Haem Flashcards
What is Hb like in neonates?
HIGH
to compensate for low oxygen concentration in utero
Why does Hb in neonates progressively fall?
Due to decreased RBC production
What are normal Hb ranges for neonate / infant / child?
neonate: >140
infant (1m-1y): >100
Child (1y-12y) >110
What are mechanisms of anaemia split into
Reduced production
- ineffective erythropoiesis (e.g. iron deficiency)
- red cell aplasia (NO PRODUCTION)
Increased destruction (haemolysis)
Blood loss
What are causes for red cell aplasia
Parvovirus B19
Diamond-Blackfan
What are causes for ineffective erythropoiesis
Iron deficiency
folic acid deficiency
Chronic inflammation, chronic renal failure
What are causes of haemolysis
RBC membrane disorder (e.g. hereditary spherocytosis)
RBC enzyme disorder (e.g. G6PD deficiency)
Haemoglobinopathy (thalassaemia, sickle cell)
Immune (haemolytic disease of newborn, AI haemolytic anaemia)
What are main causes of iron deficiency anaemia in neonates?
inadequate intake
malabsorption
blood loss
What are sources of iron for infants
breast milk
infant formula
cows milk
solids e.g. cereal
what are clinical fts of iron deficiency anaemia in the newborn
Asymptomatic until Hb<60 Fatigue Slow feeding Pale Pica (inappropriate eating of non-food e.g. soil)
What are investigations for iron deficiency anaemia
Blood film: microcytic hypo chromic anaemia (low MCV, low MCH)
Iron studies (ferritin low, serum iron low, TIBC high)
What is management for iron deficiency anaemia?
Dietary advice
Ferrous sulphate PO
How do you monitor iron deficiency anaemia
Check Hb after 4 weeks - levels should rise by 2g/100
Otherwise check compliance
Once Hb levels are normal, continue iron tx for 3 months to replenish stores
What are specific tests for hereditary spherocytosis
Dye binding assay
Osmotic fragility test
How do you manage hereditary spherocytosis:
Supportive
RBC transfusion
Folic acid supplementation
Consider phototherapy / exchange transfusion if baby also has jaundicer
What is G6PD deficiency
G6PD > rate limiting step in pentose phosphate pathway > necessary to prevent oxidative damage to RBC
Deficiency means they are susceptible to oxidants > haemolysis
What are triggers for G6PD deficiency haemolysis
Antimalarials
Antibiotics
Alnalgesics (aspirin)
Chemicals (Naphtaline, fava beans)
What is pattern of inheritance of G6PD
X linked recessive
What are clinical features of G6PD
NEONATAL JAUNDICE
Trigger
Pallor
Dark urine with haemoglobin AND urobilinogn
How do you diagnose G6PD
measure G6PD activity in blood
What is haemolytic disease of the newborn
Haemolysis due to antibodies against blood group antigens (ABO/RhD)
How do you identify haemolytic disease of the newborn
COOMBS TEST +
Essentially picks up if there are any RBC circulating with antibodies on them
What are main causes of blood loss in the foetus / newborn
maternal occult haemorrhage
TTTS
Why does anaemia of prematurity occur
Inadequate EPO production
Low RBC lifespan
Frequent blood sampling
Iron / folate deficiency
What is another word for bone marrow failure
APLASTIC ANAEMIA
What are 2 inherited causes of aplastic anaemia
Fanconi
Schwachmai-Diamond Syndrome
Explain Fanconi Anaemia
TRIAD
- congenital abnormalities
- defective haematopoesis
- high risk AML/Tumours
What are the congenital abnormalities in Fanconi Anaemia
NORD
NEURO
- micropthalmia,
- microcephaly,
- developmental delay
ORTHO:
- short stature, hip dislocation, scoliosis, SHORT THUMB
RENAL
- renal aplasia/hypoplasia
- horseshoe kidney
- double ureter
DERM
- cafe au last spots
