The blood core final

Advanced Clinical Science 1
First Semester
Iyad Hussein
DDS, MDentSci(Leeds), Stat.Exam (GDC/UK), MFDSRCPS(Glasg)
Dubai College of Dental Medicine

Functions
and Properties of Blood
 A vehicular organ that perfuses all other organs
 Blood and interstitial fluid deliver nutrients to cells
and remove wastes
 Haemostatic governors are carried to and from
appropriate sites

Functions of Blood
 Transport:
 Carriage O2
 Platelets that contributes to the haemostatic process
 chemicals dissolved in plasma (nutrients, waste,
hormones, etc)
 metabolic heat for disposal

Functions of Blood
 Regulation:/Homeostasis
 pH: plasma contains pH buffers
 Temperature: plasma water absorbs heat
 Osmosis: plasma solutes maintain osmolality

Functions of Blood
 Protection:
 plasma precursor proteins form blood clot when
stimulated
 Suspended cells attack bacteria and viruses and
 plasma contains antibodies for immunity

Blood
 5 litres of blood in an
adult
 7% of body weight in
adults and 8-9% in
children
 55% H2O and dissolved
solutes (plasma) & 45%
Cells (formed elements)

Fluid compartments
ICF
ECF
Interstitial
Capillary
Membrane Cell Membrane
~ 15% of
body weight
~ 40% of
body weight
~ 5% of
body
weight

Plasma
 A clear yellowish fluid remaining after
the cells have been removed
 Plasma
 Electrolytes
 Proteins
 Fibrinogen: clotting
 Albumins: osmosis
 Globulins: antibodies
 Nutrients
 Aminoacids
 Nitrogenous waste
 Gases
 Vitamins
 Hormones
 Carbohydrates
 Lipids
 Serum is the fluid and solutes remaining
after the cells and fibrinogen have been
removed

Blood Cells (Formed elements)
Haematopoiesis

Blood cells
 All blood cells originate
from the bone marrow:
pelvis, vertebrae,
irregular flat bones, ileac
crest
 Haematopoiesis: Stem
cell differentiation,
proliferation and
maturation along
distinct specialised cell
lines

Formed
elements (Cells)
 Leukocytes
 Granulocytes
 Neutrophils: Phagocytosis
 Eosinophils: Allergic
response
 Basophils:Release
Histamine and heparin-
inflammatory response
 Agranulocytes:
 Lymphocytes: cell
mediated and humoral
immunity
 Monocytes: Phagocytosis
 Erythrocytes:
Haemoglobin O2
transport
 Thomboctyes: Blood
clotting

Erthrocytes (Red blood cells)
 Biconcave flexible discs (like
doughnuts with thin centres
rather than holes)
 Erythropoitein originating
from kidney stimulates RBC
formation in reponse to
hypoxia of tissues/cells
 Normally RBC= 4.2-6.2
million cells/mm3
 Haematocrit: refers to
proportion of cells or
formed elements (RBC
mainly) indicating viscosity
of blood

RBCs
 RBC production and maturation
depends on
 VB12, Fe, Folic acid, VB6,
aminoacids
 Haemoglobin:
 Globin portion, two pairs of amino
acid and
 Four Haeme groups, each
containing a ferrous iron atom to
which 02 attaches to
 Haeme provides the red colour of
haemoglobin
 Oxyhaemoglobin: 02 saturated Hb:
bright red colour arterial blood
 Deoxyhaemoglobin: found in
venous blood. Reduced

 Small CO2 proportion carried in
blood by Haemoglobin
(Carbaminohaemoglobin)
attached to Nitrogen in an
aminoacid group a different site
from 02
 Carbon is transported in blood
as Bicarbonate ion.
 O2 can be easily be displaced by
carbon monoxide which binds
tightly to Fe causing fatal
hypoxia
 Life span of RBC is 120 days
 Aged RBCs undergo
phagoctyosis in the spleen or
liver

Hb
 Hb broken down into
 Globin: Aminoacids
 Haeme:
 Iron: liver haemosedrin or
ferritin
 Bilirubin: liver then bile
after being conjugated
 Excess haemolysis of RBC
severe serum bilirubin
leading to Jaundice

Leukocytes
 Number 5-10,000/mm3
 1% of blood volume
 Granulocytes (3 types)
 Agranulocytes (2 types)
 Leukopoeisis: is the
production of white blood
cells (WBCs)
 Leukopoeisis stimulated by
colony stimulating factors
(CSFs) produced by
macrophages & T
lymphocyes
 Granuloctye CSF or multi
CSF (interleukin 3 (IL3)
may be produced to
increase certain type of
WBCs during an
inflammation
 WBC leave capillaries by
diapedesis when defence is
needed

Leukocytes
Agranulocytes
 Lymphocytes: 30-40% of WBC
 T-lymphocytes: Cell mediated
immunity
 B-Lymphocytes: Humoral
immune response
 Plasma cell: antibodies
produced
 Memory cells
 Neutrophils (Polymorphnucleates-
PMNs) 50-60% of WBC: survive 4
days. They are the first to respond to
any tissue damage. Immature PMNS
Increased in numbers when a
bacterial infection occurs.
Phagocytosis

Leukocytes
Granulocytes
 Basophils: appear to migrate
from the blood into tissues
and become mast cells. They
release Histamine and
heparin
 Eosinophils: combat the
effects of histamine.
Increased in allergic reactions
and parasite infection
 Monocytes: They can enter
the tissues and become
macrophages Act as
phagocytes when tissue
damage occurs

A differential count
 Indicates the
proportions of specific
types of WBCs in the
blood and helps make a
diagnosis
 Bacterial infection:
increases PMNs
 Allergic reaction:
increase eosinophil
counts

Thrombocytes
 Platelets
 Essential for Haemostasis
 Not cells
 Smaller Non nucleated
fragments from larger
megakaryocotes
 Platelets stick to damaged
cells as well as each other
 Platelet plug formed
 Adhere to rough surfaces and
foreign material
 ASA (Acetosalisylate acid)
Aspirin reduces this adhesion
increasing bleeding tendency
 Primary haemostatic plug
initiates clotting process or
haemostasis/coagulation
 Von Willebrand factor
essential for platelet adhesion

Stem Cell
Erythroblast
Normoblast
Reticulocyte
Erythocytes
Myeloblast
Eosinophilic
Myelocytes
Band Cell
Segmented cell
Eosinophilic
granulocyte
Neutrophilic
Myelocytes
Band Cell
Segmented cell
Neutrophilic
granulocyte
Basophilic
Myelocytes
Band Cell
Segmented cell
Basophlic
granulocyte
Monoblast
promonocyte
monocyte
(agranulocyte)
Lymphoblast
Prolymphocyte
Lymphocyte
(agranulocyte)
T-Lymphocyte B-Lymphocyte
Megakaryoblast
Megakaryocyte
Thombocytes
Platelets

The Blood
Remember
 Erythrocytes, Leucocytes,
Thrombocytes

http://www.youtube.com/watch?v=_HgTRo
esu8M&list=PLDDDE4C372FAB6A37

Haemostasis Step 3
Coagulation cascade
Inactive factors in the blood
become active
Haemostasis Step 2
Thromocytes adhere to each other
and tissue
Platelet plug: primary haemostasis
Haemostasis Step 1
Immediate response Vasoconstriction of blood vessels
Haemostasis: Classical concept

Blood disorders
 Clotting /
coagulation
disorders
 Platelet disorders
 Vascular disorders
 Blood dyscriasis

Haemostasis:
 Primary Haemostasis
(Vascular & Platelet)
 Secondary Haemostasis
(Blood Clotting)
 Tertiary Haemostasis
(Fibrinolysis)
http://www.youtube.com/watch?v=HFNWG
Cx_Eu4&list=PL08FA078F564D6A69

Primary Haemostasis
 Tissue injury
 Vasoconstriction
 Retards blood loss
 Platelets adhere to
subendothelial cells
 Primary platelet plug
forms with vWf
 ADP, Thrombaxane
A2(TXA) PAF released
 Increased platelet
adhesion

Abnormalities
in 1o Haemostasis
 Abnormal platelets
numbers
 Abnormal vWF
 Defects in blood wall
vessels
 Failure of primary plug
 Leads to
 Haemorrhage from
mucosal surfaces
 Epistaxis
 Melaena
 Haematuria
 Petechiae
 Ecchymotic
haemorrhages
 Immediate bleeding

1o Haemostasis inhibitors
Natural inhibitors of platelet
function Medical inhibitors
 Bradykinin
 Prostacyclin
 Nitric oxide
 Released by endothelial cells
 Inhibitors of vWF
 Aspirin for prevention of
thrombosis by disabling
cyclooxygenase and
preventing thrombaxane A2
from being released thus
preventing platelet adhesion

2o Haemostasis
 Fibrin formation
 Platelet plug:
Phospholipid surface for
factor binding
 CASCADE
 Intrinsic
 Extrinsic
 Common

Coagulation cascade
Intrinsic pathway: activated by
endothelial injury in blood vessels
Extrinsic pathway activated
by tissue and platelet injury
Dubai College of Dental MedicineCOMMON PATHWAY

Common pathway
Factor V
Platelet Phospholipid
Prothrombin Activator
Prothrombin to Thrombin
Fibrinogen to Fibrin

http://www.youtube.com/watch?v=cy3a__O
Oa2M

2o Haemostasis inhibitors
 Lipoprotein associated molecule called tissue factor
inhibitor (TFTI)
 Antithrombin (AT) by the liver
 Heparin enhances AT action
 Protein C &Protein S (Vit K dependent proteins)
 Warfarin a Coumarin: Vit K anatagonist

Abnormalities
in 2o Haemostasis
 Leads to
 Serious bleeding in to
cavities
 Chest
 Joints
 Cranuim
 Subcutaneous
haematomas
 No petechial
haemorrhages are seen

Tertiary Haemostasis
(Fibrinolysis)
 Formation of Plasminogen, and then plasmin
 Plasmin is the main enzyme for fibrinolysis

Tertiary
Haemostasis Inhibitors
 Thrombin activated fibrinolytic inhibitor
 Alpha2 antiplasmin
 Plasminogen activator inhibitor
 Anti fibrinolytic drugs such
 Epsilon aminocaprioc acid and
 Tranexamic acid

Lab TESTS
 Full Blood Count: Level of
platelets (Normal 150-400 X
109/L. Minimum 40 X 109 /L
 Bleeding time
 Prothrombin Time (PT) which
tests the extrinsic pathway
(normal 10-15seconds)
 Activated Partial
Thromboplastin (APTT) Time
tests the intrinsic pathway
(Normal 25-35 seconds)
 PFA 100 (Platelet Function
Analysis): Screen for von
Willebrand’s and platelet
dysfunction

