DOCSLIB.ORG

The Hematological Complications of Alcoholism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Hematological Complications of Alcoholism The Hematological Complications of Alcoholism HAROLD S. BALLARD, M.D. Alcohol has numerous adverse effects on the various types of blood cells and their functions. For example, heavy alcohol consumption can cause generalized suppression of blood cell production and the production of structurally abnormal blood cell precursors that cannot mature into functional cells. Alcoholics frequently have defective red blood cells that are destroyed prematurely, possibly resulting in anemia. Alcohol also interferes with the production and function of white blood cells, especially those that defend the body against invading bacteria. Consequently, alcoholics frequently suffer from bacterial infections. Finally, alcohol adversely affects the platelets and other components of the blood-clotting system. Heavy alcohol consumption thus may increase the drinker’s risk of suffering a stroke. KEY WORDS: adverse drug effect; AODE (alcohol and other drug effects); blood function; cell growth and differentiation; erythrocytes; leukocytes; platelets; plasma proteins; bone marrow; anemia; blood coagulation; thrombocytopenia; fibrinolysis; macrophage; monocyte; stroke; bacterial disease; literature review eople who abuse alcohol1 are at both direct and indirect. The direct in the number and function of WBC’s risk for numerous alcohol-related consequences of excessive alcohol increases the drinker’s risk of serious Pmedical complications, includ- consumption include toxic effects on infection, and impaired platelet produc- ing those affecting the blood (i.e., the the bone marrow; the blood cell pre- tion and function interfere with blood cursors; and the mature red blood blood cells as well as proteins present clotting, leading to symptoms ranging in the blood plasma) and the bone cells (RBC’s), white blood cells from a simple nosebleed to bleeding in marrow, where the blood cells are (WBC’s), and platelets. Alcohol’s produced. (For more information on indirect effects include nutritional the brain (i.e., hemorrhagic stroke). Fin- the blood’s composition and on the deficiencies that impair the production ally, alcohol-induced abnormalities in various types of blood cells and their and function of various blood cells. the plasma proteins that are required for These direct and indirect effects of production, see sidebar, pp. 50–51.) 1 alcohol can result in serious medical In this article, the terms “chronic alcohol abuse” or Alcohol’s adverse effects on the blood- “chronic excessive alcohol consumption” refer to the building, or hematopoietic, system are problems for the drinker. For example, ingestion of 1 pint or more of 80- to 90-proof alcohol anemia2 resulting from diminished (i.e., about 11 drinks) per day. However, alcohol- RBC production and impaired RBC related hematological problems can occur at much HAROLD S. BALLARD, M.D., is associate lower consumption levels. The drinker’s risk for chief of hematology and oncology at metabolism and function can cause developing these problems grows with increasing the New York Department of Veterans fatigue, shortness of breath, lighthead- alcohol consumption. Affairs Medical Center, New York, edness, and even reduced mental capac- 2For the definition of this and other technical terms New York. ity and abnormal heartbeats. A decrease used in this article, see the central glossary, pp. 93–96. 42 ALCOHOL HEALTH & RESEARCH WORLD Hematological Complications of Alcoholism blood clotting can lead to the formation of blood clots (i.e., thrombosis). This article summarizes current ALCOHOL’S EFFECTS ON IRON METABOLISM information on the consequences of excessive alcohol consumption on the In addition to interfering with the proper absorption of iron into the bone marrow and on the production hemoglobin molecules of red blood cells (RBC’s), alcohol use can lead and function of RBC’s, WBC’s, plate- to either iron deficiency or excessively high levels of iron in the body. lets, and plasma proteins. Because iron is essential to RBC functioning, iron deficiency, which is commonly caused by excessive blood loss, can result in anemia. In many alcoholic patients, blood loss and subsequent iron deficiency are caused ALCOHOL’S EFFECTS ON THE by gastrointestinal bleeding. Iron deficiency in alcoholics often is diffi- BONE