- hypo/hyperpigmented
How do you diagnose Fanconi anaemia
increased chromosomal breakage of peripheral blood lymphocytes
How do you manage Fanconi
BM transplant
What is the triad in Schwachman-Diamond Syndrome
TRIAD Schwachman-Diamond Syndrome:
- BM failure
- pancreatic failure
- skeletal abnormality
Give examples of inherited bleeding disorders
haemophilia
vWF deficiency
Give examples of congenital clotting disorders
protein C deficiency
Protein S deficiency
Antithrombin deficiency
FV leiden
What is mode of inheritance for haemophilia
X linked recessice
What is hallmark feature of haemophilia
Recurrent DEEP bleeding into joints, muscles
What is a bad consequence of haemophilia
arthritis
How do you manage haemophilia
Recombinant F8 for HA
Recombinant F9 for HB
Also give prophylactic F8 if severe HA to reduce risk of joint damage
Also Desmopressin (DDAVP) in mild haemophilia A
What is hallmark feature of vWD
SUPERFICIAL BLEEDING
epistaxis, menorrhagia
How do you manage vWD
Type 1 (poor quality): DDAVP
T2/3: plasma derived F8 concentrated
What must you avoid in vWD/haemophilia
IM injections
aspirin
NSAIDS
What is a dangerous consequence of vitamin K deficiency in babies
Haemorrhagic disease of the newborn
What is vitamin K necessary for
F2, 7, 9, 10
Protein C, S production
What is the cause of ITP
Antiplatelet IgG antibodies
Cause destruction of circulating platelets
How does ITP present
In children, few weeks after viral infection
Children develop petechiae, purpura, superficial bruising
Epistaxis, mucosal bleeding
*** beware of intracranial bleeding
How do you manage mild ITP
self resolving
manage at home with corticosteroids or IVIG
How do you manage severe ITP
IVIG, corticosteroids, platelet transfusion
Explain how MAHA occurs
MECHANISM NOT DISEASE
clot forms in blood vessel > blood cannot flow nicely > sheared into small fragments > schistocytes on blood film + anaemia, jaundice
Explain how HUS occurs
E coli 0157:H7
produces shiga-like toxin
Toxin damages endothelium of glomerular vessel
causes platelet aggregation > thrombocytopenia
shearing of RBC > MAHA
less end organ perfusion > RENAL failure
What is the triad of HUS + other symptom to remember
MAHA + THROMBOCYTOPOENIA + RENAL FAILURE
+ diahrroea
How does TTP occur
antibodies against ADAMTS13
causes vWF to stick together > clots form > platelets all stuck together
cause same as above + diminished end organ perfusion to brain as well, causing perfusion
What is PENTAD of TTP
MAHA + RENAL FAILURE + THROMBOCYTOPOENIA
+ FEVER + ALTERED MENTAL STATE
What is the cause of DIC
sudden increase in exposure to tissue factor (due to sepsis, tumour, pancreatitis, pregnancy, trauma)
Causes activation of coagulation cascade > clotting
body attempts to reverse the clotting via normal anti clot mechanism
causes massive consumption of all clotting factors
How does DIC present
in VERY UNWELL patient
Everything is wrong: high PT, APTT, low platelets
EXPLAIN aetiology of DIC
Increase in tissue factor
Causes activation of coagulation cascade > clotting
body attempts to reverse the clotting via normal anti clot mechanism
causes massive consumption of all clotting factors
what does ITP stand for
Immune / Idiopathic Thrombocytopenic Purpura
What is the function of desmopressin in haemophilia/VWD
stimulates release of F8 and vWF
How do you differentiate ineffective erythropoiesis from red cell aplasia on blood test
LOW RETICULOCYTES in red cell aplasia
HIGH RETICULOCYTES in ineffective erythropoesis
What should you suspect if reticulocytes are low?
