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Anaemia

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Paediatrics (Haematological disorders) Mind Map on Anaemia, created by v.djabatey on 22/02/2014.
v.djabatey
Mind Map by v.djabatey, updated more than 1 year ago
v.djabatey
Created by v.djabatey about 10 years ago
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Resource summary

Anaemia
  1. definition
    1. an Hb level below normal
      1. neonate: Hb< 14 g/dl
        1. 1-12 months: Hb< 10 g/dl
          1. 1-12 years: Hb<11 g/dl
        2. causes
          1. reduced RBC production
            1. ineffective erythropoiesis
              1. normal/increased rate of RBC production but differentiation or survival of RBCs is defective
                1. e.g. iron def
                  1. main causes =
                    1. inadequate intake
                      1. common in infants
                        1. additional Fe needed for rise in blood vol that goes w/ growth & to build up child's Fe stores
                          1. 1 year old kid needs Fe intake of about 8 mg/day (about same intake as dad)
                        2. sources of iron
                          1. breast milk
                            1. low iron content
                              1. but 50% of Fe in it is absorbed
                            2. infant formula
                              1. supplemented w/ adequate Fe amount
                              2. solids introduced at weaning
                                1. e.g. cereals
                                  1. supplemented w/ iron
                                    1. but only 1% absorbed
                                2. high iron sources
                                  1. red meat
                                    1. beef
                                      1. lamb
                                      2. liver
                                        1. kidney
                                          1. oily fish
                                            1. pilchards
                                              1. sardines
                                            2. average iron sources
                                              1. pulses, peas, beans
                                                1. wholemeal prods
                                                  1. fortified breakfast cereals with added vit C
                                                    1. dark green veg
                                                      1. broccoli
                                                        1. spinach
                                                        2. dried fruit
                                                          1. raisins
                                                            1. sultanas
                                                            2. nuts & seeds
                                                              1. cashews
                                                                1. peanut butter
                                                            3. foods to avoid in excess in toddlers
                                                              1. cow's milk
                                                                1. low iron content & poorly absorbed
                                                                2. tea
                                                                  1. tannin inhibits Fe uptake
                                                                  2. high fibre foods
                                                                    1. phytates inhibit Fe absorption
                                                                  3. caused by
                                                                    1. delay in introduction of mixed feeding beyond 6 months old
                                                                      1. diet insufficient in iron-rich foods
                                                                        1. esp if it contains large amounts of cow's milk
                                                                      2. Fe absorption increased when eaten w/ fresh fruit & veg (rich in vit C)
                                                                      3. malabsorption
                                                                        1. blood loss
                                                                        2. clinical features
                                                                          1. asymptomatic until Hb < 6-7g/dl
                                                                            1. as anaemia worsens, kids tire easily & young infants feed more slowly
                                                                              1. any sx and signs of
                                                                                1. blood loss
                                                                                  1. malabsorption
                                                                                  2. pallor of
                                                                                    1. conjunctivae
                                                                                      1. tongue
                                                                                        1. palmar creases
                                                                                        2. pica
                                                                                          1. = inapprop eating of non-food material
                                                                                            1. e.g. soil, chalk, gravel, foam rubber
                                                                                          2. adverse effect on behaviour & intellectual function
                                                                                          3. diagnosis
                                                                                            1. microcytic hypochromic anaemia (low MCV & low MCH)
                                                                                              1. low serum ferritin
                                                                                              2. differentials (of microcytic anaemia)
                                                                                                1. beta-thalassaemia trait
                                                                                                  1. usually kids of Asian, Arabic or Mediterranean origin
                                                                                                  2. alpha-thalassaemia trait
                                                                                                    1. usually kids of African or Far Eastern origin
                                                                                                    2. anaemia of chronic disease e.g. due to renal failure
                                                                                                    3. Mx
                                                                                                      1. dietary advice
                                                                                                        1. oral Fe supplementation
                                                                                                          1. well tolerated preps that don't stain teeth
                                                                                                            1. Niferex (polysaccharide Fe complex)
                                                                                                              1. Sytron (sodium iron edetate)
                                                                                                              2. continue til Hb normal & then for at least another 3 months to replenish Fe stores
                                                                                                                1. w/ good compliance Hb will rise by 1g/dl per week
                                                                                                                2. failure to respond to this Rx means child isn't getting enough
                                                                                                                  1. but ix other causes esp
                                                                                                                    1. malabsorption
                                                                                                                      1. e.g. due to coeliac disease
                                                                                                                      2. chronic blood loss
                                                                                                                        1. e.g. due to Meckel divertiulum
                                                                                                                  2. NEVER GIVE A BLOOD TRANSFUSION
                                                                                                                    1. even kids w/ Hb as low as 2-3 g/dl due to Fe def have reached this level over a long period & can tolerate it
                                                                                                                    2. Rx of Fe def w/ normal Hb
                                                                                                                      1. i.e. kids w/ low serum ferritin that haven't yet developed anaemia
                                                                                                                        1. giving oral Fe is CONTROVERSIAL
                                                                                                                          1. Arguments for
                                                                                                                            1. Fe needed for brain development
                                                                                                                              1. Fe def anaemia assoc w/ behavioural & intellectual def
                                                                                                                              2. Arguments against
                                                                                                                                1. risk of accidental poisoning w/ oral Fe
                                                                                                                                  1. oral Fe is toxic
                                                                                                                              3. give dietary advice
                                                                                                                                1. & offer option of additional Rx w/ oral iron
                                                                                                                          2. e.g. folic acid def
                                                                                                                            1. chronic inflammation
                                                                                                                              1. JIA
                                                                                                                              2. chronic renal failure
                                                                                                                                1. rare stuff
                                                                                                                                  1. myelodysplasia
                                                                                                                                    1. Pb poisoning
                                                                                                                                  2. diagnostic clues to this =
                                                                                                                                    1. normal reticulocyte count
                                                                                                                                      1. abnormal mean cell vol (MCV) of RBC
                                                                                                                                        1. low in Fe def
                                                                                                                                          1. raised in folic acid def
                                                                                                                                      2. complete absence of RBC production (RBC aplasia)
                                                                                                                                        1. Parvovirus B19 infection
                                                                                                                                          1. Diamond-Blackfan anaemia (congenital red cell aplasia)
                                                                                                                                            1. rare (5-7 cases/10^6 live births)
                                                                                                                                              1. 20% of cases have fam hx; rest sporadic
                                                                                                                                                1. gene mutations in ribosome protein (RPS) genes implicated in some cases
                                                                                                                                                  1. most cases present at 2-3 months old; 25% present at birth
                                                                                                                                                    1. clinical features
