Hemolytic Anemias Flashcards
Hemolytic anemias
Physiology of RBC loss
Hemolytic anemias: Short RBC life span associated with features of accumulation of hemoglobin catabolism due to RBC destruction –> associated with increase in erythropoeisis and reticulocytosis
Physiology of RBC Loss:
- RBCs normally are made in the marrow and survive for 100-120 days
- for the first day, RBCs still contain ribosome which can be stained as reticulin in reticulocytes = bluish hue of cytoplasm
- reticulocyte counts are normally 1%
- as the body tries to make more blood, the reticulocyte count is even higher
Consequences of RBC Hemolysis
- anemia - pallor, shortness of breath, etc.
- expansion of the marrow space with skeletal deformity (tower skull)
- growth retardation
- funny looking RBCs
- increased reticulocytes
- increased bilirubin, uric acid and LDH
- bilirubin gall stones
- splenomegaly
First step in making a diagnosis of hemolytic anemia
Identify presence of hemolysis
- hemolytic anemias frequently have RBCs that differ from normal RBC size and shape - see differences on blood smear
- hematologists look at the shape of RBCs and the shape and color of their inclusions to help determine the cause of hemolysis or other causes of anemia
Peripheral RBC morphology
- acanthocytes
- basophilic stippling
- bite cells
- burr cells
- cabot’s ring
- howell-Jolly bodies
- acanthocytes - liver disease, abetaliproteinemia, postsplenectomy
- basophilic stippling - lead tox, thalassemia
- bite cells - G^PD deficiency, oxidant drug hemolysis
- burr cells - uremia, ulcers, gastric CA
- cabot’s ring - splenectomy, mebaloblastic, hemolytic
- howell-Jolly bodies - splenectomy, megaloblastic, hemolytic
Peripheral RBC morphology
- pappenheimer bodies
- schistocytes
- spherocytes
- stomatocytes
- target cells
- teardrop cells
- pappenheimer bodies - sideroblastic anemia, splenectomy
- schistocytes - microangiopathic hemolytic anemia, prosthetic heart valves, burns
- spherocytes - hereditary, immune hemolytic anemias
- stomatocytes - hereditary, immune, membrane expanded by cholesterol
- target cells - liver dx, spleen out, thalassemia, HbC
- teardrop cells - myelofibrosis, myelophthesis
Laboratory diagnosis of hemolytic anemia
- low hgb can normochromic normocytic, microcytic hypochromic or macrocytic
- RBC shape/fragments
- reticulocyte count
Hemolytic anemia diagnostic features
- reticulocytosis
- blood smear = might see hypochromic microcytic anemia or may be normal
- signs of heme degradation
Extravascular vs. intravascular hemolysis
- Lab findings
Extravascular: Removal of RBCs by the reticuloendothelial system (spleen macrophages)
- increased indirect and direct bilirubin
- increased LDH
- increased free hgb
- decreased haptoglobin
- methemoglobin increased –> a form of catabolized hemoglobin that increases as haptoglobin is depleted because there is no more protein to buffer it
- bilirubin in the urine
- hemosiderinuria
- hemoglobinuria
Intravascular: Destruction of RBCs in the circulation with free hemoglobin release
- increased direct bilirubin
- increased LDH
- decreased haptoglobin
- bilirubin in the urine - rarely
Second step in diagnosing hemolytic anemia
Identify the mechanism of hemolysis
- intrinsic defect/intracorpuscular
- extrinsic defect/extracorpuscular –> immune or non-immune mediated
Intrinsic hemolytic anemias
- Abnormal RBC membrane = spherocytosis, elliptocytosis, paroxysmal noctural hemoglobinuria
- Enzyme disorder = G6PD of pyruvate kinase deficiency
- Abnormal hemoglobin = sickle cell, thalassemias
Hereditary spherocytosis
Defect of the RBC membrane (mutation in the ankyrin protein) that renders the erythrocytes spheroidal and susceptible to splenic sequestration and destruction
- defects in membrane binding to cytoskeleton lead to membrane separation and loss as microvesicles –> small dense micropherocytic RBCs result that have reduced osmotic fragility
Diagnosis and management of spherocytosis
Diagnosis:
- blood smear = anemia, spherocytosis
- osmotic fragility test
- bone marrow = increased erythropoeisis
- clinically = jaundice (increased bilirubin) + splenomegaly
Treatment:
- folic acid treatment is recomended to prevent aplastic anemia due to the hyperactive bone marrow
- splenectomy in symptomatic patients
Hereditary elliptocytosis
Autosomal dominant inherited defect
- elliptical RBC and variation in RBC shape = poikilocytosis
Paroxysmal nocturnal hemoglobinuria
- RBC membrane defect of DAF (CD55) + membrane inhibitor of lysis (CD59)
- both factors protect RBCs from complement damage
- patients have heightened sensitivity of complement because of the loss of DAF
- a sucrose hemolysis test can be performed to demonstrate heightened sensitivity to complement
G6PD deficiency
- G6PD assessed by submitting RBCs to oxidative stress
- medications like primaquine will trigger intravascular hemolysis 3 days after taking the drug
- other triggers of oxidative stress = sulfonamids, nitrofurantoin, fava beans
Mechanism of hemolysis
- oxidative stress
- hemoglobin denaturation with precipates called Heinz bodies
- cause RBC membrane damage and hemolysis with bite cell formation
