Normal RBC count
Females- about 4-5million/ulMales- 4.3-5.7 million/ul
Hemoglobin females
12-16 gm/dl
Hemoglobin males
14-17 gm/dl
Anemic female Hgb and Hct
Hgb less than 12 gm/dl, Hct less than 37%
Anemic male Hgb and Hct
Hgb less than 13.5gm/dl, Hct less than 40%
Hct normal
About 45% (3 times the hemoglobin amount)
Mean corpuscular volume - definition
average size of RBC- 90 fL +/- 8
Mean corpuscular hemoglobin concentration
Amount of hemoglobin in each RBC- should be 33-37 g/dL. Should be 33% of the total cell weight
Reticulocytes in females
0.5-2.5%
Reticulocytes in males
0.5-1.5%
Platelet count
150-400,000/ul
WBC count
5,000-10,000/ul
Whole blood components
55% plasma, 45% formed elements, buffy coat
plasma components
92% water, proteins, and other solutes
Formed elements components
rbc, wbc’s, and platelets
WBC components
Neutrophils, lymphocytes (T cells, B cells, NK cells), monocytes, eosinophils, basophils
Where does RBC maturation occur in adults and kids?
Adults- shifts to vertebra, sternum, and ribsChildren- long bones
Where is the marrow taken from in BMT?
Iliac crests
Examples of chronic blood loss causing anemia?
GI bleeds, gynecalogic disturbances
Mild microcytic hypochromic anemia defined as…
MCV greater than 70 fl
Severe microcytic hypochromic anemia defined as…
MCV less than 70 fL
Patient presents with SOB, fatigue, increased heart rate, decreased BP, increased respiration, hypoxia, and admits many cravings for ice and sand. You order CBC- what do you find and what may be the cause?
CBC shows low hemoglobin and hematocrit- anemia. MCV is 72 fL, MCHC is below normal. Causes could be iron deficiency anemia (most common, associated with pica), thalassemia, sideroblastic anemia, anemia of chronic disease, lead toxicity
Which disorders are associated with MCV less than 70 fL
Microcytic hypochromic anemia caused often by iron deficiency or thalassemia
Difference between causes of macrocytic vs. microcytic
Microcytic usually associated with disorders of hemoglobin synthesis.Macrocytic is associated with disorder with maturation of RBC
Total body iron
2-4 grams
How is iron absorbed in body from food?
10% from heme sources (red meat), and only 1% from non-heme sources (leafy vegetables, multivitamins)
Why do women tend to have lower iron levels than men?
because women lose 2-3mg/day when menstruating
How much iron in 1 ml of packed RBC’s?
I mg of iron
Fe2+ vs. Fe3+
Fe3+ is ferric, Fe2+ is ferrous. Iron needs to be reduced to ferrous form for it to be absorbed into epithelial cells in GI system
Apoferritin
Protein without iron
Lab values to check for if you think person has microcytic hypochromic anemia due to iron deficiency
Low ferritin levels (decreased iron stores in body), decreased serum iron, High indirect transferrin level or high total iron binding capacity, and low %age of saturated transferrin
Ferritin normal values
20-400 ng/ml
What can cause iron deficiency
Bleeding (thrombocytopenia or coag disorders), medications like motrin, NSAIDs, not getting enough in diet, or pregnancy- baby taking iron
Chronic bleeding leading to iron deficiency anemia is….
losing 2-4 ml/day
Why is TIBC increased in iron deficiency anemia?
Because body thinks liver needs more protein to carry iron, so starts to produce more transferrin, levels increase. But saturation of transferrin goes down because the problem is not that there’s a deficiency of iron-carrying protein, problem is there is not enough iron
Deficiency of of iron in stages
Iron stores are depleted first (takes a long time for lab values to get low), iron deficiency erythropoiesis- more RBC’s made because body senses low partial pressure of oxygen, and because of decreased iron have decreased Hg content (Low MCHC) and small RBC’s getting made (low MCV)
Tx of iron deficient microcytic hypochromic anemia
Ferrous sulfate PO 325 mg TID. In 2 months, normal levels. (F/U in 1 month- should be halfway to normal). Continue for 3-6 months to replenish iron stores.
If give ferrous sulfate to patient 325 mg TID. During follow up in 1 month, there iron levels are still low. What may be the problem and what is next plan?
