Reduced amount of Hb in blood
Anaemia
Too much Hb in blood
Polycythaemia
Reduced platelets in blood
Thrombocytopenia
Too many platelets in blood
Thrombocytosis
Too much iron in blood
Haemochromatosis
Circulating iron
Transferrin
Stored iron
Ferritin (in the liver)
Functional iron
Hb
Haematocrit
% of Hb in blood
The production of cells derived from pluripotent stem cells
Haematopoiesis
The two lineages of a multipotential haematopoietic stem stell (Haemocyoblast)
Left: Common Myeloid Progenitor
Right: Common Lymphoid Progenitor
Extended lineage of the myeloid family
- Megakaryocyte
- Erythroblast
- Mast Cell
- Myeloblast
A megakaryocyte becomes
Thrombocytes (Platelets)
A myeloblast gives lineage to?
- Basophil
- Neutrophil
- Eosinophil
- Monocyte
An erythroblast gives rise to an
Erythrocyte (RBC)
A monocyte becomes
Macrophage
Extended lineage of the lymphoid family
- Natural Killer cell (NK)
- Small lymphocyte
A small lymphocyte becomes
- T cell lymphocyte
- B cell lymphocyte
A B cell lymphocyte becomes
Plasma cell
- Segmented nucleus
- Neutral staining granules
Neutrophil
- Bi-lobed nucleus
- Bright orange granules
Eosinophil
- Large deep purple granules (containing histamine)
- Associated with IgE
Basophil
- Single large nucleus
- Faintly staining granules
- Vacuolated
Monocyte
- Large nucleus
- Rim of cytoplasm
Lymphocyte
Neutrophils usually indicated
Bacterial infection
Lymphocytes usually indicate
Viral infection
Eosinophils usually indicate
- Allery/ Atopy
- Parasitic infection
Basophils can indicate
- Polycythaemia Rubra Vera
- Chronic myeloid Leukaemia
Granular leukocytes
WBC that contain granules
- Neutrophils
- Basophils
- Eosinophils
Agranular Leukocytes
WBC that contain a single nucleus and have few/no granules
- Monocytes
- Lymphocytes
The process of producing RBCs
Erythropoiesis
Haemoglobin is made out of
- Haem (porphyrin ring and Fe2+)
- Globins
Adult Haemoglobin: HbA
- 2 x Alpha chain globins
- 2 x beta chain globins
97% of Hb
Variant of adult haemoglobin: HbA2
- 2 x alpha chain globins
- 2 x delta chain globins
2.5% of Hb
Foetal haemoglobin: HbF
- 2 x alpha chain globins
- 2 x gamma chain globins
0.5% of Hb
However is very high in foetus and 1st year of life
Haemoglobin life span
120 days
Thrombocyte life span
7-10 days
Neutrophil life span
7-8 hours
Haematopoiesis in an embryo takes place in
- Yolk sac (until week 10)
- Liver (starts week 6)
- Bone Marrow (starts week 16)
Haematopoiesis at birth takes place in
- Bone marrow
- Liver
- Spleen
Haematopoiesis in an adult takes place in
Bone marrow of:
- Skull
- Ribs and sternum
- Pelvis
- Proximal femur
As you get older your bone marrow turns from red to
Yellow ( as it’s more fatty)
What anatomical landmark do you aim for when taking a bone marrow biopsy
Posterior Superior Iliac Spine
Describe how erythropoiesis begins
- Interstitial fibroblasts and the proximal tubule in the kidney sense hypoxia
- The kidneys produce erythropoietin (EPO)
- EPO then stimulates the bone marrow to produce more RBCs
- The increase in O2 levels in the blood causes EPO levels to drop
What is needed for erythropoiesis to take place
- Globins - from amino acids
- Haem - from iron stores
- B12
- Folate
Stimulation by EPO
What is the end cell produced in erythropoiesis
Reticulocyte (an immature RBC)
What is the maturation stages of a RBC
- Pronormoblast
- Early normoblast
- Intermediate normoblast
- Late normoblast
- Reticulocyte
- Erythrocyte
Hypersegmented nucleus in a neutrophil
(~7-9 segments)
This usually means macrocytic anaemia
(Due to an inefficient breakdown of cell)
