Anaemia Flashcards
Anaemia
What are the two causes of raised Hb?
True polycythaemia
Pseudopolycythaemia
What is the normal pathway for erythrocytosis?
Tissue hypoxia
Raised EPO production from kidney
RBC production in bone marrow
What are the two types of true polycythaemia?
Primary (polycythaemia vera)
Secondary (high EPO)
What are some causes of secondary polycythaemia?
COPD
Renal cell carcinoma
High altitude
Smoker
What is polycythaemia vera?
Clonal haematopoietic disorder of bone marrow resulting in erythrocytosis
May be associated with thrombocytosis, leukocytosis, and splenomegaly
What is the genetic link with PCV?
85% are related to a JAK2 V617F mutation
What are the symptoms of PCV?
Asymptomatic Headache, dizziness, fatigue Aquagenic pruritus- itching after shower Blurred vision Tinnitus Thrombosis Gangrene
What are the signs of PCV?
Choreiform movements
Hepatosplenomegaly
Red face, fingers, palms, toes, heels
What are the investigations for PCV?
FBC- raised Hb, Hct, WCC, platelets
Gene mutation screen for JAK2 V617F
What is anaemia?
Reduction in Hb, red cell count, and packed cell volume below reference age and sex
What are some general features of anaemia?
Pale conjunctivae, mucous membranes + skin
Fatigue
Faintness
Dyspnoea, tachycardia (if severe)
Intermittent claudication/angina (severe)
What are the three types of anaemia and what are the MCV levels that distinguishes them?
Microcytic (<80)
Normocytic (80-96)
Macrocytic (>96)
What are the causes of microcytic anaemia?
Iron deficiency anaemia (IDA)
Thalassaemia
Anaemia of chronic disease
Sickle cell anaemia
What are the 3 broad causes of IDA? Give examples for each
Blood loss (GI malignancy, menstruation, peptic ulcer, IBD) Increased demand (pregnancy/growth/breast feeding) Decreased absorption (malnutrition, coeliac, IBD, post-gastrectomy)
What are the investigations for IDA?
FBC Iron studies Blood film Upper GI endoscopy + colonoscopy (if unexplained) Coeliac serology (IgA TTG antibodies)
What is the management for IDA?
Treat underlying cause
Animal iron>plant
Oral Fe
IV/IM Fe if poor tolerance/uptake
What can cause ACD?
Chronic inflammation (RhA)
Chronic infection (TB)
Chronic malignancy
No other obvious cause of anaemia
What are the investigations for ACD?
Raised ESR/CRP
FBC- low Hb, low/normal MCV
Iron studies:
- low serum iron
- high/normal ferritin (acute phase protein)
- low/normal transferrin
- normal transferrin sat
What is normal haemoglobin made of?
2 alpha globin chains
2 beta globin chains
What are the two main types of thalassaemia?
Alpha thalassaemia Beta thalassaemia (most common)
How many genes code the alpha Hb chain?
4 genes, 2 from each parent
Chr 16
How does alpha thalassemia present depending on number of defective genes?
- Alpha thalassaemia silent (1 absent gene)
- Alpha thalassaemia trait (2 absent genes)
= these cause very mild anaemias - Haemoglobin H (3 absent genes) = significant, requires transfusions
- Haemoglobin Barts (4 absent genes) = death in utero
What are the characteristics of alpha thalassaemia silent?
No clinical symptoms
What are the characteristics of alpha thalassaemia trait?
Low MCV + MCH
Can be confused with IDA
Hb electrophoresis shows low/normal HbA2
What are the characteristics of haemoglobin H?
Microcytic hypochromic anaemia Target cells and Heinz bodies Hepatosplenomegaly Presents in childhood/early adulthood Needs lifelong transfusions
What are the characteristics of haemoglobin Barts?
Often fatal in utero unless intrauterine transfusions
What are the types of beta thalassaemia?
Beta thalassaemia minor
Beta thalassaemia trait/intermedia
Beta thalassaemia major
What are the characteristics of beta thalassaemia minor?
Asymptomatic heterozygous carrier Mild/absent anaemia Low MCV Normal ferritin Electrophoresis shows increased HbA2
What are the characteristics of beta thalassaemia trait?
