Haematology Flashcards
What are causes of microcytic anaemia?
Thalassaemia Iron deficiency Sideroblastic anaemia Late stages of anaemia of chronic disease Lead poisoning
What are the causes of normocytic anaemia?
Acute blood loss Anaemia of chronic disease Aplastic anaemia Haemolytic anaemia Hypothyroidism
What are the causes of macrocytic anaemia?
B12 deficiency
Folate deficiency
Reticulocytosis
Alcohol-induced anaemia
What are the causes of iron deficiency anaemia?
- Blood loss
- Reduced iron intake
- Increased demand e.g. pregnancy, malignancy
- Reduced absorption e.g. PPIs, IBD, coeliac
What haematinics would you expect in IDA?
Low ferritin
Low transferrin saturation
Increased transferrin concentration
Increased total iron binding capacity
What is pernicious anaemia?
Cause of B12 deficiency anaemia
Autoimmune condition with ab being produced against gastric parietal cells or intrinsic factor
Intrinsic factor is produced by gastric parietal cells and allows B12 to be absorbed in the distal ileum.
What is the gold standard test to look for pernicious anaemia?
Intrinsic factor antibody testing
How can B12 be replaced in anaemia?
In dietary deficiency: oral cyanocobalamin
Pernicious/malabsorptive: IM hydroxycobalamin 3x weekly for 2 weeks and then 3 monthly
If B12 and folate deficiency exist together, which should you replace first?
B12
Folate can increase development of subacute degeneration of the cord.
What are examples of inherited haemolytic anaemia?
Spherocytosis (autosomal dominant) Elliptocytosis (autosomal dominant) Thalassaemia (autosomal recessive) Sickle cell anaemia (autosomal recessive) G6PD deficiency (X-linked recessive)
What are examples of acquired haemolytic anaemia?
Warm/cold autoimmune HA
Paroxysmal nocturnal haemoglobinuria
Microangiopathic HA (small vessels cause destruction of RBCs)
Prosthetic valve haemolysis
What triad of features suggests haemolytic anaemia?
Anaemia
Splenomegaly
Jaundice
Which tests suggests an autoimmune cause of haemolytic anaemia?
Direct Coombs test = positive
What can trigger an aplastic crisis in hereditary spherocytosis?
Parvovirus infection
What can trigger an aplastic crisis in G6PD deficiency?
Infection Fava/broad beans Ciprofloxacin Sulphonylureas Anti-malarials
Which blood film finding is classic of G6PD deficiency?
Heinz bodies
How is sickle cell anaemia diagnosed?
Heel-prick test in newborns
Pregnant women tested
Haemoglobin/genetic testing
What would you see on a blood film in sickle cell?
Sickle-shaped cells,
Howell-Jolly bodies,
presence of nucleated red blood cells,
cell fragments can be seen on the blood smear
How is sickle cell generally managed?
Avoid dehydration Ensure up to date with vaccinations Prophylactic penicillin V Hydroxycarbamide to stimulate the production of HbF Blood transfusion Bone marrow transplant
What can trigger sickle cell crises?
Infection Dehydration Cold Stress Significant life events
What are the signs and symptoms of thalassaemia?
Anaemia Splenomegaly Jaundice and gallstones Poor growth and development Pronounced forehead and cheekbones
How is thalassaemia diagnosed?
- FBC: microcytic anaemia
- Hb electrophoresis
- Genetic testing
What are the three types of Beta thalassaemia and their genotypes?
Thalassaemia minor: heterozygous deletion, one normal copy
Thalassaemia intermedia: 2 defective genes or 1 mutation and 1 deletion
Thalassaemia major: homozygous gene deletion
How is thalassaemia major managed?
Regular blood transfusions, iron chelation and splenectomy
Bone marrow transplant can be curative
What is the main risk of recurrent transfusions in thalassaemia?
Iron overload
Causes fatigue, liver cirrhosis, reduced fertility, osteoporosis, diabetes, HF, arthritis
Rx: iron chelation
How is leukaemia diagnosed?
FBC: anaemia, thrombocytopenia, neutropenia, ?^ lymphocytes
Blood film / peripheral blood smear
LDH often raised
Bone marrow biopsy = main definitive investigation
CXR + more detailed imaging for staging
In which populations are ALL most common?
children aged 2-5
Adults > 45
Which leukaemia is most associated with Downs and Klinefelter’s syndrome?
ALL
Which leukaemia is most common in adults?
CLL
Which leukaemia is most associated with causing warm AIHA + transforming into lymphoma?
CLL
What is seen on blood film in CLL?
Smear/smudge cells
Which leukaemia is currently INCURABLE?
CLL
Slow growing so often don’t need treating straight away
Can induce emission but will eventually relapse
In which population is AML most common?
