PEDIATRIC HEMATOLOGY 2012

HEMATOLOGY LECTURE BLOOD

COMPONENTS
Indications Dosage

Dr Ma. Teresa S. Fajardo

FRESH WHOLE ExchangeTransfusion 20 mL/kg BW
BLOOD Acute Blood Loss
I. BLOOD TRANSFUSION (Component Therapy) -absence of Component

PACKED RBC ANEMIA Desired Hct - Actual

Blood Transfusion is not a totally safe Procedure. -infectious,neoplasms, Hct x BW (kg)
CRF, CHF, Uremia, BM
A. Blood Component Therapy Failure Acute Anemia:
• giving only the particular blood fraction the Pre-Surgical Anemias 10mL/kg
patient needs, leaving the rest of the Acute Blood Loss Chronic Anemia:
components for other purposes and avoiding 5mL/kg
waste

INDICATIONS FOR BLOOD TRANSFUSION FRESH FROZEN Acquired Prothrombin 10-15mL/kg

PLASMA Complex Deficiency
1. To Maintain Blood Volume & Sustain the Oxygen- (APCD)
Hemophilia
carrying capacity function of the erythrocytes
DIC
2. To Promote or Maintain Coagulation
3. For Exchange Transfusion CRYO- Hemophilia A 1 unit/ 7-10lbs BW
4. Use in Extra-Corporeal Circulation in open heart PRECIPITATE Von-Willebrand'sFactor
surgery (Factors and Hypofibrogenemia (1bag= 100 U of Factor
5. When Rapid Correction of deficiency is desired, Fibrinogen) DIC VIII)
in nutritional deficiency states
PLATELET Thrombocytopenia sec 1 U / 7-10 lbs
Distribution of ABO and Rh(D) Blood Groups in 4,000 CONCENTRATION to: 1 U / 10-15 T?
Filipinos: Infection
Bone Marrow Failure
ITP
Blood Group Percent DIC
Chronic Inflammation
A 44.0 Chronic Disease

B 24.4 HAZARDS OF BLOOD TRANSFUSION

A. Hemolytic Reactions
AB 26.3
1. Incompatible Blood
2. Interdonor-Intercompatibility inMultiple
Rh Negative (D-) .09
Transfusion
Rh Positive (D+) more than 99
B. Non-Hemolytic Reactions
1. Leukocyte of Platelet Antibodies
Pre-requisites of a Blood Donor 2. Plasma Protein Antibodies
1. No history of Previous Blood-related Illnesses
2. Age 16-60 years old C. Transmission of Infection
3. Systolic BP : 100-160mmH 1. Bacterial Contamination
4. Diastolic BP : 70-100mmHg 2. Hepa A & B, Non-A & Non-B
5. Screened for Malaria, Syphilis, Hepatitis B&C, HIV 3. Malaria
4. Syphilis
COMPATIBILITY TESTING 5. Ebstein-Barr Virus
Cross-Matching 6. CMV
• to protect patients from incompatible 7. Toxoplasmosis
transfusion 8. HIV
• have RBC that will survive maximally in
circulation D. Circulatory Overload
E. Suppression of Erythropoesis
F. Excessive Iron Deposition
G. Antibody Formation
H. Allergic Reactions
I. Massive Transfusion & Extra-corporeal Circulation
J. Air Embolism
K. Electrolyte Disturbance
1. Hyperkalemia
2. Citrate Intoxication
L. Graft vs. Host Disease
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CLASSIFICATION OF DISORDERS OF HEMOSTASIS

