Hemolytic Anemia in children...Hemolytic anemia Premature destruction of erythrocyte or red...
Transcript of Hemolytic Anemia in children...Hemolytic anemia Premature destruction of erythrocyte or red...
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