Haematology Flashcards
80% of chidhood leukaemias are what type? what are 15% of the others?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
5 syndromes that have increased likelihood of developing leukaemia?Type of anaemia assocaited with AML?
Down's Syndrome (AML in early life, ALL later) Bloom Syndrome Fanconi Syndrome (AML) Noonans Syndrome Kostmanns Syndrome Diamond black fan anaemia
What leukaemia do Down’s Syndrome individuals have increased chances of developing?
AML in early life (1/100)
ALL in later life
Bloom syndrome risk of developing leukaemia?
1/8
Noonan’s syndrome what is the leukaemia they are prone to developing? how is it treated?
Juvenille myelomonocytic leukaemia
Need bone marrow transplant without chemo beforehand
Type of leukaemia has nearly a 100% concordance in twin children?
infant acute lymphoblastic leukaemia
What is the Kinlen hypothesis of leukaemia development?
after intense population mixing there are higher rates of infection in the previously unexposed individuals
What type of leukaemia can benzene cause?
Acute myeloid leukaemia
If blast cells are found in the peripheral blood stream what is this known as? who is most effected?
Transient myeloproliferative disorder
Down’s syndrome
How long does transient myeloproliferative disorder last for?
8-12 weeks
What are you more likely to develop if you suffer transient myeloproliferative disorder?
Acute myeloid leukaemia
Clinical presentation of leukaemia?
low Hb - pallor, tired low neutrophils - infections, sepsis low platelets - petechiae, bruising bone pain hepatosplenomegaly lymphadenopathy Leukaemic skin deposits
What does a bone marrow aspirate differentiate between?
Myeloid leukaemias, T cell, B cell precursors (early pre b, pre-b, c(mu))
3 trisomies that relate to development of leukaemia?
4,10,17
which 3 gene mutations lead to leukaemia?
BCR-ABL
TEL-AML1
MLL
What 4 fusion transcripts does PCR tell you regarding leukaemia diagnosis?
BCR-ABL (p190:p210)
MLL-AF4
E2A-PX1
TEL-AML1 t(12:21)
Which type of mutation is Philadelphia positive ALL?
BCR - ABL (p190:p210)
Why do you perform a lumbar puncture in leukaemia?
See if there has been any infiltration into the CNS with blast cells
CSF count of white cell and blasts. what is classified as CNS 1, CNS 2 and CNS 3?
CNS 1 = less than 5 WBC, no blasts
CNS 2 = less than 5 WBC but blasts
CNS 3 = more than 5 WBC and blasts
What prophylaxis is given to children to prevent leukaemia spreading to the CNS?
Methotrexate
When is minimal residual disease checked for in children with leukaemia?
after 1 month of chemo, PCR
What is the risk of relapse if you dont have minimal residual disease less than 1 in 1x10^4
30-40%
5 drugs that can cause secondary AML
Cyclophosphamide Ifosfamide Melphanan Etoposide Myelodysplasia
How does infant ALL present differently to older children?
High WCC
CNS involved
myeloid features
CD10 negative - pro-b phenotype
What 3 MLL gene arrangements are common in Infant ALL?
MLL T(4:11) MLL T(11:19) MLL T(9:11)
Define primary immune thrombocytopenia?
an isolated platelet count of less than 100 x10^9, normal WBC and RBC
What is primary immune thrombocytopenia sometimes called?
Idiopathic thrombocytopenic purpura
What is primary immune thrombocytopenia usually following in children?
infection, viral illness
Persistent vs chronic primary immune thrombocytopenia?
Persistent = 3 months - 1 year Chronic = over a year
How long does primary immune thrombocytopenia usually persist for?
6 months
What is the most common bleeding sites associated with primary immune thrombocytopenia?
GI, epitaxis
Intracranial haemorrhage but rare
What does bone marrow film show in primary immune thrombocytopenia?
increased number of megakaryocytes
What is usual presentation of a child with primary immune thrombocytopenia?
Petechiae rash following by viral illness/URTI
History of bleeding - gums, epitaxis, bruising, blood in stools
Diarrhoea
When would a rash be more suspicious of meningitis than primary immune thrombocytopenia?
If there was a fever
What questions do you ask in the history of someone with suspected primary immune thrombocytopenia ?
Any vaccinations? Any fevers? is purpura non-blanching (will be) any anaemia (shouldnt be) Any lymphadenopathy or splenomegaly (shouldnt be)
Differential diagnosis for low platelet counts?
Meningitis - usually very unwell
viral - parvovirus B19, CMV, HIV
Leukaemia
Primary immune thrombocytopenia
Rare causes of thrombocytopenia?
aplastic anaemia - fanconi anaemia, radiation, virus, drugs
Evans syndrome
What are the 3 features of Evans syndrome?
anaemia, thrombocytopenia and a positive Coombs
Presentation of thrombocytopenia what investigations are performed?
