Hemolytic anaemia

For paediatrics usage.

1. Hemolytic Anaemia

2. HAEMOLYTIC ANEMIA Definition: a naemia that arised due to increase destruction of erythrocyte Classification: INTRACORPUSCULAR HEMOLYSIS Membrane Abnormalities (Spherocytosis) Haemoglobin defects (Thalassemia, Sickle cell Anaemia) Enzyme defects (G6PD Deficiency) EXTRACORPUSCULAR HEMOLYSIS Nonimmune (Drug related, Mechanical) Immune (Autoimmune, Alloimmune)

3. HEREDITARY SPHEROCYTOSIS наследственный сфероцитоз или болезнь Минковского-Шоффара

4. EPIDEMIOLOGY 1:5000 in Caucasians Its inheritance, often autosomal dominant (⅔), and autosomal recessive (⅓) Maybe no FHx, caused by new mutation Northen europe are most common but also in SE Asia

5. ETIOLOGY AND PATHOGENESIS Mutation in the genes for protein of RBC membrane ( spectrin , ankyrin or band 3) Producing spheroidal shaped and osmotically fragile RBCs that are trapped and destroyed in the spleen, resulting in shortened RBC lifespan.

6. Clinical Features Anaemia (Hb=9-11g/dl, transiently fall during infection) Intermittent jaundice (severe: in 1st few day of life/childhood) Splenomegaly Haemolytic crises (hemolysis) Pigmented gallstones in adolescents and young adults due to increased bilirubin excretion Aplastic crises (reticulocytopenia) with Parvovirus B19 infections (2-4 weeks) Megaloblastic crises

7. Diagnosis

8. COMPLICATION Gout, Leg ulcers Chronic erythematous dermatitis of legs Extramedullary hematopoesis Hematologic malignancies : multiple myeloma, leukemia, hepatoma Heart disease: CCF, cardiomyopathy

9. TREATMENT If Hb > 10 gm/dl and retics < 10%- no Rx If severe anemia, poor growth, aplastic crises and age <2yrs- transfusion If Hb < 10 gm/dl and retics > 10 % or massive spleen- splenectomy Folic acid- 1 mg/day (mild) ** Splenotomy To be delayed as long as possible Mild cases: no need, unless gallstone developed Avoided for patients < 5 years age because of the increased risk of postsplenectomy sepsis Give pneumococcal, haemophilus and meningococcal vaccination 4-6 weeks prior to splenectomy and prophylactic oral penicillin to be given post-splenectomy.

10. THALASSEMIA Талассемии

11. INTRODUCTION Inherited blood disorder presenting with anaemia at 4 - 6 months of age Common presenting symptoms are pallor, lethargy, failure to thrive and hepatosplenomegaly Most often in Indian subcontinent, Mediterranean, and middle East In Malaysia, the β-thalassaemia carrier rate is estimated at 3-5%, most of whom are unaware of their carrier / thalassaemia minor status. Must perform prenatal dx: DNA analysis of chorionic villius sample

12. Β-Thalassemia Types: Beta-Thalassemia major ( β o /β o genotype ): most severe form, HbA (α2β2) cannot be produced because of the abnormal β­globin gene. Beta- Thalssemia intermedia ( β + /β o or β + /β + genotype) : milder, varies severity; beta globulin allow small HbA or large amount of HbF to be produced Beta Thalassemia minor ( β/β o or β/β + genotype ): Only one of the two β globin alleles contains a mutation, so β chain production is not terribly compromised and patients may be relatively asymptomatic.

13. Sx Severe anemia, transfusion dependent, 4-6months of life, a/w jaundice Growth failure Extramedullary hemopoiesis (Hepatosplenomegaly, bone marrow expansion) Management: Lifelong monthly bld transfusion Iron chelation for repeated bld transfusion (desferrioxamine) Bone marrow transplantation

14. Sickle Cell Anaemia Серповидноклеточная анемия

15. Pathogenesis HbS form due to mutation in beta globulin gene Changes in AA encoded frm glutamine to valine

16. Clinical manifestation Anaemia: Hb=6-10g/dl with jaundice frm chronic hemolysis Infection (due to hyposplenism ) Painful crises: vaso-occlusive crises lead to pain ( dactylitis) Hemolytic, aplastic,sequestration crises Priapism: might cause copora carvenosa fibrosis and subsequent erectile incompetence Splenomegaly Long term problems: gallstone, renal failure, cardiac elargement, delayed puberty and short stature, adenotonsillar hypertrophy, leg ulcer, stroke and cognitive problems

17. Diagnosis Electrophoresis: polymerization of HbS CBC: decrease Hb, ESR; leucocytosis, thrombocytosis, reticulocytosis Blood smear: sickle shape RBC Increase in serum bilirubin

18. Treatment Acute crises Oral/ IV analgesia- pain crises Antibiotics- Infection Exchange transfusion- indicated for acute chest syndrome, stroke and priapism Chronic problem Hydroxyurea: recurrent admission with pain crises and acute chest syndrome Bone marrow transplant (frm HLA identical sibling)

19. Glucose-6-Phosphate Dehydrogenase (G6PD) Defeciency недостаточность глюкозо-6-фосфат дегидрогеназы

20. Introduction G6PD- essential for pentose oxidative pathway and prevent oxidative damage to RBC Lacking cause oxidant induced hemolysis X linked recessive, predominantly in males Heterozygous female: normal; affected only when female are homozygous

21. Clinical Manifestation: Neonatal jaundice: onset on 1st 3 day of life Acute hemolysis- precipitated by: Infection (pnemonia, hepatitis, typhoid fever Certain drugs ( antimalaria, antibiotics,analgesics-aspirin and chemicals) Fava beans Napthalene in mothball Diagnosis: Enzyme increase during hemolytic crises Reticulocytosis Increase conjugated and unconjugated bilirubin,LDH, alkaline phosphate Treatment: Parents given list of drugs, food and chemical to avoid Rerely use transfusion

22. Autoimmune hemolytic anemia АУТОИММУННЫЕ ГЕМОЛИТИЧЕСКИЕ АНЕМИИ

23. Diagnosis and Treatment Diagnosis: Biochemical analysis: increase LDH, unconjugated bilirubin; decreased serum iron Urine: hemosiderinuria Direct Coomb Test -ve Treatment: Treating underlying dz Plasmapheresis IV Ig Apoptotic inhibitor