Lab Med - Anemia & Coagulation

reticulocyte

the precursor to a RBC

1%

What % of circulating RBCs will be reticulocytes?

1. decreased production

2. increased destruction

What are the 2 possibilities that would result in anemia?

decreased

Decreased RBC production results in anemia; we would see a(n) [increased, decreased] reticulocyte count.

increased

Increased RBC destruction results in anemia; we would see a(n) [increased, decreased] reticulocyte count.

anemia

condition in which there is reduced O2 delivery to tissues; results from decreased production or increased destruction of RBCs (or excessive blood loss!)

- low Hgb

- low Hct

- low RBC

- indices to indicate which type of anemia it is!

What are some CBC values we have to pay attention to when we are diagnosing anemia? Are these lab values high or low?

- easier release of O2 to tissues and more efficient RBCs

- CV: heart works harder to keep tissues perfused

- Skin: vasoconstriction & deoxygenated Hgb causes pale, dusky color

- poor wound healing

- Bone Marrow: increases RBC production due to increased erythropoietin from the kidney

What are some effects of anemia on the body?

- CV: angina, intermitten claudication, muscle cramps, palpitations

- neuro: headaches, lightheadedness, roaring in ears, fainting, irritability, restlessness

- Pulm: DOE

What are some common symptoms of anemia?

tachycardia, mucosal pallor, orthostatic BP

What are some common signs of anemia?

smooth tongue or mucosal changes!

What are some indications on a pt that could tell us about nutritional deficiencies that cause anemia?

- microcytic, hypochromic

- macrocytic

- normocytic, normochromic

- other

What are the classifications of anemia?

microcytic anemia

Classification of Anemia:

- anemia w MCV < 80

Causes:

- thalassemias

- iron deficiency anemia

- anemia of chronic disease

- sideroblastic anemia

TICS

- thalassemias

- iron deficiency anemia

- anemia of chronic disease

- sideroblastic anemia

What pneumonic do we use to remember the causes of microcytic anemias? What does it stand for?

Iron Deficiency Anemia

Classification of Anemias:

most common microcytic anemia!

- chronic anemia that will eventually exhaust iron stores

- microcytic, hypochromic RBCs

breast milk provides a marginally adequate supply (cow's milk is low in Fe)

- infant formulas fortified with Fe

What type of iron sources do infants have? What's high in iron? What's low in iron?

milk anemia

type of anemia infants can get

- the idea that infants need supplemental feedings or supplemental Fe as they begin to grow

True!

True/False:

If an adult has a minimal Fe deficiency (most likely due to diet), it's usually subclinical, unless another issue exacerbates the deficiency.

- menstrual loss

- malabsorption (dietary Fe is adequate but not properly absorbed)

- pregnancy

Most adults have a minimal iron deficiency that are subclinical. It becomes clinical when one of the following issues may exacerbate the deficiency.

CBC - low H&H, low MCV

- Fe, TIBC, % saturation, ferritin levels

How do we usually find iron deficiency anemia? What test do we run, and what do we find?

ferritin level

What lab do we use to monitor the status of a patient diagnosed with iron-deficiency anemia?

ferritin

storage form of Fe

TIBC

total iron binding capacity

- measures the blood's capacity to bind with transferrin

transferrin

transports circulating Fe

% saturation

test run that tells us the amount of Fe binding sites that are occupied

- start with oral Fe supplement

- monitor with ferritin levels every 2-3 mos

- if no response: consider IV Fe treatment

What is the treatment plan for iron deficiency anemia?

thalassemia

Classification of Anemia:

- a microcytic anemia

- decreased rate of production of globin chains due to a defect in coding, sequencing, transcription, or processing in gene translation

Hgb electrophoresis

What test do we run to diagnose thalassemia?

by which global chain is affected

- alpha thal - decreased production of alpha chain

- beta thal - decreased production of beta chain

How do we classify thalassemia? explain.

beta thalassemia

thalassemia:

caused by point mutations rather than deletions resulting in reduced or absent beta-globin chain synthesis

- beta chain production is affected

- can be homozygous (beta thal major) or heterozygous (beta thal minor)

Beta0

Beta Thalassemia:

- defects that result in absent beta-globin chain expression

Beta+

Beta Thalassemia:

- defects that result in reduced, but not absent beta chains

Beta Thalassemia Minor

heterozygous beta thalassemia (1 normal, 1 abnormal beta chain)

- clinically, virtually no symptoms

- very mild anemia since erythropoiesis is only mildly inefficient

- must check Fe level

beta thalassemia intermedia

homozygous for mild beta thalassemia

- chronic hemolytic anemia

Beta thalassemia major

homozygous (both beta chains are defective)

