care Current Reviews 2018, 6:1 h v t i l e a w DOI: 10.4172/2375-4273.1000219 e s H Health Care: Current Reviews ISSN: 2375-4273 Review Article Open Access Protein S Deficiency Presenting with Hemorrhage in a Term Neonate Fairouz Ayari*, Takoua Bensmail, Essid Latifa, Wiem Barbaria and Samia Kacem Neonatology Intensive Care Unit of the Maternity and Neonatology Center, Tunis, Tunisia Abstract Unexplained bleeding symptoms in otherwise healthy full-term usually present a diagnostic challenge for treating physicians requiring prompt and accurate laboratory investigations to ensure appropriate treatment and possibly avoid long-term morbidity. We report a case of a term neonate with severe protein S deficiency manifested by systemic hemorrhage and multiple organ failure at 9 days of age. We review how protein S influences the coagulation and the fibrinolytic pathways, discussing therapeutic approaches of neonates with purpura fulminans. Keywords: Protein S deficiency; Blood sample; Thrombophilic dis- resuscitation with 20 ml/kg bodyweight (BW) saline solution and, after order blood sampling, intravenous administration of 10 mg vitamin K, 20 ml/kg BW fresh frozen plasma, 20 ml/kg BW packed red blood cells Introduction (5 transfusion cycles), 20 mg/kg BW Phenobarbital and vasoactive Protein S (PS) is an antithrombotic plasma protein that acts mainly drugs. Cerebral ultrasound revealed intraventricular haemorrhage, as a cofactor of activated protein C (APC) anticoagulant activity in the abdominal ultrasound showed splenic hemorrhage and cardiac degradation of factor Va and activated factor VIII [1]. PS circulates in ultrasound showed a floating intracardiac thrombus.
    [Show full text]
  • WFH Treatment Guidelines 3Ed Chapter 7 Treatment Of
    96 TREATMENT OF SPECIFIC 7 HEMORRHAGES Johnny Mahlangu1 | Gerard Dolan2 | Alison Dougall3 | Nicholas J. Goddard4 | Enrique D. Preza Hernández5 | Margaret V. Ragni6 | Bradley Rayner7 | Jerzy Windyga8 | Glenn F. Pierce9 | Alok Srivastava10 1 Department of Molecular Medicine and Haematology, University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa 2 Guy’s and St. Thomas’ Hospitals NHS Foundation Trust, London, UK 3 Special Care Dentistry Division of Child and Public Dental Health, School of Dental Science, Trinity College Dublin, Dublin Dental University Hospital, Dublin, Ireland 4 Department of Trauma and Orthopaedics, Royal Free Hospital, London, UK 5 Mexico City, Mexico 6 Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA 7 Cape Town, South Africa 8 Department of Hemostasis Disorders and Internal Medicine, Laboratory of Hemostasis and Metabolic Diseases, Institute of Hematology and Transfusion Medicine, Warsaw, Poland 9 World Federation of Hemophilia, Montreal, QC, Canada 10 Department of Haematology, Christian Medical College, Vellore, India All statements identified as recommendations are • In general, the main treatment for bleeding episodes in consensus based, as denoted by CB. patients with severe hemophilia is prompt clotting factor replacement therapy and rehabilitation. However, different types of bleeds and bleeding at particular anatomical sites 7.1 Introduction may require more specific management with additional
    [Show full text]
  • 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.