II. TRANSFUSION REACTIONS
Signs and Etiology Management A. PURPURAS without MAJOR COAGULATION FACTORS
Symptoms
1. With Low Platelet Count
ALLERGIC Pruritus Ab against Anti-Histamines a. Acquired Thrombocytopenia (ITP)
(Mild) Rashes Plasma b. Hereditary Thrombocytopenia (Fanconi
Hives Proteins
Anemia)
ALLERGIC Pruritus Ab against Anti-histamines c. Neonatal Thrombocytopenia (Isoimmune
(Severe) Hives WBC, Platelets, Antipyretics Purpura)
Anxiety Plasma Vasopressors
Fever Proteins, IgA Steroids 2. With Normal Platelet Count
Chills Washed RBC A. Qualitative
Flushing a. Acquired Thrombocytopathies (Aspirin)
Tachycardia
b. Heritable Thrombocytopathies (Glanzman's Dse)
Dyspnea
Hypotension
B. Vascular Disorders
Anaphylaxis a. Acquired (HSP)
b. Heritable (Ehler-Danlos Syndrome)
ACUTE Anxiety ABO 1. Treat shock
HEMOLYTIC Chest Pain Incompatibility -Vasopressors and B. MAJOR COAGULATION DISORDERS
Headache Steroids A. Decreased Activity of 1 or more Coagulation
Dyspnea Factors
Chills 2. Maintain adeq.
a. Heritable (Hemophilia)
Fever Airway
Shock b. Acquired (DIC)
Bleeding 3. Inc Renal BF c. Neonatal (Hemorrhagic Disease of the Newborn)
Hgbemia B. With Normal/Increased Coagulation Factors
Hgbnuria 4. IVF a. Heritable Thrombotic Disorder
(Def of Antithrombin II)
5. Maintain b. Acquired
Diuresis (OCP)
6. Treat Bleeding

7. Dialysis COAGULATION FACTORS

I - Fibrinogen
8. Give Bld II - Prothrombin
Components as III - Tissue Thromboplastin
needed IV - Calcium
V - Pro-accelerin / Labile Factor
SEPTIC or Chills Gram(-) sepsis Treat shock VI - NONE
TOXIC Fever from infected - Vasopressors
VII - Pro-convertin
Hypotension Blood - IVF
-Broad spec. Serum Prothrombin Conversion Accelerator
Antibiotics (SPCA)
Stable Factor
III. BLEEDING DISORDERS VIII - Anti-Hemophilic Globulin (AHG)
Anti - Hemophilic Factor (AFG)
Hemostasis IX - Christmas Factor
- sum total of those specialized functions within the Plasma Thromboplastin Component
circulating blood and its blood vessels that are designed X - Stuart-Power Factor
to stop hemorrhage XI - Plasma Thromboplastin Antecedent
XII - Hageman Factor
Components of Hemostatis XIII - Fibrin Stabilizing Factor
1. Vascular Phase
2. Platelet Phase
3. Plasma Phase

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PRIMARY vs. SECONDARY HEMOSTATIC DEFECTS

Clinical Manifestations
HEMOSTATIC MECHANISM CHARACTER PRIMARY SEONDARY
PRIMARY SECONDARY
Onset of Bleeding immediate delayed
Vasoconstriction Intrinsic and Extrinsic Pathway
Platelet Formation (Formation of Fibrin Thrombus) Bleeding from yes no
Plug (Adhesion & Aggregation) Abrasions

Laceration yes no
VASCULAR PLATELET PHASE PLASMA PHASE
PHASE Surgery yes no
Fragility of Thrombocytopenia Problem in the
different BV I. Destruction different Type of Bleeding
a. Acquired Clotting Factors
Scurvy - ITP Petechiae yes no
Vasculitis - Infection APCD
Henoch- - Renal Failure Hemophilia
Schonlein b. Hereditary DIC Ecchymoses small large
Purpura (HSP) - Wiskott-Aldrich Synd. Liver Disease multiple spreading
Allergic - Fanconi Syndrome
Vasculitidis II. Decreased Production Hematoma sometimes yes
Dengue - Aplastic Anemia
- Leukemia Hemarthrosis no yes
Thrombasthenia
a. Acquired
- Infection IMMUNE THROMBOCYTOPENIC PURPURA
- Renal Failure • acquired hemorrhagic disease
b. Hereditary • characterized by:
- Glanzman Thrombasth • thrombocytopenia
- Bernard-Soullier Synd • purpura
Prevention of Formation of Platelet and Fibrin Clot • absence of other causes of thrombocytopenia
PROSTACYCLIN - vasodilator • no organomegaly
- prevents platelet aggregation • BM aspirate : abundant Megakaryocytes
• Acute >2x Chronic
Receptors for Thrombin (neutralizes clotting activity) • Etiology : Autoimmune Disorder
• Anti-coagulant Protein C • Females >3x Male
• Anti-thrombin 3
Acute Chronic
SITE OF BLEEDING
Platelet Clot Fibrin Clot peaks @ 2-6 years peaks @ 10-30 years

