Haematology Flashcards
what are the findings on Hb electrophoresis for
sickle cell
B thalassaemia trait
B thalassaemia major
a thalassamia trait
sickle cell - HbS present
B thalassaemia trait - HbA2 increased
B thalassaemia major - HbF present
a thalassamia trait - normal
what are the normal Hb ranges in paeds?
o Neonate <140g/K
- anaemian is if its 90g/L
o 1 month → 1 year <100g/L
o 1 year → 12 year <110g/L
How does G6PD disease present?
pattern of inhertiance? epidemiology?
rx: avoid triggers
Common/ High prevalence (10–20%) in: meditarranean, middle eastern, Far East, Central African
X-linked
Triggered by; Infection, Fava beans, Napthalene,
Drugs (antimalarials, antibiotics, high dose aspirin)
Neonatal jaundice
Intermittent intravascular haemolysis
+ Fever, malaise
Dark urine, splenomegaly
Rx: avoid triggers, treat jaundice
• Folic acid supp
± transfusions rarely required ± splenectomy
What would ivx show in G6PD disease?
- Definitive diagnosis by measuring G6PD enzyme activity in RBCs
- Also ↑reticulocyte count, macrocytosis
- Heinz bodies, bite cells
- Pts have normal blood picture between episodes
what is the aetiology, presentation and mx of Phenylketonuria?
- Either a deficiency of phenylalanine hydroxylase (classic PKU)* that leads to LESS breakdown of amino acid phenylalanine = build up to toxic levels.
- If untreated → present with developmental delay at 6-12 months. intellectual disability, seizures, behavioral problems, and mental disorders.
Musty odour due to phenylacetic acid metabolite
- RF: fair-haired, blue eyed, eczema and seizures
- Treatment: restrict dietary phenylalanine (lifelong) and monitor blood plasma levels regularly
- enzyme supplements
- nutrition supplements
- or in synthesis or recycling of its biopterin cofactor.
what are some of the dietary measures in PKU?
The diet requires restricting or eliminating foods high in Phe, such as soybeans, egg whites, shrimp, chicken breast, spirulina, watercress, fish, nuts, crayfish, lobster, tuna, turkey, legumes, and lowfat cottage cheese.
Starchy foods, such as potatoes and corn are generally acceptable in controlled amounts
FDA has approved an enzyme substitute called pegvaliase which metabolizes phenylalanine. It is for adults who are poorly managed on other treatments.
what is the aetiology, presentation and mx of MCADD?
- Auto recessive disorder of fatty acid metabolism
- Unable to metabolise fatty acids beyond medium chain and into acetyl-CoA
• Gluconeogenesis is inhibited – body cannot metabolise fat
The disorder is characterized by hypoglycemia and sudden death without timely intervention, most often brought on by periods of fasting or vomiting.
Vomiting, lethargy, seizures = classic
Coma and hypoketotic hypoglycemia, often triggered by minor infection
Can present with liver disease - hepatomegaly
Common cause of SIDS (<2y) (preceded by minor illness)
• metabolic acidosis
Ivx:
• Guthrie
• Low glucose in response to fasting
- Urinalysis – +ve medium-chain dicarboxylic aciduria and absent ketones
- Mass spectrometry - lots of medium-chain acids
- Management → avoid long periods not eating/fasting, high calorie diet, daily carnitine supplements
What is homocystinuria?
aetiology and presentation?
A metabolic disorder that stops the body from breaking down the amino acid Homocysteine due to deficiency of cystathionine synthetase deficiency
Caused by gene mutations - Autosomal recessive
Inability to break down homocysteine = toxic build up and Nervous system damage
Presentation:
Children may have mild sx but worsens with age
Weak bones,
Tall & long thin arms n legs (Marfanoid appearance)
Near sightedness / diminished visual acuity
Spine curvature (scoliosis) + osteoporosis
Pale skin + hair
chest deformity
Developmental delay
slow weight gain
Progressive learning difficulty, psych disorders and Seizures/convulsions
thromboembolic episodes: strroke/MI
How is homocystinuria ivx ?
