APPROACH TO HEMOLYTIC ANEMIA

Candidate: Dr SARATH MENON.R

K.B.ILLAVA HEMATOLOGY DIVISION DEPT.MEDICINE, MGM MEDICAL COLLEGE,INDORE

OBJECTIVES Lab indication of hemolysis

Intravascular v/s extravascular hemolysis

D/D of hemolytic anemia

Diagnose hemo.anemia with peripheral smear &

ancillary lab tests

HEMOLYTIC ANEMIA

Definition: Those anemias which result from an increase in

RBC destruction coupled with increased erythropoiesis

Classification: Congenital / Hereditary Acquired

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

CLASSIFICATION

MAHA Transfusion rx PNH Infections Snake bite

Hemoglobinopathies Enzymopathies Membrane defects AIHA

Intravascular hemolysis Extravascular hemolysis

HOW IS HEMOLYTIC ANEMIA DIAGNOSED?

Two main principles

One is to confirm that it is hemolysis

Two is to determine the etiology

HOW TO DIAGNOSE HEMOLYTIC ANEMIA New onset pallor or anemia

Jaundice

Splenomegaly

Gall stones

Dark colored urine

Leg ulcers

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

HEMOLYTIC FACIES- CHIPMUNK FACIES

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)

 

URINEBilirubinHemosiderinHemoglobin

+00

+++ severe cases  

POLYCHROMATOPHILIC CELLS

THE KEY TO THE ETIOLOGY OF HEMOLYTIC ANEMIA

The history

The peripheral blood film

PATIENT HISTORY

Acute or chronic Medication/Drug precipitants G6PD AIHA Family history Concomitant medical illnesses Clinical presentation

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%

PERIPHERAL SMEAR

WHAT IS THE DIAGNOSIS ? SICKLE CELL ANEMIA

DIAGNOSIS – OTHER TESTS

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

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

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

DIAGNOSIS? SICKLE THALASSEMIA`

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%

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 +

DIAGNOSIS?

TARGET CELLS

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

BETA THALASSEMIA Mutn. Beta globin expression

M.C- derange splicing of m-RNA

HYPOCHROMIA ,MICROCYTIC anemia

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 %

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%

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%

ALPHA THALASSEMIASdisease 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

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

BLISTER CELLS

HEINZ BODIES

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

Clinical Features: Acute hemolysis:

Drugs,infections,asso with diabetic acidosis Favism Neonatal jaundice Congenital nonspherocytic hemolytic anemia

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

2. Pyruvate Kinase DeficiencyARDeficient ATP production, Chronic

hemolytic anemiaClinical featureso hydrops fetaliso neonatal jaundiceo compensated hemolytic anemia Inv;

P. Smear: PRICKLE CELLS ( Contracted rbc with spicules) Decreased enzyme activity

PRICKLE CELL

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-

DIFFERENTIAL DIAGNOSIS Hereditary spherocytosis

Autoimmune hemolytic anemia

Other diagnostic tests- osmotic fragility - coombs test

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

C/F:PallorJaundiceSplenomegalyPigmented gall stones- 50%

COMPLICATIONS

Clinical course may be complicated with

Crisis: Hemolytic Crisis: associated with infection

Aplastic crisis: associated with Parvovirus

infection

Inv: Test will confirm Hemolysis

P Smear: Spherocytes

Osmotic Fragility: Increased

Screen family members

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

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

Inv:

hemolysis, MCV decreased

P Smear: microspherocytosis,

Confirmation: Direct Coomb’s Test / Antiglobulin test

• 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)

Inv: e/o hemolysis P Smear: Microspherocytosis DAT positive with polyspecific and anticompliment

antisera

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?

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

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 –

MICROANGIOPATHIC HEMOLYTIC ANEMIA

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

MICROANGIOPATHIC HEMOLYTIC ANEMIA(MAHA) Other findings - leukocytosis -

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

ACQUIRED HEMOLYSIS Infection

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

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

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

CONCLUSION Hemolytic anemia can be recogised by

clinical picture- - history & physical

- lab test to confirm hemolysis

- peripheral smear to guide further

tests

THANK YOU