Haematology Flashcards
Blood made up of?
plasma (the liquid of the blood) that contains red blood cells, white blood cells and platelets. The plasma also contains lots of clotting factors such as fibrinogen (forms blood clots)
Once the clotting factors are removed from the blood what is left is called the serum.
Serum contains:
o Glucose
o Electrolytes such as sodium and potassium
o Proteins such as immunoglobulins and hormones
Bone marrow is found?
pelvis, vertebrae, ribs and sternum
Blasts
nucleated precursor cell
- erthyro
- myelo
Reticulocytes
immediate red cell precursor, ‘polychromasia’
Myelocytes
nucleated precursor between neutrophils and mylo-blasts
Haemopoiesis Myelopoiesis or Granulopoiesis Lymphopoiesis Erythropoiesis Thrombopoiesis
The formation of blood cells o (Neutrophils, eosinophils, basophils, monocytes/macrophages) B and T cells RBC platelets
Embryo of blood cells
Orignate in mesoderm
Yolk sac (stops at week 10) then liver (week 6) then marrow (week 16)
3rd to 7th month – spleen
Myeloid: erythroid ratio
relationship of neutrophils and precursors to proportion of nucleated red cell precursors
What regulates haemopoiesis?
- Intrinsic properties of cells (e.g stem cells vs progenitor cells vs mature cells)
- Signals from immediate surroundings and the periphery (microenvironmental factors)
- Specific anatomical area (‘niche’) for optimal developmental signals
How do we assess haemopoiesis?
Morphology of cells
immunophenotyping
• Identify patterns of protein (antigen) expression unique to a cell lineage
• Use antibodies (in combination) specific to different antigens
Pluripotent Haematopoietic Stem Cell
undifferentiated cells that have the potential to transform into a variety of blood cells.
They initially become:
o Myeloid Stem Cells
o Lymphoid Stem Cells
o Dendritic Cells (via various intermediate stages)
Properties of Pluripotent Haematopoietic Stem Cell
- Self-renewal: a property of stem cells, lost in descendants
- Proliferation: increase in numbers
- Differentiation: descendants commit to one or more lineages
- Maturation: descendants acquire functional properties and may stop proliferating
- Apoptosis: descendants undergo cell death
RBC surivive for how long?
3 months
RBC order
Pronormoblast early normoblast intermediate normoblast late normoblast reticulocyte erythrocyte
Platelets precursor and lifespan
megakaryocytes and 10 days
Neutrophil maturation
myeloblast to promyelocyte to myelocyte through metamyelocyte forms eventually to band forms and neutrophils
Neutrophil structure and function
- Segmented nucleus (polymorphs): nucleus condenses into many lobes?
- Neutral staining granules
o Short life in circulation almost 1 day
o Phagocytose invaders
o Kill with granule contents and die in the process (causes pus to go green)
o Attract other cells and complement
o Increased by body stress – infection, trauma (fractured bone) and infarction (MI)
Eosinophils structure and function
o Usually bi-lobed
o Bright orange/red granules
o Fight parasitic infection
o Involved in hypersensitivity (allergic reactions)
o Often elevated in patients with allergic conditions (e.g. asthma, atopic rhinitis
Basophils structure and function
o Quite infrequent in circulation
o Large deep purple granules obscuring nucleus
o Circulating version of tissue mast cell o Role? o Mediates hypersensitivity reactions o Fc Receptors bind IgE o Granules contain histamine
Monocytes
o Large single nucleus (can be kidney shaped)
o Faintly staining granules often vacuolated
o Got open chromatin structure than other cells
o Circulate for a week and enter tissues to become macrophages
o Phagocytose invaders
Kill them
antigen to lymphocytes: MHC II – T helper cells
o Attract other cells
o Much longer lived than neutrophils
Central (Primary) lymphoid tissues
o Bone marrow
o Thymus
Peripheral (Secondary) lymphoid tissues
o Lymph nodes
o Spleen
o Tonsils (Waldeyer’s ring)
o Epithelio-lymphoid tissues
Lymphocytes structure and function
o Mature – small with condensed nucleus and rim of cytoplasm o Activated (often called atyical) – large with plentiful blue cytoplasm extended round neighbouring red cells in the film, nucleus more open structure
Target cells
central pigmented area, surrounded by a pale area, surrounded by a ring of thicker cytoplasm on the outside.
o This makes it look like a bull’s eye target.
o These can be seen in iron deficiency anaemia and post-splenectomy.
