Haematology Flashcards
What is plasma
Liquid component of blood.
What is the buffy coat comprised of
Leukocytes and platelets
order of plasma protein abundance and how to test
Test by electrophoresis. Serum albumin most abundant (at positive anode) then globulins: alpha 1, alpha 2, beta 1, beta 2, gamma)
What is serum
Plasma minus clotting factors
Order of fluids in body from most to least
Intracellular, extracellular/interstitial fluid, blood plasma, then cellular fluid
Name the functions of plasma
Clotting ( clotting factors and Von willebrand) , Immune defence (antibodies and complement proteins) , osmotic pressure maintenance (albumin ), metabolism ( glucose AA’s and vitamins transported in plasma), Endocrine (Many hormones soluble in plasma), Excretion (Cell metabolism waste products travel in blood like urea)
Serum albumin production, functions
Produced by the liver.
Transports lipids, hormones and ions
Maintains osmotic pressure of plasma
Albumin transports fatty acids released from triglycerides in lipolysis, for tissue use
Difference between preparing plasma and serum
Plasma is relatively quick - add an anticoagulant and spin
Serum is taken into a tube without an anticoagulant allowed to clot then centrifuged so takes a little bit longer but a silica coat will form between the two layers making it a cleaner sample
Alpha 1 globulin production and functions
A1AT is produced by the liver, it inhibits proteases and protects tissues from enzymes especially neutrophil elastase which is released by neutrophils during inflammation and damages tissues.
What does deficient A1AT cause
Degradation of lung tissue leading to a loss of elasticity and respiratory problems. This type of globulin is the most vulnerable to inhaled pollutants
Example of alpha-2 globulins and their function
Haptogloblin which binds to the Haemoglobin release from red blood cells when they die, the spleen will remove the haptoglobin-Haemoglobin complex, it avoids toxic levels of oxygen which could produce radical species
Alpha-2 macros login is a protease inhibitor and can inactivate fibrinolysis, stops the breakdown of fibrin in blood clotting
Measuring what can help to diagnose haemolytic anaemia
Haptoglobin as more red blood cells are lysed and therefore haptoglobin is binding to more
Examples of beta globulins, their functions and where they’re produced
Produced in the liver
Beta globulins include C3 and C4 as well as transferrin
Transferrin transports dietary iron and iron for, ferritin stores
Gamma globulin examples and diagnostic use
Immunoglobulins and C reactive proteins
Large peak of gamma globulins indicate infection or myeloma
Role of Mg2+
Cofactor for many enzymes
How are intracellular and extracellular contents of plasma balanced
NA+ plentiful in the plasma whilst K+ is plentiful intracellularly. The positive charge from K+ inside the cell is balanced by extracellular Cl- and anions like proteins nuclei acids and phosphorylated proteins
Why is the NA/K ATPase pump significant
Needed to maintain functioning of electrically excitable cells like neutrons and muscle fibres. 1/3 of AT{ consumed during rest is to power this pump.
When ATP is depleted what happens to cells
Cells become more spherical and intracellular and extracellular concentrations change and NA+ and H2O move in
Name the three usages of plasma in regards to disease and disease protection and explain
Biomarkers- study of plasma proteome and it’s links with disease, medications and lifestyle to make treatment decisions. Elevated levels become biomarkers of disease
Passive immunotherapy- immunoglobulins can transfer immunity from on to another e.g take plasma from a donor: concentrate IVIG (intravenous immunoglobulin G) as IVIG contains large amounts of IgG antibodies so can protect against common pathogens the donor has been exposed to - good for lupus patients
3) Hyperimmune globulin - donors screened via ELISA for high levels of IgG against a certain pathogen, the IgG fraction is isolated and concentrated providing passive immunity to a specific pathogen for someone. Given after someone has high risk exposure to a pathogen like rabies, hep B, etc. vaccines provide active immunity but take weeks for a response.
