Heme cumulative

sorry this is prob too long :/

What is included in a CBC w/ differential?

• WBC count

• Hgb/Hct

• RBC count

• RBC indices

• WBC differential

• platelet count

What does a differential measure?

percent of each type of leukocyte

what is a normal Hgb value for males?

14-18 g/dl

what is a normal Hgb value for females?

12-16 g/dl

what is a normal Hct value for males?

42-52 %

what is a normal Hct value for females?

37-47%

what is a normal MCV value?

80 - 100 um

What measure is best to classify anemias?

MCV

what is normal range of MCH?

30-34 pg/cell

what is normal range for MCHC?

31-37 g/dl

What does an increased retic count reflect?

ongoing or recent RBC production activity

ex: post bleeding, post hemolysis (hemolytic anemia), response to therapy

what does a decreased retic count reflect?

decreased RBC production

ex: anemia, aplastic anemia, decreased EPO, post XRT, bone marrow replacement by benign or malignant process

What is IPF?

method to quantify reticulated platelets

(increased in conditions w/ inc plt production)

what is the most abundant cell type?

erythrocytes / RBCs

What is HgF?

normal Hgb product in the RBCs of a fetus and im small amounts in infants

What are the granulocytes?

neutrophils, eosinophils, basophils

What are the agranulocytes?

lymphocytes, monocytes

where does hematopoiesis occur in adults?

red bone marrow of long bones and axial skeleton

precursors cells

Where is EPO produced?

in the kidneys by cells that sense the adequacy of tissue oxygenation

What is anisocytosis?

abnormal variation in size

what is microcytosis?

cell size < 6 um or MCV < 80

what is macrocytosis?

cell size > 8 um or MCV > 100

what is hypochromia?

cells w/ dec concentration of Hgb

what is poikilocytosis?

abnormal cell shape

what is spherocytosis?

spherical, w/o pale centers

What is a crescent shaped cell known as?

sickle cell

what are target cells?

dark center and periphery w/ clear ring in the center (bullseye)

what are schistocytes?

fragmented irregularly contracted cells

What is the definition of anemia?

condition in which there are decreased number of circulating erythrocytes or decrease in total amount of hgb resulting in decreased oxygen transport

What are generic sx of anemia?

fatigue, weakness, malaise, pallor, SOB, dizzy/lightheaded

What is pica?

abnormal craving ice or other non food items (sign of anemia)

What are PE findings you might see in an anemic patient?

• pale skin, conjunctiva, mucosa

• check tongue and mouth for lesions

• nail defects

• tachycardia, murmurs

• dyspnea, esp w/ exertion

What workup would you order for anemia?

• CBC w/ diff (dec H&H)

• RBC indices → MCV, MCH, MCHC

• reticulocyte count

• fecal hem occult looking for occult GI bleeding

• urinalysis (hematuria)

MCV ≤ 80 fL is considered …

microcytic

MCV 81-99 fL is considered …

normocytic

MCV ≥ 100 is considered …

macrocytic

If reticulocytes are low, where is the problem?

in the marrow (marrow failure or lack of substrate); reflects dec RBC production

if reticulocytes are high, where is the problem?

not in the marrow (appropriate response is to compensate); reflects ongoing or recent RBC production activity

What is the pathophysiology of iron deficiency anemia (IDA)?

• depletion of iron stores (common in children and menstruating/pregnant individuals)

• iron becomes limiting factor in heme biosynthesis

• heme deficiency then limits Hgb assembly

• Hgb deficiency limits RBC production

• RBC cells become (microcytic, low MCV) and deficient in hgb (hypochromic, low MCH)

Where is iron primarily absorbed?

in the duodenum

What are possible causes of iron deficiency?

