DOCSLIB.ORG

Congenital Methemoglobinemia Identified by Pulse Oximetry Screening Jennifer Ward, Jayashree Motwani, Nikki Baker, Matthew Nash, Andrew K

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Congenital Methemoglobinemia Identified by Pulse Oximetry Screening Jennifer Ward, Jayashree Motwani, Nikki Baker, Matthew Nash, Andrew K Congenital Methemoglobinemia Identified by Pulse Oximetry Screening Jennifer Ward, BMBS,a Jayashree Motwani, MBBS,b Nikki Baker, MSc,a Matthew Nash, MBChB,a Andrew K. Ewer, MD,a,c Gergely Toldi, MDa Congenital methemoglobinemia is a rare condition caused by cytochrome b5 abstract reductase deficiency, cytochrome b5 deficiency, or hemoglobin M disease. Newborn pulse oximetry screening was developed for the early detection of critical congenital heart disease; however, it also enables the early identification of other hypoxemic conditions. We present the case of a term neonate who was admitted to the neonatal unit after a failed pulse oximetry screening at 3 hours of age. Oxygen saturations remained between 89% and 92% despite an increase in oxygen therapy. Chest radiograph and echocardiogram results were normal. A capillary blood gas test had normal results except for a raised methemoglobin level of 16%. Improvement was Departments of aNeonatology and bHaematology, seen on the administration of methylene blue, which also resulted in an Birmingham Women’s and Children’s Hospital, Birmingham, increase in oxygen saturations to within normal limits. Further investigation United Kingdom; and cInstitute of Metabolism and Systems Research, University of Birmingham, Birmingham, United revealed evidence of type I hereditary cytochrome b5 reductase deficiency as Kingdom a result of a CYB5R3 gene mutation with 2 pathogenic variants involving Drs Ward and Toldi were responsible for neonatal guanine-to-adenine substitutions. Although mild cyanosis is generally the care and drafted and reviewed the manuscript; Dr only symptom of type I disease, patients may later develop associated Nash and Ms Baker were responsible for neonatal symptoms, such as fatigue and shortness of breath. If an early diagnosis is care and reviewed the manuscript; Dr Motwani provided expert hematology advice and follow-up missed, these patients are likely to present later with a diagnostic conundrum and reviewed the manuscript; Dr Ewer acted as an and be subject to extensive investigation. This case represents the success of expert on newborn pulse oximetry screening and pulse oximetry screening in the early identification of subclinical hypoxemia drafted and reviewed the manuscript; and all authors approved the final manuscript as submitted. in this infant. After the exclusion of other pathologies, a routine investigation DOI: of capillary blood gas provided the information that led to a diagnosis, which https://doi.org/10.1542/peds.2018-2814 allowed for early and effective management. Accepted for publication Nov 8, 2018 Address correspondence to Gergely Toldi, MD, Neonatal Unit, Birmingham Women’s Hospital, Mindelsohn Way, Birmingham B15 2TG, United Kingdom. E-mail: [email protected] Methemoglobinemia is a rare condition cyanosis (the leading symptom) may in which there is an abnormally high present early, the diagnosis of PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). level of methemoglobin in the blood. In congenital methemoglobinemia is methemoglobin, the iron in the heme often delayed in affected children Copyright © 2019 by the American Academy of Pediatrics group is in the ferric rather than the because of a failure to recognize due FINANCIAL DISCLOSURE: ferrous state of normal hemoglobin, to its low incidence. In other cases, The authors have indicated they have no financial relationships relevant to this meaning that it cannot bind oxygen. cyanosis may be mild and clinically article to disclose. Therefore, methemoglobin is not not apparent. FUNDING: No external funding. functional in oxygen carriage. Pulse oximetry screening was POTENTIAL CONFLICT OF INTEREST: The authors have In contrast with acquired developed for the early detection of indicated they have no potential conflicts of interest methemoglobinemia caused by critical congenital heart disease and has to disclose. environmental oxidizing agents, innate become a standard screening tool for reductase deficiency resulting in neonates in several countries.4,5 To cite: Ward J, Motwani J, Baker N, et al. congenital methemoglobinemia is However, pulse oximetry also allows for Congenital Methemoglobinemia Identified by a rare condition, with only a few cases the identification of other forms of Pulse Oximetry Screening. Pediatrics. 