Module 2A - Haematology Flashcards
What are the components of plasma?
- red blood cells
- white blood cells
- platelets
- clotting factors (eg. fibrinogen)
Once clotting factors are removed from blood plasma, what is left is called the serum, what does serum contain?
- Glucose
- Electrolytes –> sodium and potassium
- Proteins –> immunoglobulins (antibodies) and hormones
Thrombopoiesis/erythropoeisis/granulopoiesis/monopoiesis
Blood cells are produced and developed in the bone marrow, this process is called haematopoiesis, draw the lineage starting with a blood stem cell (pluripotent haematopoietic stem cell).
- Thrombopoiesis: megakaryoblasts –> megakaryocytes –> platelets
- Erythropoiesis: erythroblasts –> reticulocytes –> erythrocytes –> RBCs
- Granulopoiesis: granulocytes –> basophils + eosinophils + neutrophils
- Monopoiesis: monocytes –> macrophages + dendritic cells
- B cells –> plasma cells
- NK cells = large granular lymphocyte
What are reticulocytes? and how long do red blood cells survive on average?
- reticulocytes are immature red blood cells
- 120 days (4 months)
B lympocytes (B cells) mature in the ______ ________ and differentiate into; _______ _____ and ________ ______.
T lymphocytes (T cells) mature in the ________ ______ and differentiate into; CD4 cells (T _______ cells), CD_ cells (cytotoxic T cells), and _______ ______ cells
B lymphocytes (B cells) mature in the bone marrow and differentiate into; plasma cells and memory B cells.
T lymphocytes (T cells) mature in the thymus gland and differentiate into; CD4 cells (T helper cells), CD8 cells (cytotoxic T cells), and Natural killer cells.
What are antigens? and name the most relevant antigens in blood transfusions.
- Antigens –> molecules present on the surface of red blood cells (RBCs) that can trigger an immune response if recognized as foreign by the immune system
- ABO system –> Includes A and B antigens. Blood types are A (A antigen), B (B antigen), AB (both A and B antigens), and O (no A or B antigens).
- Rh system –> Includes the D antigen. Blood can be Rh-positive (D antigen present) or Rh-negative (D antigen absent).
What are antibodies? and name the most important antibodies in the context of blood transfusions.
- Antibodies are proteins produced by the immune system that specifically recognize and bind to antigens. In the context of blood transfusions, antibodies can react against foreign blood group antigens.
- Anti-A and Anti-B Antibodies: Present in individuals who lack the corresponding antigens (e.g., a person with blood type A has anti-B antibodies).
- Anti-D Antibodies: Can be produced by Rh-negative individuals if they are exposed to Rh-positive blood.
What is the importance of anti-D in the context of blood transfusions?
- Anti-D is an antibody against the Rh(D) antigen
- Hemolytic Disease of the Newborn (HDN): If an Rh-negative mother is sensitized to Rh-positive blood (e.g., from a previous pregnancy with an Rh-positive baby), she can produce anti-D antibodies that can cross the placenta and destroy the Rh-positive red blood cells of the foetus in subsequent pregnancies.
- Transfusion Reactions: If an Rh-negative person receives Rh-positive blood, they can develop anti-D antibodies, leading to complications in future transfusions.
What is a ‘group and screen’?
A pre-transfusion test.
- Blood Grouping: Determining the ABO and Rh blood type of the patient.
- Antibody Screening: Detecting any unexpected antibodies in the patient’s plasma that could react with transfused blood.
2 types
What is ‘crossmatching’?
- Crossmatching is a compatibility test between the donor’s and recipient’s blood. It involves mixing a small sample of the recipient’s plasma with a sample of the donor’s red blood cells to check for agglutination (clumping) or hemolysis (destruction of red blood cells). There are two types:
- Immediate Spin Crossmatch: A rapid test that detects ABO incompatibility.
- Antiglobulin Crossmatch (Coombs’ test): A more detailed test that detects other antibodies that might cause transfusion reactions.
Describe the ABO blood group system
- AB: universal recipient for ABO system (but can only donate to AB)
- O: universal donor for ABO system (but can only receive from O)
What pre-transfusion (blood transfusion) tests should be done?
- Group and Screen –> Determine ABO and Rh blood type, and screen for unexpected antibodies
- Crossmatch –> Ensure compatibility between donor and recipient blood
What are the 4 blood components that can be given by transfusion?