Combination of homozygous beta and alpha thalassaemias
Moderate anaemia that doesn’t require transfusions
Splenomegaly, gallstones, bone deformities, recurrent leg ulcers
What are the characteristics of beta thalassaemia major?
Presents first 2-3 months of life
Severe anaemia, failure to thrive, recurrent infections
Bony abnormalities due to bone marrow hypertrophy
Extramedullary haematopoiesis
Electrophoresis shows HbF and reduced/absent HbA
What are the investigations for thalassaemia trait? What would they show?
FBC- low Hb, low MCV
Iron studies would be NORMAL
Gel electrophoresis
What is the management for severe thalassaemia?
Blood transfusions Iron chelators Bone marrow transplant: -only curative treatment -causes infertility
What are the types of macrocytic anaemia?
Megaloblastic
Normoblastic
What is a megaloblast?
developing RBCs in the bone marrow with a delayed nuclear maturation relative to their cytoplasm
What are the causes of megaloblastic macrocytic anaemia?
Vit B12 deficiency
Folate deficiency
What are the causes of normoblastic macrocytic anaemia?
Pregnancy Alcohol excess Reticulocytosis Liver disease Hypothyroidism Haematological disorders (eg. aplastic anaemia) Drugs (eg. hydroxycarbamide)
What are the causes of Vit B12 deficiency?
Low intake (eg. vegans)
Impaired absorption:
Stomach: pernicious anaemia, gastrectomy
Small bowel: Crohn’s, coeliac, tropical sprue
What is pernicious anaemia?
Autoimmune condition of atrophic gastritis and the destruction of parietal cells
Lack of intrinsic factor, which is needed for B12 absorption
What are the symptoms of B12 deficiency?
Progressive anaemia Weight loss Change in bowel habits Muscle weakness Symmetrical paraesthesia Visual impairment Memory disturbance
What are the signs of B12 deficiency?
Progressive anaemia Jaundice (ineffective erythropoiesis- RBC precursor breakdown) Glossitis Angular stomatitis Polyneuropathy
What are the investigations for B12 deficiency?
FBC and film:
-low Hb, high MCV, low reticulocytes, hypersegmented neutrophils
Serum vit B12- low
Serum autoantibodies: 90% parietal cells, 50% IF
What is the management for B12 deficiency?
IM hydroxycobalamin or oral cyanocobalamin
What are the causes of folate deficiency?
Poor intake -elderly, poverty, alcohol XS, eating disorders Malabsorption -Coeliac, Crohn's, tropical sprue XS utilisation -pregnancy, adolescence, prematurity, haemolytic anaemia, malignancy, inflammatory diseases Drugs -methotrexate, phenytoin
What are the investigations for folate deficiency?
FBC and film -low HB, high MCV, low reticulocyte, hypersegmented neutrophils Serum folate -low Red cell folate (diagnostic) -low
What is the management for folate deficiency?
Treat underlying cause
Folic acid replacement
What are the causes of normocytic anaemia?
Acute blood loss Anaemia of chronic disease Combined microcytic and macrocytic e.g. iron and folate deficiency Marrow infiltration/fibrosis Endocrine disease Haemolytic anaemia
What is myelofibrosis?
A disorder of haematopoietic stem cells and progressive marrow fibrosis
What are the clinical features of myelofibrosis?
Insidious onset
-FLAWS
Splenomegaly
Hepatomegaly (extramedullary haematopoiesis)
What are the investigations for myelofibrosis?
FBC- anaemia
Peripheral blood smear:
- leukoerythroblastic change
- characteristic “tear drop” poikilocyte red cells
Bone marrow aspiration- dry tap
Bone marrow biopsy- hypocellular marrow fibrosis
50% primary MF have JAK2
What are the hereditary causes of haemolytic anaemia?
Membrane defects
- hereditary spherocytosis
- hereditary elliptocytosis
Metabolic defects
- G6PD deficiency
- pyruvate kinase deficiency
Haemoglobinopathies
- thalassaemia
- sickle cell disease
What are the acquired causes of haemolytic anaemia?
Autoimmune
Non-autoimmune:
- drugs
- infx
- hypersplenism
- paroxysmal nocturnal haemoglobinuria
- MAHA
- HUS
- thrombocytopenic purpura
- DIC
What are the clinical features of haemolytic anaemia?