> 70s
What is seen on blood film in AML?
Auer rods, myeloid blast cells
Which leukaemia is most likely to present with splenomegaly and sweating rather than anaemia and infection?
CML
What biologic agent is most used in CML?
Imatinib
What are the features of tumour lysis syndrome?
Hyperuricaemia
Hyperkalaemia
Hyperphosphataemia
Secondary hypocalcaemia
What management is used in tumour lysis syndrome?
Cardiac monitoring Aggressive fluid resuscitation Calcium glutinate, insulin, dextrose, salbutamol etc Rasburicase for hyperuricaemia Phosphate binders
Which cells do leukaemia affect?
Cancer of the white blood cells, affecting both myeloid and lymphoid cell lineages.
What cells are affected by lymphoma?
Lymphocytes of the lymphatic system
What are risk factors for Hodgkin’s lymphoma?
HIV, EBV, Family history, Autoimmune conditions e.g. sarcoid, RA
What symptoms are associated with lymphoma?
Lymphadenopathy: usually non-tender, rubbery, tender when drinking alcohol
Fever, weight loss, night sweats
Fatigue, cough, SOB
Recurrent infection, itching, abdominal pain
How is lymphoma diagnosed?
Bloods: FBC, LDH
FBC may show anaemia / neutropenia / thrombocytopenia but not always
Lymph node USS and biopsy
CT/MRI/PET staging scans
How can you differentiate Hodgkin’s and non-hodgkin’s lymphomas?
Hodgkins: presence of Reed-Sternberg cells on lymph node biopsy
Abnormally large, multinucleated B cells with nucleoli
Which conditions are associated with Burkitt’s lymphoma?
EBV
HIV
Malaria
Starry sky appearance on biopsy
Which lymphoma is associated with H. Pylori infection ?
MALT lymphoma
What staging system is used in lymphoma and what is it?
Ann-Arbour staging
1- confined to one region
2- more than one region affected but on the same side of the diaphragm
3- regions affected on either side of the diaphragm
4- Widespread involvement, including organs
What is myeloma?
Cancer of the plasma cells (antibody-producing B cells)
What are the features of myeloma?
CRAB
Hypercalcaemia
Renal disease
Anaemia
Bone pain
Hyperviscosity is also a feature of myeloma- easy bruising + bleeding, eye vessel disease, purple palmar erythema, heart failure
What is myeloma bone disease?
Reduced osteoblast activity and increased osteoclast activity, causing lytic lesions to form in bones
Most commonly affects skull, spine, long bones and ribs
This leads to hypercalcaemia as a result of increased osteoclast activity
How is myeloma diagnosed?
FBC: anaemia, neutropenia, thrombocytopenia
Ca 2+, ESR + plasma viscosity all raised
Urine electrophoresis: presence of bence jones proteins
Serum protein electrophoresis, light chain assay and immunoglobulins
X-ray- punched out, lytic lesions, raindrop skull
Bone marrow biopsy to confirm diagnosis
Whole body MRI
How is myeloma managed?
Combination chemotherapy
Stem cell transplants in clinical trials currently
VTE prophylaxis important due to increased viscosity - aspirin/LMWH
Bisphosphonates for osteoclast suppression
Radiotherapy can help with bone pain
Orthopaedic surgery to stabilise bones/fractures
Management of renal impairment.
What is a myelodysplastic syndrome?
Condition whereby myeloid cell lineages don’t mature properly, leading to the production and release of immature blood cells. This causes low levels of the cell affected: neutropenia, anaemia, thrombocytopenia.
These conditions are most common in the over 60s or those who have previously had chemo/radiotherapy.
Blood films will show blast cells, then diagnosis is confirmed with bone marrow aspiration and biopsy
What is myelofibrosis?
Often the result of a myeloproliferative disorder. Where cell line proliferation causes bone marrow fibrosis in response to cytokine production e.g. fibroblast growth factor. This leads to anaemia and leukopenia, meaning haematopoiesis has to occur in the liver and spleen to compensate.
This results in splenomegaly, hepatomegaly and portal hypertension.
What are signs of polycythaemia vera?
Conjunctival plethora (redness)
Ruddy complexion
Splenomegaly
Headache Pruritus Abnormal bleeding Fatigue, night sweats and bone pain Redness of palms, fingers, soles and toes
How would you investigate myelofibrosis?
FBC: may show polycythaemia, thrombocythaemia or primary myelofibrosis (anaemia + either raised or low WCC/platelets)
Blood film: poikiloctes (teardrop-shaped red blood cells)
Bone marrow biopsy = diagnostic test
Dry bone marrow aspiration
Genetic testing: JAK2, MPL and CALR mutations associated
How is polycythaemia vera managed?
