Anemia

Question 1

where does erythropoiesis occur

Answer 1

• bone marrow

- Under the influence of stromal framework, cytokines, and erythropoietin

Question 2

EPO

Answer 2

• EPO is produced by the kidney in response to adequacy of tissue oxygenation
• EPO enhances growth and differentiation of the erythroid progenitors into normoblasts
• EPO=erythropoietin; The hormone tells stem cells in the bone marrow to make more red blood cells. EPO is made by cells in the kidney. These cells release more EPO when blood oxygen levels are low.

Question 3

normoblast and reticulocytes

Answer 3

• When a normoblast extrudes its nucleus to form a RBC it is called a reticulocyte
• Reticulocytes retain ribosomal network for about 4 days (3 d in marrow, 1 d in blood) then lose RNA and become mature RBC (1% total circulating RBC are reticulocytes)
• Mature RBC circulates 110-120 days in blood

Question 4

RBCs - role and breakdown

Answer 4

• Macrophages detect senescent signals in old RBCs and remove them from circulation
• RBCs carry oxygen linked to hemoglobin from the lungs to tissue capillaries
• Oxygen is then released from Hgb

Question 5

Composition of hemoglobin

Answer 5

• Hemoglobin is made of two α chains and two β chains
• Normal adult Hgb is 98% Hgb A (α2β2 chains)
• Hgb A2 is normally 1-2% of adult Hgb (α2δ2 chains)
• Hgb F is normal fetal Hgb but should be <1% of normal adult Hgb (α2γ2 chains)

Question 6

definition of anemia

Answer 6

• Hemoglobin (Hgb) measures the concentration of the major oxygen carrying pigment of whole blood
• Hematocrit (Hct) is the percent of a sample of whole blood occupied by intact red blood cells
• Red blood cell (RBC) count is the number of red blood cells in a specified volume of whole blood
• Males (Hgb < 13.5 or Hct < 41%)
• Females (Hgb <12.0 or Hct < 36%)
• Ranges can vary by laboratory or standards used; may not apply to special populations
• Volume status may affect the reported values of Hgb, Hct or RBC count
• H/H and RBC count are all concentrations and dependent on the RCM as well as plasma volume.
• In pregnancy the “normal” range changes
• Patients living at high elevations will have higher values
• Smokers will have higher Hct due to high CO exposure in cigarettes
• African Americans tend to have lower Hgb levels compared to Caucasians

Question 7

Morphologic approach to anemia

Answer 7

-Categorizing anemia by the alterations in RBC size and the reticulocyte response
-Mean corpuscular volume (MCV) measures the average RBC volume (size)
• Macrocytic anemia = MCV > 100 fL
• Microcytic anemia = MCV < 80 fL
• Normocytic anemia = MCV 80-100 fL

Question 8

kinetic approach to anemia

Answer 8

-Mechanism responsible for the fall in Hgb concentration
-Decreased RBC production
• Lack of nutrients (diet, malabsorption, blood loss)
• Bone marrow disorders or suppression
• Low levels of EPO, thyroid hormone, androgens
-Increased RBC destruction
• Hemolytic anemias
-Blood loss

Question 9

etiology of anemia

Answer 9

• Microcytic (IDA, Thalassemia)
• Normocytic (ACD)
• Macrocytic (B12/Folate deficiency, With inc retics: Hemolysis)
• These are the most common anemias by category

Question 10

signs and symptoms of anemia

Answer 10

• Symptoms occur due to decreased oxygen delivery to tissues or hypovolemia from blood loss reflecting the fall in Hgb
• Symptoms may occur at rest, with exertion, or when cardiac compensation is impaired depending on the severity and underlying condition(s)
• Do they have signs of anemia and symptoms that will help to lead me to the specific diagnosis
• When they have mild anemia, they only have sxs at rest
• When the anemia progresses, they have a harder time with lower level activity (sxs with less and less exertion)
• Exertional dyspnea, dyspnea at rest, varying degrees of fatigue, bounding pulses, palpitations, “roaring” sound in the ears
• Severe anemia may cause lethary, confusion and can lead to congestive heart failure, angina, arrhythmias, MI
• Acute bleeding with severe volume depletion may lead to fatigue, muscle cramps and can progress to postural dizziness, lethargy, syncope, hypotension, shock and death

