Anemias Flashcards
Microcytic, Hypochromic anemias
Iron deficiency, thalassemias; decreased MCV, MCH, MCHC
Normocytic, normochromic anemias
acute bleeding, and associated w/ chronic disease
Macrocytic
B12 and folate deficiency
Iron Deficiency Anemia
Microcytic, hypochromic, w/ anisopoikilocytosis; Major cause of microcytic anemia
Chronic blood loss leads to IDA
Iron Deficiency leads to heme production defect
Cause: Occult gastrointestinal bleed, nutritional deficit, malabsorption, hemolysis,
Clinical: Pallor, koilonychia (spoon nails), pagophagia, PICA,
Iron Cycle
Iron mostly in hemoglobin
1g/day lost through exfoliated skin, but no natural method of excretion
Controlled by 3 proteins: Transferrin - delivers iron to cells, duodenum; Transferrin receptor - binds/absorbs iron laden transferrin at cell surface; Ferritin - binds iron for storage
Total body iron: 2-4g
Balance intake/loss
Anemia of Chronic Disease
Most common anemia in hospitalized patients
Normocytic, normochromic anemia
Suppressed response to EPO due to inflammatory cytokines
Defective reutilization of iron, iron sequestered in phagocytes,
Low serum iron, low transferrin, low transferrin saturation, high serum ferritin, increased BM stores mostly in macrophages
Associated Chronic Diseases: Renal Failure - chronic bleed, hemolysis, decreased EPO; DM; inflammation; cancer, liver disease;
Alcoholism: directly toxic, nutritional deficiency, chronic bleeds, congestive splenomegaly/portal hypertension, lipopretein abnormalities (acanthocytes)
Megaloblastic Anemias
Two most common causes: B12 and Folate deficiency
CBC shows pancytopenia
Macrocytic anemia, anisopoikilocytosis, and hypersegmented nuetrophils; BM shows giant bands and nuclear/cytoplasmic asynchrony
Clinical: anemia, atrophic glossitis, gastric gland atrophy, nuerologic deficits in B12 ONLY
Vitamin B12 Deficiency
PERNICIOUS ANEMIA - most common cause = malabsorption (intrinsic factor dysfunction/deficiency)
Rarely due to dietary insufficiency, B12 stores last years except in strict vegans
Cause: likely autoantibodies against intrinsic factor; Type I - block binding of B12 and intrinsic factor
Type II - Bind B12/IF complex and stop absorption
Associated w/ autoimmune diseases: Hashimoto’s Thyroiditis, Adrenalitis, Grave’s Disease
Tests: Serum B12 levels, methylmalonic acid and homocysteine levels, Autoantibody tests;
Schilling test*
Treatment: IM B12, corrects anemia, corrects neurological deficits if
Folate Deficiency
Usually Dietary insufficiency
Liver stores can deplete in 3-6 months
No neurologic deficits
Tests: Serum and RBC folate levels, homocysteine levels, Autoantibody tests
Treatment: Folate supplement, folate supplement partially corrects B12 deficiency but does not affect neurologic deficits
Aplastic Anemia
Stem cell injury/suppression
Normocytic, normochromic anemia, pancytopenia, NO reticulocytosis, hypocellular BM = dry tap
Aquired Causes: IDIOPATHIC, autoimmune suppression by T cell mechanism (most common), chemicals, toxins, drugs, radiotherapy/radiation, viral infections (Hep., EBV, HIV, parvo),
Hereditary: Fanconi Anemia - AR, defects in DNA repair, congenital anomalies (hypoplastic radii, thumbs, organs), may evolve into MDS, acute or chronic myeloid leukemia
Treatment: Supportive - transfusions, antibiotics, immunosuppression, BM transplant if
Pure Red Cell Aplasia
Normocytic anemia
No reticulocytosis
Few to absent erythroblasts in BM
Autoimmune disease - T cell or IgG autoantibody against RBC precursors; associated w/ SLE, CLL, lymphomas, THYMOMAS,
Primary - Diamond Blackfan Syndrome = severe anemia first year of life w/ other congenital anomalies
Secondary - infections: Parvovirus B19, solid tumors, rheumatic disease (SLE, sjogrens), drugs, idiopathic
Treatment: stop drugs if cause, thymoma resection, High dose IV immunoglobulin for parvo, Immunosuppression (ATG + cyclosporine)
Sideroblastic Anemias
Rare
Failure to incorporate iron into protoporphoryin to form hemoglobin
Dimorphic (macro/micro), hypochromic,
High serum iron, high transferrin saturation, high ferritin
Hereditary: X-linked recesssive - due to defects in Amino-levulonic acid synthase (ALA synthase)
Aquired: Myelodysplasia, drugs, toxins (lead, zinc), nutritional deficiency
Treatment: pyradoxine (B6), treat underlying condition (remove toxin exposure, stop drug)
Acute hemolytic anemia sx
fatigue, pallor, jaundice, splenomegaly, CHF
Chronic hemolytic anemia sx
fatigue, pallor, jaundice, splenomegaly, CHF, gallstones, abnormal bone growth and fractures
Hemolytic anemia lab findings
Unconjugated bilirubin Decreased serum haptoglobin Increased serum LDH reticulocytosis Schistocytes
Extravascular hemolysis
Occurs outside bloodstream
