MD311 - T6 RBC disorder

Macrocytic anemia - lab test

increase MCV, normal MCHC

Microcytic hypochromatic anemia - lab test

decrease MCV, MCH, MCHC

Normocytic anemia - lab test

normal mcv, mch, mchc

Mechanistic Classification of Anemia - Type

Production defect, Maturation disorders, RBC survival defects

Anemia - Definition

the decrease in the competence of blood to carry oxygen causing hypoxia

Cause of Anemia - Type

Hemorrhage, Hemolysis, Decrease in Production

Adaptation to Anemia - how is the severity defined - criteria

rate of onset, severity of blood loss, ability for body to adapt

20% blood loss (1000ml) - results in

can have no symptoms, no clinical signs

30-40% blood loss (1500ml to 2000ml) - results in

circulatory collapse and shock

50% blood loss (2500ml) - results in

death

how does body adapt to anemia - mech

increase in oxygenated blood flow, increase in oxygen utilization by tissue

body adapt to anemia by increase oxygen utilization, how? - mech

increase in 2,3-BPG in erythrocyte, decrease in oxygen affinity

Anemia - diagnosis

dietary habits medication, exposure to chemical, symtomps related (fatigue, muscle loss, headache, vertigo, syncope, dypsnea), previous record of abnormal blood examination, family history

Anemia (won’t state the obvious one la) - symptoms

koilonychia, glosstitis, hepatospleenomegaly, jaundice, hypotension, mongolian face, bone deformities in congenital anemia

koilonychia - definition

thin concave nails

Male normal Hb and Ht - value

13, 39

FeMale normal Hb and Ht - value

12, 36

Pregnant normal Hb and Ht - value

11, 33

Newborn normal Hb and Ht - value

15, 45

Child normal Hb and Ht, 3m to 4 yrs - value

11, 33

Reticulocyte count - definition

measure of BM productivity

Reticulocyte - site

2-3 days in BM, 1 day in blood

Reticulocyte count (%) - equation

reticulocyte*100 / 1000rbc

Corrected reticulocyte count - definition

mean to adjust the reticulocyte count proportion to the severity of anemia → reticulocyte % is falsely high in anemia because it's relative to fewer total RBCs

Corrected reticulocyte count - equation

patient Ht * %reticulocyte / normal Ht(45%)

Reticulocyte production index - definition

adjust the reticulocyte count based on maturation time

Reticulocyte production index - equation

(patient’s Ht/ 45%normal Ht) x. (reticulocyte count%/ reticulocyte maturation time(days))

hypoproliferative anemia reticulocyte count - value

<75000/miu liter

maturation anemia reticulocyte count - value

<75000/miu liter

hemolytic anemia reticulocyte count - value

>100000/ miu liter

abnormal blood loss or nutritional supplementation reticulocyte count - value

>100000/ miu liter

Anemia classified on 3 levels - type

morphologic, etiologic, mechanistic

morphologic classification of anemia - type

macro, micro hypochromatic , normocytic normochromatic anemia

etiologic classification of anemia - type

blood loss, excessive destruction, impare rbc production

mechanistic classification of anemia - production defect - example

BM failure, defective erythropoietin in kidney, Aplastic Anemia, Red cell aplaosa, PNH

mechanistic classification of anemia - maturation disorder on erythrocyte - 2 types

nuclear and cytoplasmic

mechanistic classification of anemia - maturation disorder on erythrocyte, nuclear - example

impaired DNA synthesis and mitosis, deficiency of vit 12 or folate, chemo agent

mechanistic classification of anemia - maturation disorder on erythrocyte, cytoplasmic - example

defect in hb production, iron deficiency, globin chain production disorders i.e. thalassemia, heme biosynthesis disorder i.e. sideroblastic anemia

mechanistic classification of anemia - erythrocyte survival defect, intrinsic defects in erythrocyte - example

heriditary spherocytosis, sickle cell anemia, g6pd deficiency (membrane, hb and enzyme defect accordingly), pyrvate kinase deficiency

mechanistic classification of anemia - erythrocyte survival defect, extrinsic factor - example

turbulent blood flow, microangiopathies, diverse immune mediated hemolytic anemia

mechanistic classification of anemia - erythrocyte survival defect - 2 types

intrinsic defect in erythrocyte and extrinsic defect

MCV - normal value

80 - 95 fl

MCH - normal value

27 - 32 fl

MCHC - normal value

30 - 35 g/dl

MCV < 80 - morphologic classification - type

microcytic hypochromatic anemia

MCV 80 -100 - morphologic classification - type

normocytic anemia

MCV > 100 - morphologic classification - type

macrocytic anemia

MCV < 80 problems with - further lab test

iron profile

MCV 80 - 100 problems with - further lab test

reticulocyte count

MCV > 100 problems with - further lab test

macrocyte and hypersegmented neutrophil on blood smear

etiological classification - blood loss acute - example

accident, GI bleeding

etiological classification - blood loss chronic - example

hypermenorrhea, parasitic (malaria) infection

etiologic classification - membrane defect - example

heriditary spherocytosis, hereditary elliptocytosis

etiological classification - enzymatic defect - example

pyruvate kinase deficiency, G6PD deficiency

etiological classification - hemoglobin defect - example

thalassemia, hematoglobinopathies

etiological classification - classification

intracorpuscular defect and extracorpuscular defect

etiological classification - immune hemolytic anemia - example

autoimmune hemolytic anemia, alloimmune hemolytic anemia (ABO incompatible)

