Haematology Flashcards
How is anaemia defined?
(not an objective)
Anaemia is defined as decreased haemoglobin in the blood such that there is inadequate oxygen delivery to tissues
- Hb <135g/L in men, Hb <115g/L in women
List the typical symptoms and signs of a patient with anaemia
Symptoms:
- Asymptomatic: a slowly falling haemoglobin allows for haemodynamic compensation
- Non-specific: fatigue, weakness, headaches
- Cardiovascular: dyspnoea on exertion, angina, intermittent claudication, palpitations
Signs:
- Pallor
- Tachycardia
- Systolic flow murmer
- Cardiac failure
Specific signs for certain types of anaemia:
- Koilonychia: spoon shaped nails in iron deficiency anaemia
- Jaundice: in haemolytic anaemia
- Leg ulcers: often seen in sickle cell disease
- Bone marrow expansion: leading to abnormal facial structure or pathological fractures, in thalassemia (rare)
What is the MCV?
What is the MCH?
MCV = size of each red blood cell
MCH = amount of haemoglobin in each red blood cell
How is anaemia classified?
By the MCV
- Low MCV (<80fL) = microcytic anaemia
- Normal MCV = normocytic anaemia
- High MCV (>96fL) = macrocytic anaemia
What are the common causes of microcytic anaemia?
(generallly due to a problem with making haemoglobin - often to do with the iron)
- Iron deficiency anaemia (IDA) - most common
- Thalassemia (any of a group of hereditary haemolytic diseases caused by faulty haemoglobin synthesis)
- Lead poisoning
- Sideroblastic anaemia (rare)
What are the common causes of normocytic anaemia?
- Acute blood loss
- Anaemia of chronic disease
- Renal anaemia
- Haemolytic anaemias (can be macrocytic due to reticulocytosis)
- Marrow failure
- Pregnancy
- Connective tissue diseases
- Diamorphic blood film (combined microcytic/macrocytic processes)
What are the common causes of macrocytic anaemia?
(generally due to shortage of DNA precursors )
(can be megoblastic or non-megoblastic anaemia)
- B12 deficiency (pernicious anaemia/Crohn’s)
- Folate deficiency (Coeliac disease)
- Alcholol excess (or severe liver disease)
- Myelodysplastic syndromes
- Severe hypothyroidism (myxoedema, can be normocytic)
- Drugs
List the common causes of iron deficiency anaemia
- Blood loss
- menstruation
- bleed e.g. GI bleed
- hookworm (most common worldwide but rare in UK
- Decreased absorption
- In coeliacs
- Pts on antacids (less ferric to ferrous iron conversion)
- Post gastrectomy
- Increased demend:
- In growth
- Pregnancy
- Inadequate intake
- premature infants/prolonged breast fed infants most at risk
What investigations would you do for a patient with suspected iron deficency to confirm it?
Blood film:
- Cells would be Microcytic and Hypochromic (paler than normal) with poikilocytosis (shape variation) and anisocytosis (size variation)
Serum iron:
- Decrease
Total iron binding capacity:
- Increased
Serum ferritin: (represents amount of stored iron)
- Decreased
Soluble transferrin receptor: (most specific test)
- Increased
What investigations would you do on a patient with confirmed iron deficiency anaemia?
- Find and treat underlying cause
- Coeliac serology the only further investigation necessary if good history of menorrhagia
- In all other patients without an obvious cause of bleeding, check coeliac serology then refer for GI investigation (gastroscopy & colonoscopy)
- Stool microscopy may be advised if recent foreign travel
What is thalassemia?
- Genetic disorders of Hb synthesis, common in the Middle/Far East
- Caused by deficient alpha or beta chain synthesis, thus resulting in alpha or ß thalassemia
Outline the physiological absorption of vitamin B12
- Dietary B12 is bound to proteins and is provided by aminal sources e.g. meat, eggs, fish, milk
- Pepsin and acid pH in the stomach break down these proteins and release free vitamin B12
- Free vitamin B12 binds to Intrinsic factor (IF) - produced by parietal cells or R proteins in the upper GI tract
- The R-proteins complexes are degraded by pancreatic proteases, unlike the IF-B12 complexes
- Receptors for the IF-B12 complex are present on the brush border of the terminal ileum, where B12 is absorped.