2019; 143(3):e20182814 reported in the literature.1–3 Although hypoxemic conditions, such as Downloaded from www.aappublications.org/news by guest on September 25, 2021 PEDIATRICS Volume 143, number 3, March 2019:e20182814 CASE REPORT respiratory disease, infection, and sample was taken, revealing normal involved in converting metabolic conditions.6 results except for a raised methemoglobin to hemoglobin. It methemoglobin level of 16%. The does so by converting the ferric iron In this article, we present the case of methemoglobin level in a maternal in the heme group to ferrous iron so a term neonate who was admitted to capillary blood sample taken at the that hemoglobin can function. The the neonatal unit after a failed pulse same time was 1.1%. patient’s gene analysis revealed 2 oximetry screening. The initial pathogenic variants involving diagnosis of methemoglobinemia was Following the advice of the pediatric guanine-to-adenine substitutions. established within the first 24 hours hematology team, the patient was One of these variants has previously of life. To our knowledge, this is the given a 1 mg/kg intravenous dose of been reported in the literature as first case of congenital methylene blue, which resulted in the being pathogenic in congenital methemoglobinemia in which the methemoglobin falling to 1.1% in the methemoglobinemia type 1.8 diagnosis was facilitated by neonatal first 24 hours. This resulted in an pulse oximetry screening. improvement in oxygen saturations, The patient was discharged from the and oxygen was weaned. In addition, hospital at 2 weeks of age. She was regular ascorbic acid was commenced breastfeeding and generally well at CASE REPORT at a dose of 30 mg/kg per day orally the time of discharge. She was The patient was born postterm by divided into 4 doses. The managed after discharge and normal delivery as the third child of methemoglobin again gradually continued to have twice-weekly nonconsanguineous parents. The increased, reaching a maximum of measurements of methemoglobin delivery was uncomplicated, and there 18%, and additional doses of levels and to receive methylene blue were no risk factors for sepsis. The methylene blue were required every as required. The 2 older siblings as patient presented to the neonatal team 3 to 4 days. A limit of 10% well as both parents of the patient within 3 hours of birth after routine methemoglobin was set before giving had normal methemoglobin levels. pulse oximetry screening because both additional methylene blue. A lower preductal and postductal saturations threshold for oxygen saturations of were found to be low (right hand 92% 80% was tolerated, and oxygen was DISCUSSION and foot 94% and right hand 93% and discontinued. Standard pulse oximeters measure foot 97% on repeat). There was no Because of a raised C-reactive protein oxygen saturation by passing 2 evidence of respiratory distress, but level at 24 hours of age (maximum wavelengths of light through the because of the unexplained low 17 mg/L), the patient received 5 days tissues into a detector. By measuring saturations, the infant was screened of antibiotics; however, the blood the changes in absorbance at each for possible infection and commenced culture result was negative. wavelength, they can identify the on antibiotics. The oxygen saturations absorbance caused by hemoglobin improved to within normal limits at Hemoglobin electrophoresis revealed bound to molecular oxygen in the the time of commencing antibiotics, so a fetal hemoglobin of 71.6%, which is pulsing arterial blood. However, pulse the patient was transferred back to the normal for a newborn (range oximetry only measures the postnatal ward for routine care. After 60%–80%). Hemoglobin DNA studies percentage of bound hemoglobin, a few hours, the patient had an revealed heterozygosity for the 3.7 resulting in a false reading when additional pulse oximetry assessment kilobase single a-globin gene hemoglobin binds to something other in the postnatal ward, at which time deletion, resulting in a carrier state of than oxygen. The finding that the oxygen saturations were between a plus thalassemia, which is a benign postductal saturations were initially 89% and 92%. The infant was and common condition.7 There is no found to be higher in our patient may otherwise asymptomatic but was evidence to suggest any link between be related to this inaccuracy. Because transferred to the neonatal unit for