Blood test mind map

Bleeding time test
 Used to assess adequacy
of platelet function
 When bleeding stops
 Normal range 1-6
minutes
 Prolonged in platelet
disorders
 Drugs: aspirin

APTT
 Measures effectiveness of
intrinsic pathway to mediate
fibrin clot formation
 Tests all factors except factor
VII
 Time taken to form a clot
after adding Koalin a surface
activating factor and cephalin
a substitute for platelet factor
to patients plasma
 APTT range 25-35s
 Used to monitor Heparin
therapy

Prothombin time
 Measures effectiveness of
extrinsic pathway to
mediate clot formation
 When Ca and tissue factor
are added to pt’s plasma
 Normal PT time indicates
normal factor VII
 Range 10-15s
 Used to monitor Warfarin
therapy
 INR is based in PT (pts’s
PT/Control PT)

Vascular disorders
 Increased capillary fragility
leading to Purpuras
 Conditions
 Hereditary Haemorrhagic
telangiectasia
 Haemangiomas
 Vit C deficiency
 Connective tissue
disorders
 Ehlers Danlos

Scurvy
 Vitamin C (also called ascorbic acid)
is vital for the body as it is needed to
make collagen. Collagen is a type of
protein found in many different
types of tissue, such as skin, blood
vessels, bones and cartilage (which
covers the surface of joints).
 Without vitamin C, collagen can't
be replaced and the different types
of tissue break down, leading to
symptoms of scurvy, including:
 muscle and joint pain
 tiredness
 the appearance of purpura on the
skin
 bleeding and swelling of the
gingivae
 The symptoms of scurvy usually
begin three months after a
person stops getting enough
vitamin C in their diet.

Vascular Disorders
Marfan’s Syndrome
 Autosomal inherited
connective tissue disorder
 Skeletal, Cardiac and
dermatological
mallformations
 Prevalence: 2-3 per 10,000
 M=F
 Phenotypes within family
varies
 Skin with striae
 Heart and blood vessels
deformities such as mitral
valve regurgitation/prolapse
 Eyes /lens dislocaction
glucoma, myopia
 Joints:hypermobility
 Skeleton: Mishapen chest
 Arachnodactyly
 Maxillary and mandibular
retrognathia, high arched
palate long face

Vascular disorders
Osler-Weber-Rendu
Syndrome
 Hereditary Haemorrhagic
Telangiectasis
 Gene mutation
 AD trait with high penetrance
 1 in 5000-8000
 Vascular dysplasia
 Telangiectasia: (small dilated
blood vessels-Spider like)
 Arteriovenous malformations in
the skin, mucosae and viscera

Vascular disorders
 Could be seen in
adolescence 62%
diagnosed by age 16
 Recurrent epistaxis
 Affects nasal, lip tongue
mucosae: demarcated red
papular spider like lesions
 May affect RT, GIT, Liver
Brain
 Investigations include CT,
MRI, angiography
 DD: Von Willebrand’s

Inherited
Vascular disorders
Ehlers- Danlos Syndrome Management:
 AD 1:5000 live births
 Collagen/Protein distruption
lead to fragile connective
tissues
 Laxity of joints
 Laxity of ligaments
 Fragile skin
 Presents as ready bruising,
dissecting aortic aneurysm
 Hyper-elasticity of skin
 Possible IE risk
 Vascular disorders:
 Local measures only
 Be aware of risk of IE

Inherited Vascular disorders
• Ehlers- Danlos Syndrome

Platelet Disorders
 Platelets originate from the
megakaryocyte residing in
the bone marrow. The life-
span of a platelet is about
eight days.
 The normal platelet level is
150−400 x 109/l
 Inherited platelet
abnormalities tend to
affect platelet function
rather than platelet
number, resulting in a
qualitative defect.

Platelets
 Patients with decreased platelets or decreased platelet
function will lead to
 Failure of initial clot formation
 Will bleed immediately after trauma or surgery (Unlike
haemophilia patients start 4 hours after)
 Petcheiae
 Ecchymosis
 Purpura
 Spontaneous gingival bleeding
 Prolonged after toothbrushing

Inherited qualitative
platelet abnormalities
In inherited qualitative
platelet abnormalities,
the platelet count, which
is taken as part of a Full
Blood Count (FBC) test,
is normal but the
bleeding time is
prolonged, as it is
platelet function that is
impaired

Inherited
qualitative platelet
disorders
Glanzmann’s disease
 AR
 Infancy and early childhood
 Petechiae/epistaxis
 Normal platelet count
 Increase in BT
 Failure of platelet aggregation
 Abnormal sequence in the
glycoprotein receptors on the
platelet membranes

Inherited
qualitative disorders
Bernard Soulier Syndrome
 Congenital
thrombocytopenia
 AR
 Rare
 Larger platelets
 Absence of membrane
glycoprotein

Platelet disorders
 Thrombocytopenia is a platelet count below 150x109/l
 < 5 x 109/l oral petechiea, submucoasal and mucosal
bleeding
 <15 x 109/l dermal petechiea
 <25 x 109/l spontaneous haemorrhage
 <75 x 109/l post surgical haemorrhage
 Primary
 Idiopathic thrombocytopenic purpura
 Pancytopenia
 Aplastic anaemia
 Secondary
 Systemic disease-Leukaemia
 Drug induced: BM suppression chemotherapy
 Physical agents: irradiation

Continue
platelets disorders
 Thrombocytosis: increased number of thrombocytes (≥
500X 109/L Myeloproliferative disorders: abnormal bleeding
 Platelet function disorders: numbers are fine but function
abnormal
 Congenital/Inherited
 Von Willebrand’s (discussed in coagulation disorders)
 Acquired:
 Drugs: NSAID such as Aspirin. That contain cyclo-
oxygenase inhibitors will result in blockage of
thombaxane A2, decreasing platelet aggregation

Rx Aspects
Local haemostatic measures
 Platelet transfusion are
needed
 Sequestrations of platelets
very rapid
 1 unit of platelets =10X109/L
 Half before surgery and half
after
 Platelet rich plasma: PRP or
 Platelet rich concentrate
(PRC)

Idiopathic
Thrombocytopenia
Purpura (IPT)
Idiopathic thrombocytopenic purpura
can be classified in two major forms
(Acute and Chronic)
The acute form affects children and
young adults
Autoimmune
The condition may occur as an
immune response to sensitization
by an antecedent viral infection in
which platelets are somehow
affected by the immune response to
the primary infection.
Anti-platelet antibodies have been
detected in proportion to platelet
destruction and the antibodies
decrease after recovery from the
condition The interval between
infection and onset is 2–21 days.

Idiopathic
Thrombocytopenia Purpura (IPT)
 Idiopathic thrombocytopaenic
purpura is the most common
acquired bleeding disorder
occurring in previously healthy
children.
 It occurs in four out of 100 000
children per year, equally affecting
boys and girls between 2 and 4 years
of age .
 The condition is benign and self-
limiting, with a high possibility of
recovery. It is considered to be an
autoimmune disorder because of
the anti-platelet antibodies which
coat the platelet, and lead to its
phagocytosis and destruction by the
reticulum endothelial system,
mainly the liver and spleen

ITP
Acute ITP has also been
related to Epstein–Barr
and varicella zoster
infections, upper airway
infections otitis media
streptococcal infections
(acute
glomerulonephritis) and
vaccination (after
measles-mumps rubella
vaccination).

ITP
Chronic ITP develops in 15–
30% of children with acute
ITP, and females are most
affected (female:male ratio
= 3:1).
Pathophysiology of this
condition suggests an
autoimmune process and a
disregulated immune
response which may remit
over time in 80% of cases.
Clinical symptoms are
generally milder.

ITP
 The clinical features of ITP
include petechiae, ecchymoses,
haematomas, epistaxis,
haematuria, mucocutaneous
bleeding, and occasionally,
haemorrhage into tissues.
 Apart from the signs of bleeding,
the patients are otherwise well,
and there is generally no
enlargement of the liver, spleen
or lymph nodes even though the
spleen tip may be palpable in
about 10% of patients with acute
ITP

ITP
Haematological results
 severely depressed platelet count (below 20 X109/l in acute
ITP, and between 30 -100 x109/l in chronic ITP
 abnormal bleeding time and clot retraction.
 White cell count is normal and anaemia is only present
when significant blood loss has occurred.
 The severity of clinical findings may be independent of the
severity of platelet deficiency.
 Platelet-associated antibodies have been detected in 75%
of patients with ITP.
 Serum anti-platelet IgG antibodies are detected in 50–85%
of patients.

ITP Rx
If treatment is considered necessary, it may include
 corticosteroids,
 intravenous immunoglobulin or
 Intravenous anti-D immunoglobulin for acute
episodes.
 Splenectomy may be necessary for a small proportion
of patients with chronic ITP that has proved resistant
to therapy
Side effects

Management
of ITP in children
 First-line/initial
treatment options to
raise platelet counts in
Children
 Intravenous anti-D
immunoglobulin. IV
anti-D immunoglobulin
 Intravenous
immunoglobulin (IVIg).
IVIg raises the platelet
 Predniso(lo)ne/corticost
eroids.

Chronic ITP

ITP Complications
rare and mainly include Intracranial haemorrhage (0·1–
0·9%)
Sub-glottic airway haemorrhage.
Although the clinical course may be alarming, mortality
is low and prognosis is excellent with 80–90% rates of
complete remission, irrespective of treatment.

ITP
differential diagnosis
 Differential diagnosis of ITP must be made with
 drug-induced thombocytopaenias (e.g. barbiturates,
phenylbutazone, sulphur drugs, quinine or prolonged
glucocorticoid therapy),
 hereditary thombocytopaenias (e.g. von Willebrand disease,
Wiskott– Aldrich syndrome, Bernard–Soulier syndrome or
Henoch–Schlonlein purpura),
 vitamin C deficiency,
 viral infections (e.g. HIV, Mononucleosis, Hepatitis),
 autoimmune disorders (e.g. systemic erythematous lupus),
 aplastic anaemia,
 acute leukaemia or non- Hodgkins lymphoma

Clotting
disorders/Coagulopathies
 Inherited
 Haemophilia A
 Haemophilia B
 von Willebrand’s disease
 Acquired
 Hepatic disease
 Vitamin deficiency
 Anticoagulant therapy
 Disseminated intravascular coagulation (following
overwhelming infection or hypoxia)

Clinical
Manifestations of
inherited bleeding disorders
 Ecchymoses
 Haematoma
 Haemarthrosis
 Joint deformity

 Hemophilia A is a deficiency of factor VIII and haemophilia
B (Christmas disease) is a deficiency of factor IX.
 Normal range 50-100 IU/dL 1 unit of FVIII per millilitre
(100%)
 The severity is linked the level of FVIII coagulant (VIIIc)
 Factor VIII is a glycoprotein of the following
 Factor VIIIR.Ag (which is von Willebrand Factor which binds
to platelets and is a carrier for Factor VIIIc)
 Factor VIIIc which participates in the clotting pathway
 VIIIR:RCO (Ristocetin co-factor) which enhance platelet
aggregation

Haemophilia is an X-linked hereditary disorder.