Where do red blood cells come from and what from
From the bone marrow, derived from haematopoeitic stem cells which make lymphoid stem cells ( lymphoid progenitor) to make lymphocytes like T cell, B cell and NK cells and myeloid stem cells (myeloid progenitor) where erythrocytes, platelets, monocytes, granulocytes, basophils, eosinophils and mast cells are derived
What is haematopoeisis
Formation and development of blood cells
Two functions of haematopoeitic stem cells
Ability to self renew as daughter cells become the stem cells again
Can differentiate to mature progeny where the daughter cells follow a differentiation pathway
Order the differentiations of myeloid stem cells from longest life span and state their function
Erythrocyte longest about 120 days for oxygen transport
Platelet 10 days for Haemostasis
Monocyte few days for defence against infection phagocytoses and kills
Neutrophil 7-10 hours defence against infection phagocytoses and kills
Eosinophil less than neutrophil is against parasitic infection seen in allergies
Lymphocyte variable lifespan for humour also (b cells making antibodies) and cellular immunity (T cells directly killing)
Sites of haematopoeisis in foetus
At 3 weeks the yolk sac makes haematopoeitic stem cells
At 6-8 weeks the liver makes HSC expands and maintains supply
At 10 weeks the bone marrow develops haematopoeitic activity and this is where haematopoeitic activity will occur in adults ( pelvis, femur sternum)
What is haematopoeisis regulated by and disruption of this regulation leads to what
Regulated by genes, transcription and growth factors as well as the micro-environment
Disruption causes an in balance between proliferation and differentiation leading to leukaemia or bone marrow failure.
What are haematopoeitic growth factors
Glycoproteins that bind to cell surface receptor to regulate proliferation and differentiation of HSC. They regulate function of mature blood cells
Name the growth factor of erythrocytes
Erythropoietin
Name the growth factors of granulocytes and monocytes
G-CSF, G-M CSF, cytokines like IL’s
CSF is colony stimulating factor
From the lymphoid progenitor, T cell progenitors, B cell progenitors and NK progenitors arise: what is the difference between them
B and NK progenitors are located in the bone marrow. Whereas e T cell progenitors make T cells in the thymus which then move to the bone marrow.
T and NK cells are cytokine producing whereas B cells are antibody producing
Another word for platelets
Megakarytocyte
How does erythropoiesis occur
From the common myeloid progenitor arises a proerythroblast turns into (early, intermediate and late) erythroblasts and then reticulocytes and erythrocytes.
Down the line the nucleus and cytoplasm looking parts becomes more clear ( happens in bone marrow) then in the peripheral blood these become reticulocytes and erythrocytes. Reticulocytes still have some RNA and stain darker
Requirements for erythropoiesis
Folate, B12, Erythropoeitin, Iron
What will low folate, iron and B12 do to cells and what does it cause
Will cause anaemia.
If low iron then red blood cells will be microcytic (often in pregnancy, childhood or low iron resource nations)
If low B12 or folate then red blood cells will be macrocyctic ( due to alcohol excess, pregnancy or veganism )
What is erythropoietin secreted in response to
Hypoxia. Anaemia or hypoxia will stimulate EPO, EPO will stimulate the bone marrow to produce more red blood cells which removed the stimulus to make more red blood cells. Demand supply feedback loop
Function of Iron
Oxygen transport in blood, mitochondrial proteins like cytochromes a,b,c needed for ATP production and cytochrome P450 for hydroxylations
Iron absorption, what non heme contain and iron homeostasis
Iron absorbed in duodenum haeme Fe2+ ferrous form is best absorbed, non heme Fe3+ ferric needs reducing sources like cytochrome B or Vitamin C for absorption.
Excess iron is toxic to heart and liver so absorption is regulated by hepcidin which blocks iron absorption or liver releasing iron.
Iron is absorbed in heme ferrous 2+ form by dmt-1 but as the non heme ferric form can’t be absorbed cytochrome-b or vitamin c turns it into its ferrous form. once inside the cell it can bind to apoferritin forming a ferritin mycelle the change of Fe2+ to Fe3+ crystallises a protein shell this means lots of iron is stored here and will be pooped out as it a not reversible. Once entering the cell however if the iron is needed it can bind to ferroportin which absorbs Fe2+, this step can be inhibited by hepcidin. If not inhibited, hephaestin will convert the iron from the ferrous to ferric form, the ferric form will then bind to apotransferrin and pushed out of the cell
What can inhibit erythropoeisis other than low iron, B12, EPO and folate
IL-1, TNF-alpha, IL-6, IFN gamma can inhibit the secretion of erythropoeitin which is needed for erythropoeisis, it can also decrease responsiveness of erythroblasts to EPO. They can also increase hepcidin which can inhibit erythropoeisis can also result in anaemia as hepcidin stops Fe absorption, transport and availability.
