Haematology Flashcards
What is used to diagnose anaemia
Low haemoglobin
If you have a patient with low haemoglobin, what would you then check
Mean cell volume
Normal haemoglobin? For women and men?
Women- 120-165 g/l
Men- 130-180 g/l
Normal mean cell volume
80-100 femtolitres
3 types of anaemia
Microcytic
Normocytic
Macrocytic
Microcytic anaemia causes
‘TAILS’
T- thalassaemia
A- anaemia of chronic disease
I- iron deficiency anaemia
L- lead poisoning
S- sideroblastic anaemia- enough iron but not used —> same effect as iron deficiency
Normocytic anaemia causes
‘3As and 2 Hs’
A- acute blood loss
A- anaemia of chronic disease
A- apastic anaemia
H- haemolytic anaemia
H- hypothyroidism
What type of anaemia can hypothyroidism cause?
Normocytic anaemia
Megaloblastic anaemia causes
B12 deficiency
Folate deficiency
Normoblastic anaemia causes
Alcohol
Reticulocytosis- usually from haemolytic anaemia or blood loss
Hypothyroidism
Liver disease
Drugs e.g. azathioprine
Two types of macrocytic anaemia and difference between them?
Megaloblastic and normoplastic
Megaloblastic- caused by impaired DNA synthesis meaning cell can’t divide normally, instead of dividing just grows
Symptoms of anaemia
Tiredness
SOB
headaches
Dizziness
Palpitations
Worsening other conditions e.g. angina, HF, peripheral vascular disease
Symptoms specific to iron deficiency anaemia
Pica- dietary cravings for abnormal things
Hair loss
Generic signs of anaemia
Pale skin
Conjunctival pallor
Tachycardia
Raised resp rate
Specific signs of iron deficiency anaemia
Koilonychia- spoon shaped nails
Angular chelitis- sores on side of mouth
Atrophied glossitis- smooth tongue due to atrophy of papillae
Brittle hair and nails
What type of anaemia would jaundice indicate?
Haemolytic anaemia
Investigations for anaemia
Haemoglobin
Mean cell volume
B12
Folate
Ferritin
Blood film
Where is iron absorbed
Duodenum and jejunum
Iron needs to remain in the Fe2+ form to be absorbed. What medication can alter this and why?
PPIs
Stomach acid keeps iron in Fe2+ form. Without iron turns to Fe3+ which can’t be absorbed. PPIs can reduce acid and reduce iron absorption
What inflammatory conditions can cause iron deficiency anaemia and why?
Iron absorbed in duodenum and jejenum so inflammation here can reduce absorption.
Coeliac disease
Crohn’s disease
General causes of iron deficiency anaemia
Insufficient dietary intake
Increased iron requirements e.g. pregnancy
Iron lost e.g. slow bleed e.g. colon cancer
Inadequate absorption e.g inflammation in Bowel
Most common causes of iron deficiency anaemia in adults and children
Adults- blood loss
1st- menstruating women
Then, GI tract
Most common: oesophagitis and gastritis
Consider: GI tract cancer, Crohn’s or UC
Children- dietary insufficiency
What carrier protein carries iron around the blood?
Transferrin
What is ferritin
Form iron takes when deposited and stored in cells
What causes increased ferritin in blood
Any form of inflammation e.g. infection or cancer
Low ferritin in blood highly suggestive of iron deficiency
What does high and low ferritin levels in blood indicate
Low: likely iron deficiency anaemia
High: likely related to inflammation rather than iron overload.
Can still have normal ferritin with iron deficiency anaemia
What test is more commonly used to measure transferrin in blood
Total iron binding capacity
What happens to Total Iron Binding Capacity (TIBC) in iron deficiency
Increases
Indicates increased transferrin
What happens to TIBC and transferrin levels in iron overload
Decreases
What investigation is done for unclear cause of iron deficiency anaemia
Oesophago-gastroduodenoscopy (OGD) and colonoscopy to rule out cancer of GI tract
Management of iron deficiency anaemia
Depends on severity
Blood transfusion
Iron infusion e.g. cosmofer. Avoid in sepsis
Oral iron e.g. ferrous sulphate 200mg TDS. Expect 10g/l per week
What protein is needed for the absorption of vitamin B12?