                                                                                                                                                      1. sx of anaemia
                                                                                                                                                        1. congenital anormalies
                                                                                                                                                          1. short stature
                                                                                                                                                            1. abnormal thumbs
                                                                                                                                                          2. Rx
                                                                                                                                                            1. oral steroids
                                                                                                                                                              1. monthly RBC transfusions
                                                                                                                                                                1. for kids who are oral steroid unresponsive
                                                                                                                                                                2. stem cell transfusion
                                                                                                                                                              2. Transient erythroblastopenia of childhood
                                                                                                                                                                1. usually triggered by viral infections
                                                                                                                                                                  1. same haematological features as D-B anaemia
                                                                                                                                                                    1. but TEC
                                                                                                                                                                      1. always recovers
                                                                                                                                                                        1. usually within several weeks
                                                                                                                                                                        2. no fam hx
                                                                                                                                                                          1. no congenital anomalies
                                                                                                                                                                            1. no RPS gene mutations
                                                                                                                                                                        3. rare stuff
                                                                                                                                                                          1. Fanconia anaemia
                                                                                                                                                                            1. aplastic anaemia
                                                                                                                                                                              1. leukaemia
                                                                                                                                                                              2. diagnostic clues
                                                                                                                                                                                1. low reticulocyte count despite low Hb
                                                                                                                                                                                  1. normal bilirubin
                                                                                                                                                                                    1. -ve direct antiglobulin test (Coombs test)
                                                                                                                                                                                      1. red cell precursors on bone marrow exam
                                                                                                                                                                                  2. increased RBC destruction (haemolysis)
                                                                                                                                                                                    1. immune
                                                                                                                                                                                      1. haemolytic disease of the newborn
                                                                                                                                                                                        1. autoimmune haemolytic anaemia
                                                                                                                                                                                          1. common in neonates, but not kids
                                                                                                                                                                                          2. characterised by reduced RBC lifespan
                                                                                                                                                                                            1. due to haemolysis (increased RBC destruction) in
                                                                                                                                                                                              1. the circulation (intravascular haemolysis)
                                                                                                                                                                                                1. liver or spleen (extravasc haemolysis)
                                                                                                                                                                                              2. normal RBC lifespan = 120 days & bone marrow makes 173000 RBCs/day
                                                                                                                                                                                                1. in haemolysis RBC survival lasts a few days
                                                                                                                                                                                                  1. bone marrow prodn rises 8x
                                                                                                                                                                                                    1. so haemolysis only -> aneamia when bone marrow can not make up for premature destructn of RBCs anymore
                                                                                                                                                                                                  2. intrinsic abnormalities
                                                                                                                                                                                                    1. the main cause of haemolytic anaemia in children
                                                                                                                                                                                                      1. red cell mb disorders
                                                                                                                                                                                                        1. hereditary spherocytosis
                                                                                                                                                                                                          1. occurs in 1 in 5000 births in Caucasians
                                                                                                                                                                                                            1. usually autosomally dominantly inherited
                                                                                                                                                                                                              1. but in 20% no fam hx & caused by new mutations
                                                                                                                                                                                                              2. caused by mutations in genes for proteins of RBC mb
                                                                                                                                                                                                                1. spectrin
                                                                                                                                                                                                                  1. ankyrin
                                                                                                                                                                                                                    1. band 3
                                                                                                                                                                                                                      1. -> red cell losing part of mb when it goes through spleen
                                                                                                                                                                                                                        1. reduction in surface:vol ratio -> spheroidal shape, so less deformable than normal RBCs
                                                                                                                                                                                                                          1. so destroyed in microvasc of spleen
                                                                                                                                                                                                                      2. clinical features
                                                                                                                                                                                                                        1. fam hx makes diag suspicious
                                                                                                                                                                                                                          1. variable manifestations
                                                                                                                                                                                                                            1. can be asymptomatic
                                                                                                                                                                                                                              1. jaundice
                                                                                                                                                                                                                                1. usually develops during childhood
                                                                                                                                                                                                                                  1. but may be intermittent
                                                                                                                                                                                                                                  2. may cause severe haem jaundice in 1st few days of life
                                                                                                                                                                                                                                  3. anaemia
                                                                                                                                                                                                                                    1. presents in childhood of mild severity (Hb 9-11 g/dl)
                                                                                                                                                                                                                                      1. but Hb may drop temporarily during infections
                                                                                                                                                                                                                                    2. mild to moderate splenomegaly-depends on rate of haemolysis
