Haematology Flashcards
Common symptoms for anaemia
Weakness, fatigue and lethargy Shortness of breath and reduced exercise tolerance Headaches and syncope Angina and palpitations Conjunctival pallor Tachycardia Tachypnoea Orthostatic hypotension
Different types of anaemia and some examples
Microcytic (low MCV) e.g. iron deficiency, sideroblastic, thalassemias.
Normocytic (normal MCV) e.g. bone marrow suppression, acute blood loss, chronic diseases.
Macrocytic (high MCV) e.g. B12 and folate deficiency, alcoholism, haemolytic anaemias.
What happens in severe anaemia
Hyperdynamic circulation - tachycardia, cardiac enlargement, flow murmur.
Also get angina, ankle oedema, dyspnoea at rest.
Where is iron absorbed, how is transported and what are some good food sources
Absorbed in duodenum and jejunum.
Transported by transferrin
Meat, wholegrain (brown rice), curly kale.
Causes of iron deficiency
Blood loss in GI bleed (hookworm) or menorrhagia
Inadequate intake in diet
Increased requirement e.g. infants
Poor absorption e.g. GI surgery or coeliac
Some signs only really seen in iron deficiency anaemia
Koilonychia (spoon nails) Atrophic glossitis (red sore tongue) Angular cheilosis (inflammation at side of mouth) Hair loss Pica (weird food cravings e.g. clay)
Patient has iron deficiency anaemia but also complains of sore tongue, sore mouth/lips, difficulty swelling. What is wrong with them and what will you see in endoscopy
Plummer-Vinson syndrome
Oesophageal webs
Investigations and expected results for iron deficiency anaemia
FBC = low Hb, Low MCV, Low MCHC (Hb concentration)
Blood film = microcytic hypochromic anaemia with different sized (anisocytosis) and different shaped (poikilocytosis) cells.
Iron studies = low ferritin, low transferrin saturation, high TIBC (iron binding capacity).
Investigate possible cause = coeliac serology (IgA-tTG), endoscopy for GI malignancy.
Management of iron deficiency anaemia
Treat cause (Mirena coil for menorrhagia, gluten free diet etc etc).
Oral iron e.g. ferrous sulphate 200mg PO. Should see rise in Hb of 10g/L in a week. Continue for 3 months even if Hb normalises.
If severe - blood transfusion.
Side effects of oral iron
Nausea
Constipation
Dark stools
Abdo discomfort
Differential for low iron but high TIBC (no blood film results yet)
Pregnancy. Ferritin may be high in pregnancy.
FBC = low iron, low MCV, high MCHC
Film = different sized and shaped, hypochromic.
Iron studies = low ferritin, low transferritin, high TIBC, high reticulocytes.
Iron deficiency
Sideroblastic anaemia
Poor erythropoiesis. Increased iron absorption and iron loading in organs.
X-linked genetic inheritance or acquired from myeloproliferative or myelodysplastic disorders.
Ix = FBC = low Hb. Iron studies = high ferritin, normal TIBC, high serum iron. Blood film = dimorphic population of cells, microcytic, hypochromic. Bone marrow biopsy = ringed sideroblasts.
Rx = pyridoxine and transfusion if severe. Treat cause.
Name some chronic diseases which can cause anaemia of chronic disease
Renal failure Rheumatoid arthritis SLE Malignancies (lymphoma) Chronic infection (TB)
Investigations for anaemia of chronic disease
FBC = low Hb.
Blood film = normocytic and normochromic.
Iron studies = low serum iron, normal/raised ferritin, low transferrin, low TIBC.
Raised ESR and other markers of the chronic disease.
2 types of macrocytic anaemia
Megaloblastic and non-megaloblastic.
Megaloblastic = delayed nuclear maturation e.g. B12 and folate deficiency, cytotoxic drugs.
Non-megaloblastic = alcohol excess, pregnancy, hypothyroidism.