Where is Vitamin B12 found
Meat, fish, eggs, liver, kidney, milk, cheese
Where is folic acid found
Green leafy vegetables, cauliflower, Brussels sprouts, liver and kidney, fruit, yeast
How is Vitamin-B12 absorbed
B12 in the stomach bound to R-protein which is called heptacorrin and this is so the stomach acid doesn’t digest it. Then in the small bowel (ileum) the R protein is digested and it binds to intrinsic factors which are made by parietal cells as intrinsic factors cant be digested. So now you have B12-IF complex which binds to cubulin in ileum to take it into the endothelial cells- the lining. Complex is broken down and B12 binds to transcoalamin II to be taken into blood and to the liver
Inadequate secretion of intrinsic factors is what
Pernicious anaemia
What can cause B12 deficiency
Inadequate diet-veganism, malabsorption in coeliac disease, lack of stomach acid- achlorhydia, inadequate IF secretion-pernicious anaemia
What do Vitamin B12 and Folate deficiency cause
DNA synthesis is inhibited
Both are needed to make dTTP which is a precursor of DNA. dTTP is used to make thymidine
Also affects any rapidly dividing cell so cells grow in bone marrow but can’t divide normally, epithelial cells of mouth and gut affected as cells rapidly divide to replace, gonad nerves are affected
Where is folic acid absorbed and when is more folate needed
Absorbed in small intestine, more needed during pregnancy and for conditions where more red blood cells need to be made like sickle cell anaemia and haemolytic anaemias
Where do blood products go after RBC destruction
Iron from Haemoglobin travels on the plasma bound to transferrin returns to the bone marrow. The heme is broken down into bilirubin and excreted
What does erythrocyte function depend on
Integrity of the membrane
Haemoglobin structure and function
Cellular metabolism
Defect causes haemolysis
Describe the red blood cell membrane
Are biconcave in shape to allow manoeuvrability
Membrane made of lipid bilayer supported by proteins and cytoskeleton contains transmembrane proteins to maintain integrity shape and elasticity of red cell
What do disruptions in vertical membrane linkages cause (ankyrin/spectrin) causes
Hereditary Spherocytosis
Cells will be round and lack central pallor, is the loss of cell membrane without same amount of cytoplasm so become round. Cells are less flexible and removed
What does the disruption of horizontal membrane linkages cause
Hereditary elliptocytosis
Shells become elongated
In metabolism to generate ATP, deficiency of what can cause problems for red blood cells. Describe its effects
Glucose 6 phosphate dehydrogenase is important in the hexose monophosphate shunt (HMP shunt). The HMP shunt aids in glutathione metabolism which protects red blood cells from damage so without G6PD oxidants may be generated in the blood stream due to infections or exogenous sources like drugs or broad beans.
X linked inheritance so usually makes affected
G6PD causes intermittent intravascular haemolysis once exposed to the oxidant. Causes the appearance of bite cells - irregular, smaller, lost central pallor. The Haemoglobin is denatured and forms round inclusions called Heinz bodies
Comes about because has a selective advantage as is resistant to falciparum malaria
From the myeloid progenitor cells megakaryocytes, erythrocytes, mast cells and what can be made. And what can this cell further divide into
Myeloblast
Can differentiate into basophil, neutrophil, eosinophil and monocytes. monocytes can make macrophages
What do granulocytes refer to
Neutrophils basophils and eosinophils as they have granules in cytoplasm for microbicidal function
What do granulocytes signal through
Myeloid growth factors such as G-CSF, GM-CSF and M-CSF to proliferate and survive
Describe what you see within neutrophils
C shape or segmented nucleus, has multiple loves and dense granules inside too
Describe neutrophil migration
Chemotaxis begins to move to tissues, marinated within the vessel lumen, adhere to the endothelium, roll, diapedisis and migrate into the tissues. There they phagocytose microorganisms
Describe an eosinophil function and what you would see in a microscope
Fight against parasitic infection
Very red in the stain, two lobes (bilobed)
Describe basophils appearance in a stain and what it’s granules contain
Will appear very purple and dense as it’s granules contain histamine, heparin and other proteolytic enzymes \involved in immune response especially Type 1 hypersensitivities
What do monocytes look like and what do they do
Monocytes has a curved bean foetus looking nucleus
