Download - Approach to Congental Hemolytic Anemias
![Page 1: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/1.jpg)
APPROACH TO CONGENTAL HEMOLYTIC ANEMIAS
Dr. Somendra ShuklaFellow Neonatology
![Page 2: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/2.jpg)
Other questions to guide you
Is this acute or chronic? Is this acute or chronic? Is there a family history? Is there a family history? Does the child appear ill, or have signs of Does the child appear ill, or have signs of systemic disease? systemic disease? Are the liver and spleen large? Are the liver and spleen large? (extramedullary extramedullary sites of sites of hematopoiesis hematopoiesis) Exposure to infectious disease: HIV, Exposure to infectious disease: HIV, malaria, dengue malaria, dengue
![Page 3: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/3.jpg)
But first, is there really anemia?
• Anemia: Central venous hemoglobin < 13 g/dL or capillary hemoglobin < 14.5 g/dL in infant > 34 weeks and 0-28 days old
![Page 4: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/4.jpg)
![Page 5: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/5.jpg)
The Three Primary Measures
MeasurementA. RBC count (RCC) 5 million B. Hemoglobin 15 g%C. Hematocrit (PCV)45
A x 3 = B x 3 = C - This is the rule of thumbCheck whether this holds good in a given result
If not -indicates micro or macrocytosis or hypochro.
![Page 6: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/6.jpg)
The Three Derived Indiceseasurement Normal
A. RCC 5 million B. Hemoglobin 15 g%C. Hematocrit 45 %
MCV C ÷ A x 10 = 90 flMCH B ÷ A x 10 = 30 pgMCHC (%) B ÷ C x 100 = 33%
![Page 7: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/7.jpg)
Anemia – Second Test
RETICULOCYTE COUNT %
NormalLess than 2%
• ‘RBC to be’ or Apprentice RBC• Fragments of nuclear material• RNA strands which stain blue
![Page 8: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/8.jpg)
Reticulocyte
No definite nucleus
Reticulum of RNA
Deep blue staining
Light blue cytoplasm
Cell size about 10 µ
![Page 9: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/9.jpg)
Reticulocytes
Leishman’sSupravital
![Page 10: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/10.jpg)
Reticulocyte Production IndexFor example, the RPI is calculated as follows
Reticulocyte count 9%Hb content 7.5 g%1. Correction for Anemia
= 9 x (7.5 ÷ 15) = 9 x 0.5 = 4.5 %2. Correction for life span
4.5 ÷ 2 = 2.25 %3. Thus, the RPI is 2.25
![Page 11: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/11.jpg)
www.drsarma.in
Anemia
Hypoproliferative Hemolytic
RPI < 2 RPI > 2
![Page 12: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/12.jpg)
The Reticulocyte production index (RPI, also called a corrected reticulocyte count)
•raw reticulocyte count is misleading in anemic patients. •reticulocyte count is not really a count but rather a percentage: it reports the number of reticulocytes as a percentage of the number of red blood cells. •In anemia, the patient's red blood cells are depleted, creating an erroneously elevated reticulocyte count
![Page 13: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/13.jpg)
www.drsarma.in
Workup – Third Test
• The next step is ‘What is the size of RBC’ ?• MCV indicates the Red cell volume (size)• Both the MCH & MCHC tell Hb content of RBC• If the RPI is 2 or less• We are dealing with either
– Hypoproliferative Anemia (lack of raw material)– Maturation defect with less production– Bone marrow suppression (primary/ secondary)
![Page 14: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/14.jpg)
www.drsarma.in
Mean Cell Volume (MCV)
• RBC size is measured indirectly by• The Mean Cell Volume (MCV) and RDW
Microcytic
< 80 fl
MCV
Normocytic Macrocytic
80 -100 fl > 100 fl
< 6.5 µ 6.5 - 9 µ > 9 µ
![Page 15: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/15.jpg)
www.drsarma.in
Anemia Workup - MCV
Microcytic
MCV
Normocytic Macrocytic
Iron Deficiency (IDA)Chronic InfectionsThalassemiasHemoglobinopathiesSideroblastic Anemia
Chronic diseases, CKDEarly IDAHemoglobinopathiesPrimary marrow disordersCombined deficienciesIncreased destruction
Megaloblastic anemiasLiver disease/alcoholHemoglobinopathiesMetabolic disordersMarrow disordersIncreased destruction
![Page 16: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/16.jpg)
Presentation of hemolytic anemia
• Jaundice is usually the first symptom• Compensatory reticulocytosis• Pallor presents after 48 hours of age• Unconjugated hyperbilirubinemia of > 10-12
mg/dL• Tachypnea and hepatosplenomegaly may be
present
![Page 17: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/17.jpg)
Hemolytic Anemia
• Definition:– Those anemias which result from an increase in
RBC destruction
• Classification:– Congenital / Hereditary– Acquired
![Page 18: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/18.jpg)
Laboratory Evaluation of HemolysisExtravascular Intravascular
HEMATOLOGIC
Routine blood filmReticulocyte countBone marrow examination
Polychromatophilia
Erythroid hyperplasia
Polychromatophilia
Erythroid hyperplasia
PLASMA OR SERUM
BilirubinHaptoglobinPlasma hemoglobinLactate dehydrogenase
Unconjugated , Absent N/ (Variable)
UnconjugatedAbsent (Variable)
URINEBilirubinHemosiderinHemoglobin
000
0++ severe cases
![Page 19: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/19.jpg)
Inherited or acquired:
• Inherited HA are usually caused by intrinsic defect.• While acquired HA are caused by an extrinsic
defect.• However there are some exceptions: Paroxysmal
nocturnal haemoglobinuria (PNH) which is an acquired intrinsic defect, and severe hereditaryG6PD enz deficiency which requires the presence of an extrinsic trigger such as the antimalarial drug for the intrinsic defect to manifest.