Question 11

history needed for anemia

Answer 11

• Is the anemia acute, subacute, or chronic?
• Patient’s ethnicity and family history? (May point to inherited cause such as thalassemia or hemoglobinopathy)
• Past medical history? (PUD, RA, renal failure, CHF, liver dz, blood trx)
• Use of medications? (Aspirin, NSAIDs, hydroxyurea)
• Toxic habits or exposures?(Lead exposure, alcohol abuse, nutritional status)
• Looking for clues as to cause of anemia
• Hydroxyurea treats sickle cell anemia by helping to prevent formation of sickle-shaped red blood cells; drug class is anti-metabolite.
• Lead exposure causes microcytic anemia in children
• EtOH abuse / liver dz associated with macrocytic anemia, folate deficiency

Question 12

physical examination of anemia

Answer 12

• Organ or multisystem involvement
• Assess patient’s condition (sick or not)
• Tachycardia, dyspnea, fever, postural hypotension
• Jaundice, pallor, petechiae -> common for pts with any type of anemia to have pallor in the conjunctiva
• Lymphadenopathy, HSM, bone tenderness -> may be indicative of lymphoma or blood cancer
• Signs and symptoms of recurrent infxns
• Stool occult blood
• Looking for signs of anemia as well as signs of etiology (cancer, vitamin/mineral deficiency, heart disease, etc)

Question 13

diagnostic studies for anemia

Answer 13

• CBC with platelets and WBC differential
• Reticulocyte count -> baby RBCs (normal is 1% of the blood) (Only helpful if you look at in comparison to the other counts, If you have a person with low RBC count, you would expect the reticulocyte count to be high: If the reticulocyte count is normal with anemia, this means that something is not working)
• Peripheral blood smear
• Specific tests to narrow differential diagnosis as indicated (Iron, TIBC, transferrin saturation, ferritin, LDH, indirect bilirubin, haptoglobin, Folate, vitamin B12 levels, TSH, other specific endocrine studies)
• IDA: low serum iron, high TIBC, low transferrin, low ferritin
• Hemolysis: elevated LDH, elevated bili, low haptoglobin
• HYPOCHROMIC MICROCYTIC ANEMIA = Iron deficiency anemia!!
• Its very rare to see hyperchromic cells! Much more normal to see hypochromic or normochromic cells

Question 14

CBC includes:

Answer 14

• RBC, WBC, Hgb, Hct, MCV, MCH, MCHC, RDW, platelet count

- RDW tells you how much variation there is in the red blood cell line

Question 15

MCH, MCHC and MCV

Answer 15

• MCH and MCHC generally parallel MCV
• MCV tells the size of the RBC (Macrocytic, microcytic, normocytic)
• MCHC tells the concentration (color) of the Hgb (Hypochromic, hyperchromic, normochromic)

Question 16

reticulocyte count

Answer 16

• Reticulocyte count helps further distinguish the cause of anemia
• High retic count reflects increased erythropoietic response of bone marrow to continued hemolysis or blood loss
• Low retic count is usually evident of deficient RBC production in bone marrow (Low retic count with pancytopenia worrisome for aplastic anemia, An inappropriately normal retic count is also worrisome for bone marrow disease)

Question 17

reticulocyte shift

Answer 17

-With worsening anemia and increasing erythropoietin stimulation, bone marrow reticulocytes (left) leave the marrow at an earlier stage in their maturation. This prolongs the maturation time in the circulation from one day to as long as 2.5 days (right).

