5. Inravascular hemolysis (1):Inravascular hemolysis (1):
- red cells destruction occurs in vascular space- red cells destruction occurs in vascular space
- clinical states associated with Intravascular hemolysis:- clinical states associated with Intravascular hemolysis:
acute hemolytic transfusion reactionsacute hemolytic transfusion reactions
severe and extensive burnssevere and extensive burns
paroxysmal nocturnal hemoglobinuriaparoxysmal nocturnal hemoglobinuria
severe microangiopathic hemolysissevere microangiopathic hemolysis
physical traumaphysical trauma
bacterial infections and parasitic infections (sepsis)bacterial infections and parasitic infections (sepsis)
6. Inravascular hemolysis (2):Inravascular hemolysis (2):
- laboratory signs of intravascular hemolysis- laboratory signs of intravascular hemolysis::
indirect hyperbilirubinemiaindirect hyperbilirubinemia
erythroid hyperplasiaerythroid hyperplasia
hemoglobinemiahemoglobinemia
methemoalbuminemiamethemoalbuminemia
hemoglobinuriahemoglobinuria
absence or reduced of free serum haptoglobinabsence or reduced of free serum haptoglobin
hemosiderynuriahemosiderynuria
7. Extravascular hemolysis :Extravascular hemolysis :
- red cells destruction occurs in reticuloendothelial system- red cells destruction occurs in reticuloendothelial system
- clinical states associated with extravascular hemolysis :- clinical states associated with extravascular hemolysis :
autoimmune hemolysisautoimmune hemolysis
delayed hemolytic transfusion reactionsdelayed hemolytic transfusion reactions
hemoglobinopathieshemoglobinopathies
hereditary spherocytosishereditary spherocytosis
hypersplenismhypersplenism
hemolysis with liver diseasehemolysis with liver disease
- laboratory signs of extravascular hemolysis:- laboratory signs of extravascular hemolysis:
indirect hyperbilirubinemiaindirect hyperbilirubinemia
increased excretion of bilirubin by bileincreased excretion of bilirubin by bile
erythroid hyperplasiaerythroid hyperplasia
hemosiderosishemosiderosis
14. Hereditary microspherocytosisHereditary microspherocytosis
1. Pathophysiology1. Pathophysiology
- red cell membrane protein defects (spectrin deficiency)- red cell membrane protein defects (spectrin deficiency)
resulting cytoskeleton instabilityresulting cytoskeleton instability
2. Familly history2. Familly history
3. Clinical features3. Clinical features
- splenomegaly- splenomegaly
4. Laboratory features4. Laboratory features
- hemolytic anemia- hemolytic anemia
- blood smear-microspherocytes- blood smear-microspherocytes
- abnormal osmotic fragility test- abnormal osmotic fragility test
- positive autohemolysis test- positive autohemolysis test
- prevention of increased autohemolysis by including glucose in- prevention of increased autohemolysis by including glucose in
incubation mediumincubation medium
5. Treatment5. Treatment
- splenectomy- splenectomy
15. Paroxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria
1. Pathogenesis1. Pathogenesis
- an acquired clonal disease, arising from a somatic mutation in a- an acquired clonal disease, arising from a somatic mutation in a
single abnormal stem cellsingle abnormal stem cell
- glycosyl-phosphatidyl- inositol (GPI) anchor abnormality- glycosyl-phosphatidyl- inositol (GPI) anchor abnormality
- deficiency of the GPI anchored membrane proteins- deficiency of the GPI anchored membrane proteins
(decay-accelerating factor =CD55 and a membrane inhibitor(decay-accelerating factor =CD55 and a membrane inhibitor
of reactive lysis =CD59)of reactive lysis =CD59)
- red cells are more sensitive to the lytic effect of complement- red cells are more sensitive to the lytic effect of complement
- intravascular hemolysis- intravascular hemolysis
2. Symptoms2. Symptoms
- passage of dark brown urine in the morning- passage of dark brown urine in the morning
16. 3. PNH –laboratory features:3. PNH –laboratory features:
- pancytopenia- pancytopenia
- chronic urinary iron loss- chronic urinary iron loss
- serum iron concentration decreased- serum iron concentration decreased
- hemoglobinuria- hemoglobinuria
- hemosiderinuria- hemosiderinuria
- positive Ham’s test (acid hemolysis test)- positive Ham’s test (acid hemolysis test)
- positive sugar-water test- positive sugar-water test
- specific immunophenotype of erytrocytes (CD59, CD55)- specific immunophenotype of erytrocytes (CD59, CD55)
4. Treatment4. Treatment::
- washed RBC transfusion- washed RBC transfusion
- iron therapy- iron therapy
- allogenic bone marrow transplantation- 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
