Haem: anaemia Flashcards
limits for anaemia in men and women
Men: <135 g/L (13.5g/dL), Women: < 115g/L (11.5g/dL)
very general causes of anaemia
reduced production of RBCs
increased loss of RBCs (haemolytic anaemias)
increased plasma volume (pregnancy)
symptoms of anaemia
fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia
Signs of anaemia
pallor, in severe anaemia (Hb < 80g/L) → hyperdynamic circulation e.g. tachycardia, flow murmurs (ejection-systolic loudest over apex) → heart failure
causes of anaemia with low MCV
fast
Fe deficiency
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia
causes of normocytic anaemia
acute blood loss
anaemia of chronic disease
bone marrow failure
renal failure
hypothyroidism
haemolysis
pregnancy
causes of macrocytic anaemia
FATRBCM
Fetus (pregnancy)
Antifolates
Thyroid (hypothyroidism)
Reticulocytosis (release of larger immature cells e.g. with haemolysis)
B12 or folate deficiency
Cirrhosis (Alcohol excess or liver disease)
Myelodysplastic syndromes
Signs of iron deficiency anaemia
Koilonychia, atrophic glossitis, angular cheilosis, post-cricoid webs (Plummer-Vinson syndrome), brittle hair and nails
What might you see on the blood film of iron deficiency anaemia?
microcytic
hypochromic
anisocytosis
poikilocytosis
pencil cells
Causes of IDA
Blood loss:
Menorrhagia
Meckel’s diverticulum (older children)
Peptic ulcers / Gastritis (chronic NSAID use)
Polyps/colorectal Ca (most common cause in adults >50yrs)
Hookworm infestation (developing countries)
Increased utilisation:
Pregnancy
Growth of children
Decreased Intake:
Prematurity- loss of Fe each day fetus is not in utero
Suboptimal diet
Decreased absorption:
Coeliac: absence in villous surface in duodenum
absorption
Post-gastric surgery: rapid transit, ↓ acid which helps Fe absorption
Intravascular haemolysis:
Microangiopathic Haemolytic anaemia
PNH
Chronic loss of Hb in urine → Fe deficiency
Investigations of IDA
if no obvious cause then patients should have OGD + colonoscopy, urine dip, coeliac investigations
Treatment of IDA
Treat the cause
Oral iron (SE: nausea, abdominal discomfort, diarrhea/constipation, black stools).
(alternate days almost as quick at improving anaemia and has less toxicity)
IV iron such as Ferrinject / Monofer (anaphylaxis risk)
Indications: poor oral absorption, failure of oral iron trial, or need for rapid rise (e.g. imminent major surgery)
Note: in sepsis and severe infection, iron will not absorb well and can fuel sepsis. Blood transfusions are better in this scenario.
Anaemia of chronic disease causes
Cytokine driven inhibition of red cell production
Causes:
* Chronic infection (e.g. TB, osteomyelitis)
* Vasculitis
* Rheumatoid arthritis
* Malignancy etc
Anaemia of chronic disease pathophysiology
- Inflammatory markers like IFNs, TNF and IL1 reduce EPO receptor production (and thus EPO synthesis) by kidneys
- Iron metabolism is dysregulated. IL6 and LPS stimulate the liver to make hepcidin, which decreases iron absorption from gut (by inhibiting transferrin) and also causes iron accumulation in macrophages
Ferritin levels in anaemia of chronic disease
Ferritin (intracellular protein, iron store) high:
Fe sequestered in macrophage to deprive invading bacteria of Fe (unless the patient has co- existing iron deficiency anaemia)
Why does renal failure cause anaemia of chronic disease?
not cytokine driven but due to Erythropoietin (EPO) deficiency (EPO made by kindey)
Mechanism underlying sideroblastic anaemia
Ineffective erythropoiesis → iron loading (bone marrow) causing haemosiderosis (endocrine, liver and cardiac damage due to iron deposition)
haemosiderin is a storage product of iron from erythrocyte breakdown found in cells
How is sideroblastic anaemia diagnosed?