Question 18

WBC count and differential

Answer 18

• Leukopenia + anemia usually due to bone marrow suppression, hypersplenism, vitamin B12 or folate deficiencies
• Leukocytosis + anemia typically indicates infection, inflammation, or hematologic malignancy (Means high white blood cell count and anemia)
• Inc neutrophils in infxn; inc monocytes in myelodysplasia; inc eosinophils with parasites or allergic disease; dec neutrophils s/p chemo; dec lymphocytes in HIV or steroid tx

Question 19

platelet count

Answer 19

• Thrombocytopenia with anemia: DDx includes hypersplenism; malignancy involving bone marrow; autoimmune platelet destruction; sepsis; vitamin B12 or folate deficiency
• Thrombocytosis with anemia: DDx includes myeloproliferative disease; chronic iron deficiency; inflammatory, infectious, or neoplastic disorders

Question 20

peripheral blood smear

Answer 20

• Can provide information not otherwise available in a CBC with diff
• Morphology of RBC and other cells in the blood can be helpful in determining diagnosis
• High power view of a normal peripheral blood smear. Several platelets (black arrows) and a normal lymphocyte (blue arrow) can also be seen. The red cells are of relatively uniform size and shape. The diameter of the normal red cell should approximate that of the nucleus of the small lymphocyte; central pallor (red arrow) should equal one-third of its diameter.
• Normal RBCs are about the same size of a neutrophil or WBC

Question 21

approach to anemia

Answer 21

• Anemia may be the initial manifestation of a systemic disorder, and is one of the major signs of disease
• A cause for anemia should always be sought
• Use the history, physical exam, and simple laboratory tests to evaluate the potential cause of the anemia
• ANEMIA IS NEVER NORMAL!! A cause should always be figured out
• Is the patient bleeding (now or past)?
• Is there evidence for hemolysis?
• Is the bone marrow suppressed?
• Is the patient iron deficient? Why? Do they have celiac or some other issue with absorption of iron
• Is the patient deficient in folate or cyanocobalamin? Why?
• Evidence of hemolysis varies depending on etiology; ask about rash or skin changes, splenomegaly, family history, dark colored urine, recent medication use, pain, fever
• MOST COMMON cause of anemia IS GI BLEED!!!

Question 22

megaloblastic anemias

Answer 22

-are a heterogeneous group of disorders that share common morphologic characteristics. The morphological hallmark of megaloblastosis is a megaloblast. Megaloblasts are large cells with an increased nuclear/cytoplasmic ratio in which nuclear maturation is delayed, while cytoplasmic maturation is more advanced. Peripheral smears reveal that RBCs are macrocytic and occasional megaloblasts are present. Megaloblasts are usually abundant in bone marrow aspirates. Megaloblastic changes are not limited to RBCs since hypersegmented neutrophils can be seen on peripheral smears, and pancytopenia occurs in megaloblastic anemias.

Question 23

iron deficiency anemia

Answer 23

• Most common cause of anemia worldwide
• Iron is necessary for the formation of heme
• Most iron is circulating in Hgb
• Iron is stored primarily as ferritin (This is one of the first levels to decrease when looking at iron deficiency anemia)
• Iron is absorbed from the diet in the gut
• Iron is normally lost through skin/mucosal exfoliation, menstrual blood loss

Question 24

causes of iron deficiency

Answer 24

• Deficient diet
• Decreased GI absorption
• Increased iron requirements (Pregnancy and lactation)
• Blood loss (GI, menstrual, blood donation, GI bleed is the most common cause of the most common type of anemia)
• Hemoglobinuria
• Iron sequestration (Pulmonary hemosiderosis - This is extremely uncommon so you probably wont see it)
• Peripheral smear from a patient with iron deficiency shows pale small red cells with just a scant rim of pink hemoglobin; occasional “pencil” shaped cells are also present. Normal red cells are similar in size to the nucleus of a small lymphocyte (arrow); thus, many microcytic cells are present in this smear. Thalassemia can produce similar findings.
• Some of the RBCs are normal, some of them are much smaller, and many of them are very pale

Question 25

clinical presentation of iron deficiency

Answer 25

• Easy fatigability, tachycardia, palpitations, dyspnea with exertion; pica
• Skin and mucosal changes: smooth tongue, brittle nails, cheilosis (sores around the corners of the mouth)
• Dysphagia due to esophageal webs
• Stool positive for occult blood if GI bleeding is the cause of IDA

