Anaemia Flashcards
Haemolytic anaemia
a) define
b) lab results
c) Coombs’ test - direct vs indirect
d) causes of haemolytic anaemia
e) Extravascular (splenic, hepatic) vs intravascular
a) Destruction of RBCs before 120 days
b) - Low Hb, high reticulocytes, raised unconjugated bilirubin, raised LDH
- If intravascular*: low haptogloblins, with haemoglobin and haemosiderin in the urine
*Extravascular occurs in liver, spleen and thymus mainly
c) Direct antiglobulin test (DAT):
- Takes sample of blood to test for antibodies to the patient’s own RBCs
- Positive in autoimmune haemolysis (e.g. warm or cold autoimmune HA),
Indirect antiglobulin test:
- Takes sample of serum (non-blood) to test for antibodies in the serum that would react with another blood sample if mixed
- 2 uses: testing for Rhesus antibodies in pregnant women, and testing for ABO incompatibility PRIOR to transfusions (cross-matching)
d) - Alloimmune - ABO incompatibility, Rh disease
- Autoimmune - warm IgG (autoimmune disease like RA, cancer esp. lymphoma, infections, idiopathic) and cold IgM (Mycoplasma, Mononucleosis)
- Haemoglobinopathy - SCD, thalassaemia
- Membranopathy - spherocytosis, paroxysmal nocturnal haemoglobinuria
- Microangiopathic - TTP, DIC, HUS, HELLP syndrome, drug-induced, leaky prosthetic heart valves, scleroderma renal crisis
- Systemic - hypersplenism, liver disease, malignant HTN
- Traumatic - burns, endovascular devices, aortic stenosis
e) Intravascular - urinary haemosiderin (Fe), low haptoglobin, positive Schumm test
https://www.aafp.org/afp/2018/0915/p354.html
Haptoglobins
a) What are they?
b) If haptoglobins are significantly decreased (and Hb low/ reticulocytes increased) this indicates what?
c) If haptoglobins are normal/only slightly decreased, but Hb low and reticulocytes are increased, this indicates what?
a) Produced by the liver, binds free Hb
b) Intravascular haemolysis
c) Extravascular haemolysis (e.g. in spleen)
Cold agglutinin disease
a) Causes
b) Pathophysiology
c) Test to confirm
d) Other ‘cold antibody’ diseases
e) Management
a) Primary
Secondary - mycoplasma, glandular fever… also lymphoma, myeloma, HIV, malaria
b) Cold agglutinins are auto-antibodies that cause haemolysis when exposed to cold temperatures
- may cause acrocyanosis/ Raynaud’s
c) Direct Coombs’/ Direct antiglobulin test (DAT)
- Forms cold agglutinins due to IgM in ‘cold’ autoimmune haemolytic anaemia
- (Positive for IgG in ‘warm’ autoimmune haemolytic anaemia)
- If lymphoma suspected, test for antigen i
d) Cryoglobulinaemia
- Immune complexes that precipitate at Temp <37C
- Type 1 causes Raynaud’s/acrocyanosis
- Type 2 and 3 (associated with Hep C) cause vasculitic picture
Paroxysmal cold haemoglobinuria
- Donath-Landsteiner antibodies
- Haemoglobinuria/flank pain when exposed to the cold
e) Avoid cold exposure
Folic acid supplements
May require immunosuppression
Low Hb + high reticulocytes
a) + jaundice
b) no jaundice
a) Haemolysis
b) Bleeding
Methaemoglobinaemia
a) What is it?
b) When should it be suspected?
