RBC Disorders-
the conclusion
Dr Bhavya J Menon
Dept of Pathology
DMMC
HEMOLYTIC ANEMIA
HA due to intrinsic mechanisms
Congenital
► Defects in red cell membrane
Hereditary spherocytosis, Hereditary elliptocytosis
► Defects in globin structure
Sickle cell anemia, Unstable Hb disease
► Defects in globin synthesis
Thalassemia
► Deficiency of red cell enzymes
G6PD deficiency, Pyruvate kinase deficiency
Acquired
Paroxysmal nocturnal hemoglobinuria
HEMOLYTIC ANEMIA
HA due to extrinsic mechanisms
Immune hemolytic anemia
HDN, blood transfusion reactions, autoimmune HA
Red cell fragmentation syndromes
Microangiopathic HA, HA due to prosthetic valves
HA associated with infections
Black water fever, Clostridial sepsis
HA caused by chemical agents
Snake and spider venoms, acute drug reactions
HA caused by physical agents
Thermal injury
Microangiopathic
Hemolytic Anemia
MAHA- Microangiopathic Hemolytic
anemia
• Hemolytic Uremic Syndrome
• Thrombotic Thrombocytopenic Purpura
Thrombotic microangiopathies
• Classic childhood HUS
• Adult HUS
-Infection,Antiphospholipid ab
-Complications of pregnancy &
contraceptives
-Vascular renal disease
-Drugs
-Radiation
• Familial HUS
• Idiopathic TTP
Pathogenesis
Endothelial injury&
Activation
Platelet activation
Vascular obstruction,
Vasoconstriction & Distal
ischemia
Classic(Childhood hemolytic
anemia)
• 75% in children after intestinal infection
with Shiga like toxin E.coli 0157:H7
• Sudden onset of bleeding
manifestations
• Severe oliguria, hematuria
• Microangiopathic hemolytic anemia
• Renal injury
• Thrombocytopenia
• Adult HUS-
• Familial HUS
-Recurrent thrombosis
-Higher mortality rate
-Inherited def of complement
regulatory factor H
Thrombotic thrombocytopenic
purpura TTP
• Genetic defect of ADAMTS-13
-Overlap with HUS
• MAHA
• Thrombocytopenia
• Acute renal injury
• Fever
• Neurological symptoms
Schistocytes
• Fragmented or greatly distorted
red cells
• Smaller than normal red cells
• Triangular or helmet-shaped
• Seen in red cell fragmentation
syndromes
• Prosthetic valves and cardiac
anomalies
• Microangiopathic HA
• HUS, TTP, DIC,
disseminated Ca
• Platelet count and D-dimer test
Schistocytes &
Helmet cells
Mechanism of hemolysis
• Cardiac valve prosthesis: Shear stresses produced by
turbulent blood flow & abnormal pressure gradients
• Microangiopathic hemolytic anemia: Occurs when red
cells are forced to squeeze thro abnormally narrow
vessels
• March hemoglobinuria
Anemia of chronic
disease
Anemia of Chronic disease
• Type of anemia seen in a wide range of chronic
inflammation, infection& malignant diseases.
• Apparent during first few months of disease & then
becomes constant
• Rarely severe
• Correlation between the cause & severity
1.Chronic microbial infection such as
osteomyelitis, bacterial endocarditis
& brain abscess
2. C/C immune disorders-
CAUSES Rheumatoid arthritis, Regional
enteritis
3. Neoplasms- Hodgkin lymphoma
Ca of lung & breast
Anemia of chronic disease
• Most important cause of ACD is impaired red cell
production assoc. with disease
• Assoc.with erythroid proliferation & impaired Fe
utilisation
• Mimics Fe defn. anemia
Pathophysiology- ACD
Defect in reuse of Fe
block in transfer from storage pool to erythroid
precursors
Marrow hypoproliferation due to inappropriately
low level of erythropoietin response
Low erythropoietin is due to action of IL1,TNF alpha
& IF gamma secreted by underlying infection/inflm.
