anemia approach
DESCRIPTION
anemia diagnosis approach and managementTRANSCRIPT
Approach to the Patient with Nutritional and Hemolytic
ANEMIA
Laboratory Evaluation
Usual initial studies
– CBC – differential (includes RBC
indices,MCV,MCH,MCHC)– Reticulocyte count– Peripheral blood smear– TLC & DLC– Platelet count
Suspected iron deficiency
• Free eryhrocyte protoporphyrin• Serum ferritin levels• Stool for occult blood• Endoscopy upper and lower bowel
Suspected vit B12 & Folate deficiency
– Bone marrow– Serum B12 levels (180-914 pg/ml)– Serum folate level (3-17 ng/ml)– Red cell folate (400-800 ng/ml)– Vit B12 absorption test (schilling test)– Retic count newborn3.2+-1.4% and children
1.2+-0.7%
Suspected hemolytic anemia
1-Evidence of red cell breakdown– Blood smear– Serum bilirubin level– Urine urobilinogen excretion– Serum haptoglobin
2-Evidence of red cell regeneration– Reticulocyte count – Blood smear– Skeleton radiography
3-Evidence of type of hemolytic anemia Corpuscular
(a) Membrane
-Blood smear
-Osmotic Fragility test
-Autohemolysis test
(b)Hemoglobin
-Sickle test
-Hemoglobin electrophoresis
-Hemoglobin F Determination
-heat stability test
(c) Enzymes
-Heinz-body preparation
-Enzyme assay(G6PD def,pyruvate kiase def.)
3-Evidence of type of hemolytic anemia Extra Corpuscular
immune
- Antiglobulin test
- Acid serum lysis test
- sucrose lysis test- Donath landsteiner antibody- -ANA
PS(microcyte), retic count & iron studies
N or Reduced retic count
Low serum iron,low
ferritin,increase TIBC
Iron deficien
cy anemia
Low serum iron,
N or high ferritin,
N or low TIBC
ESR or CRP
Elevated
Inflammatory disease
Normal
Anemia of chronic disease
N or increase serum iron,
N or low TIBC & ferritin
Hb electophoresis(HPLC)abnormal
Hb pathies , Thallasemia
Normal
Sideroblastic anemia
Increase Retc count & abnormal red cell morphology
Hb electophoresis
Hb ss, Hb sc, S-B thallasemia
Retic count
N or reduced
Serum iron
lowAnemia of
chronic
early iron deficienc
y
N or high
Bone
marrow
biopsy
Infiltration(leukemia ), aplastic anemia ,MDS,
Screen for renal ,endocrine hepatic disease
negative
positiveAne
mia of
renal ,endocrin
e hepa
tic disease
Increase Retic count
+ve test for hemolysis
yes
Hemolytic anemia
No
Hemorrage or
recovery from
nutritional deficiency
PS (macrocyte),hyper segnented eutrophils
yes
Megaloblastic likely
B12 & folic acid level ,Bone marrowLow
level,megaloblast
ic changes in bone marrowMegaloblastic anemiaB12
& folat
e therapy
No megalobla
stic change in
bone marrowLook for
other cause
Hypothyroidism,Drug(phenytoin or sulphonamides)
,CHD,Down
syndrome,
Intrinsic faco
r deficienc
y
No
Non megaloblastic
Retic count
decreased
LFT, T3T4T
SHabnormal
Hypothyroid,Liver Ds
normalBMA
Aplastir A,Red cell aplasia,MDS
increased
Hemolysis ,hemorrha
ge
Red cell indices & iron studies in childrenRed cell indices
birth .5-2 yr 6-12 yr 12-18 yr(girls)
12-18yr(boys)
MCV 108 78 86 90 88
MCH 34 27 29 30 30
MCHC 33 33 34 34 34
RDW 12.8 + 1.2% SD of RBC Vol x 100 MCV
Serum Fe 60-170 ug/dl
Ferritin (median)
40(15-200)ng/ml
100(15-300)ng/ml
TIBC 250 - 400ug/dl
Transferrin saturation
20-50% Fe x 100 TIBC
Lab tests of iron deficiency of increased severity
NORMAL Fe deficiencyWithout anemia
Fe deficiency With mild anemia
Fe deficiency With severe anemia
Serum Iron 60-150 60-150 <60 <40
Iron Binding Capacity
300-360 300-390 350-400 >410
Saturation 20-50 30 <15 <10
Hemoglobin Normal Normal 9-12 6-7
Serum Ferritin 40-200 <20 <10 0-10
Laboratory assessment of microcytic anemia
Test Fe Defic Anemia ofinflammation
Thal
Ferritin Low* NL/high NL
Serum Fe Low Low NL
TIBC High NL/low* NL
% Sat Low Low NL
Retic index
NL/low NL/low NL/high
*best discriminators of Fe defic vs anemia of inflammation
KINETICS OF ERYTHROPOIESIS
Hyporegenerative (marrow not working well)
Hyperregenerative (marrow working)
Calculating the reticulocyte index will usually tell you which category your patient is in
Reticulocyte Response
Reticulocyte Index correlates best with RBC production– Correct for low RBC count (absolute retic count)– Correct for immature retics if present (factor of
2)
“Normal” RI = 1 but should go up in anemia if marrow function normal– Normal or low RI in anemia implies
hyporegenerative state– Very high RI (>4) suggests hemolysis
Corrected reticulocyte count
(Spuriously elevated when no. of RBC fall in anemia, hemolysis)
% = retic count x actual hematocrit
Normal hematocrit
Absolute reticulocyte count (50-100 x109/L)-
Retics/ L = Retics(%) X RBC count
