Hemolytic Anemias

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Hemolytic Anemias

• Normal RBC life span 120 days. This is
  shortened in hemolytic anemias.
• Common manifestations to all HA are anemia,
  jaundice, red color urine, and splenomegaly.

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Lab tests

• High retic count, polychromasia RBCs, abnormal
  RBC shape, ? SUCB, ? SLDH2, ? SGOT, ?S
  haptoglobin (plasma a-globulin synthesized by the
  liver that binds to globin of hemoglobin).
• Intravascular hemolysis ---- release Hb into
  plasma (hemoglobinemia)
• Plasma Hb ?, hemosiderinuria, hemoglobinuria
• Extravascular hemolysis ---- by RES Mf

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Classification

• I- Hereditary II- Acquired
• I. Hereditary -----
• A) RBC membrane defects
• 1. Hereditary spherocytosis (HS)
• 2. Hereditary elliptocytosis
• 3. Hereditary pyropoikilocytosis.

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Hereditary spherocytosis (HS)

• Inheritance --- AD
• Incidence ---- 11000-4500
• Defect --- A molecular defect is present
  in one of membrane cytoskeleton proteins
• e.g. spectrin, protein3 or ankyrin leading to
  loss of membrane ? ratio of surface area to
  volume causing spherocytosis.
• These spherocytes are less deformable than normal
  RBCs therefore can't traverse the splenic
  interstices engulfed by splenic Mf.

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SS

• Anemia,
• splenomegaly,
• jaundice,
• pigment gall stones and
• chronic leg ulcerations.

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Lab tests

• Blood film spherocytes, MCV?, MCHC?.
• Osmotic fragility test
• ? RBC fragility on exposure to hypotonic
  solutions"sucrose lysis test"
• autohemolysis test on 24h sterile
  
• incubation.
• BMA Erythroid hyperplasia

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DDx

• Autoimmune HA (AIHA)
• Hemolysis induced by splenomegaly of cirrhosis
• Clostridial infection
• Snake envenomation.

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?

• Splenectomy
• corrects anemia but not the defect.
• Cholecystectomy
• Folic acid supplement.

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2. Hereditary elliptocytosis

• Normally elliptocyte RBCs are seen in birds
  reptiles.
• Inheritance --- AD
• Ovalocytosis in southeast Asia
• Mild hemolysis.
• Osmotic fragility test is normal.

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3. Hereditary pyropoikilocytosis (rare)

• RBCs undergo disruption at temp. of
• 44-45? (N up to 49?)
• Spectrin deficiency defective assembly.
• Responds partially to Splenectomy.

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B) RBC enzyme defects

• 1. G6PD deficiency (HMPS enzyme)
• Epidemiology ----
• 1200 million populations.
• It partially protects from malaria
  infection (provide defective home for
  merozoites).
• Mediterranean, African southern China.
• Inheritance X-linked recessive (Lyonization)

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• Hemolysis on exposure to oxidant stress ---
• metabolic acidosis
• Drugs e.g. Aspirin, antimalarial, sulfa,
  nitrofurantoin
• Toxins e.g. moth balls (naphthalene),
• Fava beans consumption (favism)
• S S --- hemolysis within hours of exposure
  to oxidant stress.
• Hemoglobinuria, peripheral vascular
  collapse, jaundice.
• Episode is self-limited because only the
  old RBCs hemolyse
• Lab --- PCV?, plasma Hb?, SUCB?, plasma
  haptoglobin?.
• Blood film Heinz bodies in RBCs
  (crystal violet ve inclusions readily removed by
  spleen causing Bite cells)
• RBC enzyme level 1 month after
  hemolytic episode.

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2. Glutathione reductase def 3. Pyruvate
kinase def -- AR
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II. Acquired ----

• Normal RBCs destroyed in the circulation
  prematurely.
• Damage mediated by Abs, toxins, or
  abnormalities in the circulation.

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1. Entrapment

• --- Hypersplenism
• Spleen efficiently traps destroys RBCs with
  minimal defects.
• Large spleen causes pooling of RBCs in
  nutrient-poor environment full of phagocytic
  cells.
• Seen in inflammatory congestive splenomegaly
  rather than infiltrative. Pancytopenia seen.
• ? -- Splenectomy.

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2. Immune hemolytic anemia

• Usually autoimmune, rarely alloantibodies due to
  blood transfusion AIHA --- of 2 types
• Warm Abs IgG that reacts at normal body temp.
  