- In the blood the vitamin B12 binds to haptocorrin (holotranscobalamin) - active B12
- It can be stored in the liver (even in total malabsorption, body stores will last for 3 years)
Outline the physiological absorption of folate
- Folate is not itself present in nature, but occurs as polyglutamates dihydrofolate (DHF) or tetrahydrofolate (THF)
- DHF and THF is found in green vegetables and offal, however cooking causes 90% loss of the folate
- DHF and THF are converted to folate in the upper GI tract, and folate is then absorbed in the jejunum
The body’s reseveres of folate are low (only last 3 months if folate deficient diet)
Describe the pathophysiology of B12 and folate deficiency causing a macrocytic anaemia
Both B12 and folate deficiency lead to megaloblastic anaemia by a common mechanism:
- B12 acts as a co-enzyme for the conversion of folate (B9) to activated folate
- Activated folate is required for DNA synthesis, and thus if there is a deficiency in either B12 or folate, DNA synthesis malfunctions
- In this case, the DNA fails to ‘stop’ erythrocyte development, leading to very large ells, which eventually are trapped and destroyed in the reticuloendothial system
What is pernicious anaemia?
(not an objective)
- Autoimmune disease resulting in the severe B12 deficiency
- There are three autoantibodies that may contribute towards disease
- Autoantibodies against parietal cells
- Blocking antibodies (most common)
- Prevent IF-B12 binding
- Binding antibodies
- Prevent IF binding to ileal receptors
What is leukocytosis?
Increase in the total number of white blood cells in the blood
What is included in a white blood cell count?
Give the roles of each
- Neutrophils: ingest and kill bacterial, fungi & cellular debris
- Lymphocytes: produce antibodies for cell-mediated immunity
- Eosinophils: role in allergic reactions, and defence of parasitic infection
- Monocytes: precursor of tissue macrophages
- Basophil: release histamine in inflammatory reactions
What are the differentials for neutrophilia?
Neutrophilia is increased number of neutrophils
- Bacterial infection
- Inflammatory reactions
- Disseminated malignancy
- Stress e.g. surgery, burns
- Myeloproliferative conditions
- Corticosteroid therapy
What are the differenitals for neutropenia?
Neutropenia is low levels of neutrophils
- Viral infections
- Severe sepsis
- Neutrophil antibodies e.g. SLE
- Bone marrow failure
- Hypersplenism e.g. Felty’s
- Cytotoxic drugs
What is the complete absence of circulating neutrophils called?
What can cause it?
Agranulocytosis
Side effect of carbimazole (used to treat hyperthyroidism)
What are the differentials for lymphocytosis?
Lymphocytosis is a high number of lymphocytes
- Viral infections
- Chronic infections (TB, hepatitis)
- Myeloproliferative conditions
Remember lymphocytes produce antibodies for cell-mediated immunity
What are the differentials for lymphopenia?
Lymphopenia is low levels of lymhocytes
- Bone marrow failure
- Corticosteroid therapy
- SLE
- Uraemia
- HIV infection
- Cytotoxic drugs
Describe the mechanism of action of aspirin
- Low dose (75mg) aspirin irreversibly inhibits cyclo-oygenase (cox inhibitor) , preventing conversion of arachidonic acid to endoperoxides such as PGI2 (platelet aggregators) or TXA2 (vasoconstrictor and aggregator)
- After administration of the drug, the nuclei of endothelial cells are quickly able to secrete mRNA for PGI2 production
- The anucleate (lacking nucleus) platelets cannot form TXA2, so levels decrease until new platelets are formed in approx 7 days
- Low-dose of aspirin every 24-48 hours thus decrease synthesis of TXA2 without massively affecting PGI2 production
Define thrombocytopenia
What are the clinical features of thrombocytopenia?