(>1 lakh/dl indicate increase marrow activity)
Retic Index
Time Maturation
1
45
Hct % Retic RI
Retic Index Response
< 2 Inappropriate2 – 3 Not sure> 3 Appropriate
When Hct 25 or less, use 1/2 for maturation time term
Example – Labs:
Hct 25, WBC 12.0, Platelets 545, MCV 92,
Retic 5.8% (normal 0.5 to 2.2%)
days 2
1
45
25 5.8% RI RI = 1.6
too low
Calculation iron def. B-thal trait
(mentzer)
MCV >13 <13
RBC
(Srivastava)
MCH >3.8 <3.8
RBC
Hyporegenerative anemia
• Nutritional deficiency (iron, B-12, folate) • Marrow dyscrasia (leukemia,
myelodysplasia, aplastic anemia etc)• Thalassemia• Low EPO state (renal disease,
inflammation, endocrinopathy)
Retic index not appropriately increased
Hyperregenerative anemia
• Hemolysis • Blood loss
Retic count increase generally less striking than in hemolysis
Retic index increased
Normal Polychromasia
Normal rbcMicrocytosis, hypochromia
Normal Macrocytic/megaloblastic
Microangiopathic hemolytic anemia
Spur cell anemia (liver disease)
Hereditary spherocytosis
Increased DestructionIMMUNE MEDIATED
Cold Agglutinin– Paroxysmal nocturnal hemoglobinuria– Post mycoplasmal hemolytic anemia
Warm Agglutinin– Drug induced– Autoimmune hemolytic anemia– Transfusion reaction
Increased DestructionNON-IMMUNE MEDIATED
Extra-corpuscular– Macro-circulatory
HypersplenismExtracorporeal circulation
– Micro-circulatoryDICTTPHUS
Intra-corpuscular– RBC Wall (membrane or enzyme defects)– Heme or globin abnormalities (HbS, C)
Functional Tests for Macrocytic Anemias
Homocysteine: high may mean
deficiencies of folate, B12 or B6Methylmalonic acid distinguish between B12 and folate deficiencies (↑ in B12 deficiency)Schilling test: radiolabeled cobalamin is used to test for B12 malabsorption
Methylfolate TrapMethylfolate TrapIn the absence of B12, folate in the body exists as 5-methyltetrahydro-folate (an inactive form)B12 allows the removal of the 5-methyl group to form THFA
Diagnosis of Folate Deficiency
Folate stores are depleted after 2-4 months on deficient dietMegaloblastic anemia, low leukocytes and plateletsTo differentiate from B12, measure serum folate, RBC folate (more reflective of body stores) serum B12High formiminoglutamic acid (FIGLU) in the urine also diagnostic
Iron deficiency anemia
Pathophysiology-
-dietry history
-Pica history –cause lead poisoning & helminthic infections.
C/F – irritability, anorexia weakness fatiguebleg cramps breathlessness & tachycardia.
CCF & spleenomegaly in severe anemia.
Angular stomatitis glossitis koilonychia &platynychia in severe cases.
Investigation-
PS – M/C H/C ,anisocyte, poikilocyte & RDW, MCV MCHC reducedtotal no. of RBCs reduce(unlike in thallasemia it is increase)
Serum Fe &Ferritin reduced but TIBC increased Transferrin saturation reduced to16%.
High free erythroprotoporphyrin precedes anemia
Megaloblastic anemia
Pathophysiology- impaired nuclear maturation due to lack of MTHF folic acid derivative need for DNA synthesis.
-premature death of cell before release from the bone marrow,termed as “ineffective erythropoisis”
-affect all cell line result in anemia, thrombocytopenia and leukopenia.
Dietry history malabsorbtion ,infestation pernicious anemia H/O autoimmune dissorder.
C/F – anemia anorexia, irritability.
Characterstically glossitis stomatitis hyperpigmentation of skin on knuckle & terminal phalanges hepatospleenomegaly (30 to 40%)
-neurologycal sign preced anemia.
-petechiae & hemorrhagic menifestation (25%)
- Signs of malabsorption- wt loss, diarrhoea abd distention & steatorrhea.
Neurological sign- loss of position & vibratory sensation.memory loss , confusion neuro psychiatric symptoms. Theses signs may persist despite correction of deficiency.
Lab investigationMacrocyte cell , cytopenias & hypersegmented neutrophil,serum B12 level & folic acid level.
-Shilling test
(Include intrinsic factor D/F between pernicious anemia & malabsorbtion (common in child))
- Bone marrow to rule out leukemia, MDS & aplastic anemia
- Bone marrow show- cellular Nuc/Cyt asynchrony in RBCs precursor
- -serum LDH & indirect bilirubin
Hemolytic anemiaC/F acute hemolysis- weakness, pallor & fatigue. Jaundice is prominent. Red urine suggest hemoglobinuria
- spleenomegaly in autoimmune & congenitaal hemolytic anemia.
-Gall stone (spherocytosis)
-hemolytic facies
-leg ulcer in(sickle cell anemia)
Lab investigation
Devide in 3 groups-
1- increase in RBCs destruction
2- comansatory increase in the rate of erythropoisis
3- features of etiology of hemolytic anemia
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