Intrinsic factor
What is the Pathao physiology of pernicious anaemia?
Autoimmune condition. Antibodies against parietal cells or intrinsic factor. Therefore vit B12 can’t be absorbed
Symptoms of Vit B12 deficiency
Peripheral neuropathy- numbness and tingling in hands and feet
Loss of vibration sense or proprioception
Visual changes
Mood or cognitive changes
Diagnostic investigation for pernicious anaemia
Instrinsic factor antibody- 1st line
Gastric parietal cell antibody- sometimes also done
Management of dietary cause of B12 deficiency
Cyanocobalamin
Management of pernicious anaemia
Absorption problem!
Hydroxycobalamin 1mg IM, 3 times weekly, for 2 weeks. Then every 3 months
If neuro symptoms e.g. 1mg every other day til improvement in symptoms
If folate and B12 deficiency simultaneously, how would you treat it?
Treat B12 deficiency first- dietary cyanocobalamin or IM hydroxycobalamin
Then treat folate deficiency
If given folic acid with B12 deficiency, can cause subacute combined degeneration of cord
Two main types of haemolytic anaemia?
Inherited
Acquired
Types of inherited haemolytic anaemias? (5)
Hereditary spherocytosis
Hereditary elliptocytosis
Thalassaemia
Sickle cell anaemia
G6PD deficiency
Acquired haemolytic anaemias?
Autoimmune haemolytic anaemia
Alloimmune haemolytic anaemia (transfusionrractions and haemolytic disease of newborn)
Paroxysmal nocturnal haemoglobinuria
Microangiopathic haemolytic anaemia
Prosthetic valve related haemolytic
Features of haemolytic anaemias
Features of destroyed RBCs
- anaemia
- spenomegaly
- jaundice
What would a FBC and a blood film show in haemolytic anaemia?
FBC- Normocytic anaemia
Blood film- schistocytes- fragments of RBCs
( direct Coombs test is +ve in autoimmune haemolytic anaemia)
How is hereditary spherocytosis inherited?
Autosomal dominant
(Most common inherited haemolytic anaemia in Northern Europe)
Sphere shaped RBCs that easily break down when passing through spleen
How would hereditary spherocytosis usually present?
Jaundice
Gallstones
Splenomegaly
Often in an aplastic crisis due to parvovirus
How is hereditary spherocytosis diagnosed?
Clinical and family history
Spherocytes on blood film
FBC- raised MCHC (mean corpuscular haemoglobin conc)
Raised reticulocytes- rapid turnover of RBCs
Treatment for hereditary spherocytosis?
Folate supplements
Splenectomy
+/- cholecystectomy if gallstones problematic
Difference between hereditary spherocytos and hereditary elliptocytosis?
Presentation and management the same.
Elliptocytosis has ellipse shaped RBCs rather than sphere shaped
What is G6PD deficiency inheritance pattern?
X linked recessive
What often can cause a G6PD deficiency crisis? (Key info for exams is G6PD triggers)
Infections
Medications - primaquine (antimalarial), ciprofloxacin, sulfonyureas, sulfasalazine, other sulphonamide drugs
Fava beans- broad beans
How does G6PD deficiency usually present?
Jaundice- usually neonatal
Gallstones
Anaemia
Splenomegaly
HEINZ BODIES on blood film
How is G6PD deficiency diagnosed?
G6PD enzyme assay
Two types of autoimmune haemolytic anaemia?
‘Warm type’ and ‘Cold type’ autoimmune haemolytic anaemia
Due to the antibodies having different effects at different temps.
Warm more common
What is cold type autoimmune haemolytic anaemia often secondary to?
Aka- cold agglutin disease
Lymphoma, leaukaemia, lupus, infections e.g. mycoplasma, EBV, CMV, HIV
Management of autoimmune haemolytic anaemias?
Blood transfusions 🩸
Prednisolone/ steroids
Rituximab- monoclonal antibody against B cells
Splenectomy
What causes alloimmune haemolytic anaemia?
Blood transfusions or haemolytic disease of the newborn.
Due to foreign RBCs or antibodies in blood
How does paroxysmal nocturnal haemoglobinuria usually present?
