Formation and function of blood

Dr Roshan Niloofa
 Composition of Blood

• Blood is responsible for…..

– Transporting gases (oxygen & carbon dioxide)
– Transporting waste products
– Transporting nutrients
– Helping remove toxins from the body
• Blood makes up 6–8% of our
total body weight.

• Normal adult blood volume is 5 L.

• Blood is made up of cellular

material in a fluid called plasma.
• Blood is a circulating tissue consisting of three
types of cells.
1. Red Blood Cells  Erythrocytes
2. White Blood Cells  Leukocytes
3. Platelets  Thrombocytes

• The cells listed above are suspended in a liquid

known as plasma.
 Formation of Blood
• Hematopoiesis  the formation and development of blood cells
• In adults the cellular elements are produced in the bone marrow.
• Some WBCs are produced in the lymphatic tissue and bone marrow.
• Blood cells need certain nutrients to form properly.
• Examples include…..
—Iron
—Folic acid
—Vitamin B12

•All blood cells formed come

from a hematopoietic stem cell.
•These cells can become any
blood cell.
 Composition of Blood
• The blood is made up of cells
that are suspended in liquid
called plasma.
• Plasma makes up 55% of the blood.
• Plasma is made of 90% water and
10% proteins, lipids, carbohydrates,
amino acids, antibodies, hormones,
electrolytes, waste, salts, and ions
• Blood cells make up the remaining
45% of the blood.
• Red blood cells make up 99% of the blood cells.
• White blood cells and platelets make up the other 1%.
• Each type of blood cell performs a different function.

• Red blood cells (Erythrocytes)

• White blood cells (Leukocytes)

• Platelets (Thrombocytes)
 Red Blood
Cells
• Erythrocytes or RBCs
— Most abundant cell in the blood
(4 million – 6 million per microliter of blood)
— Formed in the bone marrow
— Mature forms do NOT have a nucleus
— Shaped as biconcave disks
— 6-8 micrometers in diameter
—Life span of about 120 days
— Hemoglobin (iron protein)is
found in the RBC
— Hemoglobin carries oxygen from the
lungs to the rest of the body and carbon
dioxide binds to the RBC and is taken to
the lungs to be exhaled.
 White Blood Cells
• Leukocytes or WBCs
— Largest sized blood cells
— Lowest numbers in the blood
(4,500 – 11,000 per microliter)
— Formed in the bone marrow
and some in lymph glands
— Primary cells of the immune system
— Fights disease and foreign invaders
— Contain nuclei with DNA,
the shape depends on type of cell
— Certain WBCs produce antibodies
— Life span is from 24 hours to several years
— Size is 8-20 micrometers in diameter
— There are five different types of WBCs
1. Neutrophils
2. Eosinophils
3. Basophils
4. Lymphocytes
5. Monocytes
 Platelets
— Thrombocytes or PLTs

— Formed in the bone marrow

— Fragments from the cytoplasm of megakaryocytes

— Smallest of the blood cells

— 1-4 micrometers in diameter

— Shape can be round, oval, or appear spiky

— Life span of around 8-12 days

• Platelets
— Involved in the clotting process

— Seal wounds and prevent blood loss

— Help repair damaged vessels

— 150,000 – 400,000 per microliter of blood

—Platelets stain bluish with reddish or purple granules

Eosinophil and red blood
cells

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White blood cell
T cells

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White blood cell

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White and red blood cells

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White blood cell

False-coloured transmission electron micrograph of a leukocyte (white blood cell). Nuclear lobes are shown by the label B.
Credit: David Gregory and Debbie Marshall, Wellcome Images

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Lymphocyte and red blood cell

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Bone marrow

Light microscopy image of bone marrow. Red blood cells can be seen in red.
Credit: Ivor Mason, Wellcome Images.

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Blood film

Light microscopy image showing a normal blood film with red blood cells and several white blood cells (leukocytes). Blood films are small amounts of blood smeared across a slide and examined
under the microscope. They can be used to investigate disorders of the blood and some parasitic infections, including malaria.
Credit: Wellcome Images.

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Blood cells

Digital artwork showing microscopic detail of red blood cells, platelets and white blood cells.
Credit: Wellcome Images.

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Red blood cells

Scanning electron micrograph of red blood cells clearly showing their biconcave disc shape.
Credit: Annie Cavanagh, Wellcome Images.