Venesection
Aspirin
Chemotherapy
How is primary myelofibrosis managed?
Allogenic stem cell transplant
Chemotherapy
Supportive treatment of portal HTN, anaemia and splenomegaly
What are the causes of thrombocytopenia?
Decreased production:
Sepsis, B12/folate deficiency, liver failure (low thrombopoietin production), leukaemia, myelodysplastic syndrome
Increased destruction:
ITP, TTP, HITT, HUS
Medication: sodium valproate, methotrexate, PPO, isotretinoin
What is ITP?
Immune thrombocytopenia
Isolated thrombocytopenia in the absence of any identifiable cause.
Most common in children following a preceding viral infection.
What is the treatment for ITP?
Prednisolone, IVIG
Rituximab
Splenectomy in refractory
Important to monitor platelet count and educate r.e. symptoms of spontaneous bleed
BP control, suppress menstruation
What is TTP?
Thrombotic thrombocytopenic purpura
Tiny clots form in the small vessels, using up the platelets and causing bleeding under the skin.
Dysfunctional ADAMTS13 protein causes overactivity of vWF
Can be inherited or autoimmune
What are features of TTP?
Haemolytic anaemia + thrombocytopenia
Usually pentad of : fever, renal failure, haemolytic anaemia, thrombocytopenia, and neurological changes
Blood film shows: fragmented red blood cells (schistocytes) and thrombocytopenia.
What is HITT?
Antibodies produced against platelets in response to heparin treatment.
AB target platelet factor 4, bind to platelets and activate clotting mechanisms
This causes a hypercoagulable state + thrombosis, followed by platelet breakdown.
Diagnosed by testing for HITT antibodies
What is the most common inherited bleeding disorder?
von Willebrand disease
What is the inheritance pattern of von Willebrand disease?
Autosomal dominant
What are the types of vWD?
Can be type 1-3
type 1: partial deficiency of vWF
type 2: mutation causes defective vWF to be produced
type 2b: mutation causes overactivity of vWF
type 3: almost total deficiency of vWF (most serious)
What tests are used to diagnosed vWD?
FBC= normal PT= normal APTT = prolonged vWF antigen = low vWF function assay= reduced in t2
How is vWD managed?
No day-to-day treatment.
In haemorrhage: desmopressin, vWF infusion +/- Factor VIII
For menorrhagia: tranexamic/mefanamic acid, norethisterone, COCP/mirena, hysterectomy
What are the two types of haemophilia and what are their inheritance pattern?
Haemophilia A = deficiency in factor VIII
Haemophilia B = deficiency in factor IX
Both inherited via x-linked recessive pattern
How is haemophilia diagnosed?
FBC: normal or may be anaemic if history of bleeding
PT: normal
APTT: prolonged
Mixing studies: APTT corrected on mixing with normal blood
How is haemophilia managed?
IV infusions of deficient factor: can be in response to bleed or prophylactic
In a bleed, desmopressin and TXA often also given
What coagulation results would you expect in vitamin K deficiency?
Prolonged PT and APTT
What drug is used for iron chelation?
desferrioxamine
What do howell-jolly bodies indicate?
Hyposplenism
Can occur in coeliac disease
What are potential complications of blood transfusion?
Non-haemolytic febrile reaction - slow/stop transfusion + paracetamol
Minor allergic reaction- temporarily stop + antihistamine
Anaphylaxis- stop, IM adrenaline
Acute haemolytic reaction- stop, send sample for Coomb’s test, fluids
Transfusion associated circulatory overload- slow/stop, IV furosemide
Transfusion associated lung injury- stop, oxygen, supportive
What is factor V leiden?
Inherited thrombophilia (hypercoagulable state) Gain of function mutation
What is Fanconi anaemia + what are its features?
Autosomal recessive.
Features haematological: aplastic anaemia increased risk of acute myeloid leukaemia neurological
skeletal abnormalities:
short stature
thumb/radius abnormalities
cafe au lait spots
Which triad describes the pathophysiology of VTE?
Virchow’s triad:
hypercoagulability, stasis of blood flow, endothelial injury
What is the management of suspected VTE?
LMWH
What is long-term management for VTE?
DOAC, LMWH, warfarin
LMWH first line in pregnancy and malignancy, otherwise apixaban often first line
3m treatment if obvious or reversible cause
6m treatment if active cancer, unprovoked, recurrent or irreversible cause
What is Budd-Chiari syndrome?
Thrombus in the hepatic vein, blocking the outflow
Associated with hypercoagulable states + can cause acute hepatitis
Triad: abdo pain, hepatomegaly and ascites
What do hypersegmented neutrophils on blood film indicate?
Megaloblastic anaemia