Red urine in morning (containing haemoglobin and haemosiderin)
Or thrombosis: PE, DVT, hepatic vein thrombosis
Smooth muscle dystonia e.g. oesophageal spasm or erectile dysfunction
Management of paroxysmal nocturnal haemoglobinuria
Eculizumab- monoclonal antibody targets complement component 5 in complement system
Or bone marrow transplant
What’s the pathophysiology of paroxysmal nocturnal haemoglobinuria?
A genetic mutation in haematopoietic stem cells in bone marrow occurs in patients lifetime
Results in loss of proteins on surface of RBCs that inhibit the complement system
What is the pathophysiology of microangiopathic haemolytic anaemia? (MAHA)
Structural abnormalities in small blood vessels cause haemolysis of RBCs. Usually secondary to an underlying condition
What conditions is microangiopathic haemolytic anaemia often secondary to?
Haemolytic uraemia syndrome
DIC
TTP- thrombotic thrombocytopenia purpura
SLE
Cancer
Management of prosthetic valve haemolysis?
Monitor
Oral iron
Blood transfusion if severe
Revision surgery if needed
What chains does normal haemoglobin consist of?
2 alpha chains
2 beta globin chains
What are the 2 types of thalassaemia?
How are they inherited?
Alpha thalassaemia- defects in alpha-globin chains
Beta thalassaemia- defects in beta-globin chains
Both autosomal recessive
Pathophysiology of thalassaemia?
Altered alpha or beta chains meaning RBCs are more fragile so break down easily and collect in spleen
Bone marrow expands to produce more RBCs so more susceptible to fractures and prominent features e.g. forehead and cheekbones (malar eminences)
Signs and symptoms of thalassaemia?
Microcytic anaemia- low mean corpuscular vol
Generic anaemia sx- fatigue, pallor
Jaundice
Gallstones
Spenomegaly
Poor growth
Pronounced forehead and malar eminences (cheek bones)
How is thalassaemia diagnosed?
FBC- microcytic anaemia
Haemoglobin electrophoresis- ?globin abnormalities
DNA testing
Pregnant women offered screening
What’s a common long term problem seen in treated thalassaemia patients?
How is this monitored?
How is it managed?
Iron overload- due to faulty RBCs, transfusions and increased iron absorption in response to anaemia
Serum ferritin
Iron chelation
How does iron overload present?
Often seen in thalassaemia patients
Similar to haemochromotisisn:
Fatigue
Liver cirrhosis
Infertility and impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
Where are the genes for alpha and beta thalassaemia coded?
Alpha- chromosome 16
Beta- chromosome 11
What are the 3 types of beta thalassaemia?
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
Gene defect can be abnormal copies and retain some function or deletion with no function.
What is the pathophysiology and therefore presentation of thalassaemia minor?
Only 1 abnormally functioning gene (no deletion) and 1 normal —> mild microcytic anaemia
Monitor
What is the pathophysiology and therefore presentation of thalassaemia intermedia?
2 abnormal genes or 1 abnormal with 1 deletion.
More severe microcytic anaemia
Monitoring, possible blood transfusion
What is the pathophysiology and therefore presentation of thalassaemia major?
Homozygous deletion (rather than just abnormal)
… severe microcytic anaemia (often failure to thrive young)
Splenomegaly
Bone deformities
Regular transfusions
Iron chelation
Splenectomy
Bone marrow transplant- ?curative
How is sickle cell anemia inherited.
Autosomal recessive. Genetic advantage for carrier for malarial resistance.
Abnormal gene on beta globin chain on chromosome 11
Complications of sickle cell anaemia
Anaemia
Increased risk of infection
Stroke
Avascular necrosis in larger joints e.g. hip
Pulmonary hypertension
Priapism- painful persistent erection
CKD
SSickle cell crisis
Acute chest syndrome
What are known triggers of a sickle cells crisis?
Infection
Dehydration
Cold
Stress
What is a splenic sequestration crisis? How is it managed?
Sickle cells blocking blood flow to spleen —> enlarged painful spleen —> pooling in spleen —> severe anaemia and hypovolaemic shock
Supportive, blood transfusions, fluid resus for anaemia and shock.
Splenectomy preventative
What is an aplastic crisis?
