Hematology 1

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<p>Lab Results + Physical Exam+ Patient History</p>

Lab Results + Physical Exam+ Patient History

what are the three hematologic diagnostics?

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Hematology – science of blood and the blood forming tissues

● Anemia – condition with diminished oxygen carrying capacity of the

blood (destruction/loss/diminished production)

● Ineffective Hematopoiesis – failure to produce or release mature

forms of cells into the peripheral blood or cells destroyed in marrow

● Extramedullary Hematopoiesis – formation of blood cells in sites

other than bone marrow; primarily liver and spleen

● Hemolysis – destruction of red blood cells

● Peripheral Blood Smear – thin film of EDTA anticoagulated blood on a glass slide; stained and examined microscopically

● “Shift to the Left” – an increase in the immature forms of cells in the

peripheral blood

________ – science of blood and the blood forming tissues

_________ – condition with diminished oxygen carrying capacity of the

blood (destruction/loss/diminished production)

__________– failure to produce or release mature

forms of cells into the peripheral blood or cells destroyed in marrow

__________– formation of blood cells in sites

other than bone marrow; primarily liver and spleen

__________ – destruction of red blood cells

___________– thin film of EDTA anticoagulated blood on a glass slide; stained and examined microscopically

____________ – an increase in the immature forms of cells in the peripheral blood

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Whole Blood has :

Platelets, RBC, WBCs, Lymphocytes, Monocytes, Eosinophils , Basophils, Neutrophils

Dont blem it on me

what is 7 things is blood composed of?

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Blood cell production; starts before

birth and continues throughout life:

➢ Embryo: Yolk sac

➢ Fetus: Liver, Thymus, Spleen, and

Marrow of all bones

➢ Birth: Bone Marrow (primarily)

❑ Flat bones (sternum, ribs, skull,

vertebrae, pelvis) and Long

bones (femur, humerus)

❑ Extramedullary: Spleen and

Liver

When & Where does blood Cell production (heamtopoiesis) begin?

Specifically in the:

Embryo

Fetus

Birth:

:

Extramedullary:

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<p><u>Platelets</u></p><p><span>Stem cell → common myeloid → megakaryoblast → Promegakaryocyte → megakarycyte → Thrombocyte</span></p><p><span><u>RBC</u></span></p><p><span>Stem cell → common myeloid → Proerythoblast (pronormoblast) → Basophilic erythroblast → polychromatic erythoblast → orthochromatic erythroblast→ polychromatic erythrocyte (reticulocyte) → Erythrocyte</span></p><p><span><u>Granulocytes</u></span></p><p><span>Stem cell → common myeloid → myeloblast → Promyelocyte → Myelocyte → metamyeloctye → Band → Granulocyte</span></p><p><u>Monocytes</u></p><p><span>Stem cell → common myeloid → myeloblast → monoblast → promonocyte → monocyte</span></p><p><span><u>B&amp;T</u></span></p><p>Stem cell → common lymphoid progenitor → Prolymphocyte (NK cells come from here) → Small lymphotcyte → B (futher differentiate into plasma) or T</p>

Platelets

Stem cell → common myeloid → megakaryoblast → Promegakaryocyte → megakarycyte → Thrombocyte

RBC

Stem cell → common myeloid → Proerythoblast (pronormoblast) → Basophilic erythroblast → polychromatic erythoblast → orthochromatic erythroblast→ polychromatic erythrocyte (reticulocyte) → Erythrocyte

Granulocytes

Stem cell → common myeloid → myeloblast → Promyelocyte → Myelocyte → metamyeloctye → Band → Granulocyte

Monocytes

Stem cell → common myeloid → myeloblast → monoblast → promonocyte → monocyte

B&T

Stem cell → common lymphoid progenitor → Prolymphocyte (NK cells come from here) → Small lymphotcyte → B (futher differentiate into plasma) or T

Where are platelets formed from?

Where are RBCs formed from?

Where are Granulocytes formed from?

Where are the Monocytes formed from?

Where are B & T blood lines

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➢ Red Blood Cells (RBCs) – Erythrocytes

➢ White Blood Cells (WBCs)

➢ Granulocytes ❑ Neutrophils ❑ Eosinophils ❑ Basophils

➢ Monocytes

➢ Lymphocytes

➢ Thrombocytes - Platelets (PLTs)

What are the types of mature blood cells?

What do they all look like?

