Anaemia Flashcards
General features of anaemia
- fatigue, weakness
- pallor due to vasoconstriction and blood redistribution
- dyspnoea (in severe anaemia can –> incipient cardiorespiratory failure)
- Palpitations and tachycardia
- Headaches and tinnitus
- chest pain (exacerbation of angina)
Causes of microcytic anaemia
- Iron deficiency anaemia
- Anaemia of chronic disease
- Thalassaemia
- Sideroblastic anaemia
Causes of iron deficiency anaemia
- Inadequate intake
- impaired absorption
- increased loss
- increased requirements
symptoms of iron deficiency anaemia
- Nail flattening and koilonychia
- glossitis
- angular stomatitis
- dysphagia due to oesophageal web and gastritis
Blood tests results in iron deficiency anaemia
- low MCHC (hypochromic)
- low serum iron
- low ferritin
- TIBC high
- transferrin saturation low
What would a blood film show in iron deficiency anaemia?
- small, pale red cells
- anisopoikilocytosis (variance in size and shape)
- pencil cells
What is anaemia of chronic disease?
Defects in iron utilisation, mainly caused by inflammation as cytokines trigger changes in intracellular iron metabolism
Blood test results in anaemia of chronic disease?
(anaemia is rarely severe)
- MCV/MCHC low or normal
- high ferritin
- low serum iron
- TIBC may be low
- transferrin saturation low
- reticulocutes low for the degree of anaemia
What does alpha thalassaemia major involve?
- Deletion of all 4 genes so no synthesis of alpha chains
- Hb-Barts hydrops syndrome
- death occurs in utero as HbF and HbA both need alpha chains
What does alpha thalassaemia traits involve?
- deletion of 1 gene –> slight lowering of MCV and MCHC
- deletion of 2 genes minimally lowers Hb with a raised red cell count, polychormasia and microcytosis
What does ß thalassaemia major involve?
- No functional ß chains are produced - apperent between 3 - 6 months when [HbF] decreases
- Severe anaemia, failure to thrive, hepatosplenomegaly
- Compensatory bone marrow expansion –> skull bossing and maxillary enlargement (hair on end appearance)
- Blood film shows hypochromic microcytic red cells, target cells, tear drop cells and nucleated red cells
What does ß thalassaemia intermedia involve?
- Some ß chains produced **?
- patients present later, 2 - 5y/o
- Mild anaemia, moderate bone changes and normal growth
What does ß thalassaemia trait involve?
- Usually asymptomatic
- Mild anaemia with microcytic hypochromic red cells
- often confused with iron deficiency
Investigations: Hb electrophoresis and hb analysis
Holistic treatment of ß thalassaemias?
- Education on risk of acute events
- genetic counselling
- traits and intermedia often don’t need treatment
- Major requires regular transfusions (2 - 4 weeks, splenectomy can reduce frequency) with chelation therapy
- stem cell transplant
What is sideroblastic anaemia?
- defects in haem synthesis and other pathways needed for erythroblast mitochondria
- this lead to decreased Hb production and abnormal iron metabolism
- this leads to accumulation of iron arranged in a ring in the nucleated immature erythroblasts
Symtoms of iron overload: cardiac or hepatic dysfunction
Blood results in sideroblastic anaemia?
- variably severe anaemia
- usually microcytic hypochromic but can sometimes be dimorphic (depends on cause)
- systemic iron overload may be present
peripheral blood smear would show ring sideroblasts with perinuclear ring of iron granules
management of sideroblastic anaemia?
- control anaemia - transfusion if severe
- prevent organ damage from iron overload
Causes of normocytic anaemia?
- Haemolytic anaemia
- Hereditary normocytic anaemia
- acquired normocytic anaemia (autoimmune)
- Aplastic anaemia
- Sickle cell anaemia
- combined microcytic and macrocytic anaemias
- anaemia of chronic disease
What happens in haemolytic anaemia?
Increased destruction of RBCs can be:
- Intravascular - RBC destruction due to complement-mediated lysis or direct RBC trauma - schistocytes
- Extravascular - accelerated RBC destruction by the reticuloendothelial system, due to immune targeting by antibodies (phagocytosis occurs in the spleen and liver) - spherocytes
What are the types of hereditary normocytic anaemia?
- Membrane defects
- Metabolism defects
- Abnormal Hb
Hereditary normocytic anaemia: what are the types caused by membrane defects?