Haemophilia A
 Mainly affects Males and Homozygous females
 Bleeding is inversely correlated with residual factor
VIII deficiency.
 Females are carriers, they may exhibit symptoms
 In 1/3 cases no family history
 Registered in HRC (Haemophilia Reference Centre)

Clinical Severity
 <1 U/dl
 2 – 10 U/dl
 >10- 30 U/dl
 Severe: Frequency
spontaneous bleeding
 Moderately severe: Some
spontaneous bleeds,
bleeding after minor
trauma.
 Mild: bleeding after
surgery or trauma

Laboratory Diagnosis
 Bleeding time: Normal
 Coagulation Profile:
 PT – Normal
 APTT – Prolonged
 Factor Assay: Low factor
VIIIc
 Normal vWF

CLINICAL
PRESENTATION
 Haemarthrosis: Joint bleeds
 Joint deformities
 Cephalohaematoma.
 Prolonged cord bleed.
 Prolonged bleeding after circumcision.
 Large bruises
 Bleeding after minor trauma
 Post extraction bleeding (Delayed)
 Post ID block: Fatal

Cephalohaematoma.

Treatment
 In essence to control post
op bleeding as local
measures insufficient.
 Level of factor VIIIc
dictates
 Consult Haematologist
prior to procedure
 Aim is to raise VIII to
adequate levels
 DDAVP
 Tranexamic acid
 Recombinant Factor VIII
 Check if FVIII given
Prophylactically to prevent
joint damage
 Dental extractions: Factor
levels 50-75%
 Local measures
 GA: Factor level high for
endotracheal intubation
 Hospital setting
 Book bed
 Consult a HRC

Outline of management of
haemophiliacs requiring surgery
Operation FVIII required Preop give Post op schedule
Dental extraction,
Dentoalveolar or
Perodontal surgery
Minimum of 50%
at operation
FVIII iv
Transexamic acid
20mg/kg Iv or oral
Local measures
Maxillofacial
surgery
75-100% at
operation at least
50% 7 days preop
FVIII iv Local measures
Inpatient rest for 7
days
Soft diet
10 days Tranexamic
acid
Amoxicillin
If bleed Repeat
FVIII
Rest as in patient
10 days
Repeat Factor VIII
bdDubai College of Dental Medicine

Future
therapy for Haemophilia
 Factor VII and IX genes were
isolated in the 1980s leading to the
development of Recombinant
Factor concentrates, although once
they enter the circulation these
proteins disappear within several
hours.
 Gene therapy makes it possible to
deliver the normal missing Factor
gene directly into cells by injecting
it into a virus which acts as vector
for the Factor VIII gene, which is
then injected into the body and
invades the host’s Hepatocytes.
 Clinical trials indicate that gene
therapy may be promising

Challenges
to management of
Haemophilia patients
 Hepatitis/HIV;
 Haemophiliacs with
Inhibitors;
 Mobility;
 vCJD if blood
transfusions have been
received.

Haemophiliacs
with inhibitors Consult haematologists
 FVIII inhibitor level should be checked preop
 Patients with low titre of inhibitors treat as those
who have no antibodies
 High titre patients
 Avoid traumatic procedures
 Human FVIII inhibitor bypassing fractions (FEIBA)
can be effective: they activate factor X bypassing
the intrinsic pathway
 Dangerous: Can cause uncontrolled thrombosis

Haemophilia A in a nut shell
• X-linked recessive disorder mainly
affecting males (rarely female
haemophiliacs do occur)
• Deficiency in Factor VIII
• Prevalence 5 per 100000 of
population
• Haemorrhage stops immediately
after injury but after 1 hour oozing
starts
• Could be fatal: haematocranium,
internal organ haemorrhage,
haemarthrosis, dental extractions.
• Could be mild, moderate or severe
(mild FVIII level: >25%, Severe <1%)
 Diagnosis: prolonged APTT,
Normal PT & Bleeding time, low
factor VIII
 Treatment:
 VIII replacement with
 plasma (fresh or frozen)
 porcine factor VIII, or
 recombinant FVIII
 desmopressin (vasopressin
analogue that releases factor
VIII)
 Tranexamic acid
(antifibrinolytic drug)
systemically

Haemophilia B
 Deficiency in factor IX
 Complications as Hm A
 One tenth as common as Hm
A
 Female carriers have mild
symptoms and bleeding
tendencies
 Treatment with
 synthetic factor IX

Von Willebrand’s in a nutshell
 Pseudohaemophilia
 Most common inherited bleeding disorder
 Affects males and females
 Deficiency in vWF which helps form the primary plug (platelet)
 Reduced platelet activity
 Reduced factor VIII
 Treatment
 Vasopressin DDAVP
 EACA (epsilon aminocaproic acid)
 Tranexamic acid
 Fresh frozen plasma

vW
Named after Dr. Erik von Willebrand who describe
hereditary bleeding disorder distinguished from
haemophilia in 1924
● The protein was purified in 1970s
 AD (Gene locus 12p13)
● Produced in
 Megakaryocyte
 Endothelium,
 Subendothelial CNT

vW
Has functions of binding for platelet, FVIII,
and collagen
● Binds platelet to exposed collagen
● Chaperone of FVIII

Von Willebrand’s
 Most common inherited
bleeding disorder (1% of
the population)
 F=M
 AD pattern
 vW factor lowest in O
group
 Binds with collagen and
platelet glycoprotein
receptors
 Carrier protein for Factor
VIII and increases it half
life by protecting it from
degradation
 Aids platelet adhesion to
damaged endothelium
and other platelets

vW
Type 1: vary degree of
decrease, vWF:
Rco/vWF:Ag > 0.6
● Type 1 Vicenza: normal
production and secretion
of vWF but has increase
excretion
● A person with blood group
O has lower vWF level
than other ABO blood
group
Type 2: abnormal function
○ 2A: decreased larger
multimer,
vWF:Rco/vWF:Ag < 0.6
○ 2B: increase affinity to
platelet, hyperresponse to
RIPA
○ 2M: decrease affinity to
platelet GPIb○ 2N:
decrease affinity to FVIII,
FVIII: c/vWF:Ag< 0.5
● Type 3: severe or totally
absence of vWF

vW features
 Epistaxis
 Skin Purpura
 Menorrhagia
 GIT bleeding (melaena)
 Bleeding following dental extractions

vW
Manifestation of platelet binding problem or
severely decrease FVIII half life
● Present with mucocutaneous bleeding
● Or haemophilia-like in type 2N and type 3
● History of bleeding diathesis in first-degree
relatives
● Significant bleeding may be determined by
bleeding score of 3 in male and 5 in female

vW Diagnosis
 Prolonged bleeding time
 Prolonged APTT: As Factor VIII is a glycoprotein of the
following
 Factor VIIIR.Ag (which is von Willibrand Factor which
binds to platelets and is a carrier for Factor VIIIc)
 Low Factor VIIIc which participates in the clotting
pathway
 VIIIR:RCO (Ristocetin co-factor) which enhance platelet
aggregation
 All these are low when a factor VIII assay is conducted

Treatment
 Desmopressin (DDAVP 1-
desamino-8-D-arginine
vasopressin)
 Nasal spray
 Not indicated in type 2B as
it can stimulate release of
dysfunctional vW factor
 Type 3 managed as severe
Haemophilia A as there is a
complete lack of vW
 Human Plasma transfusion
(No recombinant available
yet)

Acquired
Bleeding Conditions
Drug related Medical condition related
 Antiplatelet drugs
 NSAID
 Aspirin
 Other NSAID
 Clopidogrel
 Dypyrimadole
 Fibrinogen receptors inhibitors
 Anticoagulants
 Warfarin
 Heparin
 Corticosteriods
 Chemotherapy
 Fibrinolytic drugs
 Liver disease
 Renal Disease
 Bone Marrow disorders
 Immune disorders
 Acquired Haemophilia
 Acquired Thrombocytopenia
 Vitamin K Deficiency and
malabsorption

Patients on anticoagulant therapy
 Those with valvular heart
disease and prosthetic valves
to reduce the risk of
remobilisation
 Oral Warfarin (Coumadin)
 Anti Vit K depletes FII,VII,
IX, X
 3-4 days for onset
 Assessed by PT
 Needs to be stopped 3-5 days
pre op, then patient is
heparinised , which is
omitted on day of surgery or
given Enoxaparin (Short
acting)
 Heparin Sodium (Heparin)
 Short acting inhibits IX,X,XII
 Subcut or IV
 Enoxaparin sodium (Clexane)
 Inhibits X and thrombin
 INR monitored and balanced
by Haematologists

Liver disease
 Liver plays major part in
haemostasis
 Produce coag factors
 Produces Thrombopoietin a
glycoprotein which regulates
platelet production by bone
marrow
 Failure of normal function of
liver leads to malabsorption
of fat soluble vitamins such
as Vit K which is required for
the synthesis of coag factors
 In Chronic liver disease. PT
and APTT are prolonged

Liver disease
 LFT tests should be carried
out
 Vit K IV injections may be
required
 Fresh frozen plasma may
be required in patients
with Jaundice
 Increased risk of bleeding
 Consult the Physician
 Local Measures
 Liver transplantation and
immunosupressive therapy

Renal Disease &
Bleeding
 Impaired platelet formation
as thrombopoietin hormone
which stimulates
megakaryocytes to mature
into platelets
 Impaired platelet adhesion
due to defective vWF as
glomerular endothelial cells
express vW
 A decrease in platelet factor
III (thomboxane) which
impairs conversion of
prothrombin to thrombin in
the clotting cascade
 Vasodilation from raised
prostacycline levels
 Haemodialysis patients
taking heparin to facilitate
their treatment

Renal disease
and dental
 Consult the renal physician
and haematologist
 Invasive dental treatment
should not be done on
dialysis as patients
heparinised
 Exclude bleeding disorders
prior to block LA
 Local haemastatic
measures
 DDAVP could be used
following treatment
 Drug doses

Bone Marrow
Disorders

Bone marrow
disorders
 Consult with haematologist
 Haematological malignancies: Timing of treatment; Invasive
treatment carried out when patient in remission and between
chemotherapeutic regimes
 Prior to chemotherapy, radiotherapy and BMT a thorough dental
assessment should be done: teeth with poor prognosis removed
before treatment commences
 Prevention
 Thrombocytopenia: platelet transfusions
 Patients who have BMT may be thrombocytopenic and
leucopenic for 6 months: defer
 Immunosupression therapy
 Local measures

Immune disorders

Blood dyscrasis
 Erythrocyte disorders
 Haemolytic anaemias
 Deficiency anaemia
 Sickle cell anaemia
 Thalassaemia
 Polycythaemia
 Leukocyte disorders
 Leukaemia
 Leukocytosis
 Leucopenia
 Lymphoma

Anaemia
 a condition marked by a
deficiency of red blood cells
or of haemoglobin in the
blood, resulting in pallor and
weariness.
 Nnormal hemoglobin range is
generally defined as 13.5 to
17.5 grams (g) of
haemoglobin per deciliter
(dL) of blood for men and
12.0 to 15.5 g/dL for women.
The normal ranges for
children vary depending on
the child's age and sex.

