Hemolytic Anemia Flashcards
What is Intrinsic hemolytic anemia?
Disorder with the RBC itself like disorders of the red cell membrane, metabolic hemolysis, and disorders of Hb synthesis
What are examples of Intrinsic anemias involving disorders with the red cell membrane?
hereditary spherocytosis, hereditary elliptocytosis, stromatocytosis, acanthocytosis, and PNH
What are examples of Intrinsic anemias involving disorders of metabolic hemolysis?
Hexosemonophosphate shunt (G6PD) and pyruvate kinase disorders
What are examples of Intrinsic anemias involving disorders of Hb synthesis?
Sickling hemoglobinopathies and thalassemias.
What is extrinsic hemolysis?
Disorders that affect the RBC like Microangiopathic conditions, immune hemolytic anemia, infectious conditions, and hypersplenism.
What are examples of Microangiopathic conditions?
Cardiac valve mechanical hemolysis, TTP, DIC, and burns
What are some examples of immune hemolytic anemia?
Auto-immune hemolytic anemia(idiopathic and secondary), warm antibodies, cold antibodies, allo-immune hemolytic anemias, transfusion reactions, erthroblastosis fetalis
What are some examples of infectious conditions causing hemolytic anemia?
Malaria, babesiosis, and clostridial sepsis
What is the mechanism of extravascular hemolysis?
RBC phagocytosed by macrophages in the spleen and liver (RE system)
Why are RBCs phagocytosed in extravascular hemolysis?
RBCs are coated with IgG or and or C3b, or RBCs are abnormally shaped like sperocytes or sickle cells
Would you see an increase in unconjugated bilirubin in extravascular hemolysis?
Yes
Would you see an increase in LDH in extravascular hemolysis?
Yes
What is intravascular hemolysis?
Hemolysis that occurs within blood vessels caused by things like enzyme deficiencies, complement mediated destruction of RBCs, and mechanical damage (i.e. valve stenosis)
What two findings will you see in intravascular hemolysis?
Decreases serum haptoglobin and hemoglobinuria
What are the clinical features of hemolytic anemia?
Pallor of mucus membranes, jaundice, and splenomegally. There is No bilirubin in urine. May see gallstones (from bilirubin) and ulcers around the ankle (esp. sickle cell pts)
What characterizes Aplastic crises?
Parvovirus infection which usually turns off erythropoiesis, so you see a sudden drop in anemia and a drop in the reticulocyte count
What is hereditary spherocytosis?
Autosomal dominant disorder affecting mostly northern europeans. Mutation in ankyrin (most common) or spectrin, or band 3, which are all RBC membrane proteins
What are the clinical findings of hereditary sperocytosis?
Jaundice, gallstones, splenomegally, and aplastic crisis.
What are the lab findings of hereditary sperocytosis?
Normocytic anemia with sperocytes, increased MCHC, and increased osmotic fragility
How would you treat hereditary spherocytosis?
Splenectomy
What is hereditary elliptocytosis?
Autosomal dominant, defective spectrin.
What are the clinical findings of hereditary elliptocytosis?
Most have none to mild anemia and splenomegally
What are the lab findings hereditary elliptocytosis?
Elliptocytes on peripheral blood smear.
What is the treatment of hereditary elliptocytosis?
Splenectomy only if symptomatic
What is PNH?
Rare, acquired disorder in marrow stem cells. Absent DAF and CD59; therefore RBCs are no longer protected from complement deposition which results in intravascular hemolysis
What are the clinical findings in PNH?
Hemoglobinuria which may cause Fe deficiency, thrombosis, and risk for developing acute myelogenous leukemia
What are the peripheral blood findings in PNH?
Normocytic anemia with pancytopenia.
How do you diagnose PNH?
Flow cytometry, sugar water test
What is G6PD deficiency?