- hereditary spherocytosis - RBCs lose membrane and become spherica, can’t pass through spleen so die early
- Hereditary elliptocytosis - similar to HS but elliptical RBCs
Hereditary normocytic anaemia: what are the types caused by metabolism defects?
- G6PD deficiency - needed to reduce NADPH - only source of it is in red cells so leaves them susceptible to oxidative stress
- Pyruvate kinase deficiency - red cells become rigid as a result of reduce ATP formation
Hereditary normocytic anaemia: what are the types caused by abnormal Hb?
- Thalassaemia
- Sickle cell anaemia
What are the types of acquired normocytic anaemias?
- Autoimmune
- Alloimmune
- Drug-induced
- Secondary
Acquired normocytic anaemias: what happens when it is autoimmune?
- Caused by antibody production against self cells
- Characterised by DAT (coomb’s test)
- Warm autoimmune
- Ab reacts with RBCs more strongly at 37oC
- red cells usually coated with IgG
- Cold autoimmune
- reacts more strongly with RBCs at 4oC
- red cells usually coated in IgM
Acquired normocytic anaemias: what happens when it is alloimmune?
- Transfusion of incompatible blood –> acute haemolytic transfusion reaction
- Haemolytic disease of newborn: if mother is RhD- but baby is + the mother will make antibodies against RhD which can cross the placenta - injections of anti-D given to avoid this
Why would a secondary acquired normocytic anaemia occur?
Red cell survival can be shortened in many systemic disorders e.g. malaria, burns, hypersplenism, mechanical heart valve
Symptoms of acquired normocytic anaemias
- jaundice
- splenomegaly
- dark urine
Blood test results in acquired normocytic anaemias
- Reticulocytosis
- elevated serum bilirubin (unconjugated)
- elevated LDH
- low haptoglobin (binds to free Hb - low levels means more free Hb)
Blood film results in acquired normocytic anaemias
- Hereditary spherocytosis - spherocytes
- Hereditary elliptocytosis - elliptical RBCs
- G6PD deficiency - Heinz bodies (oxidised, denatured Hb)
- may see schistocytes
Management of acquired normocytic anaemia?
- removal of cause
- oral corticosteroids
- rituximab
- splenectomy
aplastic anaemia
- pancytopenia due to aplasia of the bone marrow (failure)
- substantial decrease in no. of haematopoietic pluripotent stem cells due to:
- a fault in remaining ones
- or an immune reaction against them
- makes them unable to divide and differentiate to populate the bone marrow
Types of primary aplastic anaemia?
- Congenital
- Fanconi and non-fanconi
- Acquired
- Idiopathic acquired is the most common type
Causes of secondary aplastic anaemia?
- Ionising radiation - radiotherapy, nuclear power stations
- Chemicals - benzene, TNT, insecticides, hair dye
- Drugs - busulphan, cyclophosphamide, anthracyclines, sulphonamides, gold
- Infection - viral hepatitis
Symptoms of aplastic anaemia
- recurrent infection (esp mouth and throat)
- bleeding/easy bruising (bleeding gums, epistaxis, menorrhagia)
Investigation results of aplastic anaemia
- Anaemia is normally normocytic and normochromic
- Leucopenia (selectively granulocytes then lymphocytes in severe)
- Thrombocytopenia
- Reticulocytopenia
- No abnormal cells in blood film
- Bone marrow - hypoplasia and loss of haematopoietic tissue and replacement with fat (>75%)
Management of aplastic anaemia
- Removal of any known cause
- Supportive care
- blood products must be filtered and irradiated
- blood transfusion, platelet concentrates
- prevention and treatment of infection
- Immunosuppressive therapy
- antilymphocyte globulin, corticosteroids, cyclosporin
- Allogenic stem cell transplant
What is sickle cell anaemia?
- Group of Hb disorders where the sickle ß-globin gene inherited HbS is insoluble and forms crystals when exposed to low [O2]
- Deoxygenated Hb polymerises into long fibres - red cells sickle and may block large vessels or part of the microcirculation –> infarcts of various organs
- AS recessive
What happens during a severe sickle cell crisis?
