Anemia Flashcards
(54 cards)
Describe the sequential suppression and activation of individual globin genes
γ-globin + α-globin chains form HbF.
After birth switch from HbF to adult hemoglobin (HbA), transcriptional switch from γ- to β-globin
Outline the steps in RBC destruction
120 days in circulation macrophage remove RBC globin --> AA iron --> liver or spleen as ferritin/hemosiderin non-iron heme --> bilirubin
How does marrow respond to hypoxia?
EPO production stimulate erythropoiesis
Most common symptoms associated with anemia
Tachycardia, dyspnea, fever, postural hypotension
Weakness, SOB, dizziness
Fatigue, limited exercise tolerance
Pallor (palms, nail beds, face, conjuctivae, palmar crease)
Jaundice
Presence/absence of lymphadenopathy, hepatosplenomegaly, bone pain
Bleeding/bruising signs
What lab tests are used to diagnose anemia?
CBC/PBS-- MCV Retic bilirubin LDH iron studies bone marrow (aspirate, biopsy) creatinine hemoglobin electrophoresis
Pathophysiology of iron deficiency in children, adults, pregnancy
adults: overt/occult bleeding, blood donation, decreased intake
children: increased growth
female: menstration, pregnancy, lactation
reduced absorption: celiac disease, atrophic gastritis, bariatric surgery
PE findings for iron deficiency
blue sclerae, atrophic glossitis (loss of tongue papillae), angular cheilitis, koilonychias
Lab findings for iron deficiency
- CBC: low RBC count, low hemoglobin, low reticulocytes, low MCV
- PBS: erythrocytes with increased central pallor
- Decreased serum iron and ferritin
- Decreased transferrin saturation
- Increased total iron binding capacity
Treatment for iron deficiency
- Iron supplements (ferrous sulfate)
- Parenteral iron
- Increase dietary iron, vitamin C, transfusion
Pathophysiology of folate deficiency
THF (folate derivative) needed to synthesize thymine
DNA replication delayed, no mitosis, defective, large cells with fragile membranes
PE findings unique for B12 deficiency
neurological symptoms: tingling, burning in feet, hands, arms, legs
Lab tests for B12 and folate deficiency
-PBS (hyper-segmented neutrophils), CBC (MCV >100)
-Serum B12, folate low
-MMA and homocysteine levels high
-IF antibody—positive
-Parietal cell antibody (produce IF) positive
Gastrin—increased, seen in pernicious anemia
DD for bone marrow failure
Marrow infiltration—malignancies (leukemia, lymphoma, multiple myeloma), infection, primary myelofibrosis
Bone marrow aplasia—nutrition deficiency, aplastic anemia, infectious, immune destruction, medication
Stem cell damage or suppression—chemo, radiation, drugs, toxins
Nutrition deficiency
Investigations for bone marrow failure
CBC w/ WBC differential, RBC indices, PBS
Retic. Count
PT/PTT (coagulopathy)
Electrolytes, renal, liver function tests, LDH, Ca, uric acid (tumor lysis syndrome, hypercalcemia, renal failure, hyperuricemia may be associated with diseases that also cause pancytopenia, including multiple myeloma, leukemia, lymphoma)
Bone marrow biopsy
Cause of aplastic anemia
drugs, radiation, toxins, viral infections
Autoimmune in most cases
Treatments for Aplastic Anemia
Allogenic HCT
Immunosuppressive therapy
History & PE findings for hemolytic anemia
Symptoms of anemia in the absence of bleeding
Jaundice
Dark urine (intravascular hemolysis)
Initiation of new medication with potential for causing hemolysis
History of unexplained anemia/hemolytic anemia in family members
History of pigmented gallstones
Splenomegaly
Define intracorpuscular versus extracorpuscular defects in hemolysis
Intracorpuscular defects: altered properties of the RBC are responsible for hemolysis
Extracorpuscular defects: RBC normal but destroyed due to mechanical, immunologic, infectious, or metabolic/oxidant damage
Describe the direct and indirect antiglobulin test.
Direct antiglobulin (Coombs) test: Take patient RBC and incubate with anti-human IgG and anti-human C3d antibodies Indirect antiglobulin test: find antibodies in serum; patient’s plasma incubated with test red cells, observed for agglutination
Pathophysiology for hereditary spherocytosis
HS has defective spectrin; lead to reduced vertical associations between the cytoskeleton and membrane, progressive membrane loss –> reduced ratio of RBC SA to volume, progressively more spherical cells
Hemolysis bc reduced deformability, impairing passage through constricted regions of the microcirculation
Phagocytosis by splenic macrophages promotes further membrane loss, further impairs passage through the narrow fenestrations of the splenic cords, they fail to pass and get phagocytosed
Pathophysiology for G6PD
G6PD involved in production of NADPH, oxidative protection, oxidative damage causes Heinz bodies, phagocytosed
investigation for Hereditary sphereocytosis
Coombs negative (non-immune), spherocytes on PBS, positive family history, negative testing for other inherited hemolytic anemias
Low Hb, high retic, high LDH, bilirubin, low haptoglobin
Confirmatory test: EMA (eosin-5-maleimide)
Treatments for Hereditary sphereocytosis
supportive measures, such as folic acid supplementation, transfusions, EPO, splenectomy
HbF composition
<1% by early childhood
two alpha globins and two gamma globins