Heinz Bodies
individual blobs seen inside red blood cells caused by denatured globin.
They can be seen in G6PD and alpha-thalassaemia.
Howell-Jolly bodies
individual blobs of DNA material seen inside red blood cells.
o Normally this DNA material is removed by the spleen during circulation of red blood cells.
o They can be seen in post-splenectomy and in patients with severe anaemia where the body is regenerating red blood cells quickly.
Schistocytes
fragments of RBC
haemolytic uraemic syndrome, disseminated intravascular coagulation (DIC) or thrombotic thrombocytopenia purpura.
They can also be present in replacement metallic heart valves and haemolytic anaemia.
Sideroblasts
immature red blood cells that contain blobs of iron.
They occur when the bone marrow is unable to incorporate iron into the haemoglobin molecules. They can indicate a myelodysplasic syndrome
Smudge cells
ruptured white blood cells that occur during the process of preparing the blood film due to aged or fragile white blood cells.
o They can indicate chronic lymphocytic leukaemia.
Spherocytes
spherical red blood cells without the normal bi-concave disk space.
They can indicated autoimmune haemolytic anaemia or hereditary spherocytosis.
Consequences of red blood cell structure
Full of haemoglobin: High oncotic pressure (draws water in), oxygen rich environment (oxidation risk)
o Na/K+ ion pump: Keeps water out – as there is a drive for water to go into due to high oncotic pressure. Don’t want it to inflate
- No nucleus: Can’t divide, can’t replace damaged proteins - limited cell lifespan
- No mitochondria: Limited to glycolysis for energy generation (no Krebs’ cycle)
- High Surface area/volume ratio: Need to keep water out
- Flexible: Specialised membrane required that can go wrong
Haemoglobin structure
- A tetrameric globular protein (4 subunits)
- HbA (Adult) is 2 alpha and 2 beta chains
- Heme group is Fe2+ in a flat porphyrin ring
- One heme per subgroup
- One oxygen molecule binds to one Fe2+ (Oxygen does NOT bind to Fe3+)
RBC recycling
- Globin chains recycled to amino acids
- Heme group broken down to iron and bilirubin (porphyrin, biliverdin, bilirubin)
- Bilirubin taken to liver and conjugated
- Then excreted in bile (colours, faeces and urine)
Protects us from free radicals?
- Glutathione protects us from hydrogen peroxide by reacting with it to form water and an oxidised glutathione product (GSSG).
- This can be replenished by NADPH which in turn is generated by the hexose monophosphate shunt
- The rate limiting enzyme in this process is glucose-6-phosphate dehydrogenase (G6PD)
Hb affect
Allosteric affect
one oxygen binds to a subunit the Hb shape changes. This alters how easy it is for the next O2 to bind to a different subunit
Rapapoport lubering shunt
- Curve is shifted right by molecules that interact with Hb (H+, CO2, 2,3 BPG).
- This results in more O2 delivered to tissues.