- Painful vaso-occlusive crises - precipitated by infection, acidosis, dehydration or deoxygenation –> infarcts of varous organs
- Visceral sequestration crises: sickling within organs and pooling of blood
- aplastic crises: may occur due to parvovirus or folate deficiency - sudden fall of Hb usually requiring transfusion
- Haemolytic crises: increased rate of haemolysis with a fall in Hb but increase in reticulocytes - usually accompanies a painful crisis
*
Treatment of sickle cell anaemia
- avoid precipitating factors
- vaccinations: pneumococcal, Hib and men. and penicillin to reduce infection rate
- Hydroxycarbamide is patients with recurring complications
- Transfusions sometimes given as prophylaxis in those having frequent crises
- Stem cell transplantation indicated in severe cases
- Crises treatment: rest, warmth, rehydration, Abx if infection is present and analgesia
Investigations of sickle cell anaemia
- DNA based arrays show replacement of ßsubunits with HbS
- Haematuria is the worst and most common symptom - maybe due to minor infarcts of the renal papillae
*Caution needed with anaesthesia, pregnancy and high altitudes
Causes of macrocytic anaemia?
- B12/Folate deficiency
- Pernicious anaemia
- Pregnancy
- Liver disease
what is megaloblastic anaemia?
- Caused by B12 or folate deficiency
- defective DNA synthesis
- causes delayed maturation of the nucleus of RBCs
- RBCs die in the bone marrow or enter the bloodstream as enlarged, misshapen cells with reduced survival time.
Why does folate deficiency occur?
- Insufficient dietary intake (found in greens, legumes)
- Increased demand e.g. in pregnancy, lactation
- Intestinal malabsorption occurs in small intestine disorders such as coeliac
- Drugs and toxins - alcoholism, sulfathalazine, mtx, trimethoprim, anti-convulsants
Symptoms of folate deficiency?
weight loss and headaches
Investigation findings in folate deficiency
- Blood tests:
- high MCV and MCHC can precede anaemia by a few weeks
- low serum folate
- Blood film:
- hypersegmented neutrophils
Management of folate deficiency
Folic acid 1mg PO OD
* ensure no B12 deficiency
Causes of B12 deficiency
- Dietary intake (contained in dairy products)
- stores in the liver last for years so dietary deficiency leads on to chronic deficiency
- can be due to malabsorption (e.g. gastric band)
symptoms of B12 deficiency
Weight loss, headaches and paraesthesia
Investigation findings in B12 deficiency
- Blood tests - low serum B12
- Blood film - hypersegmented neutrophils
What is pernicious anaemia?
- autoimmune disorder - most common cause of B12 deficiency
- B12 binds to IF (produced by parietal cells) and is then absorbed in the terminal ileum.
- Deficiency arises from reduced secretion of IF
Investigation findings in pernicious anaemia
Blood tests
- positive for intrinsic factor antibodies
and/or - positive antiparietal cell antibody
Management of pernicious anaemia
Hydroxycobalamin 1mg IM every 3 months (after initial loading every 2 weeks)
How to remember causes of microcytic anaemia
TAILS
thalassaemia
anaemia of chronic disease
iron deficiency anaemia
lead poisoning
sideroblastic anaemia
pathophysiology of thalassaemia
- Normally Hb has 2 alpha and 2 beta chains
- Here unequal synthesis of these chains creates abnormal Hb which damages the cell membrane and deforms the cell
- abnormal cells are destroyed mostly by BM, some by spleen
Beta thalassaemia trait?
- autosomal recessive condition, significant microcytosis disproportionate to the anaemia
- heterozygous defect, so usually asymptomatic
- Hb electrophoresis shows raised HbA2 and HbF (HbA2 lacks the beta chain)
Beta thalassaemia major signs and symptoms?
- Homozygous defect - total lack of beta chains, defect on chromosome 7
- starts aged 3 - 6 months (when HbF levels decline)
- Severe anaemia - abnormal RBCs get destroyed
- Marrow expansion –> skull bossing, maxillary enlargement
- Jaundice
- Extramedullary erythropoiesis
- Failure to thrive
Beta thalassaemia major investigations and management?
- FBC - microcytic anaemia
- Hb electrophoresis - v. increased HbF, increased HbA2
- Blood film - target cells, nucleated RBC
Management: - Lifelong transfusions
- SE: Haemochromatosis (Fe overload)
- SC desferrioxamine - decrease risk of Fe overload
- Bone marrow transplant may be curative
Alpha thalassaemia
Trait (mild) asymptomatic
–/aa or a-/a-
Blood film: hypochromic microcytes
HbH disease (less mild)
moderate anaemia - may need transfusions
some haemolysis, can lead to HSM and jaundice
Hb Barts –/–
Incompatible with life, causes death in the womb
Hydrops fetalis
How to remember causes of macrocytic anaemia?
FATRBC
- *F**oetus
- *A**lcohol
- *T**hyroid (hypo)
- *R**eticulocytosis
- *B**12/Folate megaloblastic
- *C**irrhosis
Once classified as macrocytic, what next?
