10.5 Anaemia Part 1 Flashcards
What can cause anaemia?
- Absolute RBC reduction (e.g. bleeding)
- Relative RBC reduction (pregnancy; increased plasma)
- Decreased Hb quality (e.g. thalassaemia)
What % of blood is made of plasma, RBCs, and buffy coat (platelets + WBCs)?
RBCs: 45%
Plasma: 55%
Buffy coat (WBCs + Platelets): ~1%
What can be found in blood plasma when centrifuged?
- Albumin
- Immunoglobulins
- Fibrinogen
- Complement
- Coagulation factors
What are the anaemia Hb cutoffs for men, women, and pregnant women?
Men: 130g/L
Women: 120g/L
Pregnant women: 110g/L
What factors can influence someone’s normal Hb levels?
- Sex
- Ethnicity
- Altitude
What symptoms might be look for in a patient with suspected haemolytic anaemia?
- Jaundice
- Dark urine
What initial underlying causes might we check in a patient with suspected anaemia?
- Diet
- Blood loss
- Malabsorption
List some investigations in anaemia diagnosis
- Red cell parameters
- Reticulocyte count
- WCC and platelets
- Biochemistry (liver/renal function)
- Haemolysis: bilirubin, LDH, haptoglobin
- Blood smear
What is MCV in haematology?
Mean cell volume
What is MCH in haematology?
Mean cell haemoglobin
What is MCHC in haematology?
Mean corpuscular haemoglobin concentration (amount of Hb per unit volume)
What total proportion of the population is anaemic?
24.8% (!!!!)
What are the two most common demographics for anaemia?
- Preschool-age children
- Pregnant women
Is anaemia more common in men or women?
Women
What is the most common cause of anaemia?
Iron deficiency
What are some possible causes of iron deficiency anaemia?
- Physiological (growth, pregnancy, breast feeding)
- Dietary imbalance
- Malabsorption (coeliac disease)
- Bleeding (menstruation, GI malignancy)
What would you do in a patient who you suspect has iron deficiency anaemia?
- Confirm deficiency (blood film, iron studies)
- Investigate cause (history, exam, endoscopy, coeliac disease screen)
Symptoms of iron deficiency anaemia
- Tiredness
- Lack of concentration
- Giddiness
- Dyspnoea on exertion
- Palpitations, angina
- Pica
Signs of iron deficiency anaemia
- Pallor
- Tachycardia
- Glossitis
- Angular stomatitis
- Koilonychia
What is anisocytosis?
Different sizes
What is poikilocytosis?
Different shaped cells
Why might transferrin be elevated in iron deficiency?
Because the body is trying to transport as much iron as possible, and can’t afford to waste any
What is the relationship between transferrin and ferritin?
Inversely proportional
Does transferrin have low or high saturation in thalassemia?
High; there is not enough haemoglobin, but there is still a fair amount of iron.
List some common causes of iron deficiency that you would ask about in a history
- Menstrual history (menorrhagia?)
- Surgical history; bariatric surgery?
- Abnormal bleeding, such as in GI malignancy (family history, older age, GI symptoms such as malaena or abdominal pain).
How long does it take for a 20g/L rise in haemoglobin after starting iron supplementation?
About 3 weeks
Broadly, describe the pathogenesis of anaemia of chronic disease
Inflammation decreases RBC production and decreases how long they survive, as well as reducing absorption of iron into bloodstream. Therefore, regardless of iron intake, less iron can be transported around the body.
What conditions is anaemia of chronic disease associated with?
- Rheumatological disorders
- Inflammatory bowel disease
- Chronic infections
- Malignancies
Describe a specific pathophysiology of anaemia of chronic inflammation relating to IL-6
- Interleukin 6 increases hepcidin production
- This blocks ferroportin, thus preventing iron from entering the bloodstream
- Leads to inability to transport this iron to the bone marrow or to any other tissue
Hepcidin blocks ferroportin, preventing iron from moving into the bloodstream. At what places in the body can this occur?
- Splenic macrophages (recycling)
- Duodenum (absorption)
- Ferritin (storage)
How can IFN gamma cause anaemia in the context of chronic inflammation?
- Biases haematopoiesis towards myelopoiesis (leukocyte production)
- Inhibiting erythropoiesis
- Activates macrophages to eat erythrocytes
- Shortened RBC lifespand
What is the effect of chronic inflammation on EPO production?
- Decreases
- And the body becomes resistant
Does TNF alpha inhibit or increase erythropoiesis?
Inhibit
How would we treat a patient with anaemia of chronic inflammation?
- Address underlying issue
- Blood transfusion (if bad)
- EPO and IV iron
What is thalassemia?
Reduced or absent synthesis of a globin chain, resulting in an imbalance of alpha and beta chains
What are structural haemoglobin variants?
Mutations in the Hb gene resulting in changes in the normal amino acid sequence in the globin chain resulting in abnormal structure
Which chromosome does alpha thalassemia usually relate to in terms of mutations?
16
How many mutated Hb alpha genes can you have with no symptoms.
0, 1, or 2
Whaat is it called when someone has one alpha Hb mutation?
Alpha thalassemia trait
True or false: a person who inherits two defective alpha Hb genes will probably be asymptomatic
True
What is it called when a person carries three defective alpha hb genes?
Hb H disease
What types of anaemia are caused by Hb H disease?
Microcytic (small cells because not enough Hb) and haemolytic (defective, insoluble haemotetramers are borken down in spleen)
Is Hb H disease transfusion dependent, non transfusion dependent, or both?
Both
What happens if a person inherits four defective alpha Hb genes?
- Incompatible with life
- Foetus dies in utero
Alpha + vs alpha 0 thalassemia. Is this the same as for beta thalassemia?
Alpha +: decreased production
Alpha 0: no production
Yes. This is the same as beta thalassemia.
Which chromosome does the beta thalassaemia trait lie on?
11
List some consequences of iron overload in beta thalassaemia
- Liver toxicity
- Cariomyopathy
- Endocrine: hypogonadism, hypothyroidism, insulin resistance
How could beta thalassaemia cause growth deficiency?
- Excessive iron due to increased dietary absorption and transfusion
- Iron deposits in pituitary
- Downregulates growth hormone release
Describe treatment of thalassaemia
- Regular blood transfusion: aims to reduce extramedullary haematopoiesis, reduce ineffective haematopoiesis, and promote normal growth/development
- Iron chelation (remove iron)
- Multidisciplinary support
What is the only known cure of thalassaemia
Stem cell transplant from unaffected sibling
List the three most common structual Hb variants
- Sickle cell anaemia (HbS)
- HbE
- HbC
Describe genetic transmission of beta thalassaemia
Autosomal recessive
Describe genetic transmission of sickle cell disease
Autosomal recessive
HbS trait vs Sickel cell disease
trait: carrier of HbS gene
disease: both affected genes
In what areas is sickle cell anaemia common?
- Africa
- India
- Middle east
- Mediterranean
Why are sickle cells worse than regular RBCs?
When deoxygenated, they precipitate out of blood, and cannot squeeze through gaps as well
List some clinical manifestations of sickle cell disease
- Vaso-occlusive complications: stroke, ACS, dactylitis (blood trapped in fingers/toes)
- Chronic haemolysis
- Anemia
- Infections
- Renal impairment