- Red blood cells
- Platelets
- FFP (Fresh Frozen Plasma)
- Cryoprecipitate
Indications for red blood cell transfusions
- acute blood loss (to restore oxygen-carrying capacity)
- chronic anaemia and symptomatic (Hb levels need to be <70/80g/L)
Indications for platelets transfusions
- thrombocytopenia –> low platelet count
- surgical/procedural prophylaxis –> to prevent bleeding in pts with low platelet counts
- active bleeding –> when platelet count is significantly reduced and patient is actively bleeding or undergoing major surgery
Indications for FFP transfusions
- coagulopathy –> when there is bleeding and abnormal clotting tests (INR >1.5 or APTT >1.5 times normal)
- massive transfusion protocols
- liver disease –> with significant bleeding or before invasive procedures
Indications for cryoprecipitate transfusions
- Fibrinogen deficiency –> cryoprecipitae is rich in clotting factors
- Massive haemorrhage –> as part of massive transfusion protocols to maintain fibrinogen levels
- 71yr old man. pale and tired
- Hb 70g/L (130-170)
- MCV 69fl (83-101)
- Differential diagnosis?
- Next tests?
Findings: microcytic anaemia
Differentials:
- iron-deficiency anaemia
- thalassaemia
- anaemia of chronic disease
- (sideroblastic anaemia, lead poisoning)
Next tests:
- Iron studies –> serum ferritin (low in iron-deficiency anaemia), serum iron (low in iron-deficiency anaemia), Total iron-binding capacity (elevated in iron-deficiency anaemia), transferrin saturation (low in iron-deficiency anaemia)
- Peripheral blood smear
- FIT (faecal immunochemical test) –> checks for blood –> GI bleeding in men with unexplained iorn-deficiency anaemia –> cancer
- reticulocyte count –> assess bone marrow function
- Haemoglobin electrophoresis –> identify thalassaemias
- Inflammatory markers –> CRP/ESR –> anaemia of chronic disease
- 70yr old woman. Pale. Glossitis (inflammation of the tongue)
- Hb 68g/L (120-150)
- MCV 112fl (83-101)
- Differential diagnosis?
- Next tests?
Findings: macrocytic anaemia
Differentials:
- Vit B12 deficiency (often associated with glossitis)
- Folate deficiency
- alcoholism
- livre disease
- hypothyroidism
- myelodysplastic syndromes
- drugs (methotrexate, azathioprine)
Next tests:
- Vit B12 and Folate levels
- Peripheral blood smear
- Reticulocyte count (assess bone marrow response to anaemia)
- Thyroid function tests
- Liver function tests (LFTs)
- serum iron studies (to rule out concurrent iron-deficiency)
- 83yr old woman. Tiredness. PMH (RA, Type 2 DM)
- Hb 85g/L (120-150)
- MCV 89fl (83-101)
- Differential diagnosis?
- Next tests?
Findings: Normocytic anaemia
Differentials:
- anaemia of chronic disease
- acute blood loss
- chronic kidney disease (renal failure)
- Mixed B12/folate and iron deficiency
- bone marrow disorders (aplastic anaemia)
- haemolytic anaemia
Next tests:
- FBC
- Reticulocyte count (low - inadequate production, high - increased destruction or loss of RBCs)
- Iron studies (check for iron-def anaemia)
- Renal function tests
- Inflammatory markets (CRP, ESR)
- Stool occult blood test (check for GI bleeding)
- Bone marrow biopsy
- 63yr old man. Tiredness. Dark urine.
- Hb 85g/L (130-170)
- MCV 105fl (83-101)
- Differential diagnosis?
- Next tests?
Findings: macrocytic anaemia, dark urine suggests possible haemolysis or liver dysfunction
Differentials:
- Haemolytic anaemia
- Vit B12 deficiency
- Folate deficiency
- Liver disease
- alcoholism (liver damage can cause dark urine)
- Myelodysplasia
Next tests:
- FBC
- Peripheral blood smear (haemolysis)
- Reticulocyte count
- Lactate dehydrogenase (LDH)
- Bilirubin (indirect unconjugated, direct conjugated)
- Vit B12 and Folate lvls
- LFTs
- Urinalysis
- Coombs test
- G6PD assay
- Bone marrow biopsy
- 60yr old woman. Hypertension - annual review.
- Hb 120g/L (120-150)
- MCV 65fl (83-101)
- Differential diagnosis?
- Tests?
