Haem - Anaemia Flashcards
Microcytic anaemia causes?
MCV in fL?
Iron deficiency anaemia
Thalassaemia
Anaemia of chronic disease (can also be normocytic)
MCV <80fL
Normocytic anaemia causes?
MCV in fL?
Anaemia of chronic disease
Bone marrow failure
-aplastic anaemia
MCV 80-100fL
Macrocytic anaemia causes?
MCV if fL?
Megaloblastic - folate/B12 deificency Non megaloblastic - Alcohol - Haemolysis (raised reiticulocytes)
MCV >100fL
Causes of Iron Deficiency Anaemia?
Loss of blood - eg. GI
Incresaed demand/use of Fe - eg. pregnancy
Decreased intake of Fe - dietary (vegetarian)
Decreased absorption of Fe - eg. Coeliac
Clinical features of Iron def anaemia?
Signs of anaemia: pallor, lethargy, SOB
Atrophic glossitis, angular stomatitis
Koilonychia (spoon-shaped nails)
Conjunctival pallor
Iron def anaemia investigations?
Bloods: FBC = low iron, low ferritin
Blood film:
microcytic,
hypochromic (central pallor of >1/3 cell size), anisocytosis (size variation),
poikilocytosis (shape variation)
SBA key words: Iron deficiency anaemia ?
Low ferritin
SBA tip: Unexplained anemia investigation?
Colonoscopy = ?colorectal cancer causing blood loss?
Anaemia of chronic disease definition?
Anaemia seen in chronic conditions. Effects of inflammatory cytokines.
Causes of anaemia of chronic disease?
Infection, inflammation, malignancy:
Chronic inflammatory/autoimmune disease - Rheumatoid arthritis
Chronic infections - TB
Malignancy
Clinical features of anaemia of chronic disease?
Signs of anaemia: pallor, lethargy, SOB
Signs of underlying diesase
Anaemia of chronic disease investigations?
Bloods: FBC - low iron, NORMAL/HIGH ferritin!
Blood film: normocytic or microcytic
Why is ferritin normal or high in anaemia of chronic disease?
Ferritin is an acute phase protein.
In chronic disease it will be elevated and can mask low iron.
SBA key words: Anaemia of chronic disease?
Normal/ high ferritin
What kind of anaemia is aplastic anaemia?
Normocytic
Aplastic anaemia definition?
Anaemia caused by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (pancytopaenia)
Causes of aplastic anaemia?
Idiopathic: - autoimmune mechanisms -> destruction Acquired: - Drugs - anti-epileptics - Viral infection - Parvovirus B19
Clinical features of aplastic anaemia?
Anaemia: Pallor, Lethargy, SOB
Thrombocytopenia: Bruising, Petechiae (bleeds)
Leukopenia: increased infections
Aplastic anaemia investigations?
Bloods:
- low Hb, normal MCV
- low WCC, low Platelets
- low reticulocytes
Blood film
- exclude leukaemia
Bone marrow trephine biopsy -> hypocellular marrow
SBA key words: Aplastic anaemia?
Low Hb
Low WCC
Low platelets
B12 deficiency anaemia causes?
Decreased intake - diet (vegetarians)
Decreased absorption - Crohn’s (ileal resection), Pernicious anaemia (autoantibodies against Intrinsic Factor/Parietal Cells)
Clinical features of B12 deficiency?
Peripheral neuropathy
Ataxia
Glossitis
B12 deficiency anaemia investigations?
Bloods: - low Hb, high MCV, low serum B12 Blood film: - Macrocytes (large RBCs) - Megaloblastic anaemia - hypersegmented neutrophil nuclei (>5 lobes)
SBA key words: B12 deficiency?
Peripheral neuropathy
Hypersegmented neutrophils
Folate deficiency anaemia causes?
Decreased intake - alcoholics!
Increased demand - pregnancy, high cell turnover (malignancy, haemolysis)
Decreased absorption (jejunum): coeliac
Drugs: methotrexate
Clinical features of folate deficiency?
