Paediatric haematology Flashcards
What is the definition of anaemia?
A condition in which there is a deficiency of red cells or of haemoglobin in the blood to meet the body’s needs.
Normal ranges for blood in children
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What is the pathogenesis of anaemia
- Blood loss
Acute haemorrhage
Chronic gut bleeding leading to iron deficiency - Decreased Production
Nutritional deficiency e.g. iron, folate, B12, Vitamin C
Bone marrow failure e.g. DBA, TEC
Infiltration e.g. Acute Leukaemia, Neuroblastoma, Lymphoma, Osteopetrosis, Storage Disease - Increased consumption
Acquired e.g. immune, drugs, parasites, MAHA
Inherited e.g. red cell membrane defects, enzyme defects
What are the blood parameters?
Hb (always check normal range for age and sex)
Is the abnormality isolated to a single cell line or part of multiple cell lines (?BM failure, infiltration, immune, hypersplenism)
MCV (microcytic, normocytic, macrocytic)
EG of microcytic RBC conditions
Fe Deficient
Thalassaemia
Sideroblastic anaemia
Chronic disease
Lead toxicity
Copper deficiency
Haemoglobin E trait
Severe malnutrition
Macrocytic RBC
Newborn
Aplastic anaemia
Hypothyroidism
Megaloblastic anaemia
Increased erythropoiesis
Fanconi anaemia
PNH
Drugs
Post splenectomy
Normocytic RBC
Acute blood loss
Infection
Renal failure
Early Fe deficiency
Bone marrow infiltration
Haemolysis
Hyperslpensim
Drugs
What are reticulocytes?
Immature red blood cells
Typically 1% of RBC in humans
Develop in bone marrow and then circulate in blood for 1 day prior to developing into mature RBC.
Useful in establishing if marrow producing RBC effectively
What are blood films?
Very helpful in the diagnosis of anaemia
It establishes if hypochromic, microcytic, normocytic, macrocytic
It shows specific morphological abnormalities e.g. spherocytes, sickle cells, elliptocytes, schistocytes etc.
Allows review of other cell lines also e.g. platelets, white blood cells
Most common anaemia of childhood and what can cause it
Fe defi
LBW, dietary- excessive cows milk intake, occult GI bleeding (e.g. hookworm), cow’s milk intolerance
Presentation of Fe deficiency
pallor, irritability, anorexia when Hb<50, tachycardia, cardiac dilatation, murmur, poss. splenomegaly
Blood results of Fe deficiency
microcytic, hypochromic, low-normal retics
Low ferritin and serum iron, Increased TIBC
High ZPP
Treatment of Fe
ORAL THERAPY – Mainstay
Oral iron dose is 6mg/kg/day of elemental iron
reticulocytosis in 72 hr, Hgb responds at ~10g/L per wk, iron stores replenished by 3 mo
treatment is needed for 3-6 months
constipation common
commonest cause of failure is non-compliance
address cause- usually diet
What is haemolysis?
Increased RBC turnover, shortened RBC lifespan
RBCs are fragile- especially abnormal ones
Spleen filters out and breaks down senescent RBCs, and must work overtime, and can result in effective asplenia (e.g. in sickle cell)
RBC degradation products must be handled
What are the intra corpuscular causes of RBC destruction
Haemoglobin
Enzyme
Membrane
What are extra corpuscular causes of destruction of RBC
Autoimmune
Fragmentation
Hyper splenism
Plasma factors
Presentation of haemolytic anaemias
Hydrops fetalis
Neonatal hyperbilirubinaemia
Neonatal ascites
Anaemia/failure to thrive
Splenomegaly
Cholecystitis/gall stones
Hyperbilirubinaemia
Leg ulcers
Aplastic crisis
Thromboembolism
Severe anaemia at birth features
Haemolytic disease of the newborn
Bleeding
umbilical cord
internal hemorrhage
What is haemolytic disease of the newborn?
Rh negative mother previously sensitised to Rh pos cells
Transplacental passage of antibodies
Haemolysis of Rh Pos fetal cells
S + S of haemolytic disease of the newborn?
Signs and Symptoms
severe anemia
compensatory hyperplasia & enlargement of blood forming organs (spleen and liver)
Treatment
prevention of sensitization with Rh immune globulin
intrauterine transfusion of affected fetuses
What are the 3 main presentations of G6PD?