this gene deletion and standard pulse oximeters are not low-flow nasal prong oxygen therapy methemoglobinemia, and this is an capable of differentiating between and further investigation. incidental finding. Glucose-6- different forms of bound hemoglobin, phosphate dehydrogenase revealed The oxygen saturations remained including dyshemoglobins, they do normal activity. unchanged despite oxygen therapy. not necessarily distinguish between Despite an escalation of oxygen Gene analysis was performed on the severe and mild methemoglobinemia. therapy to 100% high-flow oxygen, CYB5R3 gene from which the A noninvasive method that allows for the saturations remained between cytochrome b5 reductase enzyme is the continuous measurement of 89% and 92%. A chest radiograph transcribed. This enzyme exists
Load more

Recommended publications
  • Hemoglobinopathies: Clinical & Hematologic Features And
    Hemoglobinopathies: Clinical & Hematologic Features and Molecular Basis Abdullah Kutlar, MD Professor of Medicine Director, Sickle Cell Center Georgia Health Sciences University Types of Normal Human Hemoglobins ADULT FETAL Hb A ( 2 2) 96-98% 15-20% Hb A2 ( 2 2) 2.5-3.5% undetectable Hb F ( 2 2) < 1.0% 80-85% Embryonic Hbs: Hb Gower-1 ( 2 2) Hb Gower-2 ( 2 2) Hb Portland-1( 2 2) Hemoglobinopathies . Qualitative – Hb Variants (missense mutations) Hb S, C, E, others . Quantitative – Thalassemias Decrease or absence of production of one or more globin chains Functional Properties of Hemoglobin Variants . Increased O2 affinity . Decreased O2 affinity . Unstable variants . Methemoglobinemia Clinical Outcomes of Substitutions at Particular Sites on the Hb Molecule . On the surface: Sickle Hb . Near the Heme Pocket: Hemolytic anemia (Heinz bodies) Methemoglobinemia (cyanosis) . Interchain contacts: 1 1 contact: unstable Hbs 1 2 contact: High O2 affinity: erythrocytosis Low O2 affinity: anemia Clinically Significant Hb Variants . Altered physical/chemical properties: Hb S (deoxyhemoglobin S polymerization): sickle syndromes Hb C (crystallization): hemolytic anemia; microcytosis . Unstable Hb Variants: Congenital Heinz body hemolytic anemia (N=141) . Variants with altered Oxygen affinity High affinity variants: erythrocytosis (N=93) Low affinity variants: anemia, cyanosis (N=65) . M-Hemoglobins Methemoglobinemia, cyanosis (N=9) . Variants causing a thalassemic phenotype (N=51) -thalassemia Hb Lepore ( ) fusion Aberrant RNA processing (Hb E, Hb Knossos, Hb Malay) Hyperunstable globins (Hb Geneva, Hb Westdale, etc.) -thalassemia Chain termination mutants (Hb Constant Spring) Hyperunstable variants (Hb Quong Sze) Modified and updated from Bunn & Forget: Hemoglobin: Molecular, Genetic, and Clinical Aspects. WB Saunders, 1986.
    [Show full text]
  • The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: a Review
    Journal of Clinical Medicine Review The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review Felix Scholkmann 1,2,*, Tanja Restin 2, Marco Ferrari 3 and Valentina Quaresima 3 1 Biomedical Optics Research Laboratory, Department of Neonatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland 2 Newborn Research Zurich, Department of Neonatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; [email protected] 3 Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; [email protected] (M.F.); [email protected] (V.Q.) * Correspondence: [email protected]; Tel.: +41-4-4255-9326 Abstract: Following the outbreak of a novel coronavirus (SARS-CoV-2) associated with pneumonia in China (Corona Virus Disease 2019, COVID-19) at the end of 2019, the world is currently facing a global pandemic of infections with SARS-CoV-2 and cases of COVID-19. Since severely ill patients often show elevated methemoglobin (MetHb) and carboxyhemoglobin (COHb) concentrations in their blood as a marker of disease severity, we aimed to summarize the currently available published study results (case reports and cross-sectional studies) on MetHb and COHb concentrations in the blood of COVID-19 patients. To this end, a systematic literature research was performed. For the case of MetHb, seven publications were identified (five case reports and two cross-sectional studies), and for the case of COHb, three studies were found (two cross-sectional studies and one case report). The findings reported in the publications show that an increase in MetHb and COHb can happen in COVID-19 patients, especially in critically ill ones, and that MetHb and COHb can increase to dangerously high levels during the course of the disease in some patients.