- 2,3 BPG (or sometimes called DPG) is increased in chronic anaemia
ABO system - dominance
A and B are dominant over O
A and B are co-dominant
O is silent: lack of A or B
RhD
- 2 alleles D and d, inherit one from each parent
- d is silent
- Very immunogenic
- Anti-D antibody can cause transfusion reactions and haemolytic disease of the fetus and newborn
- Avoid exposing RhD negative people to D antigen through transfusions
Pre transfusion testing: ABO grouping
1) Use reagents with known antibody specificity to identity antigens present on red cells (Antisera)
2) Use red cells with known antigen specificity to identify antibodies present in plasma
o Reagent red cells
o Group B reagents cells – anti B in patient plasma
Antisera: looking for the postive result
ABO/D grouping: steps
- ) Tests patients red cells with anti-A, anti-B and anti-D antisera
a. Identify antigens on the red cells
b. IgM reagents – direct agglutination - ) Test patients plasma against reagent red cells of group A and group B
a. Identify antibodies in the plasma
3.) Define the patient blood group
Antibody screening
• Test patient plasma against several reagent red cells which express a known range of antigens
• Identify antibodies in the plasma
• Use the indirect anti-globulin test
o Addition of anti-human globulin (AHG) to plasma/red cell suspension facilities red cell agglutination
Indication for red cell transfusion
Symptomatic anaemia Hb < 70 g/L (80g/L if cardiac disease)
Major bleeding
Always consider cause before transfusion – is there an alternative
Transfuse a single unit of red cells and then reassess patient
Indications for platelets
- Prophylaxis in patients with bone marrow failure and very low platelet counts
- Treatment of bleeding in thrombocytopenic patient
- Prophylaxis prior to surgery/procedure in thrombocytopenic patien
Indications for FFP transfusion
- Treatment of bleeding in patient with coagulopathy (PT ratio >1.5)
- Prophylaxis prior to surgery or procedure in patient coagulopathy (PT ratio >1.5)
- Management of massive haemorrhage
- Transfuse early in trauma (1FFP to one 1 unit)
Acute transfusion reactions (ATR)
usually within 24 hours
Intravascular haemolysis of transfused cells
ATR signs/symptoms
- Chills, rigor, rash, flushing, feeling of impending doom, collapse, loin pain and resp distress
- Fever, tachycardia, hypotension,
ATR Mx
- Stop transfusion
- Assess patient urgently ABCDE (bp, pulse, temp, o2 sats, clinical examination)
- Recheck compatibility tag against patient details and inspect for evidence of contamination
- Document event in medical notes
- Repeat transfusion blood samples
- Bloods for FBC, coagulation screen, renal function and measures of haemoltis, blood cultures
Transfusion associated circulatory overload (TACO) signs/symptoms
o Respiratory distress within 6 hours of transfusion
o Raised BP
o Raised JVP
o Positive fluid balance
TACO risk factors
Elderly patients, cardiac failure, low albumin, renal impairment and fluid overload
TACO Mx
- Oxygen and supportive care as required
- Diuretics
- Consider slowing rate of further transfusions
- Consider diuretics with future transfusion
- Only transfuse minimum volume required
- Aim to identify patients at risk before first transfusion
Mild reactions from blood transfusion
Isolated temp rise > 38 and rise of 1-2 degrees or rash only
Causes of mild reactions of blood transfusion
Febrile non-haemolytic transfusion reaction
o Less common since universal leucodepletion
o Consider premedication with paracetamol if patient suffers repeated reactions
Mild allergic reaction
o Rash/itch but normal observations
o Commoner with plasma rich components
o Treat with anti-histamines
Delayed haemolytic transfusion reactions
Patient mounts delayed immune response to red cell antigen – usually IgG
o positive DAT
extravascular haemolysis 5-10 days post transfusion
transfused cells destroyed
o Hb may drop, raised bili, LDH
o Positive DAT and detection of alloantibody
Anaemia
Reduced total red cell mass, we use Haemoglobin concentration is a surrogate marker
Anaemia is defined as a low level of haemoglobin in the blood.
result of underlying disease and not disease itself
Anaemia ranges
120-165: women
130-180: men
MCV: 80-100 (both)
Microcytic Anaemia
Deficient haemoglobin synthesis: cytoplasmic defect
• Hb is synthesised in the cytoplasm
• To make Hb need all the building blocks. One of these is lacking in microcytic anaemias
o Globins: too put haem groups in to
o Haem: Porphyrin ring & Iron (Fe 2+)
- The nuclear machinery is intact however- so cells can keep dividing
- As a result the cells are microcytic (small)
- And as the contain little Hb they are hypochromic (lacking in colour)
Under 80: problem with haemoglobinisation
Microcytic anaemia causes
o T – Thalassaemia
o A – Anaemia of chronic disease: normal body iron
o I – Iron deficiency anaemia: most common
o L – Lead poisoning
o S – Sideroblastic anaemia: excess iron build up in mitochondria (blue granules around nucleus) due to failure to incorporate iron in to haem.
