HEMOLYTIC ANEMIAS:-
 Normal life span of rbc is 120 days
 Premature destruction
 Increase in reticulocyte index
 Intravascular hemolysis
 Free Hb binds to haptoglobin
 Hemoglobinuria,hemoiderinuria
 Haptoglobin levels are reduced
 Extravascular hemolysis by liver and spleen
 Megaloblastosis due to folate deficiency
 Compensated and decompensated hemolysis
CLASSIFICATION :-
 Abnormalities of RBC interior
a. enzyme defects
b. hemoglobinobathies
 RBC membrane abnormalities
a. hereditary spherocytosis
b. paroxysmal nocturnal hemoglobinuria
c. spur cell anemia
 Extrinsic factors
a. hyperspleenism
b. antibody: immune hemolysis
c. microangiopathic hemolysis
d. infections, toxins etc
HEREDITARY SPHEROCYTOSIS :-
 inherited as autosomal dominant
 25% cases have no family history
 Common are deficiency of betaspectrin or
ankyrin
CLINICAL FEATURES :-
 Chronic haemolytic state
 Haemolytic crisis
 Megaloblastic crisis
 Anaplastic crisis : parvovirus B-19 suppresses
bonemarrow
 Symptomatic cholecystitis
INVESTIGATIONS :-
 CBC – spherocytes
 Direct coombs test – negative
 Osmotic fragility test – sensitivity to lysis in
hypotonic solution
 Flow cytometry – binding of eosin 5- maleimide
to rbc
TREATEMENT :-
 Folic acid supplement
 Spleenectomy
 Transfusion
HEREDITARY ELLIPTOCYTOSIS :-
 The G6PD gene located on x chromosome
 Pivotal in HMP shunt
 Produces NADPH to protect RBC cells
 Affects males
CLINICAL FEATURES :-
 Precipitating factors : antimalarials
 chronic compensated state
 favism ( toxin present in weeds )
 acute illness
INVESTIGATIONS :-
 CBC : elliptic rbc cells
 G6PD levels
TREATEMENT :-
 stopping precipitants
 transfusion support
WARM ANTIBODY IMMUNOHEMOLYTIC
ANEMIA :-
 mid age and females
 causes
a. idiopathic
b. lymphomas
c. SLE and other collagen vascular diseases
d.Drugs –methyl dopa type
Penicillin type
Quindine type
e. post viral infections
INVESTIGATIONS :-
 blood smear –hemolysis , reticulocytosis
 direct coombs test
TREATEMENT :-
 treating the cause
 prednisone
 transfusion
 spleenectomy
 immunosuppression
COLD AIHA :-
 active at lower body temperature
 IgM antibodies
 Elderly persons
 Underlying lymphoma
 Donath Landsteiner antibody
 Mycoplasma
TREATEMENT :-
 Treat the cause
 Steroids
PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA :-
 An intra corpuscular defect acquired at the stem
cell level
 Inactivating somatic mutation in a single
hematopoietic stem cell of a gene on the x
chromosome (pig-A) for GPI
 Absence of CD55 and CD59
 Complement mediated hemolysis
CLINICAL FEATURES :-
 Haemolytic anemia
 Venous thrombosis
 Deficient hematopoiesis
INVESTIGATIONS :-
 Evidence of intravascular hemolysis ,
hemogolinemia, elevated LDH, hemosidenuria
 Leukopenia
 Thrombocytopenia
 Acidified serum lysis test
 Sucrose lysis test
 Flow cytometry
TREATEMENT :-
 Transfusion
 Glucocorticoids
 Acute thrombosis –anticoagulants
 Marrow transplantation
 Anti-thymocyte globulin – treating marrow
hypoplasia
APLASTIC ANEMIA :-
 Hypoproliferative anemia with marrow failure
a. aplastic anemia
b.myelodysplasia : normal stem cell to abnormal
premalignant cells leading to acute leukaemia
c. myelophthisis : bone marrow is normal and
there is infilteration of other cells.
Pancytopenia occurs
d. pure red cell aplasia
 pancytopenia – anemia
leukopenia
thrombocytopenia
 aplastic anemia – pancytopenia and bone
marrow hypocellularity
ETIOLOGY
 radiation – acute sequela
 chemicals – benzene
 drugs
a. dose dependent
 cancer chemotherapy
 alkylating aents, antimetabolites
 idiosyncratic
a. chloraphenicol , NSAIDS (long standing
osteoarthritis)
b. anticonvulsants, sulfanamides
 infections
a. hepatitis
b. infectious mononucleosis – EBV
c. parvovirus B19
 immunologic disorders
a. transfusion associated GVHD
b. SLE (collagen vascular disease)
 Paroxysmal nocturnal hematuria
 Congenital disorders
a. fanconi’s anemia
b. dyskeratosis congenital
c. shwachmann diamond syndrome
 pregnancy
CLINICAL FEATURES :-
 onset
a. abrupt
b. insidious
 bleeding most common early symptom
 anemia symptoms
 infection
 history of drug intake, chemical exposure or
preceding viral illness
 lymphadenopathy,splenomagaly absent
LAB STUDIES :-
 peripheral smear
 bone marrow
a. aspiration
b. biopsy – hematopoietic cells< 25% of marrow
space
TREATMENT :-
 bonemarrow transplantation – young patient
with fully histocompatible sibling donor
 restrict transfusion
 immunosuppression
a. anti lymphocyte globulin
b. anti thymocyte globulin
c. cyclosporine
 supportive therapy
a. antibiotics
b. transfusion support
MYELODYSPLASIA :-
 characterized by cytopenias
 dysmorphic (or abnormal appearing ) and
usually cellular bone marrow
 ineffective blood cell production
 occurs in elderly persons
 more in males
CLASSIFICATION :-
 refractory anemia (RA)
 refractory anemia with ringed
sideroblasts(RARS)
 refractory cytopenia with multilineage dysplasia
(RCMD)
 refractory anemia with excess blasts – 1 (RAEB –
1 and 2)
 myelodysplastic syndrome, unclassified
 MDS with isolated del (5q)
ETIOLOGY :-
 Radiation
 Benzene
 Alkylating agents such as busulfan, nitrosourea
or procarbazine
 Cytogenetic abnormalities – aneuploidy
CLINICAL FEATURES :-
 Asymptomatic – 50%
 Anemia
 Fever and weight loss- absent
 Splenomegaly
 Skin lesions - sweet’s syndrome
(febrile neutrophilic
dermatosis)
LAB STUDIES :-
BLOOD
 Anemia
 Bi or pancytopenia
 Isolated neutropenia or thrombocytopenia
 Macrocytosis is commom
 May be dimorphic
BONE MARROW
 Usually normal or hypercellular
 Dyserythropoietic changes and ringed
sideroblasts
 Hypogranulation and hyposegmentation in
granulocytic precursors
 Increase in myeloblasts
 Vitamin B12 or folate-normal
 Rule out viral infections, drug reaction and
chemical intoxicity
TREATMENT :-
 Unsatisfactory
 Stem cell transplantation – cure
 5 azacytidine inhibits DNA methylation
 G-CSF

 Supportive care