Haematology Flashcards
Haemoglobin types by age
Newborn: HbF predominant, with HbA and HbA2
Children >1y: HbA prominent with HbA2 (2%)
High Hbf within first year means some children are asymptomatic of disease .e.g. sickle cells
Haematological values at birth and infancy
Hb at birth 140-215g/L Hb 2m: 100g/L Preterm 4-8w: 65-90g/L Blood volume term infant 80ml/Kg Preterm blood volume 100ml/Kg Folic acid, iron and vit B12 stores depleted by 2-4m in preterm infants WCC neonates: 10-25 x 10^9/L Platelet count at birth 150-400 x 10^9/L
Definition of anaemia
Neonate: Hb<140g/L
1m-12m: Hb<100g/L
1y-12y: Hb <110g/L
Mechanisms of anaemia
Reduced red cell production -Red Cell aplasia -Ineffective erythropoiesis Increased red cell destruction -Red cell membrane disorder -Red cell enzyme disorder -Haemaglobinopathies -Immune Blood loss (uncommon in children) -Feto-maternal bleeding -Chronic GI blood loss -Inherited bleeding disorder
Causes Red cell Aplasia
Parvovirus B19 infection (only in children with Dx haemolytic anaemia) Diamond Backfan Anaemia Transient eryhtoblastopenia of childhood Fanconi anaemia Aplastic anaemia Leukaemia
Causes Ineffective erythropoiesis
Iron deficiency Folic acid deficiency Chronic renal failure Chronic inflammation Myelodysplasia Lead poisoning
Causes increase haemolysis
RBC membrane disorder: Hereditory spherocytosis
RBC enzyme deficiency: G6PD deficiency
Haemoglobinopathy: thalassaemia, sickle cell
Immune: haemolytic disease of the newborn, autoimmune haemolytic anaemia
Diagnosis Ineffective erythropoeisis
Normal reticulocyte count
Abnormal MCV
-Low in iron deficiency
-Raised in folic acid deficiency
Causes iron deficiency
Inadequate iron intake (common in infants)
Malabsoprtion
Blood loss
Iron intake requirements
1y: 8mg/day
Adult female: 15mg/day
Adult male: 9mg/day
Iron sources in childhood
Breast milk (low content highly available) Infant formula (supplemented iron) Cows milk (high content poor absorption) Dietary: solids introduced at weaning -cereals supplemented (poor absorption)
Diagnostic features on blood film
Spherocytes: hereditory spherocytosis
Sickle cells/target cells: sickle cell disease
Hypochromic/microcytic red cells: thalassaemia, iron deficiency, anaemia of chronic disease
Hb HPLC diagnostic features
Sickle cell: HbS and no HbA
Beta thalassaemia major: only HbF present
Beta thalassaemia trait: Increase HbA2
Alpha thalassaemia trait: HPLC normal
Inhibition of iron absorption
Tanin in tea
Phytates in high fibre food
Clinical features iron deficiency anaemia
Typically asymptomatic until 60g/L
Tire easily
Feed slowly
Pale- conjunctivae, tongue, palmar creases
Pica: inappropriate eating non-food materials
Behaviour and intellectual decline
Diagnosis iron deficiency
Microcytic hypochromic anaemia
-low MCV, low MCH
Low serum ferritin
Mx Iron deficiency
Dietary advice Supplementation with oral iron -Syntron (sodium iron edetate) -Nifarex (polysccharide iron complex) -Continues until Hb normal + 3m Normal Hb rise with supplements ~ 10g/L/week
Diagnosis of Red cell aplasia
Low reticulocyte count Low Hb Normal bilirubin Negative Coombs test Absent red cell precursors on bone marrow
Features Diamond-Backfan anaemia
Rare Family history (20%) Present at 2-3m or birth Symptoms of anaemia Associated with congenital abnormality .e.g. short stature, abnormal thumbs
Mx Diamond Backfan anaemia
Oral steroids
Monthly rbc transfusions (steroid unresponsive)
Stem cell transplantation
Features transient erythroblastopenia of childhood