Ring sideroblasts seen in the marrow (erythroid precursors with iron deposited in mitochondria in a ring around the nucleus)
Causes of sideroblastic anaemia
myelodysplastic disorders, following chemotherapy, irradiation, alcohol excess, lead excess, anti-TB drugs or myeloproliferative disease
Treatment of sideroblastic anaemia
Remove the cause and consider Pyridoxine (vitamin B6 promotes RBC production). Consider giving EPO
Interpretation of Plasma Iron Studies
Investigations for pancytopaenia
check for splenomegaly: myelofibrosis and lymphoproliferatives disorders
- B12/Folate/Iron (note: iron deficiency alone shouldn’t cause pancytopenia)
- Abdo exam for spleen (myelofibrosis)
- Reticulocyte count (if low= BM not responding appropriately = BM failure= aplastic anaemia, BMF syndromes)
- Blood film (abnormal cells i.e. acute leukaemia high WCC but could be low, hairy cell leukaemia, LGL leukaemia, dysplastic changes i.e. myelodysplasia)
- Myeloma screen (infiltrated bone marrow= pancytopenia)
- Parvovirus (immunosuppressed patients + blood PCR test)
- Medications review
Unless there is a clear cause on above tests, patients are likely to require a bone marrow biopsy to diagnose
Macrocytic anaemia causes
Megaloblastic: B12 deficiency, folate deficiency, cytotoxic drugs.
Non-megaloblastic: Alcohol (most common cause of macrocytosis without anaemia), reticulocytosis (e.g. in haemolysis), liver disease, hypothyroidism, and pregnancy
Other haematological disease: Myelodysplasia, myeloma, myeloproliferative disorders, aplastic anaemia
Megaloblastic blood film
Hypersegmented polymorphs, leucopenia, macrocytosis, anaemia, thrombocytopenia with megaloblasts
Megaloblasts are red cell precursors with an immature nucleus and mature cytoplasm. B12 and folate are required for nucleus maturation
sources of B12
meat and dairy
Causes of B12 deficiency
Dietary (e.g. vegans)
Malabsorption:
* Stomach (lack of intrinsic factor produced by gastric parietal cells)→ Pernicious anaemia, post gastrectomy
* Terminal ileum (absorption) due to ileal resection, Crohn’s disease,bacterial overgrowth, tropical sprue and tapeworms
B12 clinical features
- Mouth: Glossitis, angular cheilosis
- Neuropsychiatric: Irritability, depression, psychosis, dementia.
- Neurological: Paraesthesiae, peripheral neuropathy (loss of vibration and proprioception first, absent ankle reflex, spastic paraperesis, subacute combined degeneration of spinal cord)
Pernicious anaemia - what is it
Autoimmune atrophic gastritis → achlorhydria and lack of gastric intrinsic factor
Most common cause of a macrocytic anaemia in Western countries (Usually >40yrs)
Pernicious anaemia test
Parietal cell antibodies (90%), Intrinsic factor antibodies (50%), Schilling test (outdated)
Treatment B12 deficiency
Replenish stores with IM hydroxocobalamin (B12) with 6 injections over 2 weeks.