➢ Red Blood Cells (RBCs) –

➢ White Blood Cells (WBCs)

➢ Monocytes

➢ Lymphocytes

➢ Thrombocytes -

<p>What are the types of mature blood cells?</p><p></p><p>What do they all look like?</p><p>➢ Red Blood Cells (RBCs) –</p><p> ➢ White Blood Cells (WBCs) </p><p>➢ Monocytes</p><p> ➢ Lymphocytes </p><p>➢ Thrombocytes -</p>
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Protein stimulators: ETI erythropoietin, thrombopoietin, interleukin

protein inhibitors: interferons, lymphotoxis

Name the 3 protein stimulators

Name the 2 protein inhibitors

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<p>Low Oxygen is Felt</p><p>Kidney Secrete Erythropoietin Hormone</p><p>Erythropoietin stimulates enhanced erythropoiesis in bone marrow</p><p>Bone Marrow Erythropoiesis results in increased rbc count</p><p>Oxygen Level returns to normal in the body</p><p>Days 1-5:</p><p>CMP → Proerythroblast → Erythroblast → Reticulocyte → Erythrocyte</p>

Low Oxygen is Felt

Kidney Secrete Erythropoietin Hormone

Erythropoietin stimulates enhanced erythropoiesis in bone marrow

Bone Marrow Erythropoiesis results in increased rbc count

Oxygen Level returns to normal in the body

Days 1-5:

CMP → Proerythroblast → Erythroblast → Reticulocyte → Erythrocyte

How is RBC production regulated?

how do RBCs form?

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Orthochromic

Streaks of RNA/DNA, stain grey/blue

What stage of RBC creation do we lose the nucleus to make room for the Heme group

What are the differences between reticulocytes and mature RBCs

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<p><span>Lose pliability → cleared by phagocytes in spleen, liver, bone marrow, lymph → iron, proteins, etc are reused → waste products (bile pigments) are excreted</span></p>

Lose pliability → cleared by phagocytes in spleen, liver, bone marrow, lymph → iron, proteins, etc are reused → waste products (bile pigments) are excreted

Describe the destruction and recycling process of RBCs

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Purple top less than 24 hrs old (mix gently), bone marrow sample (slides must be made A$AP), Green top, light blue top

What specimens can be used for CBCs?

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hemocytometer: (manual - green for WBCs, Red for everything else)

How can you run a hemocytometer?

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➢ CBC – complete blood count RBC: red blood cell (erythrocyte) count – total number in (x 1012/L)

Hb/Hgb: hemoglobin – amount of protein transports oxygen (g/dL; g/L) (10 g/dL =100 g/L)

Hct: hematocrit – packed RBCs (%; L/L)(42% = 0.42 L/L) RBC Indices: parameters that reveal size and amount of Hb in individual RBCs

MCV: mean corpuscular volume (fL/cell) – average size of RBCs]

MCH: mean corpuscular hemoglobin (pg/cell) – average amount of Hgb in RBCs

MCHC: mean corpuscular hemoglobin concentration (g/dL) – average concentration of Hgb in RBCs

RDW: red cell distribution width – variability in RBC volumes (anisocytosis)

PLT: platelet (thrombocyte) count – total number in (x 109 /L) MVP: mean platelet volume (fL/cell)

WBC: white blood cell (leukocyte) count – total number in (x 109 /L) Differential: % of each individual ty

CBC

Hb/Hgb:

Hct:

RBC indices

MCV:

MCH:

MCHC:

RDW:

PLT

WBC

Differential

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RBC

rbc direct count

Hemoglobinopathies, reactive conditions, hypoxic environments, EPO tumors, polycythemia vera

Anemia

dehydration (physio), COPD, CHF, Cancer, smoking, high altitude, excess EPO

what is the total number of microliter of blood?

is rbc direct count/analyzer?

what causes erythrocytosis

what causes erythrppenia

increased HgB indicates right

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Hemoglobin (Hb / Hgb)

● Concentration of hemoglobin in whole blood

● Direct measure

○ Expressed in grams per deciliter (g/dL or g/L)

● Indication of oxygen-carrying capacity

● Interpretation of levels

○ Increased = physiologic (dehydration), pathologic (COPD,

CHF, Cancer), smoking, living in high altitudes, excess

erythropoietin

○ Decreased = anemia

what is concentration of hemoglobin in whole blood >

Is hemoglobin a direct or indirect measure, and how it is measure?

What is hemoglobin an indication of>

What are increased hemoglobin levels indicating?

what are decreased hemoglobin levels indicating?

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Hematocrit (Hct)

● Portion of blood occupied by RBCs

● Expressed as % (%; L/L) [Example...42% = 0.42 L/L]

● Directly measured by centrifugation / automation or

calculated using the following formula

HCT (%)= (RBC x MCV) / 10

● Usually directly proportional to RBC and Hb

○ “Rule of Three” = (RBCx3=Hb, Hbx3 = Hct)

● Indicator of blood volume changes or hydration status

○ Low = anemia, blood loss

○ High = Polycythemia, dehydration

what describes the portion of blood occupied by RBCs?

is hematocrit direct or indirect measure?

what is the hct formula?

hematocrit is usually directly proportional to what?

rule of 3?

