Ch 22 - Haem disorders Flashcards
By which point should all the HbF be converted to HbA?
6 months
Define anaemia - give vaules for neonates/ children
Low Hb Neonate
IDA: causes (3), iron sources (3)
inadequate intake (delay in introduction of mixed feeding beyond 6 months) malabsorption blood loss Iron sources - breast milk; low iron but high absorption, supplemented formula, cow’s milk; high iron but low absorption, solids at weaning
IDA: features (4), Ix (1), management (2)
lethargy, weight loss, FTT, poor feeding, pallor, Pica - inappropriate eating of non-food material e.g. chalk Ix - blood film - hypochromic microcytic RBCs; low serum ferritin Management - dietary advice, PO iron until Hb normal
Red cell aplasia: causes (3)
Diamond-blackfan anaemia transient erythroblastopenia of childhood parvovirus B19 - only if have haemolytic anemia
Red cell aplasia: Ix (5)
low reticulocytes normal Hb, Br Negative Coombs absent erythroblasts on BM examination
What is diamond blackfant anaemia & how to manage (2)
RPS gene mutations + FH > 2-3months of age > anaemic symptoms, abnormal thumbs > oral steroids +/- monthly blood transfusions
transient erythroblastopenia of childhood trigger (1), features (1)
Viral infection > same features as DBA - but no RPS mutations or anomalies & always recovers
hereditary spherocytosis: what is it?
autsomal dom mutations in genes relating to membrane proteins - spectrin/ankyrin > causes sphere shape Sphere shape & lack of these proteins > inflexible + more prone to rupture So taken to spleen for haemolysis > haemolytic anaemia
hereditary spherocytosis: features (4)
FH jaundice anaemia splenomegaly aplastic crisis gallstones
hereditary spherocytosis: Ix (4)
Blood film > spherocytes Unconjugated hyperbilirubinaemia Osmotic fragility test Coombs -ve
Management of hereditary spherocytosis (3)
Oral folic acid splenectomy aplastic crisis - blood transfusions
G6PD deficiency: definition, features (6), Ix (2), management (1)
D - X-linked def in G6PD enzyme. Mediterranean/middle east F - precipitated by flava beans, dugs e.g. nitrofurantoin, aspirin, quinines, fever malaise, increased free plasma Hb, decreased haptoglobins Ix - RBC G6PD acitivity M - avoid precipitants
Sickle cell disease: cause, types (4), pathogenesis
C - mutation in codon 6 of b-globin gene - AA changes from glutamine > valine - reduces charge on Hb (glutamine -ve and valine neutral)
T: HbSS - majority of Hb is HbS
HbSC - HbC is due to another mutation on B-globin gene (no normal B globin > so no HbA)
Sickle ß thalassemia - no HbA (HbS from 1 parent & ß-thalaessmia trait from another)
Sickle Trait - asymp carriers - 1 HbS & 1 normal ß-globin > 40% of Hb is S.
Pathogenesis: HbS polymerizes > Sickling of RBCs > microcirculation trapping > vaso-occlussion. Ischaemia worsens if cold, dehydrated, low pO2
SCD: Features (7)
- anaemia - lethargy, pallor, jaundice
- Infection - increased susceptiblity to encapsulated pathogens - due to hyposplenism 2ndary to microinfarction of spleen in infancy (due to sickling) (spleen produces opsonins) e.g. pneumococci, haemophillus influenza
- painful crises - vaso-occluive crises; commonly present with hand-foot syndrome: dactylitis + swelling + pain of fingers and/or feet from vaso-occlusion, acute chest syndrome - most serious vasoc-occlusive crises; may require ventilation
- acute anaemia - sudden drop in Hb due to: haemolytic crises (perhaps w. infectio) aplastic crises, sequestration crises - sudden splenomegaly + abdo pain + circulatory collapse from accumulation of sicled cells in spleen
-
Priapism
- splenomegaly
SCD: management (prophylaxis (2), acute crises (3), chronic problems (2))
Prophylactic daily oral penicillin (protects against pneumococcal) + Folic acid for increased haemolysis
Acute crises: analgesia + good hydration + O2 + exchange transfusion
chronic problems (recurrent crises): Hydroxyurea - increases HbF, BMT
ß-Thalassaemias: Types (3), features (6), Ix (3), Rx (3)
T: Major - no HbA, Intermedia - Some HbA + lots of HbF, Trait - asymp - raised HbA2 & HbF
F - severe anaemia, FTT, pallor, jaundice, bossing of skull & maxiallry growth (rare in developed countries due to transfusions), hepatosplenomegaly. Compliactions of iron overload from transfusions - cariomyopathy, DM, cirrhosis
Ix - microcytic hypochromic anaemia (often misdiagnosed as IDA), to differentiate - will see high HbA2 & normal ferritin (low in IDA)
M - Lifelong monthly transfusions, Desferrioxamine (iron chelation), BMT
a-Thalassaemia: 3 types & 2 features for each