etiological classification - non-immune hemolytic anemia - example

Mechanical → microangiopathic hemolytic anemia, chemical → March hemoglobinuria, infection → clostridium tetani (tetanus), hyperspleenism

etiologic classification - extracorpuscuplar defect - type

immune hemolytic anemia and non immune hemolytic anemia

hemolytic anemia - etiology

increase rbc destruction or decrease rbc life span

extravascular hemolysis - definition

lysis in reticuloendothelial system by macrophage in secondary organ (spleen, liver, bm, lymph node)

intravascular hemolysis - definition

lysis in circulation, free hb seen in circulation, urine (hemoglobinemia, hemoglobinuria), iron in urine → hemosiderin

extravascular hemolysis normal - value

80%-90% of aged rbc is lysis by this method

aged rbc - characteristic

decrease ATP synthesis, defective selective permeability, defect in surface volume ratio, rigid membrane, unable to passs through splenic sinus (trapped by macrophages)

Intravascular hemolysis normal - value

10% of aged rbc is lysis by this method

Intravascular hemolysis presentation - lab test

hemogloninemia, hemoglobinuria, hemosiderin

hemolytic anemia - symptoms

anemia, increase bilirubin, gallstone, bm hyperplasia, hepatospleenomegaly

picture for summary

hemolytic anemia

hereditary spherocytosis - which type of anemia

membrane defect, intracorpuscular rbc defect

hereditary spherocytosis - genetic

75% case → autosomal dominance (ankyrin gene and beta spectin gene), autosomal recessive (alpha spectin gene), 25% - non-inheritted → spontaneous mutation.

hereditary spherocytosis - pathophysiology

Defects in the membrane skeleton protein (spectin ankyrin) → unstable membrane→ influx of Na+ → Osmosis → spherocyte → less deformable → trapped and lysis in spleen

hereditary spherocytosis - severity

homozygous (recessive>dominant) → severe, heterozygous → mild to moderate

hereditary spherocytosis - presentation

anemia, jaundice, splenomegaly

Heriditary spherocytosis - Key Mech

Na+ influx → osmosis

Heriditary Spherocytosis - laboratory finding

Smear - spherocyte + microspherocyte + polychromasia, MCHC >36%, Increase RDW, Increase Osmotic fragility

Hereditary Elliptocytosis - description

Presence of ovalocyte or elliptocyte in blood

Hereditary Elliptocytosis - genetic

Most commonly Autosomal Dominance

Hereditary Elliptocytosis - pathophysiology

defect in a/b spectin protein, protein 4.1 → loss horizontal linkage integrety = horizontal defect

Hereditary Elliptocytosis - Key

horizontal defect

Hereditary Elliptocytosis - types

Southeast Asian Ovalocytosis, Common Hereditary elliptocytosis, hereditary pyropoikilocytosism spherocytic hereditary epplitocytosis

Hereditary pyropoikilocytosis - pathophysio

spectin dimer dimer association defect, ankyrin 3 interaction - horizontal defect

Hereditary pyropokilocytosis - presentation

severe form, variable poikilocyte

Southeast Asian Ovalocytosis - most commonly found in

melanesian and malaysian population

Southeast Asian Ovalocytosis Smear - Key

Stomatocyte + Theta cell

Southeast Asian Ovalocytosis - Genetic

protein band 3 SLC4A1 defect

Acantocytosis - cause

Severe Liver Disease, result of altered plasma lipids

Abetalipoproteinemia - cause

Rare Autosomal recessice disorder → caused by MTP gene mutation

G6PD deficiency - prevalance

High prevalence in malaria endemic zone → Mediterranean population

G6PD deficiency - genetic

X-linked recessive → male

G6PD deficiency - clinical

Male - all symptomatic, Female - Homozygous - symptomatic

G6PD deficiency - variants

>127 variants

G6PD deficiency - clinical complication

3: acute hemolytic anemia, neonatal jaundice, congenital non-spherocytic hemolytic anemia

G6PD deficiency - congetinal non-spherocytic hemolytic anemia - key

we won’t see spherocyte in smear

G6PD deficiency - acute hemolytic anemia - key

3 triggers: Certain drug (primaquine for malaria), infection (ticket), fava beans

G6PD deficiency - acute hemolytic anemia - mech

increase oxidative stress from triggers (drug, infection, fava beans) → hemolysis

G6PD deficiency - neonatal jaundice - key

Infant - hyperbilirubinemia = kernicterus

G6PD deficiency - congentital non-spherocytosis hemolytic anemia - presentation

chrononic hyperbilirubinemia, decrease haptoglobin, increase LDH level.

G6PD deficiency - presentation

Asymptomatic hemolytic crisis, intracerebral hemolysis, Hemoglobinuria

Hemolytic crisis - lab finding

defect spherocyte, bite cell, blister cell, Heinz bodies

G6PD deficiency - screening test

Fluorescent spot test → from NADPH (Dark = deficiency)