Haematology Flashcards
What do multipotent stem cells differentiate into?
Myeloid and lymphoid progenators
What do myeloid progenitor cells differentiate into
Megakaryocytes- platelets
Erythroblasts- retics- red cells
Myeloblasts- myeloblasts- neuts, basophils eosinophils and monocytes
What do lymphoid progenator cells differentiate into?
Plasma cells
T cells
B cells
Name the CD4 numbers for the following NK cells T helper cells T killer cells B cells
NK- CD56
T helper- CD 4
T killer- CD 8
B cells CD 19 and 20
What are the three stages of haematopoiesis
When do neutrophils develop?
Can EPO cross the placenta?
How does red cell life span change over time
Mesoblastic- yolk sac
Hepatic- 2 to 24 weeks- liver
Myeloid
Myeloid stage
No
Increases over time
What is the normal structure of HbA
What chromosomes are involved
What are the three types of embryonic hb? What Greek letters are present?
What makes up Hb F
What makes up Hba2? How much is normally found in adult blood?
2 alpha, 2 beta 4 haem groups containing iron
Alpha-16
Beta-11
Gower 1,2 and Portland- zeta alpha and epsillon
HbF 2 alpha 2 gamma
HbA2 2 alpha 2 delta
HbA to A2= 30:1
What are the 5 subtypes of microcytic anaemia
Thalassaemia Anaemia of chronic disease Iron def Lead poisoning Sideroblastic
On a normal blood film, what do platelets and red cells look like
Red cells- discs with a pale centre
Platelets- smallest cells on the film
When do iron stores run out?
Can it be synthesised by the body?
What is the most common cause of iron deficiency in toddlers?
What type of anaemia is seen?
What is seen on blood film?
What should be given along with iron? Why?
How long will it take to see a reticulocyte response?
5-6 months No Excessive cows milk- poorly absorbed Hypochromic microcytic Ansiocytosis, rod cells and target cells Vitamin C- helps the absorption 3 days
Alpha thalassaemia
Which chromosome is the defect?
What are the 4 possibilities and how will they present?
Is it a quantity or a quality problem?
16
1 allele missing- silent carrier
2 missing- microcytic anaemia
3 missing hbH- above plus hepatomegaly and haemolysis
4- incompatible with life- hydrops
Quantity
Beta thalassaemia What is the inheritance and which chromosome What are the three forms What are the complications of major? When does major present and why
AR- 11
1) carrier= 1 allele defective. Asymptomatic. Increased hbf and a2
2) intermedia-2 allele (one less severe) mild symptoms
3) major 2 alleles- transfusion dependant, splenomegaly and abnormal faces
Colelothiasis and haemochromatosis
6 months- normal transition point to HbA
What is seen on blood film in lead poisoning
Basophilic stippling and sideroblasts
Sideroblastic
What is it?
How is it inherited?
What syndrome is it associated with?
Unable to use iron properly, iron accumulates in mitochondria
X linked
Pearson syn
What should be monitored for iron overload
When is chelation started
What infection is associated?
Serum ferritin levels
>1000
Yersinia
What do the direct and indirect Coombs pick up
Direct- antibodies on red cells
Indirect- antibodies to red cells in serum
What is the genetic defect in sickle cell anaemia
Point mutation in ch11 (abnormal beta chains)
Glutamine to valine
When does sickle cell anaemia present?
What is a sequestration crisis
How could Vaso occlusive disease present?
What is the infection risk
What normally triggers an aplastic crisis
What is seen on blood film. What indicates the spleen issues
What is the definitive diagnostic test?
6 months/ picked up on screening. Chronic haemolytic anaemia( jaundice, gallstones, tachycardia, splenomegaly and sickle faces- maxillary hyperplasia)
Sudden reduction in circulating volume, sequestration In The spleen
Pain dactylysis priapism
Encapsulated organisms (functionally asplenic from 5 yrs)parvovirus b19
Sickle cells target cells and Howell jolly bodies. Targets and HJBs
Hb electrophoresis
Treating sickle cell disease
What level of HbS should you aim for with transfusions
What else do they need
<30%
Pneumococcal and meningococcal vaccines Penicillin prophylaxis
What is the defect in g6pd def?
