Anemia & Red Cell Disorders Flashcards
definition of anemia
- decreased O2 carrying capacity of blood: decreased erythrocytes and/or decreased amount of hemoglobin per cell
RBC measurements
- hemoglobin
- hematocrit
- RBC count
- RBC indices
RBC indices
- MCV: mean cell volume = Hct/RBC (size)
- MCHS: mean cell hemoglobin concentration = Hg/Hct (central pallor)
- MCH: mean cell hemoblobin = Hg/RBC
- RDW: red cell distribution width= anisocytosis (variation in red cell size)
Clinical features of anemia
- weakness
- fatigue
- pallor
- rapid pulse
Classification of anemia: physiologic
- blood loss: acute & chronic
- increased rate of destruction: hereditary & acquired
- impaired red cell production
Classification of anemia: morphologic
- microcytic (MCV100fl): B12, folate deficiency, reticulocytosis
- normocytic (MCV80-100fl): many disorders
Acute blood loss
- early on major problem in loss of blood VOLUME
- hemodilution then lowers hemoglobin level
- increase in reticulocyte count occurs 1 week after acute hemorrhage
Chronic blood loss
- anemia occurs when hemorrhage exceeds bone marrow regerative capacity or if iron stores are depleted
- bleeding is MAJOR cause of IRON deficiency anemia
Hemolytic anemia
- red cells destroyed in peripheral blood
- RBC survival
Lab findings in hemolytic anemia
- increased indirect bilirubin & LDH
- decreased haptoglobin: free Hg binds and cleared by liver
- increased reticulocytes and polychromasia on blood smear
Mechanisms of hemolysis
- intracorpuscular: membrane defect: hereditary pherocytosis, enzyme defect: G6PD deficiency, disorder of Hg synthesis: sickle cell, thalassemia
- extracorpuscular: anti RBC antibodies, vascular wall defects, toxins
Intravascular hemolysis
- RBCs destroyed w/in vessels
- increased Hg, decreased haptoglobin, urine positive for hemoglobin and hemosiderin
- Ex: fragmentation hemolysis (DIC, TTP), marathon running
Extravascular hemolysis
- RBCs destroyed w/in macrophages, mainly in spleen
- urine is negative for hemoglobin and hemosiderin
- Ex: hereditary spherocytosis
Hereditary spherocytosis
- autosomal dominant common in euopeans (1/5000)
- deficiency of spectrin, band 3, or ANKYRIN* most common
- decreased membrane stability–spherocytes–removed by spleen
- splenectomy is curative but only needed if severe hemolysis
G6PD deficiency
- abnormalities in hexose-monophosphate shunt (decreased protection against oxidant stress
- cells cannot reduce glutathione due to lack of NADPH
- most common are G6PD A- & G6PD mediterranean
- DIAGNOSIS made by quantitating levels of G6PD in blood
G6PD deficiency: inheritance & hemolysis
- X linked
- hemolysis occurs when patient is exposed to drugs, becomes infected, or eats FAVA BEANS
- hemolysis is self limited: stay away from above
- avoidance of oxidant stress is major therapy
Histology of G6PD deficiency
- heinz bodies: increased Hg on one side of RBC
- blister cells: spleen eats half of RBC that has too much Hg
Sickle cell anemia
- VALINE substituted for GLUTAMIC acid at position 6 of B-globin gene
- globin chains aggregate under deoxygenating conditions in the HOMOZYGOUS condition
- sickle cells removed by macrophages and cause vascular occlusion: bone pain, splenic atrophy
Sickle cell trait
- heterozygous condition, 8% of african americans
- benign condition
Sickle cell histology
- howell jolly bodies: small purple dots in RBCs = remnants of nuclei
Hemoglobin distribution in sickle cell anemia
- have Hg S and no Hg A
Thalassemia
- decreased alpha or beta chain production
- hypochromic microcytic anemia
- ineffective erythropoiesis & hemolysis
- heterozygosity leads to protection from plamodium falciparum malaria
Alpha thalassemia
- gene DELETION of one to all four alpha globin chains
- one or two gene deletion asymptomatic with microcytosis, +/- minimal anemia in two gene deletion
- three gene deletion leads to moderate anemia
- four gene deletion leads to HYDROPS FATALIS - intrauterine death
Beta thalassemia
- POINT mutations in beta globin gene
- most commonly due to SPLICING mutations
- decrease beta chain formation & excess alpha chains precipitate causing membrane damage
Beta thalassemia trait
- heterozygosity for beta gene mutation
- mild anemia w/ microcytosis
- lab testing reveals an increase in A2 level (increased alpha2:delta 2) –which amounts to ~5% total Hg (higher than normal)
Clinical and histologic findings in beta thalassemia
- systemic iron overload
- microcytic red cells: increased central pallor, decreased MCV & MCHC
