Haematology Flashcards
What does serum contain?
Glucose, Electrolytes, proteins e.g. antibodies and hormones
What do red blood cells develop from?
reticulocytes which originate from myeloid stem cells
What are platelets made by?
megakaryocytes which develop from myeloid stem cells
What is the normal platelet count?
150-450 x10^9/L
Myeloid stem cells become myeloblasts, which can then become what?
Monocytes then macrophages
Neutrophils
Eosinophils
Mast cells
Basophils
What is Anisocytosis and what condition can it be seen in?
Variation in size of red blood cells
can be seen in myelodysplastic syndrome and many types of anaemia
What are Target cells and what conditions can they be seen in?
red blood cells with a central pigmented area surrounded by a pale area, surrounded by a ring of thicker cytoplasm on the outside. They look like a bull’s eye target.
These are mostly seen in iron deficiency anaemia and post-splenectomy
What are Heinz bodies and what conditions are they seen in?
individual blobs (inclusions) seen inside red blood cells. These blobs are denatured (damaged) haemoglobin.
They are mostly seen in G6PD deficiency and alpha-thalassaemia.
What are Howell-Jolly bodies and what conditions are they seen in?
blobs of DNA material seen inside red blood cells
seen after splenectomy , sickle cells and severe anaemia
In what condition would you see a high number of reticulocytes on blood film?
haemolytic anaemia
What are smudge cells and what condition are they seen in?
ruptured white blood cells that occur while preparing the blood film when the cells are aged or fragile.
They are particularly associated with chronic lymphocytic leukaemia.
What are spherocytes and what conditions are they seen in?
sphere-shaped red blood cells without the bi-concave disk shape.
They can indicate autoimmune haemolytic anaemia or hereditary spherocytosis.
State 4 causes of microcytic anaemia
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
state 5 causes of normocytic anaemia?
A – Acute blood loss
A – Anaemia of chronic disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism
state 2 causes of macrocytic megaloblastic anaemia
B12 deficiency
Folate deficiency
State 3 causes of normoblastic macrocytic anaemia
Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs, such as azathioprine
What are some generic symptoms of anaemia?
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions, such as angina, heart failure or peripheral arterial disease
State 2 symptoms specific to iron deficiency anaemia
Pica
Hair loss
State 3 generic signs of anaemia
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
State 4 signs specific to iron deficiency anaemia
Koilonychia
Angular cheilitis
Atrophic glossitis
brittle hair and nails
What is a key sign of haemolytic anaemia ?
Jaundice
What blood tests would you do in someone with anaemia of unknown cause?
Full blood count for haemoglobin and mean cell volume
Reticulocyte count
Blood film
Renal profile
Liver function bilirubin (raised in haemolysis)
Ferritin (iron)
B12 and folate
Intrinsic factor antibodies for pernicious anaemia
Thyroid function tests
Coeliac disease serology
Myeloma screening (e.g., serum protein electrophoresis)
Haemoglobin electrophoresis for thalassaemia and sickle cell disease
Direct Coombs test for autoimmune haemolytic anaemia
What type of anaemia does iron deficiency cause?
microcytic hypochromic anaemia
State 4 causes of iron deficiency anaemia
Insufficient dietary iron (e.g., restrictive diets)
Reduced iron absorption (e.g., coeliac disease)
Increased iron requirements (e.g., pregnancy)
Loss of iron through bleeding (e.g., from a peptic ulcer or bowel cancer)
What are some causes of a raised ferritin?
Inflammation (e.g., infection or cancer)
Liver disease
Iron supplements
Haemochromatosis
What does total iron-binding capacity do with iron deficiency anaemia?
increase
What are the 3 options for treating iron deficiency anaemia?
