This document discusses hemolytic anemias, which are classified based on whether there is a red blood cell abnormality or an extracorpuscular factor causing hemolysis. Specific types covered include hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, sickle cell anemia, autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria, and hereditary microspherocytosis. The mechanisms, clinical features, laboratory findings, diagnosis, and treatment are described for several of these hemolytic anemia subtypes.
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. Inravascular hemolysis (2):
- laboratory signs of intravascular hemolysis:
indirect hyperbilirubinemia
erythroid hyperplasia
hemoglobinemia
methemoalbuminemia
hemoglobinuria
absence or reduced of free serum haptoglobin
hemosiderynuria
7. 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
14. Hereditary microspherocytosis
1. Pathophysiology
- red cell membrane protein defects (spectrin deficiency)
resulting cytoskeleton instability
2. Familly history
3. Clinical features
- splenomegaly
4. Laboratory features
- hemolytic anemia
- blood smear-microspherocytes
- abnormal osmotic fragility test
- positive autohemolysis test
- prevention of increased autohemolysis by including glucose in
incubation medium
5. Treatment
- splenectomy
15. Paroxysmal nocturnal hemoglobinuria
1. Pathogenesis
- an acquired clonal disease, arising from a somatic mutation in a
single abnormal stem cell
- glycosyl-phosphatidyl- inositol (GPI) anchor abnormality
- deficiency of the GPI anchored membrane proteins
(decay-accelerating factor =CD55 and a membrane inhibitor
of reactive lysis =CD59)
- red cells are more sensitive to the lytic effect of complement
- intravascular hemolysis
2. Symptoms
- passage of dark brown urine in the morning
16. 3. PNH –laboratory features:
- pancytopenia
- chronic urinary iron loss
- serum iron concentration decreased
- hemoglobinuria
- hemosiderinuria
- positive Ham’s 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
17. SICKLE CELL ANEMIA
Definition: chronic hemolytic anemia occuring
almost exclusively in blacks and characterized
by sickle-shaped red cells(RBCs) caused by
homozygous inheritance of Hemoglobin S
18. SICKLE CELL ANEMIA-pathogenesis
- In Hb S, valine is substituted for glutamic acid in
the sixth amino acid of the ß chain.
- Deoxy-Hb S is much less soluble than deoxy Hb A;
it forms a gelatinous network of fibrous polymersthat cause RBCs to
sickle at sites of low pO2.
- Hemolysis-because sickle RBCs are too fragile to withstand the
mechanical trauma of circulation
- Occlusion in microvascular circulation caused by distorted, inflexible
RBCs adhering to vascular endothelium
19. SICKLE CELL ANEMIA-incidence
- Homozygous - about 0,3% of blacks in the USA
(have sickle cell anemia)
- Hetezygotes-8-13% of blacks, (are not anemic, but the
sickling trait=sicklemia can be demonstrated in vitro)
20. SICKLE CELL ANEMIA-clinical features
IN HOMOZYGOTES
1. Clinical complications due to severe hemolytic anaemia
- slowed growth and development in children
- bilirubins stones
- aplastic crisis
- congestive heart failure from chronic anemias and cardiac
overload compensation
2. Consequences of vaso-occlusion of the microcirculations (tissue
ischemia and infarction)
- infarction of spleen, brain, marrow, kidney, lung, aseptic
necrosis, central nervous system and ophtalmic vascular lesions
22. SICKLE CELL ANEMIA-therapy
Preventive measures:
prevention or remedy of: infections(penicillin prophylaxis and
pneumococcal vaccination), fever, dehydratation,acidosis,
hypoxemia, cold exposure
Blood transfusions for very severe anemia
New approaches to therapy;
1. Activation of Hb F synthesis -5-azacytidine
2. Antisickling agents acting on hemoglobin or membrane
3. Bone marrow transplantation