c) Causes
d) Diagnosis
e) Treatment
a) Oxidising substances convert the HbFe2+ molecule into HbFe3+ which cannot bind to oxygen. This leads to low O2 saturations in spite of high oxygen pressures, and poor oxygen delivery to the tissues
b) Suspect in refractory hypoxemia
- Especially where there is cyanosis in patients with sats in the 80s (usually cyanosis only presents with sats <80%)
c) - Congenital
- Drugs - dapsone, sulfonamides, chloroquine, benzocaine, rasburicase
d) - MethHb concentration on ABG: if >30% or >20% with symptoms diagnostic
- Brownish discolouration of blood when applied to white gauze (normal deoxygenated blood will turn red on gauze when oxygenated)
- High disparity between PaO2 (very high) and SpO2 (low)
e) Methylene blue
(contraindicated in G6PD deficiency)
B12 deficiency
a) in vegans - how long does it take to present?
b) also causes deficiency of…?
c) Why can it cause raised bilirubin
d) Causes
e) Neurological complications
a) Several years, as B12 stores in the body are plentiful. Hence does not really occur acutely
b) Folate
RBC, WCC and PLT count
c) B12 needed for erythrocyte maturation. In its absence, erythrocytes cannot mature and undergo haemolysis
d) - Nutritional - vegans
- Gastric - lack of intrinsic factor or lack of gastric acid
- Ileal - lack of absorption
- Pancreatic - lack of enzyme breakdown
- PPI/H2RA use (reduced gastric acid)
e) Subacute combined degeneration of the cord:
- Dorsal columns - paraesthesia, numbness, loss of proprioception and vibration sense
- Lateral CST - spastic weakness (but often absent ankle jerks)
- Spinocerebellar tracts - gait ataxia
Others:
- Peripheral neuropathy
- Optic atrophy
- Dementia
Transfusion reactions
a) Acute haemolytic reaction
b) Delayed haemolytic reaction
c) Other types
a) Acute haemolytic reaction (ABO or Rh incompatibility)
- low BP, high HR, back pain
- Anaemia, high LDH, bilirubin
- Positive direct Coombs (DAT) test
- May have haemoglobinuria
b) Delayed haemolytic reaction:
- Occurs >24 hours after transfusion (but often presents around 2 weeks later)
- Caused by boosting of a previously generated alloantibody
- Results in haemolytic anaemia with
- Positive direct antiglobulin test
- Positive blood transfusion antibody screen
- Spherocytosis is seen on blood film
- May cause unexplained fever
c) Febrile response to donor WBCs
- acute (20 mins), fever, rigors.
- Generally resolved by slowing transfusion and giving paracetamol
Infected sample
- rapid onset of sepsis, more common in PLT transfusion (stored at higher temperatures, likely s. aureus)
Anaphylaxis
- anaphylactic IgE reaction to donor proteins (previously sensitised)
- more common in IgA deficiency
TRALI
- Acute <6 hours - cough, SOB, hypoxia, frothy sputum
- perihilar nodules and lower zone infiltration on CXR - pulmonary oedema
- Due to donor antibodies against recipient
TACO
- Fluid overload post-transfusion
- Distinguished from TRALI by presence of peripheral oedema, raised JVP, hypertension, risk factors for CCF
Hyperkalaemia
Spherocytosis
a) The only anaemia causing what finding?
b) Other diagnostic finding
c) Presentation
d) Complications
e) Management
f) Epidemiology
g) Proteins affected and inheritance
a) Raised MCHC and increase red cell distribution width
(but with normal or low MCV)
b) Osmotic fragility
- not often done due to unreliability
- blood film usually diagnostic now
c) Haemolytic anaemia, jaundice, gallstones, splenomegaly
d) - May be asymptomatic
- Haemolytic crises
- Aplastic crises (triggered by infection e.g. parvovirus B19)
- Megaloblastic crises (due to folate deficiency)
- Gallstones
e) Folate supplementation
- Splenomegaly if severely affected (consider cholecystectomy at same time if symptomatic gallstones)
- Transfusions as needed
- Steroids for acute flares may reduce need for transfusions
f) Caucasian (most common inherited cause of anaemia in Europeans), Japanese
g) Most common (60%) are autosomal dominant, with mutation in spectrin and ankyrin proteins
Thalassaemia
a) THAL mnemonic
b) How does electrophoresis differentiate alpha vs beta-thalassaemia?
