Haem1 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 the types 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 Aquagenic pruritus 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 the symptoms of anaemia?
Asymptomatic Fatigue Faintness Dyspnoea Angina pectoris Intermittent claudication
What are the signs of anaemia?
Pale skin Pale mucous membranes Tachycardia Koilonychia Cardiac failure
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
Sideroblastic anaemia
What are the causes of IDA?
Blood loss (commonly uterus, GI tract) Increased demand (pregnancy/growth) Decreased absorption (SI disease, post-gastrectomy) Poor intake (vegans)
What are the investigations for IDA?
FBC- low Hb, MCv Iron studies: -low serum iron -low ferritin -high transferrin -low transferrin saturation Blood film: -microcytic, hypochromic RBCs with anisocytosis and poikilocytosis Upper GI endoscopy + colonoscopy Coeliac serology (IgA TTG antibodies)
What is the management for IDA?
Treat underlying cause
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 is the cause of ACD?
Cytokine release Blocks EPO production Blocks Fe flow out of cells Increased intracellular Fe storage Increased RBC turnover
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 chains
2 beta chains
What are the two main types of thalassaemia?
Alpha thalassaemia
Beta thalassaemia
How many genes code the alpha Hb chain?
4 genes, 2 from each parent
What are the types of alpha thalassaemia?
Alpha thalassaemia silent (1 absent gene)
Alpha thalassaemia trait (2 absent genes)
Haemoglobin H (3 absent genes)
Haemoglobin Barts (4 absent genes)
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
Beta thalassaemia major
What are the characteristics of beta thalassaemia minor?
Asymptomatic heterozygous carrier
Mild/absent anaemia
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 at 2-3 months with profound 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?
FBC- low Hb, MCV Iron studies: -normal serum iron -normal ferritin -normal transferrin -normal transferrin saturation Hb electophoresis -alpha trait: low/normal HbA2 -beta trait: high HbA2
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 -microangiopathic haemolytic anaemia --haemolytic uraemic syndrome --thrombocytopenic purpura --disseminated intravascular coagulation
What are the clinical features of haemolytic anaemia?
Same as 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 are the causes of sickling?
Hypoxia
Dehydration
Infection
Cold
What are the consequences of sickling?
Haemolysis
Vaso-occlusion -> tissue ischaemia
What are the symptoms of sickle cell anaemia?
6-8g/dL with reticulocytosis Can be asymptomatic Sequestration crisis: -stroke/TIA -lung: acute chest syndrome -spleen: rapid splenomegaly with fall in Hb -corpus cavernosa: priapism, impotence Vaso-occlusion: -dactlyitis -bone pain of long bones, ribs, spine, pelvis -avascular necrosis of bone marrow Bone marrow aplasia (parvovirus B19) Gallstones from chronic haemolysis
What is acute chest syndrome?
SOB
Cough
Fever
Due to sickle cell sequestration crisis
What are the investigations for sickle cell anaemia?
Diagnosed at birth with heel prick test FBC- low Hb, high reticulocyte Peripheral blood film: -sickle cells -target cells and Howell-Jolly bodies if hyposplenic Hb electrophoresis- HbS, no HbA
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
