Anaemia Flashcards
What is Anaemia?
Decreased Hb in the blood such that there is inadequate oxygen delivery to tissues
What are the Hb levels indicating anaemia?
Hb <135g/L in men
Hb <115g/L in women
What are the Sx of anaemia?
Can be asymptomatic Fatigue Weakness Headaches Dyspnoea on exertion Angina Intermittent claudication Palpitations
What are the signs of anaemia?
Pallor
Tachycardia
Systolic flow mumur
Cardiac failure
What peripheral signs are indicative of different anaemia types?
Koilonychia (IDA)
Jaundice (haemolytic anaemia)
Leg ulcers (sickle cell disease)
Bone marrow expansion (thalassaemia)
What are the three main types of anaemia?
Microcytic (<80fl)
Normocytic (80-96fl)
Macrocytic (>96fl)
What are the common causes of microcytic anaemia?
Iron deficiency anaemia (commonly blood loss)
Thalassemia
Lead poisoning
Sideroblastic anaemia
What are the common causes of normocytic anaemia?
Acute blood loss Anaemia of chronic disease Renal anaemia Haemolytic anaemia (can be macro) Marrow failure Pregnancy CT diseases Diamorphic blood film
What are the common causes of macrocytic anaemia?
B12 deficiency Folate deficiency Alcohol excess Myelodysplastic syndromes Severe hypothyroidism
What are the clinical signs of IDA?
Koilonychia
Angular stomatitis
Brittle nails/hair
What are the common causes of IDA?
Blood loss (hookworm, heavy menstruation, GI bleed) Dec absorption (coeliacs, antacids, post gastrectomy) Inc demand (growth, pregnancy) Inad intake (premature infants/prolonged breastfed)
What are the appropriate investigations to confirm IDA?
Serum Fe, ferritin, total iron binding capacity
Serum soluble transferrin receptors (increased)
Blood film
What signs of IDA would be present on a blood film?
Typically hypochromic
Sideroblasts
Signs of thalassaemia
What further investigations are necessary after confirming IDA?
Coeliac serology
GI investigation (OGD, colonoscopy)
Stool microscopy
How is IDA managed?
Address underlying cause
Oral ferrous sulphate 200mg t.d.s
Increase dietary Fe intake
What are the common side effects of Ferrous Sulphate?
Cramping, bloating
N/V
Constipation
Black stools
What investigations are appropriate in suspected anaemia of chronic disease?
Serum Fe (dec)
TIBC (dec)
STR (normal)
Ferritin (inc)
How long should treatment for IDA be continued?
Monitor after 1mo
-improvement in sx
-increase of Hb 20g/L
3mo after bloods return to normal
What is the Rule of 10’s?
Max rise in Hb in 1wk is 10g/L
If >10g/L decline in 1wk then blood is being lost
When transfusing 1 bag will raise Hb 10g/L
What is Paterson-Brown Kelley (Plummer Vinson) Syndrome?
Rare disease occurring in post-menopausal women Characterised by -dysphagia -odynophagia -IDA -glossitis -chelitis -oesophageal webs
How is Paterson-Brown Kelley (Plummer Vinson) Syndrome?
Iron supplementation & mechanical widening of oesophagus
What is Thalassemia?
Genetic disorders of Hb synthesis
-deficient a/b chain synthesis
What are the two main types of B-thalassemia?
B-thalassemia minor (trait)
B-thalassemia major (Cooley’s anaemia)
Describe B-thalassemia minor
Carrier state
Usually asymptomatic, mild microcytic anaemia worsening in pregnancy
-HbA2/HbF raised
Describe B-thalassemia major
Abnormality in both b-globin genes
Survival possible due to HbF
How does B-thalassemia major present?
In first year with -severe anaemia -hepatosplenomegaly -failure to thrive Facial deformities (due to extramedullary haematopoiesis)
What are the abnormalities on a blood film in B-thalassemia major?
Hypochromic microcytic cells
Target cells
Nucleated RBCs
How is B-thalassemia major managed?
Lifelong blood transfusions
What are the main types of a-thalassemia?
Major/hydrops fetalis/Bart’s hydrops
HbH disease
Minor
Carrier
Describe a-thalassemia major
Deletion of all 4 globin genes
-death in utero
Describe HbH disease
Deletion of 3 globin genes
-moderate microcytic anaemia w/ haemolysis
Describe a-thalassemia minor
Deletion of 2 globin genes
-asymptomatic carrier w/ reduced MCV
Describe a-thalassemia carrier
Deletion of 1 globin gene
-clinically normal
What is sideroblastic anaemia?
