SICKLE CELL DISEASE Flashcards
The term SCD includes all the conditions in which the clinico- pathological manifestations are attributable to the _________________________ in association with another haemoglobin variant.
presence of sickle haemoglobin (Hb S)
EPIDEMIOLOGY
___________ has the largest burden of SCD in the world.
Nigeria
Genetics of SCD
SCD is a common genetic problem with enormous challenges.
It is inherited as autosomal ___________ genes
The affected gene is located in the _____ codon of chromosome ______
recessive
6th; 11
The Hb S is due to a ___________ mutation resulting in the replacement of __________ by __________ in the ___th amino acid position of the _____ chain of normal haemoglobin, Hb ____
single point
glutamic acid ; valine
6th ; ß
A
HEMOGLOBIN GENOTYPES
There are 4 important genotypes among patients of West African origin:
______ disease (Sickle cell anaemia)
______ disease
______________
_________________
SS disease (Sickle cell anaemia)
SC disease
Sß+ thalassaemia
Sß0 thalassaemia
Implications of HbS
The red blood cells (RBC) in HbSS have low __________________________, this disfigures them into the peculiar sickle shape and stimulates _________ into aggregates of dense fractions.
These are either removed ( ____________ ) and/or destroyed ( _____________ ) by R.E.S. (________/__________ )
oxygen carrying capacities
stickiness
sequestrated; haemolysed
spleen/liver
Implication of HbS /2
The dense cells of the RBC cohort have an adhesive tendency towards _______________
The injury to the vascular endothelium triggers the ___________ pathway. This partly explains the _________________________ and reactive thrombocytosis seen in SCD
vascular endothelium
coagulation
thomboembolism platelet consumption
Implication of HbS /3
Vaso-occlusion results from:
_____________ damage from sRBC adhesion
platelet _____________ in the _____________
thrombocytosis
_________ dehydration occassioned by hyposthenuria
All these lead to ____________ in the micro –circulation.
endothelial ; aggregation ; micro circulation
chronic ; sludging
A high level of ______ haemoglobin (Hb___) is known to prevent the ___________ of deoxygenated HbS and thereby ameliorates the severity of the disorder
fetal; F
polymerization
Implication of HbS /4
The end results of repeated sequestration and haemolysis are (a) __________ and (b) __________ /compensatory __________.
Whilst the protein component of the haemolysed RBC is ________________ , the iron containing haem component is deposited in the __________, __________ and __________; excess of which can cause __________.
When breakdown of RBC exceeds excretion, it results in __________ and __________ disease
anaemia ; hypersplenism
thrombo- cytosis.
excreted in urine,
liver, kidney and heart
haemosiderosis. ; jaundice ; gall bladder disease
Implication of HbS /5
Repeated tissue anoxia/infarction in:-
KIDNEYS- __________ Dsease
BRAIN - ————,_______
LUNGS - ___________
GUS - __________
EYES - __________
Proliferative glomerular
CVA, Seizures
Acute chest syndrome (ACS)
Priapism
Proliferative retinopathy
Implication of HbS /5
Repeated tissue anoxia/infarction in:-
LIVER - _______________
SPLEEN - ____________
HEART - ____________
Hepatomegaly
Fibrosis/ Cirrhosis.
Autosplenectomy
Ischemic heart disease
Implication of HbS /5
Repeated tissue anoxia/infarction in:-
BONE -
__________ crisis (BPC)
Aseptic _____________________
_____________
Bone pain
necrosis of head of femur
Osteomyelitis
Implication of HbS /6
Immunity - _____________ arising from repeated infarcts in the spleen is largely responsible for the diminished immunity in SCD
Autosplenectomy
DIAGNOSIS
Pre-natal diagnosis (PND)
•__________ guided __________ sampling in the __________ trimester of pregnancy
•___________________________ diagnosis (PIGD) The diagnosis requires polymerase chain
reaction (PCR) to amplify DNA for analysis
ultrasound ; chorionic villus ;first
pre-implantation genetic diagnosis (PIGD)
DIAGNOSIS /2
•__________ test
1% Sodium methabisulphite
__________ test
•Hb genotype
Cellulose acetate electrophoresis
Agar gel electrophoresis
Fast track test
Sickling test
Solubility test
Clinical Manifestation
Sß0 thalassaemia
SC and Sß+ thalassaemia
proliferative sickle retinopathy.