MARROW AND ON RBC cult to diagnose, however, because it may be masked by symptoms of PRODUCTION other nutritional deficiencies (e.g., folic acid deficiency) or by coexisting liver disease and other alcohol-related inflammatory conditions. For an Alcohol is the most commonly used accurate diagnosis, the physician must therefore exclude folic acid drug whose consequences include the deficiency and evaluate the patient’s iron stores in the bone marrow. suppression of blood cell production, Conversely, alcohol abuse can increase iron levels in the body. For or hematopoiesis. Because its toxic example, iron absorption from the food in the gastrointestinal tract may effects are dose dependent, however, be elevated in alcoholics. Iron levels also can rise from excessive significantly impaired hematopoiesis ingestion of iron-containing alcoholic beverages, such as red wine. The usually occurs only in people with increased iron levels can cause hemochromatosis, a condition character- severe alcoholism, who also may suffer ized by the formation of iron deposits throughout the body (e.g., in the from nutritional deficiencies of folic liver, pancreas, heart, joints, and gonads). Moreover, patients whose acid and other vitamins that play a role chronic alcohol consumption and hemochromatosis have led to liver in blood cell development. Chronic cirrhosis are at increased risk for liver cancer. excessive alcohol ingestion reduces the number of blood cell precursors in the bone marrow and causes characteristic cavities (i.e., vacuoles) or characteris- tions) may induce similar structural structural abnormalities in these cells, tic iron deposits. changes in the granulocyte precursors. resulting in fewer-than-normal or non- The precise mechanism underly- functional mature blood cells. As a Development of Vacuoles in RBC ing vacuole development in blood result, alcoholics may suffer from Precursors cell precursors currently is unknown. moderate anemia, characterized by Microscopic analyses of early blood enlarged, structurally abnormal RBC’s; The most striking indication of alco- cell precursors grown in tissue cul- mildly reduced numbers of WBC’s, hol’s toxic effects on bone marrow ture suggest that when the cells are especially of neutrophils; and moder- cells is the appearance of numerous exposed to a wide range of alcohol ately to severely reduced numbers of large vacuoles in early RBC precursor concentrations, the membrane sur- platelets. Although this generalized cells. It is unknown whether these rounding each cell is damaged. These reduction in blood cell numbers (i.e., vacuoles affect the cell’s function and alterations in membrane structure may pancytopenia) usually is not progres- thus the drinker’s health; however, play an influential role in vacuole sive or fatal and is reversible with ab- their appearance generally is consid- formation. ered an indicator of excessive alcohol stinence, complex aberrations of 3 hematopoiesis can develop over time consumption. The vacuoles usually Sideroblastic Anemia that may cause death. appear in the pronormoblasts 5 to 7 Many bone marrow abnormalities days following the initiation of heavy One component of RBC’s is hemo- occurring in severe alcoholics affect alcohol consumption. Moreover, the globin, an iron-containing substance the RBC precursor cells. These abnor- vacuoles on average disappear after 3 that is essential for oxygen transport. malities most prominently include to 7 days of abstinence, although in Sometimes, however, the iron is not precursors containing fluid-filled some patients they persist for up to 2 incorporated properly into the hemo- weeks. globin molecules. Instead, it is con- 3Less commonly, vacuole development in pronor- To a lesser extent, vacuoles also verted into a storage form called moblasts also can occur after treatment with the develop in the granulocyte precursors ferritin, which can accumulate in RBC antibiotic chloramphenicol. The two conditions can of alcoholics. This finding is not precursors, often forming granules that easily be distinguished, however, because in contrast specifically alcohol related, however, encircle the cell’s nucleus. These fer- to the alcohol-induced vacuolation, chloramphenicol- induced vacuolation is accompanied by the disappear- because other events that interfere ritin-containing cells, which are called ance of virtually all later RBC precursors. with WBC production (e.g., infec- ringed