May have chronic GI disease like chrome’s or diarrhea causing them to lose iron that is given to them (iron absorbed in epithelial cells in GI tract- if GI problem, not retaining the nutrients in body). IV sodium ferric gluconate 1.5-5 gm
What inhibits absorption of iron and what helps?
Ascorbic acid, like Vitamin C. Avoid antacids.
What prescription iron medications are well tolerated than iron salts?
Carbonyl iron or polysaccharide complex
Systemic manifestations of iron deficient microcytic hypochromic anemia
Neuropsychiatric - RLS, pica, plummer vinson syndrome, esophageal webs and strictures, koilonychia, angular stomatitis, glossitis
Cause of sideroblastic anemia
Hereditary or acquired deficiency (of Vitamin B6 if acquired) causing hemoglobin synthesis disorder because of failure of heme to get incorporated into porphyrin molecule
How to distinguish whether someone has sideroblastic or iron deficient anemia?
Both have low MCV and MCHC. But sideroblastic anemia has increased or normal iron levels, and increased % of transferrin saturated, increased ferritin levels, normal TIBC
Why do thalassemias produce a double whammy?
Because you get impaired RBC production, and also increased destruction becaues of defects in globin synthesis- recognized and destroyed by macrophages in spleen
What chromosomes are alpha and beta thalassemias associated with?
Alpha- chromosome 16 (4 genes)Beta- chromosome 11 (2 genes)
Mutations in beta thalassemias
Point mutations commonly
What are target cells and basophilic stippling associated with?
B-Thalassemia minor
Diagnosis of beta thalassemia minor anemia
Microcytic, hypochromic anemia, so decreased Hgb, Hct, MCV, and MCHC. Characteristics- target cells, basophlic stippling, normal or increased reticulocytes. R/O iron deficient anemia and sideroblastic anemia (if don’t see ringed sideroblasts). Enlarged spleen, liver- extramedullary hematopoiesis, erythroid hyperplasia. HEMOCHROMATOSIS, BONE ISSUES
Why do patients with beta thalassemia major need to be transfused?
because without transfusion, their hemoglobin is 3-6 gm/dL
Do you see manifestations in someone with both beta chains mutated in thalassemi?
This person is homozygous, so have beta thalassemia major. Normal at birth because of HbF, which has 2 alpha and 2 gamma chains. Will see manifestations after 6-9 months and require transfusions
Hemochromatosis
Iron overload occuring in transfusions of more than 100 units of blood, seen in (beta) thalassemias
Diagnosis of beta thalassemias
Electrophoresis- can look at migration of alpha and beta chains
Tx for beta thalassemia minor
Screen- genetic testing of common genes, esp if family history or of mediterranean descent
Tx for beta thalassemia major
Blood transfusions with iron chelation (taking iron out to avoid hemochromatosis), BMT, agents to increase HgF (hydroxyurea)
Hydroxyurea
agent that increases HbF, and therefore oxygen carrying capacity. Can be prescribed in beta thalassemia major
Mutation in alpha thalassemia usually caused by…
gene deletion (in contrast to beta thalassemias caused by POINT mutation)
alpha thalassemias can cause non-alpha chains to be unpaired resulting in
gamma tetramers in newborns, and beta tetramers in children and adults
What is HgH disease
alpha thalassemia with only 1 normal alpha gene, resulting in beta 4 tetramers
In which type of alpha thalassemia would you expect to see high levels of bilirubin and LDH?
Hemoglobin H disease- only 1 normal alpha gene, resulting in chronic hemolytic anemia
classifications of alpha thalassemias
silent carrier, alpha thalassemia trait, hemoglobin H disease, and 0 normal genes in fetus that is stillborn
What do you expect the RBC count to be in alpha thalassemia
Normal or increased. Even though RBC’s are being destroyed, there is increased hematopoiesis to try and get the count up
Diagnosis of alpha thalassemias
electrophoresis- will be normal for thalassemia trait or mild anemia, but abnormal in hemoglobin H disease
You would expect to see target cells in…
alpha and beta thalassemias
Tx for alpha thalassemias
Transfusions
Microcytic hypochromic Anemia of chronic disease most commonly associated with
Infections, autoimmune diseases, cancer, and chronic solid organ rejection
Patient with viral infection, causing them to be very tired. Have SOB, fatigue, pale conjunctiva, tachycardia. You suspect anemia. What does CBC and bone marrow smear tell you?
