The blood core final

Advanced Clinical Science 1First Semester

Iyad HusseinDDS, 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:ReleaseHistamine and heparin-inflammatory response

Agranulocytes: Lymphocytes: cell

mediated and humoralimmunity

Monocytes: Phagocytosis

Erythrocytes: Haemoglobin O2 transport

Thomboctyes: Blood clotting


Erthrocytes (Red blood cells) Biconcave flexible discs (like

doughnuts with thin centresrather 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


http://www.flickr.com/photos/shirleytwofeathers/2671691775/

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 bilirubinleading 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


LeukocytesAgranulocytes Lymphocytes: 30-40% of WBC

T-lymphocytes: Cell mediated immunity

B-Lymphocytes: Humoralimmune 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


http://www.vetcpdonline.co.uk/images/art_2_haemo_slide_fig7.jpg

LeukocytesGranulocytes 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


http://www.vetcpdonline.co.uk/images/art_2_haemo_slide_fig7.jpg

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 eosinophilcounts


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

EosinophilicMyelocytes

Band Cell

Segmented cell

Eosinophilicgranulocyte

NeutrophilicMyelocytes

Band Cell

Segmented cell

Neutrophilicgranulocyte

Basophilic Myelocytes

Band Cell

Segmented cell

Basophlicgranulocyte

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=_HgTRoesu8M&list=PLDDDE4C372FAB6A37




Haemostasis Step 3

Coagulation cascadeInactive 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=HFNWGCx_Eu4&list=PL08FA078F564D6A69



Primary Haemostasis Tissue injury

Vasoconstriction

Retards blood loss

Platelets adhere to subendothelial cells

Primary platelet plug forms with vWf

ADP, ThrombaxaneA2(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

Ecchymotichaemorrhages

Immediate bleeding


http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://commons.wikimedia.org/wiki/File:Oral_petechiae.JPG&ei=FDx4VNLiNtjdatSIgMAJ&bvm=bv.80642063,d.ZGU&psig=AFQjCNEJ8aa6-FzNIaNGiHIa83QxxKG5bA&ust=1417252233094176

1o Haemostasis inhibitorsNatural 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 cascadeIntrinsic 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__OOa2M



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 petechialhaemorrhages are seen


Tertiary Haemostasis(Fibrinolysis) Formation of Plasminogen, and then plasmin

Plasmin is the main enzyme for fibrinolysis


http://www.lipidsonline.org/slides/slide01.cfm?q=fibrinolysis&pg=1

TertiaryHaemostasis Inhibitors Thrombin activated fibrinolytic inhibitor

Alpha2 antiplasmin

Plasminogen activator inhibitor

Anti fibrinolytic drugs such

Epsilon aminocaprioc acid and

Tranexamic acid



http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://walkin-clinic.co.uk/medical-testing-full-blood-profile&ei=eT94VJOsD8jxasiPAg&bvm=bv.80642063,d.ZGU&psig=AFQjCNG0Da-N2p8xkcea10GfMHVsB2OgqQ&ust=1417253107082426

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://lifeinthefastlane.com/cicm-saq-2012-2-q12/&ei=sD94VJ_SE4_fapCHgaAK&bvm=bv.80642063,d.ZGU&psig=AFQjCNEwa6IdSouwR7t0nenBouOeYJ14UA&ust=1417253143482073

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://lifeinthefastlane.com/cicm-saq-2012-2-q12/&ei=sD94VJ_SE4_fapCHgaAK&bvm=bv.80642063,d.ZGU&psig=AFQjCNEwa6IdSouwR7t0nenBouOeYJ14UA&ust=1417253143482073

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 cephalina 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 Warfarintherapy

INR is based in PT (pts’sPT/Control PT)


Vascular disorders Increased capillary fragility

leading to Purpuras

Conditions

Hereditary Haemorrhagictelangiectasia

Haemangiomas

Vit C deficiency

Connective tissue disorders

Ehlers Danlos


https://www.google.ae/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=https://www.healthtap.com/topics/smokeless-tobacco-chewing-asthma&ei=ezVsVInQF8bhaqzpgOgD&bvm=bv.80120444,d.d2s&psig=AFQjCNFtDddl7SVT3FvxW9qPs2QZ3UT9Dg&ust=1416464095817959

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.


http://www.nhs.uk/Conditions/vitamins-minerals/Pages/Vitamin-C.aspx

Vascular DisordersMarfan’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 dislocactionglucoma, myopia

Joints:hypermobility

Skeleton: Mishapen chest

Arachnodactyly

Maxillary and mandibularretrognathia, high arched palate long face


Vascular disordersOsler-Weber-RenduSyndrome 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


InheritedVascular disorders

Ehlers- Danlos Syndrome Management:

AD 1:5000 live births

Collagen/Protein distruptionlead 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 disordersGlanzmann’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 disordersBernard 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 AspectsLocal 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

AutoimmuneThe 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


ITPAcute 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).


ITPChronic 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, mucocutaneousbleeding, 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 RxIf 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-Dimmunoglobulin. IV anti-D immunoglobulin

Intravenous immunoglobulin (IVIg). IVIg raises the platelet

Predniso(lo)ne/corticosteroids.