Blood film to check where megaloblastic
Megaloblastic anaemia (decreased B12/folate) = hypersegmented neutrophil
Alcohol/liver disease = target cells
After blood film, what to order in macrocytic anaemia?
- Megaloblastic anaemia - serum B12, red cell folate
- LFT
- bilirubin slightly elevated in B12/folate deficiency as megaloblasts get destroyed and release it
- also may show liver disease causing macrocytosis
- TFT-screen thyroid
what might a bone marrow biopsy show in macrocytic anaemia?
megaloblastic erythropoiesis
Folate:
source?
storage duration?
absorption site?
deficiency caused by?
sources: greens, nuts, liver
stores last 4 months
absorbed in proximal jejunum
deficiency caused by decreased intake/absorption and increased loss/usage
Also caused by ethanol, phenytoin, methotrexate
Folate deficiency treatment
- Assess and treat underlying cause
- Give B12 first unless levels are normal
- Folate 5mg/d PO
B12 deficiency
Sources?
Storage duration?
Absorption site?
Causes of deficiency
Sources: meat, fish, dairy
Stores last for 4 years
Absorbed in terminal ileum, requires intrinsic factor made by gastric parietal cells
Used in DNA and myelin synthesis
Deficiency caused by vegan diet (rare due to food fortification), reduced absorption (GI: pernicious anaemia, Crohn’s, terminal ileum resection, gastrectomy)
Features of B12 deficient macrocytic anaemia
- glossitis
- skin - lemon tinge (pallor + v. mild jaundice)
- neurological symptoms
- paraesthesia, peripheral neuropathy, distal sensory loss
- gait disturbance
- degeneration of spinal cord (severe)
Investigations of B12 deficiency macrocytic anaemia
- FBC - microcytic anaemia, decreased WCC and platelets if severe, bone marrow failure leads to pancytopenia if too deficient
- intrinsic factor/anti-parietal cell antibodies (pernicious)
B12 deficiency management
if dietary deficiency - oral cyanocobalamin
if malabsorption - IM hydroxycobalamin
what is pernicious anaemia?
- Autoimmune disease, autoantibodies against parietal cells or IF –> reduced acid production and decreased IF
- Usually >40y/o, increased incidence in blood group A
- Associations with thyroid disease, vitiligo, Addison’s, decreased HPT, 3x risk of gastric adenocarcinoma
What is haemolytic anaemia?
Active destruction of red blood cells which leads to anaemia.
Can be extravascular (occurs in spleen) or intravascular
What does the haemolysis screen involve?
- Increased unconjugated bilirubin (released in RBC degradation)
- Increased reticulocyte count (baby RBCs)
- Schistocytes (fragmented RBCs) in intravascular haemolysis
- Haemoglobinuria in intravascular haemolysis
Causes of acquired haemolysis
- Immune - warm (IgG), cold (IgM)
- Mechanical - MAHA’s, mechanical heart valve
- Infection (malaria)
- Burns
- PNH
hereditary causes of haemolysis
- enzyme - G6PD, pyruvate kinsase deficiency
- membrane - spherocytosis, elliptocytosis
- haemoglobin - sickle cell, thalassaemia
Autoimmune haemolytic anaemias: warm?
- IgG, binds at 37degrees
- Extravascular haemolysis
- Ix - DAT/Coomb’s tests - positive
- Aetiology: idiopathic, SLE, RA, Evan’s
- Treatment - immunosuppression, splenectomy
Autoimmune haemolytic anaemias: cold?
- IgM, binds at 4degrees
- Intravascular haemolysis
- Ix: DAT/Coomb’s tests +ve for complement
- Aetiology: idiopathic, mycoplasma
- Treatment: keep warm, rituximab
What is hereditary spherocytosis?
Autosomal dominant defect of RBC membrane, producing large spherocytes whcih get trapped and haemolysed in spleen (extravascular)
Features: splenomegaly, jaundice, pigment gallstones
Complications of aplastic crisis?
Aplastic crisis
Even transient bone marrow suppression (e.g. parvovirus) causes problems due to patient’s high rate of RBC destruction/short RBC lifespan
Megaloblastic crisis
What are reticulocytes? When do they increase?
- Precursors to RBCs
- Rise during anaemia as body tries to fix low oxygenation by increasing no. of RBCs
- Increased in blood loss and haemolytic anaemia
- low in Iron deficiency anaemia as BM does not have the iron to create red cells
