Haemotology Flashcards
What are the three main categories of anaemia?
Microcytic anaemia <80
Normocytic anaemia 80-100
Macrocytic anaemia >100
What are the causes of microcytic anaemia?
TAILS
Thalassaemia Anaemia of chronic disease Iron deficiency anaemia Lead poisoning Sideroblastic anaemia
What are the causes of normocytic anaemia?
3As and 2Hs
Acute blood loss Anaemia of chronic disease Aplastic anaemia Haemolytic anaemia Hypothyriodism
What are the causes of macrocytic anaemia?
Can be megaloblastic or normoblastic.
Megaloblastic anaemia:
B12 deficiency
Folate deficiency
Normoblastic macrocytic anaemia: Alcohol Reticulocytosis Hypothyroidism Liver disease Drugs such as azathioprine
What are the symptoms of anaemia?
Tiredness SOB Headaches Dizziness Palpitations
What are the symptoms of iron deficiency anaemia in particular?
Pica: abnormal dietary cravings such as dirt
Hair loss
What are the generic signs of anaemia?
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
What are the signs of specific causes of anaemia?
Iron deficiency:
- Koilonychia
- Angular chelitis
- Atrophic glossitis
- Brittle hair
Haemolytic anaemia:
- Jaundice
Thalassaemia:
- Bone deformities
CKD:
- Oedema, HTN and excoriations of the skin
What are the initial investigations for anaemia?
Hb MCV B12 Folate Ferritin Blood film
What are the causes of iron deficiency anaemia?
Blood loss is the most common cause in adults.
Dietary insufficiency is the most common cause in growing children
Poor iron absorption
Increased requirements during pregnancy.
How is iron mainly absorbed and what interferes with this process?
In the duodenum and jejunum.
Medications that reduce stomach acid such as PPIs stop the acid keeping iron in the soluble form.
Conditions that result in inflammation of the duodenum or jejunum such as coeliac disease or crohn’s disease
What is transferrin saturation?
If you measure iron in the blood and then measure the total iron binding capacity of that blood, you can calculate the proportion of the transferrin molecules that are bound to iron, the transferin saturation.
What is the significance of ferritin in blood tests?
Low ferritin means the pt most likely is anaemic.
High ferritin may be due to inflammation as extra is released in response to infection or cancer.
Normal ferritin can still mean that the patient in iron deficient.
What can cause the results of iron test results to be high?
- Supplementation with iron
- Acute liver damage
What is the management for iron deficiency anaemia?
Oral iron e.g. ferrous sulfate 200mg three times daily. This slowly correct the iron deficiency but can cause constipation and black coloured stool.
Iron infusion. There is a small risk of anaphylaxis but it quickly corrects iron deficiency
Blood transfusion. Immediately correct the anaemia but not the underlying iron deficiency
Define pernicious anaemia
is a cause of B12 deficiency.
Give the pathophysiology of pernicious anaemia
Parietal cells of the stomach produce intrinsic factor which is essential for the absorption of vitamin B12 in the ileum.
Pernicious anaemia is an autoimmune condition where antibodies form against the parietal cells or intrinsic factor.
What are the symptoms of B12 deficiency?
- Peripheral neuropathy or paraesthesia
- Loss of vibration sense or proprioception
- Visual changes
- Mood or cognitive changes.
What is the diagnostic test for pernicious anaemia?
- Intrinsic factor antibody is the first line investigation
- Gastric parietal cell antibody can also be tested but is less helpful
What is the management of B12 deficiency?
Dietary deficiency can be treated with oral replacement with cyanocobalamin.
Pernicious anaemia: 1mg IM hydroxycobalamin 3 times weekly for 2 weeks then every 3 months.
Why must you treat a patients B12 deficiency before treating their folate deficiency?
Treating patients with folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord.
Which are the inherited haemolytic anaemias?
Hereditary spherocytosis Hereditary elliptocytosis Thalassaemia Sickle cell anaemia G6D deficiency
Which are the acquired haemolytic anaemias?
- Autoimmune haemolytic anaemia
- Alloimmune haemolytic anaemia
- Paroxysmal nocturnal haemoglobinuria
- Microangiopathic haemolytic anaemia
- Prosthetic valve related haemolysis
What are the investigations for haemolytic anaemia and what will they show
FBC shows normocytic anaemia
Blood film shows schistocytes
Direct coombs test is positive in autoimmune haemolytic anaemia
Describe the inheritance, presentation, diagnosis and management of hereditary spherocytosis and elliptocytosis
- Autosomal dominant
- Causes sphere shaped RBCs
Presents:
- jaundice
- gallstones
- splenomegaly
- notable with aplastic criss in the presence of parvovirus
Diagnosis:
- family history
- clinical features
- spherocytes on the blood film
- MCHC raised on FBC
- Reticulocytes will be raised
Treatment:
- folate supplementation and splenectomy.
Elliptocytosis is the same except the RBCs are elllipse shaped.
Describe the aetiology, presentation and triggers of G6PD deficiency
Condition where there is a defect in the RBC enzyme G6PD.