Phagocytose and present antigens to lymphoid cells. Monocytes migrate to cells and become macrophages to phagocytose. Macrophages store and release iron
Describe T, B lymphocytes and NK cells when they are stimulated to be made and what they look like on a stain
Germinal centre exposed to an antigen,
B cells will differentiate into a plasma cell to secrete antibodies- on a stain B cells have a rounded nucleus and a two tone cytoplasm balayage
T lymphocytes are in cell mediated immunity have a veryyy large round nucleus basically no cytoplasm
NK cells part of innate immune system kill tumour and infected cells, have a weird shaped nucleus and lots of dots
What are the abnormalities of leukocytes (white cells)
REACTIVE OR SECONDARY CHANGES- normal healthy bone marrow responds to infection inflammation or infarction
PRIMARY BLOOD CELL DISORDERS- leukocyte count or morphology is abnormal due to acquired somatic DNA damage affecting a haemopoeitic precursor: gives rise to leukaemia, myelomas, myeloproliferative disorders
What is leukocytosis and some examples
Too many white cells: neutrophilia, eosonophilia, basophilia, lymphocytosis, monocytosis
Usually change in neutrophil count
What is leukopenia
Reduction in total white blood cell number
Neutropenia and lymphopenia
Usually neutrophils
Causes of neutrophilia
Infection (bacterial), inflammation, infarction: any tissue damage
Seen in pregnancy ( may see toxic granulation which is heavy granulation of neutrophils) and after exercise. Also after taking corticosteroids (steroids stop fro, getting into tissue so stays in blood).
Toxic changes occur and left shift with the presence of early myeloid progenitor cells
What disorder causes neutrophilia basophilia and left shift
Myeloproliferative disorder
What is left shift
Increase in non segmented neutrophils (more neutrophil precursors in blood) known as band forms clump together and weird c shape nucleus
What occurs in myeloproliferative disorder aka chronic myeloid leukaemia, what are the signs
Increase in all granulocytes and their precursors
Due to translocation between chromosome 9 and ‘22 in a HSC Ph chromosome. This translocation creates gene BCR-ABL1 which has tyrosine kinase activity and drives blood cell proliferation
Signs: splenomegaly
BCR-ABL1 signals between cell surface and nucleus, tyrosine kinase inhibitors may help
What is the cause of neutropenia
After chemotherapy and radiotherapy, from autoimmune disorders, severe bacterial infections, viral infections and drugs
Has an physiological link to ethnic groups
Neutropenia puts you at high risk for infections need urgent AB’s
What is it called when there is an increase in the amount of neutrophil lobes, what type of shift and what causes it
Neutrophil hypersegmentation
From lack of vitamin b12 and folic acid
What is eosinophilia due to
Allergy of parasitic infection : asthma, eczema and drugs
Can occur in leukaemia
Eosinophils will have usual two lobes but many more granulocytes
What is basophilia due to
Leukaemia
Causes of monocytosis
Chronic bacterial infection or inflammation
Some types of leukaemia
What is lymphocytosis caused by, how will the film look
Viral infection, or a lymphoproliferative disorder aka cancer
Chronic lymphocytic leukaemia
Often atypical lymphocytes, scalloped margins that hug surrounding blood cells. Will see smudged cells
Differences between acute and chronic lymphoid leukaemia
I’m both bone marrow is infiltrated by lymphoblasts causing haematopoeisis problems.
Acute- severe and sudden onset
Chronic- leukaemia cells are mature but abnormal
acute lymphoblastic leukaemia under microscope, and clinical features
Acute - anaemia, neutropenia, thrombocytopenia, cells have less cytoplasm
Prominent bruising from thrombocytopenia
Pale child due to low Hb
Treatment for acute lymphoblastic leukaemia
Give red cells, platelets and antibiotics
Systemic chemotherapy
Intrathecal chemotherapy
Causes of lymphopenia
HIV infection, Chemotherapy, Rdiotherapy, Corticosteroids
Severe infection
Why is homeostasis important
Can stimulate coagulation after injury
Limit response to injury stop thrombosis
Start fibrinolysis to breakdown clot and heal
What does homeostasis result from
Vasoconstriction to respond to injury
Primary homeostasis to make platelet plug (platelet adhesion and aggregation)
Secondary homeostasis to form stable fibrin clot ( blood coagulation)
Describe primary homeostasis- platelet adhesion
Platelet adhesion- platelets stick to damaged endothelium to the glycoproteins. -late let’s either bind to collages (GPIa receptor) or Willebrand factor receptor (GPIb). This bonding activates the platelets changing them from disks to rounded with spicules.