    [Show full text]
  • Congenital Methemoglobinemia-Induced Cyanosis in Assault Victim
    Open Access Case Report DOI: 10.7759/cureus.14079 Congenital Methemoglobinemia-Induced Cyanosis in Assault Victim Atheer T. Alotaibi 1 , Abdullah A. Alhowaish 1 , Abdullah Alshahrani 2 , Dunya Alfaraj 2 1. Medicine Department, Imam Abdulrahman Bin Faisal University, Dammam, SAU 2. Emergency Department, Imam Abdulrahman Bin Faisal University, Dammam, SAU Corresponding author: Atheer T. Alotaibi , [email protected] Abstract Methemoglobinemia is a blood disorder in which there is an elevated level of methemoglobin. In contrast to normal hemoglobin, methemoglobin does not bind to oxygen, which leads to functional anemia. The signs of methemoglobinemia often overlap with other cardiovascular and pulmonary diseases, with cyanosis being the key sign of methemoglobinemia. Emergency physicians may find it challenging to diagnose cyanosis as a result of methemoglobinemia. Our patient is a healthy 28-year-old male, a heavy smoker, who presented to the emergency department with multiple minimum bruises on his body, claiming he was assaulted at work. He appeared cyanotic with an O2 saturation of 82% (normal range is 95-100%) in room air. He also mentioned that his sister complained of a similar presentation of cyanosis but was asymptomatic. All these crucial points strengthened the idea that methemoglobinemia was congenital in this patient. The case was challenging to the emergency physician, and there was significant controversy over whether the patient's hypoxia was a result of the trauma or congenital methemoglobinemia. Categories: Emergency Medicine, Trauma, Hematology Keywords: methemoglobinemia, cyanosis, hypoxia, trauma Introduction Methemoglobinemia is an important cause of cyanosis; however, clinical cyanosis is challenging in regard to forming a concrete diagnosis as causes are multiple especially in the absence of cardiopulmonary causes [1].
    [Show full text]
  • Methemoglobinemia in Patient with G6PD Deficiency and SARS-Cov-2
    RESEARCH LETTERS Methemoglobinemia in A 62-year-old Afro-Caribbean man with a medi- cal history of type 2 diabetes and hypertension came Patient with G6PD Deficiency to the hospital for a 5-day history of fever, dyspnea, and SARS-CoV-2 Infection vomiting, and diarrhea. Auscultation of his chest showed bilateral crackles. He was tachycardic, hypo- tensive, and dehydrated, with a prolonged capillary Kieran Palmer, Jonathan Dick, Winifred French, refill time and dry mucous membranes. Lajos Floro, Martin Ford Laboratory tests showed an acute kidney injury. Author affiliation: King’s College Hospital National Health Service Blood urea nitrogen was 140 mg/dL, creatinine 5.9 Foundation Trust, London, UK mg/dL (baseline 1.1 mg/dL), capillary blood glu- cose >31 mmol/L, and blood ketones 1.1 mmol/L. DOI: https://doi.org/10.3201/eid2609.202353 A chest radiograph showed bilateral infiltrates, and We report a case of intravascular hemolysis and methe- a result for a SARS-CoV-2 reverse transcription PCR moglobinemia, precipitated by severe acute respiratory specific for the RNA-dependent RNA polymerase syndrome coronavirus 2 infection, in a patient with un- gene was positive (validated by Public Health Eng- diagnosed glucose-6-phosphate dehydrogenase defi- land, London, UK). ciency. Clinicians should be aware of this complication of The patient was treated for SARS-CoV-2 pneu- coronavirus disease as a cause of error in pulse oximetry monitis and a hyperosmolar hyperglycemic state and a potential risk for drug-induced hemolysis. with crystalloid fluid, oxygen therapy, and an insulin infusion. His creatinine increased to 9.3 mg/dL, sus- oronavirus disease is a novel infectious disease pected secondary to hypovolemia and viremia, and Cthat primarily manifests as an acute respiratory acute hemodialysis was started.
