3. Hemolytic Anemia
๏ฌ Definition:
๏ฌ Those anemias which result from an increase
in RBC destruction
๏ฌ Classification:
๏ฌ Congenital / Hereditary
๏ฌ Acquired
5. Inravascular hemolysis (1):
- red cells destruction occurs in vascular space
- clinical states associated with Intravascular hemolysis:
acute hemolytic transfusion reactions
severe and extensive burns
paroxysmal nocturnal hemoglobinuria
severe microangiopathic hemolysis
physical trauma
bacterial infections and parasitic infections (sepsis)
6.
7. Inravascular hemolysis (2):
- laboratory signs of intravascular hemolysis:
indirect hyperbilirubinemia
erythroid hyperplasia
hemoglobinemia
methemoalbuminemia
hemoglobinuria
absence or reduced of free serum haptoglobin
hemosiderynuria
8. II. Extracorpuscular factors
A. Immune hemolytic anemias
1. Autoimmune hemolytic anemia
- caused by warm-reactive antibodies
- caused by cold-reactive antibodies
2. Transfusion of incompatible blood
B. Nonimmune hemolytic anemias
1. Chemicals
2. Bacterial infections, parasitic infections (malaria), venons
3. Hemolysis due to physical trauma
- hemolytic - uremic syndrome (HUS)
- thrombotic thrombocytopenic purpura (TTP)
- prosthetic heart valves
4. Hypersplenism
9. Extravascular hemolysis :
- red cells destruction occurs in reticuloendothelial system
- clinical states associated with extravascular hemolysis :
autoimmune hemolysis
delayed hemolytic transfusion reactions
hemoglobinopathies
hereditary spherocytosis
hypersplenism
hemolysis with liver disease
- laboratory signs of extravascular hemolysis:
indirect hyperbilirubinemia
increased excretion of bilirubin by bile
erythroid hyperplasia
hemosiderosis
12. Laboratory features:
1. Laboratory features
- normocytic/macrocytic, hyperchromic anemia
- reticulocytosis
- increased serum iron
- antiglobulin Coombsโ test is positive
2. Blood smear
- anisopoikilocytosis, spherocytes
- erythroblasts
- schistocytes
3. Bone marrow smear
- erythroid hyperplasia
13. 3. PNH โlaboratory features:
- pancytopenia
- chronic urinary iron loss
- serum iron concentration decreased
- hemoglobinuria
- hemosiderinuria
- positive Hamโs test (acid hemolysis test)
- positive sugar-water test
- specific immunophenotype of erytrocytes (CD59,
CD55)
4. Treatment:
- washed RBC transfusion
- iron therapy
- allogenic bone marrow transplantation
14. Introduction
๏ฌ Mean life span of a RBC-120days
๏ฌ Removed Extravascularly by- Macrophages
of RE system
15. Classification of Hemolytic Anemias
Hereditary 1. Abnormalities of RBC interior
a.Enzyme defects: G-6-PD def,PK def
b.Hemoglobinopathies
2. RBC membrane abnormalities
a. Hereditary spherocytosis etc.
