1. Introduction to Hemolytic Anemias

2. HEMOLYTIC ANEMIAS Introduction Definition Pathogenesis Classification
General clinical features
Laboratory evaluation of hemolysis

3. Hemolytic Anemias Definition
A group of disorders leading to anemia caused by a reduction in red cell life span.
RBC’s normally survive days .
Bone marrow has the capacity to increase erythropoiesis times than normal.
Anemia is the result of premature destruction of red cells exceeding the erythropoietic capacity of the bone marrow.

4. Hemolytic Anemias Classification
Hemolytic anemias may be classified as
I- Hereditary or acquired or
II- Intracorpuscular or Extracorpuscular

5. Hemolysis may occur in two compartments
I- Intravascular or
II- Extravascular ( eg: spleen )

6. Unconjugated bilirubin Expired CO Kidney
Red cell destruction
Extravascular
Intravascular
Free plasma Hb
RES
Hpt and Hpx Hb
Globin
Haem+globin
methem
Haem
Hb- Hpt complex
Plasma
protein pool
Haemopexin-methem
Excess Hb
methaemalbumin
Plasma
iron pool
Liver
Protoporphyrin
Unconjugated bilirubin
Expired CO
Kidney
metHb
Liver Hb
Haemosiderin
Conjugated bilirubin
GI tract
Urine
Urobilinogen
Faeces

7. In some types of hemolytic anemias hemolysis occurs particularly as an intravascular hemolysis.
eg: Paroxsysmal nocturnal hemoglobinuria
Traumatic or microangiopathic hem. anemia
(eg:cardiac hemolytic anemia,march hemoglobinuria,TTP)
Acute hemolytic transfusion reaction etc

8. A Simple Classification of Hemolytic Anemias
1- Abnormalities of RBC interior
a. Enzyme defects
b. Hemoglobinopathies & Thalassemia Maj
2-RBC membrane abnormalities
a. Hereditary spherocytosis, elliptocytosis etc
b. Paroxysmal nocturnal hemoglobinuria
c. Spur cell anemia
3- Extrinsic factors
a. Hypersplenism
b. Antibody : immune hemolysis
c. Traumatic & Microangiopathic hemolysis
d. Infections , toxins , etc
Hereditary
Intracorpuscular
Acquired
Extracorpuscular

9. Clinical Manifestations in Summary
Onset may be acute or insidious
Symptoms and signs of anemia
Jaundice
Acholuric
Without pruritus
Symptoms and signs spesific to the type of hemolytic anemia
Symptoms related to the underlying disease
Splenomegaly
Most congenital hem. anemias except sickle cell
Some of the acquired hem. anemias
Cholelithiasis (gall stones) symptoms
Leg ulcers (sickle cell, spherocytosis)
Skeletal abnormalities (thalassemia)
Crises (chronic hemolytic disease)
Aplastic crises (HPV-B19)
Hemolytic
Megaloblastic
Changes in urine color

10. Laboratory findings I- Increased RBC destruction
Decreased RBC life span
Increased haem(heme) catabolism
Increased serum unconjugated bilirubin*
Increased endogenous CO production
Increased urobilinogen excretion
Increased serum LDH*
Absence or decrease of serum haptoglobin*
> 1 g /dl /week fall in blood Hb level*
Reduced glycosylated Hb
Signs of intravascular hemolysis
Hemoglobinemia*
Hemoglobinuria*
Hemosiderinuria*
Methemalbuminemia
Reduced serum hemopexin level
*common practice

11. Laboratory findings II-Increased bone marrow activity and RBC production
Blood
Reticulocytosis
Macrocytosis
Polychromatophilia
Erythroblastosis
Leukocytosis and thrombocytosis
Bone marrow
Erythroid hyperplasia
Ferrokinetic
Increased plasma iron turnover
Increased RBC iron turnover
Biochemical
Increased RBC creatine
Increased activity of RBC enzymes eg: hexokinase, etc