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Blood transfusion
Aim is to maximise patient safety by:

• Helping clinicians to decide when allogeneic red cell

transfusion is appropriate
• Minimising the avoidable risks of transfusion
• Helping clinicians to provide appropriate advice on
options for treatment, in particular where patients
are anxious about the risks of transfusion.
 How safe?
• The risks from blood transfusion have never been
lower, the risk of any adverse outcome is very small,
at 1 in 12,000, less than the risk of being killed in a
road traffic accident or of dying from flu.
• No transmission of variant Creutzfeldt-Jakob disease
by transfusion has yet been documented and the risk
of contracting HBV, HCV or HIV from blood
transfusion is minimal.
• Blood transfusion remains essential for the
continued safe performance of major surgery.
• The fact that profound anaemia can be
tolerated perioperatively does not mean that
it is advisable or acceptable.
• In a healthy patient, mild degrees of anaemia
are well tolerated and transfusion can be
avoided.
• Autologous donation is only appropriate for
surgical patients undergoing major blood
losing operations, where there is a likelihood
that it will be used.
• If a patientís haemoglobin level is greater than 145
g/l then for most common operations autologous
blood should not be collected, as 90% would only be
discarded.
• Improvements in the quality of transfused blood, by,
for example, the removal of white blood cells,
eliminate the theoretical risk that transfusion might
lead to cancer recurrence or postoperative infection.
 Haemoglobin transfusion thresholds

• Guidelines and consensus statements have

consistently expressed the transfusion threshold as
a range, usually between 70 and 100 g/l
haemoglobin.
• Clinical indicators further defining the need for
allogeneic transfusion in between.
• No evidence was found to suggest that
cardiovascular function is improved at haemoglobin
values >100 g/l.
 Transfusion is unjustified at haemoglobin levels >100 g/l.

• Experimental data from healthy individuals

indicates that electrocardiogram (ECG)
changes of myocardial ischaemia appear at
haemoglobin levels below 50 g/l.
• A review of consensus statements supported
a lower limit of 70 g/l and also suggested that
patients with cardiovascular problems should
have this limit raised to 80 g/l.
Transfusion is required at haemoglobin levels <70g/l.

• The largest randomised controlled trial (RCT) of

transfusion thresholds was performed in over 800
patients admitted to intensive care.
• Patients were randomised to a conservative (70-90
g/l) or liberal (100-120 g/l) threshold
• No difference in 30 or 60-day mortality was found.
• In addition, there was no significance difference in
ventricular dysfunction.
 Transfusion is required at haemoglobin levels <70g/l.

• In another study,428 low risk CABG patients were

randomised to a restrictive (<80 g/l) or liberal (>90
g/l) transfusion policy.
• No difference in mortality, postoperative MI, or
significant ventricular complications was seen, nor
was there any significant effect on patient
rehabilitation.
• Patients under 55 years of age, or with less severe
disease, had statistically better survival using the
conservative policy
 Patients with cardiovascular disease
• Or those expected to have covert cardiovascular
disease (e.g. elderly patients or those with peripheral
vascular disease) are likely to benefit from
transfusion when their haemoglobin level falls below
90 g/l.
 The factors determining risk of allogeneic
transfusion are:
• low preoperative haemoglobin / haematocrit, either before intervention
or on day of surgery
• low weight
• small height
• female sex
• age over 65 years
• availability of preoperative autologous blood donation (PABD)
• estimated surgical blood loss
• type of surgery
• primary or revision surgery.
 PREOPERATIVE AUTOLOGOUS BLOOD DONATION

• preoperative autologous blood donation (PABD) is a

convenient, predictable, safe and widely practised form
of transfusion support.
• PABD cannot be made available to all patients, since it
requires time to pre-donate and a starting
haemoglobin greater than 110 g/l,94 which effectively
excludes most emergency surgery.
• For a preoperative autologous blood donation
programme to work, hospital admission and operative
dates must be guaranteed, as donated blood has a
limited storage life of 35 days.
 PABD should be targeted to:

• Men who present with haemoglobin 110-145

g/l
• Women who present with haemoglobin 130-
145 g/l.
 ERYTHROPOIETIN

• Human erythropoietin is a glycoprotein hormone

that regulates erythropoiesis.
• Hypoxic or haemorrhagic stress results in the
secretion of erythropoietin by the kidney.
• Erythropoietin is available as recombinant human
erythropoietin (epoietin a and b) and has been
widely used in the treatment of anaemia of chronic
renal failure.
 The effect of erythropoietin

• The effect of erythropoietin in minimising

allogeneic blood exposure compared to
placebo has been studied in patients
undergoing orthopaedic , cardiac or colon
cancer surgery.
• With the exception of one study, all showed
a significant reduction in allogeneic
transfusion
 Erythropoietin

• Erythropoietin use should be targeted to

patients aged under 70 years who are
scheduled for major blood losing surgery and
who have a presenting haemoglobin <130 g/l.
• Erythropoietin can be used to prepare patients
with objections to allogeneic transfusion for
surgery that involves major blood loss.
 DOSE OF ERYTHROPOIETIN