sideroblasts, cannot mature VOL. 21, NO. 1, 1997 43 patients contain ringed sideroblasts ALCOHOL-RELATED RBC in their bone marrow. Alcohol may DISORDERS cause sideroblastic anemia by interfer- Alcohol-related abnormalities in RBC Liver ing with the activity of an enzyme that disease Hypersplenism mediates a critical step in hemoglobin production manifest themselves not only in the bone marrow but also synthesis. (For information on other through the presence of defective effects of alcohol on iron metabolism, Blood loss RBC’s in the blood. For example, see box, p. 43) Abstinence can reverse grossly enlarged RBC’s can occur in this effect: The ringed sideroblasts the blood—a condition called macro- generally disappear from the bone cytosis—as well as oddly shaped marrow within 5 to 10 days, and RBC RBC’s that are subject to
Load more

Recommended publications
  • Total Serum Phosphate Levels Less Than 3.0 Mg/Dl. • Mild Hypophosp
    HYPOPHOSPHATEMIA DEFINITION: Total serum phosphate levels less than 3.0 mg/dL. Mild hypophosphatemia: 2.5-3.0 mg/dL. Moderate hypophosphatemia: 1.0-2.5 mg/dL. Severe hypophosphatemia: < 1.0 mg/dL. INCIDENCE IN CRITICAL ILLNESS: Common. ETIOLOGY: Transcellular shift: Refeeding syndrome (abrupt initiation of carbohydrate causes an insulin spike, which increases cellular phosphate uptake); exogenous administration of insulin; respiratory alkalosis. Renal loss: Diuretics; osmotic diuresis in diabetic ketoacidosis; hyperparathyroidism (primary and secondary; decreases urinary resorption of phosphate); proximal renal tubular dysfunction (Fanconi’s syndrome). Insufficient intestinal absorption: Malnutrition; phosphate-binding antacids; vitamin D deficiency; chronic diarrhea; nasogastric tube suction; malabsorption. Extreme catabolic states: Burns; trauma; sepsis. CLINICAL MANIFESTATIONS: Cardiovascular: Acute left ventricular dysfunction; reversible dilated cardiomyopathy. Hematologic: Acute hemolytic anemia; leukocyte dysfunction. Neuromuscular: Diffuse skeletal muscle weakness; rhabdomyolysis; bone demineralization; acute and chronic respiratory failure secondary to diaphragmatic weakness (impaired ventilator weaning); confusion and lethargy; gait disturbance; paresthesias. TREATMENT: It is impossible to accurately predict the exact quantity of phosphate repletion required because most phosphate is intracellular. Moderate hypophosphatemia: Oral supplementation is usually adequate (provided the gastrointestinal tract is functional).
    [Show full text]
  • Predictors of Autoimmune Hemolytic Anemia in Beta-Thalassemia
    Blood Cells, Molecules and Diseases 79 (2019) 102342 Contents lists available at ScienceDirect Blood Cells, Molecules and Diseases journal homepage: www.elsevier.com/locate/bcmd Predictors of autoimmune hemolytic anemia in beta-thalassemia patients with underlying red blood cells autoantibodies T ⁎ Monia Ben Khaleda,b, , Monia Ouedernia,b, Nessrine Sahlia,b, Nawel Dhouibb, Ahmed Ben Abdelazizc, Samia Rekayaa,b, Ridha Koukia,b, Houda Kaabid, Hmida Slamad, Fethi Melloulia,b, Mohamed Bejaouia,b a Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia b Pediatric Immuno-Hematology Unit, Bone Marrow Transplantation Center Tunis, Tunis, Tunisia c Information System Directions, Sahloul University Hospital, Sousse, Tunisia d National Center of Blood Transfusion, Tunis, Tunisia ARTICLE INFO ABSTRACT Editor: Mohandas Narla In beta-thalassemia patients, erythrocyte autoantibodies can remain silent or lead to Autoimmune Hemolytic Keywords: Anemia (AIHA).The aim of this study was to identify predictors of AIHA in beta-thalassemia patients with Autoimmune hemolytic anemia positive Direct Antiglobulin Test (DAT), in Tunisia. Thalassemia This longitudinal prognosis study was carried out on beta-thalassemia patients with a positive confirmed Transfusion DAT. Predictors of AIHA were identified the Kaplan-Meier method. A Cox model analysis was used to identify Autoantibodies independent predictors. Red blood cells Among 385 beta thalassemia patients, 87 developed positive DAT (22.6%). Autoimmune hemolytic anemia Direct antiglobulin test was occurred in 25 patients. Multivariate analysis showed that AIHA was independently associated with beta- thalassemia intermedia and similar family history of AIHA. Splenectomy in patients with positive DAT was independently associated with an increased risk of AIHA (HR = 6.175, CI: 2.049–18.612, p < 0.001).
