Transcript Hemolytic_anemia

HEMOLYTIC ANEMIA
OUTSIDE THE RED CELL
WITHIN THE RED CELL
1. Membrane defects
AUTO-IMMUNE
NON-IMMUNE
- HS
1. Warm
1. Hypersplenism
- HE
2. Cold
- Hereditary pyropoikilocytosis
3. Transfusion reactions
- Hereditary stomatocytosis
4. Drug associated
2. Fragmentation syndromes
- grafts / valves / AS
- HTN / Pre-eclampsia
- March hemoglobinuria
- MAHA
- TTP/HUS
- DIC
- hemangioma
2. Enzyme defects
-G6PD
-Pyruvate kinase
3. Hemoglobin defects
- SCA
- Thalassemias
- Unstable hemoglobin
2. Infections/Toxins (Malaria,
Babeosis, Bartonella, Clostridium
welchii, snakes, spiders)
3. Drugs
4. Liver dz (Spur cell)
5. PNH
HEMOLYTIC ANEMIA
Intravascular Causes in Yellow
OUTSIDE THE RED CELL
WITHIN THE RED CELL
1. Membrane defects
AUTO-IMMUNE
NON-IMMUNE
- HS
1. Warm
1. Hypersplenism
- HE
2. Cold
- Hereditary pyropoikilocytosis
3. Transfusion reactions
- Hereditary stomatocytosis
4. Drug associated
2. Fragmentation syndromes
- grafts / valves / AS
- HTN / Pre-eclampsia
- March hemoglobinuria
- MAHA
- TTP/HUS
- DIC
- hemangioma
2. Enzyme defects
-G6PD
-Pyruvate kinase
3. Hemoglobin defects
- SCA
- Thalassemias
- Unstable hemoglobin
2. Infections/Toxins (Malaria,
Babeosis, Bartonella, Clostridium
welchii, snakes, spiders)
3. Drugs
4. Liver dz (Spur cell)
5. PNH
Alf Alving, Scientist, U.S. Army
(mid 1950s)
RBC
Extravascular Hemolysis
RES
HBG
Fe
Transferrin
CO
Storage and
recycled in
marrow
Lung
Biliverdin
Uncojugated
bilirubin
Conjugation
Bile
Intravascular Hemolysis
RBC LYSIS
HBG
HAPTOGLOBIN
REMOVED BY LIVER
HBG TAKEN UP BY RENAL
TUBULAR CELLS
HEMOGLOBINEMIA
HEMOSIDERIN
HEMOGLOBINURIA
CELLS SLOUGHED IN
URINE 1 WEEK LATER
Classic Presentation
1. New onset pallor and anemia
2. Splenomegaly
3. Jaundice
3.  Indirect bilirubin (<5)
4.  Reticulocyte percentage
5.  LDH (esp LDH-2)
6.  RBC life span
7.  Haptoglobin
< 25
- 83% SENS
- 96% SPEC
HEMOLYTIC ANEMIA
OUTSIDE THE RED CELL
WITHIN THE RED CELL
1. Membrane defects
AUTO-IMMUNE
NON-IMMUNE
- HS
1. Warm
1. Hypersplenism
- HE
2. Cold
- Hereditary pyropoikilocytosis
3. Transfusion reactions
- Hereditary stomatocytosis
4. Drug associated
2. Fragmentation syndromes
- grafts / valves / AS
- HTN / Pre-eclampsia
- March hemoglobinuria
- MAHA
- TTP/HUS
- DIC
- hemangioma
2. Enzyme defects
-G6PD
-Pyruvate kinase
3. Hemoglobin defects
- SCA
- Thalassemias
- Unstable hemoglobin
2. Infections/Toxins (Malaria,
Babeosis, Bartonella, Clostridium
welchii, snakes, spiders)
3. Drugs
4. Liver dz (Spur cell)
5. PNH
Hereditary Spherocytosis
-
Autosomal Dominant
~1:3000
Spectrin, Ankyrin, Protein 3
Dx: osmotic frag., neg. direct Coombs
Tx: Splenectomy, cholecystectomy,
vaccine, folate
Hereditary Eliptocytosis
-
Autosomal Dominant
~1:4500
Protein 4.1
Dx: >75% elliptic RBC
Tx: Splenectomy
Hereditary Stomatocytosis
-
Autosomal Dominant
Lack of Protein 7.2 (stomatin)
 Permeability to Na, K
Stomatocytes, xerocytes  target cells
Tx: Splenectomy
Stateville Penitentiary, near Joliet, IL
(mid 1950s)
Warm Immunohemolyis
-
Most common in adult women (CT, SLE)
IgG bound to RBC activate phagocytes and
complement
Dx: + direct Coombs
Tx:
-
1. Prednisone 1mg/kg ( RES, Ab production)
2. Splenectomy
3. Cyclophosphamide
4. Azathioprine
5. IV gamma globulin
6. Transfusions (cross-matching impossible)
Cold Immunohemolyis
-
monoclonal production of cold agglutinins
response to infection (M. pneumoniae, EBV)
IgM mediated complement attack (no Fc)
Tx:
-
1. Underlying cause
2. Splenectomy, Steroids, have minimal role
-
1931 – Nobel prize for
discovery of hexosemonophosphate shunt
and glycolytic pathway
(Otto Meyerhof, Gustav
Embden students)
-
1931-1944 discovery
of cytochromes, flavin
adenine dinucleotide,
nicotinamide adenine
dinucleotide.