c) Which thalassaemia is hydrops fetalis associated with?
d) Give the different types of alpha and beta thalassaemia
e) Epidemiology of thalassaemia
a) Target cells
Haemoglobin A2 raised
Low MCV (often very low for mild degree of anaemia)
b) Alpha thalassaemia has normal electrophoresis
c) Alpha-thalassaemia
d) Alpha thalassaemia classified according to presence of HBA1 and HBA2 genes (4 alleles in total):
1. Alpha thalassaemia silent carrier. One allele is missing or damaged, individuals typically have no thalassaemia-related signs or symptoms.
2. Alpha thalassaemia carrier. Two alleles are missing, tend to cause few or no health problems.
3. Haemoglobin H disease. Three alleles are missing
4. Alpha thalassaemia major. All four alleles are missing
Note: hydrops fetalis is associated with homozygous alpha thalassaemia (both parents with trait or disease)
Beta-thalassaemia classified according to symptoms:
1. Beta thalassaemia minor (also called beta thalassaemia trait). People with beta thalassaemia minor may have mild anaemia, but usually don’t need any medical treatment.
2. Beta thalassaemia intermedia. People with beta thalassaemia intermedia have moderately severe anaemia and some will need regular blood transfusions and other medical treatment.
3. Beta thalassaemia major (also called Cooley’s anaemia). People with beta thalassaemia major have severe symptoms and life-threatening anaemia. They need regular blood transfusions and other medical treatment.
e) Common in South and SE Asia and Mediterranean areas. Also, South America and Africa
Splenectomy planned
- When is the best time to give pneumococcus vaccine?
a) At least 2 weeks pre-operatively
Causes of a raised MCV
a) Haematological vs non-haematological
a) Haematological:
- Aplastic anaemia
- Reticulocytosis (as reticulocytes are large than mature RBCs. So high MCV can be present in haemolytic anaemias)
- Myelodysplastic syndrome
- Myeloid leukaemia
- Red cell aplasia
Non-haematological:
- B12 or folate deficiency (megaloblastic)
- Alcoholism - direct toxic effect on bone marrow, liver disease and low folate
- Liver Dx
- Hypothyroidism
- Drugs - azathioprine, MTX
Causes of low MCV
- Iron deficiency
- Anaemia of chronic disease
- Thalassemia
- Sideroblastic anemia*
*Inability to incorporate iron into the cells
- Causes: congenital (rare), primary (MDS), secondary (malignancy, lead poisoning, drug-induced)
- Features: microcytic anaemia with HIGH ferritin/iron overload, ringed sideroblasts in the marrow
Lead poisoning
a) Clinical presentation
b) Blood film
c) Treatment
a) - Abdominal pain
- Anaemia (often microcytic, hypochromic)
- Motor neuropathy
b) Basophilic stippling
c) Lead chelators:
- EDTA
- D-penicillamine
64 year old gentleman due to undergo elective AAA repair. Pre-operative testing shows anti-C and anti-Kidd antibodies to blood.
a) How should he be managed?
a) - Preoperative EPO supplementation and autologous RBC harvesting via venesection
- Intraoperative RBC salvage
- (N.B. Even O negative blood is likely to contain the C-antigen and Kidd-antigen and react with his antibodies)
Pure red cell aplasia
a) What is it?
b) Features on lab results
c) Causes
d) Treatment
a) Anaemia secondary to the failure of erythropoiesis
b) - normocytic, normochromic anaemia
- reticulocytopenia in the peripheral blood and absent or infrequent erythroblasts in the bone marrow
- other cell lines unaffected
c) - Autoimmune disease
- Viral infections e.g. HIV, Parvovirus B19
- Diamond-Blackfan anaemia, a congenital cause presenting in infancy
- EPO use
d) - Treat underlying cause
- May respond to immunosuppression
- Stop EPO if this is given