Question 26

diagnostic studies for iron deficiency

Answer 26

• Low serum ferritin is the initial abnormality
• TIBC rises as iron stores become increasingly depleted
• Serum iron and transferrin saturation levels decline as iron stores are depleted
• RBC level decreases, and RBC become microcytic and hypochromic
• Peripheral smear also may show anisocytosis and poikilocytosis
• Poikilocytosis = abnormally shaped RBC
• Anisocytosis = RBC are unequal in size

Question 27

treatment of IDA

Answer 27

• Identify and treat the cause
• Oral iron therapy: FeSO4 325mg po tid is preferred Rx (Can cause GI upset, She usually starts pts on 325 qd for a week or two and then slowly titrate up), Should see return to baseline in H/H in 2 mos, Continue 3-6 mos after achieving normal labs to replenish iron stores, Causes nausea, constipation in many pts, If they are taking their iron with milk every day then their constipation will probably actually get worse! Legumes, spinach, raisins, prunes, etc are great sources of iron, It takes a long time to replenish iron stores so that wont be normal for a long time (You monitor with H and H for a couple weeks and check iron panel and then every couple of months, you repeat these labs)
• Parenteral iron therapy (Intolerance to oral iron, refractory IDA, GI disease, uncorrectable continued blood loss)

Question 28

iron supplements

Answer 28

• Iron difficult to tolerate; constipation, GI upset, dark stools
• Ferrous sulfate 1st line; try Slow Fe or plant based iron, less absorption

Question 29

anemia of chronic disease

Answer 29

• Many chronic systemic diseases associated with mild to moderate anemia
• RBC survival is decreased – so instead of being around for 120 days, only around for 100 (for example)
• Bone marrow fails to compensate adequately for shorter RBC lifespan
• Iron is sequestered in reticuloendothelial system
• Usually this is mild anemia -> usually normocytic
• Common causes: Chronic infection or inflammation, Cancer, Liver disease, Chronic renal failure (Somewhat different pathophysiology, Decrease in EPO, More severe anemia than other chronic diseases)

Question 30

clinical presentation of anemia of chronic disease

Answer 30

• Patients presents with signs and symptoms of the causative illness and symptoms of anemia (Fatigability, tachycardia, palpitations, DOE)
• Should be suspected in patients with known chronic diseases
• May have coexistant iron or folic acid deficiencies that complicate the diagnosis

Question 31

diagnostic studies for anemia of chronic disease

Answer 31

• Low Hgb/Hct
• Normal or slightly decreased MCV
• Normal reticulocyte count and smear
• Low serum iron, TIBC, transferrin saturation; Normal or increased serum ferritin (The body starts to store ferritin so ferritin will be increased!! This is different from iron deficiency where you have low ferritin and high TIBC)
• Low serum EPO in renal failure

Question 32

Treatment of ACD

Answer 32

• Treatment is not usually necessary
• Purified recombinant erythropoietin is used in renal failure and some types of cancer or inflammatory diseases (eg: RA)
• Hemodialysis is also used in patients with renal failure
• Treat any coexistant iron or folate deficiency
• patients may have more than one type of anemia; pts with chronic dz are usually older and may also get GIB or other problems leading to another type of anemia such as IDA

Question 33

thalassemias

Answer 33

• Hereditary disorders with reduction in the synthesis of globin chains (α or β) leading to reduction in Hgb synthesis
• Anemia is caused by defective hemoglobinization of RBC
• Positive family history or lifelong personal history of microcytic anemia
• Microcytosis out of proportion to the degree of anemia

Question 34

alpha-thalassemia

Answer 34

• α-Thalassemia is due primarily to a gene deletion causing reduced α-globin chain synthesis
• No change in percentage distribution of Hgb A, A2, and F
• Affects primarily people from SE Asia and China
• Hemoglobin H disease is a severe form with excess β-chains that form a β4 tetramer
• α-thalassemia minor (trait) pts are clinically normal and may have a mild microcytic anemia
• In Hgb H disease patients will have a chronic hemolytic anemia of variable severity, pallor and splenomegaly (It is an abnormality in 3 Hgb and only 1 Hgb normal)

