Haem - Anaemia and Haemolytic anaemia Flashcards
What investigations should be done in a pancytopenia
Examination for splenomegaly (myelofibrosis and lymphoproliferative disorders)
Bloods:
- B12/folate/iron
- Reticulocyte count (low implies aplastic anaemia/BM failure)
- Blood film: ?blasts, ?hairy cell leukaemia, ?LGL leukaemia, ?dysplasia (myelodysplasia)
- Myeloma screen
- Parvovirus PCR
Bone marrow biopsy for diagnosis
What are the causes of anaemia according to impaired synthesis vs destruction
Synthesis
Inefficient: marrow infiltration, iron deficiency, EPO deficiency, myelofibrosis
Ineffective: SCD, thalassaemia, B12/folate def, sideroblastic anaemia
Destruction
Congenital: SCD/thalassaemia, G6PD-D, PKD, spherocytosis/elliptocytosis
Acquired: Immune (CLL, SLE, mycoplasma, EBV) or non-immune (malaria, trauma, MAHA)
What are the causes of microcytic anaemia
Iron deficiency
Thalassaemia
Anaemia of chronic disease
Lead poisoning
Sideroblastic anaemia
What would the iron studies show for iron deficiency, thalassaemia and anaemia of chronic disease
Iron deficiency: Low iron, ferritin, transferrin saturation | high TIBC
Thalassaemia: low iron | normal ferritin, TIBC and transferrin saturation
Chronic disease: low iron and TIBC| normal ferritin (Or raised if inflammation), normal transferrin saturation | raised ferritin
What is a hallmark feature of lead poisoning on blood film
Basophilic stippling
What are the features of sideroblastic anaemia on blood film
Sideroblastic cells
Hypochromic, dimorphic RBCs
What are the causes of macrocytic anaemia
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.
What are the features of megaloblastic anaemia on blood film
Hypersegmented polymorphs
Leucopenia
Macrocytosis
Anaemia
thrombocytopenia
Megaloblasts (RBC precursors with immature nucleus but mature cytoplasm)
What are the causes of vitamin B12 deficiency
Dietary (e.g. vegans) - B12 found in meat and dairy
Malabsorption:
- Stomach (lack of intrinsic factor which is 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.
What are the clinical features of B12 deficiency
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)
What is pernicious anaemia and what investigations should be done for diagnosis
Autoimmune atrophic gastritis → achlorhydria and lack of gastric intrinsic factor
Most common cause of a macrocytic anaemia in Western countries (Usually >40yrs)
Specific tests: Parietal cell antibodies (90%), Intrinsic factor antibodies (50%), Schilling qtest (outdated)
What are the 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
What is the management for B12 and folate deficiencies
B12: Replenish stores with IM hydroxocobalamin (B12) with 6 injections over 2 weeks. (if pernicious anaemia → 3-monthly IM injection)
Folate: oral folic acid (B12 is checked and replaced prior to folic acid otherwise folic acid may exacerbate the neuropathy of B12 deficiency)
What are the features of intravascular haemolytic anaemia on blood results
Raised free plasma Hb
Reticulocytosis (unless aplastic)
Raised unconjugated bilirubin and urobilinogen
Raised LDH
Low haptoglobins
May have pigmented gallstones
Haemoglobinuria (dark red urine)
Methaemalbuminaemia (Haem + albumin in blood)
What are the features of extravascular haemolytic anaemia on blood results
Anaemia
Reticulocytosis (unless aplastic)
Raised unconjugated bilirubin and urobilinogen
Raised LDH
May have pigmented gallstones
Splenomegaly
What are the causes of intravascular haemolytic anaemia
Malaria
G6PD and PK deficiencies
Mismatched ABO blood transfusion
Cold anti-body haemolytic syndromes
Drugs
Microangiopathic HA’s (i.e. TTP)
Paroxysmal nocturnal haemoglobinuria
What are the causes of extravascular haemolysis
Autoimmune
Alloimmune
Hereditary spherocytosis [AD inheritance]
