MGD ETA1 REVISION: COAGULATION

CASCADE,   HAEMOGLOBINOPATHIES &

CHROMOSOMAL ABNORMALITIES

Esther Elusope and Tofunmi Sesby-Banjoh 

Outline Haemostasis, Clotting cascade and Coagulopathies 

Hb, Mb and Haemoglobinopathies 

Chromosomal abnormalities 

Q&As 

Additional Resources and Concept maps 

HAEMOSTASIS AND CLOTTING
CASCADE 
 COAGULATION
HAEMOSTASIS CASCADE
HAEMOGLOBINOPATHIES 
 HAEMOGLOBIN Hb Variants​ ​

 Important molecule for oxygen transport  • Most common

in adults (90%
 Made up of 4 polypeptide chains each containing 4 haem groups  HbA ​
total Hb) ​
(a2, b2) 
 4x haem = each containing protoporphyrin ring + Fe  • 2a chains, 2b
 4x globin = 4 polypeptide chains (2a, 2b chains)  chains ​

 There are other variants of Hb – which have different combinations

of these chains
   HB vs MB • Less common
HbA2 ​
variant (2% of Hb) ​
(a2, d2) 
• 2a chains, 2d chains​
                   Hb (RBC)                     Mb (Muscle) 
§ 4 polypeptide  § Single polypeptide 
§ 4 haem  § Single haem 
§ Binds 4x o2 molecules § Binds diatomic o2 molecules • More common
(cooperativity) (no cooperativity) HbF ​ in foetus ​
(a2, g2)  • 2% og adult Hb ​
§ Sigmodal curve (haldane effect)  § Hyperbolic curve  • 2a chains, 2g chains​
§ Lower affinity for o2  § Higher affinity for o2 
Quick recap of mutations (MGD L3)  Sickle Cell Alpha Beta
SNPs eg nonsense, missense, silent, frameshift  Disease Thalassemia Thalassemia
Insertions 
Deletions 
Mutation Missense point Gene deletion  Reduced production(
B+) /absence (Bo)

Epidemiology  Areas with malaria Asians  Asians 

prevalence eg Sub Africans  Mediterraneans 
suharan Africa, S.E M. East Asia 
Asia
HAEMOGLOBINOPATHIES  

Types  HbSS Silent (1deletion)  Trait 

HbSC Trait (2 deletions)  Intermediate
HbSBthal  HbH (3 deletions)  Major 
Etc  Hb Barts (hydrops
fetalis) 

Treatment 
SS = prevent vasocclusive crisis 
Silent = none   Features  • Sickle shaped • Symptomatic • Failure to thrive 
RBCs  after birth  • Neonatal
HbA, Hb B major = regular blood transfusions   • Pain from vaso- • Mild/severe jaundice 
- folate supplement   occlusive crisi  anaemia  • Hepatosplenome
- iron chelation   • Mild/moderate galy 
anaemia • Frontal bossing 
- splenectomy  
- stem cell transplant 
CHROMOSOMAL
ABNORMALITIES
• NUMERICAL (changes to the number of • STRUCTURAL (physical changes to the
chromosomes)  structure of one or more chromosomes) 

