CMS Heme exam

erythrocytes (RBC)

what is the most abundant cell type that transports O2 and contains hemoglobin?

4 globin chains and 4 heme groups

hemoglobin is composed of______

it is responsible for oxygen and carbon dioxide transport

heme

O2 binds to______ and carries O2 molecules to the tissues

globin

CO2 binds to ____ -->excreted out by the lung

2 a-chains

2 b-chains

Hemoglobin A is composed of 4 globin or protein chains

leukocytes (WBC)

___ in the blood have the primary function of immune response

Two categories: granulocytes and agranulocytes

neutrophils, eosinophils, basophils

what are the granulocytes WBC

neutrophils

what granulocyte is involved in acute bacterial infections

◦Phagocytic

eosinophils

what granulocyte is involved with Parasitic worm infections

basophils

what granulocyte is involved in Inflammatory response and vasodilation

◦Histamine containing granules

lymphocytes and monocytes

what are the agranulocytes WBC

lymphocytes

what agranulocyte has two primary populations

◦T cells: acts directly against target

◦B cells: utilizes antibody production against target

monocyte

what agranuloyte has Circulating macrophages

◦Phagocytic

Hematopoiesis

formation of red blood cells that occurs in red bone marrow of long bones and axial skeleton

hematopoietic stem cell

all blood cells arise form the _____

kidneys

hematopoiesis is under the influence of EPO in the ______.

EPO is produced by cells that sense tissue oxygenation

reticulocytes

immature RBCs

takes 4 days to mature---> 120 circulation then removed by macrophages

common myeloid progenitor and common lymphoid progenitor

the hematopoietic stem cells can divide into ______ and _____

megakaryocyte, erythrocyte, mast cell and myeloblast

common myeloid progenitor turns into

basophils, neutrophils, eosinophils, and monocytes

what does a myeloblast turn into

macrophages

monocytes turn into

B and T lymphocyte and natural killer cells

the common lymphoid progenitor turn into

MCV

the size of RBC

reticulocyte count

what lab eval measures for immature RBS, normally seen in vary small amounts

elevated

if bone marrow is working well (normal) there will be _________ levels of reticulocyte count

haptoglobin

molecule that binds free circulating hemoglobin (released form RBCs when it breaks apart)

this prevents toxicity

low

______ haptoglobin is a useful lab marker of hemolysis , because it means RBCs are being destroyed and the haptoglobin is being used up

Ferritin

____ is the main storage form of iron in the body

reflects your total body iron stores.

low

if iron is ______

There's no iron to store, so ferritin levels drop — this is a hallmark of iron deficiency anemia.

iron deficiency

IF FERRITIN IS LOW =

increases

If inflammation is present: Ferritin also behaves like an acute-phase reactant, meaning it ______

transferrin

iron transporter molecule

Total Iron Binding Capacity (TIBC)

measures the blood's capacity to bind iron with transferrin, the main iron transport protein.

increases

If iron is low, the body makes more transferrin to try to pick up more iron → TIBC_____

So TIBC is inversely related to body iron stores.

iron saturation

measures the percentage of transferrin that are carrying iron.

normal is 20-50%

serum iron

measures the amount of free circulating iron in serum

*least helpful*

Hemoglobin Electrophoresis

a laboratory test that separates and measures different types of hemoglobin found in the blood.

Coombs (DAT)

test is used to detect antibodies that are bound directly to the surface of red blood cells

These antibodies can cause the RBCs to be destroyed — leading to hemolysis.

agglutination (clumping)

coomb's test:

1. A patient's RBCs are taken from a blood sample.

2. These cells are mixed with Coombs reagent

3. If the patient's RBCs are already coated with antibodies, the Coombs reagent will bind to those antibodies and cause _____

Positive Coombs test,

Agglutination = ________meaning antibody-coated RBCs are present.

immune-mediated hemolysis

what does a postive direct coombs tets mean?

*RBCs are being destroyed because antibodies are attached to them

Bone Marrow Aspiration and Trephine (Core) Biopsy

A bone marrow exam helps evaluate how blood cells are being produced.

It typically includes two components:

anemia

condition characterized by:

-A decreased number of circulating red blood cells (RBCs) or

-A decrease in total hemoglobin (Hb) → resulting in reduced oxygen-carrying capacity of the blood.

anemia

Because oxygen delivery is reduced with _____

-Fatigue

-Weakness

-Malaise

-Pallor (pale skin/mucous membranes)

-decreased production of RBC (bone marrow not making enough)

-increased destruction of RBC (hemolysis)

-blood loss

what can cause anemia

Microcytic

size of RBC

MCV ≤ 80 fL =

Normocytic

size of RBC

MCV 81-99 fL =

Macrocytic

size of RBC

MCV ≥ 100 fL =

problem in the bone marrow

reticulocyte counts in anemia

if reticulocytes (immature RBC) are LOW =

problem is not in the bone marrow

reticulocyte counts in anemia

if reticulocytes (immature RBC) are HIGH =

microcytic anemia

anemia with MCV

iron deficiency

what is a major cause of microcytic anemia

duodenum

where is iron usually absorbed?

*our body likes to hold onto iron (only small amount is lost throughout the day*

-occult or GI loss

-failure to meet increased requirements (menstruation or pregnancy)

-inadequate dietary intake

-malabsorption of iron

-chronic hemolysis

Iron deficiency develops when iron loss or demand exceeds intake and absorption.

The main causes can be grouped into 5 categories:

heme

patho behind iron deficiency:

Ferritin drops as stored iron in the liver, spleen, and bone marrow is used up

iron is required to make ______

microcytic

less heme = less hemoglobin per RBC ---> RBC appears more pale (hypochromic)

the bone marrow tries to make RBCs but with insufficient hemoglobin the marrow compensates and produces ________ RBC

iron deficiency anemia

Hypochromic, (pale) microcytic anemia due to underproduction of RBCs caused by insufficient iron.