What are the causes of acquired haemolytic anaemia
Immune:
- Warm: CLL, SLE
- Cold: mycoplasma, EBV
Non-immune:
- Mechanical: metal valves, trauma
- PNH, MAHA
- Infections e.g. malaria
- Drugs
What are the causes of inherited haemolytic anaemia
Membrane defect: hereditary spherocytosis/eliptocytosis
Enzyme defect: G6PD deficiency, pyruvate kinase deficiency
Haemoglobinopathies: SCD, thalassaemia
What are the features of hereditary spherocytosis (inheritance, pathology, presentation)
Autosomal dominant (25% recessive or de novo)
Norther Europe more common
Spectrin or ankyrin deficiency
S/S: susceptibility to parvovirus B19, gallstone development, splenomegaly (extravascular haemolysis)
What investigations should be done to diagnose hereditary spherocytosis
Blood film: Spherocytes seen
Osmotic fragility test: raised (lysis in hypotonic solution)
Di-binding test
Flow cytometry (EMA binding test)
Cryohaemolysis test
DAT coombs NEGATIVE
What is the management for hereditary spherocytosis
Folic acid
± splenectomy
What is paroxysmal nocturnal haemoglobinuria
Acquired loss of protective surface GPI markers on RBCs → complement-mediated lysis → chronic intravascular haemolysis
Nocturnal haemolysis
Morning haemoglobinuria and Thrombosis (± Budd-Chiari syndrome)
Bone marrow failure
What are the investigations and management for paroxysmal nocturnal haemoglobunuria
Ham’s test / Flow cytometry of GPI-linked proteins
Iron/folate supplements
Prophylactic vaccines/antibiotics
Eculizumab
What are the consequences of haemolysis
Anaemia
Erythroid hyperplasia
Increased folate demand
Susceptibility to parvovirus B19. gallstones, iron overload, osteoporosis, and hepatic siderosis
What is the difference between hereditary spherocytosis and hereditary elliptocytosis
Spherocytosis: vertical interaction, spectrin/ankyrin deficiency
Elliptocytosis: horizontal interaction, spectrin mutation
What is haemolysis in G6PDD triggered by
Anti-malarials e.g. primaquine
Sulphonamides, ciprofloxacin, nitrofurantoin
Vitamin K
Fava beans
Henna
Naphthalene (moth balls)
Infections
What is G6PDD
deficiency in G6PD which catalyses the first step in the pentose phosphate pathway to generate NADPH
Common in Mediterranean populations
X-linked
Untreated → neonatal jaundice → kernicterus
What are the features of G6PDD on investigation
Film: bite cells, nucleated RBCs, Heinz bodies. (methyl violet stain)
What is the testing and management for G6PDD
Testing:
- Fluorescent spot test (G6PD and NADP)
- Methaemoglobin (Methylene blue)
- Guthrie spot
- G6PD activity
management: folate supplements, phototherapy in neonates
Avoid precipitants
Transfuse if severe
Genetic screening
What are the features of pyruvate kinase deficiency on blood film
Echinocytes (“hedgehog-like”)
Spherocytes
What are the features of warm autoimmune haemolytic anaemias and what are the causes
37oc
IgG
Positive coombs test
Spherocytes seen on blood film
Causes: idiopathic, lymphoma, CLL, SLE, methyldopa
What are the features and causes of cold agglutinin disease (autoimmune haemolytic anaemia)
<37oC
IgM
Positive Coombs test
Often with Raynaud’s
Causes: idiopathic, lymphoma, infections (EBV, mycoplasma)
What is the management for warm AIHA
Steroids
Splenectomy
immunosuppression
What is the management for cold AIHA
Treat underlying condition
Avoid cold
Lymphoma → chemotherapy
What are Donath-Landsteiner antibodies
Stick to RBCs in cold → complement-mediated
haemolysis on rewarming (self-limiting as IgG so dissociate at higher temp than IgM)
What are the causes of MAHA
HUS
TTP
DIC
Pre-eclampsia
What is TTP
Antibodies against ADAMTS13 → long strands of vWF which shear RBCs (haem emergency)
Pentad:
1. MAHA
2. Fever
3. Renal impairment
4. Neuro abnormalities
4. Thrombocytopenia