Neonatal jaundice
Chronic non-spherocytic haemolytic anaemia
Intermittent episodes of intravascular haemolysis
Features of G6PD
Sporadic haemolysis
Typically induced by drugs, fava beans, fever, acidosis
Intravascular haemolysis - haemoglobinuria, rigors, fever, back pain
Treated by stopping precipitant, transfusion, renal support
Features of hereditary spherocytosis
Commonest hereditary haemolytic anaemia in Europeans - 1/5000; probably rarer in Africa
Typically autosomal dominant, but no family history in 25% cases
Heterogeneous - deficiencies of spectrin (41.5%), ankyrin (1.5%), band 3 (17%), band 4.2 (21.5%)
Clinical effects vary from mild to transfusion dependence; tends to be similar within families
What is sickle cell disease?
The most common serious genetic disorder in England affecting over 1 in 2000 live births. (Autosomal recessive)
A term covering a number of different but similar conditions that affect haemoglobin.
Types most commonly seen in UK:
Sickle Cell Anaemia (HbSS)
Sickle Haemoglobin C disease (HbSC)
Sickle Beta Thalassaemia (HbS/β thal)
Pathophysiology of sickle cell disease
Substitution of valine for glutamic acid on β chain (HbS)
HbS polymerises when deoxygenated leading to sickle shape
Occlusion of the microvascular circulation producing vascular damage, infarcts, pain
Shortened survival of red cells leading to haemolysis
How will we diagnose sickle cell disease?
Blood Film
Sickle solubility
HPLC
What can we do to treat sickle cell disease?
Education – keeping warm, well hydrated
Prophylactic Penicillin V to prevent infection due to splenic hypofunction (anti malarials when required)
Ensure immunisations are up to date to prevent infection
Screening such as TCD monitoring, G+M
Effective pain management (NICE requirement)
Prompt treatment of infections
Bone Marrow Transplant
Hydroxycarbamide
New agents e.g. Crizanlizumab, L-Glutamine
What are some complications of HbSS
Enuresis
Priapism
Avascular necrosis
Chronic ankle ulceration
What is thalassaemia?
Normal Adult HbA = α2β2,
HbA2 = α2δ2
HbF = α2γ2
Thalassaemia = reduced rate of one or more of the globin chains
Autosomal recessive
α thal (4 α globin genes per cell αα/αα)
β thal (2 globin genes per cell)
What is Beta thalassaemia
β Thalassaemia Trait ( carrier state)
asymptomatic
Mild anaemia, low MCV, Raised Hb A2
Features of B Thalassaemia
β Thalassaemia Major
Progressive Severe Anaemia, low MCV, Hb F and A2 increased
Jaundice
Splenomegaly
Failure to thrive
Skeletal Deformity
Delayed puberty
Death early teens/adulthood
B Thalassaemia management
Genetic Counselling, AN diagnosis
Regular blood transfusion
Complications of Iron overload
Liver, Heart, Pancreas, Endocrinopathy
Iron chelation
Bone Marrow Transplantation/Gene Therapy
What is haemostasis and what does it depend on?
Coagulation cascade - pl
Platelets
Numbers
Function
Coagulation factors
Vascular integrity
Coagulation cascade
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Factors involved in Intrinsic pathway
Prekallikrein
HMWK
FXII
FXI
FIX
FVIII
Factors involving Extrinsic pathway
FVII
Common pathway in coag cascade
FV
FX
Prothrombin
Fibrinogen
What are the causes of thrombocytopenia
Increased Plt destruction (Immune and non immune)
Dec Platelet production
Disorders of platelet pooling
Pseudothrombocytopenia
What causes increased PLT destruction (IMMUNE) in thrombocytopenia
ITP
Secondary to infection (HIV, Hepatitis, CMV, EBV, Parvovirus, mumps, measles, pertussis)
Drug induced – valproate, ciprofloxacin, ibuprofen, phenytoin, ranitidine, heparin, captopril
Autoimmune –Evans syndrome
SLE
NAIT
Hyperthyroidism
What causes increased plt destruction (Non immune) in thrombocytopenia
Microangiopathic (TTP, HUS)
Kasabach-Merritt Syndrome
Drugs
Infection (viral associated haemophagocytic syndrome) (bacterial infection)
Disseminated Intravascular Haemolysis
What causes decreased platelet production in thrombocytopenia
Constitutional (TAR, CAMT)
Ineffective thrombopoiesis ( B12, Folate Deficiency, severe iron deficiency))
Infiltration (Leukaemia, Non haem infiltration, Osteopetrosis, storage disease)
Metabolic disorders (Ketotic glycinaemia, MMA, Acidaemia)
Bone Marrow Failure (Aplastic Anaemia)
What are some disorders of platelet pooling
Hypersplenism (Portal Hypertension, Gauchers disease)
What is pseudo thrombocytopenia?