An erythroblast contains
A nucleus
Reticulocytes contain
RNA
Hence why they are polychromatic
Reticulocytosis happens
In episodes of acute blood loss or haemolytic anaemia
The bone marrow produces RBCs rapidly, to compensate, hence why they are still immature reticulocytes
The destruction and breakdown of RBCs
Haemolysis
Site of haemolysis
Spleen
Describe Haemolysis
- RBCs are taken out of the circulation by macrophages and taken to the liver
- Iron is taken to iron stores (becoming ferritin)
- Porphyrin becomes unconjugated bilirubin and is taken to the liver to become conjugated
- Globulin chains are recycled into amino acids
During haemolysis, globulins are recycled as
Amino acids
During haemolysis, Fe2+ is
Recycled to iron stores
During haemolysis, the porphyrin ring is broken down into
bilirubin
Haemolysis causes
Haemolytic anaemia due to loss of RBC
Signs of haemolysis
- Spherocytes in blood film
- Reticulocytes
- Jaundice
- Fatigue
Two types of haemolytic anaemia
- Extravascular
- Intravascular
Extravascular haemolysis
happens in the liver and spleen by macrophages
Intravascular haemolysis
happens in the circulation
Examples of Extravascular haemolysis
- Liver disease
- Hypersplenism
Signs of extravascular disease
Bilirubinuria (dark yellow urine)
Examples of intravascular haemolysis
- HBO transfusion reaction
- G6PD deficiency
- Malaria
- Prosthetic valve
- Paroxysmal nocturnal haemoglobinuria
- Autoimmune Haemolytic anaemia
Signs of intravascular haemolysis
Haemoglobinuria
“Pink urine, black on standing”
2 types of autoimmune haemolytic anaemia
- Warm
- Cold
Warm autoimmune haemolytic anaemia is a
Delayed reaction
Cold autoimmune haemolytic anaemia is an
Immediate reaction
IgG is involved in
Warm autoimmune haemolytic anaemia
IgM is involved in
Cold autoimmune haemolytic anaemia
Causes of Warm autoimmune haemolytic anaemia
- Autoimmune disorders (SLE)
- Chronic lymphocytic leukaemia (CLL)
- Infections
- Drugs (penicillin)
Causes of cold autoimmune haemolytic anaemia
- Infections (EBV, mycoplasma)
Direct Coomb’s Test
Detects antibodies on the RBC surface
Is used to narrow down the cause of haemolysis
Positive Direct Coomb’s Test
- Autoimmune haemolytic anaemia
- Drug-induced haemolytic anaemia
- Haemolytic disease of the newborn
Heinz bodies indicate
G6PD Deficiency Haemolytic Anaemia
Pathophysiology of G6PD deficiency
a defect in glucose-6-phosphate dehydrogenase causes red blood cells to break down prematurely
Pathophysiology of Paroxysmal Nocturnal Haemoglobinuria
Your body thinks your blood is foreign and so it destroys it
Symptom of Paroxysmal Nocturnal Haemoglobinuria
Peeing blood
Polycythaemia Rubra Vera
A myeloproliferative neoplasm which causes the bone marrow to produce too many red blood cells
Polycythaemia RV is usually due to a default in
JAK 2 gene
Polycythaemia RV presents with
- Itch (after hot bath)
- Patient looks red
- DVT
- Splenomegaly
- Gout
- Headache
Treatment for Polycythaemia RV
- Hydroxycarbamide (marrow suppression)
- Venesection
Presentation of haemochromatosis
- Liver disease
- Heart problems
- Bronzing of the skin
- Diabetes (iron deposition kills islet cells)
- Arthritis
Types of Haemochromatosis
- Primary
- Secondary
Primary Haemochromatosis
Inherited
(decreased hepcidin, so the channels for iron release in the gut open more often, so iron is in serum)
- High Transferrin (>50%)
- High Ferritin (>200 (F), >300 (M))
Gradual increase, and so present in their 40s
Causes end-organ damage
Secondary Haemochromatosis
More acute
Too many blood transfusions (so iron overload)
