AnaemiaDr Zain Ul Abidin

Bahawal Victoria HospitalBahawalpur, PK

xe.zain@gmail.com

Normocytic anaemia

Presented by :-Dr.Tahira Zainab

Normocytic anaemia:-Normocytes

Normal sized cell

Normal MCV (80-96fL)

Acute blood lossanaemia of chronic

diseaseRenal failureAutoimmune

rheumatic feverMarrow

infilteration/fibrosisEndocrine disease Haemolytic anmia

Haemolytic anaemia:-

• anaemia caused by increased destruction of red blood cells.

• Life span of RBC’s decreased from 120 to fewer days.

• Break down occurs in macrophages of bone marrow,liver and spleen.

Sites of haemolysis:-

• Extravascular haemolysis• Most common; spleen and liver macrophages are sites

of destruction.

• Intravascular haemolysis• Hemoglobin is liberated and binds to hepatolobulins• Deposited as hemosiderin• Hemosiderin excreted in urine• Free Hb oxidized to methaemoglobulin

spectrophotometry of plasma forms bands;schumm’s test.

Evidence of haemolysis

• Radioisotop labled red cells 51c labelled red cells• Raised plasma Hb levels• Haemosiderinuria• Low haptoglobins• Schumm’s test

• Compensated haemolytic anaemia erythroid hyperplasia

• Reticulocytes increased in peripheral blood film.

Consequences:-

Causes:-Inherited Acquired

Red cell membrane defect Immune

Hereditary spherocytosis Autoimmune, warmHereditary eliptocytosis ColdHaemoglobinopathies Alloimmune

Thalassaemia Haemolytic transfusion reactionSickle cell disease Haemolytic disease of newbornMetabolic defects Allogenic bone marrow transplantation

G6PD deficiency Drug induced

Pyruvate kinase deficiency Non immune

Pyrimidine kinase deficiency Acquired membrane defects paroxysmal nocturnal haemoglobinuriaMiscllaneousMechanicalInfections e.g. malaria

Drugs Renal and liver disease

Inherited:-

• Red cell membrane defects

– Hereditary spherocytosis

– Hereditary eliptocytosis

Hereditary spherocytosis:-

• Most common hereditary hemolytic anaemia• Due to deficiency of structural protein Ankyrin

commonly and spectrin.• Fragile and spherical cells destructed in spleen

Clinical Features:-

• Jaundice may be present at birth or delayed for years or asymptomatic throughout life.

• Symptomatic patients develop anaemia,spleenomegaly and ulcers on legs.

• Haemolysis pigmented gallstones

Investigation:-

• Mild anaemia• Blood film shows spherocytes• Serum birlirubin and urinary urobilinogen will

be raised• Osmotic fragility• Direct antiglobulin (coomb’s test) Is negetive

Treament:-

• Raised bilirubin,gallstones present splenectomy

• Postponed in until after childhood• Preceded by immunization and lifelong

penicillin• Spherocytes persist but Hb normal• Prophylactic folate supplements

Hereditary eliptocytosis:-

• Milder than spherocytosis• Deficiency of protein spectrin/actin 4.1

complex leading to weakness of horizontal protein interaction

• Requires spleenctomy in severe cases

Hereditary stomatocytosis:-

• Red cells in which pale central area appears slit like

• Rare condition, alcohol is one of causes• Spleenectomy contraindicated as it may leade

to severe thromboembolic events.

Haemoglobinopathies:-

– Thalassaemia

– Sickle cell anaemia

• Already discussed

Metabolic defects:-

– G6PD deficiency

– Pyruvate kinase deficiency

– Pyrimidine 5’ nucleotidase deficiency

Normal metabolism:-

• ATP required for membrane integrity,shape maintanace and other works is obtained via

• Glycolytic pathway 90%• HMP shunt 10%

• In addition to provide ATP;HMP shut provides reducing power in form of NADPH (enzyme required G6PD)– Maintains reduced glutathion to combate oxidative stress

• Combates oxidative stress and prevents Hb oxidation to • methaemoglobin;that precipitates as heinz bodies

G6PD deficiency:-• Required to convert NADP to NADPH;• Common condition presenting as hemolytic anaemia• Gene involved is on X chromosome;that’s why more

common in males• Over 400 structural types• On severity of haemolysis and enzyme deficiency WHO

classified variants;common are…• African or milder type A ;haemolysis only in older cells,self

limiting haemolysis b/c new cells have sufficient enzyme• Mediterranean or B type; severe deficinecy

Clinical syndromes:-

• Acute drug induced haemolysis• Chronic haemolytic anaemia• Neonatal jaundice• Precipitated by infection• In all conditions presents as anaemia,jaundice

and haemoglobinuria

Investigation:-

• Blood counts normal between attacks

• During attacks;– Blood film shows; bite

cells,blister cells,heinz bodies

– reticulocytosis• Evident haemolysis• Enzyme assay

Treatment:-

• Offending drug should be stopped

• Infections treated• Blood transfusion

may be life-saving• Splenectomy not

usualy required

Pyruvate kinase deficiency:-

• Common after G6PD deficiency• Presents as anaemia and blood film

disorders,pyruvate kinase activity low• Treated by blood transfusion• Splenectomy in severe cases