    [Show full text]
  • Pilot Study of a Nasal Airway Stent for the Treatment on Obstructive Sleep
    Diso ep rde le rs S f & o T l h a e n r r a u p Hirata and Satoh, J Sleep Disord Ther 2015, 4:4 o y Journal of Sleep Disorders & Therapy J DOI: 10.4172/2167-0277.1000207 ISSN: 2167-0277 Research Article Open Access Pilot Study of a Nasal Airway Stent for the Treatment on Obstructive Sleep Apnea Yumi Hirata1* and Makoto Satoh2,3* 1Division of Sleep Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan 2International Institute for Integrative Sleep Medicine, University of Tsukuba, Japan 3Ibaraki Prefectural Center for Sleep Medicine and Sciences, Japan *Corresponding author: Makoto Satoh and Yumi Hirata, International Institute for Integrative Sleep Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan, Tel: +81 29 853 5643, fax: +81 29 853 5643; E-mail: [email protected], [email protected] Received date: May 26, 2015, Accepted date: Jun 27 2015, Published date: Jul 05, 2015 Copyright: © 2015 Hirata Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Study background: Obstructive sleep apnea (OSA) is a common disease characterized by repetitive upper airway obstruction during sleep. OSA is associated with an increased risk of cardiovascular morbidity. Continuous positive airway pressure (CPAP) has been established as a standard therapy for OSA, but it is not always tolerated by OSA patients. Objective: In a pilot study, we evaluated the therapeutic effects of the nasal airway stent (NAS), a new nasopharyngeal device placed in the nasopharynx, on OSA and snoring.
    [Show full text]
  • Pancytopenia; Study for Clinical Features and Etiological Pattern at Tertiary Care Settings in Abbottabad
    The Professional Medical Journal www.theprofesional.com ORIGINAL PROF-2253 PANCYTOPENIA; STUDY FOR CLINICAL FEATURES AND ETIOLOGICAL PATTERN AT TERTIARY CARE SETTINGS IN ABBOTTABAD Dr. Atif Sitwat Hayat1, Dr. Abdul Haque Khan2, Dr. Ghulam Hussian Baloch3, Dr.Naila Shaikh4 1. MBBS, M.D (Medicine) Assistant Professor of Medicine, ABSTRACT... Background: Pancytopenia is an important hematological problem encountered Isra University Hospital, Hala Road in our day-to-day clinical practice. The aim of our study was to evaluate clinical features and Hyderabad, Sind, Pakistan. 2. MBBS, FCPS (Medicine) etiological pattern of pancytopenia at tertiary care settings in Abbottabad. Methods: This Associate Professor of Medicine prospective study was conducted at Northern Institue of Medical Sciences (NIMS) and Ayub Liaquat University of Medical and Health Sciences Jamshoro, Sind, Pakistan. Teaching Hospital Abbottabad from 25th August 2009 to 31st July 2010. A total of 85 patients 3. MBBS, Dip Card, M.D (Medicine) fulfilling the criteria of pancytopenia were randomly selected by time-based sampling. Associate Professor of Medicine Pancytopenia was diagnosed by anemia (hemoglobin ≤ 10.0g/dl), leucopenia (WBC ≤ 4.0×109/L) Liaquat University of Medical and 9 Health Sciences Jamshoro, Sind, Pakistan. and thrombocytopenia (platelets ≤ 150×10 /L). All data has been entered and analyzed by SPSS 4. MBBS, DCP version 10.0. Results: Out of 85 patients, 62(72.94%) were males and 23(27.05%) females with Senior Lecturer, Liaquat University of Medical and M to F ratio of 2.69:1. The mean age (±SD) of males was 30.20±15.42 years, while that of females Health Sciences Jamshoro, Sind, Pakistan.
    [Show full text]
  • Section 8: Hematology CHAPTER 47: ANEMIA
    Section 8: Hematology CHAPTER 47: ANEMIA Q.1. A 56-year-old man presents with symptoms of severe dyspnea on exertion and fatigue. His laboratory values are as follows: Hemoglobin 6.0 g/dL (normal: 12–15 g/dL) Hematocrit 18% (normal: 36%–46%) RBC count 2 million/L (normal: 4–5.2 million/L) Reticulocyte count 3% (normal: 0.5%–1.5%) Which of the following caused this man’s anemia? A. Decreased red cell production B. Increased red cell destruction C. Acute blood loss (hemorrhage) D. There is insufficient information to make a determination Answer: A. This man presents with anemia and an elevated reticulocyte count which seems to suggest a hemolytic process. His reticulocyte count, however, has not been corrected for the degree of anemia he displays. This can be done by calculating his corrected reticulocyte count ([3% × (18%/45%)] = 1.2%), which is less than 2 and thus suggestive of a hypoproliferative process (decreased red cell production). Q.2. A 25-year-old man with pancytopenia undergoes bone marrow aspiration and biopsy, which reveals profound hypocellularity and virtual absence of hematopoietic cells. Cytogenetic analysis of the bone marrow does not reveal any abnormalities. Despite red blood cell and platelet transfusions, his pancytopenia worsens. Histocompatibility testing of his only sister fails to reveal a match. What would be the most appropriate course of therapy? A. Antithymocyte globulin, cyclosporine, and prednisone B. Prednisone alone C. Supportive therapy with chronic blood and platelet transfusions only D. Methotrexate and prednisone E. Bone marrow transplant Answer: A. Although supportive care with transfusions is necessary for treating this patient with aplastic anemia, most cases are not self-limited.