Anaemia
Hypochromic
microcytic
Normochromic
normocytic Macrocytic
Iron deficiency
anaemia
Thalassamia
Siderblastic anamia
Chronic disease
Myeloproliferative
Disease
Aplastic anaemia
Preleukaemia
Acute blood loss
Vitamin B12 or Folate
deficiency
Aplastic anamia

 http://uk.youtube.com/
watch?v=u7VJSVW-
Dqs&feature=related
Sickle cell anaemia

What is Sickle Cell Anaemia (SCA)?
 First described in Chicago in 1910 by James
Herrick as an inherited condition that
results in a decrease in the ability of red
blood cells to carry oxygen throughout the
body
 Sickle red blood cells become hard and irregularly shaped
(resembling a sickle)
 Become clogged in the small blood vessels and therefore do not
deliver oxygen to the tissues.
 Lack of tissue oxygenation can cause excruciating pain, damage to
body organs and even death.

Mechanism -HbS• When sickle haemoglobin (HbS) gives up its oxygen to the
tissues, HbS sticks together
– Forms long rods form inside RBC
– RBC become rigid, inflexible, and sickle-shaped
– Unable to squeeze through small blood vessels, instead
blocks small blood vessels
– Less oxygen to tissues of body
• RBCs containing HbS have a shorter lifespan
– Chronic state of anaemia

Sickle: Phenotype-Genotype
SCD represents a group of inherited disorders with predominance of HbS and
includes the following conditions:
 homozygous sickle cell anaemia (HbSS);
 sickle haemoglobin C disease (HbSC);
 sickle/beta-thalassaemia (HbS/pthat); and,
 other compound heterozygous conditions.‘
HbSS is the most clinically severe; however, some individuals affected by this
condition may not be aware of it until theydevelop a sickle cell crisis.
.

Diagnosis
1. Haemoglobin Electrophoresis
 Simple Blood test
 Routine screening in high risk groups
• During pregnancy
• Before anaesthesia
2. Prenatal Testing
 Amniocentesis
 16 and 18 weeks of the pregnancy
 small risk of causing a miscarriage (1 in 100)
 Chorionic villus sampling (CVS)
 9th or 10th week of pregnancy
 very small amount of material from the developing placenta
 slightly higher chance of miscarriage

Diagnosis and Treatment of Sickle Cell
Anaemia

Early Symptoms
and Complications
 Typically appear during infant's first year
 1st symptom: dactylitis and fever (6 mo-2 yrs)
 Pain in the chest, abdomen, limbs and joints
 Enlargement of the heart, liver and spleen
nosebleeds
 Frequent upper respiratory infections
 Chronic anemia as children grow older
 Over time Sickle Cell sufferers can experience damage to
organs such as liver, kidney, lungs, heart and spleen
 Can result in death

Medical Complications
pain episodes
strokes
increased infections
leg ulcers
bone damage
yellow eyes or jaundice
early gallstones
lung blockage
kidney damage and
loss of body water in urine
blood blockage in the spleen
or liver (sequestration)
eye damage
low red blood cell counts
(anemia)
delayed growth

1. Fever
2. Chest pain
3. Shortness of Breath
4. Increasing tiredness
5. Abdominal swelling
6. Unusual headache
Danger Signs of a Crisis
7. Any sudden weakness or
loss of feeling
8. Pain that will not go away
with home treatment
9. Priapism (painful erection
that will not go down)
10. Sudden vision change
SEEK URGENT HOSPITAL TREATMENT IF IN CRISIS

Potential precipitants of sickle cell
crisis
• Acute infections are a well-known trigger of sickle cell crises. Dental infections
should therefore be prevented but, if infection occurs, it should be immediately
and effectively treated;"
• hypothermia can facilitate red cell sickling. Anaesthetic drugs may enhance
sickling. Hypothermia must be avoided in SCD patients who undergo treatment
under general anaesthesia;“
• dehydration is a trigger for sickle cell crisis." When general anaesthesia is
required, the administration of intravenous fluids before, during and after surgery
is recommended;'" and,
• hypoxia in association with general anaesthesia can trigger a sickle cell crisis.

1. Taking the folic acid (folate) daily to help make new red cells
2. Daily penicillin until age six to prevent serious infection
3. Drinking plenty of water daily (8-10 glasses for adults)
4. Avoiding too hot or too cold temperatures
5. Avoiding over exertion and stress
6. Getting plenty of rest
7. Getting regular check-ups from knowledgeable health care
providers
Daily Preventative Measures

Treating Complications
 Pain-killing drugs and oral and intravenous fluids
 To reduce pain and prevent complications.
 Transfusions
 Correct anaemia
 Treat spleen enlargement in children before the condition
becomes life-threatening
 Regular transfusion therapy also can help prevent recurring
strokes in children at high risk of crippling nervous system
complications.

 Variability and Unpredictability
 Some are mildly affected and largely free from pain, while
others have frequent and severe pain
 Most children go through good and bad patches
 Doctors cannot predict who will be severely affected.
 No easily overt detectable signs of sickle pain
 So children known to have sickle cell disorder who say
they are in pain must be trusted
 If they can rely on the adults around them to take them
seriously, they are less likely to take advantage of their
condition to seek attention or avoid distasteful tasks.
Psychosocial Issues

 Hydroxyurea
 The first effective drug treatment for adults with severe
sickle cell anemia reported in early 1995
 Daily doses of the anticancer drug, hydroxyurea, reduced
the frequency of painful crises, acute chest syndrome,
needed fewer blood transfusions
 Increases production of fetal haemoglobin in the blood
 Fetal haemoglobin seems to prevent sickling of red
cells
 cells containing fetal haemoglobin tend to survive
longer in the bloodstream
Developing Treatments

 Bone marrow transplantation
 Shown to provide a cure for severely
affected children with sickle cell disease
 Only about 18 percent of children with
sickle cell anemia are likely to have a
matched sibling.
Developing Treatments

The Ultimate Cure?
Gene Therapy
1. Correcting the “defective gene” and inserting it
into the bone marrow
2. Turning off the defective gene and simultaneously
reactivating another gene that turns on
production of fetal haemoglobin.
No real cure for Sickle Cell Anaemia at this time.
“In the past 30 years, the life expectancy of people
with sickle cell anemia has increased. Many
patients with sickle cell anaemia now live into
their mid-forties and beyond.”

Sickle cell anaemia
 Inherited autosomal
recessive disorder
 10% American African
 25% Central Africans
affected
 SC trait: heterozygous
(HbAS)
 SC anaemia: homozygous
(HbSS)
 Results in the substitution
of a single amino acid in
the haemoglobin chain

Sickle cell anaemia
 Painful joints
 Swelling hands and feet
 Failure to thrive
 Splenomegaly
 Susceptibility to infections
 Renal impairment
 Retinal and conjunctival
damage
 Erythroctyes contain HgS and
have a short life
 Erythrocytes become
clumped together blocking
vessels
 Haemolytic
anaemia/jaundice
 Causes pain and necrosis in
multiple organs
 Child is pale, tired, weak and
breathless.

Sickle cell and dentistry
To prevent a sickling crisis we need
to prevent:
 Trauma and pain
 Infection
 Hypoxia
 Acidosis
 Dehydration
Prevention, avoid extractions
All patients of Afro-Caribbean
origin should be screened for SCA
prior to a GA
 SC trait: GA is possible but 100%
oxygen saturation maintained
 SC disease: GA hazard!!
 LA/RA is safe
 Antibiotics may be required
preoperatively
 Oralfacial features of sickle
cell disease
 Painful jaw infarcts:
?toothache
 Pulpal necrosis
 Stepladder bone trabeculae
pattern
 Enlarged maxilla and
increased overjet

Haemoglobin
 Adult blood contains
HgA (has 2 globin chains
α2,β2) & HgA2 (has 2
globin chains α2,γ2)
 Children have fetal
haemoglobin HgF
(α2,δ2)
 Haemoglobin is a
protein formed from four
polypeptide chains
called globins, in the
centre of each of which
is a small non-protein
part called a haem group
(haima is Greek for
‘blood’). Each of the
haem groups has an iron
atom within it.

Thalassaemias
 AR disease prevalent among
Mediterranean peoples and
common in the UAE.
 Thalassa (θάλασσα) is Greek
for the sea, Haema (αίμα) is
Greek for blood.
 One of the globin (α or β or δ)
chains is absent or reduced
 Homozygous α- thalassaemia
(deletion of α chain)
incompatible with life,
heterozygous α- thalassaemia
has few symptoms (seen in
Asians)
 Homozygous β - thalassaemia
(thalassaemia major: Cooley’s
anaemia) , life threatening.
 Heterozygous β –
thalassaemia asymptomatic

Epidemiology
1.5% (80-90 million people) of the world's population are carriers of β
thalassaemia and 5% are carriers of α thalassaemia.
β thalassaemia is prevalent in areas around the Mediterranean, in the
Middle East, in Central, South, and Southeast Asia, and in Southern
China.
α thalassaemia is prevalent in Southeast Asia, Africa, and India.
Increasing migration of populations at risk to non-endemic countries has
resulted in increasing prevalence of thalassaemia gene mutations in all
parts of the world.

Thalassemia a Major Public Health
Issue in UAE
The number of carriers of the genetic disease thalassemia in the UAE may go
up to 1 million.
approximately 600,000 people in the Emirates are carriers of the disease.
 The Dubai Thalassemia Centre is the Emirate’s only dedicated facility
to manage this condition by providing internationally recognised levels of
care in chronic disease management for thalassemic patients.
 “About 420 patients receive regular treatment and blood transfusions at
the centre,” , “Each patient requires approximately 34 units of blood
annually through an average 17 transfusions. However, additional units of
blood may be required depending on the patient’s condition, also it
receive extra patients who visit the center for transfusions from time to
time.”

