practical pediatric hematology

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Editor

Anupam Sachdeva

Associate Editor

SP Yadav

National Coordinator

National Training Project - Practical Pediatric Hematology

National Advisory Committee

SC Arya (Delhi)

VP Choudhury (Delhi)SK Sood (Delhi)

Panna Choudhury (Delhi)

MR Lokeshwar (Mumbai)

Bharat Agarwal (Mumbai)

Z Currimbhoy (Mumbai)

Mamta Manglani (Mumbai)

Rashmi Dalvi (Mumbai)

RK Marwaha (Chandigarh)

JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTDNew Delhi • Panama City • London

®

Indian Academy of Pediatrics Presidential Action Plan 2006

Pediatric Hematology–Oncology Chapter

Reference Manual

for

National Training Project

Practical

Pediatric HematologySecond Edition


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© 2012, Anupam Sachdeva

All rights reserved. No part of this book may be reproduced in any form or by any means without theprior permission of the publisher.

Inquiries for bulk sales may be solicited at: [email protected]

This book has been published in good faith that the contents provided by the contributors contained

herein are original, and is intended for educational purposes only. While every effort is made to

ensure accuracy of information, the publisher and the editors specifically disclaim any damage,

liability, or loss incurred, directly or indirectly, from the use or application of any of the contents of

this work. If not specifically stated, all figures and tables are courtesy of the editors. Where appropriate,

the readers should consult with a specialist or contact the manufacturer of the drug or device.

Practical Pediatric Hematology

First Edition: 2006

Second Edition: 2012

ISBN 978-93-5025-921-4

Printed at

®


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Indian Academy of Pediatrics

Presidential Action Plan 2006


The Executive Board of Central lAP 2005

President lAP (2005)

Raju C Shah


Nitin K Shah


MKC Nair

Vice President lAP (2005)

Anoop Kumar Verma

Secretary General

Bharat R Agarwal

Treasurer

Deepak Ugra

Editor-in-Chief, IP

Panna Choudhury

Editor-in-Chief, IJPP

A Balachandran

Joint Secretary

AK Dutta

Santosh T Soans BD Gupta D Gunasingh

P Venkateshwara Rao TM Ananda Kesavan K Meer Mustafa Hussain

V Ram Narsimha Reddy MA Mathew P Velusamy

Garima Saikia TU Sukumaran Ashok Kumar Rai

Radha Krishna Sinha MI Agnihotri Vineet K SaxenaRK Marwaha Chandra Has Sharma VN Tripathi

Ajay Gambhir KSH Chourjit Singh Debasis Biswas

Anupam Sachdeva Pramod Jog Sukanta Chatterjee

Satish V Pandya Sandeep Bapu Kadam Col MK Behera

Baldev S Prajapati Rajendra V Kulkarni Rajesh Mehta

Dinesh Khosla Yashwant Patil (President’s Sp. Rep.)

Brij Bhushan Sahni Gadadhar Sarangi Tanmay Amladi

M Govindaraj Harmesh Singh (AAA)


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Indian Academy of Pediatrics

Presidential Action Plan 2006


The Executive Board of Central lAP 2006

President lAP

Nitin K Shah

President Elect, lAP

Naveen Thacker

Immediate Past President, lAP

Raju C Shah

Secretary General, lAP

Deepak Ugra

Treasurer, lAP

Rohit C Agrawal

Editor-in-Chief, IP

Panna Choudhury

Editor-in-Chief, IJPP

A Balachandran

Joint Secretary, lAP

Bharat R Agarwal

K Umamaheswara Rao R Nisarga Prem Prakash Gupta

P Venkateshwara Rao Santosh T Soans Ashok Gupta

P Sudershan Reddy Guhan Balraj MP Jeyapaul

Arati Deka TU Sukumaran K Nedunchelian

Sachidanand Thakur MA Mathew K Chandrasekaran

Pradeep Sihare Mukesh Kumar Khare Vineet K Saxena

Sunil Gomber CP Bansal VN Tripathi

Ajay Gambhir Anand K Shandilya Mahesh Kumar Goel

Baldev S Prajapati Yashwant Patil Nabendu Choudhuri

Satish V Pandya Tanmay Amladi . Sutapa Ganguly

VN Mehendiratta Vijay Yewale Col MK Behera

Subhash Singh Slathia KSH Chourjit Singh Anupam Sachdeva

Bijay Prasad BK Bhuyan (President’s Sp Rep.)

M Govindaraj Kul Bhushan Sharda Kamlesh Shrivastava

(AAA)


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Dedicated to

The stalwarts of Pediatric Hematology

in our Country


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Contributors

Anshul Gupta MDDepartment of Pediatric Hematology and Oncologyand Bone Marrow TransplantationRajiv Gandhi Cancer Institute and Research CentreDelhi, India

Anupam SachdevaDirectorPediatric Hematology and Oncology andBone Marrow TransplantationChairman

Department of Academics andConvenor ResearchSir Ganga Ram HospitalNew Delhi, India

AP DubeyProfessor-Director and HeadDepartment of PediatricsSir Ganga Ram HospitalNew Delhi, India

Archana KumarProfessorDepartment of Pediatrics

Chhatrapati Shahuji Maharaj Medical UniversityLucknow, Uttar Pradesh, India

Arun SoniConsultant NeonatologistInstitute for Child HealthSir Ganga Ram HospitalNew Delhi, India

ATK RauPediatric Hematologist and OncologistProfessor and HeadDepartment of PediatricsMS Ramaiah Medical CollegeBengaluru, Karnataka, [email protected]

Bharat R AgarwalConsultant PediatricHeadDepartment of Hematology and OncologyBJ Wadia HospitalMumbai, Maharashtra, India

Biju George DMProfessorDepartment of HematologyChristian Medical CollegeVellore, Tamil Nadu, India

Deepak Bansal MD DNBAdditional ProfessorHematology/Oncology UnitAdvanced Pediatric CenterPostgraduate Institute of Medical Education

and Research, Chandigarh, [email protected]

Dhiren GuptaConsultant Pediatric Intensive CareUnit Institute of Child HealthSir Ganga Ram HospitalNew Delhi, India

Gauri KapoorDepartment of Pediatric Hematologyand Oncology and Bone Marrow TransplantationRajiv Gandhi Cancer Institute and Research Centre

Delhi, IndiaHimani ManchandaFellow in Pediatric Hematology and OncologyInstitute of Child HealthSir Ganga Ram HospitalNew Delhi, India

IC VermaCenter of Medical GeneticsSir Ganga Ram HospitalNew Delhi, India

Jagdish ChandraDirector, ProfessorDepartment of PediatricsLady Hardinge Medical CollegeKalawati Saran Children’s HospitalNew Delhi, India

Leni Mathew MDProfessorDepartment of PediatricsChristian Medical CollegeVellore, Tamil Nadu, India


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x Practical Pediatric Hematology

LS Arya MD DCHSenior ConsultantIndraprastha Apollo HospitalSarita ViharNew Delhi, India

Mammen Chandy MD FRACP FRCPA FRCPDirectorTata Medical CenterKolkata, West Bengal, India

MB AgarwalConsultant HematologistBombay HospitalMumbai, Maharashtra, India

Mir Sadaqat Hassan ZafarFellow in HematologySir Ganga Ram HospitalNew Delhi, India

Mohammed RamzanFellow in Pediatric Hematology and OncologyInstitute of Child HealthSir Ganga Ram HospitalNew Delhi, India

MR LokeshwarConsultant, PediatricianLilavati HospitalMumbai, Maharashtra, India

Neha RastogiFellow in Pediatric Hematology and Oncology

Institute of Child HealthSir Ganga Ram HospitalNew Delhi, India

Nirmalya Roy MoulikSenior ResidentDepartment of PediatricsChhatrapati Shahuji Maharaj Medical UniversityLucknow, Uttar Pradesh, India

Nitin K ShahConsultant PediatricianPD Hinduja Hospital, MumbaiHon. Hematologist OncologistBJ Wadia Hospital for ChildrenMumbai, Maharashtra, IndiaPresidentIndian Academy of Pediatrics, 2006FellowIndian Society of Hematology and TransfusionMedicine

Nivedita DhingraFellow in Pediatric Hematology and OncologyInstitute of Child HealthSir Ganga Ram HospitalNew Delhi, India

Panna ChoudhuryConsultant Pediatrician and PresidentIAP 2009New Delhi, India

R ParakhChairmanDivision of Peripheral Vascular andEndovascular SciencesMedanta-The MedicityGurgaon, Haryana, India

RK MarwahaProfessor of Pediatric Hematology and OncologyAdvanced Pediatric CenterPostgraduate Institute of Medical Education andResearchChandigarh, [email protected]

R SaxenaProfessor and HeadDepartment of HematologyAll India Institute of Medical SciencesNew Delhi, India

Roma Kumar

Clinical PsychologistInstitute of Child HealthSir Ganga Ram HospitalNew Delhi, India

Sachin ThakurConsultant NeonatologistUSA

Samridh NagarConsultant NeonatologistAustralia

Shirish KumarConsultant HematologistGeneva, Switzerland

Shruti PatilAssistant ProfessorDepartment of PediatricsMS Ramaiah Medical CollegeBengaluru, Karnataka, India


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From the President, IAP 2006

Dear Colleagues

Evidence-based medicine is the need of the hour. Every pediatrician strives for perfection in his or her practice.While the avenue to learn decrease after one leaves the medical school, the science keeps on evolving. It isimpossible to keep pace with what is happening in the field of pediatrics in general and hence the need to specializeis now felt even by the pediatricians. It is still some time before some centers would start providing a postgraduatediploma or degree in various pediatric subspecialties. The only avenue left for learning a specialty then is throughregular updates and seminars.