Iron in cells can be detected by
Perl Staining Prussian Blue
Treatment for Primary haemochromatosis
Weekly Venesection in aim of exhausting iron stores
Treatment of Secondary Haemochromatosis
Desferrioxamine (Iron-chelating drugs)
Erythropoiesis
The production of RBCs
Mechanism of Erythropoiesis
- Hypoxia is sensed by the proximal tubule in the kidneys
- Kidneys produce erythropoietin
- Erythropoietin stimulates RBC production in the bone marrow
Role of folate
- Converts uridine to thymidine
- Needed for DNA synthesis
Daily requirement of Folate
Adult: 200 micrograms
Pregnant Women: 400 micrograms
Diabetic Pregnant Women: 5mg
Body store of Folate
4 months
Folate absorption takes place in
Duodenum and jejunum
“Coz DJs stay up fo-late playing music”
Folate deficiency is often seen in
Malnourished (e.g. alcoholics)
Role of B12
Is needed to make DNA, RNA, proteins due to S-adenosylmethionine synthesis
Daily requirement of B12
1.5 micrograms
B12 body stores last
2-4 years
B12 absorption takes place in
Ileum
“Because vegans lack B12 and they are ill”
Symptoms of B12 deficiency
- Sore tongue “glossitis”
- Neurological problems as B12 is associated with myelin development
Don’t prescribe folate without
B12 (in healthy people) as it will cause spinal cord problems (due to myelin interaction)
Iron absorption is regulated by
Hepcidin
Inhibits iron transport, and so regulates iron
- High hepcidin: iron accumulated
- Low hepcidin: iron exported
Iron absorption takes place in
Duodenum
“Because you need to iron your denum jeans”
Daily requirement of Iron
- Men: 8.7mg
- Women: 14.8mg
Chronic disease and inflammation causes
Increased hepcidin (due to IL6 and macrophages)
Which causes:
- Decrease in iron absorption release, and this leads to microcytic anaemia
Glucose-6-phosphate dehydrogenase “G6PD” pathway is responsible for getting rid of
H2O2 free radicals
Converts NADP+ to NADPH
What converts Fe3+ to Fe2+
NADH
Microcytic anaemia
- Low Hb
- Low MCV (size of RBC)
Hypochromic RBCs
Causes of microcytic anaemia
- Iron related: GI bleed, Period related, Chronic disease
- Porphyria related: lead poisoning
- Globulin synthesis: Thalassaemia
Chromosome associated with Alpha Thalassaemias
16
Chromosome associated with Beta Thalassaemias
11
2 types of thalassaemia
- Alpha
- Beta
Types of Alpha thalassaemias
- a+/a (3 alpha globulin)
- a0/a+ (1 alpha globulin) = HbH (3/4 betas)
- a0/a0 (0 alpha globulin) = Major: Hb Barts (4 gammas)
HbH presentation
- Jaundiced
- Splenomegaly
- “Golf ball occlusions” on blood film
- Common in South East Asians
Presentation of Alpha thalassaemia major (Hb Barts)
- Barts Hydrops Fetalis
- Usually always stillborn
- Oedema and hypoxic tissues
2 types of Beta thalassaemias
- Trait (b+/b) or (b0/b) = 3 or 2 betas
- Major (b0/b+) or (b0/b0) = 1 or 0 betas
Beta Thalassaemia Trait
- Increased HbA2
As 2 alpha, 2 delta chains involved
Beta Thalassaemia Major
- HbA2 or HbF
- Presents 6-24 months (due to loss of HbF), failure to thrive
- Extramedullary haematopoiesis (large head, spinal cord compression)
How to investigate/diagnose Thalassaemias
High Performance Liquid Chromatography
Macrocytic Anaemia
- Low Hb
- Increased MCV
3 types of Macrocytic Anaemia
- Megaloblastic
- Non-megaloblastic
- False Megaloblastic
Megaloblastic Anaemia
- Due to failure of DNA synthesis (caused by B12 and Folate deficiencies)
- RBC precursors cannot break down into RBCs, hence why they stay large (high MCV) and why there is less Hb (as less of them break down)
Pathophysiology of Pernicious anaemia