    [Show full text]
  • The Nosebleed Feeling
    February 2018 Academic Emergency Medicine Editor-in-Chief Pick of the Month The Nosebleed Feeling This month, I chose a paper about nosebleeds. (May I proffer from the outset, that I am avoiding the word “picked”). I admit that the problem of bleeding noses does not generate the enthusiasm of an ED thoracotomy, nor have the public health importance of opiate use. But what if I told you that your next patient is an unhappy bounce back epistaxis on Plavix? You are thinking “B-but, the other side has open beds!” Admit it. Nosebleeds are a pain for everyone. Especially the poor patient. That sentiment is why I picked--I mean, chose--the paper by Zahed et al, and why I also asked Michael Runyon to write a commentary about this paper (Topical tranexamic acid for epistaxis in patients on antiplatelet drugs: a new use for an old drug). The work by Zahed et al, may accomplish something that few papers do, and that is prompt an actual change in practice for a few folks. At the least, this paper should get your attention for a minute. Well, maybe it won’t get your attention. Maybe you’ve never experienced the nosebleed feeling. The nosebleed feeling is the dark sensation that creeps up inside you, as you witness the world’s worst parade. The world’s worst parade is led by the triage nurse, who strolls by first, holding paperwork in hand like a baton, glancing the rueful “you are screwed” glance your way. Marching onward to room 36, on your side of course, with the sorrowful procession in tow.
    [Show full text]
  • Randomized Trial of Intravenous Iron-Induced Hypophosphatemia
    CLINICAL MEDICINE Randomized trial of intravenous iron-induced hypophosphatemia Myles Wolf,1,2 Glenn M. Chertow,3,4 Iain C. Macdougall,5 Robert Kaper,6 Julie Krop,6 and William Strauss6 1Division of Nephrology, Department of Medicine, and 2Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA. 3Division of Nephrology, Department of Medicine and 4Department of Health Research and Policy, Stanford University, Stanford, California, USA. 5Renal Unit, King’s College Hospital, London, United Kingdom. 6AMAG Pharmaceuticals, Inc., Waltham, Massachusetts, USA. BACKGROUND. Hypophosphatemia can complicate intravenous iron therapy, but no head-to-head trials compared the effects of newer intravenous iron formulations on risks and mediators of hypophosphatemia. METHODS. In a randomized, double-blinded, controlled trial of adults with iron deficiency anemia from February 2016 to January 2017, we compared rates of hypophosphatemia in response to a single FDA-approved course of ferric carboxymaltose (n = 1,000) or ferumoxytol (n = 997). To investigate pathophysiological mediators of intravenous iron-induced hypophosphatemia, we nested within the parent trial a physiological substudy (ferric carboxymaltose, n = 98; ferumoxytol, n = 87) in which we measured fibroblast growth factor 23 (FGF23), calcitriol, and parathyroid hormone (PTH) at baseline and 1, 2, and 5 weeks later. RESULTS. The incidence of hypophosphatemia was significantly higher in the ferric carboxymaltose versus the ferumoxytol group (<2.0 mg/dl, 50.8% vs. 0.9%; <1.3 mg/dl, 10.0% vs. 0.0%; P < 0.001), and hypophosphatemia persisted through the end of the 5-week study period in 29.1% of ferric carboxymaltose–treated patients versus none of the ferumoxytol-treated patients (P < 0.001).