The two dosing schedules most widely used are:

• 300 u/kg subcutaneously for 14 days beginning 10 days
preoperatively (approximately £2600/course/80 kg)
or
• 600 u/kg subcutaneously three times weekly and on
day of surgery (approximately £1,600/course/80 kg)
Erythropoietin
• treatment has always been accompanied by oral or
intravenous iron therapy.
• If erythropoietin brings about a >0.50 rise in the
patientís haematocrit, a 500 ml venesection should
be undertaken.
• Patients receiving erythropoietin should have weekly
haematocrit checks.
• In fit patients undergoing major surgery,
erythropoietin can be used in combination with
autologous blood collection to reduce allogeneic
transfusion.
 ACUTE NORMOVOLAEMIC HAEMODILUTION

• Acute normovolaemic haemodilution (ANH) is

the removal of whole blood and the
restoration of blood volume with acellular
fluid, shortly before anticipated significant
surgical blood loss.
• In the context of elective surgery this may be
performed prior to surgery or during the early
part of the surgical procedure,
ANH is potentially most useful for a patient meeting all of the
following criteria:

• Substantial anticipated blood loss a relatively

low target haemoglobin (intraoperatively and
postoperatively)
• Relatively high initial haemoglobin
• ANH should be limited to patients with a
haemoglobin level sufficiently high to allow
1,000 ml of blood to be removed
 Complications of Blood Transfusion

O2 Transport

• Shift to left in O2-Hb dissociation curve so RBC's have

increased affinity for oxygen and there is less available
to tissues.
• Warm blood and avoid other things that shift O2-Hb
dissociation curve to the left such as alkalosis (bicarb)
and hypothermia.
 Complications of Blood Transfusion
• Transfusions Reactions
• Citrate Intoxication and Hyperkalemia
• Hypothermia
• Acid-Base Disturbances
 Complications of Blood Transfusion
• Microaggregates
• Infectivity-Hepatitis, HIV, CMV, Syphilis
• Dilutional Coagulopathy
 Alternatives to Transfusion

1. Minimize blood loss - controlled hypotension

2. Tolerate a lower HCT

3. Transfuse Autologous Blood

4. CELL SALVAGE
 Alternatives to Transfusion

3. Transfuse Autologous Blood

a. Preoperative donation and storage - 72 hours to
normalize plasma proteins.
b. Acute preoperative phlebotomy and hemodilution -
inexpensive compared to preop donation.
Progressively decreases the Hct of units saved.
c. Perioperative blood salvage from the surgical site
 ASPIRIN

• The most commonly prescribed antiplatelet drug is aspirin

• Aspirin increases blood loss in patients undergoing surgery.
• Aspirin is an irreversible inhibitor of cyclo-oxygenase, which platelets
(unlike vascular endothelium) are unable to regenerate.
• Aspirin therapy should therefore, in theory, be discontinued for seven
days (the life span of a platelet) prior to surgery.
• Concern has been expressed about the potential deleterious effects of
withdrawing aspirin treatment prior to surgery, on the grounds that
patients who have their aspirin therapy withheld may be more vulnerable
to ischaemia in the aspirin-free period, and that this may be more
hazardous than the consequences of bleeding in the immediate
postoperative period.
 ASPIRIN

• Although aspirin increases postoperative bleeding,

this is not always accompanied by an increased
requirement for allogeneic transfusion.
• Re-operation for control of continuing nonsurgical
haemorrhage is more common in those patients who
receive preoperative aspirin.
• However, a case control study of 8,641 patients
found significantly higher mortality in the group of
patients whose aspirin had been stopped.
 APROTININ

• Aprotinin has been shown to reduce blood

loss in cardiac and liver surgery.
Side effects:
• inadvertent re-exposure of a patient to
aprotinin, with a high risk of an anaphylactic
reaction
• possible increase in thrombosis using a drug
with anti-fibrinolytic properties.
 DOSE

• The dose required for a significant effect on

blood loss appears to be high, with the
majority of studies using a loading dose of 2
million units followed by 0.5 million
units/hour during surgery.
• A smaller dose of 20,000 units/kg was not
shown to be effective in one large study.
 TRANEXAMIC ACID

• Tranexamic acid inhibits fibrinolysis by

blocking the lysine binding sites of
plasminogen to fibrin.
• It has been used primarily in gynaecology to
reduce menstrual blood loss.
• More recently it has also been shown to be
effective in reducing bleeding in cardiac
surgery.
 DOSE

• Tranexamic acid has been used at 10-15

mg/kg
• As tranexamic acid has a half-life of two hours
there are theoretical advantages to
administering further doses postoperatively.
• One study continued tranexamic acid eight
hourly for three days