Natural History:
It is found where falciparum malaria is or was endemic
In unchecked falciparum malaria areas
_____ are fit (can survive malaria)
____ are less fit
____ are unfit
AS
AA
SS
Natural History: ……contd.
The baby is usually ________ at birth
Diagnosis of the condition can be made at birth using _______________
Between 4 – 6 months of age baby can develop _______________ crisis
By the age of 9 months – 1year baby may develop ______________
normal
agar –gel electrophoresis
acute splenic sequestration
hand and foot syndrome
CLINICAL PRESENTATION (general)
_________
__________
Sickle cell habitus:
-_________
-________
-____________ limbs
- Delayed growth and development
Pallor
Jaundice
Frontal bossing; Prognatism
Thin and long
CLINICAL PRESENTATION /2
Anaemic crises:
_____________
Megaloblastosis
________ anaemia
Hyper-__________
Splenic sequestration
Aplastic; haemolysis
CLINICAL PRESENTATION /3
Vaso-Occlusive crises:
List 6
Dactylitis
Bone pain crises
Bone infarction / infection Acute chest syndrome Priapism
Stroke
CLINICAL PRESENTATION /5a
Stroke is a major neurological complication in SCD.
In children, it results from __________ due to arterial narrowing or occlusions of intracranial arteries.
It involves _________-artery disease of the internal carotid and anterior and middle cerebral arteries of the Circle of Willis.
In adults it is usually ____________.
cerebral infarction
large; haemorrhagic
Studies have shown that “silent” lesions occur on MRI studies even in the absence of clinical signs.
These silent lesions are known as _____________________
They are diagnosed as _______ values on ___________________ (TCD) ultrasound examinations and are associated with a high risk of stroke
Silent Cerebral Infarcts (SCI).
high flow
transcranial doppler
CLINICAL PRESENTATION /5c
In children with SCA, SCI are prominent in infants and toddlers younger than ________of age.
SCI is seen in MRI in 22% of Hb-SS patients and 6% of SC disease.
Prevalence of SCI in Nigerians with SCA is not known.
4 years
Clinical presentation
Current guidelines recommend ______________ therapy for patients who have stroke and those with abnormal TCD findings before they become symptomatic (when they have flow velocities greater than ______ cm/sec).
indefinite transfusion
200
CLINICAL PRESENTATION /5e
Although TCD screening is clearly predictive, this facility is almost non existent in Nigeria
Chronic blood transfusions is impracticable due to unavailability of regular blood supply and adequate screening.
____________ (HU) is recommended for prevention of recurrent stroke.
HU is started at _____ mg/kg/d and escalated to
_____mg/kg/d while the child’s HbF response and possible hematologic toxicity are being monitored
Hydroxyurea
15; 30
CLINICAL PRESENTATION /5f
Approximately 5% to 10% of children with SCD will develop a stroke, most often in the _______ decade of life.
The peak incidence of stroke occurs in children between the ages of ____ and _______ years
first
2 and 10
CLINICAL PRESENTATION /6
ADOLESCENTS
Acute manifestations continued:
________
______ ulcer
Acute _______________
Stroke
Priapism
Leg
multi-organ failure
CLINICAL PRESENTATION /7
Chronic manifestations include:
Functional __________
________________ of the hip
_____________
Cholelithiasis
asplenia
Avascular necrosis
Hyposthenuria
MANAGEMENT
GENERAL
Regular clinic attendance
- Daily __________ intake
- Daily __________ intake
- Daily __________ intake + - __________ vaccine
- __________ check
Avoid __________ and __________; Keep (cold or warm?).
Good nutrition
folic acid
proguanil
oral penicillin intake + - Pnumovax vaccine
Haemoglobin
dehydration; Stress; warm.
MANAGEMENT /2
SPECIFIC TREATMENT:
Intravenous hydration
___________
________ therapy
Antibiotics
Blood transfusion
Anti-sickling agents e.g____________
Appropriate surgery
Prosthesis
Analgesics
Oxygen
Hydroxyurea
MANAGEMENT /4
OTHER MODLITIES OF TREATMENT:
____________ transplantation
? Gene therapy
Bone marrow