Usually associated with inherited hemolytic anemias
Spherocytes on PB smear
Intravascular hemolysis
Within bloodstream
Free hemoglobin released - leads to hemoglobinuria, hemosiderinuria
Usually associated with aquired hemolytic anemia
Beta Thalassemia Major
Decreased production of HbA (a2b2)
Beta globulin gene on chromosome 11 - usually point mutations or partial deletions
Two possible abnormal Beta alleles: Beta0 and Beta+
Beta0 produces no beta globulin (degraded mRNA)
Beta+ produces reduced beta globulin
Beta0/Beta0 = none; Beta+/Beta+ = reduced; Beta0/Beta+ = reduced
Onset at 6-9 months as switch to adult hemoglobin
Severe anemia, compensation leads to abnormal bone growth, hepatosplenomegaly
Depend on transfusions for survival
Clinical: growth retardation, distorted facies, iron overload, Compensatory increase in HbA2 and HbF Microcytic, hypochromic anemia, anisopoikilocytosis
Beta Thalassemia Minor
One normal/one abnormal allele of Beta globulin: B/B+ or B/B0
Microcytic, hypochromic anemia
important to differentiate from iron deficiency anemia: iron therapy improves IDA, but worsens Beta thalassemia minor
Increased or normal serum and BM iron in Beta thalassemia minor
Alpha Thalassemia
Four alpha globin genes, severity based on # affected alpha genes (total deletion)
Loss all 4: Hemoglobin Bart = gamma tetramers, no hemoglobin of any form, Hydrops fetalis; Burr cells
Loss of 3: Hemoglobin H = Beta tetramers, precipitates in RBC and bitten off in spleen (bite cells), after splenectomy see Heinz bodies in RBC
Loss of 2: Alpha thalessemia trait - two types; Type I - deletion of both on one chromosome, Hb Bart at birth, HbH inclusions during life; Type II - deletion of one on each chromosome, Hb Bart at birth, NO HbH inclusion need gene mapping to confirm
Sickle Cell Disease
Sickled cells - cytoskeletal damage (spectrin dimers instead of tetramers) lead to increased blood viscosity, microvascular occlusion, infarction
HbS - Valine replaces glutamate at position 6 of Beta, HbS has abnormal intermolecular bonding leading to polymerization and sickling
Homozygous (V6E) - HbF increased to ~10%, chronic hemolysis w/ vaso-occlusive crises (hand and foot syndrome [dactylitis = swollen fingers in infants] and avascular necrosis of femoral head), expanded BM for increased hematopoiesis, EMH, autosplenectomy - congestion, infarction, fibrosis (salmonella osteomylitis), chronic leg ulcers
Complications: Acute Chest Syndrome - dangerous microvascular occlusion in lung, fever, cough , chest pain, lung infiltrates, CVA, Infection/sepsis encapsulated organisms, aplastic crisis (parvo BM suppression), splenic sequestration crisis (rapid splenomegaly and hypovolemia), priapism, organ infarction, cerebral growth impairment, GALLSTONE formation from chronic extravascular hemolysis,
PB - severe anemia, Howell-Jolly bodies
Diagnosis: sickle cells in PB, sickling test, Hemoglobin electrophoresis, High performance liquid chromatography
Sickle tendency: Interaction w/ other Hb (HbA has low affinity severe hypoxia for sickling; HbF inhibits polymerization, can attenuate; HbD moderate affinity) HbC - (L6E) HbSC is sickle disorder but less severe than HbSS; Hb concentration (increase in MCHC - dehydration); thalassemias; increased pH or temp.
Hereditary Spherocytosis
Mutations in the RBC membrane skeleton protein ankyrin leads to deficiency of spectrin because lack of anchor - spherical shape less deformable
Clinical: usually chronically compensated; jaundice; splenomegaly; gallstones; anemic crises due to parvo, hematosuppression, or folate deficiency
Diagnosis: Osmotic Fragility Test; only notable disease w/ microcytosis and increased MCHC; negative Coomb’s; +family history
Treatment: folic acid, Splenectomy (treatment of choice) spherocytosis persists, but site of hemolysis removed
Glucose-6-phophate Dehydrogenase Deficiency
G6PD gives RBC antioxidant protection, RBC becomes denatured in times of oxidant stress due to inadequate production of NADPH needed to maintain GSH levels; stability of G6PD is functional defect
Heinz bodies from denatured hemoglobin
Mediterranean variant: severe decrease,
Warm Antibody Hemolytic Anemia
Antibodies reactive at body temperature
Mostly due to IgG antibodies - spleen eliminates IgG coated cells
Drug induced: methyldopa (L-dopa) - antibody against Rh blood group antigen; Penicillin-hapten - antibody against drug attached to RBC; tetracyclines, cephalosporins, tolbutamide
Disorders: Lymphatic malignancies (CLL, ect.); autoimmune disorders (SLE, rh arthritis, ulcerative colitis)
Treatment: treat underlying conditions, corticosteroids, blood transfusions, gammaglobulins, plasmaphoresis, splenectomy
May antedate onset of disease by months or years
