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 a. hepatitis b. infectious mononucleosis EBV

infections

c. parvovirus B19
immunologic disorders

a. transfusion associated GVHD b. SLE (collagen vascular disease)

Paroxysmal nocturnal hematuria Congenital disorders

a. fanconis 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 a. antibiotics b. transfusion support

supportive therapy

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 - sweets 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