Bone marrow produces sideroblasts instead of erythrocytes
What causes sideroblastic anaemia?
Congenital disorder OR
Acquired in myelodysplastic syndrome
What are the key investigations in a macrocytic anaemia?
Blood film LFTs/TFTs Serum B12/folate -if B12 low --> anti-parietal Ab, anti-IF Ab, Schilling test Bone marrow biopsy
What is the Schilling test?
Assesses B12 metabolism w/ & w/o IF
Distinguishes b/w pernicious anaemia & small bowel disease
What is the common mechanism by which B12/folate deficiency lead to a megaloblastic anaemia?
B12 co-enzyme for activation of folate
Activated folate needed for DNA synth
Deficiency leads to inc erythrocyte development
-large cells
-trapped/destroyed in reticuloendothelial system
What are the dietary sources of B12?
Meat
Fish
Eggs
Milk
How is B12 absorbed/stored?
Binds w/ IF (secreted by gastric parietal cells)
Absorbed in terminal ileum (brush border)
Stored in liver (3yr store)
Excreted in bile (70% reabsorbed)
What are the common causes of B12 deficiency?
Chronic low dietary intake (vegans) Impaired binding (pernicious, congenital IF absence, gastrectomy) Small bowel disease (resection, Chron's, UC, bacterial overgrowth)
What is Pernicious anaemia?
Autoimmune disease resulting in severe B12 deficiency
What are the three autoantibodies that may be present in pernicious anaemia?
Autoantibodies against parietal cells Blocking antibodies (stop IF-B12 binding, most common) Binding antibodies (prevent IF binding to ileum)
What is subacute combined degeneration of the cord?
Simultaneous post column (LMN) & CST (UMN) loss due to B12 deficiency
How does subacute combined degeneration of the cord present?
Peripheral neuropathy Extensor plantars Brisk knee jerk but absent ankle jerk Tone/power normal Gait ataxic
What are the major dietary sources of folate?
Leafy green vegetables/offal (as DHF/THF)
-90% lost in cooking
How is folate absorbed & stored?
DHF/THF converted to folate in upper GI
Absorbed in jejunum
Low stores (3mo)
What are the common causes of folate deficiency?
Poor nutritional intake (diet/alcohol/anorexia)
Malabsorption (Coeliac)
Anti-folate drugs (trimethoprim, methotrexate, anti-convulsants)
Excess physiological use (preg, lact, prematurity)
Excess pathological use (haemolysis, malig, inflam)
How should folate deficiency be managed?
Folic acid 5mg/day PO for 4mo
-always w/ combined B12
How should pernicious anaemia be managed?
IM B12 initially then oral B12 for maintenance
What is anaemia of chronic disease?
Normochromic/hypochromic
-low Fe, high ferritin, low TIBC, normal STR
Rarely severe
Seen in chronic infection, malignancy, CKD, rheumatoid
How does bone marrow failure appear on blood tests?
Hb, reticulocytes, WCs, platelets all low
Alterations on blood film
What are the potential causes of bone marrow failure?
Aplastic anaemia (idiopathic/drugs) Malignancies Metastatic disease Meylofibrosis Meylodysplasia Parviovirus infection
What is Haemolysis?
Breakdown of RBCs before 120days
- intravascular or extravascular
- asymptomatic –> haemolytic anaemia
What are the intrinsic causes of a haemolytic anaemia?
Haemaglobinopathies (sickle cell/thalassemia)
Membranopathies (spherocytosis/eliptocytosis)
Enzymeopathies (G6DP deficiency)
What are the extrinsic causes of a haemolytic anaemia?
Autoimmune disease (warm/cold)
Alloimmune disease (transfusion/transplant, rhesus)
Drug induced (penicillins)
Paraistes (plasmodium)
Microangiopathic haemolytic anaemia (DIC)
What are the investigation results that would indicate increased RBC breakdown?
Anaemia w/ raised MCV Raised bilirubin (unconjugated, pre-hepatic) Raised serum LDH
What are the investigation results that would indicate increased RBC production?
Reticulocyte count >2% OR 100*10^9/L
-will give a raised MCV
How can a blood film identify the cause of a haemolytic anaemia?
Hypochromic, microcytic = thalassemia Sickle cells = SCA Spherocytes = hereditary spherocytosis/AI haemolysis Eliptocytes = hereditary eliptocytosis Heinz bodies = G6PD deficiency
What further investigations are indicated in haemolytic anaemia?
Coomb's test (?immune cause) Hb electrophoresis (haemaglobinopathies) Enzyme assays Plasma haptoglobin/urinary haemosiderin -indicate intravascular haemolysis
What is Sickle Cell Anaemia?