How is it definitively diagnosed
What is the inheritance
Missense mutation
Lacking nadph- prevents cells against oxidative stress
Enzyme activity analysis
X linked
Does g6pd have hepatosplenomegaly?
No!
What can precipitate haemolysis in g6pd- 1 food and 3 drugs
How quickly do symptoms occur after exposure
Favs beans
Co trim chloramphenicol and nitrofurantoin
24-48 hours
What is seen on blood film in g6pd def
Heinz bodies and bite cells
What is the pattern of inheritance in pk def. what does the defect cause
AR
Reduced atp. Rigid cells
What causes HS What is the pattern of inheritance What is the typical presentation What is the definitive test? What other fancy test might be used
Abnormal spectrin protein AD Intermittent jaundice. Neonatal jaundice. Mild NN anaemia Osmotic fragility year EMA testing- lower than normal
Fanconi anaemia
What phenotypically is seen
What is the definitive diagnostic test
What type of anaemia do you see?
Short, Bifid thumbs, urinary retention, cafe au lait spots
Lymphocyte breakage tests
Macrocyclic
Fanconi anaemia What is the inheritance? What is the pathophysiology? What cell lines are affected? What cancers are they most at risk of
Autosomal Dom or recessive
Increased fragility of chromosomes
Initially red and plt then neutrophils
SCC and AML
Diamond blackfan anaemia
What does it cause
What cell lines will it affect
What are the classic phenotypical features
Early arrest of red cells maturing
Red cells only
Short, low IQ, webbed neck, triphalangeal thumb and renal anomalies
TEC How does it differ from diamond blackfan anaemia + what test would help?
Resolved in 1-2 months
More likely toddlers
No abnormal phenotypes
Erythrocyte adeonsine deaminase activity normal not increased like DBA
Pearson syndrome
Inheritance
What does it cause
Mitochondrial
Pancreatic dysfunction
Pancytopenia
Dyskeratosis congenita
What type of problem is it?
What 3 classic features are seen
What cancers are they at risk of
Telomere breakage
Oral leukoplakia, nail dystrophy, lacy rash
AML
Folate deficiency
What is the main source in the body?
How long do stores last?
Where is it absorbed
Dietary
3-4months
Small intestine
b12 def Where is it absorbed and stored How long do stores last for What can severe deficiency cause? What is seen on film?
Terminal ileum. Stomach
3-4 yrs
Subacute combined degeneration of the Ford- post column loss
Large hypersegmented neuts
Cyclical neutropenia
What are the features
What gene is abnormal
What might gingivitis suggest?
Cycles of low neuts every 21 days, last 3-5 days. Fever, malaise, ulcers and sore throat
ELANE
Non benign cause
Chronic neutropenia
What is the ANC normally?
What types of infections do they tend to get?
<200
Pseudomonas staph and E. coli
ITP
What normally triggers it? Timing?
What type of antibody develops? To what ?
How long should it take to resolve if acute?
What is the most serious side effect?
What is Evans syndrome?
Viruses- 1-4 weeks post IgG to glycoprotein 11b/11a Under 6 months Intracranial haemorrhage ITP and haemolytic anaemia
What enzyme is lacking in ttp
What might trigger it?
2 ways it’s different from hus ?
How is it treated?
AdamTS13
Quinine, pregnancy, surgery
Infections
Vague symptoms leading to CNS signs and less diarrhoea
Plasma exchange
What is the difference between neonatal alloimmune and autoimmune thrombocytopenia
What type of antigens are usually found in alloimmune? Against what? If Asian what?
What is the risk of ICH
Autoimmune= mum has ITP. Mum will have low PLT Alloimmune= mums platelets normal, abs to baby’s platelets
IgG-HPA1A 4a if Asian
30%
TAR syndrome
How do you differentiate from fanconi anaemia
Traombocytopenia with bilateral absent radii
TAR Have thumbs
Fanconi are bifid
What is Bernard soulier disease
Do they have any other physical features?