Oral iron (e.g., ferrous sulphate or ferrous fumarate)
Iron infusion (e.g., IV CosmoFer)
Blood transfusion (in severe anaemia)
State 3 causes of low B12
Pernicious anaemia
Insufficient dietary B12 (particularly a vegan diet, as B12 is mostly found in animal products)
Medications that reduce B12 absorption (e.g., proton pump inhibitors and metformin)
What causes pernicious anaemia?
autoimmune condition involving antibodies against the parietal cells or intrinsic factor
Where is vitamin B12 absorbed?
distal ileum
What neurological symptoms can vitamin B12 deficiency cause?
Peripheral neuropathy, with numbness or paraesthesia (pins and needles)
Loss of vibration sense
Loss of proprioception
Visual changes
Mood and cognitive changes
What 2 antibodies are used to diagnose pernicious anaemia?
Intrinsic factor antibodies (the first-line investigation)
Gastric parietal cell antibodies (less helpful)
What is the management of vitamin B12 deficiency?
IM Hydroxocobalamin
(3x weekly for 2w if no neuro symptoms, alternate days until improvement if neurological symptoms)
Maintenance depends on the cause:
Pernicious anaemia – 2-3 monthly injections for life
Diet-related – oral cyanocobalamin or twice-yearly injections
What is important to consider when a patient has B12 and folate deficiency
essential to treat the B12 deficiency first before correcting the folate deficiency. Giving patients folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord, with demyelination in the spinal cord and severe neurological problems.
What inherited conditions can lead to chronic haemolytic anaemia?
Hereditary spherocytosis
Hereditary elliptocytosis
Thalassaemia
Sickle cell anaemia
G6PD deficiency
state 2 acquired conditions that can lead to haemolytic anaemia
Autoimmune haemolytic anaemia
Alloimmune haemolytic anaemia (e.g., transfusions reactions and haemolytic disease of newborn)
Paroxysmal nocturnal haemoglobinuria
Microangiopathic haemolytic anaemia
Prosthetic valve-related haemolysis
State 3 features of haemolytic anaemia
Anaemia
Splenomegaly
Jaundice
state 3 key investigations for haemolytic anaemia
Full blood count shows a normocytic anaemia
Blood film shows schistocytes (fragments of red blood cells)
Direct Coombs test is positive in autoimmune haemolytic anaemia
What is hereditary spherocytosis?
most common inherited haemolytic anaemia in northern Europeans. It is an autosomal dominant condition. It causes fragile, sphere-shaped red blood cells that easily break down when passing through the spleen.
presents with anaemia, jaundice, gallstones and splenomegaly. A notable feature is aplastic crisis in the presence of the parvovirus.
What would a blood tests/ film in someone with hereditary spherocytosis show?
Raised mean corpuscular haemoglobin concentration (MCHC) on a full blood count
Raised reticulocyte count due to rapid turnover of red blood cells
Spherocytes on a blood film
How is hereditary spherocytosis treated?
Treatment is with folate supplementation, blood transfusions when required and splenectomy. Gallbladder removal (cholecystectomy) may be required if gallstones are a problem
What is the inheritance pattern of G6PD deficiency?
X-linked recessive
What are some triggers of haemolytic anaemia in someone with G6PD deficiency?
infections, drugs or fava beans. Key medication triggers include ciprofloxacin, sulfonylureas (e.g., gliclazide) and sulfasalazine.
How does G6PD typically present?
jaundice (often in the neonatal period), gallstones, anaemia, splenomegaly and Heinz bodies on a blood film. Diagnosis can be made by doing a G6PD enzyme assay.
What may cold autoimmune haemolytic anaemia be secondary too?
lymphoma, leukaemia, systemic lupus erythematosus and infections (e.g., mycoplasma, EBV, CMV and HIV).
What is the management of autoimmune haemolytic anaemia?
Blood transfusions
Prednisolone
Rituximab (a monoclonal antibody against B cells)
Splenectomy
In what 2 situations may alloimmune haemolytic anaemia arise?
transfusion reactions
haemolytic disease of the newborn
What is the characteristic symptoms of paroxysmal nocturnal haemoglobinuria?
red urine in the morning, which contains haemoglobin and haemosiderin.
