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APPROACH TO HEMOLYTIC ANEMIA Candidate: Dr SARATH MENON.R K.B.ILLAVA HEMATOLOGY DIVISION DEPT.MEDICINE, MGM MEDICAL COLLEGE,INDORE

Approach to hemolytic anemia

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Page 1: Approach to hemolytic anemia

APPROACH TO HEMOLYTIC ANEMIA

Candidate: Dr SARATH MENON.R

K.B.ILLAVA HEMATOLOGY DIVISION

DEPT.MEDICINE,

MGM MEDICAL COLLEGE,INDORE

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OBJECTIVES

Lab indication of hemolysis

Intravascular v/s extravascular hemolysis

D/D of hemolytic anemia

Diagnose hemo.anemia with peripheral smear &

ancillary lab tests

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HEMOLYTIC ANEMIA

Definition: Those anemias which result from an increase in

RBC destruction coupled with increased erythropoiesis

Classification: Congenital / Hereditary Acquired

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CLASSIFICATION OF HEMOLYTIC ANEMIAS

INTRACORPUSCULAR DEFECTS

EXTRACORPUSCULAR FACTORS

HEREDITARY •HEMOGLOBINOPATHIES

•ENZYMOPATHIES

•MEMBRANE-CYTOSKELETAL DEFECTS

•FAMILIAL HEMOLYTIC UREMIC SYNDROME

ACQUIRED •PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

•MECHANICAL DESTRUCTION [MICROANGIOPATHIC] •TOXIC AGENTS•DRUGS•INFECTIOUS•AUTOIMMUNE

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CLASSIFICATION

MAHA Transfusion rx PNH Infections Snake bite

Hemoglobinopathies Enzymopathies Membrane defects AIHA

Intravascular hemolysisExtravascular hemolysis

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HOW IS HEMOLYTIC ANEMIA DIAGNOSED?

Two main principles

One is to confirm that it is hemolysis

Two is to determine the etiology

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HOW TO DIAGNOSE HEMOLYTIC ANEMIA

New onset pallor or anemia

Jaundice

Splenomegaly

Gall stones

Dark colored urine

Leg ulcers

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GENERAL FEATURES

OF HEMOLYTIC DISORDERS

GENERAL EXAMINATION - JAUNDICE, PALLOR

BOSSING OF SKULL

PHYSICAL FINDINGS - ENLARGED SPLEEN

HEMOGLOBIN - FROM NORMAL TO SEVERELY REDUCED

MCV - USUALLY INCREASED

RETICULOCYTES - INCREASED

BILIRUBIN - INCREASED[MOSTLY UNCONJUGATED]

LDH - INCREASED

HAPTOGLOBULIN - REDUCED TO ABSENT

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HEMOLYTIC FACIES- CHIPMUNK FACIES

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Laboratory Evaluation of HemolysisExtravascular Intravascular  

HEMATOLOGIC

Routine blood filmReticulocyte countBone marrow examination

Polychromatophilia

Erythroid hyperplasia

Polychromatophilia

Erythroid hyperplasia

 

PLASMA OR SERUM

BilirubinHaptoglobinPlasma hemoglobinLactate dehydrogenase

Unconjugated , Absent N/ (Variable)

UnconjugatedAbsent (Variable)

 

URINE

BilirubinHemosiderinHemoglobin

+00

+++ severe cases  

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POLYCHROMATOPHILIC CELLS

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THE KEY TO THE ETIOLOGY OF HEMOLYTIC ANEMIA

The history

The peripheral blood film

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PATIENT HISTORY

Acute or chronic

Medication/Drug precipitants

G6PD

AIHA

Family history

Concomitant medical illnesses

Clinical presentation

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CASE 1

3 yr old male child presenting with pallor,jaundice,

Severe pain of long bones, fever CBC-anemia,reticulocytosis,increased WBC LAB - LDH -600 (normal upto 200) S.bilirubin- 5mg%

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PERIPHERAL SMEAR

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WHAT IS THE DIAGNOSIS ?

SICKLE CELL ANEMIA

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DIAGNOSIS – OTHER TESTS

Hemoglobin electrophoresis -HbS >80% -HbF -1-20% -HbA2 -2- 4.5% Sickling test POSITIVE

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SICKLE CELL DISEASE

Mutn .beta globin-6 Glu Val. Deoxy HbS (polymerised)

Ca influx, K leakage

stiff,viscous sickle cell

venocclusion dec.RBC survival

microinfarctions,isch.pains anemia,jaundice,

autoinfarct.spleen gallstones,leg ulcers

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CLINICAL MANIFESTATIONS

Hemo.anemia,reticulocytosis,granulocytosis Vasoocclusion-protean Painful crises Splenic sequestration crises Hand foot syndrome Acute chest syndrome

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DIAGNOSIS?