Autoimmune condition resulting in the destruction of gastric parietal cells which leads to B12 deficiency due to malabsorption
Non-megaloblastic anaemia
There are no reticulocytes etc
Due to liver disease, there is increases cholesterol and so RBCs are bound to fat/cholesterol etc and this is percieved as an increased MCV
False megaloblastic anaemia
Due to cold agglutination- reticulocytosis occurs and therefore MCV is raised
Fanconi Anaemia
- Macrocytic anaemia
- Increased HbF
- Bone marrow failure
Inheritance of Fanconi Anaemia
Autosomal recessive
Fanconi Anaemia Presentation
- Child (Usually of Jewish origin)
- Undeveloped thumbs
- Eye and ear defects
- Horseshoe kidney
- Cafe au lait spots
- Short stature
Fanconi Anaemia sufferers are at risk of
Acute Myeloid Leukaemia
Types of Sickle Cell Disease
Trait or Anaemia
Pathophysiology of Sickle Cell Disease
Valine takes place of glutamic acid
Sickle Cell Trait
One normal Beta, one abnormal beta
(B/BS)
Mainly HbA (60%), HbS (40%)
Sickle Cell Trait are asymptomatic until
Hypoxia
HbS protects you against
Malaria
Sickle Cell Anaemia (HbSS)
Two abnormal beta genes
(BS/BS)
HbS >80% the other 20% is HbF/HbA2
Inheritance pattern for Sickle Cell Anaemia
Autosomal Recessive
More commin in sub-saharan africans
Why are HbSS anaemic
Due to chronic haemolysis
Shortened RBC
Howell-Jolly bodies are seen on a blood screen
Presentation of a sickle cell crisis
- Dactylitis
- Chest pain
- A lot of pain everywhere
Due to RBCs clumping together in small veins
Investigation of HbSS
High performance liquid chromatography
to see HbS globin
Treatment of a sickle cell crisis
- Supportive
- Hydroxycarbamide (induces HbF production)
Haemostasis
The arrest of bleeding and the maintenance of vascular patency
4 pathways
4 pathways to haemostasis
Extrinsic pathway (left)
Intrinsic pathway (right)
Common pathway
Fibrinolysis
Extrinsic pathway (left side)
TF > Factor VIIa
Intrinsic pathway (right side)
Factor IXa > Factor VIII
Preceded by XIIa >XIa >IXa
Common pathway
Prothrombin > Factor Xa/V >Thrombin
Thrombin then converts fibrinogen to fibrin
What converts Prothrombin to thrombin
Factor Xa/V
What converts fibrinogen to fibrin
Thrombin
Fibrinolysis
Plasminogen > Plasmin by tissue plasminogen activator (tPA)
then plasmin converts fibrin to fibrin degredation products
Tissue plasminogen activator converts
Plasminogen to Plasmin
Plasmin converts
Fibrin to fibrin degredation products
Describe physiology of haemostasis
Enothelial wall damage exposes collagen and releases Von Williebrand Factor (VWF), platelets then adhere to the site of injury and secrete thromboxane 2 which leads to the aggregation of more platelets
Another name for prothrombin
Factor II
All coagulation factors are synthesised in
The Liver
Vitamin K carboxylates factors
II, VII, IX, X
As well as proteins S and C
Thrombin also
Accentuates factors VIII/IXa
Primary Haemostasis
Platelet plug
Secondary haemostasis
Fibrin clot
Test of primary haemostasis
PLT count
Test for Secondary haemostasis
Prothrombin time (PTT)
Activated Partial Thromboplastin time (APTT)
PTT measures
Extrinsic pathway
TF and Factor VIIa
APTT measures
Intrinsic pathway
Factors IX/VIII
“AY PTT = factor AY-TE”
Inhibitions of primary haemostasis
- Inhibited thromboxane 2 (COX2)- by NSAIDs (decreases platelet aggregation)
- Decreased Collagen- elderly people (makes it easier for endothelial walls to break)
- VWF Disease (stops platelet aggregation and intrinsic pathway from working)
- Marrow disease (thrombocytopenia)
- Immune Thrombocytopenic Purpura (ITP)
VWF Disease
Affects platelet aggregation and Factor VIII