Findings: microcytic anaemia
Differentials:
- iron-deficiency anaemia
- thalassaemia
- anaemia of chronic disease
- (sideroblastic anaemia, lead poisoning)
Next tests:
- Iron studies: serum ferritin (low in iron-deficiency anaemia), serum iron (low in iron-deficiency anaemia), Total iron-binding capacity (elevated in iron-deficiency anaemia), transferrin saturation (low in iron-deficiency anaemia)
- Peripheral blood smear
- Stool occult blood test: check for GI bleeding)
- reticulocyte count (assess bone marrow function)
- Haemoglobin electrophoresis (identify thalassaemias)
- Inflammatory markers (CRP/ESR - anaemia of chronic disease)
- 26yr old newlywed. Brother has sickle cell disease
- Concerned about risk of child with sickle cell disease
- Normal FBC, no sickle cells on blood film
- Questions?
- What is the risk of having a child with sickle cell disease?
Questions:
- Any hx of sickle cell disease, or any symptoms?
- Family hx of sickle cell?
- Partner’s hx?
- Have you or your partner undergone sickle cell testing, ever had a Hb electrophoresis test?
.
Autosomal recessive:
- risk depends on sickle cell status of both parents
- both have normal Hb: no risk
- one parent has sickle cell trait: 50% risk of inheriting sickle cell trait
- both parents have sickle cell trait: 50% chance sickle cell trait and 25% chance sickle cell disease
- One parent has sickle cell disease: each child will have sickle cell trait, but none will have disease
- one parent has sickle cell disease and other has sickle cell trait: each child has 50% chance of sickle cell disease and 50% chance of sickle cell trait
- 59yr old woman with tiredness and abdominal swelling
- O/E mass in left upper quadrant. Moves on inspiration. Has a notch in it. Can’t get above it
- What is it?
- What might be causing it?
- Questions?
- Tests?
Diagnosis: Splenomegaly
Potential causes:
- Haem disorders (CLL, NHL, myelofibrosis, sickle cell disease)
- Infections (EBV, malaria, TB)
- liver cirrhosis
- Inflammatory disorders (RA, SLE, sarcoidosis)
Questions:
- PMH: hx of haem disorders, infections, autoimmune disorders?
- SH: recent travel (infection risk?), alcohol intake (liver cirrhosis)
- FH: haem disorders, autoimmune disorders
Tests:
- Bloods: FBC, LFTs, blood cultures
- Imaging: abdo ultrasound or CT scan
- bone marrow biopsy (if haem disorders suspected)
- Serology (autoimmune antibodies)
- 21yr old man. Lump in neck. O/E lymph node 1.5cm
- Differential diagnosis?
- Questions?
- Tests?
Differentials:
- Infection (reactive lymphadenopathy)
- Inflammation: autoimmune (RA, SLE), sarcoidosis
- Malignancy: lymphoma
Questions:
- Red flag symptoms (weight loss, malaise, night sweats, fatigue)
- recent travel? smoking hx
- family hx of cancer or autoimmune disorders?
Tests:
- Lymph exam
- Bloods: infection/haematoloigcal abnormalities, serology for specific infections (EBV, HIV, CMV)
- Ultrasound neck
- Lymph node biopsy
What does this histology show?
neutrophils
What does this histology show?
lymphocytes
What does this histology show?
basophil - high in CML (chronic myeloid leukaemia)
What does this histology show?
monocyte
What does this histology show?