How is it managed?
Temporary pause in creation of new blood cells
Most often caused by parvovirus B19
Significant anaemia
Supportive: blood transfusions if needed. Often resolves within a week
What is Acute chest syndrome?
Diagnosis:
Fever or resp symptoms with
New infiltrates on X-ray
Due to infection or noninfection e.g pneumonia, bronchiolitis, pulmonary vasoocclusion, fat emboli
How is Acute chest syndrome managed?
Treat underlying cause
Medical emergency with high mortality
Antibiotics or antivirals for infections
Blood transfusion for anaemia
Incentive spirometry - machine encourages better breathing
Artificial ventilation ?intubation
What are the four main types of leukaemia?
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
What are the two cell lines that are affected in leukaemia?
Myeloid
Lymphoid
What is leukaemia?
Cancer of line of stem cells in bone marrow leading to excessive production of a type of abnormal white blood cell.
Excess production can lead to suppression and underproduction of other cell lines leading to PANCYTOPENIA (anaemia, leukopenia, thrombocytopenia)
Most common ages for the different leukaemias
“ALL CeLLmates have CoMmon AMbitions” - ages from 45 to 75 in 10year jumps.
ALL- (under 5s) and over 45
CL- over 55
CM- over 65
AM- over 75
What are some typical features of leukaemia?
Fatigue
Fever
Failure to thrive in children
Pallor (anaemia)
Petechiae and bruising (thrombocytopenia)
Abnormal bleeding
Lymphadenopathy
Hepatospenomegaly
Differentials of petechiae?
Caused by thrombocytopenia
Leukaemia
Meningococcal septicaemia
Vasculitis
HSP
Idiopathic thrombocytopenia purpura (ITP)
Non accidental injury
Diagnosis of leukaemia?
FBC- pancytopenia
Blood film- abnormal cells?
Lactate dehydrogenase (LDH)- often raised but not specific
!!Bone marrow biopsy- definitive diagnosis
Chest X-ray- infection or lymphadenopathy?
Lymph node biopsy- involvement or lymphoma?
LP- if CNS involvement?
CT, MRI, PET for staging
Which type of leukaemia is linked with Down’s syndrome?
Acute lymphoblastic leukaemia (ALL)
What would be seen on a blood film in ALL
Blast cells
What gene mutation is associated with ALL? Although less strongly associated than CML
Philadelphia chromosome- t(9:22) translocation
30% adults
3-5% children
What type of lymphocyte is usually abnormally proliferating in ALL and CLL
Often B lymphocytes
Warm autoimmune haemolytic anaemia can be caused by ….. leukaemia
Chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia can transform into …..
This is called ….. transformation
Into high grade lymphoma
Called Richter’s transformation
What is Richter’s transformation?
CLL transforms into a high grade lymphoma
What’s seen on blood film in CLL?
Smear and smudge cells
Occurs when blood is smeared, fragile WBCs rupture leaving the smudge/smear appearance
What are the three typical phases of CML?
Chronic phase- can last 5 years, often asymptomatic, often incidental finding
Accelerated phase- take up 10-20% of bone marrow and blood. Symptomatic: anaemia, thrombocytopenia, immunocompromised
Blast phase- >30% blast cells in bone marrow and blood. Severe symptoms and pancytopenia. Often fatal
Characteristic genetic association with CML?
Philadelphia chromosome. Translocation between chromosome 9 and 22. A t(9:22) translocation
Most common leukaemia in adults?
AML
AML can result from a myeloproliferative disorder such as…
Polycythaemia rubra vera
Myelofibrosis
What will a blood film show in AML?
High proportion of blast cells
AUER RODS in cytoplasm
What type of leukaemia is associated with Auer rods
Acute myeloid leukaemia
What malignancy type is most often associated with Philadelphia chromosome?
Chronic myeloid leukaemia
What are the mainstay treatment options for leukaemias?
Chemotherapy
Steroid
+/-
Radiotherapy
Bone marrow transplant
Surgery
Complications of chemotherapy?
Failure
Stunted growth in children
Infections due to immunodeficiency
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity
Tumour lysis syndrome
What is tumour lysis syndrome?