Other presenting features are anaemia, thrombosis (e.g., DVT, PE and hepatic vein thrombosis) and smooth muscle dystonia (e.g., oesophageal spasm and erectile dysfunction).
What is the inheritance pattern of thalassaemia?
autosomal recessive
What are some features of thalassaemia?
Microcytic anaemia
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
What investigations are done for thalassaemia?
FBC - low MCV
Haemoglobin electrophoresis
DNA testing
Why may iron overload occur in a patient with thalassaemia?
Increased iron absorption in the gastrointestinal tract
Blood transfusions
What symptoms/complications may iron overload in thalassaemia cause?
Liver cirrhosis
Hypogonadism
Hypothyroidism
Heart failure
Diabetes
Osteoporosis
What chromosome is affected in alpha-thalassaemia?
16
What are the management options for alpha thalassaemia?
Monitoring
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative
What chromosome is affected in beta-thalassaemia?
11
What are the 3 types of beta-thalassaemia?
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
What is the management of beta thalassaemia intermedia ?
causes more significant microcytic anaemia. Patients require monitoring and may need occasional blood transfusions. They may require iron chelation to prevent iron overload.
What are some bone changes seen in thalassaemia major
Frontal bossing (prominent forehead)
Enlarged maxilla (prominent cheekbones)
Depressed nasal bridge (flat nose)
Protruding upper teeth
What is the genetics behind sickle cell anaemia?
autosomal recessive
affecting gene for beta globin on chromosome 11
State 4 complications of sickle cell anaemia
Anaemia
Increased risk of infection
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Gallstones
Priapism (painful and persistent penile erections)
state 3 triggers for a sickle cell crisis
dehydration, infection, stress or cold weather.
What does supportive management in a sickle cell crisis involve?
Low threshold for admission to hospital
Treating infections that may have triggered the crisis
Keep warm
Good hydration (IV fluids may be required)
Analgesia (NSAIDs should be avoided where there is renal impairment)
What is the most common type of sickle cell crisis?
Vaso-occlusive crisis (VOC) is also known as painful crisis
caused by the sickle-shaped red blood cells clogging capillaries, causing distal ischaemia.
What is a splenic sequestration crisis?
red blood cells blocking blood flow within the spleen. It causes an acutely enlarged and painful spleen. Blood pooling in the spleen can lead to severe anaemia and hypovolaemic shock.
What can trigger an aplastic crisis in a patient with sickle cell anaemia?
parvovirus B19
What are the presenting symptoms of acute chest syndrome?
fever, shortness of breath, chest pain, cough and hypoxia
what will a chest x-ray show in acute chest syndrome?
pulmonary infiltrates
What are the management options of acute chest syndrome?
Analgesia
Good hydration (IV fluids may be required)
Antibiotics or antivirals for infection
Blood transfusions for anaemia
Incentive spirometry using a machine that encourages effective and deep breathing
Respiratory support with oxygen, non-invasive ventilation or mechanical ventilation
What are some general management options of sickle cell anaemia?
Avoid triggers for crises, such as dehydration
Up-to-date vaccinations
Antibiotic prophylaxis to protect against infection, typically with penicillin V (phenoxymethylpenicillin)
Hydroxycarbamide (stimulates HbF)
Crizanlizumab
Blood transfusions for severe anaemia
Bone marrow transplant can be curative
What are the 4 main types of leukaemia?
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
What are some potential presenting features of leukaemia?
Fatigue
Fever
Pallor due to anaemia
Petechiae or bruising due to thrombocytopenia
Abnormal bleeding
Lymphadenopathy
Hepatosplenomegaly
Failure to thrive (children)
What investigations are done to diagnose leukaemia?
FBC
Blood film
Lactate dehydrogenase
Bone marrow biopsy
CT/PET scans
Lymph node biopsy
Genetic tests + immunophenotyping
Who does ALL most commonly effect?
Under 5
Down syndrome
What type of anaemia may chronic lymphocytic leukaemia cause?
warm autoimmune haemolytic anaemia.