• occult/overt GI losses, traumatic, or surgical losses

• failure to meet inc requirements (rapid growth in infancy/adolescence, menstruation, pregnancy, delivery)

• inadequate dietary source (vegan diets, impoverished)

• malabsorption (GI dz/surgery, duodenal/small bowel malabsorptive dz)

• chronic hemolysis (paroxysmal nocturnal hgb (PNH), mechanical hemolysis)

what is ferritin?

protein created to store iron in the cells;

also an acute phase reactant and rises in high inflammatory states

when would ferritin decrease?

in the presence of iron deficiency in an effort to free up iron to become heme

what is the most useful test for iron deficiency?

ferritin → no other causes of low ferritin

What does serum Fe measure?

amount of free iron in the serum

what is transferrin?

holds iron in the serum

what is total iron binding capacity (TBIC)?

indirect measure of transferrinw

when is transferrin elevated?

in the presence of iron deficiency as a futile attempt to gather more iron

what is the most common cause of anemia?

iron deficiency

what is the most common cause of iron deficiency anemia?

GI bleeding or dysfunctional uterine bleeding

what is the definition of iron deficiency anemia (IDA)?

hypochromic, microcytic anemia resulting from under production of RBCs due to lack of adequate amount of iron

etiologies of IDA

• abnormal blood loss (cancer, menstruation, PUD, IBD)

• malnutrition

  • dec absorption (celiac sprue, gastrectomy/gastric bypass)

  • inc demand (pregnancy, lactation, rapid growth)

• kidney dz (CRF, dialysis)

What is the clinical presentation of IDA?

• can be asx; insidious onset

• fatigue, weak, WOB

• pallor

• palpitations

• HA, dizzy, tinnitus

• sx of underlying dz → ulcer, gastritis, melon, menorrhagia

what are unique manifestations of IDA?

• glossitis- red smooth waxy tongue w/ atrophy of papillae

• angular cheilitis- ulcerations or fissures at corners of mouth

• koilonychias- thin, friable, brittle spoon shaped nails

• pica- cravings for non food

what would iron studies look like in IDA?

• low serum iron

• high TBIC (empty seats on the bus)

• low ferritin (best test)

• dec percent transferrin saturation

what is the treatment for IDA?

• correct underlying problem

• oral iron supplementation (preferred)

  • ferrous sulfate

• IV iron supplementation

  • INFeD, Venofer, Injectafer

  • for patient’s unable to absorb or no improvement w/ oral

• blood transfusion, packed RBCs

  • reserved for prodounf anima (Hgb < 7), significant acute bleeding, hypoxia, or coronary insufficiency

What are possible SE from ferrous sulfate?

constipation, change in stool color, heartburn

What patient education should you give to an IDA patient?

• avoid tea and coffee- blocks absorption of iron

• take vit C 500mg+ to enhance iron absorption

• beware of s/sx of bleeding

• if severe, limit activities until corrected

what is thalassemia?

genetically heterogenous spectrum of dz characterized by mutations that result in reduction or absence of 1 or more globin chains

disrupts ⍺ / β chain ratio, stability of hgb, and leads to hemolysis

what are classic findings of thalassemia?

microcytosis out of proportion to the degree of anemia; normal iron studies

Patho of thalassemia?

• deficiencies of globin chain synthesis produce inadequate hgb → microcytic RBCs

• deficiency if alpha globin synthesis results in unused beta globin chains accumulating in RBC injuring cell membrane

  • these abnormal RBCs are removed from circulation early by spleen, further worsening the anemia

• similar results w/ alpha globin chain accumulation in beta thalassemia

Where is thalassemia most common?

mediterranean, asian, and African regions where malaria is endemic

What happens if you inherit only one abnormal β allele (β/β+ or β/βo)?

thalassemia trait / silent carrier

mild anemia / no transfusions

what happens if you inherit 2 abnormal β alleles (βo/βo)?

thalassemia major

marked hemolysis, profound anemia, and transfusion dependency

how many β globin genes are located on chromosome 11?

2

how many ⍺ globin genes are there on chromosome 16?

4

What does a deletion of 1 ⍺ gene (-⍺/⍺⍺) result in?

silent carrier

no clinical manifestations

what does a deletion of 2 ⍺ genes (-⍺/-⍺ or --/⍺⍺) result in?

thalassemia trait or talassemia minor

mild anemia

what does a deletion of 3 ⍺ genes (- -/-⍺) result in?