Keeping this in mind, Indian Academy of Pediatrics (IAP) has envisaged starting specialty training under itsplan of action 2006. IAP-Pediatric Hematology and Oncology (PHO) Chapter is the first to respond to the call ofIAP by starting this year the IAP PHO Training in Hematology. After the grand success of the Pediatric Oncology

training workshops, the need to start similar program in Pediatric Hematology was felt by many. This combinedwith the enthusiasm and hard work put in by Dr Anupam Sachdeva, Dr Bharat R Agarwal and their team hasresulted in this dream come true in the form of these workshops. The whole concept is well thought, well conceived,well planned and well executed. The case-based discussion while teaching the skills and the hands on experienceare two unique features of this workshop. The icing on the cake is the beautiful and picturesque manual for thedelegates to carry back home. I am sure that the manual will be a good desk companion for the delegates whilesolving the mysteries of Pediatric Hematology cases.

I am sure that the delegates will be better empowered to deal with pediatric hematology cases after attendingthe workshop. Please do give your feedback so that we can improve on the quality from time to time.

Nitin K Shah

President IAP 2006


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Preface to the Second Edition

It has been nearly six years since the first edition. There have been major advances in our knowledge. Not onlythis, a lot of new diagnostic tests are available across the country and this has made it possible for us to deal withhematological problems in a better way. During the last six years, we have held innumerable workshops andtrained a lot of pediatricians in hematology. Richer with that experience we have modified the current edition.This book now is well illustrated and has many pictures and diagrams. We hope that this will be of use not onlyto the postgraduates of pediatrics but also will be of immense use to a general pediatrician as a ready-reckonerto be kept on his desk.

Anupam SachdevaSP Yadav


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Preface to the First Edition

After the roaring success of the training project in Practical Pediatric Oncology, there was a desire in everyone ofus that we need to put together a similar course for pediatric hematology. A two-day workshop was organizedon 6th and 7th April 2002 in which experts from across the country participated and a training program wasformulated. A reference manual was to be prepared and a standard set of slides were to be made.

After a gestation of nearly three years, we bring to you the 1st edition of the Manual on Pediatric Hematology.I gratefully acknowledge the constant advice and active contribution of our President Dr Bharat R Agarwal.

I also would like to acknowledge the contribution of various experts without whose patience and work this manualwould not have been possible.

We hope that this manual and the workshops will go a long way in improving the standard of care inhematological disorders of children in our country.

I would also like to acknowledge the contribution of Dr Nitin K Shah, President IAP 2006 who has been

instrumental in giving the program a large platform by making it a part of the Presidential Action Plan 2006.I also would like to acknowledge the contribution of Dr Anil Handoo, Dr Nitin Shah, Dr MR Lokeshwar,

Dr Mamta Manglani, Dr Amita Mahajan and Dr Deepak Bansal, for parting with their clinical photographs forthe manual.

Anupam Sachdeva January 2006 Editor


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Contents

1. Interpretation of the Complete Blood Count 1Vikas Dua, Vinita Jain, SP Yadav,

Anupam SachdevaRed Cell Distribution Width 1Hematocrit 1Rule of 3s 2Blood Smear 2Role of MCV, RDW and Reticulocyte Count

in Evaluating Anemia 3Discriminant Function 6Newborn Infants 7Platelets 9White Blood Cells 10Target Cells 11Spherocytes 11Acanthocytes 11Echinocytes 12Schistocytes 12Basophilic Stippling (Aggregated Ribosomes) 12Howell-Jolly Bodies 13Siderocytes (Nonhemoglobin Iron) 13Cabot’s Rings (Nuclear Remnants) 13Polychromasia 13Nucleated RBCs 13Elliptocytes 13

Spiculated/Crenated Cells 13Bizarre Poikilocytes 13

2. Clinical Approach to a Child with Anemia 15Nitin K Shah, Himani Manchanda, MR Lokeshwar Approach to a Child with Anemia 15Is the Patient Anemic? 15Definition 15Clinical Judgment of Anemia 15How Severe is Anemia? 15What is the Type and Cause of Anemia? 16

3. Laboratory Evaluation of a Patientwith Anemia 21Ushma Singh, Shirish Kumar, SP Yadav,

Anupam SachdevaMechanisms and Pathophysiology of Anemia 21Signs of Accelerated Erythropoiesis 28Signs of Accelerated RBC Destruction 29Investigations for Hemolytic Anemia 29

4. Anemia of Prematurity 31Himani Manchanda, Sachin Thakur,Dhiren Gupta, Anupam SachdevaPathophysiology 31

Signs and Symptoms 31Evaluation 31Differential Diagnosis 32Treatment 32

5. Anemia in the Newborn 34Neha Rastogi, Anupam Sachdeva,SP Yadav, Arun SoniFetal Erythropoiesis 34Normal Hematological Values in

the Neonatal Period 34Etiology 36

Diagnostic Approach to Anemia ina Newborn 38

Treatment of Anemia in Newborn 38

6. Nutritional Anemia 41Neha Rastogi, Anupam Sachdeva,SP Yadav, Panna ChoudhuryPrevalence 41Iron Deficiency Anemia 41Iron Metabolism 42Clinical Features of IDA 43Consequences of Iron Deficiency 44Assessment of Iron Status and

Screening for Anemia 44

Treatment 46Prevention of Nutritional Anemia 47Macrocytic-Megaloblastic Anemia 49

7. National Nutritional AnemiaControl Program 53Neha Rastogi, Panna Choudhury,

Anupam SachdevaNational Nutritional Anemia Prophylaxis

Program 53Evaluation of Iron Supplementation

Program 53National Nutritional Anemia Control

Program 53

8. Aplastic Anemia: Current Issues inDiagnosis and Management 57Bharat R Agarwal, Nivedita DhingraPancytopenia in Children 57Immune Physiology of AA 57Diagnosis of AA 57Etiology of Aplastic Anemia:

Recognized Causes 59Management of Aplastic Anemia 63


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Definitive Therapy 64 Appendix 1: Practical Issues with

Immunosuppressive Therapy inAplastic Anemia 66

9. Approach to the Diagnosis of

Hemolytic Disorders 69 Mohammed Ramzan, SP Yadav, Anupam SachdevaHistory and Physical Examination 69Specific Tests to Establish the Cause of

Hemolysis 71Salient Laboratory Features of Common

Disorders Associated with HemolyticAnemia 71

10. Management of -Thalassemia Major 75 Mohammed Ramzan, SP Yadav, Anupam SachdevaTransfusion Therapy 75Splenectomy 78Folic Acid 78Chelation Therapy 78Iron Chelators 78Deferiprone (Ferripox, Kelfer, L1) Therapy 80Newer Chelating Agents 81Bone Marrow Transplantation 82Cord Blood Transplantation 82Alternative Therapies in Thalassemia 83Gene Therapy 83

11. Hemolytic Anemia (Other thanThalassemia) Management 85

MB AgarwalHereditary Hemolytic Anemias

(Intracorpuscular Defect) 85Acquired Hemolytic Anemias 87Chemical Agents 89Physical Agents 89Paroxysmal Nocturnal Hemoglobinuria 89

12. Thrombocytosis 90Vikas Dua, SP Yadav, Vinita Jain,

Anupam SachdevaNormal Upper Thrombocyte Levels in

Childhood 90Physiology of Platelet Production 90Classification 90Essential Thrombocytosis 90

Clinical Manifestations 91Treatment Options 91Reactive Thrombocytosis 92Tissue Damage 93Hypoxia 93Autoimmune Disease 94Gastrointestinal Disease without Infection 94Renal Disease 94Oncologic Disease 94Medications 94

Other Causes 94Complications 94Indications for Prophylaxis 95Primary Familial Thrombocytosis 95

13. Hemostasis: Developmental Aspects and

Rare Congenital Bleeding Disorders 97Nivedita Dhingra, SP Yadav, Anupam Sachdeva

Neonatal Hemostasis 97Intrinsic Pathway 99Extrinsic Pathway 100Common Pathway 100Protein C/Protein S Anticoagulant Pathway 100Thrombomodulin 100Antithrombin 100Fibrinolysis Pathway 100Causes of Neonatal Bleeding

(Deranged Hemostasis) 101Hemophilias A and B 101Clinical Features 102

von Willebrand Disease 102Deficiencies of the Intrinsic Pathway Contact

Activating System 102Factor XI Deficiency 103Factor X (Stuart-Prower Factor) Deficiency 104Factor V Deficiency 105Factor VII Deficiency 106Deficiencies of the Common Pathway

Prothrombin Deficiency 106Fibrinogen Deficiency 107Factor XIII Deficiency 109Congenital Factor XIII Deficiency 110Acquired Coagulation Disorders 111Vitamin K Deficiency Bleeding 112

14. von Willebrand’s Disease 115Neha Rastogi, Vinita Jain, SP Yadav,

Anupam SachdevaClinical Presentation 115Laboratory Diagnosis and Monitoring 115von Willebrand's Disease Classification 117

15. Management of Hemophilia 120Vikram MathewsProducts for Replacement Therapy 120Nonfactor Pharmacological Agents 121Management of Acute Bleeds 121Management of Chronic Complications 122

Physical Therapy and Rehabilitation 122Surgical Management 123Management of Patients with Inhibitors 123Carrier Detection and Antenatal Diagnosis 124Recent Advances 124

16. Thrombocytopenia Other than ITP andThrombasthenia 125Sunil Gomber Clinical Presentation 125


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Cryoprecipitate 193Albumin 193Immunoglobulins 194Discussion on Special Topics 194Component and Procedure Specification 195

25. Transfusion Transmitted Infections 199Deepak Bansal, RK MarwahaHepatitis B Virus 199Hepatitis C Virus 201Hepatitis D Virus 202Hepatitis A Virus 202Hepatitis E Virus 202Hepatitis GB Virus C/Hepatitis G Virus 202TT Virus 202Human Immunodeficiency Virus Types 1

and 2 (HIV1 and HIV2) 202Human T-Lymphotropic Virus I and II 203Cytomegalovirus 203Epstein-Barr Virus 204

