Hematology Flashcards
Blood is made of what percentage of water?
92% water and 8% dissolved substances (solutes)
What percentage is plasma?
50-55%
Whole blood is percentage by volume
Plasma 55%
Formed elements 45%
Plasma is made up of what volume of blood?
50-55% of blood volume of which 90% is water and 10% solute
Whole blood is made of ?
Plasma 55% of total blood
Buffy coat ( leukocytes & plasma) <1%
Erythrocytes 45%
50% of cells in blood is what?
Erythrocytes- RBC
Leukocytes- WBC
Platelet - Thrombocytes
List the plasma proteins
Albumin - most abundant-57%
Globulins
Clotting factors- (fibrinogen)
Buffy coat is made up of what?
- Platelets
2 Leukocytes - neutrophils, lymphocytes, monocytes, eosinophils and basophils
Which is the most abundant leukocyte
Neutrophils
What’s the function of blood!
Respiratory gas exchange
Transport of nutrients and waste
Themoregulation
Hemostasis
Immunity
Regulate cell function, osmotic pressure and pH
Plasma is made up of what?
Water, electrolytes and gases.
Proteins which are; albumin, globulins, fibrinogen, additional immune mediators and clotting factors
What is the function of plasma protein albumin
Albumin is most abundant protein
**Function*
works to maintain colloidal osmotic pressure within circulatory system
What’s the function of blood protein globulin(alpha, beta and gamma globulins
Gamma globulin is immunoglobulin- antibodies
Function of fibrinogen
Protein that converts to fibrin and is necessary for clot formation
Erythrocytes- RBC
Most prevalent blood cell in peripheral blood
Function:
1. Tissue oxygenation, contain Hgb
2. has compensatory capability.ie can increase number in anoxic environment
What the classification of leukocytes?
Granulocyte and agranulocyte
Examples of granulocyte are
Neutrophils
Basophils
Eosinophils
Examples of agranulocytes are
Lymphocytes and monocytes
What are platelets(thrombocytes)?
Platelets are cellular fragments stemming from the megakaryocytrs in bone marrow
Function:
Important for clotting
RBC originate from?
Myeloid stem cells
Granulocyte originates from where?
Myeloid stem cells to
myeloblast to
granulocyte ( neutrophil, basophils and eosinophils)
Cytokines
Small proteins important for cell signalling
What are the classifications of cytokines?
Autocrine action: have effects on cells that secrete them
Paracrine action: have effects on surrounding cells
Endocrine action: may also act on far away cells
What function of cytokines
Play role in inflammation, pain sepsis
Erythropoietin EPO
Red blood cell production
Eosinophils
Nucleus sometimes in 2 pieces
Has bright red granules in cytoplasm
Function:
Control inflammation, phagocytosis, defence agains parasites, allergic reaction
What are functions of eosinophils
Control inflammation
Phagocytosis
Defence against parasites
Allergic reaction
Basophil characteristics
Has bright blue granule in cell protoplasm
Function;
Allergic reaction
Parasites
Basophil function
Inflammation
Allergic reaction
Neutrophils characteristics
Nucleus is segmented
Main component of pus
Function of neutrophils
For response to infection and inflammation. Phagocytosis
Increase in number is indication of infection
Characteristics of platelet
Derived from megakaryocytes
Circulate in inactive state
Activate the clotting cascade
Where do platelet originate from
Megakaryocytes
RBC is made up of what?
4 heme and 4 polypeptide
4 iron atoms
Function of RBC?
Deliver O2
Remove CO2
RBC production and EPO
Low O2 stimulate kidney to produce erythropoietin EPO.
EPO induce bone marrow to produce RBC
In what form do platelet circulate
Inactive form
Neutrophil is important for what?
Acute response to infection and inflammation
What cells are seen in leukaemia?
Increase in immature WBC because immature cells are pushed out too quickly
In immunosuppressives individuals what do you find
Low neutrophil count
EPO is what?
Cytokine produced in kidney
Why should they be on high alert for those receiving erythropoietin? By cancer pt
It can lead to emboli and thrombus formation
EPO in oncology caused what?
Produced adverse reaction such as pulmonary emboli, thrombus and increased relapse in solid tumor
What is the use of EPO
Use to decrease transfusion in palliative patients
EPO uses?