Adhesion causes release of what’s in storage granules. Platelet membrane is invaginate to form a surface connected cannalicular where the platelet contents are released
Describe platelet aggregation
Platelets stimulated to turn arachidonic acid into thromboxane A2 which is a vasoconstrictor. The ADP released from granules and thromboxane A2 from platelets lead to further platelet recruitment and activation. Bind to P2Y12 and thromboxane A2 receptor. Activation of the platelets also causes GPIIb and GPIIIa to turn inside out so fibrinogen can bind. Once it binds it further activates platelets and links the, together forming platelet plug.
What stops platelet aggregation
Active flow of blood and release of prostaglandin PGI2 which dilates blood vessels would stop platelet aggregation
Name the two anti platelet drugs and what they do
Aspirin- stops thromboxane A2 production by blocking COX, so stops platelet aggregation. COX inhibits prostaglandins too but endothelial cells can synthesise more whereas platelets can’t. Effect lasts for 7 days until new platelets
Clopidogrel- blocks ADP receptor P2Y12, lasts for 7 days until new platelets
What is Von Willebrand factor
Glycoprotein, mediates adhesion of platelets to sites of injury and promotes aggregation, carries Factor VIII
Describe secondary Haemostasis
Fibrin formation to stabilise platelet plug. Need thrombin to cleave fibrinogen to make a fibrin clot and cause blood coagulation aka the stabilisation of platelet plug.
Where are clotting factors made and which ones from where
Most made in liver but VIII and VWF are made in endothelial cells. VWF can be made in megakaryocytes
Factors II, VII, IX, X are dependent of Vitamin K (carboxylates glutamic residues)
Turn from inactive zoo gems to active clotting factors when peptide bones broken and active site is exposed
Clotting factors work on exposed phospholipid surface to localise and accelerate reactions. Calcium important for CF to bind
Explain coagulation
INITIATION - Tissue factor exposed on endothelial cell surface when there’s vascular injury. VIIa binds to tissue factor and turns X to Xa and IX to IXa. Xa activates prothrombin (II) to become thrombin (IIa)
AMPLIFICATION- Thrombin (IIa) activates XI to XIa, V to Va, VIII to VIIIa,
PROPAGATION- XI causes more IX to IXa and with VIIIa turns more X to Xa so more thrombin generation. Thrombin will cleave fibrinogen to form insoluble fibrin clot
TF- 7a binds to TF, activates 9 and 10. 10a turns prothrombin-2 to thrombin-2a. 2a activates 11,5,8 . 11 with 8a activates more 10 so more prothrombin 2 can be generated.
.
What are three natural inhibitors of coagulation: how do they work and why are they necessary
Ensure coagulation is confined to injury site, prevent spontaneous coagulation
Protein C, Protein S and anti thrombin
Thrombin binds to thrombomodulin on cell surface activates protein C. Activated protein c inactivates Va and VIIIa if protein s is present.
Antithrombin inactivated thrombin and Xa. Heparin potentiates antithrombin
Three anticoagulant drugs and what they do
HEPARIN- indirectly works by potentiating antithrombin. Need a larger heparin gylycoaminylglycan chain to inactivate thrombin. Given Intravenously or in injection
WARFARIN- vitamin k agonist, stops glycine carboxylation so factors II, VII, IX, X not synthesised. Given as oral tablet monitored by blood testing. Takes days to effect as stops synthesis
DIRECT ORAL ANTICOAGULANTS- directly inhibit thrombin or Xa, orally given no monitoring
Principal fibrinolytic enzyme
Plasmin
How is the fibrin clot broken down
Plasminogen is activated to plasmin via t-PA. t-PA only activates when both are bound to lysine residues on fibrin. Plain then breaks down making FDP (fibrin degradation products).
Plasmin can break down fibrinogen, Va, VIIIa so antiplamin circulates
WHO are thrombolytic agents given to
Ischaemic stroke patients, t-PA given to cause thrombolysis. High risk of bleeding with use
What is an antifibrinolytic drug and how does it work
Tranexamic acid- derivative of lysine
Lysine binds to plasminogen to stop plasminogen binding to fibrin clots COMPETITIVE INHIBITION. stops fibrinolysis
Used in bleeding trauma and disorders
What is prothrombin time
Integrity of extrinsic pathway
Blood and sodium citrate spun to make platelet poor plasma. TF and phospholipid added with calcium length of time to clot is recorded.