![Page 20: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/20.jpg)
Hemoglobinuria
![Page 21: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/21.jpg)
Classification of Hemolytic Anemias
Hereditary 1. Abnormalities of RBC interior a.Enzyme defects: G-6-PD def,PK def b.Hemoglobinopathies 2. RBC membrane abnormalities a. Hereditary spherocytosis etc. b. PNH
Acquired c. Spur cell anemia3. Extrinsic factors a. Hypersplenism b. Antibody: immune hemolysis c. Mechanical trauma: MAHA d. Infections, toxins, etc
Ref : Harrison’s
![Page 22: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/22.jpg)
Features of HEMOLYSISBilirubin
LDHReticulocytes, n-RBC
Haptoglobulins+ve Urinary hemosiderin, Urobilinogen
Blood Film
Spherocytes No spherocytes Fragmentation
DCT +ve DCT –ve
AI Hemolysis H. Sherocytosis Malaria, Clostidium Hereditery enzymopathies Microangiopathic,
Traumatic
![Page 23: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/23.jpg)
Red Cell Membrane Defects
1.Hereditary Spherocytosis– Usually inherited as AD disorder– Defect: Deficiency of Beta Spectrin or Ankyrin
Loss of membrane in Spleen & RES becomes more spherical Destruction in Spleen
![Page 24: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/24.jpg)
RBC Membrane
![Page 25: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/25.jpg)
– C/F:• Asymptomatic• Fluctuating hemolysis• Splenomegaly• Pigmented gall stones- 50%
![Page 26: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/26.jpg)
Complications
• Clinical course may be complicated with Crisis:– Hemolytic Crisis: associated with infection– Aplastic crisis: associated with Parvovirus infection
![Page 27: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/27.jpg)
• Inv:– Test will confirm Hemolysis– P Smear: Spherocytes– Osmotic Fragility: Increased
Screen Family members
![Page 28: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/28.jpg)
Osmotic Fragility
![Page 29: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/29.jpg)
• Management:– Folic Acid 5mg weekly, prophylaxis life long– Spleenectomy– Blood transfusion in Ac, severe hemolytic crisis
![Page 30: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/30.jpg)
2.Hereditary Elliptocytosis• Equatorial Africa, SE Asia• AD / AR• Functional abnormality in one or more anchor
proteins in RBC membrane- Alpha spectrin , Protein 4.1
• Usually asymptomatic• Mx: Similar to H. spherocytosis• Variant:
3.SE-Asian ovalocytosis:• Common in Malaysia , Indonesia…• Asymptomatic-usually• Cells oval , rigid ,resist invasion by malarial parasites
![Page 31: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/31.jpg)
Elliptocytosis
![Page 32: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/32.jpg)
Red Cell Enzymopathies
• Physiology:– EM pathway: ATP production– HMP shunt pathway: NADPH & Glutathione
production
![Page 33: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/33.jpg)
1. Glucose-6-Phosphate Dehydrogenase ( G6PD ) Deficiency– Pivotal enzyme in HMP Shunt & produces NADPH
to protect RBC against oxidative stress–Most common enzymopathy -10% world’s
population–Protection against Malaria–X-linked
![Page 34: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/34.jpg)
(Oxidised form)(Reduced form)
![Page 35: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/35.jpg)
• Clinical Features:– Acute drug induced hemolysis:
• Aspirin, primaquine, quinine, chloroquine, dapsone….– Chronic compensated hemolysis– Infection/acute illness– Neonatal jaundice– Favism
![Page 36: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/36.jpg)
• Inv:– e/o non-spherocytic intravascular hemolyis– P. Smear: Bite cells, blister cells, irregular
small cells, Heinz bodies, polychromasia– G-6-PD level
• Treatment: – Stop the precipitating drug or treat the
infection– Acute transfusions if required
![Page 37: Approach to Congental Hemolytic Anemias](https://reader031.vdocuments.us/reader031/viewer/2022020211/577cc7471a28aba711a0823c/html5/thumbnails/37.jpg)
2. Pyruvate Kinase Deficiency– AR– Deficient ATP production, Chronic hemolytic
anemia– Inv;
• P. Smear: Prickle cells• Decreased enzyme activity
– Treatment: • Transfusion may be required