Sources of folate and where is it absorbed
Green vegetables, nuts, citrus fruits
Proximal jejunum
Where is B12 absorbed. What has lots of vitamins B12
Ileum.
Fish and dairy and meat.
What symptoms do patients with megaloblastic anaemia commonly complain (more than other types of anaemia)
Headache
Anorexia
Who are at risk of folate deficiency
Alcoholics
Pregnancy (take folic acid to prevent rural tube defects)
Over 65yrs
Investigations and expected results for folate deficiency anaemia
FBC = low Hb, high MCV. Blood film = macrocytic RBC, hypersegmented neutrophils (immature RBC and WBC). Low serum folate. Low reticulocyte count. Bone marrow biopsy shows megaloblasts.
Investigating for anaemia
FBC
Blood smear
Iron studies
Serum B12 and folate
Management of folate deficiency
Oral folic acid supplementation.
If severe = packed RBC transfusion.
Difference between B12 and folate deficiency anaemia
B12 = peripheral neurology, neuropsych signs Folate = no neuro stuff.
Who are at risk of B12 deficiency
Vegetarians and vegans 👩🏼🌾👨🏻🌾
Also Crohn’s and gastric by-pass patients.
Quick overview of B12 physiology
Binds with intrinsic factor from parietal cells in stomach.
IF-B12 complex travels to terminal ileum.
Complex binds to transcobalamin and realised into blood stream.
What colour is the skin of b12 deficiency and why
Lemon tinge - pallor from anaemia + yellow from mild jaundice and haemolysis.
What are some neurological s+s in b12 deficiency
Psych = dementia, psychosis, depression. Neuro = SUBACUTE DEGENERATION OF SPINAL CORD = distal sensory loss, absent ankle reflex, brisk knee reflex. LMN and UMN signs. Paraesthesia, numbness, loss of vibration sensation, normal pain and temperature sensation.
Ix for B12 deficiency anaemia
FBC = low Hb, high MCV
Low serum B12
Blood smear = megalocytic RBC, hypersegmented neutrophils.
Low reticulocyte count.
Management of B12 deficiency anaemia
Moderate = IM hydroxycobalamin (life long but bi-weekly) Severe = IM hydroxycobalamin + folic acid and admit to hospital for neuro assessment. Consider blood transfusion.
Pernicious anaemia
Autoimmune atrophic gastritis - anti parietal cell antibody so no IF to bind to B12.
Similar presentation to B12 deficiency (lemon-tinge, neuro and psych symptoms plus palpitations, fatigue etc etc).
Ix = same as for any anaemia - FBC (low Hb, high MCV), smear (hypersegmented neutrophils).
Special pernicious tests = IF antibody, parietal cell antibody.
Mx = IM hydroxycobalamin.
Associated with other autoimmune conditions e.g. thyroid. Also increased gastric cancer risk.
What makes up adult haemoglobin
2 alpha + 2 beta globin chains
α-thalassemia
2 separate alpha globin genes on Chr16 so 4 genres (αα/αα).
Mutations inherited autosomal recessively.
If all 4 mutated = death in utero (Bart’s hydrops).
If 3 mutations = HbH disease. Anaemia, haemolysis (jaundice, hepatosplenomegaly). FBC = low MCV. Blood film shows target/Mexican hat cells. ß4 tetramers from excess ß chains on electrophoresis. Mx = folic acid, transfusion, splenectomy.
If 2 mutated = asymptomatic carrier.
If 1 mutated = clinically normal.
Mx with genetic counselling.
Good differential for HbH (α thalassaemia)
Malaria esp as prevalent in same areas.
Target cells
Blood film of α and ß -thalassaemia disease
ß-thalassaemia pathophysiology
Mutations for ß-globin on Chr11. Ineffective erythropoiesis.
S+S start as fetal Hb changes to adult Hb (present in first year).
Anaemia
Compensatory erythroid hyperplasia = bony changes in skull, splenomegaly.
