Blood 2

04/11/2023 BLOOD AND ITS COMPONENTS 2

The blood group system


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.)


• 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 dangerous for individuals.

What are the different blood groups?


According to the ABO blood typing system there are four different kinds of blood types:

A, B, AB or O (null).

ABO blood grouping system


Blood Types


Blood group A the blood group A, means A antigens on the surface of your RBCs and B antibodies in blood plasma.

Blood group Bthe blood group B, means B antigens on the surface of RBCs and A antibodies in blood plasma.

AB0 blood grouping system


Blood group AB the blood group AB, means both A and B antigens on the surface of RBCs and no A or B antibodies at all in blood plasma.

Blood group Othe blood group O (null), means neither A or B antigens on the surface of your RBCs but have both A and B antibodies in blood plasma.


• The ABO gene is autosomal (the gene is not on either sex chromosomes)

• The ABO gene locus is located on the chromosome 9.

• Each person has two copies of genes coding for their ABO blood group (one maternal and one paternal in origin)

• A and B blood groups are dominant over the O blood group

• A and B group genes are co-dominant

ABO inheritance and genetics


This meant that if a person inherited one A group gene and one B group gene their red cells would possess both the A and B blood group antigens.

These alleles were termed A ( which produced the A antigen ), B (which produced the B antigen) and O (which was non functional and produced no A or B antigen)

What do co-dominant genes mean?


ParentAllele

A B O

A

B

O

Possible Blood group Genotypes


ParentAllele

A B O

A AA AB AO

B AB BB BO

O AO BO OO

Possible Blood group Genotypes


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 AOB B Anti-A BB or BO

AB A and B Neither ABO Neither Anti-A and anti-B OO


Why group A blood must never be given to a group B person?

Giving someone blood from the wrong ABO group could be fatal.

The anti-A antibodies in group B attack group A cells and vice versa.

https://www.nbscollection.co.uk/


more complicated, because there's another antigen to be considered - the Rh antigen.

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 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 Genotype Alleles

Produced

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


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.)


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 fromwhom?


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


Complications of blood transfusion


Non immunological transfusion reaction

1. Bacterial contamination reactions.2. Circulatory overload.3. Transfusion haemosiderosis.4. Complications of massive transfusion.5. Non immune hemolytic reaction6. Disease transmission.


1. Bacterial contamination reaction.

• Although uncommon,but this type of specific reaction can have a rapid onset and high mortality in recipients.

• The presence of bacteria in transfused blood may lead either to febrile reactions in the recipient ( due to pyrogens ) or serious manifestations of septic or endotoxic shock.

• Commonly caused by endotoxin produced by bacteria capable of growing in cold temperatures such as Pseudomonas species, E. coli, Yersinia enterocolitica.


Source of infection.

• Infection of stored blood is extremely rare.• Skin contaminants are not infrequently present in

freshly donated blood but these organisms ( predominantly staphylococci ) do not survive storage at 4 º C although they will grow profusely in platelet concentrates stored at 22 º C.

• Healthy donor who are bacteremic at the time of donation. The majority are due to Yersinia enterocolitica, which grows well in red cell components due to its dependence on citrate and Iron.

• Gram negative, endotoxin – producing contaminants found in dirt, soil and faeces may rarely grow in the storage condition of blood.


•According to CDC , most are caused by blood components contaminated by Yersinia enterocolitica.

•Since 1987, from 20 cases reported to CDC, 12 are caused by this organism.


Clinical manifestation

• Usually appear rapidly during transfusion or within about 30 minutes after transfusion with dryness, flushing of skin.

• Fever, Hypotension, Chills, Muscle pain, vomiting, Abdominal cramps, Bloody diarrhoea, Hemoglobinuria, Shock, Renal failure, DIC.


Management.

• Rapid recognition is essential• Immediately stop the transfusion.• Therapy of shock, steroids, vassopressors, fluid

support, respiratory ventilation and maintenance of renal function.

• Broad spectrum IV antibiotics• The blood component unit and any associated fluids

and transfusion equipment should be sent immediately to blood bank for investigation ie: gram stain and culture.


Prevention• Strict adherence to policies & procedures

regarding blood component collection, storage, handling,and preparation is essential to reduce the risk.

• Visual Inspection of components before release from the transfusion service include any discolouration, visible clots, or hemolysis.

• Ensure the blood components are infused within standard time limits ( 4 hours ).


Prevention

• Blood packs should never be opened for sampling, if any open method of preparation has been used, the unit should be transfused within 24 hours.

• Blood should always be kept in accurately controlled refrigerators (with alarms), maintained strictly at 2 – 6 º C, the blood should never be removed and taken to the ward or OT until it is recquired.


2. Circulatory overload• All patient will experience a temporary rise in blood

volume and venous pressure following the transfusion of blood or plasma except for those who are actively bleeding. However, young people with normal cardiovascular function will tolerate this changes provided it is not excessive.