Syphilis 204Malaria 204Creutzfeldt-Jakob Disease 205Bacterial Contamination of Blood 205Rarely Transmitted Parasites 205Inactivation of Viruses in Blood Products 205The Indian Scenario 205

26. Supportive Care in Children with Cancer 208 Mohammed Ramzan, Anupam Sachdeva,SP YadavWho Provides Supportive Care? 208Prevention and Management of Infection in

Immunocompromised Hosts 208Management 209Febrile Splenectomized Patients 210Bacterial Infections 211Fungal Infections 212Viral Infections 215Protozoan Infections 217Hematopoietic Growth Factors: Basic

Biology of Growth Factors 218Prevention of Organ Toxicity 221Pain Management 222General Guidelines for Management of

Pain in Oncology Patients 224Management of Nausea and Vomiting 225Nutritional Support 227Immunizations 229Psychosocial Support and End-of-Life Care 230

27. Hematological Manifestationsof Systemic Diseases 232Himani Manchanda, SP Yadav,

Anupam SachdevaChronic Illness 232Connective Tissue Disorders 233

Infections 233Viral Illnesses with Marked

Hematologic Sequel 235Hematologic Changes Associated with

Specific Infections in the Tropics 238Hyper-reactive Malarial Splenomegaly

Syndrome 240Clinical Features 241

28. Disseminated Intravascular Coagulation 247 Mir Sadaqat Hassan Zafar, SP Yadav,Vinita Jain, Anupam SachdevaEpidemiology 247Etiology 248Genetic Risk Factors 250Pathophysiology 250Clinical Presentation 251Laboratory Evaluation 251Diagnosis 253Differential Diagnosis 254

Scoring System 254Management (Acute Disseminated

Intravascular Coagulation) 254

29. Disorders of White Blood Cells 259 AP DubeyLeukocytosis 259Leukopenia 260Eosinophilia 260Eosinopenia 260Monocytosis 260Basophilia 260Lymphocytosis 260Lymphopenia 261

30. Hematological Changes in HIV Infection 262Nitin K ShahHematological Changes Seen in HIV 262Pathophysiology 262Anemia in HIV 262Leukopenia in HIV 263Thrombocytopenia in HIV 263Bone Marrow Changes 263Coagulation Disorders in HIV 264Hematological Malignancies in HIV 264NHL in HIV 264

31. Approach to a Patient with Splenomegalyand Lymphadenopathy 266Sunil Narain, LS Arya

32. Myelodysplastic Syndrome in Children 272Gauri Kapoor, Anshul GuptaDefinition 272Current Approach to the Classification

of Childhood MDS 272Primary and Secondary MDS 273Down’s Syndrome 273


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Plate 1

Fig. 1.1: Peripheral smear macrocytic anemia

Fig. 1.2: Peripheral smear of microcytic hypochromic

anemia

Fig. 1.3: Target cells

Fig. 1.4: Spherocytes

Fig. 1.5: Acanthocytes

Fig. 1.6: Echinocytes


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Plate 2

Fig. 1.7: Schistocytes

Fig. 1.8: Basophilic stippling

Fig. 1.9: Howell-Jolly bodies

Fig. 17.1: Typical skin manifestations in a case of ITP

(Courtesy: MR Lokeshwar)

Fig. 17.2: Mucosal bleeds in the oral cavity in ITP

(Courtesy: MR Lokeshwar)

Fig. 17.3: Peripheral blood smear showing paucity of platelets and a giant platelet (arrow)


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Plate 3

Fig. 32.1A: Dyserythropoiesis: BM

Fig. 32.1B: Dysgranulopoiesis: BM

Fig. 32.1C: Dysgranulopoiesis: PB


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Plate 4

Fig. 32.1D: Dysmegakaryopoiesis BM

Fig. 32.1E: Micromegakaryocytes BM


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1Interpretation of the

Complete Blood CountVikas Dua, Vinita Jain, SP Yadav, Anupam Sachdeva

The complete blood count (CBC) is a simple, inexpen-sive, test to order and interpret, but the results often aregiven only cursory appraisal. It tells us:1. Whether the patient is anemic2. Total leukocyte count (TLC) and differential

leukocyte count (DLC) tell us about infection

3. Whether the platelet count is low or high enough tocause bleeding or thrombosis.

There are many nuances and clues from the CBC,which help us in many clinical situations to guideadditional diagnostic evaluation. The CBC is a bargain;but its value is lost without appropriate analysis. TheCBC consists of:1. Hemoglobin concentration2. Hematocrit (packed cell volume)3. Mean corpuscular hemoglobin (MCH)4. MCH concentration (MCHC)5. Mean corpuscular volume (MCV)6. Erythrocyte count7. Leukocyte count8. Platelet count.

When a child presents with anemia, it is importantto establish whether the child has:1. Single cell line (red blood cells) involvement or2. Bi or trilineage problem (i.e. red cell, white cell, and

platelets).

A two or three cell line problem usually indicates:1. Bone marrow involvement as is seen in:

a. Aplastic anemiab. Leukemia

2. Immunologic disorder leading to destruction of

various components of blood:a. Connective tissue diseaseb. Acquired immunodeficiency syndrome (AIDS)c. Peripheral destruction of cells

i. Immunoneutropeniaii. Idiopathic thrombocytopenic purpura (ITP)

iii. Immune hemolytic anemia, singly or incombination

iv. Sequestration of cells (e.g. hypersplenism).

The automatic instruments directly measurehemoglobin, MCV, and erythrocyte count, whereasMCH, mean corpuscular hemoglobin concentration(MCHC), and hematocrit are derived from the followingformulas:

MCH = Hb (g/L)/RBC (106/dl)

MCHC = Hb (g/dl)/HCT (%)HCT = MCV (fl) × RBC (106/dl)

Hemoglobin concentration is measured by absor-bance spectrophotometry after complete lysis oferythrocytes.

RED CELL DISTRIBUTION WIDTH

The cells are made to pass singly through an electricfield or through a light source, a small resistance isgenerated, from the pulse height, the size and numberof times the resistance is generated erythrocyte numberis determined. These data can be plotted as a histogram.

In the histogram, the MCV as well as the distributionof cells that give rise to the MCV can be seen. Thismeasure of dispersion of the erythrocyte size distri-bution is called the RBC distribution width (RDW),which is the coefficient in variation of the erythrocytevolume distribution expressed as a percentage. In otherwords it is a measure of the degree of anisocytosis inthe blood.

HEMATOCRIT

The hematocrit is calculated rather than measureddirectly and this accounts for differences that occurwhen ‘spun’ and automated hematocrits are compared.

In the manual hematocrit the degree of erythrocytepacking that occurs is optimal and not complete,because small pockets of plasma are trapped in thespaces between the incompletely packed erythrocytes.The amount of plasma that is trapped is estimated tobe 3% under most conditions; however, this fraction isnot constant over the spectrum of hematocrit values andbecomes larger as the hematocrit increases. In addition,alteration in erythrocyte shape, density, and stiffness


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2 Practical Pediatric Hematology

affects the fraction of trapped plasma; for example,certain erythrocyte shapes lead to more trapping ofplasma as occurs in:1

• Spherocytes• Sickle erythrocytes

• Hypochromic cells• Reticulocytes.

RULE OF 3s

A simple rule of 3s for screening can be applied:The measured Hb concentration is three times the

RBC count, and the calculated hematocrit is three timesthe Hb level. A significant deviation means artifacts inthe value estimated2 or the RBCs are smaller or largerthan normal . For example, failure of complete cell lysiscauses interference with hemoglobin measurement. Thisoccurs in conditions that create hyperosmolar plasma(e.g. uremia). In this situation, the hematocrit and MCVare artificially elevated. Agglutination of erythrocytes,which may occur in autoimmune hemolytic anemiabecause of cold-reacting IgM antibodies, also results ina markedly increased MCV unless precautions are takento warm the blood thoroughly before analysis.3 ElevatedMCH and inaccurate hematocrit determination alsomay result. Another example is hyperleukocytosis(white blood cell count, >100,000/mm3), which cancause elevation of the Hb, hematocrit, red blood cellcount, and MCV.

BLOOD SMEAR

The examination of the blood smear can be usefulparticularly in evaluating a patient with anemia.Unfortunately, to become expert in recognizing altera-tions in blood cell morphology, blood smears must beexamined with regularity and patience. The best placeto search for properly spread erythrocytes is severalmillimeters inside the feathered edge of the smear.

Artifacts in the Blood Smear

Red Blood Cells

Erythrocyte shapes created by both artifact and disease

includes target cells, spherocytes, and stomatocytes.Artifactual spherocytes are especially common and canbe distinguished from the true spherocyte:1. They are larger than normal erythrocytes.2. The complete loss of central pallor in every cell,

unlike in true spherocytes, in which central pallorstill is present in many cells.

3. Finally, when erythrocyte morphology is trulyabnormal, the alterations in erythrocyte shape are

apparent in different areas of the same smear andon different blood smears.

Platelets and Leukocytes

Blood smear artifacts similarly can interfere with the

evaluation of platelet and leukocyte morphology.Persistent-platelet-leukocyte satellitism (resulting inspurious thrombocytopenia).

Delay in making the blood smear can adverselyaffect platelet and leukocyte:• Platelets become rounded and lose their granularity• Granulocytes may loose toxic granulation• Granulocytes may loose Dohle bodies• Nuclei become pyknotic• Cytoplasmic vacuolization also can increase.

Delay artifacts can obscure changes associated withinfection.

Importance of the Blood SmearThe blood smear can provide important informationabout erythrocyte abnormalities.