Question 35

diagnostic studies for alpha thalassemia

Answer 35

• CBC: mild anemia, Hct 28-40%, very low MCV, normal RBC count
• Peripheral smear: microcytic, hypochromic RBC with occasional target cells
• Reticulocyte count and iron studies normal
• Hemoglobin electrophoresis shows no significant abnormality
• When we are born we have 90% fetal hemoglobin and when we are born we switch to adult hemoglobin (The kids will have their first crisis around 6 months of age)

Question 36

diagnostic studies for hemoglobin H disease

Answer 36

• CBC: marked hemolytic anemia, Hct 22-32%, very low MCV
• Peripheral smear: hypochromia, microcytosis, target cells, poikilocytosis
• Reticulocyte count is elevated
• Hemoglobin electrophoresis shows a fast migrating abnormal Hgb H as 10-40% of Hgb

Question 37

beta-thalassemia

Answer 37

• This group of anemias usually caused by point mutations → premature chain termination or problems with transcription of RNA → reduced or absent β-globin chain synthesis
• Results in a relative increase in the percentages of Hgb A2 and Hgb F compared to Hgb A
• Excess α-chains are unstable and lead to damaged RBC membranes → hemolysis
• Bone marrow becomes hyperplastic
• Primarily affects people of Mediterranean origin; also some Chinese, other Asians
• Various β-thalassemia syndromes resulting from various and heterogeneous molecular defects
• Typically a Mediterranean or Greek person with MCV of ~60
• Depending on the amount of fetal hemoglobin that they have will determine the severity of the disease
• β-thalassemia minor (trait): clinically insignificant microcytic anemia
• β-thalassemia major: children normal at birth, develop severe anemia at 6 mos when Hgb F switches to Hgb A (Growth failure, bony deformities, HSM, jaundice; requiring multiple transfusions, Develop cardiac failure, cirrhosis, endocrinopathies)

Question 38

beta thalassemia trait

Answer 38

• Peripheral smear from a patient with beta thalassemia trait. The field shows numerous hypochromic and microcytic red cells (thin arrows), some of which are also target cells (blue arrows).
• They have a red dot inside where the normal white should be in the RBC

Question 39

beta thalassemia minor diagnostic studies

Answer 39

• CBC: mild anemia, Hct 28-40%, MCV low (55-75 fL), normal RBC count
• Peripheral smear: hypochromia, microcytosis, target cells, basophilic stippling
• Reticulocyte count normal or slight increase
• Hemoglobin electrophoresis may show elevation of Hgb A2 and Hgb F

Question 40

beta thalassemia major diagnostic studies

Answer 40

• CBC: severe anemia with very low Hct
• Peripheral smear: severe poikilocytosis, hypochromia, microcytosis, target cells, basophilic stippling, nucleated RBC
• Hemoglobin electrophoresis with little to no Hgb A, variable amounts of Hgb A2, and mostly Hgb F

Question 41

treatment of beta thalassemia

Answer 41

• Mild thalassemias do not usually require treatment
• Hemoglobin H disease treated with folate supplements and regular transfusions; iron chelation therapy often used; splenectomy
• β-thalassemia major is primarily treated with allogenic bone marrow transplant

Question 42

megaloblastic anemias

Answer 42

• Folic acid (folate) deficiency and cyanocobalamin (vitamin B12) deficiency
• Macrocytic anemia with macro-ovalocytes and hypersegmented neutrophils on peripheral blood smear
• Low serum levels of serum folate or vitamin B12 levels

Question 43

megaloblastic smear

Answer 43

-Peripheral blood smear showing a hypersegmented neutrophil (7 lobes) and macro-ovalocytes, a pattern that can be seen with cobalamin or folate deficiency

Question 44

vitamin B12 deficiency

Answer 44

• Vitamin B12 is an important cofactor for enzyme reactions in humans
• All vitamin B12 comes from the diet; present in all foods of animal origin
• Bound to intrinsic factor in the gut and absorbed in the terminal ileum; stored in the liver (Important for pts who have surgery of disease of the terminal ileum, People with chrons or types of bariatric surgery where they don’t absorb food through certain parts of duodenum or ileum have these deficiencies)
• Deficiency develops more than 3 years after absorption stops

