RBC Disorders Flashcards
blood - characteristics
*homogenous multifunctional specialized fluid connective tissue
*mature cellular elements ONLY: granulocytes, lymphocytes, platelets, RBCs
*specialized proteinaceous plasma fluid: immunoglobulins, coagulation factors, etc
bone marrow - characteristics
*heterogeneous site for hematopoiesis; reservoir for proliferation and differentiation
*% hematopoiesis - predictable cellularity (10% decrease in celullarity per decade of life)
*myeloid:erythroid ratio (3:1) - predictable cellular composition
lymphoreticular organs - characteristics
*immune surveillance of “interior” body surfaces and components of internal fluids
*lymph nodes, MALT, spleen, liver
anemia - defined
*red blood cell “deficiency” with inadequate O2-carrying capacity for proper metabolic function
*characterized by hemoglobin < 95% of the reference interval for age, sex, and geographic location
note - anemia is a SECONDARY MANIFESTATION of other disease process
3 mechanistic classifications of anemias
- blood loss (hemorrhage)
-acute (e.g. trauma)
-chronic (e.g. slow loss, GI/GU) - RBC destruction (hemolytic anemias)
-intrinsic abnormalities (membranopathies, enzymopathies, hemoglobinopathies)
-extrinsic abnormalities (immune mediation, RBC fragmentation syndromes) - impaired RBC production (non-hemolytic anemias)
-erythroblast maturation defects (vitamin deficiencies, hemoglobin synthesis defects)
-stem cell production failure
morphologic classification: MICROcytic anemias
*DECREASED HEMOGLOBIN SYNTHESIS
*normal cellular proliferation and DNA synthesis
*PALER, SMALLER cells
*can result from decreased synthesis of heme or improper synthesis of globins
top 4 causes of microcytic anemias
- IRON DEFICIENCY
- anemia of chronic disease
- thalassemias
- sideroblastic anemia
morphologic classification: MACROcytic anemias
*DEFECTIVE DNA SYNTHESIS
*asynchrony b/w nuclear and cytoplasmic maturation
*gigantic cells with immature chromatin: MEGALOBLASTS
-larger, normochromic red cells
-hypersegmented nuclei of granulocytes
top 4 causes of macrocytic anemias
- vitamin B12 deficiency
- folate deficiency
- drug-induced (e.g. methotrexate, dilantin, sulfa, AZT)
- other (alcoholism, liver disease, MDS, reticulocytosis)
morphologic classification: NORMOcytic anemias
*NORMAL cell size
*various pathogenetic mechanisms
-acute hemorrhage
-RBC enzyme defects (e.g G6PD deficiency)
-RBC membrane defects
-bone marrow disorders
-hemoglobin variants
-autoimmune hemolytic anemia
calculation for MCV (mean corpuscular volume)
Hct / RBC count
normal MCV range
80-100 fL
note - < 80 is microcytic; > 100 is macrocytic
calculation for MCHC (mean corpuscular hemoglobin concentration)
Hb / Hct
note - MCHC is the mean concentration of hemoglobin in RBC
reticulocytosis
a normal increase in reticulocytes in the peripheral blood in response to anemia (indicates that the bone marrow is properly compensating for the anemia)
iron deficiency anemia (IDA) - epidemiology
*primary cause of defective heme synthesis
*MOST COMMON CAUSE OF ANEMIA WORLDWIDE
*about 20% of women, 50% of pregnant women; 3% of men
iron deficiency anemia (IDA) - pathophysiology in infants/children
dietary insufficiency
iron deficiency anemia (IDA) - pathophysiology in adults
*CHRONIC BLOOD LOSS
*malabsorption
*menstruation
*blood donation
*hemoglobinuria
iron deficiency anemia (IDA) - clinical features
*insidious, slowly progressive
*fatigue, irritability, dizziness, headache, breathlessness
*PICA: craving/ingestion of unusual substance
*impaired neuromuscular activity
*brittle, pitted nails
*atrophy of lingual papillae, burning/sore mouth
*dysphagia, gastritis
iron deficiency anemia (IDA) - hematologic findings
*Hb usually < 8 g/dL (severe microcytic)
*low MCV and MDHC
*high RDW
*reticulocytosis - mild
*thrombocytosis
*bone marrow: erythroid hyperplasia mild/moderate
iron deficiency anemia (IDA) - lab findings (CBC & serum iron panel)