Anaemia signs: pallor, lethargy, SOB
Signs of underlying disease
Folate deficiency investigations?
Bloods: - low Hb, high MCV, low serum folate Blood film: - macrocytes (large RBCs) - megaloblastic anaemia -> Hypersegmented nuclei (>5 lobes)!
SBA key words: folate deficiency?
Alcoholics
Hypersegmented neutrophils
Haemolytic anemia definition?
Premature breakdown of RBCs which leads to shorter than 120 days life-span and anaemia
Causes of haemolytic anaemia
Hereditary and Acquired
Hereditary:
- Membrane defects: Hereditary Spherocytosis
- Enzyme deficiencies: G6PD Deficiency (glucose 6 phosphate dehydrogenase)
- Haemoglobinopathies: Sickle Cell Disease, Thalassaemeia
Acquired:
- Autoimmune
- Drugs - penicillin, quinine
- Infection - malaria, sepsis
- Microangiopathic Haemolytic Anaemia MAHA - HUS, TTP, DIC
Definition + investigations of Hereditary Spherocytosis?
Oval-shaped RBCs
Inv:
- Blood film - spherocytes
- Osmotic fragility test
SBA key words: hereditary spherocytosis?
Spherocytes
lol
Triggers of G6PD deficiency?
Fava beans
Moth balls
Infections
Drugs - antimalarials
G6PD deficiency investigations?
Blood film = Heinz bodies
SBA key words: G6PD deficiency?
Fava beans
Heinz bodies
Anti-malarials
Autoimmune Haemolytic Anaemia cause?
Warm/cold antibodies attach to RBCs causing their haemolysis.
Warm Antibodies IgG - agglutinate RBCs at 37C. Associated with SLE and Lymphomas
Cold Abs IgM agglutinate ar room temp or colder. Associated with infections (EBV), Lymphomas
Autoimmune Haemolytic anaemia investigations?
Coomb’s test/ Direct Antigglobulin Test (DAT)
= detects antibodies
SBA key words: Autoimmune Haemolytic Anaemia?
Coomb’s test/ Direct Antigglobulin Test (DAT)
Warm/cold antibodies
Why do Microangiopathic Haemolytic Anaemias (MAHAs) cause haemolysis and anaemia (patophysiology)?
RBCs pass through fibrin strands deposited in small vessels -> Shearing (damage) of RBCs -> intravascular haemolysis + RBC fragmentation
MAHA investigations?
Blood film: schistocytes, reticulocytes
SBA key words: MAHA?
Schistocytes (fragmented RBCs)
Features of haemolytic anaemia?
Anaemia: pallor, lethargy, SOB
Jaundice
Hepatosplenomegaly
Haemolytic anaemia investigations?
Bloods:
- low Hb, high unconjugated bilirubin
- high LDL (intracellular enzyme), high reticulocytes
Urine:
- high urobillinogen (also haemoglobinuria)
Blood film:
- reticulocytes, schistocytes
- macrocytosis
- specific abnormal cells - spherocytes, Sickle cells
SBA key words: Haemolytic anaemia?
Schistocytes
High urobilinogen
*Extra Q: What is urobillinogen?
Urobilinogen is a colourless by-product of bilirubin reduction. It is formed in the intestines by bacterial action on bilirubin. About half of the urobilinogen formed is reabsorbed and taken up via the portal vein to the liver, enters circulation and is excreted by the kidney.
**Excess info from wikipedia below (not necessary to know, but it’s a good summary of jaundice):
Increased amounts of bilirubin are formed in hemolysis, which generates increased urobilinogen in the gut. In liver disease (such as hepatitis), the intrahepatic urobilinogen cycle is inhibited also increasing urobilinogen levels. Urobilinogen is converted to the yellow pigmented urobilin apparent in urine.
The urobilinogen in the intestine is directly reduced to brown stercobilin, which gives the feces their characteristic color. It can also be reduced to stercobilinogen, which can then be further oxidized to stercobilin. This constitutes the normal “enterohepatic urobilinogen cycle”.