FBP Reticulocyte count Coagulation screen Blood group with a group and hold Peripheral blood film and bone aspirate if abnormalities are then seen
When is a bone marrow aspirate performed on children presenting with thrombocytopenia?
If abnormalities are seen on peripheral blood film
If thrombocytopenia becomes chronic
If thrombocytopenia has not resolved in 6 months what investigations do you perform?
Direct antiglobulin test
Quantitive Ig level
Virology - CMV and parvovirus and HIV
What is the bleeding score?
a score to determine whether intervention is necessary with treatment
Description of grade 1 on the bleeding scale
grade 1 = petechiae not too many, bruises less than 5 and no mucosal bleeding
Description of grade 2 on the bleeding scale
Grade 2 = more than 100 petechiae, more than5 large bruises and no mucosal bleeding
Description of grade 3 on the bleeding scale
Grade 3 = moderate bleeding and mucosal bleeding
Description of grade 4 on the bleeding scale
Grade 4 = mucosal bleeding and suspected internal haemorrhage
How do you manage patients who are monitored on the bleeding scale but discahrged home
Appropriate information to parents, contact number in emergencies at all times and only when there is a lack of significant bleeding Avoid contact activities no diving in the swimming pool helmet when cycling attend school - monitored outside no herbal remedies Chicken pox contact - medical advice
If a child must be admitted for treatment of thrombocytopenia what 2 treatment options are there?
Prednisolone 2mg/kg for 7 days and then wean over 7 days
Ig 1g/kg
What is the last resort treatment for thrombocytopenia?
Splenectomy
SE of short term steroids?
Mood, appetite, appearance
Mask leukaemia
SE of long term steroids?
Osteoporosis Hypertension Growth disorders diabetes suppress stress response suppress immune system
Why is suppressing the immune system a nasty side effect of steroids in children?
Chicken pox infection so much worse - need Varicella Ig
How many donors go into Igs?
10,000
What are the 2 treatment options for chronic ITP?
Rituximab and Eltrompopag
Short term SE of Rituximab?
Chills, fever, headache, tiredness, allergic reaction
Long term SE of Rituximab?
neutropenia, infection, haematological malignancy
What is classified as anaemic in children 3 months old through to puberty?
Below 110g/L
How can you tell whether the anaemia is normocytic/microcytic/macrocytic?
MCV
In iron deficiency anaemia what happens to MCV, MCH, MCHC?
all decrease
Iron deficiency anaemia vs chronic anaemia - what is the iron level and the iron binding capacity
In iron deficiency anaemia there is decreased iron but increase iron binding capacity whereas in chronic anaemia there is decreased iron and decreased iron binding capacity
Clinical features of anaemia in babies?
anaemic, glossitis, angular stomatitis, nail changes, irritable, cognitive changes, developmental delays
If a baby is presenting as anaemic, what do you need to rule out the cause being?
coeliac
What is the iron supplement dosage in an anaemic child?
3-6mg/kg/day
what is an acceptable increase rate of iron in baby?
10g/L every month
Hereditory haemolytic anaemias can take what 2 forms?
Defect in red cell membranes
Defect in red cell metabolism
What is an example of a defect in red cell membranes causing hereditory haemolytic anaemia?
Hereditory spherocytosis
What is hereditory spherocytosis and what symptoms does it present with? Treatment?
Spherical RBCs
Jaundice, splenomegaly, anaemia, increased reticulocyte
Treatment is qith splenectomy and iron supplements
What is an example of a defect in red cell metabolism that causes hereditory haemolytic anaemia? mode of inhertiance? How does it present?
G6PD deficiency
X-linked
presents with haemolysis after exposure to oxidising agents - antimalarials, antibiotics, mothballs, chinese remedies
Acquired haemolytic anaemia will be positive in what test?
Coombs
2 types of acquired haemolytic anaemias?
warm auto-immune haemolytic anaemias and cold auto-immune haemolytic anameias
Describe warm-autoimmune haemolytic anaemias? mediated by? associated to? presents as?
Ab present at 37 degrees
associated with other autoimmune like lupus
IgG mediated
Splenomegaly, haemolytic anaemia
What is the treatment for warm autoimmune haemolytic anaemia?
corticosteroids
IV Ig
potentially blood transfusions and folic acid supplements
what is the difference in mediating factors between warm and cold autoimmune haemolytic anaemia
Warm = IgG mediated Cold = cd3 complement mediated
What 2 infections can lead to haemolytic anaemia?
EBV
Mycoplasma
What is the name for the acute episode of haemolysis occuring after a cold episode?
Paroxysmal cod haemoglobinuria
How does ABO incompatability occur?