In patients with severe hemolysis:• Nucleated erythrocytes (sometimes accompanied by

granulocytosis and thrombocytosis)• Schistocytes in immune mediated hemolytic anemia

and hereditary spherocytosis• Spiculated erythrocytes• Acanthocytes (spur cells) in pyruvate kinase defi-

ciency• Poikilocytosis ‘bite’ or ‘blister’ cells in glucose-6-

phosphate dehydrogenase (G6PD) deficiency.Some Specific Shapes and Characteristics

Target Cells

Altered erythrocyte surface area, which, in driedsmears, results in the outward bulge of excess memb-rane into the region of central pallor, creating thecharacteristic target appearance.

Causes:

1. Iron deficiency2. Liver disease3. Hemoglobinopathies (hemoglobins C, D, and E)

4. Thalassemia5. Postsplenectomy state6. Hereditary xerocytosis7. Lecithin cholesterol acyl transferase deficiency

(LCAT deficiency).

Howell-Jolly Bodies

They are nuclear remnants that are not extruded frommature erythrocytes and indicate splenic hypofunction.


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Interpretation of the Complete Blood Count 3

Basophilic Stippling

It is caused by aggregated ribosomes in the erythrocyte(for ribosomal DNA and mitochodrial fragments in leadpoisonings) is seen with thalassemia and leadintoxication.

Rouleaux Formation

It occurs when plasma proteins block the negativecharge on the erythrocyte surface, and red cells stackin long columns. Stacking occurs in several clinicalconditions, especially when the erythrocyte sedimenta-tion rate is elevated and is readily distinguishable fromerythrocyte agglutination, in which erythrocyteaggregates are distorted and form clumps.

Leukocyte Abnormalities

Dohle bodies: They are bluish cytoplasmic inclusionsthat can be seen in the neutrophils from patients with:• Bacterial infection• Burns• Myelodysplasia• May-Hegglin anomaly• Pregnancy.

Alder-Reilly bodies: They are coarse, dark granules foundin the neutrophils from patients with mucopoly-saccharidosis.

Chédiak-Higashi syndrome, giant azurophilic granules arepresent in lymphocytes, whereas granulocytes containvery large irregular granules.

Hemoglobin and Hematocrit Values

Hemoglobin and hematocrit values relate to thenumber and content of erythrocytes, and when the

measured hemoglobin is depressed, that is, more thantwo standard deviations below the mean, anemiaexists.

Polycythemia

Several conditions may result in elevation of the hemo-globin or polycythemia. These conditions include:1. Primary (e.g. Polycythemia Vera)2. Secondary

a. Renal tumorsb. Posterior fossa brain tumorsc. Cyanotic heart diseased. Defects in synthesis of 2,3-diphosphoglycerate

leading to left ward shifts in the oxygen andhemoglobin dissociation curve.4,5

e. Alteration in the hemoglobin molecule thatincrease its affinity for oxygen.

Infants with hematocrit exceeding 65% are at risk fora hyperviscosity syndrome that can be accompanied byhypoglycemia and central nervous system injury.6

ROLE OF MCV, RDW AND RETICULOCYTE COUNTIN EVALUATING ANEMIA

CBC is a good way to organize one’s thinking aboutanemia. The MCV and the RDW provide a classificationof erythrocytes based on their size and size distribution7

(Table 1.1). In children, the MCV is less than in adultsand in children between the ages of 2 years and 10 years,the lower limit for MCV is approximately 70 fl + age(in years). The approximate upper limit for MCV isobtained by adding 0.6 fl per year to 84 fl beyond thefirst year of life until the upper limit of 96 fl in adultsis reached. Erythrocytes in children with anemia can be

Table 1.1: Classification of anemia based on red cell MCV and RDW

MCV Low MCV Normal MCV HighRDW–normal RDW–high RDW–normal RDW–high RDW–normal RDW–high

Thalassemia trait Iron deficiency Normal Mixed deficiency Aplastic Folate deficiency

Chronic disease -thalassemia Chr ds. Early Fe or folate Preleuk. deficiency B12 deficiency

Hb H Sickle/HbC Hemoglobinop. Immunetrait hemoglobin

Fragmentation Hereditary Myelofibrosis Coldspherocytosis agglutinins

Transfusion Sideroblasticanemia CLL*

ChemotherapyCLL, CML

Hemorrhage

*Caused by inclusion of leukocytes in the red cell volume distribution in CLL. Abbreviations: CLL: Chronic lymphocytic leukemia;CML: Chronic myelogenous leukemia; Hb: Hemoglobin; MCV: Mean corpuscular volume; RDW: Red cell distribution width


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either small, large or normal in size, the RDW can benormal or increased.

Reticulocyte Count

Each day ~0.8% of the RBC pool needs to be replaced

by young erythrocytes (reticulocytes) released from themarrow. Their number in the blood reflects themarrow’s response to peripheral anemia. In anemia dueto hemorrhage or hemolysis, erythropoietin (EPO)overdrive of the marrow results in reticulocytosis tocompensate for the peripheral RBC deficit provided themarrow’s capacity to produce RBC is intact. Reticulo-cytopenia in the presence of anemia indicates a disorderinterfering with red cell production. Thus, reticulocytecount indicates whether the primary source of anemiais the bone marrow or the periphery.

Corrected Reticulocyte Count

Reticulocyte count needs to be corrected for anemia asit is a percentage of the total RBC count and is spuriou-sly elevated when the number of RBC’s falls in anemia.Reticulocyte percentage may be increased due to:• More reticulocytes in circulation• Fewer mature cells.

Hence, “correction” for the degree of anemia has tobe done.

Patient PCV (L/L)Corrected = ________________________ × Actual reticulo-

reticulocyte (%) 0.45 cyte count

Absolute Reticulocyte Count

Retics/L = Retics (%) × RBC count[Normal: 50–100 × 109/L]

An absolute reticulocyte count >100,000/dl indicatesincreased marrow activity.

Reticulocyte Production Index (RPI)

• The percentage of reticulocytes may be increased bypremature release from the bone marrow (shift). Thedegree of “shift” is related to the intensity ofstimulation by EPO.

• Thus, maturation time of the reticulocyte (incirculation) is:

1 day if PCV = 0.45 L/L

1.5 days if PCV = 0.35 L/L

2 days if PCV = 0.25 L/L

2.5 days if PCV = 0.15 L/L

Reticulocyte (%) Patient PCV (L/L)RPI = _____________________ × __________________________

Reticulocyte 0.45maturation time

e.g. if PCV = 0.25 L/L and retics are 20%,

20 0.25RPI = ___ × ______ = 5.52 0.45

i.e. reticulocyte production has increased to 5.5 timesthe normal rate.

Increased MCV

Patients with increased erythrocyte volume may beclassified according to their corresponding reticulocytecount.

Macrocytosis and Elevated Reticulocyte Count

• Acute blood loss• Hemolysis.

Ancillary measures of erythrocyte destructioninclude:• Serum bilirubin• Lactate dehydrogenase (LDH).

Macrocytosis is caused by an increased number ofreticulocytes, which have a large cellular volume(140-150 fl) (Fig. 1.1).

Anemia with Diminished Reticulocyte Count

Bone marrow failure: The macrocytosis is caused by the

production of ‘stress’ erythrocyte, which display fetalcharacteristics, including increased fetal hemoglobincontent and expression of i antigen.8 For changescaused by stress erythropoiesis to occur, at least some

Fig. 1.1: Peripheral smear macrocytic anemia(For color version, see Plate 1)


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erythrocyte production is required, albeit at aninsufficient rate. For this reason, in patients withsevere aplastic anemia and pure red cell aplasia whenerythropoiesis is absent, the resultant anemia may benormochromic and normocytic; however, stress

erythropoiesis can be present in patients with thesedisorders with concomitant macrocytosis, makingthem difficult to distinguish from bone marrow failuresyndromes like Fanconi’s anemia and Diamond-Blackfan anemia (DBA).

Drugs are a common cause of macrocytosis:• Valproate• Zidovudine• Immunosuppressive agents.9

Diamond-Blackfan anemia: A congenital hypoplasticanemia that most commonly presents in infancy, with80% of cases occurring in the first 6 months of life.10

This disorder is usually characterized by macrocyticanemia with reticulocytopenia, although many patientsdo not have an elevated MCV initially because ofcomplete cessation of erythropoiesis. These patientsbecome macrocytic, however, if some recovery oferythropoiesis occurs. White blood cells and plateletcounts are generally normal, although the platelet countcan be elevated.11 Although most cases of DBA presentbefore 1 year of age, as many as 5% of cases are identi-fied later in life, for this reason, transient erythro-blastopenia of childhood (TEC), which in 90% of cases,occurs in children more than 1 year of age, can beconfused with DBA, TEC is a form of acquired anemia

in which an immune reaction seems to occur againsterythroid progenitor cells.12 Some patients with TECalso may experience neutropenia.13

Because TEC is accompanied by cessation of erythro-poiesis, the MCV is not increased initially; however, inthe recovery phase of TEC, which is heralded by amarked reticulocytosis, the MCV is elevated. Thisrecovery occurs within 1 to 2 months from the outset.Accordingly, expression of the i antigen and hemo-globin F production are low initially, increased duringrecovery from TEC (or following recovery from anymarrow insult), and then return to normal followingrecovery. In addition, the erythrocyte adenosinedeaminase level is increased in DBA (and other statesof stress erythropoiesis) but is generally normal inpatients with TEC.14

Other causes of macrocytic anemias are less commonin childhood. These are associated with hypersegmen-tation of polymorphonuclear leukocytes and macro-ovalocytes. Examination of the bone marrow demons-trates megaloblastic changes that are diagnostic.