    [Show full text]
  • Hereditary Spherocytosis: Clinical Features
    Title Overview: Hereditary Hematological Disorders of red cell shape. Disorders Red cell Enzyme disorders Disorders of Hemoglobin Inherited bleeding disorders- platelet disorders, coagulation factor Anthea Greenway MBBS FRACP FRCPA Visiting Associate deficiencies Division of Pediatric Hematology-Oncology Duke University Health Service Inherited Thrombophilia Hereditary Disorders of red cell Disorders of red cell shape (cytoskeleton): cytoskeleton: • Mutations of 5 proteins connect cytoskeleton of red cell to red cell membrane • Hereditary Spherocytosis- sphere – Spectrin (composed of alpha, beta heterodimers) –Ankyrin • Hereditary Elliptocytosis-ellipse, elongated forms – Pallidin (band 4.2) – Band 4.1 (protein 4.1) • Hereditary Pyropoikilocytosis-bizarre red cell forms – Band 3 protein (the anion exchanger, AE1) – RhAG (the Rh-associated glycoprotein) Normal red blood cell- discoid, with membrane flexibility Hereditary Spherocytosis: Clinical features: • Most common hereditary hemolytic disorder (red cell • Neonatal jaundice- severe (phototherapy), +/- anaemia membrane) • Hemolytic anemia- moderate in 60-75% cases • Mutations of one of 5 genes (chromosome 8) for • Severe hemolytic anaemia in 5% (AR, parents ASx) cytoskeletal proteins, overall effect is spectrin • fatigue, jaundice, dark urine deficiency, severity dependant on spectrin deficiency • SplenomegalSplenomegaly • 200-300:million births, most common in Northern • Chronic complications- growth impairment, gallstones European countries • Often follows clinical course of affected
    [Show full text]
  • Alpha Thalassemia Trait
    Alpha Thalassemia Trait Alpha Thalassemia Trait Produced by St. Jude Children’s Research Hospital, Departments of Hematology, Patient Education, 1 and Biomedical Communications. Funds were provided by St. Jude Children’s Research Hospital, ALSAC, and a grant from the Plough Foundation. This document is not intended to replace counseling by a trained health care professional or genetic counselor. Our aim is to promote active participation in your care and treatment by providing information and education. Questions about individual health concerns or specific treatment options should be discussed with your doctor. For general information on sickle cell disease and other blood disorders, please visit our Web site at www.stjude.org/sicklecell. Copyright © 2009 St. Jude Children’s Research Hospital Alpha thalassemia trait All red blood cells contain hemoglobin (HEE muh glow bin), which carries oxygen from your lungs to all parts of your body. Alpha thalassemia (thal uh SEE mee uh) trait is a condition that affects the amount of hemo- globin in the red blood cells. • Adult hemoglobin (hemoglobin A) is made of alpha and beta globins. • Normally, people have 4 genes for alpha globin with 2 genes on each chromosome (aa/aa). People with alpha thalassemia trait only have 2 genes for alpha globin, so their bodies make slightly less hemoglobin than normal. This trait was passed on from their parents, like hair color or eye color. A trait is different from a disease 2 Alpha thalassemia trait is not a disease. Normally, a trait will not make you sick. Parents who have alpha thalassemia trait can pass it on to their children.
    [Show full text]
  • Methemoglobinemia and Ascorbate Deficiency in Hemoglobin E Β Thalassemia: Metabolic and Clinical Implications
    From www.bloodjournal.org by guest on April 2, 2015. For personal use only. Plenary paper Methemoglobinemia and ascorbate deficiency in hemoglobin E ␤ thalassemia: metabolic and clinical implications Angela Allen,1,2 Christopher Fisher,1 Anuja Premawardhena,3 Dayananda Bandara,4 Ashok Perera,4 Stephen Allen,2 Timothy St Pierre,5 Nancy Olivieri,6 and David Weatherall1 1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 2College of Medicine, Swansea University, Swansea, United Kingdom; 3University of Kelaniya, Colombo, Sri Lanka; 4National Thalassaemia Centre, District Hospital, Kurunegala, Sri Lanka; 5School of Physics, University of Western Australia, Crawley, Australia; and 6Hemoglobinopathy Research, University Health Network, Toronto, ON During investigations of the phenotypic man hypoxia induction factor pathway is There was, in addition, a highly signifi- diversity of hemoglobin (Hb) E ␤ thalasse- not totally dependent on ascorbate lev- cant correlation between methemoglobin mia, a patient was encountered with per- els. A follow-up study of 45 patients with levels, splenectomy, and factors that sistently high levels of methemoglobin HbE ␤ thalassemia showed that methemo- modify the degree of globin-chain imbal- associated with a left-shift in the oxygen globin levels were significantly increased ance. Because methemoglobin levels are dissociation curve, profound ascorbate and that there was also a significant re- modified by several mechanisms and may deficiency, and clinical features of scurvy; duction in plasma ascorbate levels. Hap- play a role in both adaptation to anemia these abnormalities were corrected by toglobin levels were significantly re- and vascular damage, there is a strong treatment with vitamin C.