SICKLE THALASSEMIA`

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CLINICAL FEATURES OF SICKLE HEMOGLOBINOPATHIES

Condition Clinical abnorm

Hb level g% MCV,fl Hb electropho

Sickle cell trait

None,rare painlss hematuria

normal normal HbS/A: 40/60

Sickle cell anemia

Vasocclusive crises,AVN,gallstones, priapism

7-10 80-100 HbS/A:100/0HbF;2-25%

S/beta0thalasssemia

VasoocclusiveCrises,AVN

7-10 60-80 HbS/A-100/0HbF; 1-10%

S/beta+ thalassemia

Rare crises,AVN

10-14 70-80 HbS/A:60/40

HbSC --do--, retinopathy

10-14 80-100 HbS/A;50/0HbC;50%

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CASE 2

6 yr old child presenting with severe pallor,jaundice growth delay

Abnormal facies,hepatosplenomegaly+ h/o recurrent blood transfusions CBC-Hb -3gm%, MCV-58FL(Nl-86-98), -MCH- 19pg (nl-28-33) P.S- MICROCYTIC,HYPOCHROMIA with target cells +

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DIAGNOSIS?

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TARGET CELLS

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THALASSEMIA

Other diagnosis test-Hb electrophoresis DNA analysis for mutations Alpha thalassemia & beta thalassemia Beta thalassemia- major - intermedia - minor

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BETA THALASSEMIA

Mutn. Beta globin expression

M.C- derange splicing of m-RNA

HYPOCHROMIA ,MICROCYTIC anemia

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BETA THALASSEMIA MAJOR Severe homozygous Childhood, growth delay Severe anemia,hepatosplenomegaly,r/r transfusion Iron overload-endo.dysfnct

P.Smear- severe microcytosis,target cells

Hb electro- HbF - 90-96 % HbA2- 3.5 %- 5.5% HbA - 0 %

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BETA THALASSEMIA INTERMEDIA

Similar stigmata like major Survive without c/c transfusion Less severe than major Moderate anemia,microcytosis,hypochromia Hb electrophor- HbF - 20-100% HbA2 -3.5%-5.5% HbA – 0-30%

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BETA THALASSEMIA MINOR

Profound microcytosis,target cells Minimal anemia Similar bld picture of iron def.anemia Lab inv: MCV<75,Hct <30-33% Hb electr: HbA2-3.5-7.5%,HbA-80-95%,HbF-1-

5%

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ALPHA THALASSEMIAS

disease Hb A %

HbH % Hb , % MCV,fl

normal 97 0 15 90

Thalassemia traits

90-95 rare 12-13 70-80

HbH (b4) 70-95 5-30 6-10 60-70

Hb Bart(hydrops fetalis)

0 5-10 Fatal inutero or at birth

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CASE 3

45 yr old male came to opd in a remote PHC with burning micturition

Urine R/M shows numerous pus cells++++ UTI diagnosed & medical officer gave

cotrimoxazole 2 bd X 5days 1 wk later,pt developed severe

pallor,palpitation,jaundice Lab- increased LDH, S.BILIRUBIN,RETIC

COUNT P.S- shows irreg cells like

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BLISTER CELLS

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HEINZ BODIES

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DIAGNOSIS?

G-6PD DEFICIENCY INVESTIGATION- Peripheral smear- bite cells,heinz bodies, - polychromasia

G-6PD LEVEL

BEUTLER FLUORESCENT SPOT TEST- Positive-if blood spot fails to flouresce in U

V

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Clinical Features:

Acute hemolysis:

Drugs,infections,asso with diabetic acidosis

Favism

Neonatal jaundice

Congenital nonspherocytic hemolytic anemia

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Definitive risk Possible risk Doubtful risk

antimalarials PrimaquineDapsonecholrproguanil

chloroquine quinine

Sulphonamides/sulphones

SulphametoxazoleDapsone

SulfasalazineSulfadimidine

SulfisoxazoleSulfadiazine

Antibacterials/Antibiotics

Cotrimoxazole Nalidixic acidNitrofurantoin

CiprofloxacinNorfloxacin

Cholramphenicolp-Aminosalicylic acid

Antipyretic/Analgesics

Acetanilide Phenazopyridine [pyridium]

Acetylsalicylic acid High dose[>3g/d]

Acetylsalicylic acid [<3g/d]Acetaminophen

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2. Pyruvate Kinase DeficiencyARDeficient ATP production, Chronic

hemolytic anemiaClinical features

o hydrops fetalis

o neonatal jaundice

o compensated hemolytic anemia Inv;

P. Smear: PRICKLE CELLS ( Contracted rbc with

spicules)

Decreased enzyme activity

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PRICKLE CELL

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CASE 4

14 YR old female present with anemia, jaundice

Rt hypochondrial pain o/e- vitals

stable.pallor+,icterus+,splenomegaly + Usg- cholilithiasis Lab; elevated ,LDH, S.Bilirubin Peripheral smear shows-