                                                                                                                                                                                                                                      1. gallstones
                                                                                                                                                                                                                                        1. due to raised bilirubin excretion
                                                                                                                                                                                                                                        2. aplastic crises
                                                                                                                                                                                                                                          1. uncommon
                                                                                                                                                                                                                                            1. transient (2-4 wks)
                                                                                                                                                                                                                                              1. caused by parvovirus B19 infection
                                                                                                                                                                                                                                          2. diagnosis
                                                                                                                                                                                                                                            1. characteristic blood film
                                                                                                                                                                                                                                              1. specific tests (not usually needed)
                                                                                                                                                                                                                                                1. osmotic fragility
                                                                                                                                                                                                                                                  1. dye binding tests
                                                                                                                                                                                                                                                  2. direct antibody test
                                                                                                                                                                                                                                                    1. exclude autoimmune haemolytic anaemia
                                                                                                                                                                                                                                                      1. also assoc w/ spherocytes
                                                                                                                                                                                                                                                        1. so do test if no fam hx of HS
                                                                                                                                                                                                                                                    2. Mx
                                                                                                                                                                                                                                                      1. if mild chronic haemolytic anaemia
                                                                                                                                                                                                                                                        1. oral folic acid
                                                                                                                                                                                                                                                          1. these kids have raised FA req sec to increased RBC prodn
                                                                                                                                                                                                                                                        2. splenectomy
                                                                                                                                                                                                                                                          1. indications
                                                                                                                                                                                                                                                            1. poor growth
                                                                                                                                                                                                                                                              1. trouble sx of anaemia
                                                                                                                                                                                                                                                                1. severe tiredness
                                                                                                                                                                                                                                                                  1. loss of vigour
                                                                                                                                                                                                                                                                2. usually deferred till > 7 years old
                                                                                                                                                                                                                                                                  1. due to risks of post-splenectomy sepsis
                                                                                                                                                                                                                                                                  2. prior to splenectomy all pts must be checked to have had Hib, S. pneumoniae & menC vaccinations
                                                                                                                                                                                                                                                                    1. advise lifelong daily oral penicillin prophylaxis
                                                                                                                                                                                                                                                                    2. of aplastic crisis from parvovirus B19 infections
                                                                                                                                                                                                                                                                      1. 1-2 blood transfusions over 3-4 weeks when no RBCs made
                                                                                                                                                                                                                                                                      2. symptomatic gallstones
                                                                                                                                                                                                                                                                        1. consider cholecystectomy
                                                                                                                                                                                                                                                                  3. red cell enzyme disorders
                                                                                                                                                                                                                                                                    1. commonest type
                                                                                                                                                                                                                                                                      1. glucose-6-phosphate dehydrogenase def
                                                                                                                                                                                                                                                                        1. 100 million ppl globally affected
                                                                                                                                                                                                                                                                          1. high prevalence (10-20%) in ppl of ... origin
                                                                                                                                                                                                                                                                            1. central African
                                                                                                                                                                                                                                                                              1. Mediterranean
                                                                                                                                                                                                                                                                                1. Middle Eastern
                                                                                                                                                                                                                                                                                  1. Far Eastern
                                                                                                                                                                                                                                                                                  2. pathogenesis
                                                                                                                                                                                                                                                                                    1. G6PD is rate-limiting enzyme in pentose phosphate pathway
                                                                                                                                                                                                                                                                                      1. vital for preventing oxidative damage to RBCs
                                                                                                                                                                                                                                                                                      2. Red cells w/o G6PD are vulnerable to oxidant-induced haemolysis
                                                                                                                                                                                                                                                                                        1. G6PD def is X-linked
                                                                                                                                                                                                                                                                                          1. so mostly affects males
                                                                                                                                                                                                                                                                                            1. Mediterranean, Middle Eastern & Oriental popns, affected males have low/absent ezyme activity in RBCs
                                                                                                                                                                                                                                                                                              1. Affected Afro-Caribbeans have 10-15% normal activity
                                                                                                                                                                                                                                                                                              2. heterozygote girls are usually normal cos they've about 1/2 the normal G6PD activity