To treat anemia related to kidney dysfunction
To anemia due to chemotherapy
For performance enhancement in athletes
Systolic murmur/he is murmur/flow murmur occurring due to what?
Anemia because increased blood flow over heart valves
Physical signs of anemia are?
Pale skin and mucus membranes is important in diagnosis if anemia is severe- <80
In elderly and individual with CAD what are some signs present in severe anaemia that are signs of CHF
Distended neck vein, tachycardia, right upper quadrant abdominal tenderness, hepatomegaly
Neurological findings (Paresthesia, balance problem, stocking-glove neuropathy and confusion can be found in which patient?
Vitamin B12 deficiency patients
IDA anemia what are the lab findings
Microcytic,
Hypochromic
Ferritin low
Treatment of IDA
Increase iron in diet
Ferrous gluconate, sulphate or fumerate
(Give with vit C)
AE related to IDA treatment and response
Adverse effect(AE):
Nausea + constipation
IV allergic reaction
Response:
start slow, go slow
Laxatives
Increase dietary fibre
B12 anemia lab findings
Macrocyclic, normocromic
Cause of B12 anemia is what?
Malabsorption due to lack of intrinsic factor
Treatment of B12 deficiency
Oral B12 or IM
AE related treatment
Headache, joint pain, dizziness, cold symptoms
Folate deficit lab finding
Macrocytic normocromic
Serum folate test not normally performed by if done it’s low serum folate
Treatment of folate deficiency
Oral folic acid
AE related to folate deficiency treatment
Nausea, loss of appetite, confusion, irritability, allery
Thalassemia anemia lab findings
Microcytic hypochromic
Treatment of thalassmia
Regular transfusions with h chelation therapy to reduce iron overload
What’s the AE related to thalassemia treatment?
Iron overload
Response: chelation therapy to prevent iron overload
Anaemia of chronic disease lab findings
Normocytic normocromic
What is hemostasis
Arrest bleeding
What are the 3 systems involved in hemostasis?
Platelet factors
Platelets
Vasculature
Coagulation factors circulate in what forms?
Inactive forms and require enzyme cleavage to become active
What are the 4 major events in hemostasis?
Vasoconstriction and plug formation
Activation of coagulation factors and inhibition of thrombin
Fibrin clot formation and stablilization
Prevention of further coagulation and clot breakdown
What’s the process of platelet plug formation?
Vasoconstriction
Adhesion
Aggregation
Activation of coagulation factors and initiation of thrombin involves what?
Initiation of coagulation
Amplification phase
Propagation phase
What happens in primary hemostasis?
Injury to vessels exposes subendothlium (collagen) results in
Vasoconstriction of smooth muscles
Adhesion as a result of vWF which act as glue causingAggregation of platelet
Platelet aggregate as a result of fibrinogen and forms a platelets plug
Platelet aggregate perpetuate the phospholipid surface that activates coagulation factor
What is D dimer
A major product of fibrin degradation
When is d dimer test use and for what?
When coagulopathy is suspected- e.g DVT
Secondary hemostasis involves what?
Initiation:
TF release from injured cells and monocytes
TF and factor VIIa activated IX and X to generate thrombin
Amplification:
Thrombin activates factor V to factor Va, factor VIII to VIIIa and more platelet and Factor XI to XIa
Propagation:
More factor Xa is produced when TF/FVIIa complex activated FIX resulting in FIXa which along with FVIIIa cuausinf more X to convert to Xa
Xa and Va with Ca and phospholipids form prothrombinase complex conveying FII (prothrombin to thrombin FIIa)
Fibrin clot formation and stabilization
Thrombin convert fibrinogen to fibrin to form stronger clot
Thrombin activated XIII with cross link fibrin monomers to stabilize it further
Inhibition of coagulation
Thrombin binds to membrane receptor to activate protein C, activated protein C (APC),
APC combine with Protein S, to slow down factor Va and VIII a which slows the process
Thrombin becomes inactivated
Anti thrombin further inhibit thrombin
Fibrinolysis
T-PA convert plasminogen to plasmin which breaks down fibrins and it shows up as D dimer in test
What is anti thrombin
Glycoprotein synthesized in liver
Circulate in blood
Half life 2-3 days
Natural anti- coagulant
Inhibits activation of factors thrombin(factor IIa), factor Xa and to lesser extent factor XIa and Factor IX.
