Haemotology Flashcards
Why do blood groups occur?
Antigens expressed on cell surface
Two different types - A and B, can have either, neither or both
A and B are co dominant, O is recessive
Why are blood groups important?
Will have antibodies against antigens you do not have as are ubiquitous in organisms, including gut flora
Who are the universal donors/receivers for:
Blood?
Plasma products?
Blood - universal receiver AB, donor O
Opposite for plasma - Reciever O, donor AB
Why is anti-RhD (resus) important?
Resus negative can make anti RhD if exposed (in transfusion or pregnancy)
Can cause haemolytic crisis in newborns/in transfusions in future
What are blood donors tested for?
ABO/Rh blood groups
Hep viruses, HIV, syphilis
Other viruses
What blood products are formed from the components?
Buffy coat can be separated
>platelets
>white cells
Plasma can be separated into
>Clotting/coagulation factors
>Albumin
>Antibodies
Red blood cells are not separated
What are the indications for red cell transfusion?
To correct severe acute anaemia, which might otherwise cause organ damage
To improve quality of life in patient with otherwise uncorrectable anaemia
To prepare a patient for surgery or speed up recovery
To reverse damage caused by patient’s own red cells
What are the indications for platlets?
Massive haemorrhage
Bone marrow failure
Prophylaxis for surgery
Cardiopulmonary bypass
What are the plasma components?
Fresh frozen plasma
Cyroprecipitate
What is the coombs test?
Antihuman immunoglobulin added to blood, if they bunch up (haemolyse) then it is positive
What bloods do you use for red cell availability in:
Needed in minutes?
Urgently needed?
Non-urgent?
Minutes – O RhD Neg red cells (AB plasma)
Urgent – Type specific (ABO/ RhD)
Non-urgent – Full cross match
Select correct ABO/ RhD type
if allo-antibodies choose antigen negative blood
What is the major haemorrhage protocol?
call 2222
Major haemorrhage protocol activate + ward/location
Bloods delivered ASAP
What are the risks of blood transfusions?
TACO TRALI ATR Febrile, Allergic, vCJD risk
What is TACO?
Transfusion associated circulatory overload
What is TRALI?
Transfusion related acute lung injury
What steps have been taken to reduce prion disease?
Leucodepletion 1998
UK plasma not used for fractionation
Imported FFP for all patients born after 1996
How do you stop haemolytic disease of the newborn?
Prophylatic Anti-D
What hormones regluate stem cells (and can be used therapeutically)?
erythropoietin,
G-CSF,
thrombopoietin agon
What is the pathway for erthroid differentiation?
Erythroblast–>
reticulocyte–>
erythrocyte
What is ertyhropoetin?
A hormone produced by kidneys made in response to hypoxia
Increases red cell count
What is reticylocyte count?
A measure of red cell production
What are platelets?
Cells with immune an haemostastic functions
Production regulated by thrombopoetin
7 days lifespan
What is thrombopoetin?
Hromone produced in liver
Regulated by plaelet mass feedback
Agonists can be used therapeutically
What pathology affects platelets?
Thrombocytosis
>In Myeloid Malignancies: Dominic Culligan
Thrombocytopenia
>Marrow failure
>Immune destruction: ITP: Henry Watson
Altered function
>aspirin, clopidogrel, abciximab etc
What are neutrophils?
Target pathogens, especially bacteria/fungi
Include inerleukins
Production regulated by granulocyte-colony stimulating factor (G-CSF)
Regulated by immune responses
What are the stages of neutrophil differentiation?
Blast Promyelocyte Myleocyte Metamyelocyte Neutrophil
What can cause netrophilia?
Infection
>Left shift, toxic granulation
Inflammation
>eg MI, postoperative, rheumatoid arthritis
What can cause neutropenia?
‘Racial’ Decreased production >Drugs >Marrow failure Increased consumption >Sepsis >Autoimmune Altered function >eg chronic granulomatous disease
What are monocytes?
Macrophages inside blood
phagocytic cells for injestion of pathogens
What are the other meyloid cells?
Eosinophils
Basophils
What are lymphocytes?
Small white blood cells (include T/B cells)
Produced in bone marrow
>B cells mature in bone marrow, T cells in thymus
Circulate in blood, lymph and lymph nodes
Differentiate into effector cells in secondary lymphoid organs (lymph nodes or mucosal associated lymphoid tissue)
A part of the adaptive, and immune mediates systems
What lymphocytes disease?
Lymphocytosis
>Infectious mononucleosis
>Pertussis
Lymphopenia
>Usually post-viral
>lymphoma
What are the subtypes of lymphocytes?
B cells – make antibodies
T cells – Helper, cytotoxic, regulatory
NK cells
How do B cell mature?