The megaloblastic disorders are:1. Folate deficiency2. Vitamin B12 deficiency3. Inherited disorders of DNA metabolism (e.g.

inborn errors of folate metabolism)

4. Alcohol causes a mild macrocytic anemia due todirect toxicity15

5. Folic acid antimetabolites like methotrexateproduce pancytopenia more often thanmegaloblastic changes.

6. Other antimetabolites like trimethoprim cancause acute folate deficiency.

7. Hypothyroidism usually causes a normochromicnormocytic anemia, but macrocytosis maydevelop.

Decreased MCV

Microcytic anemias (Fig. 1.2) are caused by insufficienthemoglobin synthesis, resulting in hypochromia (cellswith an enlarged region of central pallor), target shapes,and in more severe cases, markedly deformed forms.In general, microcytosis is caused by:1. Iron deficiency2. The inability to utilize iron, as occurs in anemia of

chronic disease3. Thalassemia4. Lead poisoning5. Sideroblastic anemia.

Iron deficiency, is a common cause of microcyticanemia in children between 1 and 3 years of age. Iron

deficiency may potentiate the toxic effects of leadpoisoning; in most cases, the anemia seen with leadpoisoning is caused by iron deficiency and not leadtoxicity so that testing for lead poisoning in endemicregions may be warranted in the child with documentediron deficiency.16,17

Fig. 1.2: Peripheral smear of microcytic hypochromic

anemia (For color version, see Plate 1)


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Inherited disorders of hemoglobin synthesis alsocause microcytic anemia. Children with -thalassemiamajor present during the first 6 to 24 months of lifewith profound anemia hepatosplenomegaly, jaun-dice, and growth retardation, -thalassemia trait, the

much more common heterozygous state, may beconfused with iron deficiency. To differentiatebetween the two:• Erythrocyte count is generally higher in the child

with -thalassemia trait.• MCV is disproportionately low as compared to the

Hb level in thalassemia trait.• Free erythrocyte protoporphyrin (FEP) is elevated

in iron deficiency.

DISCRIMINANT FUNCTION

Calculation Iron deficiency -thalassemia traitMCV – (5 × Hb) >0 13 3.8 1530


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• Hyperparathyroidism may inhibit erythropoiesis bypromoting myelofibrosis.19,20

With high BUN, acanthocytosis may develop, andRBC lifespan is shortened.

The anemia of liver disease is multifactorial and

includes:• Hypersplenism• Concomitant vitamin-nutritional deficiency• Blood loss.

The characteristic spur cell in liver disease, whichis caused by an alteration in lipid composition of themembrane, is often a late and ominous development.

Mean Corpuscular Hemoglobin Concentration

The MCHC is a method for detecting erythrocyte cellu-lar dehydration.• Hereditary spherocytosis.• Patients with sickle cell anemia.

These populations of cells are not readily detectedby the Coulter electric impedence instrument but canbe seen with instruments that rely on light scattermethodology to measure erythrocyte indices.

NEWBORN INFANTS

CBC determinations are done in the newborn period for:• Infection• Jaundice• Pallor.

Method of collection becomes an important consi-deration. Blood samples can be obtained from a centralsite, via venepuncture, or central indwelling catheter(e.g. umbilical artery/vein), or pricking the skin of anextremity for collection of capillary blood. Bloodsamples collected from central sites are generally morereliable for hemoglobin determination; alternatively,capillary blood samples are much less reliable, with atendency for capillary blood to overestimate the actualcentral hemoglobin. This occurs despite higher plasmacontent in smaller blood vessels (i.e. capillaries) and asomewhat larger erythrocyte volume among oxygen-carrying red cells in capillary blood. In fact, the ratio of

hemoglobin values from capillary and central sites canbe as high as 1.2:1, with the greatest disparity occurringin infants who are most ill (e.g. premature infants andneonates with hypotension, acidosis, or markedanemia).21

Although premature infants tend to have lowerhemoglobin values because of the shorter period forhemoglobin synthesis in utero, the differences largelydisappear after 32 to 33 weeks.22 The erythrocyte size

is increased in premature infants because of the relativeabundance of larger fetal erythrocytes. The MCV atbirth declines continuously with gestational age, whichcoincides with the switch from to -globin chainsynthesis, as does the reticulocyte count.

Anemia in the Newborn

• Blood loss— Placental transfusion, in which an infant may

lose 10 to 20% of his or her blood— Fetal-maternal hemorrhage— Umbilical cord hemorrhage— Twin-twin hemorrhage— Internal hemorrhage

• Disorders of erythrocyte production and maturation(e.g. Diamond-Blackfan anemia)

• Hemolysis—Isoimmune

—Infectious processes• Hereditary disorders of hemoglobin and its

production• Disorders of the erythrocyte membrane (e.g.

hereditary spherocytosis)• Metabolism (e.g. G6PD deficiency).

Once anemia caused by blood loss has beendiagnosed in neonates, differentiation between chronicand acute blood loss is likely to have an impact onmanagement (Table 1.2).

Acute Blood Loss

• Normal MCV and MCH for age• May have a normal hemoglobin initially then

declines precipitiously23

• Clinically, present with distress, pallor, tachycardia,hypotension and no hepatosplenomegaly.

They require resuscitation with volume-expandingintravenous solutions and whole blood. After that, theyneed iron-replacement therapy in excess of thatprovided to normal neonates.

Neonates with Chronic Anemia

Caused by blood loss:

• Lowered Hb concentration• Depressed MCV• A peripheral blood smear shows hypochromic,

microcytic picture.

Clinically, these infants are:• Without distress• Hepatosplenomegaly• Signs of congestive heart failure


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• Do not require acute intervention• Transfusion of red cells is rarely necessary• Iron replacement therapy is indicated for these

infants.

At birth, the increased oxygen tension followingconversion from maternal to environmental oxygena-tion results in a rapid decline in erythropoiesis, asshown by reduction in reticulocyte count, hemoglobin,and erythroid progenitors in the bone marrow.Eventually, as the hemoglobin-oxygen dissociation

curve becomes progressively right-shifted, resultingfrom conversion of fetal to adult hemoglobin and as thehemoglobin level falls, a threshold of diminishingvenous oxygen saturation is reached. A signal in theform of increased erythrocytes creates a physiologichemoglobin nadir at 7 to 10 weeks of age in normalnewborns.

Agents that either impair erythrocyte production ordecrease red cell survival (e.g. infection, medications,or hemolysis) can lead to an earlier or lower nadir. Thisis commonly encountered in premature infants. Becauseof their smaller red cell mass, premature infants reachtheir nadir earlier than term infants and require a longer

period of time to recover, in part because of an impairederythropoietin response to tissue hypoxemia. Hemo-globin levels begin to fall by the end of the first weekof life and may take as many as 4 months to recover.Because of this blunted response, premature infants willmore likely develop symptoms related to inadequatetissue oxygen delivery and require transfusion of redcells or recombinant erythropoietin therapy.

Screening Hemoglobin at 4 to 6 Months of Age

Iron Deficiency

Collecting a hemoglobin and hematocrit value at 4 to 6months of age to screen for anemia is a prudent practiceamong pediatricians. The most common causes ofanemia in this age group are iron deficiency andintercurrent infection.24

Anemia caused by iron deficiency is a late step inthe pathophysiology of iron deficiency. First, as iron

stores become depleted, the serum ferritin concentrationdeclines and the RDW increases. Next, serum ironconcentration becomes depressed. Finally, iron defi-ciency begins to affect erythropoiesis, causing a decreasein the MCV and an increase in the free erythrocyteprotoporphyrin with accompanying anemia.

The first hematologic manifestation of irondeficiency is increase in the RDW (normal range inchildren, 11.5 to 14.5%).

This alteration may be more sensitive in screeningfor iron deficiency than serum ferritin, transferrinsaturation, or even serum iron level, some of which canbe altered by inflammation or even variation in iron

intake.25Moreover, the increased RDW may be useful in

discriminating microcytosis secondary to irondeficiency from thalassemia trait, in which the RDW isnormal.26

Although rigorous testing may be required to besure about the cause of anemia in the 4 month to 6month hemoglobin screen a reasonable approach in this

Table 1.2: Characteristics of acute and chronic blood loss in newborns

Characteristics Acute blood loss Chronic blood loss

Clinical features Acute distress; pallor ; shallow, rapid, and Marked pallor disproportionate to evidenceoften irregular resp; tachycardia; weak or of distress; on occasion signs of congestive

absent peripheral pulses; low or absent heart failure including heart failure including

blood pressure; no hepatosplenomegaly hepatomegalyVenous pressure Low Normal or elevated

Laboratory values

Hemoglobin May be normal initially; then drops Low at birthquickly during first 24 hours of life

Red cell morphology Normochromic and macrocytic Hypochr. and microcytic; aniso. andpoikilocytosis

Serum iron Normal at birth Low at birth

Course Prompt treatment of anemia and shock Generally uneventful

necessary to prevent death

Treatment Intravenous fluids and Whole blood; Fe; packed red cells may be necessary on

iron therapy later occasion


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cost-conscious era has been a trial of oral, iron replace-ment for children whose hemoglobin levels fall belowthe 10th percentile. Thus, in patients with anemiaaccompanied by an increased RDW and a supportivehistory who respond to a trial of iron (defined as an

increase of 1.5-2.0 g/dl in the hemoglobin after 1months of therapy), a presumptive diagnosis of irondeficiency anemia usually can be made.

Although iron deficiency is common in children 9months to 3 years of age and in teenage girls, irondeficiency anemia in children more than 3 years of agegenerally should prompt consideration of dietaryhistory and occult blood loss.

PLATELETS

Alterations in platelet numbers and platelet size canprovide important clues to disease processes. Plateletsize is often determined from review of the peripheralsmear, but mean platelet volume also can be derivedby the coulter counter. Mean platelet volume (MPV) asdetermined by automated electronic counters; isnormally between 8.9±1.5 fl.

In general, platelets tend to be larger when there isperipheral destruction, e.g. immune mediated or on amechanical basis, and normal to small in size whenproduction defects are present. In Wiskott-Aldrichsyndrome, platelets are about half of normal size andlook like dust particles. Large platelets are generallythought to be young which in part may be true, butincreased mean platelet volume and large platelets also

may be a reflection of stimulated thrombopoiesis.