    [Show full text]
  • Factor XIII Deficiency
    Factor XIII deficiency Information for families Great Ormond Street Hospital for Children NHS Foundation Trust 2 Factor XIII deficiency is a type of clotting disorder. A specific protein is missing from the blood so that injured blood vessels cannot heal in the usual way. This information sheet from Great Ormond Street Hospital (GOSH) explains the causes, symptoms and treatment of Factor XIII deficiency and where to get help. What is a clotting disorder? A clotting (or coagulation) disorder is a on in order. When all of the factors are turned medical condition where a specific protein on, the blood forms a clot which stops the is missing from the blood. injury site bleeding any further. Blood is made up of different types of There are a number of coagulation factors cells (red blood cells, white blood cells and circulating in the blood, lying in wait to be platelets) all suspended in a straw-coloured turned on when an injury occurs. If any one liquid called plasma. Platelets are the cells of the factors is missing from the body, the responsible for making blood clot. When complicated chemical reaction described a blood vessel is injured, platelets clump above will not happen as it should. This can together to block the injury site. They also lead to blood loss, which can be severe and start off a complicated chemical reaction to life-threatening. Each coagulation factor form a mesh made of a substance called fibrin. is given a number from I to XIII – they are This complicated chemical reaction always always written as Roman numerals – and follows a strict pattern – with each clotting the effects of the missing factor will vary.
    [Show full text]
  • The Rare Coagulation Disorders
    Treatment OF HEMOPHILIA April 2006 · No. 39 THE RARE COAGULATION DISORDERS Paula HB Bolton-Maggs Department of Haematology Manchester Royal Infirmary Manchester, United Kingdom Published by the World Federation of Hemophilia (WFH) © World Federation of Hemophilia, 2006 The WFH encourages redistribution of its publications for educational purposes by not-for-profit hemophilia organizations. In order to obtain permission to reprint, redistribute, or translate this publication, please contact the Communications Department at the address below. This publication is accessible from the World Federation of Hemophilia’s web site 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 The Treatment of Hemophilia series is intended to provide general information on the treatment and management of hemophilia. The World Federation of Hemophilia does not engage in the practice of medicine and under no circumstances recommends particular treatment for specific individuals. Dose schedules and other treatment regimes are continually revised and new side effects recognized. WFH makes no representation, express or implied, that drug doses or other treatment recommendations in this publication are correct. For these reasons it is strongly recommended that individuals seek the advice of a medical adviser and/or to consult printed instructions provided by the pharmaceutical company before administering any of the drugs referred to in this monograph. Statements and opinions expressed here do not necessarily represent the opinions, policies, or recommendations of the World Federation of Hemophilia, its Executive Committee, or its staff.
    [Show full text]
  • Neonatal Orthopaedics
    NEONATAL ORTHOPAEDICS NEONATAL ORTHOPAEDICS Second Edition N De Mazumder MBBS MS Ex-Professor and Head Department of Orthopaedics Ramakrishna Mission Seva Pratishthan Vivekananda Institute of Medical Sciences Kolkata, West Bengal, India Visiting Surgeon Department of Orthopaedics Chittaranjan Sishu Sadan Kolkata, West Bengal, India Ex-President West Bengal Orthopaedic Association (A Chapter of Indian Orthopaedic Association) Kolkata, West Bengal, India Consultant Orthopaedic Surgeon Park Children’s Centre Kolkata, West Bengal, India Foreword AK Das ® JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD. New Delhi • London • Philadelphia • Panama (021)66485438 66485457 www.ketabpezeshki.com ® Jaypee Brothers Medical Publishers (P) Ltd. Headquarters Jaypee Brothers Medical Publishers (P) Ltd. 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 Email: [email protected] Overseas Offices J.P. Medical Ltd. Jaypee-Highlights Medical Publishers Inc. Jaypee Brothers Medical Publishers Ltd. 83, Victoria Street, London City of Knowledge, Bld. 237, Clayton The Bourse SW1H 0HW (UK) Panama City, Panama 111, South Independence Mall East Phone: +44-2031708910 Phone: +507-301-0496 Suite 835, Philadelphia, PA 19106, USA Fax: +02-03-0086180 Fax: +507-301-0499 Phone: +267-519-9789 Email: [email protected] Email: [email protected] Email: [email protected] Jaypee Brothers Medical Publishers (P) Ltd. Jaypee Brothers Medical Publishers (P) Ltd. 17/1-B, Babar Road, Block-B, Shaymali Shorakhute, Kathmandu Mohammadpur, Dhaka-1207 Nepal Bangladesh Phone: +00977-9841528578 Mobile: +08801912003485 Email: [email protected] Email: [email protected] Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2013, Jaypee Brothers Medical Publishers All rights reserved. No part of this book may be reproduced in any form or by any means without the prior permission of the publisher.