IgG transfer from mother to baby
What can rhesus disease cause in the newborn?
Hydrops Fetalis and IUD
What can hydrops fetalis result in for the baby if left untreated?
Kernicterus
What is the dominant haemoglobin after 3-6 months of age and what is the formula version?
HbA 2alpha 2 beta
What is the dominant haemoglobin in fetal life and what is the formula version?
HbF 2 alpha 2 gamma
What is the haemoglobin that develops in 1.5-3% of people past 3-6 months of life and what is the formula version?
HbA2 2 alpha 2 delta
What mutation leads to alpha thalassaemia syndrome?
Point or delete mutation
What happens if all 4 alpha genes are lost?
hydrops fetalis
death in utero
What happens if 3 alpha genes are lost?
beta 4
HbH
microcytic, hypochromic, splenomegaly
What happens in alpha thalassaemia trait?
loss of 1 or 2 alphas
no anaemia
MCV and MCH both drop
How is alpha thalassaemia trait diagnosed differently to more severe alpha thalassaemia?
Trait = DNA analysis Severe = electrophoresis
Inheritance pattern and mutation involved in beta thalassaemia?
Autosomal recessive
point mutation
Beta 0 vs beta +?
B0 = no beta chains produced B+ = small amount of beta chains are produced
Symptoms of beta thalassaemia?
Severe anaemia, hepatosplenomegaly, marrow hyperplasia - extramedullary haemopoiesis, fractures
What will the Hb be made up of primarily in beta thalassaemia?
HbF
What is the management of major beta thalassaemia?
Blood transfusions folic acid splenectomy if needed Endocrine if there is end organ failure or puberty delay Bone marrow transplant
Symptoms of beta thalassaemia minor?
often symptomless maybe minor aneamia
What is the mutation that occurs in sickle cell anaemia?
Substitute occuring on the beta chain substituting a valine for glutamic acid at position 6
Why do red cells sickle?
when there is low oxygen tension causes them to crytallise
What occurs due to sickle HbSS?
severe anaemia, splenomegaly, gallstones
Venocclusive - infarction, infection, dehydration
Visceral crisis - chest, liver, spleen, acute abdomen
Aplastic crisis - parvovirus, folate deficiency
How do you manage a sickle cell crisis?
warm, rehydrate, treat cause, analgesia, blood plasma exchange to remove sickle, hydroxyurea to increase HbF
What is a curative treatment for HbSS?
stem cell transplant
3 times you need to be careful about sickle cell trait?
Pregnancy, anaesthetic, high altitudes
Fanconi anaemia inheritance pattern, type of anaemia, pathogenesis? risk of what else? treatment?
Autosomal recessive Aplastic anaemia Abnormal growth of skeleton Defective DNA repair AML Need bone marrow transplant
In aplastic anaemia, what will be seen on blood film and bone marrow aspirate?
Blood film - pancytopenia
Bone marrow aspirate - hypoplastic marrow with fat cells instead of haemopoietic tissue
3 forms of supportive care given in aplastic anaemia?
blood transfusions
platelet transfusions
treat infection
What treatment can be given for aplastic anaemia?
ALG - anti T cell Ig
ciclosporin or steroids
stem cell transplant
How is anaemia caused in diamond blackfan anaemia?
Red cell aplasia
Causes of transient anaemia in children?
Parvovirus B19
Transient myeloproliferative disorder
Congenital dyserythropoietic anaemia
Syndrome that can produce low neutrophil counts?
Kostmanns Syndrome
What is langerhans cell histiocytosis? LCH
Treatment?
clonal expansion of langerhan cell precursor
dendritic cell family usually destroying invading organisms
Chemotherapy
Haemophagocytic lymphohistiocytosis? HLH
Presentation?
Findings on examination?
Proliferation of macrophages, nucleating red cells, platelets
Very unwell, temperatures
Hepatosplenomegaly, deranged LFTs, coag and reduced fibrinogen, increased ferritin and triglycerides
Sees haemophagocytosis in bone marrow
Treatment of haemophagocytic lymphohistiocytosis?
Immunosuppression
Chemo
SCT
Haemophillia A is inherited how? deficiency in what? presents as? complications lead to?
APTT/prothrombin?
X linked recessive factor 8 deficiency haemoathrosis and bruising, muscle haematomas joint deformities long APTT normal prothrombin
Severe Haemophillia A diagnosed with levels below what IU/mL?
0.01 (1%)
Moderate Haemophillia A diagnosed with levels below what IU/mL?
0.01-0.05 (5%)
Mild Haemophilia A diagnosed with levels below what IU/mL?
over 0.05 (5-20%)
How do you manage someone with Haemophillia A?
Recombinant factor VIII in bleeding episode or 3 times a week prophylactically in severe cases
Haemophillia B refers to deficiency in what? inheritance pattern? management?