Macrothrombocytes (MPV Raised)

• ITP or any condition with increased plateletturnover (e.g. DIC)

• Bernard-Soulier syndrome• May Hegglin anomaly and other MYH-9–related

diseases• Swiss cheese platelet syndrome• Montreal platelet syndrome• Gray platelet syndrome• Various mucopolysaccharidosis.

Normal Size (MPV Normal)

Conditions in which marrow is hypocellular orinfiltrated with malignant diseases.

Microthrombocytes (MPV Decreased)

• Wiskott-Aldrich syndrome• TAR syndrome

• Some storage pool diseases• Iron-deficiency anemia.

The normal lifespan of platelets is 7 to 10 days.Approximately one-third of the body platelets arelocated in the spleen and two-thirds in the circulation.

Practitioners most often are interested in qualitativeaspects of platelets as well as quantitative. The CBCcannot answer functional questions, but the significanceof thrombocytopenia and thrombocytosis can beclarified. There is a wide range of normal plateletcounts, but thrombocytopenia generally is defined as aplatelet count of less than 1.5 lac/mm 3 and throm-bocytosis as values between 600,000/mm3 an d1,000,000/mm3 or more.

Thrombocytosis

Thrombocytosis in childhood rarely causes complica-

tions, although it is frequently a cause for concern.

Causes

• Primary— Polycythemia vera— Essential thrombocythemia, are unusual but

have better outcome in children27

• Reactive— Iron deficiency anemia— Hemolytic anemia— Vitamin E deficiency— Hemorrhage— Collagen vascular disorder— Kawasaki syndrome (usually 2-3 weeks into the

illness)— Nephrotic syndrome— Inflammatory bowel disease— Postsplenectomy— Postoperative state— Trauma— Various tumors— Myeloproliferative syndromes— Histiocytoses— Various drugs

– Epinephrine

– Corticosteroids– Vinca alkaloids28

Because no apparent sequelae exist to reactivethrombocytosis, antiplatelet therapy is rarely indicated(Kawasaki syndrome is a notable exception). Plateletmorphology is usually normal, as is the bleeding time.Splenomegaly is absent unless caused by the underlyingdisorder, and the duration is transitory, usuallymeasured in days to weeks.


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Thrombocytopenia

When thrombocytopenia is reported, the most commoncause is immune platelet destruction, but falsely lowplatelet counts may occur when inadequate anticoagu-lation of the blood-sample results in platelet clumping.

The precision of platelet counting by automatedinstruments is reduced in the severe thrombocytopeniarange (platelets fewer than 20,000/mm3) because lossof measurement linearity occurs. Thrombocytopenia isassociated with a wide range of infections and otherconditions. The major issues confronting practitionersare the risk of life-threatening bleeding and the possi-bility of a serious underlying condition. Isolated throm-bocytopenia without other hematologic abnormalitiesin an otherwise healthy appearing child withoutlymphadenopathy or hepatosplenomegaly almost neveris associated with childhood acute leukemia. In suchcases, idiopathic thrombocytopenia purpura (ITP) isusually the correct diagnosis. Intracranial hemorrhageoccurs only rarely in children with ITP.29

WHITE BLOOD CELLS

The total and differential white blood cell count is oftenrequested without much thought, but it can be a clueto underlying disorders. Its usefulness as a screeningtest is not great because both sensitivity and specificityare low; however, the reliability and low cost justifiesthese tests as part of the complete blood count althoughabnormalities and definitive characterizations stillrequire examination of the peripheral smear. Practi-

tioners generally are interested in the total anddifferential white blood cell count as clues to underlyinginfection. Interpretation of white count numbers isaided by the clinical context:• The age of the patient• The temperature• General appearance• Underlying conditions.

The white blood cell response to infection can behighly variable, the younger the patient and the higherthe temperature, the more one becomes suspicious if thewhite blood cell count is either above or below the

normal range.Leukopenia is associated with a wide variety of viraland bacterial infections:• Viral illness• Epstein-Barr virus• Hepatitis A and B• Respiratory syncytial virus• Rubella.

Changes usually are noted within 1 to 2 days ofinfection and often can persist for several weeks. If theclinical situation warrants, consideration should begiven to:• Salmonella

• Staphylococcal• Mycobacterial infections.

Neutropenia (neutrophil count 20,000 25%>30,000 40%30

Attention should also be paid to the band countwhen appreciable numbers of bands and moreimmature forms are present in the peripheral blood itis generally referred to as a left shift. Instead of usingthis term, considering the absolute number of bandforms may be more useful.

Beyond the neonatal period >500 bands/mm3

is anindication of infection regardless of the absolute whiteblood cell count. Although an increase in band formsclassically has been thought to be associated withbacterial infections, a recent study of children withproven viral infections (e.g. influenza, enterovirus,respiratory syncytial virus, and rotavirus) showedsignificant elevations in absolute numbers of band


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forms. Further, if toxic granules (larger than normalgranules that stain intensely), vacuolization, or Dohlebodies are reported on the peripheral smear, possiblebacterial infection also should be suspected. In the end,no substitute exists for astute clinical judgment coupled

with judicious interpretation of laboratory tests,especially when trying to differentiate a viral frombacterial process.

Monocytes are the second line of defense againstinfection. Monocytosis often is associated withmonocytic leukemia, ulcerative colitis, viral diseasessuch as mononucleosis and herpes zoster, parasiticdiseases such as rocky mountain spotted fever.Monopenia is seen in some forms of leukemia, bonemarrow failure or suppression.

Eosinophilia often is associated with rashes,wheezes, and unusual diseases. Common examples ofdiseases are parasitic infections. Eosinophilia also is

associated with drug hypersensitivity, asthma, cow’smilk allergy, hay fever, urticaria, eczema, other skindisorders, job syndrome, and malignancy. Eosinopeniais associated with corticosteroid therapy, adrenocorticalhyperfunction, stress, shock.

Lymphocytosis most often is associated with viralinfections, including infectious mononucleosis,cytomegalovirus, rubella, mumps, and hepatitis. Whiteblood cell counts of more than 30,000/mm3 with 60 to70% lymphocytes, especially if they are described asclefted or baby bottom may be caused by pertusis.Lymphopenia is associated with corticosteroid therapy,adrenocortical hyperfunction, stress, shock.

Basophilia most often is associated with chronicinflammatory and hypersensitivity reaction. Basopeniais seen with corticosteroid therapy, adrenocorticalhyperfunction, stress and shock.

Distinguishing leukemoid from leukoerythroblasticreactions is important. In leukoerythroblastic reactions,nucleated red blood cells and immature white bloodcells are found in a setting of underlying leukemia,myelophthisis, severe bleeding, or hemolysis. Leuke-moid reactions, on the other hand, are elevations in thewhite blood cell count, in excess of 50,000/mm3,sometimes leading to confusion with leukemia. Thereare many causes of leukemoid reactions, which can beeither myeloid or lymphoid.

Heinz Bodies (denatured/aggregated hemoglobin)• Normal newborn• Thalassemia syndromes• Unstable hemoglobins• HMP shunt abnormalities (G6PD deficiency)• Asplenia.

TARGET CELLS (FIG. 1.3)

Increased surface/volume ratio:• Thalassemia• Hemoglobinopathies

— Hb AC or CC— Hb SS, SC, S-Thalassemia

• Obstructive liver disease• Postsplenectomy or hyposplenic states• Severe iron deficiency• Hb E (heterozygote and homozygote)• LCAT deficiency• Abetalipoproteinemia.

SPHEROCYTES (FIG. 1.4)

Decreased surface/volume ratio, hyperdense (>MCHC)• Hereditary spherocytosis• ABO incompatibility• Autoimmune hemolytic anemia• Microangiopathic hemolytic anemia• SS disease• Hypersplenism• Burns• Severe hypophasphatemia• Post-transfusion

• Pyruvate kinase deficiency• Water dilution hemolysis.

ACANTHOCYTES (FIG. 1.5)

• Liver disease• Disseminated intravascular coagulation• Postsplenectomy or hyposplenic disorder• Vitamin E deficiency

Fig. 1.3: Target cells (For color version, see Plate 1)


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• Hypothyroidism• Abetalipoproteinemia• Malabsorption states.

ECHINOCYTES (FIG. 1.6)

• Artifact• Uremia• Dehydration• Liver disease• Pyruvate kinase deficiency

• Peptic ulcer disease or gastric carcinoma• After blood transfusion.

SCHISTOCYTES (FIG. 1.7)

• DIC• Severe hemolytic anemia• Microangiopathic hemolytic anemia• HUS

• Prosthetic cardiac valves• Connective tissue disorders• Kasabach-Merritt syndrome• Purpura fulminans• Renal vein thrombosis• Burns• Thrombotic thrombocytopenic purpura• Uremia• Malignant hypertension• Systemic amyloidosis

• Liver cirrhosis• Disseminated carcinomatosis.

BASOPHILIC STIPPLING(AGGREGATED RIBOSOMES) (FIG. 1.8)

• Hemolytic anemia, thalassemias, unstable hemoglo-bins

• Ineffective erythropoiesis

Fig. 1.4: Spherocytes (For color version, see Plate 1)

Fig. 1.5: Acanthocytes (For color version, see Plate 1)

Fig. 1.6: Echinocytes (For color version, see Plate 1)

Fig. 1.7: Schistocytes (For color version, see Plate 2)


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• Lead poisoning• Pyrimidine 5’-nucleotidase deficiency• Iron deficiency anemia.

HOWELL-JOLLY BODIES (FIG. 1.9)

• Postsplenectomy• Newborn• Megaloblastic anemia• Dyserythropoietic.

SIDEROCYTES (NONHEMOGLOBIN IRON)

• Postsplenectomy

• Chronic infection• Aplastic anemia• Hemolytic anemias.