Platelet activation during blood collection
What is the most common form immunologic thrombocytopenia
ITP
Features of ITP
Identified if well child, acute onset and no other concerning features, history with normal examination (other than bruising, petechiae etc)
Important to review blood film periodically to ensure no evolving serious bone marrow disorder
Acute 0-3 months
Persistent >3-12 months
Chronic >12 months
Treatment rarely required unless bleeding – steroids, IVIG, TPO-RA
What are coagulopathies
Various errors in clotting cascade
Bleeding disorders
hemophilia
von Willebrand disease
Hypercoagulable states
antithrombin, protein C, protein S, FVL, PT mutation, APS
What is Von willebrand disease
VWD is the commonest inherited bleeding disorder that varies in severity according to the degree of deficiency and the specific characters of the molecule that is altered.
WHAT ARE THE 2 MAIN ROLES OF VWF?
Mediates the adherence of platelets at sites of endothelial damage helping form platelet plug
Binds and transports FVIII, protecting it from degradation
What is the deficiency in VWD?
Deficiency of VWF (type 1)
Dysfunction of VWF (type 2A, B, M,N)
Complete absence of VWF (type 3)
S + S of VWD?
Easy bruising
Epistaxis
Menorrhagia
Mucosal bleeding
Following surgery or trauma
how IS vwd INHERITED?
AD or AR for type 3 or 2N
How can we investigate VWD?
Clotting often shows prolonged APTT (not always!)
VWD screen – FVIII, VWF:Ag, VWF activity
Further investigations can be performed to identify type 1 from 2
Function:antigen ratio <0.6
RIPA
Multimer Analysis
Genetic analysis
How do we manage VWD?
Tranexamic Acid
An antifibrinolytic useful for menorrhagia or mucosal bleeding
Given pre procedures IV 10mg/kg and orally 15-25mg/kg tds for other bleeding or post operatively
Desmopressin
Used to elevate FVIII and VWF levels by releasing endothelial stores.
Given IV, SC or intranasal
Perform a DDAVP trial if possible to assess response
Excessive fluid intake can reduce sodium so restrict fluid to 1L for 24 hours post dose
Avoid use if <2 years or monitor sodium closely and avoid if know atherosclerosis
Avoid in Type 2B as thrombocytopenia due to clearance of large multimers.
VWF- containing concentrates
Given if DDAVP inadequate or contraindicated
Voncento, Wilate
Given as IV bolus 12-24 hours as required by bleeding and levels.
Plasma products so ensure hepatitis vaccinations given pre where possible
What are Haemophilia A and B and what does it cause?
Deficiency of Factor VIII/IX, ↑APTT
X linked recessive- boys
Prolonged bleeding
Muscle bleeds
Joint bleeds > arthritis and deformity
Treatment Factor VIII/IX
Complications of treatment
Presentation of severe moderate and mild haemophilia
Severe - <1IU/dl or <1% of normal
Spontaneous bleeding into joints or muscles
Moderate - 1-5IU/dl or 1-5% of normal
Occasional spontaneous bleeding, prolonged bleeding with minor trauma or surgery
Mild - 5-40IU/dl or 5-40% of normal
Severe bleeding with major trauma or surgery. Spontaneous bleeding rare
How do we manage the bleeding in haemophilia?
Tranexamic Acid
Factor concentrate( standard life and extended half life) – recombinant e.g. Advate, Benefix, Elocta
Emicizumab (recombinant humanised bispecific monoclonal antibody mimicking the co-factor of activated FVIII)
When does leukaemia occur?
When WBC starts multiplying out of control
Common symptoms of leukaemia
Weight loss
Fever
Infection
Fatigue
Loss of appetite
Spleen and liver enlargement
Anaemia
Bone joint paint
Purple patches or spots
Night sweats
Types of paediatric leukaemia
ALL - 85%
AML - 13%
Others - 2%
How do we make the diagnosis of ALL
Blood count Anaemia
WCC up or down
Neutropaenia
Thrombocytopaenia
Blast cells
Bone Marrow
LP
Features of ALL
Most common malignancy
Peak age 4-7yrs
Prognosis 85% cure
Good Prognostic factors
Age 2-10
Female
WCC<50
No CNS disease
Classified also on cell type B and T cell
Treatment for leukaemia
Supportive
Prompt treatment of infection
Prevention of tumour lysis
Blood product support
Specific
Chemotherapy (ALL – Altogether, AML – Myechild)
Targeted therapy
Bone marrow transplant
Late effects of treatment
Psychological
Family and social
Growth particularly CNS RT
Endocrine
Puberty
Fertility
Intellectual
Second malignancies