Caused by release of uric acid from cells destroyed by chemo —> form crystals in interstitial tissues and kidney tubules —> AKI
Can also release potassium and phosphate (phosphate can reduce calcium. All monitored
Two main types of lymphoma?
Hodgkin’s - a specific disease
Non-hodgkins -all other lymphomas
1 in 5 lymphomas are Hodgkins
What age is Hodgkin’s lymphoma normally seen?
Bimodal distribution
~20yo and 75yo
Risk factors for Hodgkin’s lymphoma?
HIV
EBV
Autoimmune e.g. RA, sarcoidosis
Family history
Presentation of lymphomas?
Lymphadenopathyx- non tender, rubbery feel. Pain with alcohol!
B symptoms- fever, weight loss, night sweats
Other generic: fatigue, itching, cough, SOB, abdo pain, recurrent infections
Investigations for lymphoma
Lactate dehydrogenase- raised but non specific
Lymph node biopsy- DIAGNOSTIC
REED STEINBERG CELLS- IN HODGKINS
CT, MRI, PET diagnosis and staging
What staging system is used for lymphoma and what are the stages?
Ann Arbor staging
Stage 1- only 1 region of lymph nodes
Stage 2- >1 region but same side of diaphragm
Stage 3- lymph nodes on both sides of diaphragm
Stage 4- widespread outside of lymphatics
Management of lymphoma and their risks?
Chemotherapy- risk of leukaemia and infertility
Radiotherapy- risk of cancer, tissue damage and hypothyroidism
Other more common types of non Hodgkin’s lymphoma?
Burkitt lymphoma- associated with EBV, malaria, HIV
MALT lymphoma- associated w H.pylori (mucosa associated lymphoid tissue, usually around stomach)
Diffuse large B cell lymphoma- rapidly growing painless mass in patients over 65
Risk factors for non Hodgkin’s
HIV
EBV
H.pylori (MALT lymphoma)
Hep B and C infection
Exposure to pesticides, TRICHLOROETHYLENE used in some industrial processes
Family history
Monoclonal antibodies can be used to treat some non Hodgkin’s lymphomas such as…
Rituximab
What is myeloma?
Cancer of plasma cells. Type B lymphocytes (that produce antibodies)
Results in abnormal cell proliferation of one type of B cell —> high quantity of a single antibody.
Accounts for 1% of all cancers
What’s the difference between myeloma and multiple myeloma?
Multiple myeloma is myeloma affecting multiple parts of the body
What is Monoclonal gammopathy of undetermined significance (MGUS)?
Excess of single type of antibody with no other features.
May later progress
Monitored
Can lead to smouldering myeloma. Progression of MGUS, higher levels, premalignant.
Waldenstrom’s macroglobulinemia- a smouldering myeloma specifically excess IgM
What are the 5 main types of immunoglobulin (antibody)
IgA, IgG, IgM, IgD, IgE
What antibody most commonly is affected/raised in myeloma?
IgG, in >50% of cases
When the single antibody is overproduced in by the identical cancerous B/plasma cells, they’re called monoclonal paraproteins
What protein is often seen in the urine of patients with myeloma?
Bence Jones proteins.
They’re a subunit of antibodies called light chains
What disease are Bence Jones proteins seen in and where are they found?
Myeloma
In urine
What areas are more commonly affected by myeloma?
What occurs at these bony areas?
Skull, spine, long bones, ribs.
Infiltration of bone marrow can cause osteolytic lesions —> pathological #s
Why is hypercalcaemia often see in myeloma?
Bone marrow infiltration. Causes increased osteoclast activity and reduced osteoblast activity. More bone break down —> increased release of calcium from bone —> hypercalcaemia
How does myeloma sometimes lead to myeloma renal disease?
High immunoglobulin levels can block tubules
Hypercalcaemia impairs renal function
Dehydration
Treatment medications e.g. bisphosphonates can damage kidneys
Four key features to remember for my myeloma?
CRAB
C - Calcium elevated
R - Renal failure
A - Anaemia- Normocytic normochromic from replacement bone marrow
B - Bone lesions/pain
Risk factors for myeloma
Older age
Male
Black African
Family history
Obesity
Acronym for remembering myeloma investigations?