Fig. 1.8: Basophilic stippling (For color version, see Plate 2)

Fig. 1.9: Howell-Jolly bodies (For color version, see Plate 2)

CABOT’S RINGS (NUCLEAR REMNANTS)

• Hemolytic anemias• Pernicious anemia• Lead poisoning.

POLYCHROMASIA

• Reticulocytosis• Hemolytic anemia• Acute hemorrhage• Response to ‘hematinics’ in nutritional anemia.

NUCLEATED RBCs

• Normal in neonates (first few days)• Hemolytic anemia• Acute hemorrhage.

ELLIPTOCYTES

• Hereditary elliptocytosis• Hypochromic microcytic anemias• Thalassemias.

SPICULATED/CRENATED CELLS

• Acute hepatic necrosis• Uremia• Abetalipoproteinemia• Transiently after massive transfusion of stored blood.

BIZARRE POIKILOCYTES

• Red cell fragmentation syndromes (Microangio-

pathic hemolytic anemias)• Acute oxidant injury• Hereditary elliptocytosis in neonates.

Differentiation of Beta-Thalassemia Traitfrom Iron Deficiency

Beta-thalassemia IDA

trait

Hb concentration D/N D/N

Hematocrit D/N D/NRBC I D

MCV D D/N

MCH D DMCHC N DS. Iron N D

TIBC N I

% TS N D

Serum ferritin N DFree erythrocyte N I

proporphyrinHbA2 l N/D

Abbreviations: D: Decreased; N: Normal; I: Increased


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10. Alter BP. Childhood red cell aplasia. Am J Pediatr HematolOncol. 1980;2:121.

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15. McCurdy P, Rath C. Vacuolated nucleated bone marrowcells in alcoholism. Semin Hematol. 1980;17:100.

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lead poisoning with the FEP test. Pediatr Res. 1973;7:350.18. Blumberg A. Pathogenesis of anemia due to kidney disease.

Nephron. 1989;51(suppl):15.19. Caro J, Erslev AJ. Uremic inhibitors of erythropoiesis. Semin

Nephrol. 1985;5:128.20. Klahr S, Slatopolsky E. Toxicity of parathyroid hormone

in uremia. Ann Rev Med. 1986;37:71.21. Linderkamp O, Vesmold HT, et al. Capillary-venous

hematocrit differences in newborn infants. I. Relationshipto blood volume, peripheral blood flow, and acid-baseparameters. Eur J Pediatr. 1977;127:9.

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Oski FA (Eds). Hematology of Infancy and Childhood,4th edn. Philadelphia, WB Saunders; 1993. pp. 18-43.

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25. Patton WW, Cave RJ, Harris RI. A study of changes in redcell volume and hemoglobin concentration duringphlebtomy induced iron deficiency and iron repletion usingthe Technicon H1. Clin Lab Haematol. 1991;13:153-61.

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2Clinical Approach toa Child with Anemia

Nitin K Shah, Himani Manchanda, MR Lokeshwar

INTRODUCTION

Anemia is a global problem of immense health signi-ficance affecting persons of all ages and economicgroups. It is ranked as the most common chronicmalady mankind has ever suffered. Approximately1500 million people, i.e. 30% of the world populationsuffers from iron deficiency state. It is more commonin developing countries like ours. 30-50% of pregnantladies and 60-80% of school going children are reportedin some studies to be iron deficient.

APPROACH TO A CHILD WITH ANEMIA

When confronted with a case of anemia, one should tryto answer following questions:a. Is the patient anemic?b. How severely is he/she affected?c. What is the cause and type of anemia?d. What treatment should he/she be offered?

IS THE PATIENT ANEMIC?

There are two points to be noted. One is the cut offvalues of Hb and blood indices appropriate for age. Theother point is reliability of signs and symptoms,especially presence or absence of pallor as a marker ofanemia.

DEFINITION

Anemia is generally defined as a reduction in the O2carrying capacity leading to tissue hypoxia. Ideally it

is the ‘functional anemia’ at the tissue level which ismore important, as is very well demonstrated in caseof congenital cyanotic heart disease. However, there isno good marker of ‘functional anemia’ and hence onehas to rely on values of red cell mass or hemoglobinlevels to define anemia. Age appropriate cut off levelsof Hb and blood indices are shown in Chapter onLaboratory Evaluation of Anemia (Chapter 3). It isclearly seen that a child with Hb of 10 g% will be labeled

as severely anemic if he is a neonate, mildly anemic ifhe is an infant and mild to moderately anemic if he isan adolescent. Hence, age appropriate cut off levels arevery important to interpret the CBC report.

CLINICAL JUDGMENT OF ANEMIA

The common symptoms and signs of anemia are pallor,tiredness, lassitude, easy fatiguability, weakness, lackof concentration, breathlessness, puffiness, edema feet,etc. However, these symptoms are also seen in othersystemic illnesses like respiratory illness, cardiovasculardiseases, congestive cardiac failure, renal disease,myxedema, etc.

Pallor is a common sign of anemia. However, allcases of anemia do not have pallor, especially mild casesof anemia. Icterus, cyanosis or dilatation of peripheralblood vessels, like in inflammation, may mask pallor.Similarly, pallor can also be seen in non-anemicconditions as color of the skin not only depends on the

Hb content, but on the state of blood vessels of the skin,presence of edema, skin pigmentation and skinthickness. Hence, pallor can be seen in nephroticsyndrome or myxedema even in absence of anemia and,it is always prudent to rely on Hb or HCT estimationto detect anemia.

HOW SEVERE IS THE ANEMIA?

It is important to quickly assess the patient’s clinicalcondition. If the patient is severely pale and sicklooking, breathless, has tachycardia, raised JVP andtender hepatomegaly, it is suggestive of congestive

cardiac failure (CCF). Such a patient needs immediateattention and prompt treatment including diuretics,restricted fluids, oxygen support and packed cell trans-fusion. One should not waste time in lengthy diagnostictests and do as minimum tests as required. Evenremoving too much blood for various tests can behazardous as it can precipitate cardiac failure. Insteadone can arrange for packed cell transfusion and removeblood for various tests just before starting transfusion.


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If the patient is pale but comfortable and not sick,there is neither need to give packed cell transfusion norstart ‘gunshot’ therapy without proper investigationsand establishing the diagnosis. Remember, the clinicalcondition of the patient depends not only on the

severity of anemia but also on the rate of drop of Hb.A child with 5 g% Hb, when it develops slowly like iniron deficiency, may be comfortable and come walkingto your clinic whereas, if it deveops acutely dueto G6PD deficiency, the child may be brought in acollapsed state.

WHAT IS THE TYPE AND CAUSE OF ANEMIA?

Anemia can be classified in two ways. One is theetiological classification, based on the disturbance oferythropoiesis, which makes it easy to understand whyanemia develops in a case. Other is the morphologicalclassification based on the objective and the subjectivefindings of red cell size and indices, which helps us toarrive at a diagnosis. Both these are not mutuallyexclusive and are often used together to come to aconclusion as to the cause of anemia.

In normal subjects the average lifespan of red cell is120 days. These cells are destroyed everyday as theygrow old. The aged cells are removed from the circula-tion by the reticuloendothelial cells, principally in thewalls of sinusoids of RE system like liver and spleenwhere the flow of blood is slow. The cells destroyedeveryday are replaced by new cells released from bonemarrow with the result that red cell population will

consist of cells which are 1 day old to 120 days old.Approximately, 1% or so of red cells are turned overeveryday. Any disruption of this balance will lead toanemia which can occur due to decreased production,increased destruction or due to blood loss. Theetiological classification is given in Table 2.1 andmorphological classification is given in Table 2.2.

Approach to Establishing Diagnosis

Approach to an anemic patient includes:a. Detailed historyb. Thorough physical examinationc. Screening laboratory testsd. Confirmatory laboratory tests.

History taking: Following factors are important inhistory while evaluating a case of anemia. At times, itmay give clinching clue to establish diagnosis.a. Age of onset: Nutritional anemia is not seen at birth.

The commonest causes of anemia in a newborninclude hemolysis and hemorrhage. Hemolysismay be due to ABO, Rh incompatibility. Rarely

Table 2.1: Etiological classification of anemia

A. Decreased effective production

• Nutritional deficiency, e.g. deficiency of iron, folate,

vitamin B12, protien, zinc, copper.• Bone marrow failure, e.g. aplastic anemia, constitutional

hypoplastic anemia, pure red cell aplasia.

• Bone marrow inf i ltration, e .g. malignancies l ike

leukemia, lymphoma, osteopetrosis, myelofibrosis.• Impaired erythropoietin production, e.g. renal disease,

prematurity, hypothyroidism, hypopituitarism, chronic

inflammation, protein malnutrition, hemoglobin

mutants with decreased affinity for oxygen.• Ineffective erythropoiesis, e.g. Thalassemia, sidero-

blastic anemia, lead poisoning, primary dyserythro-

poietic anemia, erythropoietic protoporphyria,

megaloblastic anemia.B. Increased destruction (Hemolytic anemia)

• Extracorpuscular causes (usually acquired except PNH)

1. Mechanical, e.g. prosthetic valve, DIC, HUS, cardiac

bypass.

2. Immune, e.g. acquired immune hemolytic anemia,ABO or Rh sensitization, mismatched transfusion.

3. Infection, e.g. malaria

4. Sequestration, e.g. hypersplenism5. Complement induced, e.g. paroxysmal nocturnal

hemoglobinuria

• Intracorpuscular causes (usually congenital)

1. Membrane defect—spherocytosis, stomatocytosis,elliptocytosis

2. Enzyme defect—G6PD deficiency, PK deficiency

3. Hemoglobin defect—Sickle cell anemia, thalasse-

mia, HbC, HbD, HbE disease.• Blood loss (Hemorrhage): Acute or chronic, internal or

external

1. Internal

— Acute—Massive cephalhematoma, hemothorax— Chronic—Pulmonary hemosiderosis

2. External— Acute—massive GI hemorrhage, trauma,

hemoptysis— Chronic-peptic ulcer, rectal polyp, hookworm

infestation

NB: In many diseases there is more than one cause or

mechanism of anemia

G6PD deficiency or spherocytosis can present atbirth. Hemolysis is usually associated with icterusbesides anemia. Hemorrhage can be internal like

huge cephalhematoma, pulmonary hemorrhage,intraventricular hemorrhage or external likeumbilical bleeding, fetoplacental or fetomaternalhemorrhage, GI hemorrhage like in vitamin Kdeficiency, etc.

