UNIT 4 CLS 292 ANEMIAS STUDY GUIDE

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what is anemia? (learning objective)

most common hematologic disorder and is a reduction below normal in hemoglobin, hematocrit, or red blood cell number that is normally found in individual according to age and sex or premature RBC destruction

anemia is a secondary condition

what are the general symptoms of anemia? (learning objective)

generally related to the underlying lack of O2-carrying capacity

• fatigue

• weakness

• dizziness

• tachycardia

• pallor of skin and mucous membranes

what specific symptom would a patient with hemolytic anemia have? (learning objective)

jaundiced (due to accumulation of bilirubin)

what specific symptoms would a patient with iron-deficiency anemia have? (learning objective)

• PICA

• smoot tongue

• spoon-shaped nails (koilonychia)

what specific symptom would a patient with megaloblastic anemia have? (learning objective)

big, beefy tongue

what are the effects of sudden anemia? (learning objective)

• tissue hypoxia which causes EPO to increase

• the bone marrow is stimulated for various reasons:

  • to increase stem cell activity which results in erythroid precursors

  • shortening of maturation time

  • premature release of retics → if the hypoxia is severe, it could release of NRBCs

• essentially the sudden effects of anemia causes an increased demand of RBCs which causes the normal maturation of RBCs will be disrupted

what is the BMs response in when there is sudden anemia?

• there will be a presence of “shift” retics or stress retics

  • retics will usually lose their RNA within 24 hours in the PB but in stress retics, it will take 2-2.5 days to lose their RNA

  • stress retics are released earlier from the BM and will have increased RNA

• increased RBC production (3-fold) in moderate anemia and (5-fold) in severe anemia

• bone marrow is hyperactive with increased proliferation → erythroid hyperplasia

what determines the maturation of reticulocytes?

hematocrit → the lower the hematocrit, it will move out of the BM earlier and mature in the reticulocytes for a longer time

what is iron deficiency anemia? (learning objective)

occurs when the body storage of iron have been depleted which can occur due to inadequate dietary iron uptake, inadequate iron absorption, and abnormal iron loss

what is the normal distribution of iron?

• 60-80% of iron is function and serves in metabolic (hemoglobin/myoglobin) or enzymatic functions

• remainder of iron serves as a transport (uses transferrin to be transported) or storage forms (ferritin and hemosiderin → mostly in liver and bone marrow)

iron cannot exist alone and must be bound to a protein which is transferrin

how does iron get in and out of the body?

iron has a regulatory system which is controlled through the hormone, hepicidin→ iron will leave the body by being stored in the cells and getting sloughed off… when RBCs are degraded, macrophages will recycle them

what is the pathogenesis of iron-deficiency anemia? (learning objective)

blood loss (storage pool of RBCs is being depleted)

• GI bleed, heavy menstruation, injury or accident

really bad diet (rare)

• diet is multifaceted, meaning many things can be affecting diet

• iron may not be absorbed

treated with oral iron supplements if anemia is not due to GI bleed and always estbalish the cause of IDA first

what would the RBC morphology look like in those with iron-deficiency anemia? (learning objective)

cells are hypochromic and microcytic with increased anisocytosis and poikilocytosis (elliptocytes)… reticulocytes are decreased and platelets are increased

• anisocytosis is because each new wave of RBCs has less and less iron

• lack of iron is the cause of the decreased reticulocytes

• myeloid:erythroid ratio is usually 3:1 due to increased erythropoiesis

all RBC indices are decreased

what would the results of the iron studies look like in those with iron-deficiency anemia?

• decreased serum iron

• increased total iron binding capacity (TIBC)

  • TIBC → the total amount of Fe capable of being bound to transferrin

• decreased ferritin

  • ferritin → primary storage form of soluble iron; readily released for heme synthesis and consists of a spherical protein shell that can store up to 4500 iron atoms

  • ferritin without its shell = apoferritin

what is the first stage of iron deficiency anemia?

iron depletion

• iron stores are exhausted causing decreased ferritin

• there is no anemia yet and RBC morphology is normal

• RDW may be increased → could be the first hematologic indication of a developing iron deficiency anemia

what is the second stage of iron deficiency anemia?

iron deficient erythropoiesis

• anemia and hypochromia is not detectable

• RBCs may be slightly microcytic

• will have decreased transferrin saturation and increased erythrocyte protoporphyrin

what is the third stage of iron deficiency anemia?

iron deficiency anemia

• iron tests are markedly abnormal → severely deficient total body iron

• microcytic hypochromic RBCs

what are the general characteristics of anemia caused by abnormal iron metabolism?