May possibly be anemia of chronic disease due to viral infection. Have decreased Hgb, Hct, low MCV (or normal), and low MCHC. Bone marrow sluggish due to infection, so low EPO level, low reticulocyte count. WBC count may be elevated if infection, otherwise normal. Platelets normal. Ferritin levels increased, but body not using iron- so decreased TIBC, % transferrin saturated decreased, low serum iron
How to treat anemia of chronic disease
Treat chronic disease. Give EPO 30,000 units/week to stimulate bone marrow to produce more RBC’s
Deficiencies in folic acid and Vitamin B12 can cause….
Ineffective megakaryopoiesis- bone marrow not working well resulting in poor production of platelets (thrombocytopenia) and poor production of RBC’s (macrocytic normochromic anemia)
What effects does liver disease have in causing macrocytic normochromic anemia?
Liver produces cholesterol, so in liver disease cholesterol esterification is defective. So the cell membrane is no longer able to hold its shape, and stretches out more resulting in huge cells (macrocytic)
Why do nutiritonal defects in vitamin B12 and folate cause cells to become huge?
Because both those nutrients necessary for nuclear development (DNA synthesis). If deficient, nuclear development is slow, and cytoplasmic development becomes huge (asynchrony between nuclear and cytoplasmic development).
What kind of synthesis are vitamin b12 and folate required for
thymidine synthesis
Cellular characteristics in megaloblastic anemia
macrocytic normochromic cells, ovalocytes, low reticulocyte count, anisocytosis, pokilocytosis, hypersegmented neutrophils
Reticulocyte count in megaloblastic anemia
Low because bone marrow not working right, so can’t produce them as much - don’t have necessary ingredients for production
What disorder could you expect to see hypersegmented neutrophils in?
megaloblastic anemia
3 types of antibodies related to pernicious megaloblastic anemia
Type I antibody- blocks Vitamin B12 binding to intrinsic factorType II antibody- Prevents Intrinsic factor-Vitamin B12 binding to receptor in ileum so no absorptionType III antibody- antibody to gastric parietal cell, so intrinsic factor cannot be produced because of parietal cell damage
How is pernicious megaloblastic anemia caused?
Caused due to lack of intrinsic factor, causes included Chronic atrophic gastritis which causes loss of parietal cells, failure of intrinsic factor production, surgery in gastric bypass patients (absoption problems), dietary problems
Do you see neurological manifestations in pernicious anemia or folate deficiency anemia?
Vitamin B12 only- needed by neurons. Will see demyelination of lateral and posterior columns of spinal cord causing vibration, abnormal proprioception- irreversible process
Megaloblastic anemia with numbness, tingling, and decreased proprioception- what do you suspect?
Vitamin B12 deficiency, NOT folate deficiency
Diagnosis of pernicious megaloblastic anemia
Decreased Vitamin B12 levels, elevated methylmalonic acid levels, and Schiling Test
What acid levels would be increased in pernicous anemia?
Methylmalonic because Vitamin B12 normally converts this into succinyl CoA. If reduced levels, buildup of methylmalonic acid
Tx of pernicious megaloblastic anemia
Vitamin B12 injections 1000 mcg * 7 days, then once a week, then 1 a month
mcg is what
micrograms
Body store of folic acid and daily requirement
5,000 mcg, need 50-100 mcg/day
Diagnosis of megaloblastic anemia caused by folic acid deficiency
Red cell folate decreased (better indicator than folic acid levels), R/O pernicious anemia- normal VB12 levels and methylmalonic acid levels. Ovalocytes, hypersegmented neutrophils, elevated MCV, anisocytosis, poikiolocytosis
Tx for megaloblastic anemia caused by folic acid deficiency
Folic acid supplements
How is hereditary spherocytosis inherited?
75% autosomal dominant
Why does hereditary spherocytosis cause increased destruction of RBC’s?
Because the RBC’s become spheroidal in shape, causing spleen sequestration and destruction
Where is hereditary spherocytosis most commonly found?