At around 4 months of age erythroblastopeniaof infancy can occur. Rarely nutritional anemia canstart very early, especially in preterms. Between6 months to 2 years nutritional anemia and hemo-


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Clinical Approach to a Child with Anemia 17

globinopathies can present as anemia. Fanconi’sanemia usually presents around 4 to 6 years of age.In adolescents, especially females, folate deficiencyis a common cause of anemia due to food fads.

b. Sex: X-linked diseases will be seen in males and thisincludes G6PD deficiency and PK deficiency. Onlymales are affected. Hence, there will be similarhistory in male siblings, maternal male cousins,maternal uncles and maternal grandfather.

In adolescent age, anemia is more common infemales due to nutritional deficiency as a result offood fads and menstrual loss of iron.

c. Community: G6PD deficiency is more commonlyseen in Parsis, Bhanushalis and Sindhis. Certaincommunities are at high risk for certain hemoglo-binopathies inherited in autosomal recessivemanner. Beta-thalassemia is more common inKutchis, Lohanas, Punjabis, Sindhis, Gujarati Banias,

Kolis, Mahars and other Neo-Buddhists, Lingayatand Gaud communities. Sickle cell disease is morecommon in tribals and hilly areas of Nagpur,Vidarbha, Andhra Pradesh, Bilaspur and in Neo-buddhists. HbD disease is more common in Punjabis

and HbE disease is seen in Eastern India includingBengalis.d. Inheritance: A detailed pedigree chart should be

drawn including 2-3 generations on both parents’side to see for anyone else being affected which willgive clue to the type of inheritance. All hemoglo-binopathies and thalassemia syndromes areinherited in autosomal recessive manner. There willbe similar cases in siblings, cousins and distantrelatives affecting both sexes equally. There may behistory of consanguineous marriage. The parents aretrait but clinically normal. This is also called ashorizontal transmission.

Spherocytosis is inherited as autosomal domi-nant condition. The parents can be affected. Siblingsare affected and children can be affected. This iscalled as vertical transmission. Both sexes areequally affected. There may be skipped generationsand variable penetrance with different severityamongst the affected in same family. Hence, a childwith spherocytosis may be needing repeated trans-fusions, the father may have needed occasionaltransfusion whereas grandfather may just have mildanemia with splenomegaly without any transfusionneeded in life time!

X-linked inheritance is already discussed before.

e. Diet: A detailed diet history is very important espe-cially in infant with anemia. Exclusive breastfeedingfor 4 to 6 months, introduction of good home madeweaning food thereafter, continuation of breast milktill 18 months, avoidance of animal milk in first yearand balanced diet with occasional non-vegetarianfood consumption makes nutritional anemia anunlikely diagnosis. Iron deficiency develops wherethere is poor breastfeeding and improper time andquality of weaning food, both of which are exagge-rated by bottle-feeding. Prolonged breastfeedingespecially with improper weaning food is also acause of nutritional anemia in poor.

Perverted appetite or pica is both an effect anda cause of iron deficiency besides being seen in leadpoisoning. Eating clay or mud (geophagia), ice(phagophagia), starch (amylophagia), paper, cloth,raw cereals, paint flakes, etc. is commonly seen iniron deficiency. Clay or mud can bind whatever littleiron is present in food which further precipitates irondeficiency.

Table 2.2: Morphological classification of anemia

A. Microcytic, hypochromic anemia

MCV < 70 u3, MCH < 28 pg.

• Iron deficiency anemia• Anemia of chronic infection or inflammation• Thalassemia syndromes

• Sideroblastic anemia

• Lead poisoning• Severe protein deficiency

B. Macrocytic anemia

MCV > 85 u3

• Megaloblastic anemia1. Folate deficiency

2. V itamin B12 deficiency3. DNA metabolism defects like orotic aciduria

• Non-megaloblastic anemia1. Normal newborn

2. Reticulocytosis

3. Aplastic anemia

4. Liver disorders5. Hypothyroidism

6. Alcoholism7. Down’s syndrome

C. Normocytic anemia• High reticulocyte count—Early hemorrhage, hemolysis,

nutritional anemia on treatment.

• Low reticulocyte count—Bone marrow failure, bone

marrow infiltration, decreased erythropoietin produc-tion, infections, drugs.

• Normal reticulocyte count—Late phase of hemorrhage

or hemolysis, sickle cell anemia, unstable hemoglobin

disease, other hemoglobinopathies, osteopetrosis,dyserythropoiesis, myelofibrosis, enzyme deficiency,spherocytosis.


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Megaloblastic anemia due to folate deficiency iscommon in those villagers who consume a lot of goatmilk. Similarly, folate deficiency is commonly seenin adolescents due to food fads.

f. Drugs: Drugs can induce anemia by many ways.

Certain drugs can lead to aplastic anemia likechloramphenicol, sulpha drugs or analgesics. Drugslike penicillin, alpha methyldopa or stibophen canlead to immune hemolytic anemia. In a patient withG6PD deficiency certain drugs like aspirin, sulphadrugs, primaquine, etc. can precipitate hemolysis.Lastly certain drugs can precipitate iron deficiencylike, chronic GI bleeding following NSAID abuse;or produce megaloblastic anemia as seen withsulpha drugs, phenytoin or folate antagonists.

g. Infections and infestations: History suggestive ofintrauterine infection should be elicited whendealing with neonatal anemia especially when it is

associated with hepatosplenomegaly, IUGR, icterusand thrombocytopenia. Hypoplastic anemia can beprecipitated by hepatitis virus. G6PD deficiencyinduced hemolysis can be precipitated by manyinfections and drugs used to treat such infections.Hemolysis could also be induced by malaria. Bone

marrow suppression can occur following many viralinfections, falciparum malaria, kala-azar, fulminantsepsis or drugs used in such cases. Chronic infec-tions and inflammations like tuberculosis, repeatedrespiratory or GI infections can lead to mild to

moderate anemia of chronic inflammation.Nutritional anemia can be precipitated by wormsdue to malabsorption, nutrient deficiency and microbleeding especially with hook worm infestations.Any acute infection can lead to drop in hemoglobinby 1-1.5 g% over next one week.

h. Family history: History of any other family memberbeing affected by anemia by drawing a detailedpedigree chart. History to be elicited in family mem-bers includes history of blood transfusion,unexplained recurrent jaundice, gall stone removal,splenectomy, which suggest some hemolytic processin them. Similarly, history of anemia following drugs

in other members will suggest G6PD deficiency.

Physical examination: A detailed head to toe exami-nation is required to be done to decide the severity ofaffection and to achieve a diagnosis. Some physicalsigns help clinch the diagnosis (Table 2.3).

Table 2.3: Physical findings as clues to the etiology of anemia

Skin Hyperpigmentation Fanconi aplastic anemiaPetechia, purpura thrombocytopenia, Autoimmune hemolytic anemia with hemolytic-uremic

Carotenemia syndrome, bone marrow aplasia, bone marrow infiltration

Jaundice Suspect iron deficiency in infantsHemolytic anemia, hepatitis, and aplastic anemia

Cavernous hemangioma Microangiopathic hemolytic anemiaUlcers on lower extremities S and C hemoglobinopathies, thalassemia

Facies Frontal bossing, prominence of the Congenital hemolytic anemias, thalassemia major, severe

maxillary bones iron deficiencyEyes Microcornea Fanconi’s aplastic anemia

Tor tuosity of the conjunctival and S and C hemoglobinopathies

retinal vessels

Microaneurysms of retinal vessels S and C hemoglobinopathiesCataracts Glucose-6-phosphate dehydrogenase deficiency, galactosemia

with hemolytic anemia in newborn period

Vitreous hemorrhages S hemoglobinopathy

Retinal hemorrhages Chronic, severe anemiaEdema of the eyelids Infectious mononucleosis, exudative enteropathy with iron

deficiency, renal failure

Blindness Osteopetrosis

Mouth Glossitis Vitamin B12 deficiency, iron deficiencyAngular stomatitis Iron deficiency

Chest Unilateral absence of the pectoral muscles Poland syndrome (increased incidence of leukemia)

Shield chest Diamond-Blackfan syndrome

Hands Triphalangeal thumbs Red cell aplasiaHypoplasia of the thenar eminence Fanconi aplastic anemia

Spoon nails Iron deficiency

Spleen Enlargement Congenital hemolytic anemia, leukemia, lymphoma, acute

infection, portal hypertension


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Clinical Approach to a Child with Anemia 19

a. Ascertain severity: Pulse, blood pressure and respi-ratory rate should be recorded. Look for puffiness,edema feet, sacral edema, jugulovenous pulse,heptic tenderness, hepatojugular reflux and basalcrepitations. All these will help to diagnose

congestive cardiac failure as such patients needurgent treatment. Hypertension may be seen inanemia due to renal diseases.

b. Facies: Hemolytic facies will have frontal and parietalbossing, large head, depressed bridge of nose, malarprominance, sallow complexion, irregular maxillaryteeth with anterior overbite. Diamond-Blackfansyndrome will have box like face with patientsresembling one another rather than their familymembers. Hypothyroidism will have typical cretinfacies and may be missed unless one looks for itcarefully. Look for periorbital puffiness which cansuggest edema due to anemia, CCF or myxedema.

c. Eyes: Mongols will have mong

practical pediatric hematology

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