Progenitor B cells Pre B cells Immature B cells Naive B cells Germinal cenre Controcyte Then either Memory B cell or plasma B cell
What is positive/negative selection of B cells?
if gene rearrangement results in a functional receptor the cell is selected to survive – positive selection
If the receptor recognises ‘self’ antigens - the cell is triggered to die – negative selection: tolerance
B cells that survive this selection are exported to the periphery
What are the types of human leucocyte antigen?
Class I: displays internal antigens on all nucleated cells
Class II: displays antigens eaten by professional antigen presenting cells
What is included ina full blood count?
Haemoglobin RBC Platlets WBC Neutrophils Lymphocytes >Monoyctes >Eosinophils >Basophils
What are the different diagnostic tools?
FBC Clotting times Bleeding times (platelets) Cehmical assays >Ferritin >B12 >Folate Marrow aspirate Lymph node biopsy
What can cause splenomegaly?
Infectious Haematological-malignant >various leukaemias and lymphomas >myeloproliferative disorders Portal hypertension Haemolytic disorders Connective tissue disorders Sarcoid Malignant Amyloid
What is anaemia?
Reduction in red cells of haemoglobin content
What are the main substnaces needed for red blood cell production?
Iron
B12
Folic acid
Erythropoetin
How are red blood cells broken down?
Macrophages in spleen start process (can calso occur in liver lymph nodes etc)
Globin is broken into amino acids which is reutilised
Haem - the iron is reused, the rest is converted to bilverdin, quickly converted to bilirubin
What can genetic defects in red blood cells affect?
The red cell membrane
Metabolic pathways (enzymes)
Haemoglobin
What 5 proteins are often affected in hereditary spherocytosis?
Ankyrin Alpha Spectrin Beta Spectrin Band 3 Protein 4.2
What is hereditary spherocytosis?
Mostly autosomal dominant disease Where red blood cells are spherical Clinical presentation variable >Anaemia >Splenomegaly >pigment gallstones
How do you treat hereditary spherocytosis?
Folic acid (increased requirements)
Transfusion
Splenectomy
What are the red cell enzymes commonly disrupted?
Pryvuate kinase
Glucose-6-phosphate dehydrogenase
What is the function of the pentose phosphate shunt?
Protects from oxidative damage
What is G6PD deficiency?
Commonest disease causing enzymopathy in the world
Cells vulnerable to oxidative damage
Confers protection against malaria
>Most common in malarial (or historically) areas
X Linked
What is the presentation of G6PD deficiency?
Get blister/bite cells Variable clinical presentation Neonatal jaundice Splenomegaly Broad-bean/infection precipitated jaundice/anaemia
What is pyruvate kinase deficiency?
Reduced ATP
Increased 2,3-DPG
Cells rigid
Variable severity
>Anaemia
>Jaundice
>gallstones
What is normal adult haemoglobin?
2 alapha chains
2 Beta chains
Feotal and A2 also exist in smaller amounts, being alpha gamma and alpha delta respectively
What are the genes for haemoglobin?
2x2 alpha genes on chr16
2x: gamma gamma delta beta on chr 11
>Means that if beta is defective, delta still works
What are haemoglobinopathies?
Inherited abnormalities of haemoglobin synthesis
Reduced or absent globin chain production
>Thalassaemia (alpha α, Beta β, delta δ, gamma γ)
Mutations leading to structurally abnormal globin chain
>eg sickle cell
What is the mutation in skicle cell disease?
beta chains are slightly defective,
results in cell changing shape permanently after being exposed to hypoxia
What are the consequences of sickle cell disease?
Haemolysis leading to vaso-oclusion
This then elads to acute chest syndrome, stroke and pain
Redced life expectancy (mainly due to childhood/perinatal mortality)
What is the clinical presentation of sickle cell disease?
Increased infection risk Painful vasoocclusive crisis Stroke Chest crisis Chromic haemolytic anaemia Sequestation crises
How do you treat a painful crisis of sickle cell?
Analgesia within 30 mins (opiates) Hydration Oxygen Consider antibiotics No routine role for transfusion
What is a chest crisis of sickel cell and how do you managE?
Chest Pain
Fever
Worsening hypoxia
Infiltrates on CXRay
Manage: Respiratory Support Antibiotics IV Fluids Analgaesia Transfusion
What is the long term management for sickle cell?
Vaccination
Penicillin prophylaxis
Folic acid
Be careful if needing regular transfusions for iron overload
What are the different thalassaemias?
Homozygous alpha zero thalassaemia (a0/a0) - incompatable with life
Beta thalassaemia mahor
>No beta chains
>A transfusion dependanet anaemia
Non transfusion dependent
Thalsaemia minor - traits/carrier states
What is beta thalasemia major?
Severe anaemia Present at 3-6 months of age Expansion of ineffective bone marrow Bony deformities Splenomegaly Growth retardation
How do you treat thalassaemia major?
Chronic transfusion support - 4-6 weekly
>Normal growth and development
>BUT - Iron overloading
>Death in 2nd or 3rd decades due to heart/liver/endocrine failure if iron loading untreated
How do you stop iron overloadinh?
