Haematology Flashcards
Describe how haemoglobin changes during life. Why does this matter?
- Fetal development: HbF is main form. 2 alpha, 2 gamma. Higher affinity for O2.
- First year: HbF replaced by HbA (2 alpha, 2 beta) and HbA2 (2 alpha, 2 delta)
Diseases affecting beta globin chains (SCA, B thal) will not be obvious at birth, but will present during the first year of life as Hb switches
How does the FBC differ in neonates?
- Hb high -> quick fall
- WCC high
- Iron stores low (in preterm)
- Plts normal
Define anaemia in children
- Neonates: <140 g/L
- 1 month-12 months: <100 g/L
- 1-12 years: <110 g/L
Name some categories and causes of anaemia in children
Decreased production: bone marrow failure, Fe deficiency, folate deficiency, chronic inflammation, red cell aplasia
Increased breakdown: haemolytic anaemia eg. SCA, spherocytosis, G6PD deficiency, thalassaemia, HUS
Loss: haemorrhage, bleeding disorders causing chronic bleeding
What are some causes of Fe deficiency in childhood? What are the features (clinical and haem)?
-Poor diet eg. milk only
-Malabsorption
-Blood loss
Clinical features: pallor, fatigue, SOB, failure to thrive, pica
Haematological features: low Hb, low MCV, low ferritin
When does anaemia become symptomatic in children?
Not until Hb <60-70 g/L eg. VERY low
Describe the management of iron deficiency in children
- Conservative: dietary advice eg. dark leafy greens, red meat. Take with vitamin C eg tomatoes
- Medical: supplementation (oral ferrous sulphate). Can take with food to minimise GI upset.
-Monitor response to treatment: FBC 2-4 weeks after starting treatment -> again 2-4 months later. Continue for 3 months when normal to maintain stores.
Name some causes of red cell aplasia in children
- Parvovirus B19: in children with haemoglobinopathy
- Diamond-Blackfan anaemia: congenital
- Transient erythroblastopenia of childhood: viral trigger
How would you approach diagnosing a child with anaemia?
- Film: haemolysis? eg. SCA, spherocytosis, G6PDD, etc
- Haematinics: Fe/folate/B12 deficiency
- Reticulocyte count: low in aplasia, ^ in haemolysis
- DAT test: autoimmune cause
- Bilirubin, haptoglobin: ^ in haemolysis
- Dye binding test, osmotic fragility test
- Bone marrow biopsy
Name some causes of haemolytic anaemia in children
Neonates: Rh disease, ABO incompatibility Mostly due to intrinsic abnormalities: -G6PD deficiency -Hereditary spherocytosis -Sickle cell -Thalassaemia Immune-mediated is UNCOMMON
Describe the pathophysiology of hereditary spherocytosis
Autosomal dominant condition
Mutation in membrane proteins eg. spectrin/ankyrin
-> membrane defects -> haemolysis in spleen
What tests can be used to diagnose hereditary spherocytosis?
FBC and blood film
Dye binding test
Osmotic fragility test
What is the management of hereditary spherocytosis?
Supportive care
Daily folic acid supplements (to support turnover)
Daily pneumococcal prophylaxis (oral penicillin)
Splenectomy if needed
RBC transfusion if severely anaemic eg. parvovirus
Describe the pathophysiology of G6PD deficiency. How is it diagnosed?
X-linked defect in enzyme in the pentose phosphate shuttle
-> if oxidative damage, not fixed
-> destruction
Causes of oxidative damage include: infection, antimalarials (eg quinines), sulfonamides, quinolones, nitrofurantoin, naphthalene, fava beans
Diagnosis: between episodes: G6PD activity
Describe the pathophysiology of sickle cell disease
AR point mutation in codon 6 of the beta globin gene
GAG -> GTG means glutamine -> valine
Causes abnormal beta globin (HbS)
Sickling of cells when not oxygenated -> occlusion -> haemolysis, painful crises, strokes, etc
What are the different types of sickle cell disease? Which types have HbA?
- Sickle cell anaemia: HbSS -> no HbA
- HbSC: one HbS, one HbC (different mut) -> no HbA
- Sickle beta thal: one HbS, one beta thal -> no HbA
- Sickle cell trait: HbS (1/2 beta chains affected)
What can trigger a sickle cell crisis?
Hypoxia
Cold
Dehydration
Infection
Name some features of sickle cell anaemia
- Anaemia: fatigue, pallor
- Infection: increased risk with encapsulated bacteria
- Painful crises: hand-foot syndrome (dactylitis), acute chest syndrome
- Splenic sequestration -> hyposplenism
- Aplastic crisis: infection with parvovirus B19
- Priapism
- Long term: poor growth, heart failure, neurological damage/stroke
Describe the management of sickle cell anaemia
- Prevention: lifestyle (eg. stay warm, hydrated). High dose folic acid, vaccination, daily penicillin. Malarial prophylaxis if travelling
- Medical management: hydroxycarbamide (^ HbF), hydroxyurea, splenectomy, BMT.
- Acute crises: admit. Supportive eg. hydrate, warm, oxygenate. Pain relief (opioid + anti-emetic and laxative) Treat infection. Exchange transfusion if acute chest/priapism. Blood transfusion if severely anaemic/aplastic crisis.
Describe the pathophysiology of thalassaemias + types.
Alpha thal: defect in alpha globin chain. 4 genes.
- 2-3/4 functional: asymp/mild anaemia similar to Fe deficiency
- 1/4 functional: HbH. Mild-mod anaemia. May need transfusions
- 0 functional: Hb Barts, causes fetal hydrops. Fatal/ requires intrauterine transfusion.
Beta thal: defect in beta globin. 2 genes.
- Trait: asymp/mild anaemia.