- X-linked recessive
- triggered by infections, medications or fava beans
Presents:
- jaundice (usually in neonatal period)
- gallstones
- anaemia
- splenomegaly
- Heinz bodies on blood film
- Diagnosis can be made by doing a G6PD enzyme assay
Trigger medications:
- Antimalayrial
- ciprofloxacin
- sulfonylureas
- sulfasalazine
Give the different types and management of autoimmune haemolytic anaemias
warm type:
- idiopathic
Cold-type:
- <10 degrees
- cold agglutin disease
- often secondary to lymphoma, leukaemia, SLE and infections
Maagement:
- blood transfusions- prednisolone
- rituximab
- splenectomy
Give the causes of alluimmune haemolytic anaemia
- transfusion reactions
- haemolytic disease of the newborn
What are the undrelying causes of microangiopathic haemolytic anaemia?
- haemolytic uraemic syndrome
- disseminated intravascular coagulation
- thrombotic thrombocytopenic purpura
- SLE
- cancer
Describe the pathophysiology of sickle cell anaemia
Pts have an abnormal varient called haemoglobin S which causes RBCs to be a sickle shape.
Autosomal recessive where there is an abormal gene for beta globin on chromosome 11.
Two abnormal copies are required for sickle cell disease
What are the complications of sickle cell anaemia?
Anaemia Increased risk of infection Stroke Avascular necrosis in large joints such as the hip Pulmonary hypertension Painful and persistent penile erection (priapism) Chronic kidney disease Sickle cell crises Acute chest syndrome
What is the general management of sickle cell disease?
- avoid dehydration and other triggers of crisis
- ensure vaccines are upto date
- antibiotic prohylaxis
- hydrocarbamide can be used to stimulate production of HbF
- blood transfusion
- bone marrow transplant can be curative
Define DIC
the release of procoagulants into the circulation causes widespread activation of coagulation consuming clotting factors and platelets and causing increased risk of bleeding.
Fibrin strands fill small vessels, haemolysing passing RBCs
Fibrinolysis is also activated
Describe the presentation of DIC
Bleeding anywhere
Renal failure
Bruising
What are the causes of DIC?
Malignancy
Sepsis
Trauma
Obstetric events
What are the investigation findings in DIC?
- Thrombocytopenia
- Elevated fibrin degradation products (measured by D-dimer assay)
- Fibrinogen (decreased in acute and variable in chronic)
- PT increased
- APTT increased
- thrombin clotting time increased
What is the management of DIC?
- Correction of the underlying condition
- Treatment with blood component
- Pharmacological manipulation of thrombin and plasmin generation
Define haemophilia
Haemophilia A and B are inherited severe bleeding disorders.
A is caused by a deficiency in factor VIII
B (christmas disease)is caused by deficiency in factor IX
What is the inheritence of haemophilia?
X-linked recessive
What are the signs and symptoms of haemophilias
- bleed excessively from minor trauma
- risk of spontaneous haemorrhage without trauma
Most present in neonates with:
- intracranial haemorrhage, haematomas and cord bleeding
bleeding into joints (haemoarthosis) and muscles are a classic feature* If untreated can lead to joint damage and deformity.
How are haemophilias diagnosed?
Based on bleeding scores, coagulation factor assays and genetic testing
What is the management of haemophilia?
The affected clotting factor can be replaced by IV infusions. Either prophylactically or in response to bleeding.
Complication is the formation of antibodies against the clotting factor resulting in the treatment becoming ineffective.
Define myeloproliferative disorders and give the three to remember
Conditions due to uncontrolled proliferation of a single type of stem cell. Considered a type of bone marrow cancer.
- primary myelofibrosis
Secondary:
- Polycythaemia vera
- Essential thrombocythaemia
What are the proliferating cell lines of each of the myeloproliferative disorders’?
- Primary myelofibrosis = haematopoietic stem cell
- Polycythaemia vera = erythroid cells
- Essential thrombocythaemia = Megakaryocyte
Define myelofibrosis
Can be the result of primary myelofibrosis, polycythaemia vera or essential thrombocythaemia.
It is where the proliferation of the cell line leads to fibrosis of the bone marrow.
- cytokines released from the proliferating cells causes bone marrow to be replaced by scar tissue.
Describe the presentation of myeloproliferative disorders generally
Fatigue
Weight loss
Night sweats
Fever
Anaemia Splenomegaly Portal hypertension Low platelets Thrombosis Raised RBCs Low WBC
What is the three key signs on examination in someone with polycythaemia vera?
Conjunctival plethora
Ruddy complexion
Splenomegaly
What are the full blood count findings in myeloproliferative disorders?
PV: Raised Hb ET: Raised platelets Myelofibrosis (due to primary MF or secondary to PV or ET): - anaemia - leukocytosis or leukopenia - thrombocytosis or thrombocytopenia
What does the blood film in myelofibrosis show?
Teardrop-shaped RBCs, varying sizes of RBCs (poikilocytosis) and immature red and white cells (blasts)
Describe the diagnosis of myeloproliferative disorders
Bone marrow biopsy to establish diagnosis. Usually dry due to scar tissue formation.