How is it different from glanzman
Autosomal recessive defect of glycoprotein receptor.
Giant platelets
No!
Glanzman has normal platelet size
What does the PT and APTT measure in terms of clotting pathways?
Which conditions are therefore screened by each?
PT- extristic pathway
APTT- Intrinsic pathway
PT- vitamin k def, liver disease, DIC, anticoagulants
APTT- above plus haemophilia, VWD
What factors are involved in the extrinsic pathway?
“ intrinsic
“Common
Tissue factor and 7
12,11,9 and 8
X to Xa, 2 to 2a (prothrombin to thrombin), 13
What are vitamin K dependant factors?
2,7,9 and 10
Haemophillia
What is the usual pattern of inheritance?
How does haemophillia C differ?
What happens to the APTT and PT?
How will it change with mixing of inhibitors present
What will happen to the bleeding time?
What will give a prolonged APTT but normal reptilase time
X linked recessive 30% de novo Autosomal recessive Prolonged APTT, normal PT Won’t correct Normal Heparin contamination
Haemophillia
What are normal levels of factor 8 and 9
What classifies a mild, moderate or severe deficiency?
What is a target joint?
What is the common presentation in a neonate?
What is the most risk muscle to bleed into?
8-30-40
9-25-30
Mild-<5% mid 1-5%, severe <1%
Thinning of the synovium following a bleed. Means repeated bleeds more likely
Post circumcision bleeding
Ileopaoas
Treating haemophillia
In a bleed what should you aim factor to be in mild or severe deficiency?
When does desmopressin have a role? What does it stimulate?
What percentage will develop inhibitors?
When do they occur? Are they equal in A&B?
What tests for them?
Mild >30% Severe 100% Mild A only- stimulates release of VWF from endothelial cells 20%- A is more common 20 exposure days. Bethesda assay
How might factor 13 deficiency present
Delayed bleeding from the umbilical cord
Von Williebrand What is the inheritance? How do the three types differ? What types have low factor 8? What happens to the APTT, pt and bleeding time? Where do platelets and vwf bind to? What medication may be useful? Are boys more likely to have it than girls
AD 1-Reduced production 2-reduced quality 3- absent factor 1&2 Long APTT and bleeding time, normal pt Glycoprotein 1b Desmopressin NO
Name 5 inherited thrombophillias
Factor 5 leiden
Factor C&S def
Antiphospholipid syndrome
Homocysteinuria
How do the pharmacomechanics of unfractionated and low molecular weight heparin differ?
What is the most commonly used thrombolytic drug in children?
Unfractionated- wider action by increasing activity or antothrombin 3 (blocks extrinsic pathway)
Lmw- acts directly on 10a
TPA
Warfarin
What do you need to cover with initially
Which clotting factors does it inhibit
Heparin
2,7,9&10- vitamin K dependant
What is commonly seen on blood film in aplastic anaemia
Macrocytosis
What does cryoprecipitate contain
Fibrinogen, factor 8 and 13
What does FFP contain
All clotting factors, albumin and immunoglobulins
In DIC what should be given first
Cryoprecipitate to replenish fibrinogen then FFP
What is the half life of Factor 7 Factor 9 Factor 10 Factor 2
7- 4-6h
9- 24 hrs
10 24-48 hrs
2 60 hrs
Alpha thalassaemia
For a child to have significant disease what do the parents have to have at least
Alpha zero (2 gene deletions)
Other than haemophillia with inhibitors, what is a cause of prolonged APTT that won’t correct with mixing
Lupus
What are examples of intravascular haemolysis. What is seen in blood
Physiologically what happens
“Extra vascular
Intra- haemolysis within the vessel. HUS, DIC mechanical valves
Raised LDH ++ And low haptoglobin. Hb in urine
Extra- haemolysis in RE system
Hereditary auto/allo immune causes
Urine clear, haptoglobin and LDH less elevated