Question 45

causes of vitamin B12 deficiency

Answer 45

• Decreased production of intrinsic factor (Pernicious anemia; gastrectomy)
• Helicobacter pylori infection
• Competition for vitamin B12 in the gut
• Pancreatic insufficiency
• Decreased ileal absorption of vitamin B12 (Surgical resection; Crohn’s disease)
• Dietary and transcobalamin II deficiencies are rare causes
• Pernicious anemia = lack of intrinsic factor in stomach, can’t absorb vitamin B12

Question 46

clinical presentation of vitamin B12

Answer 46

• Changes in mucosal cells leading to glossitis; vague GI complaints including anorexia, diarrhea
• Peripheral nerves affected leading to paresthesias, dysequilibrium, dementia and other neuropsychiatric changes (Reversible if treated within 6 months)
• Pale, mildly icteric; decreased position or vibration sense on PE

Question 47

diagnostic studies for vitamin B12 deficiency

Answer 47

• Anemia of variable severity
• MCV elevated to 110-140 fL
• Peripheral smear with macro-ovalocytes, hypersegmented neutrophils; poikilocytosis and anisocytosis
• Decreased reticulocyte count
• WBC count and platelets may be decreased; pancytopenia may be present
• Abnormally low serum vitamin B12 level

Question 48

replacement of vitamin B12

Answer 48

• Parenteral therapy is most commonly used (PA: 100mcg IM daily x 1 week then weekly x 1 month then monthly for life, 1000mcg IM monthly)
• Oral therapy may also be used (1000mcg po qd continued indefinitely)
• Hypokalemia may occur at onset of treatment
• Hematologic findings normalize in 2 months

Question 49

folic acid deficiency

Answer 49

• Folic acid is reduced to tetrahydrofolate, which is a mediator of many reactions involving one-carbon transfers, such as in DNA synthesis
• Present in most fruits and vegetables
• Folic acid is absorbed in the entire GI tract
• Folic acid looks like B12 deficiency but you don’t get paresthesias

Question 50

causes of folic acid deficiency

Answer 50

• Dietary deficiency (Alcoholics, anorexia, malnutrition, overcook foods)
• Decreased absorption (Tropical sprue; drugs (phenytoin, sulfasalazine))
• Increased requirement (Chronic hemolytic anemia; pregnancy; exfoliative skin disorders)
• Loss of folic acid through dialysis
• Inhibition of reduction to active form (Methotrexate)

Question 51

clinical presentation of folic acid deficiency

Answer 51

• Mucosal changes similar to vitamin B12 deficiency and megaloblastic anemia
• No neurologic abnormalities
• Symptoms of anemia (Fatigability, tachycardia, palpitations, DOE)

Question 52

diagnostic studies for folic acid deficiency

Answer 52

• Anemia of variable severity
• MCV elevated to 110-140 fL
• Peripheral smear with macro-ovalocytes, hypersegmented neutrophils; poikilocytosis and anisocytosis
• Decreased reticulocyte count (roughly 1%)
• Decreased RBC folate or serum folate level
• Normal serum B12 level

Question 53

treatment for folic acid deficiency

Answer 53

• Replacement of folic acid (Folic acid 1mg po qd)
• Rapid improvement and correction of hematologic abnormalities in 2 months
• Treat any underlying illness

Question 54

hemolytic anemias

Answer 54

• Group of disorders in which RBC survival is reduced and the bone marrow in unable to sufficiently compensate
• Hct fall >3% per week in hemolysis
• Reticulocytosis indicates hemolysis
• Classified according to intrinsic RBC defect vs extrinsic cause
• Hemolysis presents as acute or chronic anemia, reticulocytosis, or jaundice. The diagnosis is established by reticulocytosis, increased unconjugated bilirubin and lactate dehydrogenase, decreased haptoglobin, and peripheral blood smear findings. Premature destruction of erythrocytes occurs intravascularly or extravascularly. The etiologies of hemolysis often are categorized as acquired or hereditary. Common acquired causes of hemolytic anemia are autoimmunity, microangiopathy, and infection. Immune-mediated hemolysis, caused by antierythrocyte antibodies, can be secondary to malignancies, autoimmune disorders, drugs, and transfusion reactions. Microangiopathic hemolytic anemia occurs when the red cell membrane is damaged in circulation, leading to intravascular hemolysis and the appearance of schistocytes. Infectious agents such as malaria and babesiosis invade red blood cells. Disorders of red blood cell enzymes, membranes, and hemoglobin cause hereditary hemolytic anemias. Glucose-6-phosphate dehydrogenase deficiency leads to hemolysis in the presence of oxidative stress. Hereditary spherocytosis is characterized by spherocytes, a family history, and a negative direct antiglobulin test. Sickle cell anemia and thalassemia are hemoglobinopathies characterized by chronic hemolysis.