    [Show full text]
  • A Rare Case of Congenital Methemoglobinemia With
    Case Report asymptomatic, patient with congenital methemoglobin- illness. On examination, there was generalized dusky Discussion rather abnormal hem pigment met Hb was responsible 4. Kern K, Langevin PB, Dunn BM. Methemoglobinemia after topical 11. Akhtar J, Johnston BD, Krenzelok EP. Mind the gap. J Emerg A Rare Case of Congenital Methemoglobinemia with secondary emia are frequently clinically missed especially when it bluish skin with central and peripheral cyanosis especially for this brownish/slate skin colour.14 So, unlike venous anesthesia with lidocaine and benzocaine for a difficult Med. 2007 Aug;33(2):131-132. Congenital methemoglobinemia is a rare clinical disorder intubation. Journal of clinical anesthesia. 2000 Mar occurs in dark skinned people. Here, we report a rare apparent on lips, tongue, tip of the fingers and toes. blood which contains deoxygenated blood patients met 12. Chan ED, Chan MM, Chan MM. Pulse oximetry: understanding polycythemia- Case Report and Literature Review characterized by life-long cyanosis, caused by either 1;12(2):167-172. case of congenital methemoglobinemia presented with Patient also had congested palpebral conjunctiva. There Hb containing blood remained same. Our patient its basic principles facilitates appreciation of its limitations. inherited mutant hemoglobin (Hb-M) or due to 5. Cohen RJ, Sachs JR, Wicker DJ, Conrad ME. Methemoglobinemia Respiratory medicine. 2013 Jun 1;107(6):789-799. 1 2 3 *Ara T , Haque QS , Afrose S persistent cyanosis and polycythemia who remained was no clubbing or edema. Systemic examination demonstrated all of the classical features of congenital provoked by malarial chemoprophylaxis in Vietnam. New methemoglobin Cytochrome b5reductase enzyme gene 13.
    [Show full text]
  • Prevalence and Management of Iron Overload in Pyruvate Kinase Deficiency
    LETTERS TO THE EDITOR Helsinki. In Lancaster, Pennsylvania, USA, in which all Prevalence and management of iron overload in enrolled patients are Amish, additional laboratory and pyruvate kinase deficiency: report from the Pyruvate radiological data were collected under a site-specific IRB- Kinase Deficiency Natural History Study approved protocol. All patients gave informed consent. The NHS enrolled 278 patients with PK deficiency from Pyruvate kinase (PK) deficiency is the most common June 2014 through April 2017 at 31 centers in 6 countries. red cell glycolytic enzyme defect causing hereditary non- A detailed description of the cohort is published else- spherocytic hemolytic anemia. Current treatments are where.2 Twenty-four patients were excluded due to the mainly supportive and include red cell transfusions and inability to confirm two pathogenic PKLR mutations. splenectomy.1 Regular red cell transfusions are known to Patients under one year old at enrollment were also result in iron overload; however, the prevalence and excluded (n=12) from this analysis, because ferritin is less spectrum of transfusion-independent iron overload in the reliably related to iron overload in this youngest age overall PK-deficient population has not been well group, leaving 242 participants reported herein. Patients defined. This analysis describes the prevalence and clini- were defined as regularly transfused if they had received cal characteristics of iron overload in patients enrolled in ≥6 transfusions in the 12 months prior to enrollment. At the PK Deficiency Natural History Study (NHS) with a enrollment, 82% (198/242) of patients were not receiving focus on those patients who are not regularly transfused.2 regular transfusions; 38% (53/138) of these patients had The PK deficiency NHS protocol (clinicaltrials.gov identi- iron overload as defined by ferritin.
    [Show full text]
  • The Formation of Methemoglobin and Sulfhemoglobin During Sulfanilamide Therapy
    THE FORMATION OF METHEMOGLOBIN AND SULFHEMOGLOBIN DURING SULFANILAMIDE THERAPY J. S. Harris, H. O. Michel J Clin Invest. 1939;18(5):507-519. https://doi.org/10.1172/JCI101064. Research Article Find the latest version: https://jci.me/101064/pdf THE FORMATION OF METHEMOGLOBIN AND SULFHEMOGLOBIN DURING SULFANILAMIDE THERAPY By J. S. HARRIS AND H. 0. MICHEL (From the Departments of Pediatrics and Biochemistry, Duke University School of Medicine, Durham) (Received for publication April 8, 1939) Cyanosis almost invariably follows the admin- during the administration of sulfanilamide. Wen- istration of therapeutic amounts of sulfanilamide del (10) found spectroscopic evidence of met- (1). This cyanosis is associated with and is due hemoglobin in every blood sample containing over to a change in the color of the blood. The dark- 4 mgm. per cent sulfanilamide. Evelyn and Mal- ening of the blood is present only in the red cells loy (11) have found that all patients receiving and therefore must be ascribed to one of two sulfanilamide show methemoglobinemia, although causes, a change in the hemoglobin itself or a the intensity is usually very slight. Finally Hart- staining of the red cells with some product formed mann, Perley, and Barnett (12) found cyanosis during the metabolism of sulfanilamide. It is the associated with methemoglobinemia in almost ev- purpose of this paper to assay quantitatively the ery patient receiving over 0.1 gram sulfanilamide effect of sulfanilamide upon the first of these fac- per kilogram of body weight per day. They be- tors-that is, upon the formation of abnormal lieved that the intensity of the methemoglobinemia heme pigments.