BLIP
B - Bence jones protein- request urine electrophoresis
L - serum free light chain assay
I - serum immunoglobulins
P - serum protein electrophoresis
Bone marrow biopsy- DIAGNOSTIC
Imaging looking for bone lesions? And preferred order
Whole body MRI
Whole body CT
Skeletal survey- full body xrays
X-ray signs in multiple myeloma
Punched out lesions
Lyric lesions
‘Raindrop skull’- due to lyric lesions on skull
First line treatment for myeloma?
Chemotherapy with
- bortezomoid
- thalidomide
- dexamthasone
For myeloma bone disease —> bisphosphonates
Bone pain/lesions —> radiotherapy
Orthopaedic surgery to stabilise #s
Cement augmentation
What are the three most common myeloproloferative disorders?
And what are each of the cell lines affected?
Primary myelofibrosis- haemopoietic stem cells
Polycythaemia vera - erythoid cell line
Essential thrombocytopenia - megakaryocytic cell line
What disease develops from the following proliferating cell lines
Haemopoetic stem cells —> primary myelofibrosis
Erythoid cells —> polycythaemia vera
Megakaryocyte —> essential thrombocytopenia
What type of malignancy to myeloproliferative disorders have the potential to develop into?
Acute myeloid leukaemia
What mutations are associated with myeloproliferative diseases?
JAK2 -remember this one!
—> Can be targeted by JAK2 inhibitors e.g. ruxolitnib
MPL
CALE
What is myelofibrosis?
Where proliferation of a cell line leads to fibrosis of the bone marrow, replaced by scar tissue
Due to response to cytokines released from proliferating cells e.g. fibroblast growth factor
If bone marrow is fibrotic, haematopoiesis (blood cell making) can start to occur in which areas?
What’s this process called?
Liver and spleen
Extramedullary haematopoiesis
Can lead to hepatospenomegaly and portal hypertension
Can lead to spinal cord compression if around spine
Key signs of polycythaemia vera?
Conjunctival plethora (red in conjunctiva of eyes)
‘Ruddy’ complexion
Splenomegaly
What abnormality on FBC would be seen in polycythaemia vera?
Raised haemoglobin
>185g/l in men
> 165 g/l in women
What blood test results would be raised in primary thrombocythaemia?
Raised platelet count >600x10(9) /l
What might you see on a blood film of someone with myelofibrosis?
Teardrop shaped RBCs
Poikilocytosis- varying sized RBCs
Blasts- immature red and white cells
Management of primary myelofibrosis?
Mild- monitored
Allogenic stem cell transplant? Curative but risky
Chemotherapy- not curative but controls sx
Supportive mx of anaemia, splenomegaly and portal hypertension
Management of polycythaemia vera?
Venesection- 1st line
Aspirin- reduced thrombosis risk
Chemotherapy- controlling disease
Management of essential thrombocythaemia
Aspirin- reducing thrombus risk
Chemotherapy
What is thrombocytopenia?
Low platelet count
Normal platelet 150 to 450 x10(9)/L
What are some causes of thrombocytopenia?
Production problems:
Sepsis
B12 or folate deficiency
Liver failure so less thrombopoietin made
Leukaemia
Myelodysplastic syndrome:
Destruction problems:
Medications e.g. sodium valproate, methotrexate, isotrentinoin, antihistamines, PPIs
Alcohol
ITP
Heparin induced thrombocytopenia
Haemolytic uraemia syndrome
What would a platelet count of 50x10(9) likely present with?
Easy bruising
Prolonged bleeding
E.g. nosebleeds, bleeding gums, heavy periods, blood in urine or stool
What could more likely occur with a platelet count of 10x10(9)
High risk of haemorrhaging stroke and GI bleeds
Key differentials fro abnormal or prolonged bleeding
Thrombocytopenia (low platelets)
Haemophilia A and B
Von Willebrand disease
DIC, often 2nd to sepsis
What is ITP?
Immune/idiopathic/autoimmune/primary thrombocytopenic Purpura
Antibodies against platelets
Management of ITP
Prednisolone
IV immunoglobulins
Rituximab- monoclonal antibody against B cells
Splenectomy
What type of cancer is predisposed by pernicious anaemia?
Gastric cancer