Testing for JAK2, MPL and CALR genes can help guide management
What is the management of primary myelofibrosis?
Allogenic stem cell transplantation is potentially curative but carries risks
Chemo can help control disease, improve symptoms and slow progression
Supportive management of anaemia, splenomegaly and portal hypertension
What is the management of polycythaemia vera?
Venesection to keep Hb in normal range = first line
Aspirin to reduce risk of thrombus formation
Chemo to control disease
What is the management of essential thrombocythaemia?
Aspirin to reduce risk of thrombus formation
Chemo to control disease
Give the pathophysiology of leukaemias
Genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal WBC.
Resulting in pancytopenia.
What is pancytopenia?
Combination of low RBC (anaemia), low platelets (thrombocytopenia) and low WBCs (leukopenia).
Describe the age group that leukaemia affects
ALL CeLLmates have CoMmon AMbitions
ALL: Under 5 and over 45
CLL: Over 55
CML: Over 65
AML: over 75
Describe the presentation of leukaemia
Fatigue Fever Failure to thrive Pallor (anaemia) Petechia and abnormal bruising (thrombocytopenia) lymphadenopathy Hepatosplenomegaly
Give the diagnosis of leukaemia
Initial: FBC within 48 hours
Diagnostic: Bone marrow biopsy
Others: Blood film LDH CXR Lymph node biopsy LP CT, MRI, PET
What is the pathophysiology of acute lymphoblastic leukaemia?
A malignant change in one of the lymphocyte precursor cells causes acute proliferation of one type (usually B-cell).
What condition is most associated with acute lymphoblastic leukaemia?
Down’s syndrome
What can be seen on blood film for Acute lymphoblastic leukaemia?
Blast cells
Positive staining for B cell antibodies (CD19, Cytoplasmic CD79a, CD22 and MPO negative)
What is the genetic mutation associated with acute lymphoblastic leukaemia?
Philadelphia chromosome (t(9:22) translocation)
Give the pathophysiology of chronic lymphocytic leukaemia
chronic proliferation of a single type of differentiated lymphocyte (usually B). Can cause warm autoimmune haaemolytic anaemia.
What is the complication of chronic lymphocytic leukaemia?
CLL can transform into high-grade lymphoma known as Richter’s transformation
What is seen on blood film for chronic lymphocytic leukaemia?
“smear” or “smudge” cells.
What are the phases of chronic myeloid leukaemia and their characteristics
- Chronic phase. Often asymptomatic and patients diagnosed with high WCC
- Accelerated phase. Abnormal blast cells take up 10-20% of bone marrow and blood. Patients develop anaemia and thrombocytopenia and become immunocomprimised.
- Blast phase. More than 30% of blast cells in blood. Severe symptoms and pancytopenia. Often fatal
What is the cytogenetic change in chronic myeloid leukaemia?
Philadelphia chromosome translocation of genes between 9 and 22.
Give an overview of acute myeloid leukaemia
Most common acute adult leukaemia.
Can be a result of a transformation from a myeloproliferative disorder.
Associated with auer rods
What is the management of leukaemia
Chemotherapy and steroids mainly
Also:
radiotherapy
bone marrow transplant
surgery
What is tumour lysis syndrome?
Caused by release of uric acid from cells that are being destroyed by chemo.
Uric acid forms crystals in the interstitial tissue and tubules of the kidneys and cause AKI.
Allopurinol or rasburicase are used to reduce the high uric acid levels.
Monitor calcium as phosphate is also released and that leads to low calcium.
What is the pathophysiology of nocturnal haemoglobinurea?
Phosphatidylinositol glycan A defect in RBC
What is thalassaemia?
Genetic defect in protein chains that make up haemoglobin.
defects in alpha-globin chain = alpha thalassaemia
Defects in beta-globin chains = beta thalassaemia
Both conditions are autosomal recessive
What are the signs and symptoms of thalassaemia?
Microcytic anaemia Fatigue Pallor Jaundice Gallstones Splenomegaly Poor growth and development Pronounced forehead and malar eminences
What is the diagnosis of thalassaemia?
FBC
Haemoglobin electrophoresis
DNA testing
What is management of alpha-thalassaemia?
Monitor FBC Monitor complications Blood transfusions Splenectomy Bone marrow transplant = curative
What is beta-thalassaemia split into?
Thalasasemia minor:
one abnormal and one normal gene
Thalassaemia intermedia:
one defective gene and one deletion gene
Thalassaemia major:
homozygous for the deletion genes
How long after a sickle cell crisis can you travel?
10 days
What is the management of INR >0.5-6 of the range and no bleed?
Reduce warfarin and recheck INR
What is the management of INR 6-8 without bleed?
Stop warfarin and recheck INR
What is the treatment for metaclopromide induced acute dystonia?
Procyclidine
What does the haemochromatosis iron studies show?
High transferrin saturation
High ferritin
Low TIBC
Which condition underestimates HbA1c?
Hereditary spherocytosis
How often should the pneumococcal vaccine be given to sickle cell patients?
every 5 years