Mucous Membrane Yes Sometimes complete and sustained remission sustained remission not achieved
(epistaxis, menorthagia, GI, GU) within 6 months of onset within 6 months from onset

Musculoskeletal Rare Yes 1. Single Episode 1. Continuous Episode

-variable severity -variable severity
CNS Yes Yes 2. Recurrent 2. Recurrent
-Biphasic - Multiphasic

Pulmonary Yes Rare

HEMORRHAGIC DISEASE OF THE NEWBORN

Diagnosis: • self-limited disease
• History • 1st - 5th day of Life
• Physical Examination • deficiency of Vitamin K
• Laboratory Test • Dependent Clotting
• CBC, APC • Factors II, VII, IX, X
• Bleeding Time - rough estimate (IVY upto • less common in Full-term infants
10min) • Bleeding RARELY MASSIVE
- prolonged in Thrombocytopenia • Prolonged PT, PTT
• Prothrombin Time Mgt: Vitamin K
• Partial Thromboplastin Time

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DISSEMINATED INTRAVASCULAR COAGULOPATHY RBC INDICES

• MC form of Consumption Coagulopathy in children
• Fever MCV = VOLUME of PRBC(hct) x 1000
• Bleeding from Skin, MM, GU, GI, CNS RBC Count
• exagerration of hemostatic mechanism Normal Value : 80-100 fL

Mgt: MCH = Hgb

• tx of underlying disease RBC Count
• general supportive care Normal Value : 27-34 pg
• Blood Transfusion : Hypovolemia and Shock
• Control of temperature abnormalities MCHC = Hgb
• specific measures to control DIC PRBC Volume
Normal Value : 32-36%

III. DIAGNOSTIC APPROACH TO PATIENTS WITH PALLOR Corrected RC or Reticulocyte Index:

Actual Hct x Observed RC (%)
Factors affecting Skin Color: Desired Hct
1. Hemoglobin Concentration Normal Value : 1-1.5%
2. State of Constriction
3. Dilatation of Peripheral Vessels RETICULOCYTOSIS RETICULOCYTOPENIA
4. Pigmentation and Sct. Fluid
Acute Blood Loss Bone Marrow Failure
ANEMIA Hemolytic Anemia Aplastic Anemia
• reduction in RBC mass After a Therapeutic Trial of Iron Leukemia
• reduction in blood hemoglobin concentration

RBC function - deliver and release adequate quantities of Thrombocytopenia

to the tissues to meet their metabolic demand • depletion of Iron and Iron enzymes
• associated Folate Deficiency
Criteria for Identifying Children with low Hgb and Hct • Transient Thrombopoetin Defect
Values
Microcytic Normocytic Macrocytic
Hypochromic Normochromic
AGE Hemoglobin Hematocrit
Anemia Anemia

6-23 months <10 g/dL <30% IDA Hemolytic Anemia B12 deficiency
Chronic Infection (all types) B9 deficiency
2-5 years <11 g/dL <34% Chronic BL Acute Infections
Thalassemia Acute BL Megaloblastic Anemia
Lead Poisoning ARF
6-12 years <12 g/dL <37% CRF Hemoglobin- Pernicious Anemia
Erythrocyte Mass
Deficit GI Abnorm:
Hemoglobin Level and Symptoms Malabsorption
Hemoglobin Level (g/dL) Symtpoms Syndrome,
Inflammatory Disease,
Liver Disease
9-11 little to no dysfunction
Bone Marrow Failure
5-7 exertional dyspnea or Hypoplasia

6.0 some weakness Hemolysis/Hge

Cong/Acq
3.0 dyspnea at rest Dyserythropoiesis

2-2.5 cardiac failure Peripheral Smear Chemical Studies

Hypochromia Decreased Serum Iron

EVALUATION OF THE ANEMIC PATIENT Microcytosis Increased Total Iron-Binding
• History Anisopoikilocytosis Capacity
• Physical Examination Target Cells Transferrin Saturation = <15%
Thrombocytosis Serum Iron <50 ug/dL
• Laboratory Test
Thrombocytopenia
• CBC
• RBC Indices
• Reticulocyte Count
• Examination of Peripheral Smear
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HEMOLYSIS - conditions in which the rate of RC Classification of Anemia according to Functional