                                                                                                                                                                                                                                                                                                1. females can be affected
                                                                                                                                                                                                                                                                                                  1. if homozygous
                                                                                                                                                                                                                                                                                                    1. extreme Lyonisation
                                                                                                                                                                                                                                                                                                      1. more of the normal than abnormal X chromosomes have been inactivated
                                                                                                                                                                                                                                                                                                        1. (Lyon hypothesis- in every XX cell, one X is randomly inactivated)
                                                                                                                                                                                                                                                                                                  2. clinical manifestations
                                                                                                                                                                                                                                                                                                    1. neonatal jaundice
                                                                                                                                                                                                                                                                                                      1. onset usually in 1st 3 days of life
                                                                                                                                                                                                                                                                                                        1. globally commonest cause severe neonatal jaundce requiring exchange transfusion
                                                                                                                                                                                                                                                                                                        2. acute haemolysis ppted by
                                                                                                                                                                                                                                                                                                          1. infection
                                                                                                                                                                                                                                                                                                            1. commonest ppting factor
                                                                                                                                                                                                                                                                                                            2. certain drugs
                                                                                                                                                                                                                                                                                                              1. antimalarials
                                                                                                                                                                                                                                                                                                                1. primaquine
                                                                                                                                                                                                                                                                                                                  1. quinine
                                                                                                                                                                                                                                                                                                                    1. chloroquine
                                                                                                                                                                                                                                                                                                                    2. Abx
                                                                                                                                                                                                                                                                                                                      1. sulphonamides (incl co-trimoxazole)
                                                                                                                                                                                                                                                                                                                        1. quinolones
                                                                                                                                                                                                                                                                                                                          1. ciprofloxacin
                                                                                                                                                                                                                                                                                                                            1. nalidixic acid
                                                                                                                                                                                                                                                                                                                            2. nitrofurantoin
                                                                                                                                                                                                                                                                                                                            3. analgesics
                                                                                                                                                                                                                                                                                                                              1. high dose aspirin
                                                                                                                                                                                                                                                                                                                            4. fava beans (broad beans)
                                                                                                                                                                                                                                                                                                                              1. naphthalene in mothballs
                                                                                                                                                                                                                                                                                                                                1. haemolysis is mostly intravsc
                                                                                                                                                                                                                                                                                                                                  1. assoc w/
                                                                                                                                                                                                                                                                                                                                    1. fever
                                                                                                                                                                                                                                                                                                                                      1. malaise
                                                                                                                                                                                                                                                                                                                                        1. passing dark urine
                                                                                                                                                                                                                                                                                                                                          1. urine contains Hb & urobilinogen
                                                                                                                                                                                                                                                                                                                                        2. Hb level falls rapidly & may drop < 5 g/dl over 24-48hr
                                                                                                                                                                                                                                                                                                                                    2. diagnosis
                                                                                                                                                                                                                                                                                                                                      1. measure G6PD activity in RBCs
                                                                                                                                                                                                                                                                                                                                        1. btw episodes, nearly all pts have normal blood pic & no jaundice & no anaemia
                                                                                                                                                                                                                                                                                                                                          1. during haemolytic crisis
                                                                                                                                                                                                                                                                                                                                            1. G6PD levels may be misleadingly high
                                                                                                                                                                                                                                                                                                                                              1. cos higher [enzyme] in reticulocytes made in higher nos in response to destruction of mature cells
                                                                                                                                                                                                                                                                                                                                                1. need to repeat assay in steady state to confirm diag
                                                                                                                                                                                                                                                                                                                                            2. Mx
                                                                                                                                                                                                                                                                                                                                              1. give parents advice