Normocytic Anaemia Causes
o A – Acute blood loss o A – Anaemia of Chronic Disease o A – Aplastic Anaemia o H – Haemolytic Anaemia o H – Hypothyroidism
Macrocytic Anaemia causes
If MCV high (macrocytic) consider problems with maturation
• Macrocytic anaemia can be megaloblastic or normoblastic.
• Megaloblastic anaemia is the result of impaired DNA synthesis preventing the cell from dividing normally. Rather than dividing it keeps growing into a larger, abnormal cell. This is caused by a vitamin deficiency.
• Megaloblastic anaemia is caused by:
o B12 deficiency
o Folate deficiency
Normoblastic macrocytic anaemia is caused by:
o Alcohol
o Reticulocytosis (usually from haemolytic anaemia or blood loss)
o Hypothyroidism
o Liver disease
o Drugs such as azathioprine
signs/Symptoms of anaemia
• Tiredness
• Shortness of breath
• Headaches
• Dizziness
• Palpitations
• Worsening of other conditions such as angina, heart failure or peripheral vascular disease
o Pica describes dietary cravings for abnormal things such as dirt and can signify iron deficiency
o Hair loss (gradual patchy hair loss) can indicate iron deficiency anaemia
Signs of Anaemia
• Pale skin
• Conjunctival pallor
• Tachycardia
• Raised respiratory rate
• Signs of specific causes of anaemia:
o Koilonychia is spoon shaped nails
o Angular chelitis can indicate iron deficiency
o Atrophic glossitis is a smooth tongue due to atrophy of the papillae
o Brittle hair and nails can indicate iron deficiency
o Jaundice occurs in haemolytic anaemia
o Bone deformities occur in thalassaemia
o Oedema, hypertension and excoriations on the skin can indicate chronic kidney disease
Investigating Anaemia
Hb - not as useful in rapid blood loss or haemodilution MCV B12 Folate ferritin Blood film
Oesophago-gastroduodenoscopy (OGD) and colonoscopy to investigate for a gastrointestinal cause of unexplained iron deficiency anaemia. This is done on an urgent cancer referral for suspected gastrointestinal cancer.
Bone marrow biopsy may be required if the cause is unclear
Reticulocytosis and reticulocytes
Increase red cell production
- Reticulocytes: Red cells that have just left the bone marrow
- Larger than average red cells
- Still have remnants of protein making machinery (RNA)
- Stain purple/deeper red as a consequence due to remnants of protein making machinery (RNA)
- Blood film appears ‘polychromatic’
Classification of anaemia’s (decreased production and increased loss)
Decreased production: under functioning bone marrow and decreased retic count
o Hypoproliferative – reduced amount of erythropoiesis
o Maturation abnormality – erythropoiesis present but ineffective:
Cytoplasmic defects (low MCV): impaired haemoglobinisation
Nuclear defects (High MCV): impaired cell division
Increased loss or destruction of red cells
o Bleeding
o Haemolysis
• Use retic count as a surrogate marker to distinguish between these
• If there is a reticulocytosis (increase) then look for red cell breakdown products
• If bleeding - red cells are gone, nothing to breakdown
• If haemolysing then increased products of red cell destruction are seen
o Increased unconjugated serum bilirubin
o Increased urinary urobilinogen
Iron Deficiency Anaemia
bone marrow requires iron to produce haemoglobin
o Insufficient dietary iron
o Iron requirements increase (for example in pregnancy)
o Iron is being lost (for example slow bleeding from a colon cancer)
o Inadequate iron absorption
Iron absrobed in duodenum and jejunum . Needs acid from stomach to keep in Fe2+ form (soluble).