b. PNH
Acquired c. Spur cell anemia
3. Extrinsic factors
a. Hypersplenism
b. Antibody: immune hemolysis
c. Mechanical trauma: MAHA
d. Infections, toxins, etc
Ref : Harrisonโs
16. Features of HEMOLYSIS
Bilirubin
LDH
Reticulocytes, n-RBC
Haptoglobulins
+ve Urinary hemosiderin, Urobilinogen
Blood Film
Spherocytes No spherocytes Fragmentation
DCT +ve DCT โve
AI Hemolysis H. Sherocytosis Malaria,
Clostidium
Hereditery enzymopathies Microangiopathic,
Traumatic
17. Red Cell Membrane Defects
1.Hereditary Spherocytosis
๏ฌ Usually inherited as AD disorder
๏ฌ Defect: Deficiency of Beta Spectrin or Ankyrin
๏ Loss of membrane in Spleen & RES๏
becomes more spherical๏ Destruction in
Spleen
21. Complications
๏ฌ Clinical course may be complicated with
Crisis:
๏ฌ Hemolytic Crisis: associated with infection
๏ฌ Aplastic crisis: associated with Parvovirus
infection
22. ๏ฌ Inv:
๏ฌ Test will confirm Hemolysis
๏ฌ P Smear: Spherocytes
๏ฌ Osmotic Fragility: Increased
Screen Family members
23. ๏ฌ Management:
๏ฌ Folic Acid 5mg weekly, prophylaxis life long
๏ฌ Spleenectomy
๏ฌ Blood transfusion in Ac, severe hemolytic crisis
24. 2.Hereditary Elliptocytosis
๏ฌ Equatorial Africa, SE Asia
๏ฌ AD / AR
๏ฌ Functional abnormality in one or more anchor
proteins in RBC membrane- Alpha spectrin ,
Protein 4.1
๏ฌ Usually asymptomatic
๏ฌ Mx: Similar to H. spherocytosis
๏ฌ Variant:
3.SE-Asian ovalocytosis:
๏ฌ Common in Malaysia , Indonesiaโฆ
๏ฌ Asymptomatic-usually
๏ฌ Cells oval , rigid ,resist invasion by malarial
parasites
26. Red Cell Enzymopathies
๏ฌ Physiology:
๏ฌ EM pathway: ATP production
๏ฌ HMP shunt pathway: NADPH & Glutathione
production
27. 1. Glucose-6-Phosphate Dehydrogenase
( G6PD ) Deficiency
๏ฌ Pivotalenzyme in HMP Shunt & produces
NADPH to protect RBC against oxidative
stress
๏ฌ Most common enzymopathy -10%
worldโs population
๏ฌ Protection against Malaria
๏ฌ X-linked
32. Autoimmune Hemolytic Anemia
๏ฌ Result from RBC destruction due to RBC
autoantibodies: Ig G, M, E, A
๏ฌ Most commonly-idiopathic
๏ฌ Classification
๏ฌ Warm AI hemolysis:Ab binds at 37degree
Celsius
๏ฌ Cold AI Hemolysis: Ab binds at 4 degree
Celsius
33. 1.Warm AI Hemolysis:
๏ฌ Can occurs at all age groups
๏ฌF>M
๏ฌ Causes:
๏ฌ 50% Idiopathic
๏ฌ Rest - secondary causes:
1.Lymphoid neoplasm: CLL, Lymphoma,
Myeloma
2.Solid Tumors: Lung, Colon, Kidney, Ovary,
Thymoma
3.CTD: SLE,RA
4.Drugs: Alpha methyl DOPA, Penicillin ,
Quinine, Chloroquine
5.Misc: UC, HIV
34. ๏ฌ Inv:
๏ฌ e/o hemolysis, MCV
๏ฌ P Smear: Microspherocytosis, n-RBC
๏ฌ Confirmation: Coombโs Test / Antiglobulin test
๏ฌ Treatment
๏ฌ Correct the underlying cause
๏ฌ Prednisolone 1mg/kg po until Hb reaches
10mg/dl then taper slowly and stop
๏ฌ Transfusion: for life threatening problems
๏ฌ If no response to steroids ๏ Spleenectomy or,
๏ฌ Immunosuppressive: Azathioprine,
Cyclophosphamide
35. 2. Cold AI Hemolysis
๏ฌ Usually Ig M
๏ฌ Acute or Chronic form
๏ฌ Chronic:
๏ฌ C/F:
๏ฌ Elderly patients
๏ฌ Cold , painful & often blue fingers, toes,
ears, or nose ( Acrocyanosis)
๏ฌ Inv:
๏ฌ e/o hemolysis
๏ฌ P Smear: Microspherocytosis
๏ฌ Ig M with specificity to I or I Ag
36. ๏ฌ Other causes of Cold Agglutination:
๏ฌ Infection: Mycoplasma pneumonia, Infec
Mononucleosis
๏ฌ PCH : Rare cause seen in children in
association with cong syphilis
37. ๏ฌ Treatment:
๏ฌ Treatment of the underlying cause
๏ฌ Keep extremities warm
๏ฌ Steroids treatment
๏ฌ Blood transfusion
38. Non-Immune Acquired Hemolytic
Anemia
1. Mechanical Trauma
A). Mechanical heart valves, Arterial grafts:
cause shear stress damage
B).March hemoglobinuria: Red cell damage in
capillaries of feet
C). Thermal injury: burns
D). Microangiopathic hemolytic anemia (MAHA):
by passage of RBC through fibrin strands
deposited in small vessels ๏ disruption of
RBC eg: DIC,PIH, Malignant HTN,TTP,HUS
39. Acquired hemolysis
2.Infection
F. malaria: intravascular hemolysis: severe
called โBlackwater feverโ
Cl. perfringens septicemia
3.Chemical/Drugs: oxidant denaturation of
hemoglobin
Eg: Dapsone, sulphasalazine, Arsenic
gas, Cu, Nitrates & Nitrobenzene
40. Paroxysmal Nocturnal Hemoglobinuria
๏ฌ Hematopoietic stem cell disorder
๏ฌ Mutation of phosphatidylinositol glycan class A
(PIG-A) gene
๏ฌ Glycosylphosphatidylinositol (GPI) anchors
membrane proteins
๏ฌ Without GPI, unable to regulate completment
activities on membrane
๏ฌ Hemolysis is pH dependent
๏ฌ Thrombosis can occur
41. Lab Tests for PNH
๏ฌ Acidified serum lysis test (Hamโs test): PNH cells
lyse due to complement activation in acidified
serm
๏ฌ Sugar water (sucrose hemolysis) test: RBCs
sensitive to complement will lyse in sucrose and
serum
๏ฌ Flow cytometry: lack of CD59 on RBCs, or lack
of CD59 or CD55 on granulocytes
42. Microangiopathy
๏ฌ Schistocytes
๏ฌ Triangular or helmet shaped RBC fragments
๏ฌ Destruction of RBC as they move through
damaged blood vessels
๏ฌ Endocarditis
๏ฌ Hemangiosarcoma
๏ฌ Caval Syndrome โ Heartworm Disease
๏ฌ Thrombosed IV catheter
๏ฌ Vasculitis
๏ฌ Hemolytic-uremic syndrome
๏ฌ DIC
๏ฌ Schistocytes are also seen with osmotic
fragility
๏ฌ Liver disease, iron deficiency, water
intoxication, congenital, zinc toxicity
43. Young man of 19
Complains of giddiness
weakness, pallor
Examination reveals a spleen
mild lemon yellow sclera
47. Bilirubin level of 2.5 mg/dL,
Lactate dehydrogenase (LDH) of
2140 IU/L,
Haptoglobin below 7 mg/dL
48. The direct antiglobulin test was
positive for complement (C3d) (++),
and IgG (++-).
Also was positive for agglutinins of
IgM type and had a titer of 1:1024.
50. Serologies for human
immunodeficiency virus, hepatitis B
and C viruses, and Mycoplasma
pneumoniae were negative.
Rheumatoid factor and antinuclear
antibodies were undetectable.
51. Prednisone therapy was started at
a dose of 1 mg/kg intravenously,
daily. Hemoglobin level rose to
11 g/dL, concomitantly with the
improvement of hemolytic signs.
52. A reduction of positivity of both
direct and indirect antiglobulin tests
(polyvalent serum + ; C3d + ;
IgG+ ), as well as a reduction of
cold agglutinin titers (1:128), was
observed 8 weeks after
corticosteroid therapy.
53. Three months later, corticosteroids
were tapered to a maintenance
dose of 25 mg daily.
Hemolysis recurred again with the
fall of hemoglobin to 7 g/dL.
54. The direct antiglobulin test recurred
positive for polyvalent serum (+++),
complement (+++), and IgG (+++),
while cold agglutinin titers again
became strongly positive (1:256).
56. CD20 is widely expressed on B-
cells.
CD20 could play a role in Ca2+
influx across plasma membranes,
maintaining intracellular Ca2+
concentration and allowing
activation of B cells.
57. Hemoglobin value reached
13.5 g/dL just before the third dose,
although biochemical signs of
hemolysis remained substantially
unaltered.
58. At the end of therapy, the hemolytic
signs disappeared, the direct and
indirect antiglobulin tests became
negative, and cold agglutinin titers
fell to 1:32
Immunophenotyping of bone
marrow cells showed the absence
of CD20 and CD19 B cells.