ß thalassaemia minor, intermedia or major
- Minor = trait. Asymtpmatic, only ∆ on genetic screening.
- Intermedia = presents later in life e.g toddler or young adult. Less severe symptoms.
- Major = Cooley’s anaemia. Absence of HbA, presenting within 1st year of life. Pallor, abdo distention, poor feeding, lack of activity, hepatosplenomegaly, frontal and parietal skull bossing.
Ix for ß thalassaemia
FBC = low Hb, low MCV.
peripheral blood film = tear drop cells, microcytic red cells.
High reticulocyte count
Haemoglobin electrophoresis to determine intermedia/major etc
Raised unconjugated bilirubin.
Skull x-ray = ‘hair on end’ sign (high marrow activity).
AXR = hepatosplenomegaly.
Mx for ß thalassaemia
Genetic counselling
Dietary advice.
Consider chelation
Regular transfusions (lifelong dependent), splenectomy.
Inheritance and pathophysiology of sickle cell anaemia
Autosomal recessive mutation in ß-chain for Hb creating sickle cell Hb (HbS).
On deoxygenation RBC morph shape to sickle shape. This causes clusters to block blood vessels (esp liver and spleen), intense pain (sickle cell crisis), infections and anaemia.
Types of sickle cell disease
- Sickle cell trait = heterozygotes = HbSA, no symptoms, protective against P.falciparum malaria.
- Sickle cell disease = homozygotes = HbSS, symptomatic.
- Can get a patient who inherits heterozygous sickle cell and mild thalassaemia so does present.
S+S of sickle cell disease ⛏
Present within first year of life. FHx Jaundice from haemolysis. Pallor, tachycardia, fatigue from anaemia. Splenomegaly Dactylitis Leg ulcers Present in crisis.
Sickle cell vaso-occuslive crisis.
Vaso-occulsive crisis as lots of Hb is deoxygenated at once.
Subtypes of thrombotic stroke, acute chest syndrome and priapism.
Precipitated by: stress, cold, pregnancy, dehydration, low PaO2 (exercise, anaesthesia, altitude), illness.
S+S: PAIN PAIN PAIN (limb bone), swollen joints, S+S of ischaemic area e.g. acute abdomen.
Mx = A-E resuscitation, IV analgesia (morphine), blood crossmatch, warm IV fluids, consider need for ABx and blood transfusion, inform haematologist.
Chronic complications of sickle cell disease
Chronic anaemia Chronic pain Leg ulcers Sickle Lungs = breathlessness, chest pain, restrictive lung pathology Retinopathy Gallstones Persistent erection Pulmonary HTN lots and lots
Ix for sickle cell disease
Hb electrophoresis = diagnostic. Peripheral blood smear = sickle cells, target cells and Howell-Jolly bodies from poor splenic function. FBC = low Hb Bilirubin = raised Reticulocyte count = raised Sickle solubility test
Acute complications of sickle cell disease
Vaso-occlusive crisis of bone. Mesenteric ischaemia Acute chest syndrome Sepsis Priapism (sustained painful erection) AKI Stroke Aplastic crisis Sequestrian crisis. Avascular necrosis of femoral or humeral head.
Acute chest syndrome
Can lead to ARDS and death.
Chest pain, tachypnoea, cough, SOB.
A-E resuscitation –> oxygen, fluids, analgesia.
Ix = CXR, ABG.
Mx with broad spec ABx (tazosin) and blood transfusion.
Describe 2 ways to classify haemolytic anaemia and examples for each.
Intra and extra vascular.
Intravascular = DIC, lack of G6PD.
Extravascular = sickle cell disease, hereditary spherocytosis, immune mediated IgG (lymphoma).
Acquired and Hereditary.
Acquired = immune e.g. IgG and IgM or non-immune e.g. DIC, trauma.
Hereditary = sickle cell disease, G6PD deficiency.
Coombs’ test
Direct antiglobulin test. Positive in immune mediated haemolytic anaemia.