X linked recessive (affects males). Seen in mediterranean and blacks. G6PD is only source of NADPH, which is needed for glutathione. Deficiency causes RBCs to be susceptible to oxidant stress
What are some oxidant stresses that induce hemolysis in G6PD deficiency?
Infection, drugs, and FAVA beans
What are the lab findings in G6PD deficient pts?
Normocytic anemia, heinz bodies, and bite cells
What are the clinical findings of G6PD deficient pts?
Sudden onset of back pain with hemoglobinuria that occurs 2-3 d after oxidant stress
How do you diagnose G6PD deficiency?
Enzyme level test. However, this can only be done when pt is not in active hemolysis, otherwise risk test giving a false “normal” level
What is pyruvate kinase deficiency?
Autosomal recessive. Chronic lack of ATP causing membrane rigid.
What are the clinical findings of pyruvate kinase deficiency?
Anemia with jaundice and gallstones. Increase in 2,3 DPG synthesis causes right shift oxygen dissociation curve (this somewhat offsets the effects of anemia)
What are the lab findings of pyruvate kinase deficiency?
Normocytic anemia and echinocytes (RBCs with thorny projections)
What is the most common cause of immune hemolytic anemia?
Autoimmune warm type (IgG)
What immunoglobulin is found with cold autoimmune hemolytic anemia?
IgM
What is the pathogenesis of warm (IgG) mediated hemolysis?
RBCs coated with IgG are phagocytosed by splenic macrophages, typical of extravascular hemolysis and spherocytes are produced if some of the membrane is removed
What are the clinical findings of autoimmune hemolytic anemias?
Jaundice (extravasular), splenomegally, raynauds phenomena (cold types)
What are the lab findings in warm autoimmune hemolytic anemia?
Spherocytosis, positive direct Coombs( DAT)
What is the treatment for warm autoimmune hemolytic anemia?
Remove the underlying cause (i.e. drug induced), give corticosteriods, splenectomy if don’t respond well to other treatments, immunosuppressives if don’t respond to corticosteriods, mAbs, or IV Ig’s
What is the pathogenesis of cold autoimmune hemolytic anemia?
IgM mediated hemolysis that fixes complement. Can be either intravascular (more common) or extravascular
What are the lab findings of cold autoimmune hemolytic anemia?
SImilar to warm, except red cells agglutinate in cold
What is the treatment of cold autoimmune hemolytic anemia?
Keep patients warm and treat any underlying cause. Can give rituximab or anti-CD52 mAbs
What are alloimmune hemolytic anemias?
Antibodies produced by one individual reacts with RBCs of another. Examples are ABO incompatibility and Rh disease of the newborn
What are three mechanisms of drug induced hemolytic anemias?
- Ab directed against a drug-RBC (i.e. penicillin)
- Deposition of complement via drug-Ab complex
- True autoimmune hemolytic anemia with unclear role of the drug
What are red cell fragmentation syndromes?
Arise through physical damage to RBCs, i.e. artificial heart valves or microangiopathic anemias
What is March hemoglobinuria
Damgage to RBCs between small bones of the feet like in marathoners (aka Runners anemia)
What are microangiopathic hemolytic anemias?
Microcirculatory lesions that cause RBC fragmentation; schistocytes
What are macroangiopathic hemolytic anemias?
Hemolytic process caused by valvular defects (aortic stenosis)
What are the lab findings in micro and macroangiopathic hemolytic anemias?
Normocytic anemia, long standing hemoglobinuria causes Fe deficiency. Decreases serum haptoglobin and hemoglobinuria, and schistocytes
What is MCV?
hct/RBC*10
What is MCH?
Hb/RBC*10
What is MCHC?
Hb/Hct*100
What tests do you look for in the evaluation of hemolysis?
Peripheral smear, retic count, bilirubin, LDH, plasma Hb, urine Hb, urine hemosiderin, haptoglobin, DAT, G6PD screen, Hams test, sugar water test, osmotic fragility
Should malaria be considered as a potential cause of hemolytic anemia?
Yes