• Pregnant women, patient with severe anaemia, elderly with compromised cardiovascular function will not tolerate the increase in plasma volume and acute pulmonary oedema may develop.


Clinical manifestation

• Frequently due to transfusion of a unit at too fast rate.

• Signs of cardiac failure – raised JVP, basal crepitations in both lungs, dry cough, breathlessness.


Management

• Stop the transfusion immediately.• Prop up the patient• Oxygen therapy • Intravenous diuretics should be used

appropriately.


Prevention• Packed cell should be used instead of whole blood.• Packed cells should be given slowly over 4 hours.The

usual rate of transfusion is about 200 ml per hour. In patient at risk rate of 100 ml per hour or less are appropriate.

• Diuretics should be given at the start of the transfusion and only one or two units of concentrated red cells should be transfused in any 24 hour period.

• Blood transfusion should be given during the daytime, Overnight transfusion should be avoided wherever possible.


3. Transfusion haemosiderosis

• A complication of repeated long term blood transfusion.

• Most commonly seen in thalassaemic patient.• Each unit of blood has about 200 mg of iron, while

the daily excretion rate is about 1 mg. The body has no way of excreting the excess unless the patient is bleeding.

• Assessment of storage iron levels such as ferritin levels should be done.


The use of Iron chelating agent, Desferrioxamine does not completely overcome the Iron load, but has delayed the onset of problems due to haemosiderosis.

Transfusion of neocytes or young red cells is the other alternative. However, it is expensive, time consuming, and the result are not as favourable as expected.


4. Complication of massive transfusion

• Massive transfusion is defined as the replacement of total blood volume within a 24 hour period.

• This will inevitably lead to :1. Dilution of platelets.

Blood effectively has no functional platelets after 48 hours storage, after 8 to 10 units of blood transfusion, thrombocytopenia will usually seen.Bleeding due to a slightly low platelet is uncommon, therefore routine administration of platelet after certain amount of blood transfusion is unnecessary.Regular monitoring of platelet count is more important.Platelet transfusion may be recquired if platelet count <100 x 10 9 /L with continous bleeding or surgical intervention.


2. Dilution of coagulation factors.

Stored Whole blood < 14 days has adequate levels of most coagulation factors for haemostasis.If stored blood of more than 14 days, or plasma reduced blood or red cells in optimal additive solution is used, replacement of coagulation factors with FFP is necessary.

3. Hypothermia ( defined as core body temperature less than 35 c ) is associated with large volumes of cold fluid transfusion. This may results in cardiac irregularities in

particular VF. Therefore the use of blood warmer is important.


4. Excess citrate can act on the patient’s plasma free ionized calsium and results in hypocalcaemia (transient ).Citrate toxicity occur with extremely rapid transfusion ( one unit every 5 minute ), in premature infant having ET with blood stored in citrate for longer than 5 days.

5. Hyperkalemia

Can be caused by intracellular loss of potassium from RBC during storage or infusion of intracellular potassium depleted RBC blood components such as washed RBC or frozen washed RBC .


The most important consideration in massive blood transfusion is to replace blood loss quickly and adequately. Too little blood , too late has more serious consequences than massive blood transfusion itself.


5.Non immune hemolytic reaction

• Mechanical – heat damage from blood warmer, cold, small gauge needle.

• Environment – hypotonic or hypertonic solution.


6. Disease transmission.

• Hepatitis• Syphilis• Malaria• Cytomegalovirus• Human immunodeficiency virus• Human T cell leukaemia viruses.

Donor selection criteria and subsequent screening of all donations are designed to prevent disease transmission, but these do not completely eliminate the hazards.


White blood cells

• Different from RBC– Larger in size– Irregular in shape– Nucleated– Many types– Granules are present in some type of WBC– Life span is shorter


Classification Of wbc

WBC

Granulocytes

Neutrophils

Eosinophils

Basophils

Agranulocytes

Monocytes

Lymphocytes


Neutrophils• Neutrophil

– 2-5 lobe nucleus– Primary granules

• Pink (azurophilic granules) stained by Azure stain• Grey-blue granules• Contain elastase, cathepsin G, myeloperoxidase

– Secondary granules• Specific granules• Contain lactoferrin

– Tertiary granules• Gelatinase, cathepsin

– Life 10 hours– Diameter – 10 to µM


Eosinophils

• Coarse granules in the cytoplasm, which stain pink or red with eosin

• Bilobed nucleus• Diameter - 10 to 14 µM


Basophils

• Coarse cytoplasm in the cytoplasm• Stain purple blue with methylene blue• Bilobed nucleus• Diameter - 8 to 10 µM


Monocytes

• Largest leukocytes with diameter of 14 to 18 µM

• Cytoplasm is clear without any granules• Nucleus is round, oval horse shoe shaped,

bean shaped or kidney shaped


Normal count


lymphocytes

• No granules• Two groups based on size:

– Large – diameter – 10 to 12mm– Small – diameter – 7 to 10mm

• Two groups based on function– T – lymphocytes– B - lymphocytes


• B – LYMPHOCYTES– B cells make antibodies that bind to pathogens to enable

their destruction. (B cells not only make antibodies that bind to pathogens, but after an attack, some B cells will retain the ability to produce an antibody to serve as a 'memory' system.)