eosinophil
Draw out the coagulation cascade
Coag cascade –> Extrinsic pathway
- Tissue factor is expressed on surface of many cells outside blood vessels –> but not on surface of circulating blood cells or endothelium
- When endothelium damaged –> tissue factor comes into contact with blood and combines with circulating factor VII to form a complex –> leads to activation of factor X –> triggering the common pathway
Coag cascade –> Common pathway
- Begins with activation of factor X to factor Xa via either extrinsic pathway or intrinsic pathway
- It is final stage of coagulation cascade –> leads to formation of thrombin and fibrin
- Factor Xa combines with factor V, platelet membrane phospholipids, and Ca2+ ions to convert prothrombin to thrombin
- Thrombin then converts fibrinogen into fibrin strands which form an important structural component of a thrombus
- In addition to the formation of fibrin, thrombin activates many parts of the coagulation cascade via a positive feedback loop through the intrinsic pathway leading to formation of large amounts of additional thrombin –> ‘thrombin burst’
Coag cascade –> Intrinsic pathway
- can be activated by surface contact, when damage to the vascular endothelium leads to exposure of clotting factors to negatively charged subendothelial surfaces –> mediated by the molecule Kallikrein
- thrombin generated from previous activation of the extrinsic pathway also activates the intrinsic pathway and there is a positive feedback loop which causes amplification of thrombin production
- This continuous cycle means that vast amounts of thrombin can be generated from a single initial stimulus and a thrombus can be formed quickly after injury to limit blood loss
Actions of thrombin
- Fibrin generation –> thrombin converts fibrinogen into fibrin
- Intrinsic pathway activation –> via positive feedback loop
- Factor XIII activation –> thrombin converts factor XIII into factor XIIIa (fibrin stabilising factor) which then cross-links fibrin to generate a ‘fibrin mesh’ which encapsulates activated platelets creating a thrombus and stopping bleeding
- Platelet activation –> thrombin receptors on platelets cause activation and aggregation, further enhancing the haemostatic effects of the coagulation cascade
- Regulation of clot formation
Regulation of the coagulation cascade –> without these the +ve feedback loop triggered by thrombin would lead to dangerous lvls of clotting in the blood
- Protein C is produced in response to thrombin binding to the receptor thrombomodulin on the vascular endothelium –> this leads to protein S activation which then breaks down factors Va and VIIIa in a negative feedback loop
- Antithrombin is a natural anticoagulant that is produced by the liver and destroys factors Xa, XIa, and thrombin
- (Heparin and fondaparinux enhance the natural effects of antithrombin in inhibiting thrombin and factor Xa) - Tissue factor pathway inhibitor is a protein that binds to and inactivates factor VIIa and factor Xa
What clotting factors does Warfarin act on
Warfarin is a vitamin K antagonist which prevents the synthesis of vitamin K-dependent clotting factors (II, VII, IX and X)
range
Which pathway does prothrombin time (PT) measure?
- PT measures the time taken for fibrin to form via the extrinsic pathway
- normal range –> 9-12 seconds
Causes of a prolonged PT
- Disseminated intravascular coagulation (DIC)
- Vitamin K deficiency –> Factor VII is the vitamin K dependent clotting factor with the shortest half-life
- Chronic liver disease
INR –> what is it?
- a ratio of the patient’s PT compared to a normal PT
- The INR is used to monitor the levels of anticoagulation in patients on Warfarin and adjust the dosage as necessary
normal range
Which pathway does (activated thromboplastin time) APTT measure?
- APTT measures the time taken for fibrin to form via the intrinsic pathway
- normal range is 23-38 secs
Causes of a prolonged APTT
- Disseminated intravascular coagulation (DIC)
- Clotting factor deficiencies (e.g. haemophilia A or B)
- Von Willebrand’s disease
3 conditions that cause dysfunction of the coag cascade
- Haemophilia –> a congenital deficiency in either factor VIII (haemophilia A), factor IX (haemophilia B) or factor XI (haemophilia C) –> leading to defective clotting and therefore a tendency to bleed
- Chronic liver disease –> can lead to defective coagulation as many coagulation factors are depleted as the liver’s synthetic function is impaired
- Factor V Leiden –> a common genetic mutation to the gene coding for Factor V –> it increases the resistance of factor V to activated protein C making it more difficult to break down and therefore leading to an increased tendency to clot
Haemostasis and the clotting cascade –> why vitamin K and calcium are important –> video
Dr Matt and Dr Mike video:
https://www.youtube.com/watch?v=8FTuOjO7j-s
Causes of microcytic anaemia –> MCV < 80
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
Causes of normocytic anaemia –> MCV 80-100
A - Acute blood loss
A - Anaemia of chronic disease
A - Aplastic anaemia
H - Haemolytic anaemia
H - Hypothyroidism
R - Renal failure –> reduced EPO production –> low RBCs
Causes of macrocytic anaemia –> MCV > 100
- B12 and folate deficiency –> vegan diet ?
- Reticulocytosis
- Hypothyroidism
- Liver disease
- Drugs –> azathioprine and meds that reduce B12 absorption (PPIs and metformin) + alcohol
Symptoms/signs of anaemia + specific signs of iron-deficiency anaemia
- Symptoms –> tiredness, SOB, headaches, dizziness, palpitations, worsening of other conditions
- Iron-def –> Pica, hair loss
- Signs –> pale skin, conjunctival pallor, tachycardia, raised resp. rate
If there is unexplained iron-deficiency anaemia –> what should you investigate next?