Heparin significantly increase the inhibition rate
What are the 3 factors that increase risk of thrombosis ( Virchow’s triad)
Flow stasis
Endothelial damage
Hypercoagulable state
How does flow stasis impact thrombosis?
Flow stasis occur in immobile individual e.g bedrest, long trip on airplane smoke is because of the increase blood viscosity and in chronic illness such as multiple myeloma
Epithelial damage in virchow’s triad of increase risk of thrombosis
Epithelial damage causes platelets to aggregate. People living with cancer and chronic disease has increased risk of theombosis
Hypercoagulable state
Individual with high platelet count Antos with specific cancer, are prone coagulopathy
Replacing iron in some with high ferritin could cause what?
Iron overload
Most common anemia is what?
Iron deficiency anemia
Most common anaemia in older adult is what?
Anemia is chronic diasese
Treatment of IDA
Oral Ferrous sulphate, ferrous gluconate and ferrous fumerate
What’s the commonest IDA treatment in older adult?
Ferrous fumerate due to less side effect
Side effects of oral iron
Constipation- to mitigate start slow and go slow. E.g once a day and later update to 1-2x/ day
If oral iron is not enough what do you do?
Perenteral iron
E.g venfer or Iron dextran(risk of anaphylaxis but not very common)
IDA is what type of anemia?
Microcytic homochromic anemia
B12 and folate deficiency is what type of anemia
Macrocytic anemia
Treatment of B12 and folate deficiency?
B12- cobalamin oral or injection
Folic acid form that
B12 1000mcg orally is use to treat what?
Help improve B12 deficiency in individuals that have B12 deficiency not related to pernicious anemao
Folate deficiency -anemia in pregnancy
Replace folate to prevent neural tube defect in fetus
If one has Macrocytic anemia how do you treat?
Check if it’s B12 or folate
If you replace flolate and it’s B12 deficiency, it can mask B12 deficiency and B12 deficiency untreated can cause neurological problems
Treating folate when someone has B12 deficiency?
The Macrocytic nature of the problem will go away but B12 deficiency is not addressed. Can cause neurological consequences
ASA
Has fallen out of favour
Used by client who cannot take other anticoagulant
E.g atrial fibrillation
ASA is used for what?
People with thrombotic stroke as secondary prevention
Can ASA be used in children
Not without the advice of Pediatric hematolgist
What mode of action of warfarin?
Inhibit enzyme needed to activate vit K
What are the disadvantages of warfarin?
Need frequent INR monitoring
Interact with many medications
Dose adjust based on INR
INR target 2-3
Heparin is given how
IV or SQ
Heparin and LMW Heparin are what?
Antithrombin activators
What do you use to monitor heparin
PTT or anti 10a assay
1/2 life is 60-90mins
To reverse effect of heparin what do you do?
Discontinue 4hrs before planned surgery
For urgent revasal antidote is Protamine
What’s the antidote for heparin
Protamine
LMW heparin
Indirect anticoagulants
Inhibits 10a and 2a
Administered sq
They don’t require monitoring
If needing to monitor use anti 10
1/2 life 3-6hrs
Renal my cleared
D/c 10-12 hrs before procedure
No antidote
Properties of heparin
Polysaccharide chain
Does not cross membrane (safe in pregnancy and Breast feeding)
How does heparin compare to warfarin
Heparin has rapid onset where is warfarin has slow onset
Does LMW heparin require PTT monitoring
No.
Only fractionated heparin need PTT
Difference between heparin and LMW Heparin
LMW heparin has shorter molecules
Inactivate 10a
Where as heparin inactivate 10a & thrombin
What is an example of direct thrombin inhibitors?
Diabigitran- for treating stroke related nonvalvular aerial fib and prophylactic treatment of veinous embolism
1/2 life 15hrs
Contraindicated in patient with eGFR <30
Diabigitran is contraindicated in which population?
Pt with eGFR <30
+ pregnancy
What is the dose of Diabigitran?