PT longer is there’s a problem with clotting factors: 2,5,7,10
What is APTT
Activated partial prothromboplastin time
Intrincsic pathway measured
XII activated by contact activation
Time taken to clot is measured
Prolonged APPT: reduction in clotting factors may have prolonged PT too, if only prolonged APTT then VIII, IX, XI or XII ( 8,9,11,12) deficiency
8 is haemophilia A
9 is haemophilia B
Bleeding cause by
Loss of platelets, loss of coagulation factors, more fibrinolysis
What is thrombosis
Formation of blood clot within an intact blood vessel
Obstructs blood flow
Virchow triad
Blood : venous thrombosis
Vessel wall : arterial thrombosis
Blood flow : both
All three contribute to thrombosis
What things can increase the chance of venous thrombosis
Reduced levels of anticoagulant proteins (antithrombin)
Reduced fibrinolytic activation : inhibition of plasminogen activation
Increased clotting factors of platelets: vIII higher in pregnancy, V Leiden gene mutation means protein C can’t inactivate, myeloproliferative disorders cause more platelets
Difference between Haemoglobin and myoglobin oxygen dissociation curves
Haemoglobin curve is sigmoid shows positive cooperatively as oxygen binds more
Myoglobin curve is hyperbolic 50% saturated at low partial pressures
What molecule from metabolism modulates oxygen binding
2,3 DPG ( made form 1,2 BPG in glycolysis)
Is an allosteric effector and reduces affinity for oxygen
At birth what happens to the globulin genes that are expressed
More foetal Haemoglobin before birth so more alpha and gamma globulins, at birth gamma is changed to beta to make more HbA
Why is foetal red blood cells needed before birth
Have higher affinity for oxygen (left shift on oxygen curve)
Has reduced affinity for 2,3 DPG as gamma chain is different to adult beta chain
When oxygen binds to ferrous iron molecule what can this be described as
Cooperative as changes other subunits affecting thei ability to bind to oxygen. In haemoglobin it’s positive
What is the difference between cooperation in Haemoglobin and myoglobin
Myoglobin lacks cooperativity so although saturates quickly it doesn’t release
In electrophoresis what types of Haemoglobin will migrate further
Haemoglobin A will move further to positive electrode that Sickle Haemoglobin. HbA more negatively charged as has glutamate but sickle cell turns glutamate (hydrophilic, negatively charged) into valine which is hydrophobic and uncharged
Differences between oxy Haemoglobin and deoxyhaemoglobin
Oxy is war, orange red but deoxy has blueish purplish tinge.
Oxy has two peaks in spectrophotometry, deoxy has one
Spectrophotometry can detect changes in oxygen binding by Haemoglobin by looking at peaks, this is done to check newborns respiratory status.
Oxy Hb will absorb more infrared light, less red light compared to deoxy.
Describe effect of carboxyhaemoglobin and methaemoglobin
CoHb is when carbon monoxide binds, Hb has a greater affinity for CO so readily outcompetes
MetHb occurs when ferrous iron turns to ferric so oxygen binding is impaired blood is blue chocolate coloured. Left ward shift as can cause anoxia. Need methaemoglobin reductase to reverse this.
What is a blood group
Combination of RBC antigens on the ,membrane, these antigens differ depending on oligosaccharide or AA sequence
Blood group system
Collection of one or more RBC antigens that one gene or a cluster of homologous genes control
What blood groups are most clinically significant and what is clinical significance
ABO and Rh
Clinical importance depends on capacity of antigens against a specific RBC to cause hameolysis.
Haemolysis will result in:
1) Haemolytic transfusion reactions: incompatible red cells transfused as they have the antibody for that antigen
2) Haemolytic disease of the foetus and newborn: foetus has a different RBC antigen which mother has the antibody to that
What are the types of antibodies against RBC’s
1) naturally occurring antibodies: anti-a anti-b produced when encounter the missing abo group in food or microorganisms happens at an early age.
