Blood - Level 2 Flashcards
Definitions of anaemia? Men, children, women, pregnant women and postpartum?
o In children aged 12–14 years — Hb concentration less than 120 g/L.
o In men (aged over 15 years) — Hb concentration less than 130 g/L.
o In women (aged over 15 years) — Hb concentration less than 120 g/L.
o In women who are pregnant — Hb concentration less than 110 g/L.
An Hb level of 110 g/L or more appears adequate in the first trimester, a level of 105 g/L appears adequate in the second and third trimesters.
o Postpartum — Hb concentration less than 100 g/L.
Definition of macrocytosis?
- Macrocytosis (MCV >100)
o Usually occurs due to problems with synthesis of RBCs
Physiology, absorption of folate?
Deficiency due to?
o Found in green vegetables and offal
o Absorbed in SI and stores last 4 months
o Deficiency by Diet, malabsorption, Leukaemia, heart failure, hepatitis, dialysis, drugs (alcohol, anticonvulsants, methotrexate, sulfasalazine, trimethoprim)
Physiology, absorption of vitamin B12?
Deficiency of B12 due to?
o Animal products provide only dietary source
o B12 binds to intrinsic factor secreted by gastric parietal cells and absorbed in terminal ileum
o Transported as transcobalamin and stored in liver with around 2-5 years supply
o Deficiency due to pernicious anaemia, surgery (ileal resection, gastrectomy), HIV, vegans, metformin, PPI, H2RA
Definition of pernicious anaemia?
Epidemiology?
Associated with?
o Autoimmune atrophic gastritis leading to achlorhydria and lack of gastric IF
o Usually >40 and women
o Associated with – myxoedema, thyrotoxicosis, Hashimoto’s, Addison’s, vitiligo
o Risk of gastric cancer
Causes of megaloblastic macrocytosis?
B12 deficiency
Folate deficiency
Cytotoxic drugs
Causes of non-megaloblastic macrocytosis?
Alcohol Reticulocytosis Liver disease Hypothyroidism Pregnancy
Other causes of megaloblastic macrocytosis?
Myelodysplasia, myeloma, aplastic anaemia
Symptoms of anaemia?
o Asymptomatic
o Symptoms - SOBOE, fatigue, palpitations, exacerbation of angina, pale
o Signs – pallor, bounding pulse, systolic pulmonary flow murmur
Symptoms of vitamin B12 and folate deficiency?
o Cognitive changes o SOB o Headache o Anorexia o Palpitations o Tachypnoea o Visual disturbance o Weakness, lethargy
Signs of B12 and folate deficiency?
o Anorexia o Angina o Angular stomatitis o Glossitis o Liver enlargement o Mild jaundice o Tachycardia o Weight loss
Bloods done in macrocytic anaemia?
o FBC (Low Hb, high MCV (>100))
o Serum B12 (<200ng/L) - If cobalamin levels low – check serum anti-IF antibodies
o Serum Folate (<3mcg/L) - If folate levels low & malabsorption history – Check anti-endomysial & anti-transglutaminase antibodies
o Other investigations to identify cause:
LFTs, GGT, TFTs
Blood film findings in macrocytic anaemia?
B12 and folate deficiency
• Hypersegmented polymorphs (neutrophil)
o >5% of neutrophils with 5 or more lobes, or 1 or more neutrophils with 6 or more lobes
• Oval macrocytes
Target cells if liver disease
What tests to perform to find cause of macrocytic anaemia?
o If low folate – assess dietary folic acid and check antiendomysial or anti-TTG antibodies for coeliac
o If low cobalamin – anti-IF antibodies for pernicious anaemia
When to refer to haematologist in macrocytic anaemia?
o Urgent – neurological symptoms, pregnant, malignancy suspected
o Routine – cause of B12 or folate deficiency uncertain following investigations
When to refer to gastroenterologist in macrocytic anaemia?
o Suspected malabsorption, pernicious anaemia with GI symptoms, gastric cancer suspected, coeliac disease
Management of vitamin B12 deficiency?
Treat cause
Dietary Advice - Food rich in B12 – eggs, fortified food (breakfast cereals, breads), meat, milk, dairy, salmon, cod
Hydroxocobalamin (B12) 1mg IM 3x a week for 2 weeks (if neurological symptoms - alternate days until no improvement)
If not diet related – hydroxocobalamin 1mg IM every 3 months for life
If diet – either oral cyanocobalamin 50-150mcg daily between meals or twice-yearly IM 1mg injection
Management of folate deficiency?