Pathophysiology- ACD
• Combination of decreased red cell production & red cell
survival
• In severe arthritis red cell survival is 80- 90 days
• Red cell are prematurely consumed by the overeactive
RES
Low serum iron
Common Low TIBC
features
Abundant stored Fe in
mononuclear phagocytic
system
Abnormalities of Fe metabolism
• Low Fe absorption from GIT
• Low plasma Fe conc.
• Excessive retention of Fe in RE cells
• Decreased release of erythroid cells
Morphology
• PS:-NCNC/MCHC
• Neutrophilia
• Thrombocytosis
• Reticulocytopenia
Bone marrow- ACD
• BM
Normal or increased Fe with decreased marrow
sideroblasts
ACD - Treatment
• Diagnosis:-H/o C/C disease with anemia
• Rx.treat the underlying disease
APLASTIC ANEMIA
DEFINITON
• Is a disorder of hematopoiesis
• Characterised by
PANCYTOPENIA in peripheral blood
DECREASED CELLULARITY in BM
• Bone marrow stops making blood cells due to damage
to STEM CELLS in BM
Causes of aplastic anemia
ACQUIRED
Idiopathic
Drugs and chemicals
Radiation
Infections
PNH
CONGENITAL
Fanconi anemia
Dyskeratosis congenita
Schwachman diamond syndrome
What kinds of drugs?
• Cytotoxic drugs – dose dependant
reversible
• Idiosyncratic reaction
(sulphonamides,NSAIDS,antiepileptics)
• CHEMICALS – benzene, insecticides,etc
Viruses
• Following hepatitis
• ParvoB19 infection esp in conditions of chronic
hemolysis
• EBV infection - IMN
• Cytomegalovirus infection
What could be going wrong ?
Few mechanisms like:
• Reduction in number of stem cells
• Defective stem cells
• Defective environment for hematopoiesis
• Inhibition by immunologic mechanisms( major cause)
Effects of aplastic anemia on body
Reduced number of RBCs
• fatigue,dyspnoea, c/c – heart failure
Reduced WBCs
• neutropenia – infections - fever
Effects of aplastic anemia on body
Reduced platelet count
• Bruising and bleeding manifestations
(menorrhagia,gumbleeds petechia)
• Usually NO lymphadenopathy or
hepatosplenomegaly.
• IN the presence of SPLENOMEGALY other
diagnosis should be considered.
How do you reach a diagnosis?
• Clinical picture
• Peripheral smear
PANCYTOPENIA
Diagnosed if any of the below 2 conditions are met:
Hb < 10 g/ dl
Neutrophil ct < 1500/cu. mm
Platelet count <50,000/cu mm
Differentials to be considered?
PANCYTOPENIA
• APLASTIC ANEMIA
• INFILTRATION into bone marrow (leukemias,metastatic
ca,storage disorders, myelodysplasia)
• Megaloblastic anemia
• PNH
• SLE
• MILIARY TB
• HYPERSPLENISM
How do u reach the diagnosis?
• BONE MARROW & TREPHINE BIOPSY
• Exclude all the differentials
• Picture in aplastic anemia
marked decrease in cellularity
precursors of all lineages reduced
• Correct assessment of cellularity trephine is necessary
MARROW: Hypocellular or
Hypercellular
Hypocellular
• Acquired aplastic anemia
• Inherited bone marrow failure
• Hypoplastic MDS
• Viral causes
Hypercellular
primary: BM disease
secondary: metastasis, nutrition, storage,
hypersplenism, sarcoidosis
NORMAL
BONE
MARRO
W
APLASTIC ANEMIA
Additional tests
• Viral titres & liver function test – hepatitis
• Hams test – PNH
• Chromosomal studies – Fanconis anemia
Treatment
• HEMATOPOIETIC STEM CELL TRANSPLANTATION
• IMMUNOSUPPRESSIVE THERAPY
• Supportive measures
POLYCYTHEMIA
Polycythemia denotes an
• abnormally high red cell count,
• with a corresponding increase in the hemoglobin level.
• Relative - hemoconcentration due to decreased plasma
volume, or
• Absolute - increase in the total red cell mass.
Thankyou