ABO antibodies are mostly IgM antibodies that don’t switch class, interaction between IgM antibody and RBC antigens causes agglutination - the basic of ABO blood grouping. IgM antibodies can cause haemolytic transfusion reactions through activation of complement system cannot cross placenta tho
What blood groups present what antigen and what is the antigen formed by
All begin with a common glycoproteins and fructose stem which is the H antigen
Group A- A gene codes for N-acetyl galactosamine (GalNac) making A antigen
Group B- B gene codes for galactose resulting in B antigen
Group AB- both A and B antigens
Group O- inactive enzyme made so H antigen remains unchanged
Why would there be differences in prevalences of specific blood groups in different areas
Survival advantages, e.g. blood group O has a survival advantage over malaria so is most prevalent in Africans.
Blood groups are receptors for toxins, parasites and bacteria so can be false receptors to stop the binding to tissue but also can be targeted by bacterial pathogens that carry ABO antigens.
IgM antibodies can’t cross the placenta but IgG can and there are a small amount present in the plasma which can cross the placenta what happens?
Although they can cross the placenta they can’t cause haemolytic disease of the foetus and newborn because
Foetal red cells have poorly developed antigens so can’t support IgG binding
ABO antigens are found on many cells and tissues not just red cells so IgG will likely bind to these cells
However in rare circumstances where the mother has IgG anti A and B antibodies then may cause. But after birth any of the mothers anti a and b antibodies will disappear as the baby develops it’s own IgM antibodies
For blood transfusions what things should be checked to prevent HTR in Red Blood cells and platelets
Red blood cells- ABO compatible, a to a, b to b, give o as has no antigens in emergency
Platelets- same ABO when possible to reduce risk of poor transfusion but ABO antigens on platelets is rare. It also reduces risk of haemolysis of patients own cells if anti a or b antibodies are present in plasma given - however platelets are marked with high titre negative if they don’t have high titres of antibodies so these are fine to give
What is the Rh system
Rh D positive or negative, only negative if have two recessive Rh D copies so no D antigen.
What happens if a Rh D- is exposed to Rh D+, how can this be treated
IgG anti D antibodies will be made, this may happen due to blood transfusion or during pregnancy. This will cause Haemolytic Transfusion Rejection or Haemolytic disease of the foetus and newborn if mother who is Rh- is carrying a Rh+ baby. Baby may die or survive but have brain damage from bilirubin
Ensuring correct blood transfusions, or give pregnant women anti-D immunoglobulin which destroys any Rh+ foetal Red blood cells in maternal circulation before anti-D antibodies are made SENSITISATION
For transfusion of red cells, platelets and fresh frozen plasma what has to be taken into consideration in regards to Rh groups
Red cells- same RhD type: can give Rh D- to anyone but that’s wasteful
Platelets- platelets should be same RhD type as some platelet transfusions still contain RBC fragments that can cause ALLOIMMUNISATION. If this occurs anti-D immunoglobulin must be given
Fresh frozen plasma/cryoprecipitate- any D type as there’s no red blood cells
How to check for ABO and Rh group
Group and screen
FORWARD GROUP- patients red blood cells which has their antigens tested against anti-A/B/O antibodies. Whatever agglutinates is what antigen is present on the red blood cell and therefore the patients group. Group O won’t agglutinate at all because has no A or B antigen, AB will agglutinate in both
REVERSE GROUP- patients serum which contains antibodies moxed with A and B red blood cells. Whatever doesn’t react is the patients group. Group O will agglutinate in presence of both A and B antigens, group AB won’t agglutinate as doesn’t have antibodies against either
How to test for RhD type
Patients red blood cells which will have the D antigen or no D antigen will be reacted with anti D antibodies, if they’re RhD positive it will react, if negative they don’t have the antigen so no reaction
What is an antibody screen used for
To detect alloantibodies, patients serum tested against panels of red blood cells that contain all clinically relevant RBC antigens. Have to use anti human globulin to see the agglutination
What is a cross match
Cross match is an extra step testing patients plasma against RBCs from the unit selected for transfusion , if no agglutination can be used, in emergencies O RhD - transfused and cross match skipped
How are donors blood tested to be safe
Donors excluded if they have a disease that might make donation hazardous for them or if their blood would be dangerous for recipient .
Donor education and self exclusion of people that are high risk of having blood borne infections as there is a window period of disease where infections can’t be detected
Donor health check questionnaire and health screening interview with a nurse
How are the blood donations tested
Group and screen- to determine ABO and Rh group, undergo further testing for other blood groups, tested to ensure no strong antibodies against s]certain RBC antigens
Infection screening - screening of donors prior to identify those who can’t donate. Test for HIV, Hep B,C,E, HTLV, syphillis. If positive, checked again and if still positive thrown