In biliary obstruction, below-normal amounts of conjugated bilirubin reach the intestine for conversion to urobilinogen. With limited urobilinogen available for reabsorption and excretion, the amount of urobilin found in the urine is low. High amounts of the soluble conjugated bilirubin enter the circulation where they are excreted via the kidneys. These mechanisms are responsible for the dark urine and pale stools observed in biliary obstruction.
Low urine urobilinogen may result from complete obstructive jaundice or treatment with broad-spectrum antibiotics, which destroy the intestinal bacterial flora. (Obstruction of bilirubin passage into the gut or failure of urobilinogen production in the gut.)
Low urine urobilinogen levels may result from congenital enzymatic jaundice (hyperbilirubinemia syndromes) or from treatment with drugs that acidify urine, such as ammonium chloride or ascorbic acid.
Elevated levels may indicate hemolytic anaemia (excessive breakdown of red blood cells RBC), overburdening of the liver, increased urobilinogen production, re-absorption – a large hematoma, restricted liver function, hepatic infection, poisoning or liver cirrhosis.
Types of Microangiopathic Haemolytic Anaemias?
HUS, TTP, DIC
Haemolytic Uraemic Syndrome, Thrombotic Thrombocytopenic Purpura, Disseminated Intravascular Coagulation
HUS: sign Triad?
Microangiopathic Haemolytic Anaemia,
Acute Renal Failure and
Thrombocytopenia
Causes of HUS?
Infection - E.Coli!!!
Drugs - OCP
Malignancy
Clinical features of HUS?
Anaemia - pallor
Jaundice; from haemolysis
Bruising; from thrombocytopaenia
Renal - oedema, HTN, oliguria
Investigations for HUS?
Bloods:
- anaemia; high neutrophils, low platelets
- clotting: normal PT/APTT/fibrinogen
- HIGH unconjugated billirubin, HIGH LDL from haemolysis
Blood film:
- SCHISTOCYTES (fragmented rbc)
- high RETICULOCYTES
Renal biopsy
SBA key words: Haemolytic Uraemic Syndrome?
TRIAD: MAHA, Renal failure, low platelets!
Thrombotic Thrombocytopenic Purpura: sign Pentad?
MAHA Acute renal failure Thrombocytopaenia Fever Fluctuating CNS signs!
Causes of TTP?
Idiopathic
Clinical features of TTP?
Pallor, jaundice, bruising
Renal - oedema, HTN, oliguria
CNS - Weakness, decreased vision, fits, decreased consciousness!!!
TTP investigations?
Same as HUS!
Bloods:
- anaemia, high neutrophils, low platelets
- clotting: normal PT/APTT/fibrinogen
- HIGH unconjugated billirubin, HIGH LDL from haemolysis
Blood film:
- SCHISTOCYTES
- high RETICULOCYTES
Renal biopsy
SBA key words: Thrombotic Thrombocytopenic Purpura?
PENTAD: MAHA, Acute renal failure, low platelets, fever, fluctuating CNS
Thalassaemia definition?
Group of genetic disorders characterised by reduced globin chain synthesis
Thalassaemia aetiology?
Autosomal recessive genetic defects:
- Alpha-thalassaemia - low alpha-globin chain synthesis
- Beta-thalassaemia - defect in B-globin gene on Chr 11 -> reduced/none B-chain synthesis
- B-Thalass. major - no B-chain synthesis
Phenotypic Beta-Thalassaemia classification?
Silent carrier
Beta-thalassaemia minor (aka B-thal. trait)
Beta-thalassaemia intermedia
Beta-thalassaemia major
Clinical features of Alpha-thalassaemia / Beta-thalassaemia trait (minor)?
Mild microcytic anaemia
asymptomatic
B-thalassaemia major clinical features?
Presents at 3-6 months (γ-chain synthesis switches to β-chain synthesis).
Anaemia; Failure to thrive; Infections
Thalassaemia investigations?