                                                                                                                                                                                                                                                                                                                                                1. signs of acute haemolysis
                                                                                                                                                                                                                                                                                                                                                  1. jaundice
                                                                                                                                                                                                                                                                                                                                                    1. pallor
                                                                                                                                                                                                                                                                                                                                                      1. dark urine
                                                                                                                                                                                                                                                                                                                                                      2. list of drugs, chemicals & food to avoid
                                                                                                                                                                                                                                                                                                                                                        1. i.e. ppting factors
                                                                                                                                                                                                                                                                                                                                                      3. transfusions rarely needed even for acute episodes
                                                                                                                                                                                                                                                                                                                                                2. haemoglobinopathies (abnormal haemoglobins)
                                                                                                                                                                                                                                                                                                                                                  1. cause anaemia by production of abnormal Hb
                                                                                                                                                                                                                                                                                                                                                    1. sickle cell disease
                                                                                                                                                                                                                                                                                                                                                      1. cause= mutation in beta-globin gene
                                                                                                                                                                                                                                                                                                                                                        1. so delayed presentation til > 6 months old
                                                                                                                                                                                                                                                                                                                                                          1. when most HbF present @ birth replaced by adult HbA
                                                                                                                                                                                                                                                                                                                                                        2. commonest genetic disorder in kids in UK
                                                                                                                                                                                                                                                                                                                                                          1. prevalence= 1 in 2000 live births
                                                                                                                                                                                                                                                                                                                                                            1. commonest in kids w/ black parents of tropical African or Caribbean origin
                                                                                                                                                                                                                                                                                                                                                              1. also seen in Middle East and low prevalence in other areas of world except for N. Europe
                                                                                                                                                                                                                                                                                                                                                              2. collective name for haemoglobinopathies in which HbS inherited
                                                                                                                                                                                                                                                                                                                                                                1. HbS forms cos of mutation in codon 6 of beta-globin gene
                                                                                                                                                                                                                                                                                                                                                                  1. so glutamine-> valine
                                                                                                                                                                                                                                                                                                                                                                2. 3 forms of sickle cell disease
                                                                                                                                                                                                                                                                                                                                                                  1. sickle cell anaemia (HbSS)
                                                                                                                                                                                                                                                                                                                                                                    1. pt homozygous for HbS- practically all Hb is HbS
                                                                                                                                                                                                                                                                                                                                                                      1. have small amounts of HbF & NO HbA
                                                                                                                                                                                                                                                                                                                                                                        1. because sickle mutation is in both beta-globin genes
                                                                                                                                                                                                                                                                                                                                                                    2. HbSC disease (HbSC)
                                                                                                                                                                                                                                                                                                                                                                      1. one HbS inherited from 1 parent & HbC inherited from other parent
                                                                                                                                                                                                                                                                                                                                                                        1. HbC formed due to different point mutation in beta-globin
                                                                                                                                                                                                                                                                                                                                                                          1. so have no HbA cos they've no normal beta-globin genes
                                                                                                                                                                                                                                                                                                                                                                      2. sickle beta-thalassaemia
                                                                                                                                                                                                                                                                                                                                                                        1. one HbS inherited from one parent & beta-thalassaemia trait inherited from the other
                                                                                                                                                                                                                                                                                                                                                                          1. no normal beta-globin genes & most can't make any HbA
                                                                                                                                                                                                                                                                                                                                                                            1. so sx similar to sickle cell anaemia
                                                                                                                                                                                                                                                                                                                                                                      3. sickle trait
                                                                                                                                                                                                                                                                                                                                                                        1. HbS inherited from 1 parent, normal beta-globin gene from the other
                                                                                                                                                                                                                                                                                                                                                                          1. 40% of Hb= HbS
                                                                                                                                                                                                                                                                                                                                                                          2. don't have sickle cell disease
                                                                                                                                                                                                                                                                                                                                                                            1. but are carriers of HbS