If only one parent has thalassaemia
minor, the following can occur
• 50% chance of having a child with thalassaemia minor
• 50% chance of having a normal child
• None of the couple’s children will get thalassaemia major.
If both parents have thalassaemia
minor, the following can occur:
• 25% chance of having a child with thalassaemia major
• 50% chance of having a child with thalassaemia minor
• 25% chance of having a normal child

Types of thalassemia
 Beta thalassemia
 Alpha thalassemia
 Thalassemia trait, also known as thalassemia minor
 Thalassemia intermedia is the other form of severe beta thalassemia

 beta thalassemia there is deficient synthesis of beta globin
 alpha thalassemia there is deficient synthesis of alpha globin.
 Reduced synthesis of one of the two globin polypeptides leads to deficient haemoglobin
accumulation, resulting in hypochromic and microcytic red cells.
 Thalassemia trait, also known as thalassemia minor, is found in heterozygous
individuals with impaired alpha and beta chain production.
 This does not generate clinical signs, and the presence of splenomegaly is
rare..
 Thalassemia intermedia is the other form of severe beta thalassemia.
 These patients need blood transfusion but not regularly.
The prognosis of such cases is much better than in patients with thalassemia major and
dental
treatment is comparatively less problematic.

Beta thalassemia major, historically called Cooley’s anemia, occurs when both genes
necessary for beta globin production are affected.
Beta thalassemia presents at six months of age when adult hemoglobin has replaced fetal
hemoglobin. Peripheral anemia, caused by the disease, sends signals to the bone marrow to
increase production of erythrocytes (via erythropoietin), however, erythrocyte production is
abnormal.
 The process is called ‘ineffective erythropoesis’.With time, the marrow cavities (skull
bones, facial bones and ribs) expand(erythroid hyperplasia), leading to classicalfacial features
and radiographicfindings.
 Massive erythropoesis within the bones invades bony cortex,impairs bone growth and
produces other skeletal abnormalities.
 Erythrocytes are noted to be abnormal by the reticulo-endothelial system, and are taken up by
these organs resulting inenormous hepatoslenomegaly.
 In untreated patients, death usually occurs by the end of the second decade of life from
anemia and congestive heart failure.These patients need regular transfusions to survive(every
two to fourweeks).

Diagnosis Of Thalassemia
Complete blood count-This initial haematological test gives a general idea of the cells
in the blood stream. If Mean Corpuscular Volume and Mean Corpuscular Haemoglobin are
low and iron deficiency has been ruled out, thalassemia should be considered.
Thalassemia screen test or haemoglobinopathy test. This test measures the type
and relative amounts of haemoglobin(Hb)present in the RBCs. This test is done once a
haemoglobinopathy is suspected based on family history or full blood count.
DNA mutation analysis-This test is used to investigate deletions and mutations in
alpha and beta globin producing genes. This is not routinely used but is used when a
haemoglobinopathy cannot be confirmed by the thalassemia screening test.

Clinical and Orofacial
ManifestationsYellow skin pallor, fever, malaise, and weakness
 Radiographs may show a “salt and pepper” pattern.
 Some trabeculae are prominent, and others are blurred
The most common orofacial manifestations are due to intense compensatory
hyperplasia of
the marrow and expansion of the marrow cavity.(Ronald J A Trent 2006)
 Thalassemia major patients develop skeletal class II malocclusion
subsequent to maxillary protrusion and mandibular atrophy.
 Increased overjet.
 anterior open bite.
 Malar prominence, frontal bossing give an appearance of ‘chip-munk faces’ or
rodent faces
(KharsaMA1987)

 Marrow overgrowth in maxillary bone may cause lateral displacement of orbits
(hyperteleorism).
Other oral features include :
 Spiky-shaped and short roots.
 Taurodontism.
 Multiple diastemas.
 Absence of inferior alveolar canal and thin cortex of the mandible.

Treatment Of Thalassemia
 Currently, part of the standard treatment for beta thalassemia major is lifelong
transfusions given every two to four weeks.
 The repeated transfusions gradually increase the total body iron load, resulting
in transfusional haemosiderosis with complications in the heart, endocrine
glands and the liver.
 Infection with bacteria especially Yersinia and Klebsiella are more common in
individuals who have excess body iron.

Iron chelator
Regularly transfused patients need to be on life long chelation therapy to help their bodies excrete
the excess iron. With the combination of transfusion and chelation therapy, life expectancy can be
normal. Currently three iron chelators are available for use either as mono therapy or
combination.
Deferoxamine
Deferiprone
Deferasirox
Splenectomy
The presence of hypersplenism intensifies the need for blood transfusion. This worsens the
problems posed by iron accumulation. The presence of leucopenia and thrombocytopenia hastens
the decision to remove spleen. However, splenectomy is the risk of sudden sepsis caused by
encapsulated microorganisms. Such patients frequently receive daily continued prophylaxis.
Elevation of fetal haemoglobin levels:
Administration of recombinant human erythropoietin and Hydroxyurea increases gamma-chain
synthesis to some extent , with a consequent rise in fetal hemoglobin.But, these measures cannot
substitute the blood transfusions.

Alternative therapy
bone marrow transplantation and stem cell therapy, but these too with its own
limitations.
 The potential gene therapy may be expected to allow complete curing of
patients in the future thereby greatly simplifying the dental management of these
patients. Need of the hour is prevention of thalassemia by prenatal screening.

Homozygous β - thalassaemia
(thalassaemia major)
 Absence of β chain, the body
compensates with production
of HbA2 and HbF
 Erythropoiesis is inadequate,
bone marrow goes into
overdrive
 Overgrowth of bone such as
maxilla and diploe of skull
 Hepatosplenomegaly
 Require blood transfusions
(Rx best after)
 Antibiotics if splenectomy
 Spaced dentition
 LA is safe
 Prevention, pulp therapy not
extractions bleeding
tendencies
 Liaise with haematologist if
extractions been carried out

Leukaemia
 Neoplastic proliferation of
leukocytes precursors
 Acute, chronic, lymphoblastic,
myeloblastic types
 Acute leukaemias: release of
primitive blast cells into the
peripheral blood. Account for
50% of childhood malignancy
 Acute Lymphoblastic Leukaemia
(ALL) is the commonest
childhood leukaemia (85%)

Acute lymphoblastic leukaemia ALL
 Crowding out of normal
blood cells by primitive bone
marrow cells
 Anaemia
 Thrombocytopenia
 Susceptibility to infections:
septicaemia
 Bleeding tendencies
 Initial presentation may be
spontaneous gingival
bleeding and gingival
oedematous enlargement
http://www.ukccsg.org.uk/

Management of Leukaemia (ALL)
Management of ALL focuses on
control of bone marrow.
Prevent leukaemic cells from
spreading to other sites, particularly
the CNS. monthly lumbar
punctures.
Induction chemotherapy to bring
about bone marrow remission .
Children receive prednisolone, L-
asparaginase, and vincristine for the
first month of treatment.

Managment of ALL
 Intensification therapy to
eliminate any remaining
leukaemia cells. Antimetabolite
drugs such as Methotrexate and
6-mercaptopurine (6-MP).
 CNS prophylaxis includes
radiation of the head and/or
drugs delivered directly into the
spine (intrathecal drugs).
 Remission
 Maintenance treatments
 Bone marrow transplantation
(Allogenic)

History of Blood Groups and Blood Transfusions
•Experiments with blood transfusions
have been carried out for hundreds of
years. Many patients have died and it was
not until 1901, when the Austrian Karl
Landsteiner discovered human blood
groups, that blood transfusions became
safer.
• He found that mixing blood from two
individuals can lead to blood clumping.
The clumped RBCs can crack and cause
toxic reactions. This can be fatal.

• Karl Landsteiner discovered that blood
clumping was an immunological reaction
which occurs when the receiver of a blood
transfusion has antibodies against the donor
blood cells.
•Karl Landsteiner's work made it possible to
determine blood types and thus paved the
way for blood transfusions to be carried out
safely. For this discovery he was awarded the
Nobel Prize in Physiology or Medicine in
1930.
History of Blood Groups and Blood
Transfusions (Cont.)

•The differences in human blood are due to the
presence or absence of antigens and antibodies.
•The antigens are located on the surface of the
RBCs and the antibodies are in the blood
plasma.
•Individuals have different types and
combinations of these molecules.
•The blood group you belong to depends on
what you have inherited from your parents.
What are the different blood groups?

• There are more than 20 genetically determined
blood group systems known today
• The AB0 and Rhesus (Rh) systems are the
most important ones used for blood transfusions.
• Not all blood groups are compatible with each
other. Mixing incompatible blood groups leads to
blood clumping or agglutination, which is fatal
What are the different blood groups?

Agglutination
 ABO-incompatible red cell transfusion is often fatal and its
prevention is the most important step in clinical
transfusion practice
 Anti-A and/or anti-B in the recipient’s plasma binds to the
transfused cells and activates the complement pathway,
leading to destruction of the transfused red cells
(intravascular haemolysis) and the release of inflammatory
cytokines that can cause shock, renal failure and
disseminated intravascular coagulation (DIC).
 The accidental transfusion of ABO-incompatible
blood is now classified as a ‘never event’ by the UK
Departments of Health.

According to the ABO blood
typing system there are four
different kinds of blood types:
A, B, AB or O (null).
Autosomal codominant
ABO blood grouping system

Blood group A
If you belong to the blood
group A, you have A antigens
on the surface of your RBCs
and B antibodies in your
blood plasma.
Blood group B
If you belong to the blood
group B, you have B antigens
on the surface of your RBCs
and A antibodies in your
blood plasma.
AB0 blood grouping system

Blood group AB
If you belong to the blood group
AB, you have both A and B antigens
on the surface of your RBCs and no
A or B antibodies at all in your
blood plasma.
Blood group O
If you belong to the blood group O (null),
you have neither A or B antigens on the
surface of your RBCs but you have both A
and B antibodies in your blood plasma.