Vitamin K is absorbed in the
Dueodenum
“Wearing denum is Kool”
To be absorbed Vit K needs
Bile salts
Inhibitions of secondary haemostasis
- Vit K deficiency
- DIC (used up all of your clotting factors)
- Haemophilia
Disseminated Intravascular Coagulation (DIC)
- Uses up all the clotting factors leading to bleeding, purpura and bruising
- Leading to microvascular thrombus formation = end organ failure
Treatment for DIC
FFP
Two Haemophilias
Haemophilia A: Problem with Factor VIII
Haemophilia B: Problem with Factor IX
“AY = AY-TE”
“Bee=NINE, benign”
Haemophilia affects the
intrinsic pathway
Haemophilia A affects
Factor VIII
Haemophilia B affects factor
IX
Which haemophilia is more common
Haemophilia A (5 times more common)
Presentation of Haemophilias
- Male (X-linked)
- Swellings in elbows and knees
What is prolonged in VWF Disease
- APTT: prolonged (problem with Factor VIII)
- PTT: normal
- Bleeding time: increased (problem with platelets)
What is prolonged in Vit K deficiency
- APTT: prolonged (due to Factor IX)
- PTT: prolonged (due to Factor II and Factor VII)
- Bleeding time: normal (platelets are fine)
What is prolonged in Haemophilia
APTT: prolonged (due to Factors VIII/IX)
PTT: normal (extrinsic not affected)
Bleeding time: normal (platelets are fine)
What is prolonged in DIC
- APTT: Prolonged (Affects intrinsic factors)
- PTT: (Affects extrinsic factors)
- Bleeding time: (Affects platelets)
Types of Thrombosis
- Arterial
- Venous
- Thrombophilia
Arterial thrombosis clots are
Platelet-rich clot in a high-pressure system
Endothelium breaks off, exposing endothelium leading to a platelet plug quickly fixing the problem
Factors that increase arterial thrombosis
- Enothelial damage
- HTN/smoking
- Hypercholesterolaemia
- Diabetes
Arterial thrombosis lead to
- CHD
- Angina
- MIs
Treatments for Arterial Thrombosis
- Aspirin- blocks thromboxane 2 (COX2)
- Clopidogrel (ADP inhibitor)
COX 2 (leads to platelet aggregation)
ADP (activates platelets to find more platelets)
Venous thrombosis clots are
Fibrin rich clot in a low-pressure system
Factors for venous thrombosis
Virchow’s Triad
- Stasis
- Vessel Wall damage
- Hypercoagulability
Venous thrombosis lead to
- DVTs
- PEs
- Strokes
Treatments for venous thrombosis
- Heparin
- Warfarin
- DOACs (Rivaroxaban)
- Thrombin Inhibitors (Dabigatran)
Two types of Heparin
- Unfractionated
- Low Molecular Weight Heparin (LMWH)
Mechanism of action of unfractionated heparin
Blocks thrombin
What should you monitor if on unfractionated heparin
APTT
Mechanism of action of LMWH
Blocks factor Xa
What reverses the effects of heparin
Protamine sulphate
What contraindicated protamine sulphate use
Fish allergy
as it’s made from salmon semen
Side effects of Heparin
- Heparin-Induced Thrombocytopenia
- Osteoporosis
Mechanism of action of Warfarin
Vit K antagonist
Problem with warfarin
Takes 3 days to work
Warfarin is contraindicated in
CYP interactions (Grapefruit Juice etc)
How do you reverse Warfarin
- Acute: Beriplex/ Prothrombin complex concentrate (clotting factors)
- In 24 hours: Vitamin K
International Normalized Ratio (INR)
A test for how well Warfarin is working
What should INR be between
2 - 3
An INR < 2 means
At risk of clotting
An INR >3 means
At risk of bleed
Mechanism of action of Direct Oral Anticoagulants (DOACs)
Directly inhibit active factor Xa:
- Rivaroxaban (Ban Xa is in the name)
- Apixaban
- Edoxaban
Direct thrombin inhibitor:
- Dabigatran
What is the effect of thrombophilias
Deficiency of naturally occurring anticoagulants
Increased risk of clotting