What does low hematocrit indicate

what does high hematocrit indicate

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MCHC=(Hbg/Hct) x 100

High mchc indicates= iron overload, spherocytosis, macrocytic anemia, blood disorders, medications

low mchc (under 32) indicates what=iron deficiency anemia

what is the formula for MCHC

High mchc (HYPERCHROMIA.) >36indicates

low mchc (under 32) )Hypochromia) indicates what

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MCV (size) = Hct/RBC (Reference range: 80-100 fL)

• Direct measure or calculated (10 x Hct / RBC)

• Allows the classification of anemia

what is mcv size equation

what is the mesured as?

what does MCV allow for the classification of?

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➢ RDW = variation in volume / size (normal

variabililty <5% )

❑ RDW-CV = SD of MCV x 100 / MCV

❑ RDW-SD = directly measured; not affected by MCV

• Reference range: 11.5-14.6%

Anisocytosis (varying size) vs Poikilocytosis (diff shaped)

Increase RDW indicates what?

what is the RDW equation:

How do you describe RBC which are varying sizes?

how do you describe RBC that are differently SHAPED?

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Blood smear- run for anisocytosis OR pokilcytosis

➢ Confirm CBC results

➢ Review erythrocyte morphology

➢ Maturity / presence of abnormal cells

➢ Shape: poikilocytosis (abnormal shape)

➢ Size: anisocytosis (variation in size)

➢ Color: normochromia or hypochromia

➢ Inclusions (infection) / Granulation (toxicity)

➢ Arrangement: rouleaux or aggregates

If you see anisocytosis or Poikilocytosis - what are we running?

what basic things can a blood smear look at ?

in general

shape

size

color

inclusion vs granulation

arragement

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anemia is a decrease in the total amount of RBC

Decreased blood cell PRODUCTION?

  • INTRINSIC BONE MARROW DYSFUNCTION

  • meds, dx,genetics, nutrition deficiency, hormone imbalance

blood loss?

  • periods, GI bleeds, trauma, surgery

RBC destruction?

  • hemolysis, imtravasuchalr, autoimmune, infections, toxins

  • extravascular, genetics

what is anemia?

what are major causes of Decreased blood cell PRODUCTION?

What are major causes of blood loss?

What are major causes of RBC destruction?

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Anemia: yellow eyes, SOB, weak, pale stool, chest pain, angina, heart attack, low BP, fatigue, dizziness, fainting

SEVERE anemia: red eye

what are symptoms of anemia?

what are symptoms of SEVERE anemia?

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Reflex tests:

➢ peripheral blood smear

➢ bone marrow biopsy

➢ reticulocyte count

➢ Immature reticulocyte fraction

➢ Reticulocyte hemoglobin content (CHr)

➢ haptoglobin

➢ bilirubin

➢ direct antibody test (DAT) for autoimmune

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what are some reflex test for anemia>

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decreased RBC, BLOOD LOSS, or RBC destruction

so again, what three main things cause anemia

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Reticulocyte

Haptoglobin

Bilirubin

Immature RBC with residual RNA that is newly released from the bone marrow

Protein in blood that carries free Hgb to liver for metabolism and excretion

Breakdown product of heme catabolism

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<p>Measures the number of reticulocytes in circulation</p><p>➢ Reticulocyte = immature RBC with residual RNA, newly</p><p>released from the bone marrow into the blood stream</p><p>➢ Indicator of bone marrow function to produce RBCs</p><p>MCV (they be BIG), MCHC (more hgb)</p><p>Reticulocytes can show slightly more blue than red cells<br></p>

Measures the number of reticulocytes in circulation

➢ Reticulocyte = immature RBC with residual RNA, newly

released from the bone marrow into the blood stream

➢ Indicator of bone marrow function to produce RBCs

MCV (they be BIG), MCHC (more hgb)

Reticulocytes can show slightly more blue than red cells

what does a reticulocyte count measure?

what is a reticulocyte?

what does a low or high reticulocyte count give insight to?

what measures can reticulocytes throw off balance?

How can reticulocytes present on cbc?

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High reticulocyte: normal bone barrow could be compensating for anemia

Low reticulocyte count: bone marrow dysfunction failure

see why anemia occurred

high reticulocyte count indicate

low reticulocyte counts indicate

why do we run a reticulocyte count

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corrects for variance in reticulocyte maturation time in circulation and total rbc circulation

what is the purpose of the reticulocyte INDEX

NOTE: low or high RI is similar to reticulocyte reasons

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RETIC-RET-HE/CHR

Measures retic Hgb content in real time and the functional availability of iron during Hgb synthesis

(decreased levels can predict iron deficiency anemia even before it develops)

what is the purpose of RETIC-RET-HE/CHR test?

what can RETIC-RET-HE/CHR test predict?