Conditions and medications that interefere with Fe2+ (make insoluble Fe3+)
- Therefore, medications that reduce the stomach acid such as proton pump inhibitors (lansoprazole and omeprazole) can interfere with iron absorption.
- Conditions that result in inflammation of the duodenum or jejunum such as coeliac disease or Crohn’s disease can also cause inadequate iron absorption.
Mechanisms of Iron Absorption
• Duodenal cytochrome B
o Found in luminal surface
o Reduces ferric iron (Fe3+) to ferrous form (Fe2+)
• DMT (divalent metal transporter) -1
o Transports ferrous iron into the duodenal enterocyte
• Ferroportin
o Facilitates iron export from the enterocyte
o Passed on to transferrin for transport elsewhere
• Hepcidin: The major negative regulator of iron uptake
o Produced in liver in response to increased iron load and inflammation
o Binds to ferroportin and causes its degradation
o Iron therefore ‘trapped’ in duodenal cells and macrophages
o Hepcidin levels decrease when iron deficient
Iron deficiency causes
Chronic Blood loss is the most common cause in adults e.g. heavy menstrual loss (most common in women), colon cancer (women not menstruating and men: dont forget gastritis or oesophagitis and IBD), Haematuria, ulcers, NSAIDs and parasitic infection
Achlorhydria: lack of stomach acid
Dietary Insufficiency is the most common cause in growing children
Poor iron absorption
Increased requirements during pregnancy
Iron transport
Iron travels around the blood as ferric ions (Fe3+) bound to a carrier protein called transferrin: donor tissues to transferrin receptors (marrow)
Total iron binding capacity (TIBC)
total space on the transferrin molecules for the iron to bind. Therefore, total iron binding capacity is directly related to the amount of transferrin in the blood.
Both TIBC and transferrin levels increase in iron deficiency and decrease in iron overload
Transferrin Saturation
If you measure iron in the blood and then measure the total iron binding capacity of that blood, you can calculate the proportion of the transferrin molecules that are bound to iron
Transferrin Saturation = Serum Iron / Total Iron Binding Capacity
Ferritin
form that iron takes when it is deposited and stored in cells
If low: highly suggestive of iron deficiency
if high: inflammation or iron overload
Iron deficiency Dx
confirmed by a combination of anaemia (decreased functional iron) and reduced storage iron (low serum ferritin)
Iron deficiency Ix and Mx
New iron deficiency in an adult without a clear underlying cause (for example heavy menstruation or pregnancy) should be investigated with suspicion
• oesophago-gastroduodenoscopy (OGD) and a colonoscopy to look for cancer of the gastrointestinal tract.
Mx (fastest to slowest)
o Blood transfusion. This will immediately correct the anaemia but not the underlying iron deficiency and also carries risks.
o Iron infusion e.g. “cosmofer”. There is a very small risk of anaphylaxis but it quickly corrects the iron deficiency. It should be avoided during sepsis as iron “feeds” bacteria.
o Oral iron e.g. ferrous sulfate 200mg three times daily. This slowly corrects the iron deficiency.
Oral iron causes constipation and black coloured stools.