Similar features to Diamond Backfan anaemia
Always recovers
Usually within several weeks
Features of increased haemolysis
Anaemia Hepatomegaly Splenomegaly Increased unconjugate bilirubin Excess urinary urobilinogen
Diagnosis haemolysis
Raised reticulocyte count Polychromasia on blood film (lilac colour on stained film) unconjugated bilirubinaemia Increased urinary urobilinogen Abnormal rbc appearance on film Positive direct antiglobulin test increased rbc precursors in bone marrow
Features hereditory spherocytosis
Jaundice
Anaemia
Mild-moderate splenomegaly
Aplstic crisis: transient 2-4w with parvovirus B19
Gallstones: associated with increased bilirubin
Diagnosis hereditory spherocytosis
Blood film usually diagnostic
Specific tests: dye binding assay, osmotic fragility
dDx spherocytes on film: autoimmune haemolytic anaemia (excluded by antibody test)
Genetics hereditory spherocytosis
Mutation in rbc membrane proteins
-spectrin, ankyrin, band 3
Loss of membrane on passage through spleen
Reduction in SA:V
Spheroidal cells destroyed in microvasculature of spleen
Mx hereditory spherocytosis
Oral folic acid (raised requirement)
Splenectomy (poor growth or symptomatic anaemia)
-HiB, Men C and Strep immunisations
Lifelong oral daily penicillin prophylaxis
Cholecystectomy if symptomatic gallstones
Mx Aplastic crisis
1-2 blood transfusions over 3-4w period
Features G6PD
Neonatal jaundice (within 3d) Acute haemolysis -infection -medications -fava/braod beans -naphthalene in mothballs
Drugs to avoid in G6PD
Antimalarias .e.g. primaquine, quinine, chloroquine
Anitbiotics .e.g. sulphonamides, quinolones, nitrofurantoin
Analgaesics .e.g. aspirin
Pathology G6PD
Rate limiting enzyme in pentose phophate pathway
Essential for preventing oxidative damage
RBC susceptible to oxidant-induced hymolysis
X linked
Presentation of haemolysis in G6PD
Fever Malaise Abdo pain Passage of dark urine (Hb and urobilinogen) Rapid Hb drop (<50g/L within 24-48h)
Diagnosis of G6PD
G6PD activity in RBS
May be misleadingly elevated during haemolytic crisis due to reticulocyte conc.
Repeat assay required after haemolytic episode
Mx G6PD
Safety net parents re recognition of haemolysis
Avoidance of precipitants
Transfusion rarely required
Features of sickle cell
Anaemia
Infection (associated with hyposplenism): Hib, penomoccoci, salmonella osteomyelitis
Painful crisis: vaso-occlusive, typically limbs and spine
-precipitated by excercise, stress, infection, cold, dehydration, hypoxia
Acute anaemia
Priapism
Splenomegaly
Sickle cell painful crisis types
Hand-foot syndrome: dactylitis
Acute chest syndrome
Avascular necrosis of femoral head
Long term Cx sickle cell
Short stature Delayed puberty Stroke and cognitive problems Adenotonsillar hypertrophy (sleep apnoea) Cardiac enlargement Heart failure Renal dysfunction Pigment gallstones (increased bile production) Leg ulcers Psychosocial problems
Features sequestration crises
Sudden splenic or hepatic enlargement
Abdominal pain
Circulatory collapse
Accumulated sickle cells in spleen
Types of sickle cell disease
Sickle cell anaemia: homozygous HbS
HbSc disease: no HbA and no normal beta globulin
Sickle beta thalassaemia: no HbA or beta globulin
Sickle cell carriers: 40% HbS haemoglobin
Pathogenesis sickle cell
HbS polymerises with rbc forming rigid tubularspiral bodies
Deformation of rbc into sickle shape
Reduced cell lifespan
trapped in microvasculature causing occusion and ischaemia
Mx Sickle cell
