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HEMOLYTIC ANEMIA
Afnan Shamraiz
OBJECTIVES
• Lab indication of hemolysis
• Intravascular v/s extravascular hemolysis
• D/D of hemolytic anemia
• Diagnose hemo.anemia with peripheral smear &
ancillary lab tests
NORMAL RED CELLS
No nucleusBiconcave discsCenter 1/3 pallorPink cytoplasm (Hb filled)Cell size 7- 8 µ - capill. Negative charge 100-120 days life span
THE FACTORY – BONE MARROW
Sternum, pelvis, vertebrae, long bones, skull bones, Tibia (paed)
From stem cells (pleuripotent)
75% of marrow for WBC
25% of BM for Red cells
Erythrod / Granulocyte Ratio 1:3
Large white areas are marrow fat
ERYTHROPOIESIS
15-20µm- basophilic cytoplasm, nucleus with nucleoli.
14-17µm-mitosis, basophilic cytoplasm, nucleoli disappears.
10-15µm-’POLYCHROMASIA’
Hb appears, nucleus condenses.
7-10µm- PYKNOTIC Nucleus.
Extrusion, Hb is maximum.
7.3µm- Reticulum of basophilic material in the cytoplasm.
7.2µm- Mature red cell with Hb.
RETICULOCYTE
• Reticular nuclear fragments
• Nucleus extruded
• Slightly larger than RBCs
• Fully mature with in 2 days as their contents are degraded by intracellular enzymes.
• Count = 1-2% of red cells
• Provide an index of rate of RBC formation
HAEMOLYTIC ANAEMIAS
•The normal red cell life is 110-120(half life 55-60 days) days after which the senile cells are removed by bone marrow and splenic macrophages.•Reduced red cell survival leads to increased red cell production due to erythropoietin drive that can compensate for the reduced red cell life and maintain a normal Hb level.•The mean red cell life is affected by molecular changes in either the red cell membrane or haemoglobin.
• A haemolytic state exists when the in vivo survival of the RBC is shortened.
• Anaemia occurs if the onset of haemolysis is sudden with no time for marrow compensation or in severe chronic haemolysis when the mean red cell life is very short.
• The usual marrow response in acute hemolytic anemia is reflected by a reticulocyte index of 2–3, whereas in long-standing chronic hemolysis, the increase in erythropoiesis is approximately 6-fold.
HAEMOLYTIC ANAEMIA
Intravascular• Intravascular• red cells lyse in the
circulation and release their products into the plasma fraction.
• Anemia• Decreased Haptoglobin• Hemoglobinemia• Hemoglobinuria• Urine hemosiderin• Increased LDH
Extravascular• Increased LDH
• Extravascular
• ingestion of red cells by macrophages in the liver, spleen and bone marrow
• Little or no hemoglobin escapes into the circulation
• Anemia
• Decreased Haptoglobin
• Normal plasma hemoglobin
CLINICAL FEATURES
Jaundice: generally mild and often not noticed by the patient.
Anaemia: recent onset = acquiredlong-standing = possibly congenital.
Haemoglobinuria: intravascular haemolysis.Urobilinogenuria: increased Hb catabolism.
Splenic pain: spenomegaly or splenic infarction.
Leg ulcers: intrinsic red cell disorders, e.g. sickle cell disease.Dactylitis; in sickle cell ds
Skeletal hypertrophy: severe congenital haemolytic anaemias and thalassaemias.
HEMOLYTIC FACIES- CHIPMUNK FACIES
EVIDENCE OF ERYTHROPOIESIS
• Polychromasia
• Increased reticulocyte
• “Shift” macrocytosis
• Hypercelluar BM
Nelson texrbook of paediatrics 19the.
Hem
oly
tic
an
em
ia
CELLULAR DEFECTSMembrane defects
Enzyme defectsHemoglobin
abnormalities
EXTRACELLULAR DEFECTS
Autoimmune H.AFragmentation
hemolysisHypersplenismPllasma Factors
CELLULAR DEFECTS
Membrane defects
Hereditary spherocytosis
Hereditary elliptocytosis
Hereditary pyropoikilocytosis
Hereditary stomatocytosis (possibly Rh null)
PNH (sensitivity to complement lysis -- sugar water test, Ham’s test)
Acanthocytosis
Enzyme defects G-6-P-D defficiency
Pyruvate kinase deficiency
Other glycolytic enzyme deficiencies
Phosphofructokinase d.
Triose phosphate isomerase(TPI) d.
Phosphoglycerate kinase (PKG) d.
Hemoglobin abnormalities.
Unstable hemoglobin disease
Sickle cell anemia Other homozygous
hemoglobinopathies (CC, DD, EE;
Thalassemia major Hemoglobin H disease Doubly heterozygous
disorders (such as hemoglobin SC disease and sickle thalassemia)
Hereditary methemoglobinemia
EXTRACELLULAR DEFECTS
Immune H.A
AlloimmuneHemolytic Ds of NB
ABO I.C
Rh. I.C
Other B.group I.C
Hemolytic Transfusion Reaction
Autoimmune Idiopathic(primary) Cold antibody
Warm antibody
Secondary or symptomatic (in case of lymphoma, chronic lymphocytic leukemia, Other malignant disease, Immune-deficiency states, Systemic lupus erythematosus and other autoimmune disorders, Virus and mycoplasma infections)
Paroxysmal Cold hemoglobinuria
Fragmentation hemolysis DIC, TTP. HUS
Extracarporeal membrane oxigenation
Prosthetic heart valves
Burns-thermal injury
Venom - Snake, Spider, Bee
Hypersplenism
Plasma factors
Liver disesaes
Abetalipoproteinemia
Infections(Malaria Babesia Clostridium Gram negative endotoxin)
Wilsons disesae
Venom - Snake, Spider, Bee
Nelson text book of paediatrics 19th e.