- Faecal Immunochemical Test (FIT) –> check for blood before colonoscopy
- Colonoscopy –> GI cancer as a source of bleeding
If there is unexplained anaemia –> next step?
Bone marrow biopsy –> malignancy?
Iron deficiency anaemia –> causes
- Dietary iron –> red meat, fortified cereals
- Malabsorption of iron –> coeliac disease
- Pregnancy –> increased iron requirements
- Blood loss –> heavy menstruation? peptic ulcer or bowel cancer?
Iron deficiency anaemia –> management
- Oral iron –> ferrous sulphate or ferrous fumarate
- Vitamin C can be given –> helps iorn absorption
- Iron transfusion or blood transfusion (severe anaemia)
Common side effects of oral iron
Constipation and black stools
Pernicious anaemia –> what is it?
autoimmune condition –> involves antibodies against parietal cells or intrinsic factor –> resulting in a lack of absorption of vitamin B12
Vitamin B12 deficiency symptoms
- Neurological symptoms –> peripheral neuropathy (numbness, paraesthesia) …
- Glossitis –> ‘beefy red tongue’
Autoantibodies used to diagnose pernicious anaemia
Intrinsic factor antibodies
Management of vit B12 deficiency
IM hydroxocobalamin:
- No neurological symptoms –> 3 times weekly for two weeks
- Neurological symptoms –> alternate days until there is no further improvement in symptoms
- Pernicious anaemia –> injections for life every 2/3 months
In B12 and folate deficiency –> which do you treat first?
- Treat B12 deficiency first –> giving folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord
Symptoms of haemolytic anaemia –> premature destruction of RBCs
- Anaemia symptoms
- Splenomegaly –> spleen becomes filled with destroyed RBCs –> spleen acts like a mesh –> if RBC abnormal shape then won’t fit through and gets destroyed, cells get broken down and recycled here too
- Jaundice –> unconjugated bilirubin is released during destruction of RBCs
FBC, blood film, direct Coombs test
Investigation findings in haemolytic anaemia
- FBC –> normocytic anaemia, raised reticulocytes
- Blood film –> schistocytes (fragments of red blood cells)
- Direct Coombs test –> positive in autoimmune haemolytic anaemia (not in other types)
Hereditary spherocytosis is the most common inherited haemolytic anaemia –> what inheritance pattern
Autosomal dominant
Chronic haemolytic anaemia –> causes?
- Hereditary spherocytosis
- Thalassaemia
- Sickle cell anaemia
- G6PD deficiency
- (Hereditary elliptocytosis)
Symptoms of hereditary spherocytosis
- Anaemia, jaundice, gallstones
- Splenomegaly –> due to fragile sphere-shaped RBCs that easily break down when passing through spleen –> cause blockage
- Aplastic crisis in the presence of parvovirus
G6PD deficiency –> what is it + inheritance pattern
- caused by a defect in the gene coding for glucose-6-phosphate dehydrogenase (G6PD) –> an enzyme responsible for protecting the cells from oxidative damage
- X-linked recessive
triggers, symptoms, blood film
Consequences of G6PD deficiency
- Results in acute episodes of haemolytic anaemia –> triggered by infection, drugs, or fava beans
- (triggering meds –> ciprofloxacin, sulfasalazine, and anti-malarials)
- Results in neonatal jaundice, gallstones, anaemia, splenomegaly
- Blood film –> Heinz bodies
G6PD deficiency –> blood film finding + diagnosis
- Heinz bodies on blood film
- G6PD enzyme assay –> diagnosis
For management think what drugs would suppress the immune system
Autoimmune haemolytic anaemia –> what is it + types (+ aetiology) + management
- Occurs when antibodies are created against the patient’s own RBCs –> leads to haemolysis
- Warm (more common) –> haemolysis occurs at normal/above normal temp. –> usually idiopathic
- Cold –> haemolysis occurs at lower temps –> can be secondary to lymphoma, leukaemia, SLE, and infections
Management:
- Blood transfusions
- Prednisolone
- Rituximab –> monoclonal antibody against B cells
- Splenectomy
Prostehtic valve haemolysis
- caused by turbulence flow around the valve and the shearing of the red blood cells
- the valve churns up the cells, and they break down
Iron deficiency anaemia vs anaemia fo chronic disease
- Iron deficiency –> TIBC is high (reflecting production of more transferrin to increase iron-binding)
- Anaemia of chronic disease –> TIBC is low (iron stores are elevated)
Thalassaemia –> what is it + types + inheritance pattern
- Alpha- thalassaemia –> defect in alpha-globin chains