Red cell anaemia > parvovirus B19 OR Diamond Blackfan
What investigations should you get if low reticulocytes
Parvovirus serology
BM aspirate
What is sideroblastic anaemia
Bone marrow produces ringed sideroblasts instead of healthy RBCs
This causes a microcytic anaemia
Why does sideroblastic anaemia occur
Body has iron but cannot incorporate it properly into Hb
What do sideroblasts look like
nucleated erythrocytes (precursors) with iron granules surrounding nucleus
What are causes of sideroblastic anaemia
CONGENITAL
- genetic
AQUIRED:
- Myelodysplastic syndrome
- AML
- Alcohol use
- B6 deficiency
- Lead poisoning, copper poisoning
What do you see on blood film for sideroblastic anaemia
- basophillic stippling
- target cells
What THREE TYPES of anaemia can you categorise
Microcytic (MCV<80)
Normocytic (MCV 80-100)
Microcytic (>100)
What are causes of MICROCYTIC anaemia
Iron deficiency
Thalassaemia
Anaemia of chronic disease
Sideroblastic anaemia
How can you further subdivide NORMOCYTIC anaemia
LOW reticulocytes
NORMAL /HIGH reticulocytes
What are causes of NORMOCYTIC anaemia with LOW reticulocytes
Aplastic anaemia (Fanconi, Schwachen-DIamond)
Red cell aplasia (Parvovirus 19, Diamond-Blackfan)
Malignancy
Renal disease
What are causes of NORMOCYTIC anaemia with NORMAL reticulocytes (AKA HAEMOLYTIC CAUSES)
INTRINSIC CAUSES
- Sickle cell
- Membrane defect (spherocytosis, elliptocyt, paroxysmal nocturnal haemoglobinuria)
- Enzyme deficiency (G6PD, PK deficiency)
- immune (ABO/RhD incompatibility, warm/cold AIHA)
EXTRINSIC CAUSES
- Infection e.g. Malaria
- MAHA
What are causes of MACROCYTIC anaemia
MEGALOBLASTIC
- B12/ Folate deficiency
NON-MEGALOBLASTIC
- liver diserase
- alcohol
- drugs
Explain beta thalassamia major
MOST SEVERE FORM
NO HbA - due to NO functioning beta-globin gene
How do you manage beta thalassamia major
FATAL without regular blood transfusions
Give BLOOD TRANSFUSIONS + IRON CHELçATION
BONE MARROW TRANSPLANT IS CURE
What is HYDROPS Fetalis
oedema in min 2 fluid compartments + ascites
What are causes for Hydrops
foetal anaemia (iron deficiency, parvovirus B19( Maternal infection (CMV, syphilis9 TTTS
How do you treat Hydrops foetal is
EXCHANGE TRANSFUSION
What is the whole spectrum of disease caused by Parvovirus B19
FIFTH DISEASE OR erythema infectiosum OR “slapped cheek syndrome”.
Prodrome of headache, fever, nausea
Bright red rash on cheeks (periorbital pallor)
Rash can stretch to trunk and extremities
what are examples of iron chelation regimens available for beta thalassaemia
SC desferrioxamine
Oral deferasirox
How do you manage DIC
- Treat underlying cause (usually sepsis)
- Supportive care
3, Replacement therapy (platelet transfusion for platelets, FFP for coag factors, cryoprecipitate transfusions)
Consider Protein C concentrate esp in purpura fulminans
How do you manage hereditary spherocytosis
supportive care, RBC transufion
Folic acid supplement
Consider splenectomy + encapsulated bacteria vaccine
cholecystectomy
What prophylaxis do you give for sickle cell
immunise against encapsulated organisms
Daily oral penicillin
Daily oral folic acid
Avoid triggers
How do you treat acute crisis of SCD
Oral, IV analgesia Good hydration Antibiotics for infection Oxygen if reduced sats Exchange transfusion
What management can you consider for chronic problems in sickle cell
- hydroxycarbamide (if recurrent admissions)
- splemnectomy + imms against encapsulated bacteria
- BM transplant if sevre