What is Richter’s transformation?
transformation of CLL into high-grade B-cell lymphoma.
What is characteristic to see on blood film in CLL?
Smear or smudge cells are ruptured white blood cells
What are the 3 phases of CML ?
Chronic phase
Accelerated phase
Blast phase
What chromosome is most associated with CML?
Philadelphia chromosome. This refers to an abnormal chromosome 22 caused by a reciprocal translocation (swap) of genetic material between a section of chromosome 9 and chromosome 22
What are the findings on blood film in AML?
proportion of blast cells. Auer rods in the cytoplasm of blast cells
State 4 complications of chemotherapy
Failure to treat cancer
Stunted growth and development in children
Infections due to immunosuppression
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity (heart damage)
Tumour lysis syndrome
What will blood tests show in tumour lysis syndrome?
High uric acid
High potassium (hyperkalaemia)
High phosphate
Low calcium (as a result of high phosphate)
What is the epidemiology of Hodgkin’s lymphoma?
bimodal age distribution with peaks around 20-25 and 80 years
State 3 risk factors for Hodgkin’s lymphoma
HIV
Epstein-Barr virus
Autoimmune conditions, such as rheumatoid arthritis and sarcoidosis
Family history
State 3 subtypes of Non-Hodgkin Lymphoma?
Diffuse large B cell lymphoma typically presents as a rapidly growing painless mass in older patients
Burkitt lymphoma is particularly associated with Epstein-Barr virus and HIV
MALT lymphoma affects the mucosa-associated lymphoid tissue, usually around the stomach
State 4 risk factors for non-Hodgkin’s lymphoma
HIV
Epstein-Barr virus
Helicobacter pylori (H. pylori) infection is associated with MALT lymphoma
Hepatitis B or C infection
Exposure to pesticides
Exposure to trichloroethylene (a chemical with a variety of industrial uses)
Family history
What is the key presenting symptoms of lymphoma?
enlarged lymph node or nodes might be in the neck, axilla or inguinal region. They are characteristically non-tender and feel firm or rubbery.
Patients with Hodgkin’s lymphoma may experience lymph node pain after drinking alcohol.
What are some B symptoms of lymphoma?
Fever
Weight loss
Night sweats
What are some non-specific symptoms of lymphoma?
Fatigue
Itching
Cough
Shortness of breath
Abdominal pain
Recurrent infections
What are the characteristic finding on lymph node biopsy of Hodgkin’s lymphoma?
Reed-Sternberg cells
What staging system is used in Lymphoma?
Lugano classification
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
What type of cells does myeloma affect?
plasma cells in the bone marrow
What is Monoclonal gammopathy of undetermined significance (MGUS) ?
production of a specific paraprotein without other features of myeloma or cancer
What is multiple myeloma?
where the myeloma affects multiple bone marrow areas in the body
What is Smouldering myeloma?
abnormal plasma cells and paraproteins but no organ damage or symptoms. It has a greater risk of progression to myeloma (about 10% per year).
What are Bence Jones proteins?
free light chains in the urine of someone with myeloma
What are the 4 key features of myeloma?
C – Calcium (elevated)
R – Renal failure
A – Anaemia
B – Bone lesions and bone pain
What complications may hyperviscosity syndrome cause?
Bleeding (e.g., nosebleeds and bleeding gums)
Visual symptoms and eye changes (e.g., retinal haemorrhages)
Neurological complications (e.g., stroke)
Heart failure
State 4 risk factors of myeloma
Older age
Male
Black ethnic origin
Family history
Obesity
What are some presenting features that should raise suspicion of myeloma?
Persistent bone pain (e.g., spinal pain)
Pathological fractures
Unexplained fatigue
Unexplained weight loss
Fever of unknown origin
Hypercalcaemia
Anaemia
Renal impairment
What investigations should be done for myeloma?