Splenomegaly
Increased RBC production and reticulocytes
Bone marrow erythroid hyperplasia
Polychromatic cells on blood film
Low serum folate
Increased serum bilirubin
Increased risk of iron overload and osteoporosis
What is an aplastic crisis?
Temporary suspense of RBC production Parvovirus B19 susceptibility Virus arrests the maturation of erythroid cells in bone marrow for ~10 days Sudden drop in Hb Low/absent reticulocyte count
What is hereditary spherocytosis?
Autosomal dominant condition
Commonest inherited haemolytic condition in Northern Europe
Defect in membrane causes cell to become spherical, hence gets destroyed in the spleen
What are the clinical features of hereditary spherocytosis?
Can be asymptomatic
Anaemia, jaundice, splenomegaly
What are the investigations for hereditary spherocytosis?
FBC- anaemia, reticulocytosis
Blood film- spherocytes
Coomb’s test- negative
What is Coomb’s test assessing?
If your blood contains auto-antibodies for RBCs
What are the triggers for G6PD deficiency?
Fava beans Moth balls Infections Drugs eg. quinine, sulphonamide, nitrofurantoin -anti-malaria drugs
What are the investigations for G6PD deficiency?
Peripheral blood smear- Heinz bodies
Direct measure of enzyme levels in red cells
What is sickle cell anaemia?
Autosomal recessive condition where both alleles create HbS
Deoxygenated HbS is insoluble and polymerises
What may trigger sickling in sickle cell anaemia?
Hypoxia Dehydration Infection Cold Acidosis
What are the consequences of sickling?
- increased RBC fragility –> haemolysis (plasma Hb also triggers occlusion)
- increased RBC adhesion –> microvascular occlusion + ischaemia
What are the 3 crises that may present in sickle cell anaemia?
Splenic Sequestration Crisis
- pooling of blood in spleen
Vaso-occlusive Crisis (AKA painful crisis)
- sickle shaped blood cells clogging capillaries and causing distal ischaemia
Aplastic crisis
- temporary loss haematopoesis
- triggered by infection with parvovirus B19
What is acute chest syndrome?
Due to sickle cell sequestration crisis or infection:
- SOB
- Cough
- Fever
- New infiltrates on CXR
MEDICAL EMERGENCY- supportive/underlying cause
What are the investigations for sickle cell anaemia?
Diagnosed at birth with heel prick test
FBC- low Hb, high reticulocyte
What is the management for sickle cell anaemia?
Avoid precipitating factors
Folic acid
Pneumococcal/influenza vaccination
Acute painful crisis- analgesics, oxygen, fluid, ABx
Blood transfusions if severe symptoms occur
Recurrent painful crisis- hydroxycarbamide
Splenectomy/cholecystectomy if severe
Bone marrow transplant is curative
What are the complications of sickle cell anaemia?
Swollen joints Sickle chest syndrome/pneumonia Bowel ischaemia Splenic/hepatic sequestration Cholecystitis Arrhythmia Priapism
What is autoimmune haemolytic anaemia?
Autoimmune destruction of RBCs
Diagnosed via Coomb’s test/direct antiglobulin test (DAT)
What are warm antibodies?
IgG that attaches to RBC at 37 degrees
Idiopathic/associated with autoimmune conditions, lymphomas, CLL, carcinomas
What are cold antibodies?
IgM that attaches to RBC below 37 degrees
Idiopathic/associated with infections (e.g. mycoplasma spp, EBV etc), lymphomas, paroxysmal cold
What is microangiopathic haemolytic anaemia?
Damage to endothelial surface results in fibrin strand deposition and platelet aggregation in small vessels
Red cells are fragmented as they pass causing intravascular haemolysis
What are the investigations for microangiopathic haemolytic anaemia?
Blood count and film: reticulocytosis, schistocytes
What is haemolytic uraemic syndrome?
Triad of:
- MAHA
- AKI
- thrombocytopenia
What are the causes of HUS?
Infection- shiga toxin of E. coli 0157 (Pt has diarrhoea), non E. coli related (no diarrhoea)
Drug- OCP, cyclosporin
Other- pregnancy, SLE
What are the clinical features of HUS?