• The ABO gene is autosomal
• The ABO gene locus is located on the chromosome 9.
• A and B blood groups are dominant over the O blood group
• A and B group genes are co-dominant
ABO inheritance and genetics

 There are four main blood groups: A, B, AB and O. All
normal individuals have antibodies to the A or B antigens
that are not present on their own red cells .
 The frequency of ABO groups varies in different ethnic
populations
 For example, people of Asian origin have a higher
frequency of group B than white Europeans.
 Individuals of blood group O are sometimes known as
universal donors as their red cells have no A or B antigens.
However, their plasma does contain anti-A and anti-B that,
if present in high titre, has the potential to haemolyse the
red cells of certain non-group O recipients

The ABO blood groups
• The most important in assuring a safe blood transfusion.
• The table shows the four ABO phenotypes ("blood groups")
present in the human population and the genotypes that give
rise to them.
Blood
Grou
p
Antigens
on RBCs
Antibodies in Serum Genotypes
A A Anti-B AA or AO
B B Anti-A BB or BO
AB A and B Neither AB
O Neither Anti-A and anti-B OO

Well, it gets more complicated here, because there's
another antigen to be considered - the Rh antigen.
Some of us have it, some of us don't.
If it is present, the blood is RhD positive, if not it's RhD
negative.
So, for example, some people in group A will have it, and
will therefore be classed as A+ (or A positive).
While the ones that don't, are A- (or A negative).
And so it goes for groups B, AB and O.
The Rhesus (Rh) System

Rh Blood Group System
 The Rh factor is simply a red blood cell antigen - just like
the A antigen and the B antigen that are used to determine
your blood type.
 The Rh blood group system is a classification system for
blood that depends on the presence or absence of the Rh
antigen - or factor - on your red blood cells.
 In other words, you were either born with the Rh factors on
your red blood cells, like most people, or you were born
without them, which is more rare, but significant as we will
learn in this lesson. Since the Rh factor can be either
present (+) or absent (-) we refer to people as being either
Rh positive if they have the Rh factor, or Rh negative if they
do not.

Rhesus Factor
 There are five main Rh antigens on red cells for which individuals can
be positive or negative: C/c, D and E/e. RhD is the most important in
clinical practice.
 Around 85% of white Northern Europeans are RhD positive, rising to
virtually 100% of people of Chinese origin.
 Antibodies to RhD (anti-D) are only present in RhD negative
individuals who have been transfused with RhD positive red cells or in
RhD negative women who have been pregnant with an RhD positive
baby. IgG anti-D antibodies can cause acute or delayed haemolytic
transfusion reactions when RhD positive red cells are transfused and
may cause haemolytic disease of the fetus and newborn (HDFN).
 It is important to avoid exposing RhD negative girls and women of
child-bearing potential to RhD positive red cell transfusions except in
extreme emergencies when no other group is immediately available.

• Rh antigens are transmembrane proteins with loops
exposed at the surface of red blood cells.
• They appear to be used for the transport of carbon
dioxide and/or ammonia across the plasma membrane.
• They are named for the rhesus monkey in which they
were first discovered.
• RBCs that are "Rh positive" express the antigen
designated D.
• 85% of the population is RhD positive, the other 15%
of the population is running around with RhD negative
blood.
The Rhesus (Rh) System (Cont.)

Blood
Type
Genotype
Alleles
Produced
Rh positive
RR R
Rr R or r
Rh negative rr r
Rh Blood Group and Rh Incompatibility
A person with Rh- blood does not have Rh antibodies
naturally in the blood plasma

According to above blood
grouping systems, you can
belong to either of
following 8 blood groups:
Do you know which blood group you
belong to?

Rh
 We previously learned that in the ABO blood group
system that antibodies are automatically produced
based on antigens not present on your red blood cells.
 You might think that the Rh blood group would be the
same way and assume that if you are born without the
Rh antigen that your body would automatically make
antibodies against it. However, in the Rh blood group
system, the antibodies are not automatically produced.
 Instead, a person with Rh negative blood needs to be
'sensitized' before he or she will start to produce
antibodies to the Rh antigen. Let's look at an example.

Example of Rh
 If you have a woman with Rh negative blood who has never had a blood
transfusion or any other exposure to anyone else's blood, she will not
have any antibodies against the Rh antigen. It's almost like her body
doesn't even care which Rh blood group she belongs to.
 However, if this woman gets a bad blood transfusion that contains Rh
positive blood, her body will now be 'primed,' or 'sensitized,' to the Rh
positive antigen and start to produce anti-Rh positive antibodies.
Because this was the first exposure, there's no real harm done, other
than the fact that now she has the antibodies floating around in her
bloodstream.
 The only significant point is that because the antibodies are now in her
bloodstream, she can never again come in contact with Rh positive
blood or her antibodies will attack. It's almost like she gets a free pass
for her first exposure to the wrong blood type when you talk about Rh
factor. However, this first exposure sets you up for problems if you ever
get the wrong blood again.

Erythroblastosis Fetalis
 Now, let's consider a different woman. Let's say that she is a
pregnant Rh negative woman who is carrying an Rh positive
child. During pregnancy, and especially during delivery, there is
a good chance that the child's Rh positive blood can pass
through the placenta and into the mother's bloodstream -
somewhat like the blood transfusion we talked about earlier.
What is going to happen to that first child? Well, the answer is
nothing. In fact, the first pregnancy for an Rh negative mom and
an Rh positive child typically results in a healthy baby. But, the
mother is now sensitized by Rh positive antigens that have
passed through the placenta and into her bloodstream. That
means she will start to form anti-Rh positive antibodies. This will
be a problem if she ever becomes pregnant again with an Rh
positive child, because her antibodies will reject the child.

Why is an Rh incompatibility so dangerous
when ABO incompatibility is not during
pregnancy?
• Most anti-A or anti-B antibodies are of the IgM
class (large molecules) and these do not cross the
placenta.
•In fact, an Rh−/type O mother carrying an
Rh+/type A, B, or AB foetus is resistant to
sensitisation to the Rh antigen.
•Her anti-A and anti-B antibodies destroy any foetal
cells that enter her blood before they can elicit anti-
Rh antibodies in her.

•This phenomenon has led to an effective
preventive measure to avoid Rh sensitisation.
•Shortly after each birth of an Rh+ baby, the
mother is given an injection of anti-Rh
antibodies (or Rhogam).
•These passively acquired antibodies destroy
any foetal cells that got into her circulation
before they can elicit an active immune
response in her.
Rh incompatibility during pregnancy (cont.)

The ABO Blood Group System
Laboratory Determination of
the ABO System

Several methods for testing the ABO group of an
individual exist. The most common method is:
Serology: This is a direct detection of the ABO
antigens. It is the main method used in blood
transfusion centres and hospital blood banks.
This form of testing involves two components:
a) Antibodies that are specific at detecting a
particular ABO antigen on RBCs.
b) Cells that are of a known ABO group that
are agglutinated by the naturally occurring
antibodies in the person's serum.

• Illustration of the forward and reverse
grouping reaction patterns of the ABO
groups using a blood group tile
http://www.bh.rmit.edu.au/mls/subjects/abo/resources/genetics1.htm

When RBCs carrying one or both antigens are exposed to the
corresponding antibodies, they agglutinate; that is, clump together.
People usually have antibodies against those red cell antigens that
they lack.
Human RBC before (left) and after (right) adding serum
containing anti-A antibodies. The agglutination reaction
reveals the presence of the A antigen on the surface of the
cells.

Compatibility procedures in the
hospital transfusion laboratory
 Group and screen
 The patient’s pre-transfusion blood sample is tested to
determine the ABO and RhD groups and the plasma is
screened for the presence of red cell alloantibodies
capable of causing transfusion reactions. Autoanalysers
are used
 Compatibility:
 The final step in providing safe blood is to carry out a
serological crossmatch between the patient’s plasma and
a sample of red cells from the units of blood selected for
transfusion. Auto

 Electronic issue
 This is sometimes known as computer crossmatching. Most hospitals now issue
the majority of blood by this safe and rapid technique. It relies on the fact that
if the patient’s ABO and RhD groups are reliably established, and a sensitive
antibody screen is negative, the possibility of issuing incompatible blood is
negligible. The laboratory computer can identify all compatible units in the
blood bank inventory without the need for further testing.
 Electronic issue should not be used:
 If the patient’s plasma contains, or has been known to contain, red cell
alloantibodies of clinical significance
 If the antibody screen is positive
 If the patient has had an ABO-incompatible marrow or haemopoietic stem cell
transplant
 If the patient has had an ABO-incompatible solid organ transplant in the last 3
months
 For neonates or fetuses, if the mother has an IgG red cell antibody present in
her plasma.
Compatibility procedures in the
hospital transfusion laboratory

Types of blood transfusion
 Allogenic blood from donor that is genetically
dissimilar and hence immunologically incompatible,
although from individual of the same species.
 Autologous bl0od obtained from the same individual.

People with blood group O-
are called "universal
donors" and people with
blood group AB+ are called
"universal receivers."
Blood transfusions – who can
receive blood from
whom?

Blood
Group
Antigens Antibodies Can give
blood to
Can receive
blood from
AB
A
B
O

Blood
Group
Antigens Antibodies Can give
blood to
Can receive
blood from
AB A and B None AB AB, A, B, O
A A B A and AB A and O
B B A B and AB B and O
O None A and B AB, A, B, O O

The Ten Commandments for Blood
Transfusion
 Transfusion should only be used when the benefits outweigh the risks and there are no
appropriate alternatives.
 Results of laboratory tests are not the sole deciding factor for transfusion.
 Transfusion decisions should be based on clinical assessment underpinned by evidence-
based clinical guidelines.
 Not all anaemic patients need transfusion (there is no universal ‘transfusion trigger’).
 Discuss the risks, benefits and alternatives to transfusion with the patient and gain their
consent.
 The reason for transfusion should be documented in the patient’s clinical record.
 Timely provision of blood component support in major haemorrhage can improve
outcome – good communication and team work are essential.
 Failure to check patient identity can be fatal. Patients must wear an ID band (or
equivalent) with name, date of birth and unique ID number. Confirm identity at every
stage of the transfusion process. Patient identifiers on the ID band and blood pack must
be identical. Any discrepancy, DO NOT TRANSFUSE.
 The patient must be monitored during the transfusion.
 Education and training underpin safe transfusion practice

Blood transfusion
Whole
Blood
Cells
Red
Cell
concentrate
Platelet
concentra
te
White
cells
Plasma
Cryoprecipi
tate
Fresh
Frozen
plasma
Plasma
product
s
Albumin Immunoglob
ulins
Coagu
lation
factor
s

Blood Loss
 Massive blood loss is defined by the loss of one volume
within 24 hours

Allogenic blood transfusion
problems
 Incompatibility
 Fluid overload
 Transmission of infections
 Post-transfusion purpura
 Transfusion associated graft versus host disease
 Transfusion associated acute lung injury (TRALI)
 Acute non haemolytic transfusion reactions

Diseases known to be transmitted
via allogenic blood transfusion
 Bacterial (Various)
 Chagas disease
 Cytomegalovirus
 Hep A, D, C
 HIV 1, 2
 Human T-Lymphopc viruses (HTLV1, 2)
 Malaria
 Treponema Pallidum
 West Nile Virus
 Variant Creuztfeld-Jakob Disease (Prions)

http://www.transfusionguidelines.org.uk/tra
nsfusion-handbook/contents

Therapeutic goals
 Maintenance of tissue perfusion and Oxygenation
 Restoring blood volume and Hb
 Arresting bleeding

Transfusion management of major
haemorrhage
 Major haemorrhage is variously defined as:
 Loss of more than one blood volume within 24 hours
(around 70 mL/kg, >5 litres in a 70 kg adult)
 50% of total blood volume lost in less than 3 hours
 Bleeding in excess of 150 mL/minute.