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Separates different types of Hgb in the blood via an electric current to investigate, screen, and monitor hemoglobin disorders - Normal is Hgb A, with little amounts of A2 or HgbF

Separates different types of hemoglobin in the blood by

electric current

● Used to investigate, diagnose, screen, and monitor

abnormal hemoglobin disorders

● Automated analysis

● Interpretation of results

○ Normal = predominant band of Hgb A, small amounts

Hgb A2, and HgbF (fetal)

○ HgbS = Sickle cell anemia

○ HgbC = linked to hemolytic anemia

what does HgB electrophoresis do?

What should you expect to see on a normal electrophoresis?

In adults? In a fetus?

HgbS is a sign of

HgbC is a sign of

HgbF

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microcytic (small)

hypochromic (pale)

high RDW: great variation in sizes in microcytic-hypochromic


Small and pale RBCs

○ Low MCV / Low MCHC

○ High RDW

● Most common type of anemia

● Most common cause = Iron

deficiency

what is the most common type of anemia?

Microcytic Hypochromic anemia is the most common cause of ?

how does microcytic-hypochromic anemia mean/ present in the cell?

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Normocytic normochromic

normal size and normal color

Anemia with normal sized and colored RBCs that is most commonly caused by chronic disease

what is the most common type of anemia of chronic disease?

how does the blood cell present?

how is the mcv,mchc, and rdw?

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<p>Macrocytic -Hyperchromic</p><p>Anemia</p><p>● Abnormally large RBCs with</p><p>more Hgb</p><p>○ High MCV / High MCHC</p><p>● Represented primarily by</p><p>Megaloblastic Anemias (B12,</p><p>Folate deficiencies)</p><p>● Classic feature of megaloblastic</p><p>cells (hypersegmented</p><p>neutrophils)</p><p></p>

Macrocytic -Hyperchromic

Anemia

● Abnormally large RBCs with

more Hgb

○ High MCV / High MCHC

● Represented primarily by

Megaloblastic Anemias (B12,

Folate deficiencies)

● Classic feature of megaloblastic

cells (hypersegmented

neutrophils)

what anemia is commonly found with megaloblastic anemias:

what are they

what is a classic feature of megaloblastic cells?

how would mcv/mchc present?

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Methylmalonic Acid

Measures the amount of MMA

(an organic acid by product of

protein metabolism)

• Helpful in early or mild B12

deficiency

• Increased serum MMA indicates

a decreased Vit B12

(MMA) Homocysteine

Amino acid byproduct of

methionine metabolism – not used

to build proteins

• Hyperhomocyteinemia = elevated

if Vit B6, B9, B12 deficiency

• Elevated levels increase risk of

CVD, Stroke, Thrombus,

Osteoporosis, Cognitive decline

what does MMA (methylmalonic acid measure)?

what is mma most helpful with and what does an increase in mma indicate?

what does homocysteine measure?

what does hyperhomocyteinemia measure?

what do elevated homocysteine levels increase the risk of?

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DO THE PRACTIC QS on slides

48-53

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Hemolytic anemia (normocytic normochromic)

RBCs are broken down faster than they are produced (retics UP, LDH UP) and classified as intrinsic or extrinsic

Intrinsic
defect with in the RBC usually genetic (sickle cell, G6PD, etc)

Extrinsic

Factors outside RBC usually acquired (autoimmune, medications, trauma - check spleen and liver)

what is hemolytic anemia?

Intrinsic/Intravascular Anemia:

meaning

causes

Extrinsic/Extravascular Anemia:

What should you measure if you find extrinsic anemia?

meaning

causes

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Haptoglobin

● Measures the amount of haptoglobin

○ Protein produced by the liver

○ Binds with free Hgb to prevent damage to tissues

● Removed from the blood by the liver and spleen

● Clinical Significance of levels

○ Low = oxidative stress / damage to tissues

(Hemolytic anemia, Liver disease, CVD, CA)

○ High = inflammation, medications

What does haptoglobin measure?

How is haptoglobin moved from the blood?

what does high haptoglobin indicate?

what does low haptoglobin indicate?

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Direct antibody testing (DAT)

Test that detects antibody coatings on RBCs and a positive result is associated with

  • +++indicates autoimmune problem not 100% sensitive/specific

  • can have false + in individuals

  • neg- none detected

  • autoimmune hemolytic anemia (hot/cold)

, Hemolytic disease of the newborn, transfusion reactions, drug induced hemolysis

what does direct antibody test detect?

if DAT is positive?

if DAT is negative?

what are DAT associated conditions mc?

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Hemorrhagic anemia

What type of anemia is due to excessive blood loss and has NO signs of hemolysis on lab test - can be caused by trauma, menstrual cycles, GI, medications, etc

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