NICE recommend testing for anti-parietal cell / anti-intrinsic factor antibodies as if there is an autoimmune cause rather than dietary, patients will need 3-monthly IM injections
Folate sources
DIET - green vegetables, nuts, yeast & liver, synthesized by gut bacteria (low body stores, cannot produce de novo)
Causes of folate deficiency
- Poor diet
- Increased demand: pregnancy or ↑ cell turnover (haemolysis, malignancy, inflammatory disease and renal dialysis)
- Malabsorption: coeliac disease, tropical sprue
- Drugs: alcohol, anti-epileptics (phenytoin), methotrexate, trimethoprim
Folate deficiency treatment
Give oral folic acid
Ensure B12 is checked and replaced prior to folic acid otherwise folic acid may exacerbate the neuropathy of B12 deficiency
haemolytic anaemia definition
increased breakdown of red blood cells before their 120 day lifespan
lab results in all haemolytic anaemia
high bilirubin
high urobilinogen
high LDH
reticulocytosis (high MCV and polychromasia)
pigmented gallstones
intravascular haemolytic anaemia lab results
high free plasma Hb
low haptoglobin (binds Hb)
haemoglobinuria
Methaemalbuminaemia (Haem + albumin in blood)
what examination finding may you see in haemolytic anaemia
splenomegaly
what is erythroid hyperplasia and what risks is it associated with
overproduction of erythroid cells in bone marrow in response to anaemia
associated with parvovirus B19 aplastic crisis, iron overload and osteoporosis
how does reticulocyte count change in response to anaemia
increases as bone marrow produces more in response
causes of inherited haemolytic anaemia
membrane defect:
* hereditary spherocytosis
* hereditary elliptocytosis
enzyme defect:
* G6PD deficiency
* pyruvate kinase deficiency
haemoglobinopathies:
* sickle cell diseases
* thalassaemia
causes of acquired haemolytic anaemia
immune:
* autoimmune: warm or cold
* alloimmune: haemolytic transfusion reactions
non-immune:
* mechanical: metal valves or trauma
* PNH, MAHA
* infection: malaria
* drugs
hereditary spherocytosis mode of inheritance
autosomal dominant
25% recessive or de novo
mechanism underlying hereditary spherocytosis
spectrin or ankyrin deficiency- these are membrane proteins
what are individuals with hereditary spherocytosis susceptible to
parvovirus B19 and gallstones
diagnosis of hereditary spherocytosis
extravascular haemolysis: splenomegaly
spherocytes on blood film
high osmotic fragility- lyse in hypotonic solutions
-ve DAT/ Coombs
flow cytometry EMA binding test
management of hereditary spherocytosis
folic acid
maybe splenectomy
hereditary elliptocytosis mode of inheritance
Almost all forms are autosomal dominant – spectrin mutations
Except Hereditary Pyropoikilocytosis (erythrocytes are abnormally sensitive to heat) – autosomal recessive
symptoms and diagnosis of hereditary elliptocytosis
asymptomatic usually
elliptical on blood film
South East Asian Ovalocytosis mode of inheritance
Recessive – heterozygous +/- malaria protection
Glucose-6-phosphate dehydrogenase (G6PD) Deficiency mode of inheritance and epidemiology
Commonest RBC enzyme defect – X linked
Prevalent in areas of malarial endemicity i.e. African, Mediterranean and Middle Eastern populations
Glucose-6-phosphate dehydrogenase (G6PD) Deficiency mode of inheritance and epidemiology
Commonest RBC enzyme defect – X linked
Prevalent in areas of malarial endemicity i.e. African, Mediterranean and Middle Eastern populations
blood film of G6PDD
bite cells and Heinz bodies (blue deposits,
oxidized Hb)
G6PDD S/S
attacks - rapid anaemia and jaundice
intravascular haemolysis: dark urine
what can cause G6PDD
Precipitated by oxidants as G6PD helps RBCs make glutathione which protects them from oxidant damage
- drugs (usually 2-3 days after starting) (e.g. primaquine, sulfonamides, aspirin), broad beans (within 1 day of eating)(favism), acute stressors, moth balls, acute infection
diagnosis of G6PDD
Enzyme assay ~2- 3 months after a crisis: young RBCs may have sufficient enzyme so results may appear normal
treatment of G6PDD
Avoid precipitants; transfuse if severe, genetic screening (rare subtypes give chronic haemolysis for which splenectomy can be needed)
pyruvate kinase deficiency mode of inheritance
Autosomal recessive (but autosomal dominant has been observed with the disorder)
pyruvate kinase S/S
Clinical features: can be severe neonatal jaundice, splenomegaly, haemolytic anaemia
treatment of pyruvate kinase deficiency
most do not require treatment (can incl blood transfusion or splenectomy)