Ivx:
In-utero - amniocentesis (if FH)
Physical exam - long fingers etc
Paeds ophtal referral - Eye exam - Disclocated eye lenses (subluxation of lens) - later
Labs:
Increased serum and urine homocysteine and methionine levels
How is homocystinuria treated and the prognosis ?
Mx:
1. 50% respond to high dose of co-enzyme pyridoxine (vit B6)
- If not;
A. treat with low-methionine diet (no eggs, soy, dairy, nuts and dairy)
B. supplements with cysteine and folate (+betaine)
C. Babies will need special formula, + small amount of breastmilk - Psych input as they may feel left out eg at parties etc
Prognosis if Untreated:
75% die by 30 from - thrombotic complications eg MI
What is MAPLE SYRUP URINE DISEASE?
aetiology and presentation?
- Autosomal-recessive, mutation in more than 3 genes
- Loss of alpha-keto acid dehydrogenase
→ inability to breakdown some branched-chain amino acids – leucine, isoleucine, valine
- Leading to accumulation of amino acids -> encephalopathy and progressive neurodegeneration
- Maple syrup odor in cerumen (earwax) at 12-24 hours after birth
• Poor feeding, vomiting, poor weight gain, neuro signs
- Sleepiness, irritable
- coma, brain damage (late)
- Ketosis and maple syrup odor of urine
• Developmental + psychomotor delay
What is MAPLE SYRUP URINE DISEASE?
ivx and mx?
IX:
• Ketonuria
• Increased branched chain amino acids in plasma
• Increased urine pyruvate, lactate, BCAAs
mehtylvaleric acid present
Management:
• Dietary leucine restriction - proteins, dairy restriction
• Limited breast milk
- High calories BCAA-free formula - contains nutrients they need to live
- Thiamine supplements
• Careful supplements with isoleucine and valine - as needed for growth
- Frequent growth + development checks and blood tests
- +/- liver transplant or haemodialysis - if serious
what is the aetiology, presentation and mx of ISOVALERIC ACIDEMIA
- Body cannot catabolise leucine into isovaleric acid
- Leads to buildup of leucine in blood and urine
• they smell like sweaty feet
decreased feeding, decreased weight, lethargy and metabolic crisis
lack of energy
vomiting
irritability
breathing difficulties
• Treat with low protein diet with decreased leucine
Supplements: L-carnitine or glycine - can be given especially in acute episodes
which metabolic disorder may present with
macrocephaly, hypotonia, increased risk of subdural, metabolic crisis?
GLUTARIC ACIDURIA type 1
Treat with low protein diet and L-carnitine
what are the treatment options for iron deficiency in kids?
Defined as Once Hb is <6-7g/dl
Usually give as Oral solutions:
Sodium Feredetate - market name Sytron
Ironorm drops
Take until normal Hb, then continue for a minimum of 3 months after
what will ivx show in Haemophilia?
APTT: prolonged
if so order:
1. Mixing studies - will come out normal
Factor 8/9 assay : severity based on amount of factor present/absent
PT: Normal
Bleeding time: normal
X-ray joint - if suspecting haemarthrosis
others:
vWD assay - normal
How do we mx haemophilia?
Prophylactic:
Mild Haemophilia A
1st • Desmopressin for (stimulates F8 and VWF release) + Tranexamic acid
Severe HA (eg the get spontaneous bleeding): 1st • Prophylactic injection of factor 8 replacement - give these 3 times a week or more depending on severity
Mild Haemophilia B
1st - Prophylactic factor 9 replacement until sx stopped
+ Tranexamic acid
Central venous access device (implantable port) – allows factor replacement to be done at home
If actively bleeding:
o Prompt IV infusion with F8/9 concentrate
o Raising circulating factor level to 30% normal is enough to treat minor bleeds or simple joint bleeds
o Major/life-threatening bleeds require 100% → then maintain at 30% for 2 weeks to prevent 2ndary haemorrhage – give as a regular/continuous infusion
+ Analgesia (paracetamol or codeine) - no nsaids!!