Question 55

intrinsic RBC defects: hemolytic anemia

Answer 55

 Enzyme deficiencies
 Hemoglobinopathies
 Membrane defects

Question 56

intravascular destruction of RBC: hemolytic anemia

Answer 56

 Microangiopathy
 Transfusion reactions
 Infections
 Paroxysmal hemoglobinuria

Question 57

extrinsic RBC defects: hemolytic anemia

Answer 57

	Liver disease
	Hypersplenism
	Infections
	Oxidant agents
	Microangiopathy
	Autoimmune 
	Leukemia 
	Burns

Question 58

diagnostic studies for hemolytic anemia

Answer 58

• Decreased serum haptoglobin (Normal plasma protein that binds and clears Hgb released into the plasma)
• Hemoglobinuria and positive urine hemosiderin with intravascular hemolysis
• Increased indirect bilirubin in the blood
• Elevated serum LDH levels in microangiopathic hemolysis and others
• Hemosiderin = iron-storage complex; found within cells
• Haptoglobin – protein produced by liver; acute phase reactant, identifies hemolysis

Question 59

microangiopathic smear

Answer 59

• schistocytes
• Peripheral blood smear from a patient with a microangiopathic hemolytic anemia with marked red cell fragmentation. The smear shows multiple helmet cells (small black arrows), other fragmented red cells (large black arrow); microspherocytes are also seen (blue arrows). The platelet number is reduced; the large platelet in the center (red arrow) suggests that the thrombocytopenia is due to enhanced destruction.

Question 60

heinz body hemolytic anemia

Answer 60

-Split screen view of a peripheral smear from a patient with Heinz body hemolytic anemia. Left panel: red cells with characteristic bite-like deformity (arrows). Right panel: Heinz body preparation which reveals the denatured hemoglobin precipitates.

Question 61

clinical presentation/treatment for heinz body hemolytic anemia

Answer 61

• Variable depending on the cause of the hemolysis
• Symptoms of anemia often present (Fatigue, tachycardia, palpitations, DOE)
• Treatment also depends on the underlying cause or defect

Question 62

sickle cell anemia

Answer 62

• Autosomal recessive hemoglobinopathy (Chronic hemolytic anemia)
• Single DNA base change substituting valine for glutamine in the 6th position on the β-globin chain → Hgb S
• Affecting 8% African Americans (Originally protection against malaria in Africa, Onset in first year of life when Hgb F falls)
• Variable presentations depending on inheritance pattern
• In the deoxy state, Hgb S forms polymers that damage the RBC membrane
• Factors that influence RBC sickling: Concentration of Hgb S in the RBC, RBC dehydration, Other types of Hgb in the cell (Hgb F), Anything that leads to deoxyhemoglobin state: Acidosis, hypoexmia)

Question 63

clinical presentation of sickle cell anemia

Answer 63

• Chronic hemolytic anemia produces jaundice, pigment gallstones, hepatosplenomegaly
• Poorly healing ulcers over the lower tibia, heart failure, retinopathy
• Severe hemolytic or aplastic crises may occur when bone marrow decompensates or in splenic sequestration of sickled RBC
• Chronically ill patients; poor growth and development
• Life expectancy between 40-50 years of age