PATIENT HISTORY
• Acute or chronic
• Medication/Drug precipitants
G6PD
AIHA
• Family history
• Concomitant medical illnesses
• Clinical presentation
FINDINGS IN HEMOLYTIC ANEMIA
Reticulocyte count Increased
Serum Unconjugated Bilirubin Increased
Serum LDH Increased
Serum Haptoglobin Decreased
Urine Hemoglobin Present
Urine Hemosiderin Present
Urine Urobilinogen Increased
Cr 51 labeled RBC life span Decreased
FEATURES OF HEMOLYSISBilirubin
LDH
Reticulocytes, 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
TESTS
• CBC with retics……Hb, reticulocytosis…hemolysis.TLC for infection
• Thrombocytopenia and neutopenia….hypersplenism
• LDH….increased
• Haptoglobins….decreased
• Urinary and fecal urobilinogen….increasesd
• hemoglobinuria
• Serum Blbn levels….hyperbilirubinemia(indirect)
• Bioten & Na2 Cr4…. Labelling…reduced RBC survival• METHALBUMEN….INCREASED(oxidised heme binds to albumin)
• Pink colour plasma…free Hb in plasma
TESTS….
• IDA…. Secondary to chronichemolysis
• End tidal CO…hemolysis
• Bone marrow….hyperplastic(erythroid hyperplasia)
hypoplastic, aplastic in parvo B19 infection
• Coombs test(direct and indirect)…imunune H.A
• Warm n cold antibody
• G6PD assay….G6PD deficiency
• PK assay…..Pk deficiency
• Osmotic fragility test…H.S
• Abnormal cytoskeltal proteins analysis…H.elliptiocytosis
• Thermal sensitivity….fragmentation at 45 c for15 min…pyropiokilicytosis
• Hb electropherisis…..hemoglobinopathies
TESTS…
• Decreased WBC CD55 and Cd 59, decreased RBC CD59 by flow cytometry,…..PNH
• Ham test, Sucrose lysis test….PNH
• PT,ApTT, d-dimers,FDPs….DIC
• Altered plasma cholesterol and phospholipids…liver Ds
• Absence of apolipoprotein β….abetalipoproteinmia
• Blood cultures and serlogy…for infectiuos etiology
• S.copper, seruloplasmin, penicillamin challenge test, urinary cupper……wilsons ds
• ANA…..SLE
RED BLOOD CELLS: BLOOD SMEAR
SPHEROCYTES
- hereditary spherocytosis- acquired hemolytic
anemia (e.g. AIHA)- physical or chemical
injury- heat
ELLIPTOCYTES
- heredirary elliptocytosis
- iron def. anemia- myelofibrosis with
myeloid metaplasia
- - normal (<10% of cells)
STOMATOCYTESSLIT LIKE CENTRAL PALLOR IN RBC
1. Liver Disease
2. Acute Alcoholism
3. H Stomatocyosis
4. Malignancies
(normal red cell, a stomatocyte has a centrally located linear slit or stoma (fish mouth) and the MCV is usually increased. On scanning EM, a stomatocyte looks like a ball with a single concavity (cup-shaped))
ACANTHOCYTES(IRREGULAR SURFACE SPICULES)
Irregularly spiculated cells with
bulbous/rounded ends of spicules
- abetalipoproteinemia- liver disease
ECHINOCYTES(CRENATED CELLS, BURR CELLS,PRICKLE CELLS)
Regularly contracted cells with smooth surface undulation- PK-D- uremia
BITE CELLS
Removal (“bites”) of membrane by splenic macrophages
- G6PD deficiency
DREPANOCYTES(SICKLE CELLS)
- sickle cell anemia
DACROCYTES(TEARDROP CELLS)
- thalassemia- myelofibrosis
LEPTOCYTES(TARGET CELLS)
- liver disease (obstructive jaundice)
- post splenectomy- hemoglobinopathies (hypochromic anemias)
thalassemiaHgb C diseaseHgb H disease
relative increase of cell membrane --> “target” formation
ROULEAUX
lined up RBCs in a row
- multiple myeloma
Red cells stuck together by abnormal protein (rouleaux)
HOWELL-JOLLY BODY
remnant of nuclear chromatin
single:•megaloblastic anemia•hemolytic anemia•post splenectomy
multiple:•megaloblastic anemia•other abnormal erythropoiesis
ACANTHOCYTES5-8 SPIKES OF VARYING LENGTH, IRREGULAR INTERVALS
Called Spur Cells
SCHISTOCYTES(CELL FRAGMENTS)
indication of hemolysis
- megaloblastic anemia- severe burns- traumatic hemolysis- microangiopathic
hemolytic anemia (helmet cells, triangular cells)
“helmet cell”
RADIOLOGY
• air on end appearnce
• Thalassemia
• Sickle cell
BONE LESIONS IN MYELOMA
BONY LESIONS IN S.DS
TEATMENT
• Blood transfusion
• Steriods
• Imunosupression
• Exchange transfusion
• Imunosupression
• IVIG
• Spleenectomy
• BMT
THANKS