    [Show full text]
  • Activated Protein C Resistance: the Most Common Risk Factor for Venous Thromboembolism
    J Am Board Fam Pract: first published as 10.3122/15572625-13-2-111 on 1 March 2000. Downloaded from CLINICAL REVIEW Activated Protein C Resistance: The Most Common Risk Factor for Venous Thromboembolism Dawn R. Sheppard, DO Background: Venous thromboembolism is a major cause of morbidity and mortality. Although activated protein C resistance (APC-R) is the most commonly recognized inherited risk factor for venous throm­ boembolism, little is known about its long-tenn implications on health. Methods: MEDLINE was searched from January 1989 through August 1999 using the key words ''thromboembolism," ''thrombosis," "activated protein C resistance," and "factor V Leiden." Results: One in 1000 people in the United States is affected by venous thromboembolism annually. APC-R is now understood to be responsible for up to 64% of these cases. APC-R, which occurs widely in some ethnic groups and is nearly absent in others, is due to a single point mutation in the gene for clot­ ting factor V. As a result, inactivation of factor V by activated protein C is impaired, leading to a hyper­ coagulable state. This condition creates a lifelong increased risk of thrombosis and, possibly, anticoag- ulant therapy.. Conclusion: Family physicians have a new tool for assessing risks for venous thromboembolism. Recognizing that up to 64% of patients with venous thromboembolism can have APe-R and treating this disorder with prophylactic and therapeutic anticoagulation might reduce patient morbidity and mortal­ ity from venous thromboembolism. Screening high-risk patients might now be indicated. (J Am Board Fam Pract 2000i13:111-5.) Venous thromboembolism, a serious health prob­ "thromboembolism," "thrombosis," "activated pro­ lem and an important cause of morbidity, affects tein C resistance," and "factor V Leiden." about 1 in 1000 persons annually.
    [Show full text]
  • I, Paul Knoebl
    Knoebl 2020-12-09 Public Declaration of Interests and Confidentiality Undertaking of European Medicines Agency (EMA), Scientific Committee members and experts Public declaration of interests I, Paul Knoebl Organisation/Company: Medical University of Vienna Country: Austria do hereby declare on my honour that, to the best of my knowledge, the only direct or indirect interests I have in the pharmaceutical industry are those listed below: 2.1 Employment No interest declared 2.2 Consultancy Period Company Products Therapeutic Indication 01/2009-(current) Novo Nordisk acquired hemophilia, congenital hemophilia, rare bleeding disorders 01/2012-02/2019 Baxalta (now Shire) thrombotic thrombocytopenic purpura purpura fulminans acquired hemophilia 01/2012-01/2016 Alexion thrombotic microangiopathy 03/2010-07/2018 Ablynx thrombotic microangiopathy 07/2018-(current) Sanofi Genzyme thrombotic microangiopathy 02/2019-(current) Takeda thrombotic microangiopathy Acquired hemophilia 2.3 Strategic advisory role No interest declared 2.4 Financial interests Classified as public by the European Medicines Agency DOI Form Version-number: 4 Knoebl 2020-12-09 2 No interest declared 2.5 Principal investigator Period Company Products Therapeutic Indication 01/2013-(current) Baxalta, then Shire, now Takeda BAX930 Upshaw Schulman Syndrome 01/2013-(current) Novo Nordisc Concizumab Hemophilia 09/2010-04/2014 Gilead Ambisome fungal infections 09/2010-04/2014 MSD Posaconazol fungal infections 03/2010-(current) Ablynx caplacizumab thrombotic thrombocytopenic purpura 04/2010-01/2012
    [Show full text]
  • Protein C and S Deficiency in Deep Vein Thrombosis Patients Referred to Iranian Blood Transfusion Organization, Kermanshah