- differing degrees of severity

- not clinically seen until 6 mos of age

- clinically, severe, life-threatening anemia

- growth/bone problems

supportive transfusions of RBCs to combat ineffective erythropoiesis

What is the treatment for beta thalassemia major?

alpha thalassemia

Diseases in which there are insuffiecient alpha-globin chains due to gene deletions

Mediterranean

What population is most often affected by beta thalassemia major?

alpha thal silent carrier

silent carrier of alpha thalassemia; asymptomatic

alpha thal train/minor

Hgb A is curtailed, but no increased Hgb A2 or F

- clinically normal, mild microcytic anemia

hemoglobin H disease

deletion of 3 of the 4 loci coding for the alpha chains of hemoglobin

- chronic hemolytic anemia of variable severity

- pallor

- splenomegaly

Bart's hemoglobin

Alpha thalassemia in which all 4loci are deleted and you have 4 gamma chains:

- this has a high affinity for O2, but doesn't release it to the tissues

fetus will die in 2nd trimester from anemia and congestive heart failure

What is the prognosis for Bart's hemoglobin patients?

Vitamin B12 deficiency anemia (aka pernicious anemia)

Classification of Anemia:

- macrocytic anemia (megaloblastic)

- caused by lack of vit B12, but primarily due to lack of intrinsic factor which is necessary to absorb vit B12

- inability to make IF may be result of chronic gastritic, or the result of a gastrectomy

Vit B12 deficiency anemia

What type of anemia does a patient have if they present with the following symptoms:

- weak muscles

- peripheral neuropathy

- difficulty walking

- nausea/anorexia

- weight loss

- irritability

- lack of energy/tiring easily

- diarrhea

- smooth and tender tongue

- tachycardia

- megaloblastic

northern European descent

What ethnicity of people are most often affected by Vitamin B12 deficiency anemia?

vit B12 level in serum

What lab levels are we going to use to diagnose vitamin B12 deficiency anemia?

Vitamin B12 injections

What is the treatment for Vitamin B12 deficiency anemia?

folate deficiency anemia

Classification of Anemia:

- macrocytic anemia

- can result from deficiency in diet, malabsorption, increased demand, excessive loss, or defective synthesis

folate levels:

- serum folate - indicator of recent folate intake

- RBC folate - best indicator of long-term folate stores; low RBC folate may indicate a prolonged folate deficiency

What are the labs we'll run to diagnose folate deficiency anemia? What does each one tell us?

folate replacement

What do we treat those with folate-deficiency anemia?

folate deficiency anemia

If a patient presents with the following s/s, what anemia would you diagnose them with:

- fatigue

- lethargy

- breathlessness

- feeling faint

- headaches

- pale skin

- palpitations

- tinnitus

- loss of appetite/weight loss

renal failure, RA, lupus

What are some chronic diseases that could contribute to the anemia of chronic disease?

treat the underlying cause

What is the preferred treatment for those with anemia of chronic disease?

whether the defect is intrinsic or extrinsic to the RBC

How are hemolytic anemias classified?

intrinsic

Classification of Hemolytic Anemias:

- membrane defects

- glycolytic defects

- oxidation vulnerability

- hemoglobinopathies

extrinsic

Classification of Hemolytic Anemias:

- immune (autoimmune or drug-induced)

- microangiopathic

- infection (plasmodium, clostridium, borrelia)

- hyperpslenism

- burns

hemolytic anemia

Classification of Anemia:

- some external force is causing the RBCs to lyse

- could also be autoimmune

- shortened RBC survival

- compensatory mechanism exists to increase BP, so not initially apparent

- increased bilirubin

- increased reticulocytes

- + direct Coombs test

- decreased haptoglobin

What are the labs that will indicate a patient has hemolytic anemia?

remove stimulus and support them

- if immune mediated, use steroids or immunosuppressive drugs

What is the treatment for patients that have hemolytic anemia?

direct Coombs test

indicates the presence of antibodies or complement on the surface of RBCs

- also known as a direct antiglobulin test (DAT)

hemoglobin S

most common hemoglobinopathy

- any of these present = sickle cell syndrome

sickle cell syndrome

Sickle Cell Anemia:

- present when there is any Hgb S present (AS, SS, SC)

sickle cell disease

Sickle Cell Anemia:

- present when the pt is homozygous for Hgb S (SS), so the pt lacks normal Hgb A

sickle cell trait

Sickle Cell Anemia:

- present when the patient is heterozygous for Hgb S (SA)

African Americans

What population has a much higher gene frequency of sickle cell anemia?

become less flexible and undergo intravascular dissolution

Sickle Cell Anemia:

- defective in terms of reoxygenation and becomes insoluble as deoxygenated Hgb filaments take on an elongated shape

This can be reversible! But what happens with repeated episodes to older RBC?

sickle cell trait

Sickle Cell Anemia:

- heterozygotes

- normally no clinical signs

- believed to actually confer protection against falciparum malaria infection!