Examples of hereditary causes of haemolytic anaemia
Inherited RBC defect e.g. hereditary spherocytosis.
Abnormal Hb e.g. thalassaemia, sickle cell.
Enzyme defect e.g. G6PD deficiency.
Examples of acquired haemolytic anaemia
Immune mediated:
- alloimmune (haemolytic disease of the newborn).
- warm reacting autoimmune (SLE, CLL) IgG
- cold reacting autoimmune (lymphoma) IgM.
- drugs (sulfasalazine, penicillin)
Non-immune mediated:
- infection (Mycoplasma pneumoniae)
- Trauma
- microangiopathic haemolytic anaemia (DIC, HELLP, HUS).
- hypoersplenism
Ix for haemolytic anaemia
FBC = low Hb, high reticulocyte, high MCV from reticulocytes.
Peripheral blood film = depended on cause.
Bilirubin = raised in conjugated bilirubin.
Urinalysis = ++RBC.
LDH + haptoglobin = low LDH and high haptoglobin.
Coomb’s test = immune or no immune-mediated.
Presentation of haemolytic anaemia
Anaemia = pallor, fatigue, SOB, headache,
Haemolysis = jaundice, dark urine, splenomegaly, gallstones.
RFx = FHx, other autoimmune conditions.
S+S of cause.
Mx for haemolytic anaemia
All get supportive Mx = folic acid, review meds, transfusion of packed RBC.
Immune mediated Mx = corticosteroids, splenectomy.
Drug for sideroblastic anaemia
Pyridoxine
Aplastic anaemia pathophysiology and causes
Pancytopenia (thrombocytopenia, neutropenia, anaemia) with hypocellular marrow and the absence of any abnormal cells.
Ax = autoimmune, drugs, viruses (hepatitis, parvovirus), irradiation, inherited (Fanconi anaemia).
Where to take bone marrow biopsies
Iliac crest.
Haemopoises occurs in axial skeleton (e.g. skull, vertebrae, ribs) and long bones.
Name 4 types of leukaemia and how they are different from one another
Acute myeloid leukaemia - acute neoplastic proliferation of blasts cells from bone marrow myeloid tissue, blast cells can no mature and differentiate.
Acute lymphocytic leukaemia - acute neoplastic proliferation of immature B and T lymphocytes.
Chronic myeloid leukaemia - slow progression of neoplastic proliferation of blasts cells from bone marrow myeloid.
Chronic lymphocytic leukaemia - slow progression of neoplastic proliferation of dysfunctional B cells.
But what actually is leukaemia 🤔
Excess of abnormal white blood cells in peripheral blood. either myeloid or lymphoid in origin.
Which leukaemia can be a product of another cancer and why
Acute myeloid leukaemia from chemotherapy.
AML S+S
Acute onset of symptoms.
From marrow failure = anaemia, infections, bleeding and bruising.
From cell infiltration = hepatosplenomegaly, gum hypertrophy, lymphadenopathy
Ix for AML
FBC - raised WCC, low Hb. Also do clotting profile, renal function, LFT.
Peripheral blood film - blast cells.
Bone marrow biopsy - ∆, hypercellulatiry, blast cell infiltration, AUER RODS in myeloblast cells.
Mx for acute myeloid leukaemia
Supportive care - exercise regimens, adequate hydration, information on diagnosis, safety net advice or ABx for infections.
Chemotherapy e.g. Azacitidine (pyrimidine analogue) Allopurinol to prevent uraemia from tumour lysis syndrome.
Bone marrow transplant
Acute lymphoblastic leukaemia common presentation
CHILDREN. Commonest cancer of childhood 👶
S+S of acute lymphoblastic leukaemia
Marrow failure = anaemia, thrombocytopenia and neutropenia. Esp recurrent chest, mouth, skin or perianal infections.
Infiltration = hepatosplenomegaly, lymphadenopathy, CNS involvement e.g. cranial nerve palsy, meninigms and nuchal stiffness.
