Hemolytic anaemia

Hemolytic Anaemia

HAEMOLYTIC ANEMIA➔ Definition: anaemia 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)

HEREDITARY SPHEROCYTOSIS

наследственный сфероцитоз или болезнь Минковского-Шоффара

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

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.

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

Diagnosis

COMPLICATION❖ Gout, Leg ulcers❖ Chronic erythematous dermatitis of legs❖ Extramedullary hematopoesis❖ Hematologic malignancies : multiple myeloma, leukemia,

hepatoma❖ Heart disease: CCF, cardiomyopathy

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.

THALASSEMIA Талассемии

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

Β-Thalassemia❏ Types:

a) Beta-Thalassemia major (βo/βo genotype): most severe form, HbA (α2β2) cannot be produced because of the abnormal β globin gene.

b) Beta- Thalssemia intermedia(β+/βo or β+/β+ genotype): milder, varies severity; beta globulin allow small HbA or large amount of HbF to be produced

c) Beta Thalassemia minor(β/βo 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.

Sxa) Severe anemia, transfusion dependent, 4-6months of life, a/w jaundice

b) Growth failure

c) Extramedullary hemopoiesis (Hepatosplenomegaly, bone marrow expansion)

❏ Management:

a) Lifelong monthly bld transfusion

b) Iron chelation for repeated bld transfusion (desferrioxamine)

c) Bone marrow transplantation

Sickle Cell AnaemiaСерповидноклеточная анемия

Pathogenesis● HbS form due to mutation in beta globulin gene

● Changes in AA encoded frm glutamine to valine

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

Diagnosis ●Electrophoresis: polymerization of HbS

●CBC: decrease Hb, ESR; leucocytosis, thrombocytosis, reticulocytosis

●Blood smear: sickle shape RBC

●Increase in serum bilirubin

Treatment● Acute crises

i) Oral/ IV analgesia- pain crises

ii) Antibiotics- Infection

iii)Exchange transfusion- indicated for acute chest syndrome, stroke and priapism

● Chronic problem

i) Hydroxyurea: recurrent admission with pain crises and acute chest syndrome

ii) Bone marrow transplant (frm HLA identical sibling)

Glucose-6-Phosphate Dehydrogenase (G6PD)

Defeciencyнедостаточность глюкозо-6-фосфат

дегидрогеназы

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

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

Autoimmune hemolytic anemia

АУТОИММУННЫЕ ГЕМОЛИТИЧЕСКИЕ АНЕМИИ

Diagnosis and TreatmentDiagnosis:

★ Biochemical analysis: increase LDH, unconjugated bilirubin; decreased serum iron

★ Urine: hemosiderinuria

★ Direct Coomb Test -ve

Treatment:

❖ Treating underlying dz

❖ Plasmapheresis

❖ IV Ig

❖ Apoptotic inhibitor