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Hemolytic Anemia in childrenHemolytic Anemia in children
Hematology-Oncology DivisionChild Health DepartementChild Health Departement Sumatera Utara University
Hemolytic anemia
Premature destruction of erythrocyte or red bloodPremature destruction of erythrocyte or red blood cells (RBC)
Anemia: rate of destruction exceeds the capacity of the marrow to produce RBC
RBC survival is shortened, RBC count falls erythropoetin is increasedfalls,erythropoetin is increased
Classification
1.Cellular: There are four main1.Cellular:- Intrinsic
abnormalities of the
There are four main types of Inherited Hemolytic anemia:
membrane- Enzymes 1.Hemoglobinopathies
- HemoglobinVirtually: Inherited
2.Thalassemia3.Enzyme defects4.Membrane defects
2.Extracellular Acqiured hemolytic2.Extracellular- antibodies- mechanical factors
Acqiured hemolytic anemia
Immune:- plasma factors
Virtually : Acquired- Direct complement
mediatedy q- Autoimmune HA
Warm ab IgGCold ab IgMCold ab IgM
….Classification
2.Non-Immune : 6.Oxydative drugs or
1.Mechanical trauma:HUS TTP DIC
6.Oxydative drugs or chemical
7.Severe burnsHUS, TTP,DIC
2.Thermal injury3.Acanthocytosis
8.Venom9.Infection: y
4.Severe hypophosphatemia
5 Wilson’s disease
Malaria,babesiasis, bartonellosis,Trypanosomiasis gram5.Wilson s disease,
Copper poisoningomiasis, gram negative/positive
Table 3. Some common drugs and chemicalsgthat can induce hemolytic anemia
AcetanilideDoxorubicin
NiridazoleNitrofurantoin
FurazolidoneMethylene blue
PhenazopyridinePrimaquine
Nalidixic acid Sulfamethoxazole
N Eng J Med 1991; 324;171
Mayor catagory
1.Immune mediated (alloimmune or1.Immune mediated (alloimmune or autoimmune)2.Membrane defects (spherocytosis, ( p y ,elliptocytosis)3.Enzym defects ( G6PD deficiency , pyruvate kinase deficiency)4.Hemoglobin defects ( sickle cell disease, th l i )thalassemia )
Approach to diagnosis
1 Clinical features suggesting hemolytic1. Clinical features suggesting hemolytic disease
2 Laboratory2. Laboratory3. Special hematologic investigation
Clinical features suggest a hemolytic process
1 Ethnic factors1. Ethnic factors2. Age factors3 History of anemia jaundice gallstones in3. History of anemia,jaundice.gallstones in
family4 P i t t t i i t d4. Persistent or recurrent anemia associated
reticulocytosis5 A i i t h ti i5. Anemia unresponsive to hematinics
6 Intermitent or persistent indirect6. Intermitent or persistent indirect hyperbilirubinemia
7 Splenomegaly7. Splenomegaly8. Hemoglobinuria9 M lti l ll t9. Multiple gallstones10. Chronic leg ulcers11. Exposure to certain drugs
Inherited Hemolytic Anemia
A.Red cell membrane defectA.1. Hereditary Spherocytosis
Essentials of diagnosis & typical featuresAnemia and jaundiceAnemia and jaundiceSplenomegalyPositive family history of anemia, jaundice
or gallstones.Spherocytosis with ↑reticulosytes↑Osmotic fragilility↑Osmotic fragilility Negative coombs test
A 2 Hereditary ElliptocytosisA.2. Hereditary Elliptocytosis
Autosomal dominant inheritanceMost are asymptomaticElevated reticulosyte Jaundice and splenomegalyJaundice and splenomegaly
No treatment is indicated :- folate suplementation- splenectomy
B. Enzyme Deficiencies
B.1. Glucose-6-phosphate Dehydrogenase(G6PD) Deficiency(G6PD) Deficiency
Essentials of diagnosis & typical features- Symptoms develop 24-48 hr after ingested a
substances has oxidant properties, such as aspirin, sulfonamides, and antimalarias
- African Mediterranean or Asian ancestry- African, Mediterranean or Asian ancestry- Neonatal hyperbilirubinemia- Sporadic hemolysis infection, oxidant drugs
fava beans- X- linked inheritance.
Acute : precipitous fall Hb + Ht- Acute : precipitous fall Hb + Ht- Heinz bodies in RBCs’ unstained/supravital
- Polychromatophilic cells, reticulocytosis- Enzymes activity < 10% normal- Reduction of enzymes activity more extreme in
Americans of European descent and in Asians than Americans of Africans descentthan Americans of Africans descent
- Screening tests : decoloration of methylene blue, reduction of methemoglobin, or fluorescence ofreduction of methemoglobin, or fluorescence of NADPH.