    Protein C and S Deficiency in Deep Vein Thrombosis Patients Referred to Iranian Blood Transfusion Organization, Kermanshah Mehrdad Payandeh, 1 Mohammad Erfan Zare, 1, 2 Atefeh Nasir Kansestani, 1, 2 Kamran Ma nsouri, 1, 3 Zohreh Rahimi, 1, 4 Amir Hossein Hashemian, 5 Ebrahim Soltanian, 6 Hoshang Yousefi, 6 1Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran 2Student Research Committee, Kermanshah University of Medical Scien ces, Kermanshah, Iran 3Department of Molecular Medicine, School of advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran 4Department of Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Ir an 5Department of Biostatistics, Faculty of Public Health, Kermanshah University of Medical Sciences, Kermanshah, Iran 6Research Center of Iranian Blood Transfusion Organization, Kermanshah, Iran Corresponding Author : Mohammad Erfan Zare, BSC student of M edical Lab Sciences. Medical Biology Research Center, P.O.Box: 1568, Sorkheh Lizheh, Kermanshah University of Medical Sciences, Kermanshah, Iran. E-mail : [email protected] Tel: +98 831 4276473 Fax: +98 831 4276471 Abstract Introduction: Normal homeostas is system has several inhibitor mechanisms in front of the amplifier’s natural clotting enzyme to prevent fibrin clots in the vessels. The main inhibitors of coagulation pathway are antithrombin (AT), protein C and protein S. Patients with hereditary defic iency of coagulation inhibitors are susceptible to venous thromboembolism (VTE). One of the major clinical manifestations of VTE is deep vein thrombosis (DVT). The present study has investigated the frequency of protein C and S deficiency among DVT patients that by using of these results and results from our previous study; we determined the most important hereditary risk factors for DVT in the Kermanshah Province of Iran with the Kurdish ethnic background.
    [Show full text]
  • Familial Multiple Coagulation Factor Deficiencies
    Journal of Clinical Medicine Article Familial Multiple Coagulation Factor Deficiencies (FMCFDs) in a Large Cohort of Patients—A Single-Center Experience in Genetic Diagnosis Barbara Preisler 1,†, Behnaz Pezeshkpoor 1,† , Atanas Banchev 2 , Ronald Fischer 3, Barbara Zieger 4, Ute Scholz 5, Heiko Rühl 1, Bettina Kemkes-Matthes 6, Ursula Schmitt 7, Antje Redlich 8 , Sule Unal 9 , Hans-Jürgen Laws 10, Martin Olivieri 11 , Johannes Oldenburg 1 and Anna Pavlova 1,* 1 Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn, 53127 Bonn, Germany; [email protected] (B.P.); [email protected] (B.P.); [email protected] (H.R.); [email protected] (J.O.) 2 Department of Paediatric Haematology and Oncology, University Hospital “Tzaritza Giovanna—ISUL”, 1527 Sofia, Bulgaria; [email protected] 3 Hemophilia Care Center, SRH Kurpfalzkrankenhaus Heidelberg, 69123 Heidelberg, Germany; ronald.fi[email protected] 4 Department of Pediatrics and Adolescent Medicine, University Medical Center–University of Freiburg, 79106 Freiburg, Germany; [email protected] 5 Center of Hemostasis, MVZ Labor Leipzig, 04289 Leipzig, Germany; [email protected] 6 Hemostasis Center, Justus Liebig University Giessen, 35392 Giessen, Germany; [email protected] 7 Center of Hemostasis Berlin, 10789 Berlin-Schöneberg, Germany; [email protected] 8 Pediatric Oncology Department, Otto von Guericke University Children’s Hospital Magdeburg, 39120 Magdeburg, Germany; [email protected] 9 Division of Pediatric Hematology Ankara, Hacettepe University, 06100 Ankara, Turkey; Citation: Preisler, B.; Pezeshkpoor, [email protected] B.; Banchev, A.; Fischer, R.; Zieger, B.; 10 Department of Pediatric Oncology, Hematology and Clinical Immunology, University of Duesseldorf, Scholz, U.; Rühl, H.; Kemkes-Matthes, 40225 Duesseldorf, Germany; [email protected] B.; Schmitt, U.; Redlich, A.; et al.
    [Show full text]