Northern Europe
RBC life span in hereditary spherocytosis
10-20 days
2 types of crises that hereditary spherocytosis can cause
Aplastic crisis- certain infections, like acute parvovirus infection causes shutdown of RBC productionHemolytic crisis- can occur if person also has mono- enlarged spleen, so now person has even more destruction of RBC’s
Diagnosis of HS
Low Hgb, Hct, MCV will be decreased, MCHC will be ELEVATED due to cellular dehydration, inc destruciton of RBC’s leading to increased bilirubin (possibly jaundice), reticulocytes possibly, SPHEROCYTES, OSMOTIC FRAGILITY TEST
What does osmotic fragility test test and why is it ordered?
To see how fragile RBC’s- how likely it is to burst. Can order if suspect HS- defect in membrane cytoskeleton causes it to be less flexible and more fragile
Tx in HS
Splenectomy will decrease destruction, folic acid (not curative)
How is G6PD deficiency inherited?
X linked recessive
Distinguish between spur cells and burr cells
Burr cells or echinocytes: RBC’s with multiple spikes around them as a result of increase in uric acid. Spur cells or acanthocytes- RBC’s with spiked cell membrane appearance, common in liver disease
What does a “dry tap” signify
That bone marrow is hypocellular with mostly fat- in aplastic or fanconi anemia
What will aplastic or fanconi anemia lab show
Pancytopenia, Normal MCV, and normal MCHC.
Disease associated with ashkenazi jews
hemophilia C
Disease endemic in mediterranean basin
Thalassemia
The 2 most severe forms of G6PD deficiency are seen in…
African americans and meditarranean individuals
What is protective against oxidants?
G6PD
What exposures can cause oxidative stress?
Drugs (tylenel, sulfonamids), infections, and fava beans
Heinz bodies
Result when globin chains denature forming precipitates that cause intravascular and extravascular hemolysis (seen in G6PD deficiency)
Tx for acute and chronic G6PD deficiency
acute- treat irritant, remove stressorchronic- splenectomy, folic acid
Diagnosis of G6PD deficiency
Decreased Hgb, Hct, normal MCV and MCHC, increased bilirubin
Inheritance of sickle cell disease
Autosomal recessive, Point mutation- valine for glutamic acid in beta chain
Population most affected by sickle cell trait
African americans (10%) and 30% africans because protective against malaria
What does low partial pressure of oxygen cause in sickle cell disease?
RBC gets deoxygenated, causing HbS molecules to polymerize and herniate through membrane causing efflux of water and leading to sickle cell shape change
Effects of sickle cells in circulation and spleen
Can get caught up in narrow capillaries because of inflexible shape causing death of tissue (infarction) distal to vessel obstruction in circulation and spleen. In spleen, recognized and lysed leading to enlarged spleen initially, then tiny spleen because of infarction and fibrosis
What inhibits polymerization of HbS molecules?
HbF inhibits sickling and HbA inhibits polymerization only in people with Sickle cell trait
How does hgb content in cell affect sickling?
Decreased MCHC increases polymerization of HbS molecules
How do acidic conditions affect sickling?
Low pH decreases oxygen affinity to hemoglobin, causing desaturation–so sickling more likely to occur
Sickling confined to microvascular beds with ___ transit times
slow
Manifestations of sickle cell anemia
Chronic hemolytin anemia causing jaundice, pigmented gallstones, and splenomegaly (eventually splenic infarction and fibrosis) and infarction due to vessel occlusions- pain crisis in kidney, heart, liver, lungs, and GI tract
Manifestations of sickle cell anemia in children
Bone crisis, sequestration crisis, aplastic crisis if parvovivus B19 infection, impaired growth and developement due to chronic hypoxia, and susceptibility to infection due to altered splenic function
Why should you encourage vaccinations of pneumococcus pneumonia and H influenza esp. in kids with sickle cell anemia
because spleen has altered function, more susceptible to infection
Diagnosis of sickle cell anemia
Electrophoresis to identify abnormal beta chain
What do target cells represent in sickle cell anemia?
dehydration
Tx of sickle cell anemia
avoid triggers and hydroxyurea 500-750 mg/day which increases HbF levels, inhibits WBC production, and inhibits DNA synthesis
Tx in crisis situations in sickle cell anemia
Fluids, pain management (morphine)