destruction is accelerated and the capacity of the Bone Disturbances
Marrow to respond to the stimulus of Anemia is 1. Disorders of Effective Red Cell Production
unimpaired 2. Disorders with Rapid Erythrocyte
Destruction of RC Loss
Coomb's Test
• (+) Immune Hemolytic Anemia
• (-) Osmotic Fragility Test DISORDERS OF EFFECT RC PRODUCTION
• Inc Fragility - Hereditary Spherocytosis • Depressed Net Rate of RC Production
• If Normal - Do electrophoresis • Disorders of Erythrocyte Maturation
• Abnormal Hgb: • ineffectual Erythropoiesis
• Quantitative - Thalassemia • Absolute Failure of Erythropoiesis
• Qualitative - Hemoglobinopathies
• Normal : Infection, Malaria, Inborn Errors,
Burns, Vascular Defects ANEMIA
Red Cell Indices History
Intravascular Hemolysis Extravascular Hemolysis MCV Physical examination
(w/in the circulation) (w/in Tissue Macrophages) Initial Screening MCHC Non-Hematological
and RDW Disease
destruction of RBC within reticuloendothelial cells Presumptive HDW (Renal, Thyroid,
BV Diagnosis Metabolic..)
Peripheral Smear
Jaundice Organomegaly (spleen&liver)
Hemoglobinuria more pronounced Jaundice
Hemoglobinemia Reticulocyte Count
MC cause = AI hemolytic Anemia and Indices
Infection
Direct Anti-Globulin Indirect Bilirubin
Malignancy
Test LDH, Hepatoglobin
Collagen Diseases
Confirmatory Serum B12
Immune Hemolytic Anemia Studies G6PD Screening Test Serum RBC Folate
A. Autoimmune Hemolytic Anemia Osmotic Fragility Serum Ferritin, Iron
• Idiopathic TIBC
Hgb Electrophoresis Circ. Transferrin Rec.
• Sec to underlying disorder
Serum Lead
• Passive Transfer of Maternal Ab RBC ZPP
Bone Marrow
Aspirate/Biopsy
B. Alloimmune Hemolytic Anemia
• Hemolytic Disease of the Newborn Hgb Isoectrofocusing Test for unstable Hgb
• Blood Group Incompatibility Additional Studies and other tests for Cytogenetic Studies
rare Hgb variants RBC Enzyme Panel
C. Drug-induced Hemolytic Anemia Membrane Protein
D. Paroxysmal Nocturnal Hemoglobinuria Studies

Causes of AI Hemolytic Anemia: IRON DEFICIENCY ANEMIA

• Infections • MC cause of Anemia
• Disorders associated with Autoantibody • Common in ages 6-24 months
• Immunodeficiency Syndromes
• Malignancy Forms of Iron according to its Iron-binding Agents
Stale Oxidative States (Chelators)
SIGNS OF RED CELL DESTRUCTION
• dec RBC Life Span FERROUS (Fe2+) Desferrioxamine
FERRIC (Fe3+) Transferrin
• inc catabolism of heme
• inc serum LDH
• absence of serum Haptoglobin
Distribution of Iron
• reduced Glycosylated Hgb
• Signs of Intravascular Hemolysis Uptake Losses
• Hemoglobinemia
• Hemoglobinuria Average Adult : 3-5g Skin - 1mg/day
• Hemosiderinuria (Balance=Dietary Uptake and Menstruation - 2mg/day
• Fall in Hgb level greater than 1g/dL/wk Loss)

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Etiology of IDA: EFFECTS OF IDA:

A. Inadequate Supply of Iron 1. Growth and Development Retardation
1. Lack of Iron stores at birth -Impairs Tissue Oxygen
- LBW -Weakness
- PT -Fatigue
- Twin or Multiple Births - Palpitation
- Severe IDA in Mothers - Light-headedness
- Fetal Blood Loss -Impaired Neurologic Functions
- Bleeding from the 1st few days of Life - behavioral abnormalities
2. Inadequate Intake - Deficient dietary Iron - motor incoordination
- seizures
B. Impaired Absorption 2. Epithelial Changes
1. Chronic Recurrent Diarrhea - Angular Stomatitis
2. Malabsorption Syndrome - Glossitis
3. GI Abnormalities - Flattened and Atrophic Lingual Papillae
- Plummer Vinson Dse (postcricoid esophageal web)
C. Excessive Demands for Iron for Growth as seen in PT, - Koilonychia (Spoon Nails)
LBW, Infants, Adolescents and Pregnancy 3. Miscellaneous
- Pica
D. Blood Loss - Massive Hepatosplenomegaly
1. Acute or Chronic Hemorrhage - Poor Wound Healing
2. Parasitic Infection (Hookworm, Tricruris tricura) - Bleeding Diasthesis
- Zinc Deficiency
Factors that Modify Iron Absorption: - Lead intoxication
- Pseudotumor Cerebri
2. Physical State (bioavailability) - Reactive Thrombocytosis
Heme > Fe 2+ > Fe 3+
2. Inhibitors Diagnosis of Infants Prevention
- Phytates high index of suspicion
-Tanins
- Soil 1. Prematurity 1. Admin. of Fe to expectant mothers
-Laundry Starch 2. Blood Loss 2. Early intro. of solid food
3. Fed exclusively of Milk 3. Supplemental Fe :
-Iron Overload
4. Chronic Diarrhea 10-15mg/day (6-8wks old)
3. Competitors
-Cobalt
-Lead Treatment of IDA
-Strontium 1. Determine the Cause
4. Facilitators 2. Correct the Abnormality
-Ascorbate
-Citrate Specific Treatment of IDA
-Amino Acids 1. Oral Supplementation
2. Parenteral Iron Replacement Treatment
Role of Iron • Oral FeS 6mg/kg/day (6-8 wks after normal
• DNA Synthesis Hgb is attained)
• Host of Metabolic Process • older children 100-200 mg/day of Elemental
Iron
Consequences of Iron Deficiency Anemia •
2. Anemia Poor Response to Oral Iron
3. Growth and Developmental Retardation • Non-compliance
4. Epithelial Changes • Ongoing Blood Loss
5. Miscellaneous • Insufficient Duration of Therapy
• High Gastric pH
Stages of Iron Deficiency • Inhibitors of Absorption

Utilization - incorrect diagnosis

Prelatent Iron Deficiency Depleted stores w/out a change in
Hct or serum Iron levels rarely
detected Inhibitors of Iron Absorption
• Lead Intoxication
Latent Iron Deficiency - decreased serum Iron Level • Aluminum Intoxication
- total Iron-Binding Capacity w/out a • Chronic Inflammation
change in the Hct • Neoplasia
-decreased Transferrin Saturation

Frank Iron Defiency IDA assoc with Erythrocyte

Anemia Microcytosis & Hypochromia

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Parenteral Iron Replacement

Indications
1. Poorly tolerated Oral Iron
2. Rapid Replacement of Iron Stores
3. GI absorption is compromised

IRON DEXTRAN
• IM or IV route
• Z-track injection ( done to minimize SQ leak)
• 10-15% - suffers transient arthralgia
• Reticulocytosis in 10 days
• Complete Correction in 3-4weeks

BLOOD TRANSFUSION
• indicated for:
• Severe Anemia
• Debilitated from Infection
• Signs of Cardiac Decompensation

Effect on the Fetus of Maternal IDA

• MATERNAL IRON STATUS DETERMINES THE IRON
STORES OF TE NEONATE
• AN OUNCE OF PREVENTION IS BETTER TAHNA
POUND OF CURE

Systemic Defects in IDA of Chronic Inflammation

1. Ineffective Iron Utilization
2. Low Plasma Erythropoietin Levels

Consequences of Iron Overload:

1. Heart
2. Liver
3. Endocrine

Aplastic Anemia and Leukemia may have different tyoes:

>1.5% Reticulocytosis <1% Reticulocyopenia

Blood Loss Bone Marrow Failure

Hemolysis (MC leukemia and aplastic
After Therapeutic trial of Fe anemia)

TARGET CELLS - Thalassemia

ITP - Idiopathic Immune Thrombocytopenic Purpura

- ongoing blood loss
- rpt Hgb and Hct after 3 weeks of giving FeS

Intrinsic Pathway Extrinsic Pathway

VIII, IX, X, XI II, VII, IX, X

very sensitive to deficiency of naturally occuring

Factor VIII Vit. K dependent Clotting Factors

Prolonged = >20 sec that of INR - 1-1.5%

control

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