• result of a block in the incorporation of iron into the protoporphyrin ring to form heme and defective iron utilization (usually due to the slow release iron from macrophages)

  • has a positive iron balance and could lead to an increase in iron stores (especially in spleen, liver, and BM) which results in increased serum ferritin levels

• results in a lack of iron for Hb synthesis and a blood picture that is similar to IDA

• iron is absorbed at normal rates but it is used at less than normal rates for erythropoiesis

what is sideroblastic anemia? (learning objective)

body has inefficient erythropoiesis due a defective function of the HSC

• elevated body iron storage, serum iron and serum ferritin is increased

  • decreased TIBC

• low reticulocyte count and accumulation of iron in the mitochondria of the erythroid precursors

what would the PB look like in sideroblastic anemia? (learning objective)

• ringed sideroblasts → siderotic granules surround the nucleus of the NRBCs due to the defective Hb synthesis

• will have a dimorphic population of normochromic and hypochromic cells

  • MCV, MCH, and MCHC may be normal

  • RDW will be increased and has dual peaks on the histogram

• will have a dual population of macro and microcytes

  • mild microcytes are found in sideroblastic anemia that is associated with alcoholism

• RBCs could have pappenheimer bodies

must use prussian blue to confirm sideroblastic anemia

what can cause sideroblastic anemia?

• can be sex-linked recessive gene (hereditary sideroblastic anemia)

• can be acquired and could be associated with other things like leukemia, drugs (can interfere with heme synthesis) and lead poisoning (basophilic stippling) (also benzenes)

  • more common

  • lead poisonings blocks enzymes in the heme biosynthetic pathway → can cause mental defects

    • would actually have siderocytes

usually moderate to severe anemia

what is the treatment for sideroblastic anemia?

pyridoxine therapy

• usually tried on those who have hereditary sideroblastic anemia

  • less than ½ experience a return to normal Hb levels

  • iron overload will decrease responsiveness which is treated through phlebotomy and chelation therapy

folic acid

• only given to those with megaloblastic features (seen in liver disease & alcoholism)

secondary hereditary anemia could be from a disease, toxin, or drug which is corrected through treatment of the primary disease or the elimination of toxin/drug

what is the pathogenesis of megaloblastic anemia? (learning objective)

vitamin B12 and/or folate deficiency (from bad diet, absorption problems, folate-antagonist drugs)

• deficiency makes it hard to make DNA but RNA production runs smoothly

  • nucleus which is full of DNA lags behind the cytoplasm which is full of RNA in development and the cell divides more slowly

• maturation is asynchronous (cytoplasm is mature but nucleus is immature) in the bone marrow

treatment depends on the cause of anemia

what would the RBC morphology look like in those with megaloblastic anemia? (learning objective)

red cells are macrocytic (would see great big oval macrocytes) with hypersegmented (>6) neutrophils

what is the pathogenesis of hereditary spherocytosis?

patients will have defects in the membrane cytoskeleton (spectrin, ankryin, band 3, or band 4.2) → since red cell membranes are fragile, the RBCs cannot go squeeze through the spleen properly which causes the formation of spherocytosis (eaten by macrophages)

patients who have it mild do not need treatment but it if it severe, a splenectomy can be useful

what would the RBC morphology look like in those with hereditary spherocytosis?

red cells are normochromic and normocytic… depending on patient’s particular genetic defect, there could be a ton of spherocytes (smaller than RBCs and lack central pallor) or just a few

what is the pathogenesis of G6PD deficiency?

G6PD helps reduce nasty free radicals made during cell metabolism… without enough G6PD around, the free radicals attack the molecular bonds between heme and globin becomes denatured and forms heinz bodies → spleen will pit the heinz bodies, creating a bite cell

• those who have a deficiency of G6PD are normally ok until they encounter some sort of oxidizing substance like a drug or fava beans

patient must avoid exposure to known oxidants but the hemolysis is self-limiting so it will spontaneously resolve in a week or so

what would the RBC morphology look like in those with G6PD deficiency?

patients going through an acute hemolytic episode will have fragmented cells, microspherocytes, and bite cells → supravital staining will reveal the Heinz bodies

• patients who have not been exposed to offending agents will have no anemia

• heinz bodies will decrease in number as Hb bottoms out because younger cell have greater G6PD activity

what is the pathogenesis of sickle-cell anemia (hemoglobinopathies)? (learning objective)

abnormal hemoglobin (HbS) in sickle cell anemia will change shape when it releases oxygen, causing it to polymerize and in turn distorts it into a sickle shape

• sickle cells are fragile and will stick together in small vessels, leading to ischemia → the tiny, repeated infarcts in the spleen which leads to fibrosis and eventual autosplenectomy

prevent triggers like things that will make RBCs want to give up O2 and vaccination in those who have undergone autosplenectomy

what would the RBC morphology look like in those with sickle-cell anemia? (learning objective)

during times of crisis/decreased oxygenation, there will be sickled cells in the blood and when autosplenectomy occurs, there will be a post-splenectomy blood picture which includes NRBCs, Howell-Jolly bodies, and Pappenheimer bodies

what is the pathogenesis of thalassemia? (learning objective)

quantitative diseases of Hb → characterized by a decrease in amount of the Hb chains like in alpha-thalassemia (decrease in alpha-chains) and beta-thalassemia (decrease in beta-chains)

• in thalassemia, patient ends up with a two-fold problem

  • decreased hemoglobin production (due to decrease in globin chains)

