Hemolytic Anemias
- RBCs are incapable of surviving the normal 120-day life span
- Can be due to 1)intrinsic defects in RBC structure/function or 2) a hostile environment
Definitions
1) Hemolysis – any cond. char. by a sig. decreased RBC life span
2) Compensated Hemolytic state – the resulting increased RBC production is able to keep up with the destruction
3) Hemolytic anemia – insufficient RBC production which leads to anemia, usually normocytic, normochromic.
Diagnosis of Hemolytic Anemia
1) Does anemia exist?
2) What is the marrow’s response?
- reticulocyte count (remember to use the absolute reticulocyte count or reticulocyte production index.
- Remember there are many different causes of reticulosis, therefore you need corraborating evidence of RBC destruction
3) Is there erythrocyte detritus?
- free hemoglobin, methemoglobin, methemalbumin, bilirubin, urobilinogen
- haptoglobin and hemopexin
4) What is the pathophysiological mechanism of hemolysis?
- 1st – extravascular vs. intravascular
- extra- in the sinusoids of the RE system
Ø spherocytes – result of an RBC having to escape from the clutches of the RE system
- intra- in the bloodstream
Ø schizocytes – mechanical destruction of the RBCs in the intravascular spaces
- 2nd – mechanism of the destruction
- Hx and physical
- Examine the peripheral blood film
- Inexpensive lab tests – direct Coomb’s (detects autoAbs); hemoblobin electrophoresis
Mechanical Hemolytic Anemias
- RBCs are destroyed when they pass over gross obstructions (ex. Heart valves) or are “clotheslined” by fibrin strands (ex DIC or TTP)
- Hallmark of microangiopathic hemolytic anemia = schizocytes on routine blood film
Immunohemolytic anemias
- tends to occur in states characterized by systemic autoimmunity, such as lupus
Warm autoimmune hemolytic anemia
- autoantibody of the IgG class
- hemolysis occurs at any temperature
- Drugs are main known causes
- Typically, the auto-Ab is directed against a universal component of the Rh system absent only in individuals with the extremely rare Rh-null RBC membreane type.
Cold agglutinin syndrome
- autoantibodies of the IgM class
- may occur occasionally in cases of Mycoplasma pneumonia and infectious mononucleosis.
- Most cold agglutinins are directed against the I antigen, found in almost all adults.
Paroxysmal Cold Hemoglobinuria
- very rare
- IgG class mediated
- IgG autoantibody is directed against the P antigen found on the RBCs of most all individuals
- Intravascular hemolysis upon exposure to cold temp.
Alloimmune hemolytic anemias
- the body synthesizes Abs against RBC antigens foreign to the host.
- Can be naturally occuring or acquired
- Clinical hemolysis occurs when…
1) hemolytic disease of the newborn – erythroblastosis fetalis
2) hemolytic transfusion reaction
- Diagnosis – simple agglutination test called the direct antiglobulin test (direct Coomb’s test)
- Treatment
Ø aimed at reducing the activity of the body’s misdirected immune system
Ø Glucocorticoids, immunosuppressive drugs, splenectomy
Paroxysmal Nocturnal Hemoglobinuria
- patient’s RBCs develop an acquired somatic mutation that effects the structure of the cell membrane and makes it more sensitive to nonspecific attachment and activation of complement
- results in intravascular hemolysis
- anemia and hemoglobinuria result
Glucose-6-phosphate dehydrogenase deficiency
- Remember that the free radicals (H2O2) have to be converted to H2O by glutathione peroxidase which requires NADPH to reduce the oxidized glutathione back to the reduced glutathione.
- Remember the Hexose monophosphate shunt (Step 1)
- X-linked recessive variant – depressed G6PD, so the exposure to the oxidative substances overwhelms the weakened compensatory mechanism and hemolysis results
- Wide variance of clinical activity/presentation
- Favism – catastrophic condition when someone with bad G6PD deficiency eats fava beans.
Pyruvate Kinase Deficiency
- autosomal recessive, chronic and ongoing clinically
- Phosphoenolpyruvate – Pyruvate Kinase – Pyruvate
ADP - ATP
- only source of ATP for RBC is Glycolysis (Embden-Myerhof pathway)
- ATP is necessary for the Na+K+-ATPase pump; without ATP the cell lyses.
Spherocytosis
- spherocytes are seen in a variety of hemolytic anemias, specifically those in which the RE system is involved.
Hereditary spherocytosis
- genetic variant of a cytoskeletal protein results in the bone marrow producing spherocytes de novo
- autosomal dominant
- Diagnosis – osmotic fragility test & family history
Ø spherocytes are more fragile when placed in a hypo-osmotic environment than are normal RBCs.
- increases the MCHC (seen almost nowhere else)
- Treatment – splenectomy cures it.
Hypersplenism
- any condition that cause enlargment of the spleen makes RBCs undergo hemolysis more easily
- Causes: chronic liver disease, leukemia/lymphoma, CHF
Infections of the RBC
- Malaria, Carrion’s disease, babeosis
- Clostridium perfringens sepsis
Hemoglobinopathies and Thalassemias
- See the devoted section.
- remember that not all hemoglobinopathies and thalassemias produce hemolysis
- Sickle cell anemia and hemoglobin C disease – hemolysis dominates the clinical picture
Anemias of Chronic Disease
- condition seen in individuals suffering from chronic infections, noninfectious inflammatory diseases, and neoplasms
- the following pathogenetic observations have been made in those suffering from chronic anemia
1) Decreased RBC life Span
2) Impaired iron metabolism
Ø iron accumulates in the marrow histiocytes, but uptake into the RBC precursors is impaired
3) Refractoriness to erythropoietin
Tags: Alloimmune hemolytic anemias, autoantibody, Autoimmunity, Bilirubin, erythrocyte detritus, free hemoglobin, Glucocorticoids, Hemolysis, Hemolytic anemia, Immunosuppressive drugs, Lupus, methemalbumin, methemoglobin, Paroxysmal Cold Hemoglobinuria, schizocytes, splenectomy, urobilinogen