Lab -> FBC, calcium, ESR, plasma viscosity, U&E, serum protein electrophoresis, serum-free light-chain assay, urine protein electrophoresis
Bone marrow biopsy
Imaging e.g. whole body MRI
What are the typical x-ray findings in myeloma?
Well-defined lytic lesions (described as looking “punched-out”)
Diffuse osteopenia
Abnormal fractures
Raindrop skull (sometimes called pepper pot skull) refers to multiple lytic lesions seen in the skull on an x-ray.
What are the management options in myeloma?
chemotherapy
stem cell transplant
bone disease = bisphosphonates, radiotherapy, surgery, cement augmentation
What are some complications of myeloma and it’s treatment?
Infection
Bone pain
Fractures
Renal failure
Anaemia
Hypercalcaemia
Peripheral neuropathy
Spinal cord compression
Hyperviscosity syndrome
Venous thromboembolism
What type of leukaemia do myeloproliferative disorders have the potential to transform into?
acute myeloid leukaemia
State 3 types of myeloproliferative disorders
Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia
What proliferating cell line is affected in primary myelofibrosis?
Haematopoietic stem cells
What are the blood findings in primary myelofibrosis?
Low haemoglobin
High or low white cell count
High or low platelet count
What proliferating cell line is affected in polycythaemia vera?
Erythroid cells
What is the blood finding in Polycythaemia Vera?
High haemoglobin
What proliferating cell line is affected in essential thrombocythaemia?
Megakaryocyte
What is the blood finding in essential thrombocythaemia?
high platelet count
mutations in what genes are associated with myeloproliferative disorders?
JAK2
MPL
CALR
What is myelofibrosis?
proliferation of a single cell line leads to bone marrow fibrosis, where bone marrow is replaced by scar tissue. This is in response to cytokines released from the proliferating cells
What would a blood film in myelofibrosis show?
Teardrop-shaped red blood cells
Anisocytosis (varying sizes of red blood cells)
Blasts (immature red and white cells)
What are some clinical signs of polycythaemia ?
Ruddy complexion (red face)
Conjunctival plethora (the opposite of conjunctival pallor)
Splenomegaly
Hypertension
What is the diagnostic investigation for myeloproliferative disorders?
Bone marrow biopsy
What are the management options for primary myelofibrosis?
supportive management of complications
chemotherapy
targeted therapies e.g. JAK2 inhibitors
Allogeneic stem cell transplant
What are the management options of polycythaemia vera?
Venesection
Aspirin
Chemotherapy
What are the management options of thrombocythaemia
aspirin
chemotherapy
Anagrelide
What is Myelodysplastic syndrome?
form of cancer caused by a mutation in the myeloid cells in the bone marrow, resulting in inadequate production of blood cells
What is pancytopenia?
combination of low red blood cells, white blood cells and platelets.
What affect does Myelodysplastic syndrome have on blood components?
Anaemia (low haemoglobin)
Neutropenia (low neutrophil count)
Thrombocytopenia (low platelets)
What symptoms may myelodysplastic syndrome present with?
Anaemia (fatigue, pallor or shortness of breath)
Neutropenia (frequent or severe infections)
Thrombocytopenia (bleeding and purpura)
How is myelodysplastic syndrome diagnosed?
Full blood count will be abnormal. There may be blasts on the blood film.
Bone marrow biopsy is required to confirm the diagnosis
What are the management options for myelodysplastic syndrome?
Watchful waiting
Supportive treatment (e.g., blood or platelet transfusions)
Erythropoietin (stimulates red blood cell production)
Granulocyte colony-stimulating factor (stimulates neutrophil production)
Chemotherapy and targeted therapies (e.g., lenalidomide)
Allogenic stem cell transplantation (risky but potentially curative)
what can reduce platelet production?
Certain viral infections (e.g., Epstein-Barr virus, cytomegalovirus and HIV)
B12 deficiency
Folic acid deficiency
Liver failure, causing reduced thrombopoietin production by the liver
Leukaemia
Myelodysplastic syndrome
Chemotherapy
What can increase platelet destruction?