• Cold Abs IgM react at low temp. with
  polysaccharide Abs
• (rarely IgG Donath-Landsteiner Abs in Parox
  cold Hburia) SS Anemia, jaundice, splenomegaly

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SS

• Anemia, jaundice, splenomegaly
• Warm Abs Adults, ? , 25 have underlying
  disease e.g. SLE, other collagen vascular
  diseases, lymphomas, drugs
• -- Cold Abs arise in 2 clinical
  settings
• Monoclonal ---- Lymphoid neoplasm,
  paraneoplasia
• Polyclonal ---- infections e.g. Mycop pn, inf
  mono
• Acrocyanosis (bluish discoloration of
  extremities, nose ear on exposure to cold.
  Hemolysis is also seen.
• PCH tertiary syphilis, viral inf autoimmune.

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Dx

• Coomb's test ve (antiglobulin IgG or complement)
  
• Direct --- anti-IgG or anti-C3 Abs
  agglutinate patient's RBCs
• Indirect--- serum of pt incubated with normal
  RBCs Abs detected with anti-IgG.
• Hb?, PCV?, reticulocytosis (10-30),
  spherocytosis.
• Hbemia, Hburia, hemosiderinuria in severe cases.
• Associated immune thrombocytopenia Evan's
  syndrome
• Cold agglutinins- thermal amplitude of Abs,
  exposure to cold env

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?

• No ttt for mild hemolysis.
• Corticosteroids PDN 1mg/kg bw until Hb
  is normal then tapering done over several months.
  Alternate day chronic use.
• Inhibit Abs synthesis inhibition of clearance
  of Ab-coated RBCs by mf.
• Splenectomy --- if pt not tolerate or not
  responds to steroids.
• Immunosuppressant --- azathioprine, CTX
  (for pt not responding neither to steroids nor to
  Splenectomy)
• IVIG ---- rapid cessation of hemolysis.
• Blood Transfusion may be needed. Ab is
  pan agglutinin making cross matching impossible.
  It can be done by adsorbing pan agglutinin from
  pt serum with pt RBCs from which Ab has been
  eluted. Serum cleared of auto-Ab tested for
  allo-Ab to donor bl.

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Cold Ab
Warm env Corticosteroids
Chlorambucil CTx
Ttt of underlying malignancy
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Drug Induced HA

• Mechanisms autoimm HA e.g. a-methyl dopa,
• --- Hapten e.g.
  penicillin, sulfonamides, sulfonylurea
• -- Innocent bystander e.g. quinine,
  cephalosporins.

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3. Trauma in the circulation

• March Hburia in Marathon runners.
• Prosthetic valve crush hemolysis
• Severe calcific native valve aortic
  stenosis
• Microangiopathic HA (MAHA) micro thrombi
  in microcirculation causing RBCs trapping and
  fragmentation due to shearing force.
• a- Bl vessel wall abn --- malignant
  hypertension, eclampsia, renal graft rejection,
  disseminated ca, cavernous hemangiomas, DIC.
• b- TTP --- wide spread platelet thrombi
  causing thrombocytopenia HA
• c- HUS --- similar to TTP in children
  mainly causing uremia
• d- DIC --- inappropriate activation of
  coag factors with fibrin deposition in small bl v

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4. Toxic hemolysis

• Infection malaria, babesiosis, bartonellosis
  (direct RBC parasitism)
• -- Clostridium welchii
  (produce phospholipase causing hemolysis)
• Snake spider venom
• Copper Hemodialysis fluid, Wilson
  disease
• Extensive burns
• Liver cirrhosis Spur cell anemia
  (acanthocytes)
• Abetalipoproteinemia
  similar cells
• Uremia Burr cells, echinocytes

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Paroxysmal nocturnal hemoglobinuria (PNH)

• Hemolytic disorder with intracorpuscular defect
  at stem cell level
• 3 manifestations- HA, venous th, deficient
  hematopoiesis (pancytopenia)
• Mech Defect in DAF ( CD55) MIRL (CD59)
  proteins causing RBC susceptible to lysis by
  complement.

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• Venous Th abdominal veins (hepatic, portal,
  mesenteric) causing Budd-Chiari synd, congestive
  splenomegaly, abdominal pain.
• Cerebral veins sinuses thrombosis
• Aplastic anemia 15-30

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Lab

• Ham's test (acidified serum lysis test) , sucrose
  lysis test, flow cytometry (CD55, 59)
• ? -- Bl T (washed RBCs), androgens,
  corticosteroids, heparin, ATG, BMT

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Basophilic stippling
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G6PD Def
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Retic
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Budd-Chiari
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HUS
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malaria