It is unsuitable where malabsorption is the cause of the anaemia
- expect 10 grams/litre per week rise
Iron Malutilisation: ‘Anaemia of chronic disease’
Multifactorial with inflammation at the core of it
• Multiple mechanisms all driven by inflammatory cytokines induced by infection/malignancy/autoimmune disease dysregulation
o Blunted EPO response by kidney - cytokines interfering
o Impaired iron availability to erythroid precursors: Hepcidin
o Inhibition of proliferation
o Reduced red cell survival
Differentiating iron deficiency vs anaemia of chronic disease
Ferritin
iron deficiency: reduced
anaemia of chronic disease: normal or increased
Megaloblastic anaemia causes
o B12 deficiency
o Folate deficiency
o Drugs
o Rare inherited abnormalities of metabolism
Normoblastic macrocytic anaemia causes
o Alcohol o Reticulocytosis (usually from haemolytic anaemia or blood loss) o Hypothyroidism o Liver disease o Drugs such as azathioprine o Marrow failure: associated with anaemia Myelodysplasia Myeloma Aplastic anaemia
Megoblastic pathophysiology
Megaloblast: abnormally large nucleated red cell precursor with an immature nucleus
- Megaloblastic anaemias are characterised by lack of red cells due to predominant defects in DNA synthesis and nuclear maturation in developing precursors cells (megaloblasts) in the marrow
- In maturing megaloblasts, division is reduced and apoptosis increases
- Cytoplasmic development and haemoglobin synthesis accumulation occur normally and so the precursor cell is bigger with an immature nucleus
- Once Hb level in the cell is optimal , the nucleus is extruded, leaving behind a bigger than normal red cell i.e. macrocyte
- But overall there are fever macrocytes and hence anaemia
B12 and folate are essential co factors in linked biochemical reactions regulating
- DNA synthesis and nucleus maturation e.g. blood cell effect
- DNA modification and gene activity e.g. nervous system – myelin in NS
Folate absorbed? Causes ?
Absorbed in jejunum (diffusion and actively)
- Inadequate intake: dietary cause more likely than B12 due to lesser stores e.g. alcoholics
- Malabsorption: coeliac and crohn’s disease
- Excess utilisation: haemolysis, exfoliating dermatitis, pregnancy and malignancy
- Drugs: anticonvulsants
Clinical features of B12/folate deficiency
Common to both B12 and folate
o Symptoms and signs of anaemia e.g. breathlessness and fatigue
o Weight loss, diarrhoea and infertility
o Sore tongue and jaundice: haemolysis in the bone marrow – excess bilirubin
o Developmental problems
More with vitamin B12 deficiency (?myelin)
o Neurological problems – posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations
Folate/B12 Ix
MCV high and anaemia
• Pancytopenia (all cells low) in some patients
• Blood film shows macrovaloyctes and hypersegmnted neutrophils (normally 3-5 nucleur segments)
• Assay B12 and folate levels in serum
• Check for autoantibodies
o Anti-gastric parietal cell (GPC) – flaw: sensitive not specific
o Anti-intrinsic factor (IF) – flaw: specific, not sensitive
B12/folate Mx
- Vitamin B12 (Hydroxocobalamin in Europe) injections for life in pernicious anaemia (high dose oral B12 though to be effective)
- Folic acid tablets (5mg per day) orally: different from routine pregnancy recommendation
- Only if potentially life-threatening anaemia, transfuse red cells
Spurious macrocytosis causes
reticulocytosis
Agglutinins
Pernicious Anaemia
Pernicious anaemia is an autoimmune condition where antibodies form against the parietal cells or intrinsic factor.
• A lack of intrinsic factor prevents the absorption of vitamin B12 and the patient becomes vitamin B12 deficient.
• Vitamin B12 deficiency can cause neurological symptoms:
o Peripheral neuropathy with numbness or paraesthesia (pins and needles)
o Loss of vibration sense or proprioception
o Visual changes
mood or congitive changes
Pernicious Anaemia Mx
• In pernicious anaemia oral replacement is inadequate because the problem is with absorption rather than intake.
o They can be treated with 1mg of intramuscular hydroxocobalamin 3 times weekly for 2 weeks, then every 3 months
• If there is also folate deficiency it is important to treat the B12 deficiency first before correcting the folate deficiency.
• Treating patients with folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord.