150mg BID
What are the need to know about Diabigitran therapy
Contraindicated in eGFR <30
SE: dyspepsia and gastritis
Do not give with P- glycoprotein (ketoconazole) quinidine (cause bleeding)
Antidote for Diabigitran
Idracuzimuba
Antidote for Diabigitran
Idarucizumab
Antidote for Diabigitran
Idarucizumab 5g IV bolus
What’s and example of factor 10a inhibitor
Rivtoxaban, apixaban and edoxaban
Direct factor Xa (10a) inhibitor ( Riviroxaban, apixaban and edoxaban)
Advantage:
1. fix dose
- No INR
- Low risk bleed
Disadvantage
1 unsafe in pregnancy
- Accumulate in p glycoproteins inhibitor ( ketoconazole) and CYP3A4
Apixaban effectiveness decreased by st John wort
Special consideration in Direct doctor Xa inhibitors (Apixaban and Riviroxaban)
Stop 1-2 day before procedure
Antidote to direct factor Xa inhibitors (Riviroxaban apixaban
Andexa
Cytokine - colony stimulating factor
G-CSG and GM-CSF are use where and for what?
In oncology to stimulate WBC, for neutropenic patient at risk for infection
GCSF to stimulate partial blood stem cells. Use for transplant
What are the side effects of G CSF and GM-CSF
Aches and pain in large bones
Flu like symptoms
WBC will be elevated in CBC
EPO is used where
In renal failure clients dialysis
Was used in oncology but has adverse effect- increase viscosity of blood causes thrombosis like events
Early relapse
MCV <80 means what
Microcytic
If MCV is normal?
Normocytic
If MCV is >100
Macrocytic
When looking at CBC what do you look at first
Hgb
WBC
Platelets
Looking for abnormalities
Decreased hemoglobin you look at what
MCV- volume of cell
MCHC mean corpuscular hemoglobin concentration tell what?
Tells colour of cells
List iron deficiencies that have microcytic RBC
IDA- most common anemia
Hemaglobinopathy - thalassemia
Anemia of chronic disease
Lead poisoning
Anemia has d chronic Disease
Can be microcytic but usually Normocytic
IDA
Defective synthesis of Hgb resulting in smaller that normal cells (microcytic) which contain reduce Amon cell of Hgb (hyoochromic)
Symptoms of IDA
Fatigue
Dyspnea
Pica
Pallor- pale conjunctivia
Taste disturbance
Restless leg syndrome
Headache dizziness
Other symptoms
Glossitis- inflammation of tongue
Angular stomatitis-cracks at mouth connects
Koilonychia- spoon shaped nail
Sickle cell disease
Sickle cell shape which decrease survival of cell
Coagulatanopathy
Test for sickle cell
CBC
High to normal MCV with mild anemia
Sickle cell in blood film
Sicledex- screening test
Hemoglobin electrophoresis
Hemolytic anemia workup
Thalassemia mechanism of deficency
Alpha- Thalassemia (alpha globin chain synthesis defect
Beta - Thalassemia (insufficient or absent production of beta globin chain)
Types of Thalassemia
Thalassemia minor (trait) mike asymptomatic microcytic anemia
Thalassemia intermedia
Thalassemia major-develop at early age(before 1yr) results in sever anemia
Lab: CBC anemia with low MCV, normal ferritin
Nucleated RBC film
Anemia of chronic disease
2nd most common anemia
Decrease RBC production by bone marrow
What are the causes if anemia or chronic disease
Cancer
CKD
Liver churros is
Hepatitis B &C
Auto immune (SLE and RA)
Infection (HIV/AIDS, osteomyelitis and endocarditis)
DM
Heart failure
Lab work for anemia of chronic disease
CBC
Mild anemia (Hgb 100-110g/L with normal MCV)
Low reticukocyte
Normal or high ferritin
Low serum iron/TICB/ soluble transferrin receptor
Increased CPR or ESR
Anemia of chronic disease is more common in which age group
Older adults
Why is inflammation a marker in anemia of chronic disease
It’s thought that the inflammation is responsible for the degradation of the RBC
Lead poison
Rare, found in children
Hypochromic microcytix anemia
Lead interfere with heme, causing RBC destruction and a decrease in Hgb
Dx: serum lead levels
Further diagnosis of iron deficiency anemia
Serum ferritin- diagnostic test of choice for IDA
( low level)
Serum iron level
What’s the test of choice to diagnosing Iron deficiency anemia?
Serum ferritin