Pallor (anaemia) Jaundice (haemolysis) Bruising (thrombocytopenia) Oligo/anuria (AKI) Haematuria (AKI) Oedema Hypertension Fever Fatique Abdo pain
What are the investigations for HUS?
FBC and film: normocytic anaemia, thrombocytopenia, reticulocytosis, schistocytes
U+E: raised creatinine
PT + APTT: normal
Renal biopsy
What is thrombotic thrombocytopenic purpura?
Pentad of:
- MAHA
- AKI
- thrombocytopenic purpura
- fever
- neurological dysfunction
What are the causes of TTP?
Deficiency of ADAMTS-13:
-secondary to AI process (eg. SLE), drugs, pregnancy, infection
What are the clinical features of TTP?
Same as HUS
Fever
Florid purpura
Fluctuating cerebral dysfunction (headaches, confusion, seizures, coma)
What are the investigations for TTP?
Same as HUS FBC and film: normocytic anaemia, thrombocytopenia, reticulocytosis, schistocytes U+E: raised creatinine PT + APTT: normal Renal biopsy
A 60 year old man presents with lethargy to the GP. A full blood count and smear is requested. The following is found:
Hb: 10 g/dl (13.5-18.0)
Platelets: 310 (150-400)
WBC: 14 (4-11)
Film: Leucoerythroblastic picture with tear-drop poikilocytes seen
What is the most likely diagnosis:
A. Iron deficiency anaemia B. Myelofibrosis C. Chronic myeloid leukaemia D. Haemolytic anaemia E. Myelodysplasia
B. Myelofibrosis
A 55 year old lady presents to the GP with long standing pain in her hands. On examination there are gross deformities of her fingers and joint swelling.
FBC reveals
Hb: 7.3 (11.5-16.0)
MCV: 94 (82-100)
WCC: 7 (4-11)
What is the most likely cause of the blood results?
A. Thalassaemia B. Iron deficiency anaemia C. Vitamin B12 deficiency D. Anaemia of chronic disease E. Sideroblastic anaemia
D. Anaemia of chronic disease
A 21 year old female presents with chronic fatigue and tiredness. On further questioning she reveals a longstanding history of heavy periods. On examination you notice pale conjunctivae.
What is the most likely cause of her symptoms:
A. Alcohol excess B. Iron deficiency anaemia C. Folate deficiency D. Thalassaemia E. Vitamin B12 deficiency
B. Iron deficiency anaemia
A 35 year old man presents to his GP with worsening fatigue over the past few months. He mentions that his stools have been darkening recently and he’s been having recurrent pins and needles in his hands. His has a history of Crohn’s disease which is managed with azathioprine but has had several flares this year which required hospital admission. A full blood count shows the following:
Hb: 10 (13.5-18.0)
MCV: 124 (84-100)
Platelet: 240 (150-400)
What is the most likely diagnosis:
A. Vitamin B12 deficiency B. Anaemia of chronic disease C. Alcohol excess D. Iron deficiency anaemia E. Haemolytic anaemia
A. Vitamin B12 deficiency
A 7 year old male with known sickle cell disease present to A+E with a cough and mild pain in his back for the last 2 days. He has already tried paracetamol and ibuprofen. On examination he has a blood pressure of 94/62 mmHg, heart rate of 110 bpm, respiratory rate of 30/min and a temperature of 38.4 degrees. There is no obvious source of infection.
What is the most appropriate next step?
A. Prescribe oramorph and review tomorrow
B. Prescribe daily codeine and ask GP to review in a week
C. Chest x-ray and dipstick urine (give antibiotics if +ve)
D. Admit urgently
E. Full blood count and review tomorrow
D. Admit urgently
Acute chest syndrome
SOB, fever, cough
A 22 year old female presents with lethargy. The following blood results are obtained:
Hb: 10.6 (11.5-16) Platelets: 300 (150-400) WCC: 5.5 (4-11) MCV: 65 (84-100) HbA2: 4.5% (<3%)
What is the most likely diagnosis?