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DIFFERENTIAL DIAGNOSIS

Hereditary spherocytosis

Autoimmune hemolytic anemia

Other diagnostic tests- osmotic fragility - coombs test

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RED CELL MEMBRANE DEFECTS

1.Hereditary Spherocytosis

Usually inherited as AD disorder

Defect: Deficiency of Beta Spectrin or Ankyrin Loss of

membrane surface area becomes more spherical

Destruction in Spleen

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C/F:PallorJaundiceSplenomegalyPigmented gall stones- 50%

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COMPLICATIONS

Clinical course may be complicated with

Crisis:

Hemolytic Crisis: associated with infection

Aplastic crisis: associated with Parvovirus

infection

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Inv:

Test will confirm Hemolysis

P Smear: Spherocytes

Osmotic Fragility: Increased

Screen family members

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AUTOIMMUNE HEMOLYTIC ANEMIA

Result from RBC destruction due to RBC autoantibodies: Ig G, M, E, A

Most commonly-idiopathic Classification

Warm AI hemolysis:Ab binds at 37degree Celsius Cold AI Hemolysis: Ab binds at 4 degree Celsius

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1.Warm AI Hemolysis: Can occurs at all age groups F > M Causes:

50% IdiopathicRest - secondary causes:

1.Lymphoid neoplasm: CLL, Lymphoma, Myeloma

2.Solid Tumors: Lung, Colon, Kidney, Ovary, Thymoma

3.CTD: SLE,RA4.Drugs: Alpha methyl DOPA, Penicillin , Quinine, Chloroquine

5. UC, HIV

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Inv:

hemolysis, MCV decreased

P Smear: microspherocytosis,

Confirmation: Direct Coomb’s Test / Antiglobulin test

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• 2. Cold AI Hemolysis Usually Ig M directed at the RBC I antigen

Infection: Mycoplasma pneumonia, Infec MononucleosisNeoplasms : waldenstrom macroglobulinemia ,

lymphoma,CLL,kaposi sarcoma, myeloma. C/F:

Elderly patientsExacerbations in the winter Cold , painful & often blue fingers, toes, ears, or nose ( Acrocyanosis)

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Inv: e/o hemolysis

P Smear: Microspherocytosis

DAT positive with polyspecific and anticompliment

antisera

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CASE 5

32 yr old presented 4 days history of distention of abdomen and rt hypochondrial pain and has h/o passage of dark colored urine at night for weeks

On USG- hepatomegaly,gross ascites,hepatic vein

thrombosis Lab : Hb – 7gm%. WBC- 2200, PLC- 80,000 LDH- 600, S.BR- 4 mg% urine bile pigment +,heme dip

stick++

What is the diagnosis?

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PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Acquired chronic H.A Persistent intra vascular hemolysis Pancytopenia Lab :hburia,hemosiderinuria,increased

LDH,bilirubin Risk of venous thrombosis C/F – hemoglobinuria during night P.S – polychromatophilia, normoblasts B.M – normoblastic hyperplasia Def.diagnosis-flow cytometry CD59-,CD55-

RBC,WBC - Hams’ acidified serum test

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CASE 6

25 yr old male with RHD – severe MR done MVR,after 10 days presented with pallor, palpitation,jaundice

CBC shows Hb – 7.5 gm %, Hct -22 % Lab : S.bilirubin -4.5mg% LDH -600 Retic count 10%

Peripheral smear –

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MICROANGIOPATHIC HEMOLYTIC ANEMIA

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NON-IMMUNE ACQUIRED HEMOLYTIC ANEMIA1. Mechanical Trauma

A). Mechanical heart valves, Arterial grafts: cause shear stress damage

B).March hemoglobinuria: Red cell damage in capillaries of feet

C). Thermal injury: burnsD). Microangiopathic hemolytic anemia (MAHA): by

passage of RBC through fibrin strands deposited in small vessels disruption of RBC eg: DIC,PIH, Malignant HTN,TTP,HUS

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MICROANGIOPATHIC HEMOLYTIC ANEMIA(MAHA)

Other findings - leukocytosis -

thrombocytopenia(DIC,TTP) - hemoglobinuria - deranged RFT - PT,APTT prolonged (DIC,TTP)

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ACQUIRED HEMOLYSIS

InfectionF. malaria: intravascular hemolysis: severe called ‘Blackwater fever’Cl. perfringens septicemia

Chemical/Drugs: oxidant denaturation of hemoglobinEg: Dapsone, sulphasalazine, Arsenic gas, Cu, Nitrates & Nitrobenzene

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PERIPHERAL BLOOD SMEARSpherocytes

AIHA, hereditary spherocytosis

Schistocytes

With thrombocytopenia-Familial HUS TTP or DIC

Without thrombocytopenia- heart valve hemolysis

Blister Cells

oxidative damage- G6PD Sickle cells

sickle cell anemia Heinz bodies

Alpha thalassemia

G6PD deficiency

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CONCLUSION

Hemolytic anemia can be recogised by clinical picture-

- history & physical

- lab test to confirm hemolysis

- peripheral smear to guide further

tests

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THANK YOU