Pyrimidine 5’ nucleotidase deficiency:-

• Enzyme required for RNA degradation in reticulocytes to remove residues of RNA

• Deficiency causes basophilic stipling of RBC’s• Enzyme also inhibited by lead• Causes haemolytic anaemia

Acquired hemolytic anaemias:-

– Immune

– Non immune

Immune:-

– Autoimmune• Warm and cold

– Alloimmune• HDN (haemolytic disease of newborn)

– Drud induced

Immune:-

• Autoimmune Haemolytic anaemia (AIHA):-– Increased cell destruction because of red cell

autoantibodies– Antibodies detected on cell surface (coomb’s test)– Depending on if antibodies attaches to cell at 37 Oc

or at lower temperature AIHA divided into cold and warm types

– Destruction may be complement mediated (by lysis complex) or phagocytesed by macrophages.

Warm autoantibodies:-

• IGg predominantly• Direct antiglobin test positive with IGg

alone,IGg and compliment ,or complement alone

Clinical features:-

• Middle aged female common but can occur in both sexes at any age

• Short episodes of anemia• Remintting and relapsing jaundice• Intermittent chronic pattern• Spleen palpable• May be associated with WBC’s malignancy

Rheumatoid arthritis,SLE or drugs

Investigations:-

• Evidence of haemolysis• Spherocytes present• Coomb’s test positive• Autoimmune thrombocytopenia may be

present

Treatment:-

• Corticosteroids; e.g. prednisolone 1mg/kg daily effective 80%– Reduced antibody formation– Reduced RBC destruction

• Splenectomy in no response to steroids• Immunosupperssive e.g. azathioprine• Blood transfustion

Cold autoantibodies:-

• Agglutinins reacting at 40C• Harmless usualy. At low temperature presents

just like warm antibodies present as.

Drug induced haemolytic anaemia:-

• Interaction between drug and cell membrane,three types of intraction– Antiboies to drug only;quinidine,rifampicin:-

resolves when drug withdrawn– Antibodies to cell membrane only;methyldopa– Antibodies to both; e.g. penicillin

Alloimmune haemolytic anaemia:-

• Antibodies produced in one individual react with the red cells of another. Occurs in;

• Haemolytic disease of newborn• Transfusion reactions• Allogenic transplants of bone

marrow,liver,heart,kidney.

Haemolytic disease of newborn (HDN):-

• HDN due to fetomaternal incompatibility for red cell antigens.

• Maternal antibodies only IGg cross placenta and destroy fetal red cells.

• Common types• ABO type common but milder;mother is O and fetus A• RhD incompatibility less common b/c of anti-D

prophylaxis

Note:-

• Fetal blood cells that enter maternal circulation at time of delivery caus maternal immune activation against antigens and antibody formation

• Thus chances of HDN for the next babies increase

• 1st is baby usually spared.

Clinical features:-

• May Presents as• Mild anaemia to• Intrauterine death from 18 weeks;hydrops fetalis

(hepatosplenomegaly,oedema and cardiac failure)• Kernicterus owing to severe jaundice,unconjugated

billirubin exceeding 250 µmol/L,bile deposition in basal ganglia• Permanent brain damage,spacticity• May present as deafness

Investigation:-

• Routine antenatal serology;• ABO and RhD group determined of all mothers and

repeated at 28 weeks

Postnatal care:-

• Mild cases phototherapy• Severe case; exchange transfusion indication

• Note:- blood used should be ABO compatible with mother and fetus and should lack antigen against which mother antibody is directed.

Prevention of RhD incompatibility HDN:-• Anti-D should be given to mother after delivery

when all of following present;– Mother is RhD negative– Father is RhD positive– Mother immune system not yet activated against antigen

• Dose is 500 i.u of IGg anti-D intramuscularly within 72 hours of delivery.

Non immune:-

– Acquired membrane defects• Paroxysmal nocturnal haemoglobinuria

– Mechanical– Systemic disease

Paroxysmal nocturnal haemoglobinuria:-

• Urine voided at night and morning is dark colored, cause of this timing not known

• Is caused by defective gene of proteins required for complement degradation continued complement degradation of RBC’s

Clinical feature:-

• Major clinical signs intravascular haemolysis , venous thrombosis, haemoglobinuria

• In severs cases all urine samples dark• Iron deficiency• Budd-chiari syndrome venous thrombosis in

liver• Thrombosis at other sites like GI,brain

Investigation:-

• Intravenous haemolysis evident– Radioisotop labled red cells 51c labelled red cells– Raised plasma Hb levels– Haemosiderinuria– Low haptoglobins– Schumm’s test

• Flow cytometric analysis of red cells with anti-CD55 and anti-CD59

• Bone marrow hypoplastic (exhuastion)

Treatment:-

• Chronic disorder requires supportive measures– Leukocyte depleted blood transfusion– Eculiczumab (prevent c5 cleavage)

• Long term– Anticoagulants (venous thrombosis)

• Bone marrow aplasia cases– Immunosuppression with antilymphocyte globulin or

bone marrow transplant ; survival 10-15 years• Note:- may lead to acute leukemia

Thank you all…