Low platlets
Presentation is with mucocutaneous bleeding:
- Bruising/purpura of the skin
- Epistaxis/menorrhagia
Major haemorrhage is very rare and physical examination is usually normal
What are the major causes of thrombocytopenia?
Thrombocytopenia can be due to reduced platelet production in the bone marrow or excessive peripheral destruction of platelets
Reduced production:
- Aplastic anaemia
- Marrow infiltration
- Marrow suppression
Excess destruction:
- Immune thrombocytopenic purpura (ITP)
- Other autoimmune causes:
- SLE
- Chronic lymphocytic leukaemia (CLL)
- Viruses
- Thrombotic thrombocytopenic purpura (TTP)
- Haemolytic uraemic syndrome (HUS)
- Sequestration (red blood cells trapped in spleen): hypersplenism
What are the laboratory tests that are used to assess the clotting system?
What do they assess?
Prothrombin time (PT):
- Tests the extrinsic pathway, by addition of a tissue factor substitute to the patient’s plasma
- It is prolonged in liver disease or if the patient is on warfarin
International normalised ratio (INR)
- Ratio of patient’s PT to a normal control whilst using an international reference preparation
- 0.9-1.1 is the normal range
- Used for warfarin dosing
Activated partial thromboplastin time (APTT)
- Addition of a surface activator to the plasma
- Tests the intrinsic (contact) pathway
- Its is the monitoring required for unfractional heparin
Thrombin time:
- Addition of thrombin to the patient’s plasma
- Prolonged with fibrinogen deficiency or abnormal function, or inhibitors such as heparin
- Tests final common pathway
Describe the role of liver in the coagulation cascade
- Clotting factors are primarily synthesised in the liver, and many act as serine proteases to activate other factors
Factors produced by the liver:
- I (fibrinogen), II (prothrombin), IV, V, VI, and VII
Describe the coagulation cascade
What is the role of vitamin K?
- It is a cofactor necessary for the production of the blood clotting factors:
- Factor II, VII, IX and X
- Deficiency thus leads to clotting factor deficiencies, leading to an increased PT and haemorrhage
- Protein C is dependent on vitamin K, activated protein C inactivates factors V and VIII, stopping further thrombin generation
It is absorbed in upper ileum and stored in the liver
Describe the ABO blood group system
ABO system:
- Red cells can be A, B, AB or O: named according to their surface antigens
- They will carry IgM antibodies against any antigen that they do not carry
- O group blood will carry anti-A and anti-B antigens
- AB group blood will not carry any anti-A or anti-B antigens
What is the significance of the ABO blood groups in blood transfusion?
- Incompatibilities involving many of the other antigens can cause haemolytic transfusion reactions
- Blood groups are determined by antigens of the surface of red cells, with the ABO/Rhesus group the two major blood groups
Describe the Rhesus antigen system
(not an objective)
- Blood cells can either show the rhesus D antigen (rhesus positive) or not (rhesus negative)
- If a rhesus negative individual is exposed to rhesus positive blood products, then they can develop IgG antibodies directed against the rhesus D antigen
- If exposed to rhesus positive blood products again, there will be haemolysis
- This is the pathology behing haemolytic disease of the newborn, as well as transfusion reactions
Describe the principles of cross-matching blood
(describe the tests used)
- Blood grouping: ABO and RhD groups of patients are determined
- Antibody screening: Patient serum/plasma screened for atypical antibodies that would cause significant haemolysis of transfused cells
- These two processes are automated, and donor blood of the same ABO/Rh group, and without specific antigens if atypical antibodies are found, is then crossmatched
- Indirect agglutination test: donor RBCs added to patients serum, then Coomb’s reagent is added, agglutination indicates that the patients serum has antibodies for the donor RBCs. This test is always performed pre-transfusion
-
Direct agglutination: patients ‘washed’ RBCs are added to Coomb’s reagent, and if they agglutinate that indicates that there is an autoimmune haemolytic process occuring, with the RBCs coated with immunoglobulins. This is rarely required pre-transfusion
- This is known as ‘Coomb’s’ test
All blood products need to be cross-matched except platelets