    [Show full text]
  • Case Report Aggressive Systemic Mastocytosis in Association with Pure Red Cell Aplasia
    Hindawi Case Reports in Hematology Volume 2018, Article ID 6928571, 5 pages https://doi.org/10.1155/2018/6928571 Case Report Aggressive Systemic Mastocytosis in Association with Pure Red Cell Aplasia Dhauna Karam ,1,2 Sean Swiatkowski,1,2 Mamata Ravipati,1,2 and Bharat Agrawal1,2 1Rosalind Franklin University, 3333 Green Bay Road, North Chicago, IL 60064, USA 2Captain James A. Lovell Federal Health Care Center, 3001 Green Bay Road, North Chicago, IL 60064, USA Correspondence should be addressed to Dhauna Karam; [email protected] Received 13 March 2018; Revised 20 May 2018; Accepted 20 June 2018; Published 8 July 2018 Academic Editor: H˚akon Reikvam Copyright © 2018 Dhauna Karam et al. )is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aggressive systemic mastocytosis (ASM) is characterized by mast cell accumulation in systemic organs. )ough ASM may be associated with other hematological disorders, the association with pure red cell aplasia (PRCA) is rare and has not been reported. Pure red cell aplasia (PRCA) is a syndrome, characterized by normochromic normocytic anemia, reticulocytopenia, and severe erythroid hypoplasia. )e myeloid and megakaryocytic cell lines usually remain normal. Here, we report an unusual case of ASM, presenting in association with PRCA and the management challenges. 1. Introduction and active person; he enjoyed biking and rollerblading. )e above symptoms were very unusual for him. )e patient Aggressive systemic mastocytosis is a rare disorder char- reported intermittent episodes of epistaxis, 3-4 times a week acterized by abnormal accumulation of mast cells in bone since the past month, lasting for a few minutes.
    [Show full text]
  • Hematology Unit Lab 1 Review Material
    Hematology Unit Lab 1 Review Material Objectives Laboratory instructors: 1. Facilitate lab discussion and answer questions Students: 1. Review the introductory material below 2. Study and review the assigned cases and questions in small groups before the Lab. This includes the pathological material using Virtual Microscopy 3. Be prepared to present your cases, questions and answers to the rest of your Lab class during the Lab Erythropoiesis: The process of red blood cell (RBC) production • Characterized by: − Increasing hemoglobin synthesis Erythroid maturation stages (Below): − Decreasing cell size - Average of 4 cell divisions during maturation − Decreasing cytoplasmic basophilia [One pronormoblast gives rise to 16 red cells] (increasing pink color) - pronormoblast → reticulocyte = 7 days − Progressive chromatin condensation of the - reticulocytes → mature RBC =1-2 days nuclei − Extrusion of nucleus (orthochromatic stage) − Extruded nuclei are subsequently phagocytized − Loss of mitotic capability after the early stage of polychromatophilic normoblast • Picture below: Erythroid progenitors (normoblasts) cluster around macrophages (arrows) in the bone marrow and spleen • Macrophages store iron • Iron is transferred from macrophages to erythroid precursor cells • Iron is used by normoblasts for hemoglobin synthesis aka nucleated rbc aka reticulocyte 1 Mature Red Blood Cell 7-8 microns; round / ovoid biconcave disc with orange-red cytoplasm, no RNA, no nucleus; survives ~120 days in circulation Classification of Anemia by Morphology 1.
    [Show full text]
  • Concurrent Sickle Cell Anemia and Alpha-Thalassemia. Effect on Pathological Properties of Sickle Erythrocytes
    Concurrent sickle cell anemia and alpha-thalassemia. Effect on pathological properties of sickle erythrocytes. S H Embury, … , G Monroy, N Mohandas J Clin Invest. 1984;73(1):116-123. https://doi.org/10.1172/JCI111181. Research Article The concurrence of sickle cell anemia and alpha-thalassemia results in less severe hemolytic anemia apparently as a result of reduced intraerythrocytic concentration of hemoglobin S and its retarded polymerization. We have evaluated the effect of alpha-globin gene number on several interrelated properties of sickle erythrocytes (RBC) that are expected to correlate with the hemolytic and rheologic consequences of sickle cell disease. The irreversibly sickled cell number, proportion of very dense sickle RBC, and diminished deformability of sickle RBC each varied directly with alpha-globin gene number. Sickle RBC density was a direct function of the mean corpuscular hemoglobin concentration (MCHC). Even in nonsickle RBC, alpha-globin gene number varied directly with RBC density. Despite differences in alpha-globin gene number, sickle RBC of the same density had the same degree of deformability and dehydration. These data indicate that the fundamental effect of alpha-thalassemia is to inhibit the generation of sickle RBC having high density and MCHC, and that the other beneficial effects of sickle RBC are secondary to this process. The less consistent effect on overall clinical severity reported for subjects with this concurrence may reflect an undefined detrimental effect of alpha-thalassemia, possibly on the whole blood viscosity or on sickle RBC membrane-mediated adherence phenomena. Find the latest version: https://jci.me/111181/pdf Concurrent Sickle Cell Anemia and a-Thalassemia Effect on Pathological Properties of Sickle Erythrocytes Stephen H.