Assess underlying cause – poor diet, malabsorption
Dietary Advice - Foods rich in folate – asparagus, broccoli, brown rice, brussel sprouts, chickpeas, peas
Folic acid 5mg/day PO for 4 months (never without B12 unless known normal – worsens SACDC)
In pregnancy
Prophylactic 400mcg/day given from conception until 12 weeks recommended to all
5g/day up to 12 weeks – previous/FHx NTD, anti-epileptic meds, DM, SCC, thalassaemia, BMI>30
• SCC, thalassaemia – take throughout pregnancy
Monitoring in macrocytic anaemia?
o Within 7-10 days commencing treatment – FBC, reticulocyte count
o 8 weeks – FBC, reticulocyte count, iron and folate levels
o Completion of folic acid treatment – FBC, reticulocyte count
o Cobalamin levels 1-2 months after treatment if no symptom response
Complications of vitamin B12 deficiency?
Paraesthesia, ataxia, progressive symmetrical neuropathy, numbness, memory lapses
Neural tube defects
Sterility
Subacute combined degeneration of the spinal cord
Insidious onset of peripheral neuropathy – symmetrical posterior dorsal column loss causing vibration and proprioception and LMN signs & symmetrical corticospinal tract loss causing motor and UMN signs
Triad – extensor plantars, absent knee jerk, absent ankle jerk
Complications of folate deficiency?
o Prematurity
o CVD and colorectal cancers
o Neural tube defects
o Sterility
Acquired causes of haemolytic anaemia?
Immune-mediated and Coomb’s test positive Drug-induced Autoimmune haemolytic anaemia Paroxysmal cold haemoglobinuria Acute transfusion reaction Haemolytic disease of newborn Coombs Negative Autoimmune haemolytic anaemia Microangiopathic haemolytic anaemia Infection Paroxysmal Nocturnal Haemoglobinuria
Hereditary causes of haemolytic anaemia?
o Glucose-6-phosphate dehydrogenase (G6PD) deficiency
o Pyruvate kinase deficiency
o Hereditary Spherocytosis
o Hereditary elliptocytosis, ovalocytosis – refer to haematology
o Sickle cell disease
o Thalassaemia
Definition of drug-induced haemolytic anaemia?
• Formation of RBC autoantibodies from binding to RBC membranes (penicillin) or production of immune complexes (quinine)
Description, classification and management of autoimmune haemolytic anaemia?
• Autoantibodies causing extravascular haemolysis and spherocytosis
• Classified:
• Warm – IgG-mediated, bind at body temperature, Rx = steroids/immunosuppressants
• Cold – IgM-mediated, bind at low temperature (<4o), often with Raynaud’s or acrocyanosis,
o Rx = keep warm
o May be caused by CLL, lymphoma, drugs, SLE, infection (EBV, mycoplasma)
Description of paroxysmal cold haemoglobulinuria?
- With viruses/syphilis, caused by Donath-Landsteiner antibodies sticking to RBCs in cold
- Self-limiting complement-mediated haemolysis on rewarming
Description of Rhesus haemolytic disorder?
o Usually identified antenatally when woman Rh negative and baby Rh positive
o Presents with anaemia, hydrops, hepatosplenomegaly with rapidly developing jaundice
o Usually anti-D blood group
Description of ABO incompatibility haemolytic disorder?
o Now more common than Rhesus incompatibility
o Most ABO antibodies are IgM and do not cross placenta, but some blood group O women have IgG anti-A-haemolysin which haemolyses red blood cells of a group A infant
o Occasionally group B infants affected by anti-B haemolysins
o Can cause jaundice – peaks 12-72 hours
o Anaemia is less severe and no hepatosplenomegaly
o Coombs test positive
Causes of Coombs negative autoimmune haemolytic anaemia?
Autoimmune hepatitis, hepatitis B&C, post vaccinations, drugs (piperacillin, rituximab)
Description of microangiopathic haemolytic anaemia?
Disruption in RBC circulation, causing intravascular haemolysis and schistocytes
Causes include HUS, TTP, DIC, pre-eclampsia, eclampsia
Treat underlying disease, transfusion or plasma exchange may be needed
Description of paroxysmal nocturnal haemoglobinuria?
Stem cell disorder with haemolysis (especially at night – haemoglobinuria), marrow failure + thrombophilia
Diagnosed – urinary haemosiderin, Harris test positive
Management – anticoagulation, eculizumab