    [Show full text]
  • The Coexistence of Polycythemia Vera and Iron Deficiency Anemia Somchai Insiripong1, Wattana Insiripong2
    CASE REPORT The Coexistence of Polycythemia Vera and Iron Deficiency Anemia Somchai Insiripong1, Wattana Insiripong2 1Department of Medicine, Saint Mary Hospital, Nakhon Ratchasima 30000, Thailand, 2Department of General Practice, NopparatRajathanee Hospital, Khanna Yao, Bangkok 10230, Thailand ABSTRACT Polycythemia vera (PV) is a clonal myeloproliferative neoplasm mainly characterized by an abnormal increase of erythroid precursor cells leading to increased red blood cells (RBC) production that is opposite to iron deficiency anemia (IDA) of which the RBC production is decreased due to iron deficiency. This report was aimed to present one patient who had coexistence of these two opposite entities of the RBC production. She was a 47-year-old Thai who was admitted because of acute coronary syndrome and she was accidentally found to have microcytosis of RBC despite normal hemoglobin (Hb) concentration, Hb 14.7 g%, mean corpuscular volume (MCV) 70.0 fL, white blood cells 12,400/mm3, and platelet 401,000/mm3. The Hb analysis showed only A2A, with normal Hb A2 percentage. The polymerase chain reaction for alpha thalassemia-1 genotype was tested negative. Due to neither alpha- nor beta-thalassemia trait detected, the iron study was performed: Serum ferritin 6.1 ng/mL, serum iron 64 ug/dl, and total iron binding capacity 198 ug/dl. The iron storage was seemingly insufficient; hence, iron supplement was started and continued for 4 months. Her blood tests showed: Hb 18.3 g%, MCV 87.2 fl, serum ferritin 31.7 ng/ml, erythropoietin <1 IU/l, positive JAK2 V617F mutation, and normal oxygen saturation. The diagnosis of PV was definitely concluded and she was finally treated with hydroxyurea and occasional phlebotomy.
    [Show full text]
  • Methemoglobinemia: Cyanosis and Street Methamphetamines
    J Am Board Fam Pract: first published as 10.3122/jabfm.10.2.137 on 1 March 1997. Downloaded from BRIEF REPORTS Methemoglobinemia: Cyanosis and Street Methamphetamines John D. Verzosa, MD Methemoglobin is a type of hemoglobin in which and she had not gotten much sleep during the last the ferrous ion has been oxidized to the ferric couple of days. state. It is therefore incapable of combining with Her medical history was notable only for mild or transporting the oxygen molecule, which is re­ asthma since childhood, and she denied any placed by a hydroxyl radical. Methemoglobin­ breathing difficulties for the past several days. emia can be acquired or inherited. Most cases are She was a mother of two boys, worked as a secre­ acquired and are primarily due to exposure to cer­ tary, and lived with her husband of several years. tain drugs and chemicals, such as nitrates, nitrites, She denied taking any medications (over-the­ quinones, and chlorates. Inherited methemoglo­ counter or prescription) or street drugs. binemia can result from a structural abnormality Upon initial examination, although she was of the globin chains, or it can occur as a result of a . awake and alert and answered questions appropri­ red blood cell enzyme defect in which the methe­ ately, she appeared dyspneic and slightly agitated. moglobin formed cannot be converted back to Her temperature, pulse, and blood pressure were the reduced form of hemoglobin. Methemoglo­ normal, but her respirations were 56/min, and a bin is normally present in the blood in concentra­ pulse oximetry reading was 88 percent on room tions of 1 to 2 percent and its formation is re­ air.
    [Show full text]