- ## prominent facial bones, x-ray of skull shows hair on end appearance due to increase erythropoiesis
Acquired hemolytic anemias
- immune hemolytic anemia
- fragmentation hemolytic anemia
Immune hemolytic anemia
- antibodies develop to part of red cell membrane
- IgG (most common) bound to red cell which is removed by spleen leading to formation of SPHEROCYTES, which are sequestered by spleen
- DIRECT ANTIGLOBULIN (COOMBS) test is positive
Fragmentation hemolytic anemia
- schistocytes are characteristic
- microangiopathic hemolytic anemia due to microvascular thrombi: DIC or TTP
- mechanical heart valves
Anemia of decreased production
- decreased reticulocytes: nutritional deficiencies, chronic disease, stem cell disorder in marrow
Megaloblastic anemia - impaired DNA synthesis
- morphologic findings: oval macrocytes, hypersegmented neutrophils (more than 5 lobes), hypercellular marrow w/ nuclear/cytoplasmic asynchrony
- example of ineffective erythropoieses
Causes of B12 deficiency
- dietary: rare, strict vegans
- post gastrectomy, malabsorption, fish tapeworm
- pernicious anemia (most common): autoimmune w/ antibodies to IF
- neurologic defects: demyelination of posterior columns
Folate deficiency
- dietary: rare but seen in premature infants & pregnant women
- malabsorption
- increased utilization: hemolytic anemia
- stored in live, last 2-4 months
- no neurologic defects
Why B12 and folate are necessary
- needed for DNA synthesis
Tests to differentiate b/w B12 & folate deficiency
- methylmalonic acid: B12=HIGH, folate=NORMAL
- both will have high homocysteine
Treatment of B12 or folate deficiency
- B12 or folate replacement
- hematologic symptoms of B12 deficiency can be treated w/ administration of folate but neurologic symptoms may progress
Type of anemia seen w/ folate and B12 deficiency
megaloblastic anemia
Iron deficiency
- common cause of anemia
- causes: dietary, increased requirement (kids, pregnancy), blood loss (GI, menstrual)
Morphology of iron deficiency anemia
- microcytic hypochromic cells: increased central pallor
Lab studies in iron deficiency
- decreased serum iron
- increased total iron binding capacity (transferrin)
- decreased iron saturation
- decreased serum FERRITIN
Bone marrow appearance in iron deficiency
- prussian blue stain will show no stores = no blue stain appearance
Iron deficiency treatment
- iron supplementation: oral or IV
- diagnose and treat the cause of blood loss
Anemia of chronic inflammation
- normocytic or mildly microcytic anemia due to chronic inflammatory states or infections
- very common
- mild anemia (Hct = 30%)
- symptoms & treatment relate to underlying disease
Anemia of chronic inflammation: etiology
- inflammatory cytokines stimulate hepcidin (iron regulatory protein) synthesis: iron sequestered in macrophages, decreased intestinal absorption of iron, Hg synthesis is impaired b/c iron is not delivered to erythrocytes
Iron studies in amemia
- iron deficiency: decreased ferritin, Fe, stores; increased transferrin
- chronic disease: decreased Fe, transferrin; increased ferritin, stores
- all others: decreased transferrin; increased stores, ferritin, Fe
Aplastic anemia
- marrow failure with pancytopenia (decreased all cell production)
- mostly idiopathic
- normocytic or mildly macrocytic anemia, leukopenia, thrombocytopeina
- NEED TO DO BM TO DIAGNOSE
BM appearance in aplastic anemia
- no hematopoetic cells
- all FAT
Treatment of aplastic anemia
- immunosuppressive medications: b/c cells are destroying their own marrow stem cells
- bone marrow transplant
Myelophthisic anemia
- caused by marrow replacement: metastatic cancer, leukemia/lymphoma, fibrosis
Anemia of renal failure/uremia
- decreased erythropoietin stimulation of erythroid precursors: treat by giving EPO
- anemia in myelodysplastic syndromes: neoplastic stem cell clone develops which has a maturation defect
Polycythemia
- too many red cells
- primary: polycythemia vera
- secondary: high altitude, erythropoietin secreting tumors
Polycythemia vera
- one of myeloproliferative neoplasms
- elevated Hct
- disease of late middle age
- symptom: PRURITIS (itching) after bathing
BM and blood smear in polycythemia vera
- BM has increased red cell precursors (increased megakaryocytes)
- increased red cells in blood smear
Genetics of polycythemia vera
- mutation in JAK 2 gene (V617F)
- leads to increased proliferation of BM cells
EPO levels in polycythemia vera
- decreased
- due to increased red cells
Treatment for polycythemia vera
- phlebotomy
Polychromasia
- bigger and bluer immature red cells