-
1944 – offered 2nd
Nobel prize, but
prevented from
accepting it by Hitler
Otto Warburg (1883-1970)
TTP
-
Ab inhibits protease that normally cleaves vWF
-
-
1. Intravascular hemolysis
2. Thrombocytopenia
3. Non focal neurologic findings
4.  Renal function
5. Fever
Dx
-
-
Negative direct Coombs
Fragmented RBC, but no spherocytes
Normal coagulation tests
Tx
-
Plasmapheresis, glucocorticoids, dipyridamole,
dextran, ASA
HUS
-
O157:H7 Shiga-like verotoxins that damage
renal vascular endothelial cells
Clinically similar to TTP, no neuro
manifestations
Tx
-
Plasmapheresis, dialysis, transfusions
Role of glucocorticoids, dextran, heparin uncertain
Liver disease: Spur Cell Anemia
-
 cholesterol to phospholipid ratio
Splenic traffic jam
Clinically similar to TTP, no neuro
manifestations
Limited Treatment
PNH
-
Somatic mut. on X-chromosome
Gene makes GPI anchor
Many proteins can’t attach to RBC
No DAF and membrane inhibitor of reactive
lysis (MIRL), RBC sensitive to complement
Hypercoaguable state
Dx: pancytopenia,  LAP, sucrose hemolysis,
Ham’s test (lysis in acidified serum)
Tx: Transfusion, glucocorticoids, Fe
BM transplant usually effective
G6PD
-
X chromosome, recessive
11% African American males
 sensitivity to oxidative stress
Heinz bodies, bite cells
Triggers: infection, drugs, met. acidosis,
moth balls, fava beans
Dx: enzyme assay (fluorescent spot) after
acute episode
Tx: avoid triggers
DRUGS THAT CAUSE HEMOLYTIC ANEMIA
OXIDANT
PENICILLIN TYPE
IMMUNE COMPLEX
1. Antibiotics
(Ab + Drug-Membrane) (Ab-Drug + Membrane)
- nitrofurantoin 1. Penicillins
(Most common type)
- sulfa
2. Cephalosporins
1. quinidine
- dapsone
3. Synthetic penicillins
2. rifampin
- nalidixic acid
2. Primaquine
3. Pyridium
4. Doxorubicin
5. Methylene blue
MISCELLANEOUS
1. Vitamin K (water soluble)
AUTOIMMUNE
(AutoAb to Rh Ag)
1. methyldopa
Cinchona plant, Costa Rica, containing
both quinine and quinidine, named for
the Countess of the Spanish town of
Chinchon
Hematuria, Hemoglobinuria, and Myoglobinuria
Causes of Intravascular Hemolysis
1. Transfusion reactions
2. Infections
- Clostridium welchi
- Malaria, Babeosis
- Bartonella
- Mycoplasma pneumonia
3. Fragmentation syndromes
- grafts / valves / AS
- HTN / Pre-eclampsia
- March hemoglobinuria
- TTP/HUS
- DIC
- hemangioma
4. G6PD deficiency with oxidant stress
5. PNH
6. Infusion of hypotonic solutions
7. Snake and Spider venoms
8. Some autoimmune hemolytic anemias (RhoD)