                                                                                                                                                                                                                                                                                                                                                                              1. can pass HbS to their kids
                                                                                                                                                                                                                                                                                                                                                                            2. asymptomatic
                                                                                                                                                                                                                                                                                                                                                                              1. IDed by blood test
                                                                                                                                                                                                                                                                                                                                                                        2. cause anaemia by absent/reduced prod of HbA
                                                                                                                                                                                                                                                                                                                                                                          1. alpha thalassaemia
                                                                                                                                                                                                                                                                                                                                                                            1. cause= deletions or mutations in alpha-globin gene
                                                                                                                                                                                                                                                                                                                                                                            2. beta-thalassaemia
                                                                                                                                                                                                                                                                                                                                                                              1. cause= mutation in beta-globin gene
                                                                                                                                                                                                                                                                                                                                                                                1. so delayed presentation til > 6 months old
                                                                                                                                                                                                                                                                                                                                                                                  1. most HbF present @ birth replaced by adult HbA
                                                                                                                                                                                                                                                                                                                                                                      4. ->
                                                                                                                                                                                                                                                                                                                                                                        1. anaemia
                                                                                                                                                                                                                                                                                                                                                                          1. hepatomegaly & splenomegaly
                                                                                                                                                                                                                                                                                                                                                                            1. increased blood levels of unconj biliirubin
                                                                                                                                                                                                                                                                                                                                                                              1. excess urinary urobilinogen
                                                                                                                                                                                                                                                                                                                                                                              2. diagnostic clues
                                                                                                                                                                                                                                                                                                                                                                                1. reticulocyte count (called polychromasia on blood film cos reticulocytes have characteristc lilac colour)
                                                                                                                                                                                                                                                                                                                                                                                  1. unconj bilirubinaemia & increased urinary urobilinogen
                                                                                                                                                                                                                                                                                                                                                                                    1. abnormal appearance of RBCs on blood film
                                                                                                                                                                                                                                                                                                                                                                                      1. spherocytes
                                                                                                                                                                                                                                                                                                                                                                                        1. sickle-shaped
                                                                                                                                                                                                                                                                                                                                                                                          1. very hypochromic
                                                                                                                                                                                                                                                                                                                                                                                          2. +ve direct antiglobulin test
                                                                                                                                                                                                                                                                                                                                                                                            1. only if immune cause
                                                                                                                                                                                                                                                                                                                                                                                              1. this test IDs antibody-coated RBCs
                                                                                                                                                                                                                                                                                                                                                                                            2. increased RBC precursors in bone marrow
                                                                                                                                                                                                                                                                                                                                                                                          3. blood loss
                                                                                                                                                                                                                                                                                                                                                                                            1. relatively uncommon cause in kids
                                                                                                                                                                                                                                                                                                                                                                                            2. anaemia of prematurity
                                                                                                                                                                                                                                                                                                                                                                                              1. combo of reduced RBC productn, increased haemolysis & blood loss
                                                                                                                                                                                                                                                                                                                                                                                              2. blood loss
                                                                                                                                                                                                                                                                                                                                                                                                1. fetomaternal bleeding
                                                                                                                                                                                                                                                                                                                                                                                                  1. chronic GI blood loss
                                                                                                                                                                                                                                                                                                                                                                                                    1. Meckel diverticulum
                                                                                                                                                                                                                                                                                                                                                                                                    2. inherited bleeding disorders
                                                                                                                                                                                                                                                                                                                                                                                                      1. von Willebrand disease
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