Infection prophylaxis -immunisation -daily oral penicillin Daily folic acid Reduce precipitates of crisis Hdroxycaramide (increased HbF production) Bone marrow transplant
Mx acute sickle cell crisis
Oral or IV analgaesia Good hydration Abx if infection Oxygen if reduced sats Exchange transfusion for acute chest syndrome, stroke, and priapism
Prognosis sickle cell
Premature death ~ 40y
Mortality rate in children 3% due to infection
Features Haemoglobin SC disease
Nearly normal Hb
Fewer painful crises
Proliferative Retinopathy in adolescence (periodically checked)
Osteonecrosis of hips and shoulders
Sickle cell trait
Assyptomatic
Risk with general anaesthetic (sickling possible in low oxygen tension)
Types beta thalassaemia
Major: HbA cannot be produced
Intermedia: small amount of HbA and large amount of HbF
Trait: assymptomatic
Features beta thalassaemia
Severe anaemia Jaundice Faltering growth/growth failure Extramedullary haemoppoiesis (without transfusion) -hepatosplenomegaly -bone marrow expansion -maxiallry overgrowth and skull bossing
Mx Beta thalassaemia
Transfusion dependant by 3-6m
-lifelong monthly transfusion
Iron cehlation .e.g. subcut desferrioxamine, oral deferasirox from 2-3y
Bone marrow transplantation
Complications regular transfusions
Iron deposition -cardiomyopathy -liver cirrosis -diabetes -impaired growth and sexual maturation -hyperpigmentation of skin Antibody formation Infection Venous access difficulty requiring portacath
Alpha thalassaemia types
Major (Hb barts hydrops fetalis): midtrimester fetal hydrops fatal in utero/hours postnatally
-possibility of monthly intrauterine tranfusion
HbH disease: 3 genes effected, mild/moderate anaemia
Trait: assymptomatic
Causes of anaemia in the newborn
Congenital B19 parovirus infection
Congenital red cell aplasia
Haemolytic anaemias
Blood loss
Causes of anaemia of prematuriry
Inadequate erythropoeitin production
Reduced rbc lifespan
Frequent blood sampling
Iron/folic acid deficiency (2-3m)
Causes blood loss in newborn
Feto-maternal haemorrhage
Twin-twin transfusion
Blood loss during delivery .e.g. abruption
Features Fanconi anaemia
Aplastic anaemia
AR mutation in FANC gene
Associated congenital abnormality .e.g. short stature, abnormal radii and thumbs, renal malformation, micropthalmia, pigmented skin lesions
Bone marrow failure apparent 5-6y
Ix Fanconi Anaemia
Normal blood count
Chromosomal breakage of peripheral blood lymphocytes
Cx Fanconi anaemia
Bone marrow failure
Transformation to acute leukaemia
Features Schwachman Diamond Syndrome
AR SBDS gene mutation Bone marrow failure Pancreatic exocrine failure Skeletal abnormality Isolate neutropenia Mild pancytopenia Risk of transformation to acute leukaemia
Screening tests in coagulopathy
FBC and blood film
Prothrombin time (Factors II, V, VII, X)
APTT (Factors II, V, VIII, IX, X, XI, XII)
50:50 mix with plasma in prolonged APTT and PT distinguishes factor deficiency or inhibitor prescence
Thrombin time (fibrinogen)
Quantative fibrinogen assay
D-dimers (fibrinogen degradation products)
Biochemical screen, renal and liver function tests
Features haemophilia
Recurrent spontaneous bleeding into joints and muscles
Present when starting to walk or crawl
Neonatal intracranial haemorrhage
Bleeding postcircumscision
Prolonged oozing from heel stick and venepuncture sites
Severity and factor VIII
<1% - spontaneous
1-5%- bleeds on minor trauma
>5-40% - bleeds after surgery
Mx Haemophilia