12. Laboratory Evaluation of Hemolysis
Extravascular
Hematologic
Blood film Polychromatophilia
Reticulocyte Increased
Bone marrow Erythroid hyperplasia
Plasma or serum
Bilirubin unconjugated
Haptoglobin , absent
Plasma free Hb N -
LDH
Urine
Bilirubin 0
Hemosiderin 0
Hemoglobin 0
Urobilinogen
Intravascular
Polychromatophilia
Increased
Erythroid hyperplasia
unconjugated
absent +
+ ( severe cases)

13. Laboratory tests useful in differential diagnosis
Examination of peripheral blood
Special Lab. examinations

14. Morphologic abnormalities in hemolytic anemias
Polychromasia
Spherocyte :
Elliptocytes:
Stomatocytes:
Acanthocytes:
Echinocytes:
: Reticulocytes
Her. Spherocytosis, immune hem. anemia,
burns, chemical injury to RBC
Hereditary ovalocytosis,
Hereditary stomatocytosis, alcoholism
Spur cell anemia with liver disease,
abetalipoproteinemia
Pyruvate kinase deficiency, uremia

15. Morphologic abnormalities in hemolytic anemias
Sickle cell:
Target cels:
Schistocytes:
Agglutination:
Heinz bodies:
Sickle cell anemia
Thalassemia, HbC disease, liver disease,
splenectomy
Microangiopathic hem anemia, uremia, DIC,
malignant hypertesion, eclampsia,
disseminated vasculitis or malignancy,
Cold agglutinin disease
Unstable Hb, G6PD deficiency and oxidant stress

16. Bite cells -Blister cells
G6PD deficiency
Unstable Hemoglobin

17. RBC fragmentation Helmet Cell, schistocytes
Thrombotic Thrombocytopenic Purpura (TTP),
Hemolytic uremic syndrome (HUS)
Disseminated Intravascular Coagulation
Vaskulitis
Renal graft rejection
Malignant hypertention
Burns
Artificial cardiac valves
March hemoglobinuria

18. Target cells Liver disease Thalassemia Hb C Splenectomy
Sickle cell anemia
Iron deficiency

19. Howell-Jolly bodies (Nuclear remnants) Splenectomy Hyposplenism
Megaloblastic anemia
Hemolytic anemia
(Nuclear remnants)

20. Ribosomes/RNA/mitochondrial bodies
Basophylic stippling
Lead poisoning
Thalassemia,
Unstable hemoglobines
MDS
Megaloblastic anemia
Other hemolytic anemia
Eg. 5-Nucleotidase deficiency
Ribosomes/RNA/mitochondrial bodies

21. Heinz Bodies (Denaturated Hemoglobin) RBC Enzyme defects
Unstable hemoglobin
Thalassemia
Sickle cell anemia
(Denaturated Hemoglobin)

22. Special Lab. Examinations
Coombs antiglobulin test - immune hemolysis
Osmotic fragility test - spherocytosis
Autohemolysis- G6PD,PK, spherocytosis
Membrane protein analysis- membrane defects
Red cell sickling- sickle cell anemia
Hemoglobin electrophoresis and HbA2, Hb F , HHb,etc - Hemoglobinopathies and thalassemias
Red cell enzyme assays- RBC enzyme defects
HAM and sucrose lysis tests and GPI-linked protein analysis by flow cytometry- PNH
Oxygen dissociation curve- High oxygen affinity Hb

23. Diagnostic approach
Is there anemia?
Detailed history including disease related symptoms, bleeding, drugs,ethnics, occupation , toxic exposure etc. family history
Physical exam.: Signs of hemolytic anemia (common and specific ) in addition to anemia and any signs of underlying disease

24. Diagnostic approach What are the changes in red cell morphology?
Smear examination
Red cell indexes
Are there any changes in other cell lines ?
Is there evidence of increased red cell production? Reticulocytes
Is there evidence of hemolysis?
What is the type/diagn. of hemolysis?
Special tests
Is there evidence of intravascular hemolysis?