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 haemophiliaB (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


CLINICALPRESENTATION 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 VIIIcdictates

Consult Haematologistprior 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 ofhaemophiliacs requiring surgery

Operation FVIII required Preop give Post op schedule

Dental extraction,Dentoalveolar orPerodontal surgery

Minimum of 50% at operation

FVIII ivTransexamic acid 20mg/kg Iv or oral

Local measures

Maxillofacial surgery

75-100% at operation at least 50% 7 days preop

FVIII iv Local measuresInpatient rest for 7 daysSoft diet10 days TranexamicacidAmoxicillinIf bleed Repeat FVIIIRest as in patient 10 daysRepeat 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.


Haemophiliacswith 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 HmA

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


vWNamed 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


vWHas 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


vWType 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


vWManifestation 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 ConditionsDrug 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 malabsorptionof 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 haemastaticmeasures

DDAVP could be used following treatment

Drug doses


Bone MarrowDisorders


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-GenotypeSCD 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 Complicationspain 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 orloss 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 extractionsAll 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

Thalassemia

Haemoglobin Adult blood contains

HgA (has 2 globin chains α2,β2) & HgA2 (has 2 globin chains α2,γ2)

Children have fetalhaemoglobin 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- thalassaemiahas 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 UAEThe 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 thalassaemiaminor, 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 thalassaemiaminor, 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 haemoglobinaccumulation, 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 dentaltreatment 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 Manifestations

Yellow 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)

Chip-munk Facies.

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.DeferoxamineDeferiproneDeferasirox

SplenectomyThe 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 therapybone 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


http://upload.wikimedia.org/wikipedia/commons/3/3e/Autorecessive.svg

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%)


http://upload.wikimedia.org/wikipedia/commons/0/0e/Acute_leukemia-ALL.jpg

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/

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.


http://upload.wikimedia.org/wikipedia/commons/1/1f/ALL_-_Peripherial_Blood_-_Diagnosis_-_01.jpg

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)


http://upload.wikimedia.org/wikipedia/commons/a/a1/ALL-KM-2.jpg

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 reactionwhich 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 AIf 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 BIf 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 ABIf 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 OIf 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 Group

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 Rhantigen - 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 haemolytictransfusion 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.)

BloodType

GenotypeAllelesProduced

Rh positiveRR 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 Rhpositive blood, her body will now be 'primed,' or 'sensitized,' to the Rhpositive 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 Rhfactor. 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 Rhpositive 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 alloantibodiescapable of causing transfusion reactions. Autoanalysersare 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

BLOOD TRANSFUSION

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 transfusionWhole Blood

Cells

Red

Cell concentrate

Platelet concentra

te

White cells

Plasma

Cryoprecipitate

Fresh Frozen plasma

Plasma product

sAlbumin Immunoglob

ulins

Coagulation 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/transfusion-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

Massive transfusion complications 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.

Massive transfusion complications 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.

Platelet concentrates Indication

used if there is a platelet disorder

when massive blood loss has occurred

Platelet concentrates 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 antihaemophilicfactor an antihaemophilic concentrate

prepared from plasma and is rich in clotting factors

used in people with haemophilia, von Willebrand'sdisease or other major coagulation abnormalities to prevent or control bleeding

Cryoprecipitated antihaemophilicfactor 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

Platelet concentrates Transfusion Guidelines:

Platelet count < 20,000/mm3

Platelet count <50,000/mm3 if with microvascularbleeding

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 haemolysisseveral days (2-10 days) after a subsequent transfusion

Delayed haemolytic transfusion reactions Not preventable.

A new antibody or anamnestic response has probably developed.

Delayed haemolytic transfusion 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 diseasesMalaria, 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.

Transfusion alternatives 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.

Transfusion alternatives

Alternatives to standard transfusion Inhibitors of thrombolysis (EACA or tranexamic acid)

Use of growth factors such as erythropoietin

Autologous donation (preoperative autologous blooddonation, 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 normovolaemichaemodilution (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 haemodynamicconsiderations,

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 allogeneictransfusions.

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

Why? The HIV crisis in the 1980s triggered research into

artificial blood

Obtaining regulatory approval for these products has proved difficult so far in Europe and the US

Commercial design approaches include leaving haemoglobin free in plasma, and encasing it in artificial, polymeric red blood cells

The academic community is working on bettering the basic understanding of how blood works, to further improve the products

A blood substitute The development of "artificial blood" or a "blood

substitute" has been one of the great expectations of biotechnology and modern medicine.

No manufactured substance can perform the cellular and molecular functions of blood.

In the past decades, research efforts have been directed toward developing products that have one main purpose: to perform the oxygen-carrying and gas transport function of red blood cells. These products are referred to as oxygen carriers (OC) or oxygen therapeutics.

Oxygen Therapeutics haemoglobin-based oxygen carriers.

Humans

Animals

Artificial

Recombinant

Perfluorocarbon-based oxygen carriers

Complications Massive increase in blood pressure

The concerns came to a head in early 2008, when a meta-analysis of findings from 16 clinical trials of five different products that had been used on over 3500 patients was published in the Journal of the American Medical Association “revealed a threefold increase in the risk of heart attacks in patients who received the substitutes” compared with the control group who received donor blood

The blood core final

Health & Medicine

Transcript of The blood core final