Question 64

sickle cell crisis

Answer 64

• (Acute painful episodes due to acute vaso-occlusion; associated low-grade fevers, Clusters of sickled cells occlude the microvasculature of the organ(s) involved: Bones and chest most oftens affected, Last hours to days, Occur spontaneously or due to infection, dehydration, hypoxia)
• All organ systems can be affected: heart, kidneys, liver, spleen, eyes, brain
• In a sickle cell crisis, pt will be severely deoxygenated (WBC and platelets elecated)
• In aplastic cell crisis pt will have really low WBC and plateles

Question 65

diagnostic studies for sickle cell anemia

Answer 65

• Chronic hemolytic anemia with Hct 20-30%
• Peripheral blood smear with sickled cells (5-50%), nucleated RBC, target cells, and Howell-Jolly bodies indicating hyposplenism
• Reticulocytosis 10-25%
• WBC count elevated 12-15K; thrombocytosis may occur
• Increased indirect bilirubin
• Diagnosis confirmed by Hgb electrophoresis

Question 66

peripheral blood smear from sickle cell anemia

Answer 66

-Peripheral smear from a patient with sickle cell anemia shows multiple spindly sickle cells (blue arrows), a nucleated red blood cell in the upper left, and a Howell-Jolly body (black arrow), which is a nuclear fragment normally removed by the spleen. Target cells are also present (red arrow). This patient has functional asplenia because of repeated splenic infarctions.

Question 67

hemoglobin SC disease

Answer 67

-Peripheral blood smear from a patient with hemoglobin SC disease shows numerous target cells (red arrows), partially sickled “canoe” shaped erythrocytes (black arrows), and folded (Pita bread) red cells (blue arrows).

Question 68

treatment of SC disease

Answer 68

• No specific treatment is available for the primary disease of sickle cell anemia
• Maintenance with folic acid supplements
• Blood transfusions for aplastic or hemolytic crises
• Acute crisis treated with oxygen, fluids, blood transfusion, and treatment of any underlying infection if present

Question 69

treatment of sickle cell disease

Answer 69

• Hydroxyurea (500-750mg/d orally) to reduce frequency of pain crises
• Allogenic bone marrow transplant for young patients may be curative (Most people have a splenectomy)
• Pneumococcal vaccination recommended to reduce infections

Question 70

Anemia summary

Answer 70

• Order CBC + diff for 1° eval; then retic
• Microcytic (Usually IDA, order iron studies, look for cause, Very low MCV order Hgb electrophoresis for thalassemias, SSD)
• Normocytic (Usually ACD; order iron studies, CMP, Consider hemolysis, may need haptoglobin)
• Macrocytic (Usually B12 or Folate deficiency, order levels)

Question 71

RBC transfusion

Answer 71

• Indications for blood transfusion in patients with anemia (if hgb too low): 10/30 Rule = Hgb < 10g/dL or Hct<30%, Estimated blood volume loss (>30%), Symptomatic anemia (dizzy, SOB, fatigue)
• Effect of blood on H/H: Each unit of packed RBC (300mL volume has 200mL of RBC) will raise Hct 3-4% and Hgb 1g/dL if no continued bleeding

Question 72

indications for bone marrow evaluation

Answer 72

• Unexplained anemia, leukopenia, thrombocytopenia, or pancytopenia
• Diagnosis/staging of lymphoma or solid tumors
• Diagnosis of plasma cell disorders and leukemia
• Evaluation of iron metabolism and stores
• Evaluation of storage and deposition diseases
• Evaluation of FUO; suspected unusual infections
• Unexplained splenomegaly
• Evaluation of suspected chromosomal abnormality

Question 73

bone marrow biopsy

Answer 73

• Low power view of a normal bone marrow biopsy. The overall cellularity is between 30 and 70 percent, with the remainder of the space being occupied by fat and stroma.
• Bone marrow biopsy in aplastic anemia. There are virtually no hematopoietic cells, and the marrow space consists of fat and stroma.

Question 74

when to refer to hematology/oncology

Answer 74

• There appears to be more than one type or cause of anemia (Abnormal increases or decreases in other blood cell lines, Abnormal cells in the circulation)
• A more complicated or unusual type of anemia is present (Aplastic anemia, myelodysplastic syndrome, leukemia)
• Anemia does not improve with treatment