Bloods:
↓Hb; ↓MCV; Normal Ferritin
Blood Film:
- Microcytic, Hypochromic Anaemia
- Target Cells
- ↑ Reticulocyte Count
Hb Electrophoresis:
↓HbA ↑HbF
SBA key words: Thalassaemia?
Target cell
Definition of sickle cell disease?
Chronic condition with sickling of RBCs caused by inheritance of HbS
Sickle cell disease causes/ risk factors?
Autosomal recessive inherited mutation in β-globin gene.
- Sickle Cell Anaemia = Homozygosity HbS
- Sickle Cell Trait = Carrier of one copy of HbS
Factors precipitating sickling:
- Infection; Dehydration; Hypoxia
Features of sickle cell disease?
Splenic infarction
Abdo pain
Bones - dactylitis (painful crises affecting small bones of the hand)
Lungs - SOB (“Acute Chest Syndrome” - presents like pneumonia)
Sickle Cell Disease investigations?
Bloods: ↓Hb;
- Reticulocytes - ↑in haemolytic crises, ↓in Aplastic crises
Blood film:
- Sickle Cells
- Features of Hyposplenism: Target Cells; Howell-Jolly bodies
Hb Electrophoresis
SBA key words: Sickle cell disease?
Sickle cells (duh) Crises
How would you manage an acute painful crises fo SCD?
Oxygen
IV fluids
Analgesia - IV opiates
Antibiotics
Management of chronic SCD?
Infection prophylaxis- penicillin V
Hydroxyurea - reduces crises freq. and recurrence
Red cell transfusion
Avoid precipitating factors (infection, dehydration, hypoxia)
What are the complications of Sickle cell disease?
Aplastic crises (parvovirus B19 infection)
Haemolytic crises
Gallstones; cholecystitis
What is the prognosis of SCD?
If well managed, survive to ~50 years
A 64 year old lady complains of pain in her hands. She has gross deformities of her fingers and has nodules on her elbows which she has been told are to do with the pain. Bloods: Hb 71 (115-180g/L) MCV 93 (80-100fL) WCC 5.1 (4-11 x10^9/L)
The most likely cause is:
Alcohol Anaemia of Chronic Disease Iron Deficiency Anaemia Vitamin B12 Deficiency Thalassaemia
Anaemia of Chronic Disease
Gross deformities of fingers and nodules on elbows indicate Rheumatoid arthritis. Bloods show normocytic anaemia.
A 22 year old female presents to her GP complaining of tiredness at work. Upon further questioning, she reveals she has a longstanding history of heavy periods. On examination she has pale conjunctivae. The most likely cause is:
Alcohol Anaemia of Chronic Disease Iron Deficiency Anaemia Vitamin B12 Deficiency Thalassaemia
Iron Deficiency Anaemia
tiredness, heavy periods, pale conjunctivae - the bleeding depleted her iron stores.
A 40 year old woman suffers from Crohn’s Disease. She has recently been complaining that she feels weak and notices tingling in her fingers. A blood test is performed: Hb 105 (115-180g/L) MCV 120 (80-100fL) WCC 300 (150-400 x10^9/L) The most likely explanation is:
Alcohol Anaemia of Chronic Disease Iron Deficiency Anaemia Vitamin B12 Deficiency Thalassaemia
Vitamin B12 Deficiency
Crohn’s - reduced absorption of B12.
Tingling - Peripheral neuropathy
Bloods - Macrocytic anaemia
A 35 year old man travels to South Africa. On arriving, he begins his course of antimalarial tablets. A few days later, he becomes ill with shortness of breath, pallor and bloody urine. Blood tests show he is anaemic and a blood smear shows presence of Heinz Bodies. The most likely cause is:
Disseminated intravascular coagulation Glucose-6-phosphate dehydrogenase deficiency Haemolytic Uraemic Syndrome Hereditary spherocytosis Hereditary elliptocytosis
Glucose-6-phosphate dehydrogenase deficiency
Antimalarias - drugs triggering G6PD
Heinz bodies
anaemia