Consequences of Haemolysis
- Erythroid hyperplasia (increased bone marrow red cell production)
- Excess red cell breakdown products e.g. bilirubin (clinical features differ by aetiology and site of red cell breakdown)
- Bone marrow response: Reticulocytosis and erythroid hyperplasia
Blackwater fever parasite
Falciparum malaria
Autoimmune Haemolytic Anaemia (AIHA)
- Premature destruction of normal red cells (immune)
- Autoimmune haemolytic anaemia occurs when antibodies are created against the patient’s red blood cells.
- These antibodies lead to destruction of the red blood cells
AIHA types
Warm type autoimmune haemolytic anaemia
• Haemolysis occurs at normal or above normal temperatures.
• It is usually idiopathic, secondary to:
o Autoimmune disorders (SLE)
o Lymphoproliferative disorders (CLL)
o Drugs (penicillins, etc)
o Infections
Cold: At lower temperatures (e.g. less than 10ºC) the antibodies against red blood cells attach themselves to the red blood cells and cause them to clump together.
• This agglutination results in the destruction of the red blood cells as the immune system is activated against them and they get filtered and destroyed in the spleen.
•Cold type AIHA is often secondary to other conditions such as lymphoma, leukaemia, systemic lupus erythematosus and infections such as mycoplasma, EBV, CMV and HIV.
AIHI Ix and Mx
Direct coombs test
Mx:
• Blood transfusions: stop patient becoming to anaemic and having an cardiac arrest
• Prednisolone (steroids): dampen the immune system
• Rituximab (a monoclonal antibody against B cells): destroy B cells producing antibodies
• Splenectomy
Alloimmune Haemolytic Anaemia
Alloimmune haemolytic anaemia occurs where an there is either foreign red blood cells circulating in the patients blood causing an immune reaction that destroys those red blood cells or there is a foreign antibody circulating in their blood that acts against their own red blood cells and causes haemolysis.
•The two scenarios where this occurs are transfusion reactions and haemolytic disease of the newborn.
Haemolytic transfusion reactions (antibody produced)
Red blood cells are transfused into the patient.
• The immune system produces antibodies against antigens on those foreign red blood cells.
• This creates an immune response that leads to the destruction of those red blood cells.
• presents a few days after with a blood transfusion
o Immediate (IgM) predominantly intravascular
o Delayed (IgG) predominantly extravascular
Haemolytic disease of the newborn (Passive transfer of antibody)
• There are antibodies that cross the placenta from the mother to the fetus.
• These maternal antibodies target antigens on the red blood cells of the fetus.
• This causes destruction of the red blood cells in the fetus and neonate.
o Rh D
o ABO incompatibility
o Others eg anti-Kell
Premature destruction of normal red cells (mechanical)
- Disseminated intravascular coagulation
- Haemolytic uraemic syndrome (e.g. E. coli O157)
- TTP
- Leaking heart valve
- Infections e.g. Malaria
Microangiopathic Haemolytic Anaemia (MAHA)
small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them.
•Imagine a mesh inside the small blood vessels shredding the red blood cells. This is usually secondary to an underlying condition:
o Haemolytic Uraemic Syndrome (HUS)
o Disseminated Intravascular Coagulation (DIC)
o Thrombotic Thrombocytopenia Purpura (TTP)
o Systemic Lupus Erythematosus (SLE)
o Cancer
Prosthetic Valve Haemolysis Mx
- Monitoring
- Oral iron
- Blood transfusion if severe
- Revision surgery may be required in severe cases
Abnormal cell membrane: CAUSES OF HAEMOLYSIS ACQUIRED
• Membrane Defects (all very rare)
o Liver Disease (Zieve’s Syndrome)
o Vitamin E deficiency
o Paroxysmal Nocturnal Haemoglobinuria
Paroxysmal Nocturnal Haemoglobinuria
rare condition that occurs when a specific genetic mutation in the haematopoietic stem cells in the bone barrow occurs during the patients lifetime.
• The specific mutation results in a loss of the proteins on the surface of red blood cells that inhibit the complement cascade.
• The loss of protection against the complement system results in activation of the complement cascade on the surface of red blood cells and destruction of the red blood cells.