Autosomal recessive disorder producing abnormal B-globulin chains
- HbS rather than HbA
- more common in african pts
What are the two genotypes of SCA?
HbSS - sickle cell anaemia phenotype
HbAS - sickle cell trait
-protective against falciparum malaria
-rarely symptomatic, vaso-occlusive crises can occur in hypoxia
What is the underlying pathophysiology of SCA?
HbS polymerises when deoxygenated –> produces sickle cells
-fragile, haemolyse, block small vessels
How is SCA diagnosed?
Guthrie card
Sickle cells on blood film
Hb electrophoresis to confirm/distinguish variants
What are the sx of SCA?
Anaemia in first few months of life
Acute haemolytic crises (bone infarcts/painful dactylitis)
Repeated splenic infarction (CKD, CVA)
Chronic haemolytic anaemia (60-90g/L)
What are the potential complications of SCA?
Hyposplenism CKD Bone necrosis Chronic leg ulcers Fe overload Long term pulmonary damage
What is the long-term management of SCA?
Folate supplementation
Pneumococcal vaccination & prophylactic penicillin (hyposplenism)
Hydrocycarbamide (if frequent crises)
Transfusions (2-4/wk) w/ Fe chelators
What is the curative treatment for SCA?
Bone marrow transplantation
What are vaso-occlusive crises?
Occur due to micro-vascular occlusion
- affect bone marrow, cause severe pain
- caused by cold, infec, dehydration, hypoxia
How do vaso-occlusive crises present?
Usually severe pain Can be -mesenteric ischaemia (acute abdomen) -cerebral infarcts -priapism
What are aplastic crises?
Sudden reduction in marrow production due to parvovirus B19
-self limiting (<2wks), may need transfusion
What are sequestration crises?
Pooling of blood in spleen +/- liver
- presents w/ organomegaly, severe anaemia, shock
- typically in children
- urgent transfusion required
How should a sickle cell crisis be managed?
A-E resus, O2, IV fluids Analgesiaa FBC, reticulocytes, cross-match Screen for infec Prophylactic enoxaparin Give blood transfusion
What is G6PD deficiency?
X-linked deficiency of G6PD
- most common in Africa/mediterranean males
- females have mild sx
How does G6PD deficiency present?
Asymptomatic
Oxidative crises (reduced glutathione production)
-rapid anaemia & jaundice
-bite & blister cells on blood film
What are the triggers for oxidative crises in G6PD deficiency?
Drugs (aspirin, primaquine, sulphonamides)
Broad bean consumption
Illness
How is G6PD deficiency diagnosed?
Enzyme assay 3mo after crisis
How is G6PD deficiency managed?
Precipitant avoidance +/- transfusion
What is Pyruvate Kinase deficiency?
AR condition of reduced ATP production
How does PK deficiency present?
Neonatal jaundice
Chronic jaundice w/ hepatosplenomegaly
How is PK deficiency diagnosed?
Enzyme assay
How is PK deficiency managed?
Well tolerated, no specific therapy needed
-splenectomy may help
What is Hereditary Spherocytosis?
AD membran defect –> spherical RBCs
-trapped in spleen
How does HS present?
Haemolysis
Splenomegaly
Jaundice
What is Hereditary Eliptocytosis?
AD defect
-asymptomatic
How are HS/HE managed?
Folate
Splenectomy
-curative, saved for severe disease
What is the underlying pathophysiology of an autoimmune haemolytic anaemia?
Autoantibodies –> extravascular haemolysis & spherocytosis
What are the common causes of AHA?
Idiopathic
2o to lymphoproliferative disease/other AI conditions
What are the two types of AHA?
Warm
Cold
Describe warm AHA
IgG mediated (binding at 37o) Treat w/ steroids/immunosuppressants +/- splenectomy
Describe cold AHA
IgM mediated (binding at <4o) Treat w/ cold avoidance +/- chlorambucil
What is a microangiopathic anaemia?
Mechanical haemolysis caused by physical trauma in the circulation
-shistocytes on blood film
What are the common causes of a microangiopathic anaemia?
Malignant HTN/Pre-eclampsia HUS Thrombotic thrombocytopenic purpura Vasculitis DIC Mechanical heart valves
What are allommune reactions?
Immune mediated BUT coomb’s negative reactions linked to transplantation/transfusion/rhesus
What screening for anaemia takes place before surgery?
Most common abnormality pre-op
- <60g/L = transfusion
- <100g/L = transfusion if cardiac risk/high anticipated blood loss