Factor VIII haemophilia A -Desmopressin A in mild haemophilia A Factor IX haemophilia B Circulating level to 30% Major surgery/big bleeds: -100% circulating level -maintenance 30-50% for 2w Avoid: IM injections, aspirin and NSAIDs
Cx treatments for haemophilia
Inhibitors: reduce or inhibit effect of treatment, may be amenable to immune tolerance induction
Transfusion transmitted infections
Vascular access difficulty
Features von Willebrand disease
Bruising
Excessive prolonged bleeding following surgery
Mucosal bleeding .e.g. epistaxis, menorrhagia
Mx von Willbrand disease
Desmopressin in type 1
-caution in <1y associated hyponatraemia and seizures
Plasma derived FVIII
Acquired disorders of coagulation
Haemorrhagic disease of the newborn (Vit K deficiency)
Liver disease
ITP
DIC
Causes of vitamin K deficiency
Inadequate intake
Malabsorption .e.g. coeliac, cystic fibrosis, obstructive jaundic
Antagonists .e.g. warfarin
Platelet counts and bleeding
Platelet count <150 x 10^9/L
Severe (spontaneous bleeding) <20
Moderate (bleeding in trauma or surgery) 20-50
Mild (major op or severe trauma ) 50-150
Presentation thrombocytopenia
Mild: -Bruising -Petechiae -Purpura -Mucosal bleeding Severe: -GI haemorrgae -Haematuria -Intracranial bleeding
Causes of purpura
Increased platelet destruction .e.g. SLE, ITP, HUS, DIC
Impaired platelet production .e.g. Fanconi anaemia, Wiskott-Aldrich, aplastic anaemia, marrow infiltration
Platelet dysfunction .e.g. uraemia
Vascular disoders .e.g. scurvy, meningitis, vasculitis
Features ITP
Antiplatlet IgG autoantibodies Megakaryocyte increase in bone marrow 2-10y 1-2w post viral infection Petechiae Purpura Superficial brusing epistaxis
Mx ITP
Self limiting within 6-8w Often no therapy required Treat if major bleeding -oral prednisolone -IV anti-D -IV immunoglobulin Transfusion in life threatening haemorrhage Avoid trauma and contact sports
Features chronic ITP
Platelet count low 6m after diagnosis (20%)
Mx Chronic ITP
Mainly supportive Rituximab: B lymphocyte monoclonal antibody Thrombopoietic growth factors Splenectomy (if drug failure) SLE screening
Features DIC
Due to severe sepsis or shock and circulatory collapse
Bruising
Purpura
Haemorrhage
Ix DIC
Thrombocytopneia Low fibrinogen Prolonged PT and APTT Raise fibrinogen degradation productions and D-dimers Microangiopathic haemolytic anaemia Reduction in protein C,S and antithombin
Mx DIC
Underlying cause
FFP, cryoprecipitate and platelets
Antithrombin and protein C concentrates
Pathology DIC
Coagulation pathway activation leading to diffuse fibrin deposition
Consumption of coagulation factors and platelets
Initiated through tissue factor pathways
Acquired disorders thrombosis
Catheter related thrombosis DIC Hypernatraemia Polycythaemia Malignancy SLE Persistent antiphospholipid antibody syndrome
Congenital prothrombotic disorders
Protein C deficiency Protein S deficiency Antithrombin deficiency Factor V leiden (resistant to protein C degradation) Prothrombin gene G20210A mutation
Indication for thrombosis screening
Unanticipated or extensive venous thrombosis
Ischaemic skin lesions
Neonatal purpura fulminans (or +ve fHx of)
Screening thrombophilia
Protein S Assay Protein C Assay Antithrombin Assay PCR factor V leiden Prothrombin gene mutation PCR
Features HSP purpura
lesiosn confined to buttocks, legs, arms
Swollen painful knees and ankles
Abdominal paid
Haematuria
Features septic purpura
Meningococcal or viral
Fever
Speticaemia
+ve glass test
Features leukaemia thrombocytopenia
Malaise infection pallor hepatosplenomegaly lymphadenopathy low Hb blasts on film