- Beta-thalassaemia –> defect in beta-globin chains
(defect in one chain is trait, in both is major) - Autosomal recessive
Consequences of thalassaemia
- Haemolytic anaemia –> RBCs more fragile so break down easily
- Splenomegaly –> spleen collects all the destroyed RBCs
Investigations for suspected thalassaemia
- FBC –> microcytic anaemia, raised ferritin (iron ovreload)
- Hb electrophoresis –> diagnosis
- DNA testing can look for genetic abnormality
Management for alpha-thalassaemia and beta-thalassaemia
- Alpha-thalassaemia –> blood transfusions, bone marrow transplant, splenectomy
- Beta-thalassaemia –> limiting blood transfusions and iron chelation
Pathophysiology of sickle cell disease + genetics
- At around 32-36 weeks gestation, HbF production decreases and HbA increases –> at birth half the Hb is HbF and half is HbA –> by 6 months RBCs should contain entirely HbA
- Sickle-cell –> HbS which is sickle-shaped RBCs
- Autosomal recessive condition affecting the beta-globin on chromosome 11
- one abnormal copy of the gene –> sickle cell trait
- two abnormal copies of the gene –> sickle cell disease
How is sickle cell disease picked up ?
newborn blood spot screening test at around 5 days of age
What type of anaemia does sickle cell disease cause?
Haemolytic anaemia –> abnormal shape of RBCs makes them more fragile and easily destroyed
Sickle cell crisis –> what is it + couple of types + managements
- Acute exacerbations –> triggered by dehydration, infection, stress, or cold weather
- Managed supportively –> IV fluids and analgesia
- Vaso-occlusive (most common type) –> sickle-shaped RBCs cloggin capillaries –> causing distal ischaemia and of vital organs
- Splenic sequestration –> RBCs block flow in spleen –> acutely enlarged and painful spleen –> can lead to splenic infacrtion and hypovolamic shock –> IV fluids and blood transfusions (for anaemia)
- Aplastic crisis –> parvovirus B19 is usual trigger
- Acute chest syndrome –> clot in lungs –> emergency and high mortality –> risk of ARDS
General management of sickle cell disease
- Avoid triggers –> dehydration
- Up-to-date vaccinations
- Antibitoic prophylaxis
- hydroxycarbamide –> stimulates HbF
- regular exchange transfusions
- bone marrow transplant can be curative
Raised eosinophils (eosinophilia) –> 2 causes
- allergies/atopy
- parasitic infection
Causes of neutropenia (low neutrophils)
- Infection - sepsis?
- Medications - antibiotics, immunosuppressants, chemotherapy (cytotoxic)
- B12/folate deficiency or iron deficiency
- Autoimmune disease
- HIV - any cytopenia could be due to HIV
- Bone marrow failure - seen with low Hb and low platelets
Causes of neutrophilia (high neutrophils)
- Basically infection or leukaemia
Acute leukocytosis:
- Reactive - infection, inflammation, post-surgery
- Steroids - stress response (endogenous) or medication (exogenous)
- Haematological - acute leukaemias
Chronic leukocytosis:
- Reactive - chronic infection, smoking
- Haematological - leukaemia, lymphoma (some subtypes)
- Hyposplenism - typically mild
- Pregnancy
Polycythemia (raised Hb) –> causes
- Primary –> polycythaemia vera (myeloproliferative neoplasm) –> JAK2 mutation
- Secondary: conditions that increase amount of erythropoietin (EPO) circulating in the blood (EPO is hormone produced by kidneys which stimulates bone marrow to make more RBCs) –> smoking and alcohol excess (most common), COPD, OSA, lung fibrosis, Cushing’s, EPO abuse (athletes)
Immune thrombocytopenic purpura (ITP) –> what is it + presentation + management
- a condition where antibodies are created against platelets –> an immune response against platelets leads to their destruction and a low platelet count (thrombocytopenia)
- Characteristically presents with purpura –> non-blanching lesions caused by bleeding under the skin
- Management –> spontaneous remission common, prednisolone, Rituximab, splenectomy can be considered
Blood groups video –> ABO and Rh (Rhesus)
Dr Matt and Dr Mike video:
https://www.youtube.com/watch?v=Amn2EWTY2Lk
- Rh +ve can receive both Rh +ve and Rh -ve blood
- Rh -ve can only receive Rh -ve blood
+ serious complication that can lead to
Blood transfusion reaction –> TRALI (transfusion-associated acute lung injury) –> presentation + management
- Dyspnoea, have pulmonary oedema –> can cause ARDS
- Stop transfusion –> start pt on high flow oxygen + give fluids –> treat ARDS (antibx? ventilation?)