Hgb H dz (hgb precipitates → hemolysis → splenomegaly)

mod-severe microcytic anemia (smear w/ striking hypochromia, target cells, basophilic stippling)

what does a deletion of all 4 ⍺ genes result in?

thalassemia major or hydrops fetalis

almost total hemolysis of RBCS, fetus usually dies in utero

what is the clinical presentation of thalassemia?

varies; asx or sx of anemia, hepatosplenomegaly, jaundice

what is the gold standard for evaluation of thalassemia?

hemoglobin electrophoresis

what would a lab evaluation of thalassemia show?

• microcytosis, hypochromia

• stippled cell

• target cell

• elliptical cell

What would hemoglobin electrophoresis show in thalassemia?

beta: increased Hgb F and A2

alpha: may be normal, difficult to dx

what is the treatment for thalassemia major?

• only required if sx severe

• chronic transfusion therapy

• iron chelation

• splenectomy- to stop excessive destruction of RBCs

• allogenic stem cell transplant only curative measure

Thalassemia trait (minima) manifestation

• manifests as mild-mod microcytic hypochromic anemia

• most often asx

• asian, mediterranean, and African populations

• required no tx other than genetic counseling

Why is thalassemia trait often confused w/ IDA and why is this a problem?

low MCV

places pt at risk for inappropriate/toxic treatment w/ iron

When should you always suspect thalassemia?

• low MCV is Fe deficiency has been r/o

• pt fails to respond to Fe replacement therapy

What would labs show in thalassemia trait?

• MCV < 70

• RBC count > 5.0

• normal RDW

• normal or increased iron studies

What patient education should you provide for thalassemia?

• genetic counseling

• supplements- folic acid, vit C, vit E

• drink tea and coffee (decreases iron absorption)

• do NOT give iron and avoid iron rich foods

• normal activity is tolerated

what is microcytic hypochromic anemia w/ basophilic stippling?

lead poisoning anemia

what is the pathophysiology of lead poisoning anemia?

chronic repeated lead exposure → iron is displaced by lead and zinc protoporphyrin is formed

what is the clinical presentation of lead poisoning anemia?

• often vague and non specific sx; often unrecognized

• (dx usually made via screening program or elevated blood/urine levels)

• early: loss of appetite, vomiting, irritability etc

• late or acute: CN paralysis, encephalopathy, seizures, coma

Lead values

• above 10 = toxicity

• above 45 = chelation therapy

• above 70 = medical emergency

What is the treatment for lead poisoning anemia?

• prevent further exposure

• chelation- mobilize lead from bone and encourage urinary excretion (succimer PO or Dimercaprol IM)

• supportive care- anticonvulsants, vitamin D, high calcium/phosphorous diet

chronic blood loss leads to _____ anemia ; acute blood loss leads to _____ anemia

microcytic; normocytic

what is the accelerated destruction of erythrocytes resulting in anemia?

hemolytic anemia

Types of hemolytic anemia

extravascular: through reticuloendothelial system (spleen)

intravascular: w/in circulation itself (prosthetic heart valve, G6PD, TTP)

what would a laboratory evaluation of hemolytic anemia show?

• CBC: normocytic anemia

• total bili: elevated (d/t intravascular release of hgb)

• LDH: increased

• Haptoglobin: decreased (consumed by binding to free hgb, rapidly removed by liver)

• reticulocyte count: marked increase (marrow attempting to compensate)

what is the most common RBC defect?

G6PD deficiency

Who is G6PD deficiency more common in?

males

What do Heinz bodies and bite cells indicate?

G6PD deficiency

What is the clinical presentation of G6PD deficiency?

• asymptomatic in steady state

• hemolysis occurs under oxidative stress

  • acute infx (COVID)

  • drugs- dapsone, pyridium, etc

  • diet- fava beans

  • metabolic acidosis

How is G6PD deficiency diagnosed?

quantitative enzyme assays

what is the treatment for G6PD deficiency?

• avoid triggers

• blood transfusions in acute hemolysis or blood exchange

• splenectomy (controversial)

What condition has antibodies that develop against RBCs, resulting in their destruction?

autoimmune hemolytic anemia (warm and cold)

Which AIHA is more common and typically IgG and signals macrophages in spleen to target IgG/Fc?

warm

which AIHA is typically IgM and activates complement cascade?

cold

Warm AIHA clinical presentation?

• could be asx

• anemia sx

• jaundice

• splenomegaly