Factor IX deficiency
X linked recessive
Recombinant factor IX
What is the purpose of Von Willebrand factor?
Cause adhesion of platelets to damaged endothelium
Carries factor 8
Inheritance pattern of VW disease?
autosomal dominant
Difference between Type 1, 2 and 3 VWD?
type 1 = lacking VW factor
Type 2 - defective vw factor
Type 3 = no VW factor
Clinical features of VWD?
bleeding mucous membranes haemorrhage following surgery menorrhagia Increased bleeding time Factor 8 deficiency low VWF
How do you treat VWD related bleeding episode?
pressure on the wound
antifibrinolytic like tranexamic acid
desmopressin (DDAVP)
factor 8 concentrate (human derived factor 8 and VWF)
Vitamin K deficiency effects which coagulation factors?
2, 7, 9 , 10
Haemorrhagic disease of the newborn occurs how long after delivery and caused by what? treatment?
2-4 days
Vitamin K deficiency
Treat with vit K
Haemorrhagic disease of the new born presents how?
GI bleeding, bleeding from cord, cephalohaematoma
Which babies usually experience haemorrhagic disease of the newborn?
Breast fed babies
In more severe cases of haemorrhagic disease of the newborn what can be given on top of Vit K?
FFP/prothrombin
Name 4 hereditary disorders of thrombosis?
Factor V Leiden
Protein S deficiency
Protein C deficiency
Antithrombin deficiency
Tests would you do on a child presenting with lymphadenopathy?
FBP CRP ESR LFT LDH Monospot PCRs - EBV, CMV, HIV, Toxoplasmosis, Bartonella CXR USS Biopsy
Tests for a child with splenomegaly?
Leukaemia Thalassaemia Sickle cell haemolytic anaemia - G6PD, spherocytosis, warm/cold autoimmune EBV infection Portal vein hypertension Systemic disease or storage disease
6 non haemolytic causes of anaemia?
B12, folate or iron deficiency
Malabsorption
bone marrow failure
blood loss
Haemolytic causes of anaemia?
Spherocytosis G6PD deficiency Alpha thalassaemia Beta thalassaemia Sickle cell disease Leukaemia
History questions to ask about in a child with anaemia?
Lethargy Poor feeding Breathlessness Pallor Growth Any bleeding or bruising Infections PICA How long has the problem been there? FH - ethnic minorities, sickle cell, thalassaemia DH - NSAIDs? Any blood loss Birth history, antenatal Dietary history - age of weaning
What is the nail condition that can result due to iron deficiency anaemia?
Koilonychia
Risk factors for iron deficiency anaemia?
Preterm Low birth weight multiple births exclusive breast fed for over 6 months cows milk excess
3 tests to confirm iron deficiency anaemia in child and what is usual reference ranges?
FBC, blood film, iron studies
110-130g/dL
Alternative to iron deficiency anaemia when presented with decreased Hb, MCV and MCHC?
Thalassaemia trait
Lead poisoning
Chronic disease
Dietary advice for iron deficiency anaemia?
Iron rich diet and avoids cows milk consumption
What is dose of iron supplement?
3-6mg/kg/day (max 200mg) in 2-3 divided doses
After 1 week of iron supplements whats should be checked in a child?
FBC and reticulocyte count
Normal age of presentation in sickle cell disease?
3 months - 6 years
Causes of a petechiae rash?
ITP Leukaemia Meningococcal disease Coughing, crying Trauma Viral and bacterial infections
What additional blood tests could you perform once ITP is diagnosed with low platelets?
Blood film
Reticulocyte count
Coagulation screen
Blood group
What is ITP? how long does it usually last?
Immune mediated thrombocytopenia usually following infection
Chronic after 12 months and need bone marrow aspirate
In the case of active bleeding in ITP what 2 things are given initially?
Prednisolone (2mg/kg/day for 7 days then wean over 14) and Ig (1g/kg IV
How often is platelet count taken in follow up after treatment for ITP?
Weekly for 1 month, monthly up to 6 months and then every 3 months
If thrombocytopenia persists for 6 months after treatment then what tests need to be performed?
DIrect antiglobulin test
Virology - CMV, Parvovirus, HIV
Check VZV immunity
Advice to parents about their child who has ITP?
Avoid contact sports Avoid ibuprofen Contact number for emergencies Warning signs to look out for Helmet when cycling Written information from ITP association website Inform doc if in contact with chicken pox and VZ Ig neg and on steroids Supervision in playground Emergency card
If someone with ITP bangs their head what questions do you want to ask them?
What happened Witnesses LOC? how did you feel before and after? Vomiting Cry immediately Dizzy, personality changes, sight, hearing, headache, loss of appetite, fit or collapse, seizure, clear fluid from nose or ears?