Two types of thrombophilias
- Factor V Leiden
- Antiphospholipid Syndrome
Antiphospholipid Syndrome Presentation
- Multiple pregnancy losses
- Recurrent DVTs
Antiphospholipid syndrome pathophysiology
Autoimmune disease where antibodies change beta-2-glycoprotein which effects primary and secondary haemostasis
Antiphospholipid antibodies
aPL autoantibodies
Anti-cardiolipin antibodies
Treatment of Antiphospholipid Syndrome
Aspirin- primary haemostasis
Warfarin- secondary haemostasis
When would you swap warfarin therapy for LMWH
During pregnancy as Warfarin is teratogenic
Myeloproliferative Disorders
- BCR ABL positive
- BCR ABL negative
Myeloproliferative BCR ABL positive disorder
Chronic Myeloid Leukaemia (CML)
Myeloproliferative BCR ABL negative disorders
- Polycythaemia Rubra Vera (PVC)
- Idiopathic Myelofibrosis
- Essential Thrombocythaemia (ET)
Myeloproliferative disorders are
Increase in all myeloid lineages’ cells
Myeloid disorders present with
- Weight loss
- Night sweats
- Fatigue
- Anaemia
- Splenomegaly (due to an increase in RBCs)
Chronic Myeloid Leukaemia (CML)
- Increased WBC (granulocytes)
- Increased basophils and eosinophils
Philadelphia chromosome indicates
Chronic myeloid leukaemia (9:22)
Treatment of CML
Imatinib (Tyrosine Kinase inhibitor)
Idiopathic myelofibrosis is
Fibrosis of the bone marrow leading to bad production of cells
Hence:
- Leukoerythroblastic blood film (nucleated RBCs)
- Tear-drop shaped RBCs
Leukoerythroblastic blood film
(Nucleated RBCs)
Myelofibrosis
Tear-drop shaped RBCs
Myelofibrosis
Essential Thrombocythaemia
Excessive production of platelets
(>1000)
Presentation of Essential thrombocythaemia
- Headache
- Visual problems
- Sore digits
- Bleeds a lot
Treatment for ET
- Hydroxyurea
- Aspirin
Lymphoid Cancers
- Acute (problem with precursors)
- Chronic (problem with mature cells)
Acute lymphoid cancers
- Acute Lymphoblastic Leukaemia (ALL)
- Acute Myeloid Leukaemia (AML)
Chronic Lymphoid cancer
Chronic Lymphoid Leukaemia
Acute Lymphoblastic Leukaemia (ALL) pathophysiology
- An increase in lymphoid progenitors
- A decrease in myeloid progenitors (because body is so busy making lymphoid progenitors)
ALL occurs in
Young kids
An ALL blood test would show
Increased Lymphoblasts
- Decreased RBCs
- Decreased PLTs
Increased lymphoblasts is a diagnosis of
ALL
Investigations for ALL
- Gold standard: Bone marrow biopsy
- Immunophenotyping: Establish specific cells
Treatment for ALL
- Vaccinations against gram negatives
- Antibiotics and antifungals
- Chemotherapy
Acute Myeloid Leukaemia (AML)
- An increase in myeloid progenitors
- A decrease in lymphoid progenitors (due to over-production of myeloid progenitors)
AML occurs in
Older adults (age 60ish)
A blood test of AML would show
Auer rods
Increased Myeloblasts
- Decreased RBCs
- Decreased PLTs
Auer rods
AML
Increased myeloblasts is a diagnosis of
AML
Treatment of AML
A lot of chemotherapy
Chronic Lymphocytic Leukaemia (CLL)
Increased number of Mature B Cells
CLL can travel in
The blood and the lymph
On a CLL blood film you would see
Smudge cells
Smudge cells
CLL
CLL can sometimes transform into
a Non-Hodgkin’s Lymphoma
CLL patients are more likely to get
Viral infections (Herpes zoster)
Types of Lymphoma
- Hodgkins
- Non Hodgkins
- Enlarged lymph nodes
- Chills
- Fatigue
- Weight loss
- Increased LDH
Symptoms of Lymphoma
Investigations for Lymphomas
Lymph node biopsy
Lymphoma is associated with
EBV
Hodgkins Lymphoma
- Reed-Sternberg Cells
- Painful upon drinking alcohol
- Itching
- Asymptomatic painless lymphadenopathy