Results in low hemoglobin and small, pale red blood cells.

blood loss like cancer (GI) or menstruation

what are the most causes iron deficiency anemia

asymptomatic

iron deficiency is mostly ________

but other symptoms include

-Fatigue

-weakness

-pallor

-shortness of breath

-heart palpitations

-headaches

-tinnitus

-glossitis

-angular cheilitis

-pica (craving for non nutritious food, ice or dirt)

-koilonychias (fingernails are thin)

what are som unique manifestations of iron deficiency anemia?

low

low

low

High variation

CBC of Iron deficiency anemia:

Hemoglobin:______

MCV:______

MCH:___(hypochromic)

RDW ( variation in RBC)

low

low

High

iron studies in iron deficiency anemia:

Ferritin:___

serum iron:____

TIBC (total iron binding capacity):____

iron deficiency anemia

a low ferritin level =

ALWAYS****

the body compensates by making more transferrin (iron transport protein in blood)

why would TIBC be elevated in iron deficiency anemia:

low

what would the reticulocyte count be in iron deficiency anemia?

bone marrow cannot respond appropriately due to iron deficiency

Iron stores are absent

if we did a bone marrow biopsy what would we see?

confirms depleted iron in the marrow

This Rarely needed unless diagnosis is unclear*

normal

*A ______ferritin does not exclude iron deficiency anemia because it is an acute phase reactant and may be elevated in inflammation, malignancy, or infection*

oral ferrous sulfate

treatment for iron deficiency anemia

(IV if more severe)

blood transfusion

treatment severe iron deficiency anemia (profound) HGB

thalassemia

inherited disorders causing reduced or absent globin chains, leading to globin imbalance, hemolysis, and ineffective RBC production

Microcytosis out of proportion (small RBC)

what is a classic finding of thalassemia?

________ to the degree of anemia

MCV is often much lower than expected given the hemoglobin level

no beta globin made

some beta globin made

beta thalassemia:

You have two β-globin genes (one from each parent). on chromosome 11

mutations:

β⁰=

β⁺=

silent carrier with mild anemia

β/β⁰ or β/β⁺

is you inherit only one abnormal beta mutation=

βeta Thalassemia Major

severe profound anemia with hemolysis

β⁰/β⁰

if you inherit both abnormal beta mutation=

transfusion

if you have profound anemia what is the treatment

silent carrier, no symptoms

alpha thalassemia:

there are 4 alpha globin genes on chromosome 16 (2 from each parent)

severity depend how many genes are deleted

deletion of 1 alpha gene=

thalassemia trait or minor thalassemia

Mild anemia

deletion of 2 alpha genes

Hgb H disease

moderate severe microcytic anemia

deletion of 3 alpha chains

san see splenomegaly

Thalassemia major, hydrops fetalis

total hemolysis of RBC

deletion of 4 alpha chains

hemoglobin electrophoresis

what is the gold standard diagnostic test for thalassemia

beta thalassemia:

Hemoglobin electrophoresis results:

look for low HbA and increased HbA2 and HbF

alpha thalassemia

Hemoglobin electrophoresis results:

look for HbH or Hb Bart's,

-chronic transfusion

-iron chelation, folic acid

-splenectomy

treatment for thalassemia is only required if severe symptoms (e.g., β-thalassemia major, Hgb H disease)

what are the treatments

Gene therapy (e.g., Zynteglo / betibeglogene autotemcel) and Allogeneic stem cell transplant

what is a definitive cure for thalassemia

this is new

microcytosis hypochromia, target cells, elliptical cells.

what type of cells will we see with thalassemia

stippled cell

what specific cell will we see with beta thalassemia

increased

will reticulocyte count be increased of decreased with thalassemia

lead poisoning anemia

Microcytic hypochromic anemia with basophilic stippling

lead poisoning anemia

Chronic or repeated exposure

Routes: GI tract, respiratory tract, skin, transplacental

Common sources: batteries, solders, paints, pottery, plumbing, gasoline, some homeopathic remedies

Zinc protoporphyrin (ZPP)

Lead displaces iron in heme synthesis and

_______ forms instead of heme → defective hemoglobin

lead poisoning anemia

patient presents with ◦Loss of appetite

◦Vomiting

◦Weight Loss

◦Learning Disabilities

◦Behavior Problems

Acute or Late Signs/Symptoms

◦Cranial nerve paralysis

◦Encephalopathy

◦Seizures

◦Coma

what is the diagnosis

basophilic stripping with tear drop cell

with lead poisoning anemia what would we see on a peripheral smear

chelation like succimer and dimercarpol

treatment for lead poisoning anemia

sideroblastic anemia

Defect in incorporating iron into heme → iron accumulates in mitochondria → microcytic, hypochromic anemia.

*****we have the iron but we cant take the iron and put in into the heme molecule**

ringed sideroblasts

what would we see on a bone marrow biopsy for sideroblastic anemia

(iron-loaded mitochondria around the nucleus)

elevated

what would we see on on a serum iron test (measures free circulating iron) for sideroblastic anemia?

we have the iron we just cant get it into the heme

normocytic anemia

Anemia with MCV between 80-100

reticulocyte count

If MCV is normal, then first step is to evaluate how the marrow is responding using the ______

indicates if marrow is compensating properly.

exogenous

if reticulocyte count is HIGH ->>>>the cause is ______ and the Marrow is responding appropriately and compensating

(ex: blood loss, autoimmune hemolytic anemia and G6PD)

intrinsic bone marrow problem

if reticulocyte count is LOW/ NORMAL ---> the cause is _________

Marrow not responding adequately