Transcript SZPICZAK MNOGI Definicja choroby: Choroba proliferacyjna

Classification of Hemolytic anemias
I. Red cell abnormality (Intracorpuscular factors)
A. Hereditary
1. Membrane defect (spherocytosis, elliptocytosis)
2. Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD)
deficiency, Pyruvate kinase (PK) deficiency)
3. Hemoglobinopathies (unstable hemoglobins,
thalassemias, sickle cell anemia )
B. Acquired
1. Membrane abnormality-paroxysmal nocturnal hemoglobinuria (PNH)
HEMOLYTIC ANEMIAS
Hemolytic anemias = reduced red-cell life span
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
Mechanisms of hemolysis:
- intravascular
- extravascular
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)
Inravascular hemolysis (2):
- laboratory signs of intravascular hemolysis:
indirect hyperbilirubinemia
erythroid hyperplasia
hemoglobinemia
methemoalbuminemia
hemoglobinuria
absence or reduced of free serum haptoglobin
hemosiderynuria
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
Hemolytic anemia - clinical features:
- pallor
- jaundice
- splenomegaly
Laboratory features:
1. Laboratory features
- normocytic/macrocytic, hyperchromic anemia
- reticulocytosis
- increased serum iron
- antiglobulin Coombs’ test is positive
2. Blood smear
- anisopoikilocytosis, spherocytes
- erythroblasts
- schistocytes
3. Bone marrow smear
- erythroid hyperplasia
Diagnosis of hemolytic syndrome:
1. Anemia
2. Reticulocytosis
3. Indirect hyperbilirubinemia
Autoimmune hemolytic anemia caused by warmreactive antibodies:
I. Primary
II. Secondary
1. acute
- viral infections
- drugs ( -Methyldopa, Penicillin, Quinine, Quinidine)
2. chronic
- rheumatoid arthritis, systemic lupus erythematosus
- lymphoproliferative disorders
(chronic lymphocytic leukemia, lymphomas,
WaldenstrÖm’s macroglobulinemia)
- miscellaneous (thyroid disease, malignancy )
Autoimmune hemolytic anemia caused by
cold-reactive antibodies:
I. Primary cold agglutinin disease
II. Secondary hemolysis:
- mycoplasma infections
- viral infections
- lymphoproliferative disorders
III. Paroxysmal cold hemoglobinuria
Autoimmune hemolytic anemia - diagnosis
- positive Coombs’ test
Treatment:
- steroids
- splenectomy
- immunosupressive agents
- transfusion
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
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
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
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
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
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)
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
SICKLE CELL ANEMIA-laboratory
findinges
1. Anemia-normocytic or slightly macrocytic
2. Leukocytosis(chronic neutrophilia)
3. Thrombocytosis-usually mild<1000G/l
4. Reticulocytosis
5. Peripheral smear: sickle shaped red cells,
polychromatophilia, Howell-Jolly bodies
6. Hb -electrophoresis
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