Treatment for Hodgkins Lymphoma
Chemotherapy (Brentuximab)
Radiotherapy
Non-Hodgkins
- T-Cell
- B-Cell
Prognosis for T-Cell NHL
Bad
Immature B-cell NHL
Low Grade
Mature B-cell NHL
High grade
Treatment for NHL
Rituximab
Types of high grade B-cell NHLs
- Burkitt’s Lymphoma
- Mantle Cell Lymphoma
- Waldenstorm’s Macroglobinaemia
Burkitt’s Lymphoma
- Common in Africans
- Associated with EBV
- Mandibular/Maxillary Tumours
- Sometimes intra-abdominal tumours
Stary Sky Appearance on blood film
Burkitt’s Lymphoma
Treatment of Burkitt’s Lymphoma
Chemotherapy
- Can cause tumour lysis syndrome so give with IV allopurinol or IV rasburicase to reduce this risk
Tumour Lysis Syndrome can cause
- hyperkalaemia
- hyperphosphataemia
- hypocalcaemia
- hyperuricaemia
- acute renal failure
What Ig is associated with Waldenstrom’s Macroglobulinaemia
IgM
Hyperviscosity syndrome
Grade I lymphomas
1 node group
Grade II lymphomas
2 nodal groups on 1 side of the diaphragm
Grade III lymphomas
Nodes involved on both sides of the diaphragm
Grade IV
Extra nodal disease
T cells are produced in the
Paracortex
B cells are produced in the
Follicles
Myeloma
A plasma cell malignancy in the bone marrow
Presentation of Myeloma
- Older patient
- Bone pain
- Wedge fractures of vertebrae
- Bone lesions “Pepperpot skull”- lytic punched out lesions
- Hypercalcaemia
What causes hypercalcaemia in Myeloma
IL-6 increases osteoclasts and decreases osteoblasts which leads to the breakdown of bone
Treatment of hypercalcaemia
Biphosphonates
Investigations for myeloma
- Serum electrophoresis: Monoclonal antibodies (IgG/IgA)
- Urine electrophoresis: Bence-Jones protein
- Increased ESR
- X-ray: Rain-drop skull/Pepperpot skull
Bence-jones proteins and Monoclonal antibodies
Myeloma
Treatment for myeloma
- Bortezomib (proteasome inhibitor) + Steroid
- Thalidomide + Steroid
- Cyclophosphamide + Steroid
- Daratuximab + Steroid
Monoclonal Gammopathy of Unknown Significance (MGUS)
- Paraprotein <30g/l
- Low plasma cells in bone marrow
Amyloidosis
- Amyloid is laid down everywhere (beta-pleated sheets)
- Usually associated with Myeloma
Muscle biopsy of amyloidosis patient
- Congo red stain
- Apple-green bifringent under polarized light
If a patient has Infectious Mononucleosis (EBV) never give them
Amoxicillin - causes rash
Tx: Penicillin G
Felty’s Syndrome Triad
- Rheumatoid Arthritis
- Splenomegaly
- Neutropenia
Howell-Jolly bodies are seen in
- Hyposplenism (splenectomy)
- Sickle-Cell anaemia
Blue gums is a symptom of
Lead poisoning
RBCs are stored for
35 days at 4oC
Factors (FFP) are stored for
3 years at -30oC
PLTs are stored for
7 days at 22oC
Treatment for Neutropenic Sepsis
- 1st: Piperacillim (Tazobactam if P allergy)
- Severe: add Gentamicin
Give all patients at risk antifungals (Itraconazole)
Rituximab is a
Monoclonal antibody
Imatinib is a
Tyrosine kinase inhibitor
Side effects of Vinca Alkaloid (Vincristine) Chemo
Neuropathy
Side effect of Antracycline (Daunorubicin) Chemo
Cardio toxic
Side effect of Cis-Platinum Chemo
Nephrotoxicity
Universal blood donor
O-
As they have no antigens
Universal receiver
AB+
As they have all of the antigens
ABO system is defined on chromosome
9
85% of blood types are
RhD+
Transfusion-Associated Circulatory Overload (TACO)
- Oedema
- Respiratory distress
- HTN
- Increased JVP
Within 6 hours of blood transfusion
Tx: Diuretics
Transfusion-Relate Acute Lung Injury (TRALI)
- Immune-mediated lung injury
- Hypotension
- Within 6 hours of blood transfusion
Indications for a blood transfusion
Hb <70 and symptomatic
Hb <80 and has cardio disease