MDT: Physio, Ortho
what are inhibitors in Haemophilia?
when patients have been infusion factor for a while,
the body can manufacture inhibitors which serve to break down the injected factor concentrate really quickly.
when these inhibitors are present, we must take this into account for the management:
Give Bypassing agents including recombinant factor VIIa or factor VIII inhibitor bypassing fraction INSTEAD of normal factor infusion
Whta is the aetiology and presentatoin of IDIOPATHIC THROMBOCYTOPENIC PURPURA - ITP
Aka Immune TP
Usually destruction of platelets by anti-platelet IgG autoantibodies
• Most common cause of childhood thrombocytopenia
Acute form: • 2-10y, onset often 2 weeks post-viral infection • Short history (days or weeks) o Petechiae o Purpura o ± superficial bruising o Menorrhagia
- Can cause epistaxis or mucosal bleeding but profuse bleeding is uncommon
- Intracranial bleeding is a rare but severe complication
Chronic form:
- sx last 6 months -> years
- more common in adults
what do ivx show in ITP?
Dx of exclusion
Bloods:
Low Platelet count <150x109/L
- In chronic ITP - still low 6 months after diagnosis
Blood film
Possible increase in megakaryocytes
atypical clinical features (Anaemia, neutropenia, hepatosplenomegaly, marked lymphadenopathy) should prompt a bone marrow examination to exclude acute leukaemia or aplastic anaemia
How do we mx ITP?
- In 80% children, disease is acute, benign and self-limiting, usually remitting spontaneously within 6-8 weeks
- If major bleeding or persistent minor bleeding →
- Prednisolone,
2.IVIG - works faster than pred (24hrs)
Others: - IV anti-D (Rh) - stops spleen from destoyinf platelets - must be Rh +ve
• Advise child to avoid trauma/contact sports whilst recovering
Chronic:
Supportive care, Rituximab (allows antiplatelt antibodies to be made), Splenectomy (stop pooling and destruction of platelets)
how does leukaemia present?
- Peak at 2-5 years
- Insidious presentation – malaise, anorexia, night sweats
- BM infiltration → anaemia (pallor), neutropenia (infection), thrombocytopenia (bruising, petechiae, epistaxis), bone pain
- Reticulo-endothelial infiltration → hepatosplenomegaly
- Other organ infiltration (usually with relapse) → CNS → headache, nausea, vomiting, nerve palsies, testicular enlargement
how would you ivx leukaemia?
• FBC → decreased Hb, thrombocytopenia, evidence of circulating leukaemic blast cells, increased LDH
- Clotting → +/- DIC
- Check LFTs and U&Es (renal function) before chemo
• BM aspiration and biopsy → essential to confirm diagnosis
o More than 20% blasts in BM or peripheral blood
o ID immunological and cytogenic characteristics to give prognostic info – identify translocations
• Immunological phenotyping → to further subclassify ALL o Common (75%) o T cell (15%)
• CXR to identify mediastinal masses
What is invovled in the mx of leukaemia?
Prognosis?
Chemotherapy
- Induction Phase
- > Inpatient – hospital or specialist centre
- > Chemotherapy
i. Vincristine
ii. Corticosteroids (dex)
iii. Anthracyclines
iv. +/- cyclophosphamide/cytarabone - Consolidation – outpatient (months)
- Maintenance – chemo tablets – last 2-3 years
a. Usually daily 6-mercaptopurine and weekly methotrexate
+/- ABX and antifungals as infection prophylaxis
+/- steroids
+/- allopurinol as increased uric acid levels
- If Philadelphia +ve ALL → give Imatinib
- Radiotherapy used if spread to CNS or to prepare before BM transplant
- +/- stem cell transplant if no response to chemo or radio (in CNS disease)
• 80-90% completely cured