- After hemolytic episode reticulocytes and young RBCs predominate
- Dx suspected: G6PD activity is within low normal i th f hi h ti l trange in the presence of a high reticulocyte
count
Acquired Hemolytic Anemia
1 Microangiopathic Hemolytic Anemia1.Microangiopathic Hemolytic AnemiaHallmark: - schistocytes ( red cell fragments)on peripheral blood smear analysison peripheral blood smear analysis.Infection and sepsis microagiopathy ,
t ll d fib i i RBCuncontrolled fibrinogenesis RBC destruction
S RBC d t ti th b t iSevere RBC destruction , thrombocytopenia, coagulation factor consumption, DIC
Hemolytic Uremic Syndrome ( HUS)Hemolytic Uremic Syndrome ( HUS)- Microangiopathic- Decreased von Willebrand proteaseDecreased von Willebrand protease- Infection with enteric bacteria: Escherichia
coli O157:H7Thrombotic thrombocytopenic purpura
- Decreased von Willebrand proteaseDecreased von Willebrand protease- HUS + neurologic symptoms, inherited or
acquired q
2. Immune-Mediated Hemolytic Anemias2. Immune Mediated Hemolytic Anemias- Antibody againts one or more antigenson the
surface of RBC opsonization premature destruction: - erythocytes RES
- complement-mediated lysis of RBC in the bloodstream
- Antibodies come from patients: AIHA- Antibodies come from another source : Alloimmune
hemolytic anemia Hemolytic disease of the newbornnewborn
2.1.Autoimmune Hemolytic Anemia (AIHA)(AIHA)
History: previous viral or viral like illnessHistory: previous viral or viral like illness, fatigue, pallorUssually sudden severe anemiaUssually sudden, severe anemiaDark urine:acute intravascular hemolysis complement mediated red cellhemolysis complement mediated red cell lysisJaundice sclerae pruritusJaundice sclerae,pruritusMild splenomegaly
Autoimmune Hemolytic Anemia
2.1.1.Intravascular hemolysis
Complement mediated,IgM,complement-p , g , pfixing IgG direct against RBC antigen jaundice (hyperbilirubinemia) , LDH , low haptoglobin
2.1.2.Extravascular hemolysis
Mediated by IgGMediated by IgGNO increase LDH , bilirubinRBC destroyed in RES plasmaRBC destroyed in RES, plasma
Laboratory evaluation-Moderate to severe anemia-Brisk reticulocytosis-Spherocytosis,polychromasia,RBC clumpingp y ,p y , p g
-HemoglobinuriaHemoglobinuria-Direct Coombs test (antibody bound to the
patient’s RBC) : (+)patient s RBC) : (+)-Indirect Coombs test (test for free
antierythrocyte antibody in the patient’santierythrocyte antibody in the patient s serum
Primary AIHA :
1 Warm-reactive AIHA1.Warm reactive AIHAUsually : IgG binds RBC antigen at 37oC
2 Paroxysmal Cold Hemoglobinuria2.Paroxysmal Cold Hemoglobinuria3.Cold Agglutinin Disease:
Usually IgM binds erythrocyte antigens (typically red cell surface polysaccharide)
d fi l t t t b l 37oCand fixes complement at temp.below 37oC
Classification of autoimmune hemolytic anemia
Warm-reactive autoantibodiesprimary
Paroxysmal cold hemoglobinuria (PCH)
SecondaryLymphoproliferative disordersAutoimmune disorders (SLE)
Tertiary syphillisPost-viral infection
Infectious mononucleosisEvan’s syndromeHIV associated
Drug induced hemolytic anemiaHapten mediated (PCN)Immune complex type (quinidine quinine)
Cold-reactive antibodiesIdiopathic (cold aglutinin disease)
(quinidine, quinine)True autoimmune anti-RBC type ( methyldopa)
Metabolite drivend sease)secondaryAtypical or mycoplasma
pneumoniaI f i l i
Metabolite driven
Infectious mononucleosisLymphoproliferative disorders
Treatment of Acquired Hemolytic Anemia
Methyl-prednisolone 1 to 2 mg/Kg/day/ivMethyl prednisolone 1 to 2 mg/Kg/day/iv every 6 hours should be initiated promptly.Response (+) :increasingly stable p p y p ( ) g yHb,decreasing reticulocytosis,diminishing transfusion.After stabilization,prednisone 1 to p2 md /Kg /day can be substituted for methylprednisolone gradually tapered over several weeks to months
IV ImmunoglobulinIV ImmunoglobulinExchange transfusion/Plasmapheresis : limited efficacy effective for-IgMlimited efficacy, effective for-IgMSplenectomy: refractory IgG dependent chronic extravascular hemolysischronic extravascular hemolysisImmunosuppressive drugs: cyclophosphamide 6 mercaptopurine 6cyclophosphamide,6-mercaptopurine,6-thioguanine,azathioprine,cyclosporine A
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