Medications (e.g., sodium valproate and methotrexate)
Alcohol
Immune thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
Heparin-induced thrombocytopenia (HIT)
Haemolytic uraemic syndrome (HUS)
what are some symptoms of thrombocytopenia?
Nosebleeds
Bleeding gums
Heavy periods
Easy bruising
Haematuria (blood in the urine)
Rectal bleeding
Platelet counts below 10 x 109/L are at high risk for spontaneous bleeding. Particularly concerning are:
Intracranial haemorrhage
Gastrointestinal bleeding
What causes Immune thrombocytopenic purpura (ITP)?
antibodies are created against platelets. An immune response against platelets leads to their destruction and a low platelet count (thrombocytopenia).
What are the management options for Immune Thrombocytopenic Purpura?
Prednisolone (steroids)
IV immunoglobulins
Thrombopoietin receptor agonists (e.g., avatrombopag)
Rituximab (a monoclonal antibody that targets B cells)
Splenectomy
What is the cause of Thrombotic Thrombocytopenic Purpura?
Deficiency in the ADAMTS13 protein
condition where tiny thrombi develop throughout the small vessels, using up platelets.
What does Thrombotic Thrombocytopenic Purpura cause?
Thrombocytopenia
Purpura
Tissue ischaemia and end-organ damage
How is Heparin-Induced Thrombocytopenia diagnosed?
testing for HIT antibodies on a blood sample
How long after starting heparin can Heparin-Induced Thrombocytopenia occur?
5-10 days
What are the 3 types of Von Willebrand disease?
Type 1 involves a partial deficiency of VWF and is the most common and mildest type
Type 2 involves the reduced function of VWF
Type 3 involves a complete deficiency of VWF and is the most rare and severe type
What are the presenting symptoms of Von Willebrand Disease?
Bleeding gums with brushing
Nosebleeds (epistaxis)
Easy bruising
Heavy menstrual bleeding (menorrhagia)
Heavy bleeding during and after surgical operations
What are the management options for Von Willebrand disease in response to significant bleeding or trauma or pre-op?
Desmopressin (stimulates the release of vWF from endothelial cells)
Tranexamic acid
Von Willebrand factor infusion
Factor VIII plus von Willebrand factor infusion
A deficiency in what factor causes haemophilia A?
VIII
A deficiency in what factor causes haemophilia B?
IX
What is the inheritance pattern of haemophilia?
X-linked recessive
How can haemophilia present in neonates/early childhood?
intracranial haemorrhage, haematomas and cord bleeding
How is haemophilia managed?
IV clotting factors (VIII or IX)
state 5 risk factors for a DVT
Immobility
Recent surgery
Long haul travel
Pregnancy
Hormone therapy with oestrogen
Malignancy
Polycythaemia
Systemic lupus erythematosus
Thrombophilia
What are the presenting features of a DVT?
Calf or leg swelling
Dilated superficial veins
Tenderness to the calf (particularly over the site of the deep veins)
Oedema
Colour changes to the leg
How do you measure calf circumference?
10cm below the tibial tuberosity. More than a 3cm difference is significant.
How should you use a Wells score to guide DVT investigations?
Likely: perform a leg vein ultrasound
Unlikely: perform a d-dimer, and if positive, perform a leg vein ultrasound
What is the initial management of DVT?
treatment-dose apixaban or rivaroxaban
considering catheter-directed thrombolysis in patients with a symptomatic iliofemoral DVT and symptoms lasting less than 14 days.
What conditions may you test for in a patient who has had an unprovoked DVT?
Antiphospholipid syndrome (check antiphospholipid antibodies)
Hereditary thrombophilias (only if they have a first-degree relative also affected by a DVT or PE)
What is Budd-Chiari syndrome?
obstruction to the outflow of blood from the liver caused by thrombosis in the hepatic veins or inferior vena cava
what is the classic triad of Budd-Chiari syndrome?
Abdominal pain
Hepatomegaly
Ascites