- be cautious w air travel and anesthesia

- low O2 tension (hypoxia)

- low pH (acidosis)

- increased body temp (fever)

What factors may cause an increase of sickled cells?

- severe hemolytic anemia

- bone marrow aplasia

- painful vaso-occlusive episodes

- bone deformity

What are some things that people with sickle cell anemia will have to deal with for life?

Hgb electrophoresis

lab used to confirm/deny sickle cell anemia

avoid triggers, take folic acid supplements, supporting treatments

What are the treatments for sickle cell anemia?

G6PD Deficiency Anemia

Classification of Anemia:

- lack of G6PD (enzyme that protects RBCs)

- X-linked recessive

- causes hemolytic anemia

- triggered by a stressor

African, Asian, and Mediterranean descent

What populations are most affected by a G6PD deficiency anemia?

certain oxidative drugs or fava beans

What are some stressors that can trigger G6PD deficiency anemia?

remove stressor and support them

What are the preferred treatments for G6PD deficiency anemia?

increased destruction

We classify anemias generally into 2 categories: (1) decreased production and (2) increased destruction. Which are hemolytic anemias classified as?

aplastic anemia

Classification of Anemias:

- most severe form of bone marrow failure

- results in reduction/depletion of all hematological marrow stem cells (pancytopenia)

- often cellular marrow is replaced by fat

- can be due to drug exposure, viral infections, chemical toxins, or irradiation

bone marrow aspirate/biopsy

What test do we do to diagnose aplastic anemia?

bone marrow/stem cell transplant

What is the preferred treatment for aplastic anemia?

- hypercoagulable

- excessive bleeding

Need to do a GOOD history!!

How do you know if a patient has a bleeding disorder?

- history of frequent/prolonged bleeding (gums brushing w bleeding, excessive/recurrent nosebleeds)

- bruises without apparent injury

- prolonged bleeding after dental extraction

- excessive menstrual bleeding

What are some examples of "being a bleeder" that could lead us to believing a pt has a coagulation disorder?

- gums bleeding w brushing

- excessive/recurrent nosebleeds

What are some specific signs to look for when determining if a patient has a history of frequent/prolonged bleeding?

hemostasis

the process of cessation of blood loss following a vascular injury, maintenance of fluid state in the vascular compartment, and the dissolution of the clot formed to prevent bleeding

- lack of this will lead to hemorrhage

hemorrhage

Failure of hemostasis leads to _________.

thrombosis

Failure to maintain fluidity leads to ________.

1. vascular system

2. platelets

3. coagulation cascade

4. fibrinolytic

What 4 systems does the hemostatic mechanism involve?

vascular system

the circulatory system that is involved in hemostasis

small vessels

- large vessels can't constrict enough to prevent blood loss

this is why large injuries (i.e. stab wound) cannot be fixed by our own clotting abilities!

The vascular phase of hemostasis affects only the [large, small] vessels. Why?

short-term

The vascular system is one of the systems involved in hemostasis. Vasoconstriction of small vessels is a [long-term, short-term] fix.

platelets

- form an effective primary hemostatic mechanism

- plug small holes in blood vessels

- these will eventually be reinforced with a gel-like protein (fibrin)

coagulation

defined as a chemical process whereby plasma proteins interact to convert the large, soluble plasma protein, fibrinogen, into the stable, insoluble gel = fibrin

thrombin

enzyme that converts fibrinogen --> fibrin

1. intrinsic pathways

2. extrinsic pathways

What are the 2 pathways that the coag pathway is broken down into before merging?

common pathway

the pathway formed when the intrinsic & extrinsic pathways merge during coagulation

intrinsic pathway

coag cascade:

activated by substances normally present within the blood itself

extrinsic pathway

coag cascade:

- triggered by tissue thromboplastin which isn't present in blood, but is released from injured cells

fibrinolytic system

- limits coagulation to the sites of injury and wound repair

- prevents coagulation from becoming more widespread and uncontrolled

- plays important role in balancing clot formation and clot dissolution

plasmin - digests (breaks down) fibrin & fibrinogen

What is the primary enzyme of the fibrinolytic system? What does it do?

petechiae

Failure of Hemostasis:

small, pinpoint hemorrhages