Massive transfusion
 Death by exsanguination has been described as the
loss of 150 mL of blood per minute, which results in
loss of half the blood volume in 20 minutes
 It has also been classified as blood loss of more than
5,000 mL
 10 units of blood transfused within 24 hours

Massive transfusion
 replacement of one entire blood volume within 24
hours
 50% blood volume replacement within 3 hours
 transfusion of more than 20 units of erythrocytes
 requiring 4 units of blood within an hour with
anticipation of ongoing usage

Massive transfusion
 Most MTPs call for the use of uncrossmatched type O
negative (O-) blood as the first-line infusion
preference.

O negative blood
 universality and timely availability from hospital blood
banks
 when used during massive exsanguination is potential
problems with crossmatching and incompatibility
later in the patient’s hospital stay
 more than 4 units

O+ blood
 It has been shown to be generally safe and can help
prevent blood shortages
 administer to men and postmenopausal women
 To woman of childbearing age can result in
sensitization

Massive transfusion complications
 Coagulopathy is caused by a dilutional effect on
the host's clotting factors and platelets, as well as
the lack of platelets and clotting factors in packed
red blood cells.
 Volume overload
 Hypothermia

 Hyperkalemia may be caused by lysis of stored red
cells
 Metabolic acidosis and hypokalemia may be
caused by the transfusion of a large amount of
citrated cells.
 Hypocalcemia due to citrate toxicity may occur in
those with hepatic failure, congestive heart failure
(CHF), or other low-output states.
 It is increasingly uncommon with the use of component
therapy.

 Use of blood from multiple donors increases the risk
of hemolytic reactions as a consequence on
incompatibility

2,3 DPG
 2,3-DPG An inorganic phosphate produced in red cells
 2,3-DPG binds to the beta chain of reduced haemoglobin
(Hb), lowering Hb's affinity for O2 and by extension,
facilitating O2 release to tissues, causing a "right shift" of
the O2 dissociation curve.
 2,3-DPG further shifts the curve to the right by lowering
the red cells' pH, When transfused, red cells regain 50% of
the 2,3-DPG within 3–8 hours and 100% within 24 hours.
 Increased DPG: High altitude, anaemia, chronic hypoxia,
hyperthyroidism, chronic alkalosis
 Decreased DPG: Storage of blood, hypothyroidism,
hypophosphatemia, acidosis

Banked Whole blood
 No components have been removed.
 consists of red blood cells, white blood cells and
platelets in plasma
 can be stored for 5 weeks

Banked Whole blood
 Transfusions of whole blood are rarely required.
 stored in the refrigerator, the platelets are useless and
factors V and VIII are greatly reduced.

Banked Whole blood
 transfusion of whole blood may be necessary
 certain types of major surgery
 ACUTE BLOOD LOSS > 15%
 major trauma such as a car accident or gunshot wound
requiring emergency surgery

Fresh whole blood
 Blood that is administered within 24 hours of its
donation
 Rarely indicated
 Poor source of platelets and factor VIII

Blood Component Therapy
 The process of transfusing only that portion of
the blood needed by the patient
 It allows a single unit (one pint) of donated blood
to benefit more than one patient
 Red blood cells and platelets are the most
frequently transfused blood components

Packed red cells
 The red cells from a donor unit, diluted with plasma to
a haematocrit of about 75%.
 Volume is about 200 mL.
 Storing red cells (just above freezing) allows survival
for 42 days
 ruins the platelets and neutrophils.
 but unfortunately decreases 2,3-DPG

Packed red cells
 Red blood cells contain haemoglobin
 carries oxygen throughout the body.
 Essentially provides oxygen-carrying capacity
 Product of choice for most clinical situations

Packed red cells
 Recent advances have made it possible to store red
blood cells for up to 42 days.
 Indications
 acute trauma before surgery
 people with anaemia who are having surgery

Packed red cells
 fastest way to increase the oxygen-delivering capacity
of the blood.
 A unit of whole blood or packed red cells will raise the
haematocrit by 3% and the haemoglobin by 1-1.5
gm/dL

Frozen red cells
 reduces the risk of infusing antigens, or foreign bodies,
that the body might regard as potentially dangerous
 Previously sensitized patients
 Not available for use in emergency situations
 RBC viability is improved
 ADP and 2,3 DPG maintained

Platelet concentrates
 Component: platelets, 50 ml plasma
 Essential for clotting process.
 Platelets are stored for up to five days at room
temperature.

 Indication
 used if there is a platelet disorder
 when massive blood loss has occurred

 Platelets must be stored at room temperature, so
are good only for 5 days or less.
 One unit will usually raise the platelet count 5-
10k/microliter.
 Check one hour after transfusion.
 If the platelet count does not increase as expected
(“refractoriness”), suspect DIC or immune platelet
destruction (anti-HLA).

Fresh frozen plasma
 From freshly donated blood
 Source of vit k- dependent clotting factors
 Only source of factor V

Fresh Frozen Plasma
 Indication
 For coagulopathy and deficient clotting factors
 1 unit FFP = 3% increase in CF levels
 At least 30% to ensure adequate coagulation

Cryoprecipitated antihaemophilic
factor
 an antihaemophilic concentrate
 prepared from plasma and is rich in clotting factors
 used in people with haemophilia, von Willebrand's
disease or other major coagulation abnormalities to
prevent or control bleeding

Cryoprecipitated antihaemophilic
factor
 Its contents are the major portion of the Factor VIII,
von Willebrand factor, fibrinogen, Factor XIII and
fibronectin present in freshly drawn and separated
plasma.

PACKED RED CELLS
 Haemoglobin less than 7 gm/dL
 Preoperative haemoglobin less than 9 gm/dL and
operative procedures or other clinical situations
associated with major predictable blood loss
 Symptomatic anaemia in a normovolaemic patient
 Acute loss of at least 15% of estimated blood
volume with evidence of inadequate oxygen
delivery following volume resuscitation

FRESH FROZEN PLASMA
 PT or APTT greater than 1.5 times the mean of the
reference range (PT>16, PTT>39) in a non-bleeding
patient scheduled to undergo surgery or invasive
procedure
 Massive transfusion (more than 1 blood volume or
10 units) and coag tests are not yet available
 Emergency reversal of coumadin anticoagulation
 Coagulation factor deficiency

PLATELETS
 Platelet count less than 20,000 in a non-bleeding patient
with failure of platelet production
 Platelet count less than 50,000 and impending surgery or
invasive procedure, patient actively bleeding, or outpatient
 Patients during or after open heart surgery or intra-aortic
balloon pump with diffuse bleeding
 Massive transfusion (more than 1 blood volume or 10 units)
when platelet counts are not available
 Qualitative platelet defect (bleeding time greater than 9
minutes) with bleeding

 Transfusion Guidelines:
 Platelet count < 20,000/mm3
 Platelet count <50,000/mm3 if with microvascular
bleeding
 Complicated surgeries with >10 units of blood
transfused, with signs of microvascular bleeding
 Documented platelet dysfunction(prolonged BT,
abnormal plt function tests)

CRYOPRECIPITATE
 Fibrinogen less than 100 mg/dL
 Fibrinogen less than 120 mg/dL with diffuse
bleeding
 Von Willebrand disease or hemophilia
unresponsive to desmopressin (DDAVP) and no
appropriate factor concentrates available
 Uremic bleeding if desmopressin is ineffective
 Factor XIII deficiency

major indication for whole blood
transfusion
 some cases of cardiac surgery
 massive haemorrhage when more than 10 units of red
blood cells are required in any 24-hour period

Transfusion reactions
 Haemolytic Reactions
 Allergic Reactions
 Febrile Reactions
 Bacterial Contamination
 Circulatory Overload
 Hypothermia

Transfusion reactions
 Alloimmunization
 Graft Versus Host Disease (GVHD)
 Transfusion related acute lung injury (TRALI)

Haemovigilance
 Haemovigilance is the ‘systematic surveillance of
adverse reactions and adverse events related to
transfusion’ with the aim of improving transfusion
safety.

Non-infectious hazards of
transfusion
 Acute transfusion reactions
 Febrile non-haemolytic transfusion reactions – usually
clinically mild.
 Allergic transfusion reactions – ranging from mild urticaria to
life-threatening angio-oedema or anaphylaxis.
 Acute haemolytic transfusion reactions – e.g. ABO
incompatibility.
 Bacterial contamination of blood unit – range from mild
pyrexial reactions to rapidly lethal septic shock depending on
species.
 Transfusion-associated circulatory overload (TACO).
 Transfusion-related acute lung injury (TRALI).

Allergic / urticarial transfusion
reactions
 most common usually due to allergies to specific
proteins in the donor’s plasma
 can be avoided with future transfusions by
pretreatment with antihistamines or steroids.
 Some get “hay fever / hives / wheezing” from
transfusions
 you can continue the transfusion when they are better
 and in the future, pre-treat with an antihistamine.

Haemolytic Reactions
 transfusion of an incompatible blood component.
 Most are due to naturally occurring antibodies in the
ABO antigen system and Rh groups
 may cause haemoglobin induced renal failure and a
consumptive coagulopathy (DIC).

Immediate haemolytic transfusion
reaction
 1 in ~25,000 units; fatality rate 10%
 A disaster, almost always preventable.
 Most often due to ABO mismatch due to a clerical
error (i.e., the wrong blood and/or the wrong
recipient).

Delayed haemolytic transfusion
reactions
 1 in ~6000; fatality rate 0.1%
 previously sensitized to an antigen through
transfusion or pregnancy
 can result in symptomatic or asymptomatic haemolysis
several days (2-10 days) after a subsequent transfusion

reactions
 Not preventable.
 A new antibody or anamnestic response has probably
developed.

reactions
 Most frequent: Transfusion of Rh positive red blood
cells to an Rh negative woman of childbearing age can
result in sensitization and haemolytic disease of the
newborn in future pregnancies.