Iron chelation therapy
s/c desferrioxamine infusions (desferal)
Oral deferasirox (exjade)
What is sideroblastic anaemia?
Defects in mitochondrial steps of haem synthesis
>ALA synthase mutations
>Hereditary (X-Linked)
>Aquired - Myelodysplasia
What factors affect the normal range of haemoglobin?
Age Sex Ethnic origin Time of day of sample Time taken to analyse
What are the general features of anaemia?
Tiredness/pallor Breathlessness Swelling of ankles Dizziness Chest pain Depend on age and Hb level Others relating to underlying cause
What can cause anaemia?
Disruption of bone marrow
Disruption of red cells
Destruction/loss of red blood cells
What are red cell indices?
MCV = Mean cell volume (cell size) MCH = Mean cell haemoglobin
What are the three types of anaemia?
Hypochromic microcytic
Normochormic normocytic
Macrocytic
How do you investigate the different anaemias?
Hypochromic microcytic - serum ferritin
>Normally caused by low iron
Normochormic normcytic - reticulocyte count
>Tells if bone marrow working well or not
Macrocytic
>B12/folate then bone marrow tests
>Most common cause B12/folate deficency, underlying bone marrow dysplasia
What are the causes of Hypochromic microcytic anaemia?
Low ferritin - iron deficiency
Normal/high ferritin
>Thalassaemia
>Secondary anaemia
How is iron transported?
Transported from enterocytes and macrophages by ferroportin
Transported in plasma bound to transferrin
Stored in cells as ferritin
Hepicidin (liver protein during inflammation) blocks ferroportin
What is iron deficiency anaemia?
Commonest cause
But description not diagnosis
Look for cause - ie bleeding, diet, requirements, malabsorption?
What are the clinical features of iron deficiency anaemia?
Angular cheilitis/stomatitis
Atrophic tongue
Koilonychia
How do you manage iron deficiency anaemia?
Correct deficiency
>Oral sufficienct, IV if oral intolerable
Correct cause >Diet >Ulcer therpay >Gynae interventions >Surgery
What are the causes of normochromic/cytic anaemia anaemia?
Increased reticocyte count
>Acute blood loss
>Haemolysis
Normal/low
>Secondary anaemia
Hypoplasia
What is haemolytic anaemia?
Accelerated red cell destruction (dec Hb)
Compensation by bone marrow ( inc Retics)
Haemolysis either extra (normal) or intravasculae
What can cause haemolytic anaemia?
Congenital Hereditary spherocytosis (HS) Enzyme deficiency (G6PD deficiency)
Acquired (split into immune/ non immune with immune being extra, non being intra mostly)
Auto-immune haemolytic anaemia (Extravascular
Severe infection
Artifical valve
How do you tell if a haemolytic disease is immune mediated or not?
Do a direct antiglobulin test
If positive it is autoimmune, if negative it is not
How do you diagnose haemolysis?
FBC, reticulocyte count, blood film
Serum bilirubin (direct/indirect), LDH
Serum haptoglobin
Then check mechanism
>blood film, coombs tess
How do you manage haemolytic anaemia?
Support marrow function Folic acid Correct cause >Immunosuppression if autoimmune Remove site of red cell destruction Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular
What is secondary anaemia?
70% normochromic normocytic
30% hypochromic microcytic
Defective iron utilisation
>Increased hepcidin in inflammation
>Ferritin often elevated
Identifiable underlying disease
What are the causes of macrocytic anaemia?
Megoblastic - B12/folate defiency (the definition) Or non megablastic >Myelodysplasia >Marrow infiltration >Drugs
What are the causes of B12 deficiency?
Pernicious anaemia
Gastric/ileal disease
What are the causes of folate deficiency?
Dietary Increased requirements (haemolysis) GI pathology (eg.coeliac disease)
What is pernicious anaemia?
Commonest cause of B12 deficiency in western populations Autoimmune disease Antibodies against >intrinsic factor (diagnostic) >gastric parietal cells (less specific)
Leads to malabsorption of dietary B12
Symptoms take up to 1-2 years to develop
How do you treat megaloblastic anaemia?
Replace vitamin
B12 deficiency
>B12 intramuscular injection
>Loading dose then 3 monthly maintenance
Folate deficiency
>Oral folate replacement
>Ensure B12 normal if neuropathic symptoms
What allows for normal blood flow?
Although ability to clot is always present, the endothelium encourages flow with smooth “non stick” surface
What factors contribute towards how long you bleed for?
Platelets Coagulation factors (fibrin clot)
Natural anticoagulants limit clot to that area
What is the clotting process when a blood vessel is damaged?
Platelets and coagulation factors become sticky in response to tissue factors
What can activate platelets/coagulation factors?
Abnormal Surface
Physiological activator
What are the roles of platelets in haemostasis?
Adhering
Activation
Aggregation
Providing surface for Coagulation