A. Beta-thalassaemia major B. Sickle cell anaemia C. Hereditary spherocytosis D. Beta-thalassaemia trait E. Iron deficiency anaemia
D. Beta-thalassaemia trait
Signs similar to IDA with raised HbA2
State some diseases that can cause a normocytic anaemia
Myelofibrosis Acute blood loss Aplastic anaemia Haemolytic anaemias (acquired/congenital) ACD (may be microcytic)
State some diseases that can cause a macrocytic anaemia
Liver disease Alcohol B12/folate deficiency Hypothyroid Myelodisplasia
Krusty is a 54 year old Clown and fast food franchise owner. He reports 6 kg of weight loss over the last 3 months alongside ‘stomach issues’. On examination, he has angular cheilitis, koilonychia and appears pale.
A blood film shows hypochromic red blood cells with evident anisopoikilocytosis and multiple pencil cells.
What is the diagnosis? Anaemia of Chronic Disease Thalassaemia Major Iron Deficiency Anaemia Chronic Lymphocytic Leukaemia Hyperthyroidism
IDA
a) ACD: does not explain angular cheilitis, koilonychia or the pencil cells
b) Thalassaemia major tends to present in childhood due to its severity: does not explain angular cheilitis, koilonychia or the pencil cells
c) Correct
d) CLL would have abnormal and abundant white cells present on the blood film (as well as some possible anaemic features).
e) Hyperthyroidism is not particularly associated with microcytic anaemia: does not explain angular cheilitis, koilonychia or the pencil cells
give 2 signs of IDA
On examination:
- angular cheilitis
- koilonychia
What are the 4 classic features of IDA on blood film?
- Anisopoikilocytosis (unequal size (poikilo) + shape (aniso))
- Pencil cells- cigar shaped elliptocytes
- Hypochromic cells (reduced Hb)
- Cells may show increased red cell distribution width (reticulocytes + microcytic anaemia due to increased RBC production with the same amount of Hb)
A patient presents with unexplained IDA. what is the key differential that you need to rule out?
COLON CANCER- triad of:
- IDA
- PR bleeding
- change in bowel habit
globally the most common cause of IDA is….?
parasitic infection: Ascariasis & Schistosomiasis.
What would you see on iron study of IDA?
- low serum iron
- low ferritin (stored iron in cells)
- high transferrin (iron transport protein, attempt to increase iron in blood)
- low transferrin saturation
How can iron studies differentiate IDA from ACD?
IDA:
- Ferritin = low
- TIBC(transferrin) = high
ACD:
- Ferritin = high
- TIBC(transferrin) = low
Explain the cause of ACD
Chronic disease causes cytokine release
Cytokines increase levels of hepcidin which:
- blocks GI uptake (ferroportin)
- blocks TIBC (transferrin)
- increases levels of ferritin- lock iron in cells
- blocks EPO production
This prevents the infection exploiting the body and starves it of iron.
Ferritin is an example of what?
an acute phase protein
How can alpha and beta thalassemia traits be distinguished?
Hb electophoresis
- alpha trait: low/normal HbA2
- beta trait: high HbA2 (compensatory mechanism)
Epidemiology of thalassemia?
- Very common in Cyprus
- Increased prevalence in malaria belt- thalassaemia Minor provides resistance to falciparum Malaria
State the 3 possible combinations of Hb molecule and when they present
HbA1 = 2 Alphas + 2 Beta chains HbA2= 2 Alphas + 2 Delta chains HbF = 2 Alphas + 2 Gamma chains
Alpha is often present from birth
Beta typically presents between first 3 & 6 months
Gamma declines after birth to zero at 3-6 months
Delta is always pretty low
Complication of splenic sequestration crisis
- rapid splenomegaly with fall in Hb
- causes severe haemolytic anaemia + shock
- increased risk of infection
Complications of vaso-occlusive crisis
- Dactilyitis
- Priapism
- Acute chest Syndrome- infarcts in lungs (can be a solitary event)
Complications of aplastic crisis
sudden severe anaemia
bone pain –> bone marrow ischaemia and necrosis
Which virus causes aplastic crisis in SCD?
parvovirus B-19
What would you see on blood film of a patient with sickle cell anaemia?
- Sickle cells
- Howell-Jolly bodies- nuclear remnants from RBCs. Normally they are filtered out via the spleen (occur in hyposplenism)
What would you see on Hb electropheresis of a patient with sickle cell anaemia?
HbS, no HbA
beta globin gene mutation, makes abnormal variant