    [Show full text]
  • Vol. 81 Friday, No. 73 April 15, 2016 Pages 22173–22510
    Vol. 81 Friday, No. 73 April 15, 2016 Pages 22173–22510 OFFICE OF THE FEDERAL REGISTER VerDate Sep 11 2014 19:00 Apr 14, 2016 Jkt 238001 PO 00000 Frm 00001 Fmt 4710 Sfmt 4710 E:\FR\FM\15APWS.LOC 15APWS mstockstill on DSK4VPTVN1PROD with FEDWS II Federal Register / Vol. 81, No. 73 / Friday, April 15, 2016 The FEDERAL REGISTER (ISSN 0097–6326) is published daily, SUBSCRIPTIONS AND COPIES Monday through Friday, except official holidays, by the Office PUBLIC of the Federal Register, National Archives and Records Administration, Washington, DC 20408, under the Federal Register Subscriptions: Act (44 U.S.C. Ch. 15) and the regulations of the Administrative Paper or fiche 202–512–1800 Committee of the Federal Register (1 CFR Ch. I). The Assistance with public subscriptions 202–512–1806 Superintendent of Documents, U.S. Government Publishing Office, Washington, DC 20402 is the exclusive distributor of the official General online information 202–512–1530; 1–888–293–6498 edition. Periodicals postage is paid at Washington, DC. Single copies/back copies: The FEDERAL REGISTER provides a uniform system for making Paper or fiche 202–512–1800 available to the public regulations and legal notices issued by Assistance with public single copies 1–866–512–1800 Federal agencies. These include Presidential proclamations and (Toll-Free) Executive Orders, Federal agency documents having general FEDERAL AGENCIES applicability and legal effect, documents required to be published Subscriptions: by act of Congress, and other Federal agency documents of public interest. Assistance with Federal agency subscriptions: Documents are on file for public inspection in the Office of the Email [email protected] Federal Register the day before they are published, unless the Phone 202–741–6000 issuing agency requests earlier filing.
    [Show full text]
  • The Role of Macrophages in Erythropoiesis and Erythrophagocytosis
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Frontiers - Publisher Connector REVIEW published: 02 February 2017 doi: 10.3389/fimmu.2017.00073 From the Cradle to the Grave: The Role of Macrophages in Erythropoiesis and Erythrophagocytosis Thomas R. L. Klei†, Sanne M. Meinderts†, Timo K. van den Berg and Robin van Bruggen* Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands Erythropoiesis is a highly regulated process where sequential events ensure the proper differentiation of hematopoietic stem cells into, ultimately, red blood cells (RBCs). Macrophages in the bone marrow play an important role in hematopoiesis by providing signals that induce differentiation and proliferation of the earliest committed erythroid progenitors. Subsequent differentiation toward the erythroblast stage is accompanied by the formation of so-called erythroblastic islands where a central macrophage provides further cues to induce erythroblast differentiation, expansion, and hemoglobinization. Edited by: Robert F. Paulson, Finally, erythroblasts extrude their nuclei that are phagocytosed by macrophages Pennsylvania State University, USA whereas the reticulocytes are released into the circulation. While in circulation, RBCs Reviewed by: slowly accumulate damage that is repaired by macrophages of the spleen. Finally, after Xinjian Chen, 120 days of circulation, senescent RBCs are removed from the circulation by splenic and University of Utah, USA Reinhard Obst, liver macrophages. Macrophages are thus important for RBCs throughout their lifespan. Ludwig Maximilian University of Finally, in a range of diseases, the delicate interplay between macrophages and both Munich, Germany developing and mature RBCs is disturbed. Here, we review the current knowledge on *Correspondence: Robin van Bruggen the contribution of macrophages to erythropoiesis and erythrophagocytosis in health [email protected] and disease.
    [Show full text]