  • excess unpaired alpha chains (in beta) or beta, gamma, and delta chains (in alpha) which form tetramers and lead to premature RBC destruction

mild thalassemia doesn’t require treatment but those with severe anemia, patients may need repeated RBC transfusions or even BM transplantation

what would the RBC morphology look like in those with thalassemia? (learning objective)

mild thalassemia → mild microcytic, hypochromic anemia and can sometimes have target cells or cells with basophilic stippling

severe thalassemia → whopping anemia with marked anisocytosis and poikilocytosis

what is the pathogenesis of autoimmune hemolytic anemia? (learning objective)

warm

• patient makes IgG anti-RBC antibodies which binds at 37C best which is warm

• splenic macrophages will think that the antibody-coated RBCs are appetizing and will either cull or pit them

cold

• patient makes IgM anti-RBC antibodies that bind at <37C which means they will bind in distal body parts but fall off in warm body parts

• IgM will bind a bunch of RBCs together which forms clumps and complement will bind to the RBCs too → causes intravascular hemolysis

what would the RBC morphology look like in those with autoimmune hemolytic anemia? (learning objective)

WAIHA

• PB shows prominent spherocytosis

CAIHA

• will see big RBC agglutination (clumps) if the blood smear is made at a cool temp

what is a lab test used for autoimmune hemolytic anemia?

coombs test

• mix RBCs with anti-human globulin → if RBCs are coated with antibodies, the anti-human globulin will attach to those antibodies and will make them clump

• if RBC clumping is seen, patient’s RBCs are coated with antibodies and the patient’s hemolysis is most likely immune-related

what treatment would be used in those with autoimmune hemolytic anemia?

treat underlying cause if there is one

• in WAIHA, steroids can be helpful and if that doesn’t help, a splenectomy may be done

• in CAIHA, keep patient warm

what would be considered a hemolytic anemia that was talked about in class? explain it (learning objective)

hemolytic disease of the fetus and the newborn

• during moms first pregnancy or delivery of the placenta, Rh-negative mom is exposed to baby’s RBCs which may have the D-antigen which Rh-negative moms lack

• Rh-negative mom’s immune system starts to create antibodies towards the baby’s RBCs; however, first baby is safe from HDFN

• in later pregnancies, Rh-negative mom has memory of the D-antigen and quickly makes antibodies to it

• the antibodies crosses the placenta into the fetal circulation and binds to the antigen on the fetal cells which in turn destroys the baby’s RBCs

  • baby’s heart beats harder, bone marrow tries to make more RBCs, and baby tries to fight the hypoxia → results in edema and cardiac arrest in baby

what is the pathogenesis of microangiopathic hemolytic anemia? (learning objective)

RBCs are ripped apart by physical trauma that can be caused by multiple things → disseminated intravascular coagulation (DIC), hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, malignancies (especially adenocarcinoma), sepsis, trauma, and artificial heart valves

• physical trauma → fibrin strands snag them or mechanical devices bash them

find out what causes MAHA and treat it

what would the RBC morphology look like in those with microangiopathic hemolytic anemia? (learning objective)

shows schistocytes → small, point red cell fragments

what is the pathogenesis of anemia of chronic disease? (learning objective)

occurs in patients with chronic infections, chronic inflammatory disorders or neoplastic disorders that are not due to bleeding, hemolysis or marrow involvement → basically anything that is a chronic condition (second most common)

• macrophages starts to sequester (isolate or hide away) the iron which makes the iron unavailable → prevents iron from making it into normoblasts

• patient will have low serum but normal iron stores and does not relate to nutritional deficiency

• anemias that are associated with renal, endocrine, or hepatic insufficiency are not included

ACD is usually mild that treatment will not be needed so focus on underlying disease

how can impaired BM response to anemia cause ACD?

cytokines inhibits EPO production and the erythroid precursor response to EPO → blocks the iron release from macrophages and shortens RBC survival

what would the RBC morphology look like in those with anemia of chronic disease? (learning objective)

blood will show a normochromic, normocytic anemia with minimal anisocytosis and poikilocytosis (“bland looking anemia”)… in some cases (~25%), some will be microcytic but the MCV will rarely be below 72 fL

• normochromic, normocytic is because iron is avaliable but it is not being used as much and instead is being stored → iron in circulation is not enough

• in long-standing cases → microcytic, hypochromic

what would the iron studies look like in anemia of chronic disease?

• decreased serum iron

• decreased or normal TIBC

• normal to low transferrin saturation

• normal or increased serum ferritin

  • ferritin = acute phase reactant so it will go up in any types of conditions that cause ACD

what is the pathogenesis of aplastic anemia? (learning objective)

will have very few hematopoietic precursor cells in the BM which in turn causes decreased numbers of RBCs, WBCs, and platelets in the blood → possible cause would be drugs, viruses, or hereditary conditions but in many cases, no specific cause can be ID’d

treatment includes transfusion of blood components if needed, drug therapy to stimulate hematopoiesis and suppress the immune system, and if necessary, BM transplant

what would the RBC morphology look like in those with aplastic anemia? (learning objective)

blood is pancytopenic meaning that the RBCs, WBCs, and platelets are all decreased → BM is markedly hypocellular or “empty”