*CBC: low Hb, low Hct, low RBC count, low MCV, high RDW, decreased reticulocytes
*iron studies:
-low serum iron
-LOW SERUM FERRITIN
-high TIBC
-low transferrin saturation %
*bone marrow iron stores depleted (not enough iron in the body)
iron deficiency anemia (IDA) - RBC size & appearance
*pale cells, large central pale zones
*low MCV (<80)
megaloblastic anemias
*2 types: folate deficiency anemia and vitamin B12 deficiency anemia
*characterized by macrocytic RBCs & hypersegmented neutrophils in peripheral blood
megaloblastic anemias - diagnostic approach
*moderate to severe macrocytic anemias
*MCV range from 100-150 fL (macrocytic)
*MCHC normal
*hypersegmentation of neutrophils
megaloblastic anemias - image
*hypersegmented neutrophils (>5 lobes) are an early sign of megaloblastic anemia, indicating a folate deficiency or vitamin B12 deficiency
megaloblastic anemias - bone marrow diagnosis
*hypercellular bone marrow
*large cells, immature nuclei with mature cytoplasm
WARNING - may be mis-diagnosed as leukemia
spherocytosis - image
*relatively no central pale zone
*spheres instead of flat, biconcave discs
hemolytic anemias - overview
*anemias caused by hemolysis of red blood cells
*reduction of normal RBC lifespan
*hemolytic state accompanied by compensatory hyperplastic bone marrow
laboratory tests for hemolysis
*elevated serum bilirubin (demonstration of clinical jaundice)
*decreased serum haptoglobin
*increased plasma hemoglobin
*positive Coomb’s test indicates autoimmune hemolysis
*urine hemoglobin & hemosiderin (dark urine)
*increased LDH
*look at reticulocyte count to see if bone marrow is compensating
hereditary spherocytosis - overview
*intrinsic RBC membrane defect
*renders RBCs spherical, less deformable, vulnerable to splenic destruction and hemolysis
*autosomal dominant/recessive inherited disorder
hereditary spherocytosis - clinical features
*chronic hemolytic anemia with reticulocytosis
*episodes of mild jaundice
*splenomegaly
*gallstones
*acute hemolytic crisis: fever, abdominal pain
hereditary spherocytosis - diagnosis
*normocytic anemia
*SPHEROCYTES
*very high MCHC
*reticulocytosis
*increased osmotic fragility of RBCs
*elevated LDH and total bilirubin
pure red cell aplasia - overview
*red blood cell failure
*destruction of erythropoietic cell elements
*can be acquired (including parvovirus B19) or congenital
*presents with s/s of anemia (fatigue, pallor)
pure red cell aplasia - diagnostic approach
*peripheral blood: severe normocytic, normochromic anemia with marked reticulocytopenia
*bone marrow: complete/near absence of erythroblasts; increased M:E ratio
aplastic anemia - overview
*HEMATOPOIETIC STEM CELL FAILURE
*destruction of ALL hematopoietic bone marrow elements
*majority of cases are idiopathic
aplastic anemia - clinical features
*progressive fatigue, dyspnea, palpitations
*bleeding (bruising, etc)
*infections
aplastic anemia - diagnostic approach
*peripheral blood: marked pancytopenia (low counts of all blood cell types)
*bone marrow: marked panhypoplasia (empty marrow)
aplastic anemia - bone marrow image
“empty marrow”
thalassemias - overview
*QUANTITATIVE defective production of globin (protein is normal but there is not enough)
*absence/decrease of one chain
*relative excess of other chain manifests as:
1. peripheral blood -> hemolysis
2. bone marrow -> ineffective hematopoiesis/apoptosis
hemoglobinopathies - overview
QUALITATIVE defective production of globin (makes enough but not made “correctly”)
HbS/β0 (alpha2βSβ0) sickle/beta thalassemia - characteristics
*indistinguishable from sickle cell disease
*severe microcytic anemia
*Hb quantities:
-HbA: 0%
-HbA2: > 5%
-HbS: < 90%
-HbF: < 30%
HbS/β+ (alpha2βSβ+) sickle/beta thalassemia - characteristics
*mild sickling disease
*mild to moderate microcytic anemia
*Hb quantities:
-HbA: 15-30%
-HbA2: > 3.5%
-HbS: ~70%
-HbF: < 20%
what are “target cells” a clue for
possibly a thalassemia