Draw the haematopoiesis lineage diagram
Red cell maturation –> diagram
Blood film shows target cells –> …
Iron-deficiency anaemia and post-splenectomy
Blood film shows Heinz bodies and bite cells –> …
G6PD deficiency and alpha-thalassaemia
–> damaged Hb
Blood film shows Howell-Jolly bodies –> …
Post-splenectomy or non-functioning spleen
–> spleen would usually remove the little piece of DNA seen
Blood film shows reticulocytes –> …
Haemolytic anaemia –> bone marrow trying to replace lost cells
–> immature RBCs
Blood film shows schistocytes –> …
DIC, HUS, TTP, metallic heart valve replacement
–> fragments of RBCs
defective ________ synthesis
Sideroblastic anaemia –> what is it
- defective protoporphyrin synthesis
- bone marrow cannot incorporate iron into Hb molecules –> even though there is adequate iron
- due to genetic defect or myelodysplastic syndrome
(sideroblasts shown in image)
Blood film shows smudge cells –> …
Chronic lymphocytic leukaemia (CLL)
–> ruptured WBCs
Blood film shows sickle cells –> …
sickle cell anaemia –> HbS
Blood film shows spherocytes –> …
autoimmune haemolytic anaemia or hereditary spherocytosis
–> sphere-shaped RBCs –> without biconcave disc
Blood film shows tear drop cells –> …
bone marrow cancer –> myelofibrosis
associated with?
Auer rods
- characteristic finding in AML
Hodgkin’s lymphoma blood film characteristic finding
Reed-Sternberg cells –> large multinucleated cancerous B lymphocytes
Lugano (used to be Ann Arbor) classification for Hodgkin’s and non-Hodgkin’s lymphoma
- Stage 1 –> Confined to one node or group of nodes
- Stage 2 –> In more than one group of nodes but on the same side of the diaphragm (either above or below)
- Stage 3 –> Affects lymph nodes both above and below the diaphragm
- Stage 4 –> Widespread involvement, including non-lymphatic organs, such as the lungs or liver
Note: presence of B symptoms –> ‘B’
including blood film finding
Diagnostic investigations for myeloma
- Bone marrow biopsy
- Electrophoresis to detect paraproteinaemia –> paraprotein spike
- Bence Jones poteins –> serum-free light-chain assay (in urine)
- Rouleaux formation on blood film
Blood tests –> order of draw
which contains platelet?
plasma, buffy coat, haematocrit
- Blood is split into plasma (55%), buffy coat (1%), and erythrocytes (RBCs –> 45%)
- Buffy coat –> WBCs, thrombocytes, platelets
Interpreting serum ferritin
- Ferritin is an intracellular protein that binds to and stores iron + an acute-phase protein that increases in inflammatory states
–> therefore, we need to do CRP with ferritin
What can go wrong in this pathway?
Spherocytes
- Hereditary spherocytosis
- Autoimmune haemolysis
Elliptocytes
hereditary elliptocytosis
Schistocyte (helmet cell)
DIC, TTP, HUS
give details of each phase
Haemostasis 3 stages
- Vascular spasm (vasoconstriction) –> due to release of prostaglandins (Thromboxane A2), serotonin, noradrenaline
- Platelet plug –> exposed negatively charged collagen –> platelets stick to it and vWF helps platelets to stick together and form the clot
- Clotting cascade –> stable fibrin clot formation
Role of vitamin K and Ca2+ in coagulation cascade
- Vit K carboxylates clotting factors II, VII, IX, and X –> Ca2+ then binds to negatively charged carboxyl group on the clotting factors
- Clotting factors can now bind to collagen, platelets etc. with the Ca2+ acting as a tether
Hypersegmented neutrophils on blood film suggest –>
Megaloblastic anaemia –> B12/folate def.
Aortic dissection on CT
Tennis ball appearance –> ascending aorta