• T – LYMPHOCYTES

– CD4+ (helper) T cells co-ordinate the immune response and are important in the defence against intracellular bacteria.

– CD8+ cytotoxic T cells are able to kill virus-infected and tumor cells.

• Natural killer cells: Natural killer cells are able to kill

cells of the body which are displaying a signal to kill them, as they have been infected by a virus or have become cancerous

http://en.wikipedia.org/wiki/CD4

http://en.wikipedia.org/wiki/Helper_T_cell

http://en.wikipedia.org/wiki/CD8

http://en.wikipedia.org/wiki/Cytotoxic_T_cell

http://en.wikipedia.org/wiki/Natural_killer_cell


platelets

• Small colorless, non – nucleated, and moderately refractive bodies


FUNCTIONS OF PLATELETS

• Role in blood clotting – Platelets are responsible for the formation of intrinsic prothrombin activator. This

substance is responsible for the onset of clotting.

• Role in clot retraction– In the blood clot the blood cells including platelets are entrapped between the

fibrin threads. The cytoplasm of the platelets contain the contractile proteins namely actin myosin and

thrombosthenin. The contractile proteins are responsible for clot retraction.

• Role in repair of ruptured blood vessel – The platelet derived growth factor formed in cytoplasm of

platelets is useful for the repair of the endothelium and other structures of the ruptured blood vessels.

• Role in defense mechanism– By the property of agglutination, platelets encircle the foreign

bodies and kill them by the process of phagocytosis.


• Fate of platelets

– The life span of platelets is 10 days. Platelets are destroyed by tissue macrophage system in spleen.

– So in Splenomegaly there is decrease in platelet count and in Splenectomy there is increased platelet count.


Platelet disorders• Thrombocytopenia

– Decrease in platelet count

Occurs in following conditions:– Acute infections– Acute leukemia– Aplastic and pernicious anemia– Chicken pox– Smallpox– Splenomegaly– Scarlet fever– Tuberculosis– Typhoid– Purpura


• Thrombocytosis – Increase in platelet countSeen in – Allergic conditions– Asphyxia– Hemorrhage– Bone fractures– Surgical operations– Splenectomy – Rheumatic fever– Trauma


Thrombocythemia

• Condition with persistent and abnormal increase in the platelet count– Carcinoma– Chronic disease– Hodgkin’s disease


Glanzmann thrombasthenia

• Inherited hemorrhagic disorder caused by the structural or functional abnormality of platelets.

• Platelet count is normal• Characterized by normal clotting time, normal

or prolonged bleeding time but defective clot retraction


Hemostasis

• Arrest or stoppage of bleeding• Three stages

– Vasoconstriction– Platelet plug formation– Coagulation of blood


Coagulation of blood


Conversion of prothrombin to thrombin


Extrinsic pathway


Intrinsic pathway


Test for clotting


• Bleeding time – The time interval from oozing of blood after a cut

or injury till arrest of bleeding.– It is determined by DUKE method using blotting

paper or filter paper method.– Normal duration is 3 to 6 minutes.– Prolonged in purpura


• Clotting time– The time interval from oozing of blood after a cut

injury or till the formation of clot.– Determined by Capillary tube method– Normal duration is 3 to 8 minutes– Prolonged in hemophilia


• Prothrombin time– Time taken by blood to clot after adding tissue

thromboplastin to it.– Normal duration is about 12 seconds.– Prolonged in deficiency of prothrombin, and other

factors like 1, 5, 7 and 10– Normal in hemophilia


Blood is collected and oxalated so that, the calcium is precipitated and prothrombin is not converted into thrombin, thus, the blood clotting is prevented

Large quantity of TTP with calcium is added to the blood. calcium nullifies the effect of oxalate. Thus TTP activates prothrombin and blood clotting occurs.

During this procedure the time taken by blood to clot after adding TTP is determined


• Partial prothrombin time– The time taken for blood to clot after adding

phospholipids and calcium to it.– This test is done to investigate the bleeding

disorders and to detect the presence of heparin in patients treated with heparin therapy.

– Normal duration is 30 to 50 seconds.– Prolonged in heparin therapy and deficiency of

factors like 2, 5, 7, 9, 10, 11, 12.


• Thrombin time– The time taken for the blood to clot after adding

thrombin to it.– To investigate the presence of heparin in plasma

or to detect the fibrinogen abnormalities– Normal duration is 12 to 20 seconds– Prolonged in heparin therapy and during

dysfibrinogenimia ( abnormal function of fibrinogen with normal fibrinogen level).

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