Febrile non haemolytic transfusion
reaction
 Defined to be a rise in temperature of 1 °C or more
and >=38 °C, within 24 hours of transfusion
 without evidence of a hemolytic transfusion
reaction.
 due to cytokines in the blood itself and/or
produced in the patient from sensitivity to the
HLA molecules on platelets and white cells.

Febrile transfusion reactions
 usually occur due to sensitization to antigens on cell
components, particularly leukocytes.
 chills and a temperature rise
 60-90 mins after transfusion

Bacterial contamination
 Rare
 Acquired from contaminated collection bags
 Poor cleaning of donor’s skin
 reactions are quite severe with high fever
 rigors and/or other systemic symptoms such as
hypotension, nausea or vomiting.

Bacterial contamination
 Gram – organisms, Pseudomonas sp., Coliforms and
Yersinia
 Pseudomonas sp can grow at 4°C
 Are the most common
 Platelets (kept at room temperature during their 5-day
shelf life) are a great culture medium
 especially for skin staphylococci from the venipuncture

Transfusion Related Acute Lung Injury
(TRALI)
 “noncardiogenic pulmonary edema”
 Defined to be ARDS within 6 hours of a transfusion
with no other clear cause
 occurs when donor plasma contains an antibody,
usually against the patient's HLA or leukocyte specific
antigens.

Transfusion Related Acute Lung Injury
(TRALI)
 1 in 1000; fatality rate <1% with estimates varying
widely
 The cause is apparently antibodies in the donor
plasma against the patient’s neutrophils (which, in
the sick, are marginated in the lung vessels).
 The donor antibodies cause these neutrophils to
release toxic products and thus produce ARDS.

Electrolyte toxicity (i.e., potassium)
 A real danger for newborns
 one may prefer washed red cells.
 If haemolysed blood is administered (i.e., the blood
was left on the radiator or the warmer was too hot), the
result will be catastrophic.

Hypothermia
 Red cells and fresh frozen plasma are chilly.
 An extra blanket is much safer than an electric
warming coil
 even “the special warmers for blood that don’t go over
104o F / 40o C.

Overtransfusion
 Rapid infusion of blood
 Plasma expanders, iv fluids
 Regulate BT 2-4 hrs each bag
 CVP
 diuresis

Transmission of diseases
 Malaria, Chagas’, syphilis
 Transmitted BT
 CMV
 Hepatitis C and HIV-1
 Dramatically decreased
 Better antibody and nucleic acid screening
 1 per 1,000,000 units
 Hepatitis B
 1 per 100,000 units

Transmission of diseases
 Hepatitis A
 Very rare, no asymptomatic carrier state
 “Pathogen in-activation system”
 Reduces infectious levels of all viruses and bacteria
transmissible by transfusion

Volume replacement
 Most common indication for Blood transfusion
 Acute blood loss
 Measures of hgb and hct
 Misleading in acute bleeding
 Normal in spite of severely contracted blood volume

Blood loss of 1L in a healthy adult
 Venous hct falls by
 3% in the first hour
 5% at 24 hours
 6% at 48 hours
 8% at 72 hours

Transfusion alternatives
 Transfusion alternatives have largely been developed
to reduce donor red cell transfusion in surgery, where
they are most effective as part of a comprehensive
‘patient blood management’ programme.
 Many of these techniques have wider application,
ranging from traumatic and obstetric haemorrhage to
patients who do not accept blood transfusions.

 Predeposit autologous blood donation before surgery
is of uncertain benefit and now has very restricted
indications in the UK.
 Intraoperative cell salvage (ICS) is effective (and may
be life-saving) in elective or emergency high blood loss
surgery and management of major haemorrhage.
 Postoperative cell salvage (PCS) and reinfusion can
reduce blood use in joint replacement and scoliosis
surgery.
 Acute Normovolaemic Haemodilution

 Tranexamic acid (antifibrinolytic) is inexpensive, safe and
reduces mortality.
 Recombinant activated Factor VII (rFVIIa)
 Erythropoiesis stimulating agents (ESAs), such as
erythropoietin, are standard therapy in renal anaemia and
can support blood conservation in some cancer
chemotherapy patients and autologous blood donation
programmes. They may also be effective in selected
patients with myelodysplasia.
 Safe parenteral iron preparations are now available and
may produce more rapid and complete responses in iron
deficiency anaemia.

Alternatives to standard
transfusion
 Inhibitors of thrombolysis (EACA or tranexamic acid)
 Use of growth factors such as erythropoietin
 Autologous donation (preoperative autologous blood
donation, acute normovolaemic haemodilution, cell
salvage)
 Use of haemostatics such as thrombin, fibrin sealant
or recombinant factor VIIIa
 None (improving transfusion practice so only transfuse
when appropriate)

Acute normovolaemic
haemodilution (ANH)
 In ANH several units of blood are collected into standard blood
donation packs immediately before surgery (usually in the
operating room) and the patient’s blood volume is maintained
by the simultaneous infusion of crystalloid or colloid fluids.
 The blood is stored in the operating theatre at room temperature
and reinfused at the end of surgery or if significant bleeding
occurs.
 ANH is most often used in cardiac bypass surgery where the
immediate postoperative transfusion of ‘fresh whole blood’
containing platelets and clotting factors is seen as an advantage.
 Reported hazards of ANH include fluid overload, cardiac
ischemia and wrong blood into patient errors.

Intraoperative blood salvage (IBS)
 Known as intraoperative autologous transfusion, intraoperative salvage,
or intraoperative autotransfusion.
 IBS is unique among autologous transfusion methods because of its
capacity to provide immense quantities of autologous blood very
rapidly.
 In comparison, preoperative collection is limited by time constraints
and patient tolerance,
 haemodilution is limited by blood volume and haemodynamic
considerations,
 Postoperative salvage is limited by mechanical problems and concern
about microbial contamination.
 IBS can be utilized throughout a surgical procedure and can replace
blood in proportion to the volume lost. In certain situations, most
notably liver transplantation, the rate and volume of replacement may
be extraordinary

Cell saver
 Cell Saver
(Intraoperative Cell
Salvage Machine)
Commonly known as a
"cell saver", the
intraoperative cell
salvage machine
suctions, washes, and
filters blood so it can be
given back to the
patient's body instead of
being thrown away.

Complications of IBS
●Air embolism
●A coagulopathy, which can be avoided by washing the salvaged blood.
●The "salvaged blood syndrome," which refers to the development of
disseminated intravascular coagulation (DIC) and/or increased capillary
permeability in the lungs (acute respiratory distress syndrome) or periphery
(anasarca) after the administration of washed autologous red cells . This
syndrome appears to be mediated by activation of platelets and white blood
cells during salvage. Platelet debris may be responsible for DIC, whereas
activated white blood cells may increase vascular permeability. This rare
syndrome can be prevented by avoiding the aspiration of very dilute blood and
by using citrate, rather than heparin, as the anticoagulant.
●Infection, which can be avoided by using prophylactic antibiotics and by not
aspirating from obviously infected sites.
●Fat embolism, which is preventable by extra washing and by using a
microaggregate filter for reinfusion.
●Microaggregates, consisting of white cell and platelet debris, can develop in
salvaged blood. Microembolization can be prevented by using a
microaggregate filter for reinfusion. This is standard practice in blood salvage
program

Auto Transfusion
 After preoperative autologous donation and
intraoperative hemodilution, intraoperative and
postoperative blood salvage are the third and fourth
components of a complete blood conservation
program
 In salvage techniques, blood that is shed during or
after surgery (or trauma) is retrieved, processed in
some fashion, and returned to the patient. Processing
can be as simple as filtration or, most commonly,
involves centrifugation and washing prior to re-
transfusion.

 autologous blood recovery system is designed for use
in procedures where medium- to high-volume blood
loss occurs, such as trauma cases. With the ability to
deliver moderate haematocrit and to help remove
traces of undesirable components such as free
hemoglobin
 A critical tool to help avoid unnecessary allogeneic
transfusions.
 sequestration protocol for the collection of platelet
rich plasma and platelet poor plasma, and can be run
in automatic or manual mode.

Postoperative blood salvage (PBS),
 postoperative blood collection, refers to the collection
of blood from surgical drains and reinfusion with or,
much more commonly, without processing.
 PBS is an accepted practice in cardiac surgery , in
which its safety and efficacy have been confirmed in
most, but not all, studies.
 It has also become increasing popular in orthopedic
procedures . The contribution of PBS to overall blood
conservation is generally less than that of preoperative
blood donation or intraoperative blood salvage

Pharmacological measures to
reduce transfusion
 Tranexamic acid
 Aprotinin
 Aprotinin inhibits many proteolytic enzymes and reduces fibrinolysis. It is bovine in origin and severe allergic reactions,
occasionally fatal, occur in up to 1 in 200 patients on first exposure.
 Tissue sealants
 Also known as ‘biological glues’ or ‘tissue adhesives’, tissue sealants may be derived from human or animal clotting factors
such as fibrinogen (sometimes activated by thrombin in the syringe immediately before administration) or synthetic
hydrogel polymers. They are sprayed on surgical fields or raw surfaces to promote haemostasis and reduce blood loss.
Clinical trials show that they can reduce surgical bleeding and exposure to donor blood, the effect being most significant
in orthopaedic surgery.
 Recombinant activated Factor VII (rFVIIa, NovoSeven™)
 rFVIIa directly activates blood-clot formation at sites of exposed tissue factor in damaged blood vessels, bypassing other
clotting pathways. It is only licensed for the treatment of bleeding in patients with haemophilia A or B with inhibitors
 Desmopressin (DDAVP)
 Desmopressin causes the release of Factor VIIIc and von Willebrand factor (vWF) from endothelial cells and is used to
treat or prevent bleeding in patients with mild type I von Willebrand’s disease or haemophilia A. It may reduce bleeding
in patients with uraemia and platelet dysfunction due to kidney failure. The standard dose for this indication is 0.3 µg/kg
subcutaneously or intravenously. The template bleeding time is shortened within 60 minutes and the effect lasts less than
24 hours. Repeat doses may be less effective as stores of vWF are depleted. It may also cause headaches and facial
flushing.
 Erythropoiesis stimulating agents (ESAs)
 Erythropoietin (Epo) is produced in the kidneys and increases red blood cell production in the bone marrow in response
to reduced oxygen delivery to the tissues. Recombinant human erythropoietin (rHuEpo) was initially licensed for treating
the anaemia of renal failure and longer-acting forms, such as darbopoietin alfa, have now been introduced

Why?
 First, here is continual concern as to whether the
number of active donors is sufficient to meet the
demand for blood
 Secondly, despite the low risks associated with blood
transfusion practitioners, patients and the public
perceive transfusion as a risky medical procedure

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