• Polyploidy: multiple of the haploid number • Translocation

but greater than the diploid number.
• Inversion
(Triploidy, tetraploidy). Normal in human
muscle and liver. • Robertsonian translocation
• Duplication 
• Aneuploidy: abnormal number of chromosomes • Deletion
which is not a multiple of the haploid number.
• Monosomy – loss of 1
homologous chromosome
• Trisomy – gain of 1
homologous chromosome
 AUTOSOMAL ANEUPLOIDIES
Syndrome Clinical Features
Down's Syndrome  Mild to moderate intellectual disabilities,
(Trisomy 21) CHD, Hypothyroidism, Eye disorders –
strabismus, refractory errors, Hearing
disorders, Infertility  Infertility
Edwards' Syndrome More commonly short lifespans,
(Trisomy 18) microcephaly, low set ears, small jaw,
cleft lip, cardiac abnormalities,
intellectual disabilities, feeding and
breathing problems, low birth weight
Patau's Syndrome Microcephaly, eye defects, cardiac
(Trisomy 13) abnormalities, Ear malformations,
polydactyly, short life span.
SEX CHROMOSOME ANEUPLOIDIES
Syndrome Clinical Features
Turner Syndrome (45, X) Short stature, broad chest, low set
ears, Webbed neck, CVS defects,
Triple X syndrome (47, Tall stature, microcephaly,
XXX) delayed motor skills, speech and
learning disabilities, auditory
processing defects, scoliosis
Klinefelter syndrome (47, Usually appear after puberty –
XXY) gynecomastia, small testes,
reduced testosterone production,
problems with reading and
writing, Infertility
 Menti.com 

Q&A

46 01 1 
 ADDITIONAL RESOURCES

• Coagulation cascade - https://www.youtube.com/watch?v=cy3a__OOa2M

• Sickle cell anaemia - https://www.youtube.com/watch?v=fIIJmg_1hv0
• Alpha thalassemia - https://www.youtube.com/watch?v=R-POSKAhBL0
• Beta thalassemia - https://www.youtube.com/watch?v=oH6SMG3Ykjg
• Haemoglobinopathies – MGD L8 
• Mutations – MGD L3 
• Punnett's square and Mendelian Inheritance – MGD 3
 Gaseous exchange via haldane
Autosomal recessive haemoglobinopathies
Offer genetic counselling and resulting in impaired formation of a/b globin effect:
genetic screening  chain synthesis  Hb gives up co2 when po2 lungs   
Bi Hb binds co2 when po2 tissue 
op
sy

Definition
c ho • Prevalent in areas with malaria 

e
so

ctur
ci a

n
tio
Bloods =  FBC/blood film/Hb l

Stru
• A thalassemia = Asians and

nc
electrophoresis

Fu
Africans 
Investigations  i o l ogy
Imaging = skull xray to confirm B thal  em
Epid • B thalassemia = Asians,
(hair on end appearance Mediterraneans, M. East Asians

Alpha and Beta  Thalassemia Alpha (impaired Beta (impaired

Signs and symptoms  synthesis of alpha synthesis of B globin
Failure to thrive  globin due to gene due to gene
deletion - 4 alleles mutation– 2 alleles on
Pathophysiology
on Xsome 16)  Xsome 11
Neonatal jaundice 
Key points: ​ Types  Types 
Hepatosplenomegaly  Silent (1 deletion)  Trait (B/B+)
Sickle cell = missesnse point
Trait (2 deletions)  Intermediate (B+/B+
mutation  or Bo/B+)
Frontal bossing, prominent zygomatic A thal = gene mutation
bones (reduced/absent)  HbH (3 deletions)  Major (Bo/Bo) 
B thal = gene deletion Hb Barts (4 deletions) 
Offer genetic counselling and A group of autosomal
genetic screening eg recessive disorders
haemoglobinopathy screening,
affecting B globin chain 
FOQ, chorionic villi sampling 
Bi
op
sy
ch

re
Definition
os

ctu
oc
ia

ru
Bloods =  FBC/blood l

St
Gaseous exchange via haldane effect: 
film/Hb electrophoresis/
Hb gives up co2 when po2 lungs 
Inve n
stig unc t io Hb binds co2 when po2 tissue 
at F
ions
 
• Prevalent in areas with
malaria 
Sickle cell anaemia
Epidemiology
toms 
Signs a nd symp
Pat
• Painful vaso-occlusive crisis  h oph
y Autosomal recessive disorder due to
• Increased infections  sio
Types  l og y missense point mutation of a negatively
• Mild – moderate anaemia  charged glutamate to a
• HbSA
• Hypersplenism  hydrophobic/neutral valine resulting in
• HbSS
• Complications  the formation of sticky pockets when
• HbSC
• HbSBthal  deoxygenated allowing HbS
polymerise and form sickle shape