Hb Barts/ major - all 4 alpha genes deleted - no HbA (or A2) > fetal hydrops - death inutero or few hours post natal
HbH - 3 alpha globin genes deleted - mild-moderate anaemia, sometimes transfusion dependent
a-thalassemia trait - asymp, anaemia mild or absent, may have hypochromic microcytic RBCs
Anaemia of the newborn: reduced RBC production; 2 causes, what would the Ix show (Hb, RBC, reticulocytes, Br)
- Parvovirus B19
- Diamond-Blackfan anaemia
Hb low, RBC low, reticulocytes low, Br normal
Anaemia of the newborn: haemolytic anaemia: causes (4), Ix (RBCs, reticulocytes, Br)
Main causes of haemolytic anaemias in neonates:
- immune - haemolytic disease of new born
- Hbpathies - SCD, thalassemias
- RBC membrane defects - Hereditary spherocytosis
- RBC enzyme defects - G6PD def
Ix - RBC may be spherical if membrane defect, high reticulocytes, unconjugated hyperbilirubinaemia
- if suspect immune - postive Coombs test (DAT)
Anaemia of the newborn: Blood loss causes (3), anaemia of prematurity causes (3)
Blood loss - feto-maternal haemorrhage, twin-to-twin transfusion, placental abruption. Ix - increased reticulocytes + normal Hb
anaemia of prematurity - inadequate EPO production, Fe/folic acid def, reduced RBC lifespan
Bone marrow failure syndromes: Facnconi anaemia: Defintion, features (4), Ix (2), Rx (1)
D - autosomall recessive inherited aplastic anaemia
F - short statur, renal malformations, abnormal radii/thumbs, pigmented skin lesions e.g. cafe au lait
Ix - Pancytopenia, increase chromosomal breakage of peripheral blood lymphocytes
M - SCT
NB - high risk of acute leukaemia
Shwachman-Diamond syndrome: cause, features (4)
C - autsomal recessive SBDS gene mutation (very rare), also high risk of transformation to AML
F - BM failure, pancreatic exocrine failure, skeletal abnormalities, isolated neutropenia
Haemophilia: types, features (4), Ix (2), Rx (3)
Autosomal recessive disorder: A - Factor VIII def, B- Factor IX def
Features: increased bleeding into muscles/joints, prolonged bleeding post circumcision/venepuncture, IC haemorrhage
Ix: APTT prolonged (NB APTT measures Intrinsic pathway), VIII:C or IX:C ratio low
Rx: recomb VIII or IX, avoid IM injections/ NSAIDS, DDAVP
Von Willebrand disease: vWF roles (2), features (3), Ix (1), Rx (2)
2 main roles of vWF:
- facilitates platelet adhesion to damaged endothelium
- carries factor VIII (like joey of kangaroo), protecting it from inactivation/clearance
so a vWF def results in defective plt plug formation and FVIII def.
F - bruising, prolonged post surgical bleeds, epistaxis/menorrhagia
Ix - low FVIII
Rx - type 1- DDAVP, more severe give VIII & avoid IM injections/NSAIDs
Acquired disorders of coagulation: causes (4), Vit K def - causes (3) & features (3)
C - haemorrhagic disease of newborn due to vit K def, ITP, DIC, hepatic disease
Vit K def: malabsorption - Coeliacs/CF, antagonists - warfarin, maternal anticonvulsant
F - low vit II, VII, IX, X so prolonged PT, also low Protein C/S/Z
Thrombocytopenia: causes (6)
Increased plt destruction/consumption
- Immune: ITP, SLE
- Non-immune: HUS, DIC, congenital heart disease
Impaired plt production
- congenital: Fanconi anaemia, Bernard- Soulier syndrome
- Acquired: aplastic anaemia, leukaemia
Thrombocytopenia: Platelet ranges for severe, moderate & mild thrombocytopenia. 4 features of Thrombocytopenia
Severe: <20 - spontaneous bleeding
Moderate: 20-50 - bleeding only after trauma
Mild: 50-150 - bleeding only after major trauma/operation
F - petechiae, purpura, mucosal bleeds, bruising
ITP: Features (4), Ix (1), Rx (3), Chronic ITP
Most common cause of thrombocytopenia in childhood - auto IgG against plts
F - usually post-viral onset > petechiae, purpura, bruising, epistaxis
Ix - diagnosis of exclusion; isolated thrombocytopenia
Rx - usually acute self limiting within 6-8 weeks, if need to treat - oral pred, plt transfusion if severe
Chronic ITP - > 6 months; supportive treatment; Rituximab, splenectomy
DIC: defintion, causes (4), features (3), Ix (3), Rx (4)
D - coagulation pathway activation leading to diffuse fibrin deposition in the microvasculature & consumption of of coag factors + plts
C - sepsis, burns, trauma, shock
F - bruising, purpura, haemorrhage
Ix - prolonged PT & APTT, thrombocytopenia, low fibrinogen, low anti coags e.g. Protein C/S & AT
Rx - treat underlying cause, FFP, plts, antithrombin & protein C concentrates
Thrombophilas in children: give 4 inherited abnormalities
- Factor V Leiden - fV resistant to Protein C
- Def in Protein C - autosomal dominant; thrombosis predisposition when 20-30, if homozygous life-threatening
- Antithrombin def
- Portein S def