- Intermedia: mild-mod anaemia
- Major: no HbA. Severe anaemia from infancy, requiring regular transfusions/BMT.
How does thalassaemia present?
- Anaemia (microcytic)
- Jaundice
- Extramedullary haematopoiesis: skull bossing, maxillary overgrowth, hepatomegaly
- Splenomegaly
What are some effects of repeated blood transfusions? What is the treatment?
-Iron deposition: pancreatic insufficiency, cardiomyopathy, cirrhosis, hyperpigmentation
-Risk of infection, allo-antibody formation
Important to do iron chelation therapy for children with repeated transfusions eg. desferrioxamine
How is thalassaemia diagnosed?
- Microcytic hypochromic anaemia
- Normal/high reticulocytes
- Hb high performance liquid chromatography (HPLC) or Hb electrophoresis (raised HbA2)
How is sickle cell anaemia diagnosed?
- Screening eg. Guthrie
- Microcytic hypochromic anaemia
- Normal/high reticulocytes
- Blood film
- Hb electrophoresis/HPLC
Name some causes of bone marrow failure in children. How does it present?
-Idiopathic
-Drugs: sulphonamides, chemotherapy
-Infection: hepatitis
Presents with deficiency in all 3 lineages:
-Anaemia with low reticulocytes
-Thrombocytopenia with bleeding, bruising
-Neutropenia with infections
Name some different bleeding disorders and the causes
- Haemophilia A/B: deficiency in FVIII/FIX -> secondary haemostasis defect
- vWD: deficiency in vWF -> primary haemostasis defect
- Drugs eg. anticoagulants
- Liver disease: deficiency in clotting factors
- ITP, DIC
Describe the pathophysiology of haemophilia. How does it present?
- X linked recessive condition
- Mutation in gene coding FVIII (A) or FIX (B)
- Leads to defects in secondary haemostasis
- Presents with: bruising, haemarthrosis, prolonged bleeding from larger wounds. Usually presents when children learn to walk/crawl
Describe the management of haemophilias
Conservative: avoid contact sports, injuries. No IM injections. No aspirin/NSAIDs
Medical: MDT approach with paeds, ortho, physio
- Acute bleeding: recombinant FVIII/FIX concentrate + antifibronolytics (TXA)
- Give prophylactic doses if severe, or replacement therapy if low levels as needed
- DDAVP can be used in mild Haem A to ^ vWF/FVIII
Describe the pathophysiology of vWD. How does it present?
-Several types, include deficiency of vWF +/- FVIII
-Defective platelet plug formation
-Defect of primary haemostasis
Presents with: bruising, prolonged bleeding, bleeding from gums/mucous membranes.
Describe the management of vWD
Conservative: avoid IM injections, NSAIDs/aspirin
- Mild Type 1: DDAVP- stimulates vWF and FVIII
- Severe: FVIII concentrate
How would you investigate bleeding disorders?
Initial tests:
- FBC and film
- LFTs
- Clotting screen: APTT, PT, fibrinogen
- D dimer
Further testing:
- FVIII and FIX levels
- Bone marrow biopsy
- Platelet function tests, vWF antigen, etc.
Define thrombocytopenia. Name some causes
Platelets <150 x 10^9 /L
- Malignancy: ALL
- ITP
- TTP
- HUS
- DIC
- SLE
What is the platelet count in vWD?
Usually normal
Describe the pathophysiology of ITP
- Most common cause of thrombocytopenia in kids
- Usually 2-10 years, weeks after viral infection
- IgG antibodies to platelets -> destruction
- Increase in megakaryocytes in bone marrow
How does ITP present? How is it diagnosed?
- 1-2 weeks after viral infection -> thrombocytopenia eg. petechiae, purpura, bleeding from mucous membranes
- Self-limiting, resolves in 6-8 weeks
- No other blood cell dyscrasias, no clinical signs (hepatosplenomegaly, lymphadenopathy)
- Dx: rule out other causes. FBC and film, clotting, LFTs, D dimer, HIV serology in high risk, SLE antibodies, etc. Consider bone marrow biopsy if not normal findings to rule out leukemia
Describe the management of ITP
- Life threatening or severe bleeding: platelet transfusion, IVIG, steroids
- Mild bleeding: manage at home, safety net
- Moderate bleeding: steroids, IVIG
What is DIC? When does it occur? How is it diagnosed?
Disseminated intravascular coagulation: occurs when there is increased consumption of platelets and clotting factors -> lots of small thrombi -> bleeding due to overconsumption
Can occur in sepsis, shock, trauma, burns
Usually have impairment in all clotting parameters eg. prolonged PT and APTT, low platelets, low fibrinogen, high D dimer
What can cause thrombosis in children?
Uncommon, usually due to inherited thrombophilia
eg. Protein C/S deficiency, Factor V Leiden
Also DIC, malignancy
Name some causes of bruising in children
Bruising: -Accidental injury -NAI/abuse -Malignancy -Haemophilia Purpura/petechiae: -vWD -HSP -Meningococcal sepsis -ITP
A mother brings in her 4 year old son concerned over some new bruising. What are some differentials, and what do you want to know?
- DDx: accidental injury, NAI, malignancy, haemophilia, sepsis, ITP, HUS, HSP, etc
- Onset, progression
- Describe bruising pattern, size (bruising or purpura), swollen joints
- Any explanation? Trauma? Rough playing?
- General health: weight loss, fatigue, fever, anorexia, swellings
- Anaemia screen: SOB, pallor
- Infections
- PMH including bleeding problems especially after vaccination*, DHx, allergies
- Immunisations, development screen
- FHx of bleeding disorders
- Social: changes at home, new people around, healthy relationships, DV, alcohol/drugs, social worker
