Miller Sickle Cell

Front 1

Sickle cell mutation

Back 1

Abnormality of the β-globin gene
A single nucleotide polymorphism (GAG → GTG) at codon 6
valine substituted for glutamic acid
Predisposes to polymer formation at low oxygen concentrations

Front 2

HbS mechanism

Back 2

When sickle hemoglobin (HbS) gives up its oxygen to the tissues, HbS sticks together
-Forms long rods form inside RBC
-RBC become rigid, inflexible, and sickle-shaped
-Unable to squeeze through small blood vessels, instead blocks small blood vessels
-Less oxygen to tissues of body
RBCs containing HbS have a shorter lifespan
-Normally 120 days
-Chronic state of anemia

Front 3

Sickle cell risks

Back 3

In the black African-American population, carrier rates are as high as 8%
1:600 blacks are homozygous (SS) with symptoms of sickle-cell disease (SCD)
The other forms of SCD (SC & sickle-thal) combined are as common as SS
Shortened life expectancy; increased rate of sudden cardiac death (20x)
Manifests as a chronic disease requiring life-long medical management

Front 4

Sickle cell inheritance

Back 4

Autosomal Recessive
If both parents are carriers (AS), there is a 25% chance the child will be affected
If both parents are have SCD (SS), there is a 100% chance the child will be affected
If one parent is a carrier (AS) and the other has disease (SS) there is a 50% chance the child will be affected
*not everyone knows they are a carrier/have disease

Front 5

Sickle cell penetrance

Back 5

In homozygous disease (SS) there is considerable variability in symptoms
Ranges from minimal symptoms to full disability as a result of disease
SC disease and sickle-thal --> disease variability greater

Front 6

Sickle cell cascade

Back 6

Cells sickle
Vasoocclusion leads to WBC adhesion to endothelium
Inflammation begins
Hemolysis, nitric oxide scavenging, more endothelium destruction
Coagulation activated
Membrane damage
Lose K+
RBCs are dehydrated leading to more sickling

Front 7

Sickle cell pain crisis

Back 7

60% of patients have at least
one significant pain crisis each year
Pain is secondary to tissue infarction caused by poor blood flow
Ischemia can occur in muscle, bone, or visceral organs
The amount of pain is not always related to the severity of infarction

Front 8

Sickle cell clinical manifestations

Back 8

Chronic hemolytic anemia
-Gallstones (bilirubin)
-Risk of red cell aplasia (Parvovirus)
-Decreased vascular tone
Susceptible to infection
-Functional asplenia
-Infarcted tissue
-Numerous manipulations
Vaso-occlusion
-Pain crisis
-Brain, lung, ankle, erectile vasculature susceptible

Front 9

Acute chest syndrome

Back 9

Significant vaso-occlusion occurs within the lung
Chest pain, fever, abnormal chest x-ray and hypoxia
Systemic hypoxia can precipitate additional sickling…

Front 10

Mechanism of lung injury

Back 10

Regional pulmonary hypoxia leads to sickling
Sickling increases vascular adhesion and production of vasoactive substances
Reoxygenation is followed by reperfusion injury (free radical damage)
Progressive tissue damage with altered pulmonary vascular tone, vascular proliferation in the muscle wall and hypercoagulable state causing pulmonary thrombosis and progressive loss of the vascular bed
Obliterative pulmonary vasculopathy with pulmonary hypertension

Front 11

Vaso-occlusive complications

Back 11

Stroke
Avascular osteonecrosis
Priapism (prolonged erection)
Pregnancy complications
-increased risk of thrombosis
-HbF steals oxygen from mom
Leg ulcers
Renal insufficiency

Front 12

Precipitating factors leading to vaso-occlusinve events

Back 12

hypoxia
acidosis
fever
infection
dehydration
exposure to cold

Front 13

Sickle cell hospitalizations

Back 13

Approximately 5% of patients account for 25-50% of hospitalizations
High use group has >10 hospitalizations/year
Hospital stay is longer (10 days vs. 6 days)
Young, poor, unemployed, male
Difficult interpersonal interactions
May be associated substance abuse
Higher death rate

Front 14

Sickle cell increased risk of infection

Back 14

Auto-infarction of spleen results in increased virulence by encapsulated bacteria:
-Strep pneumoniae
-Neiserria meningitidis
-Hemophilus
Incr. E. coli, S. aureus, and salmonella infxn
Risk of deadly infection is >300-fold
Therefore pediatric immunizations are important
-influenza
-pneumococcal 23 valent
-meningococcal

Front 15

Diagnosing sickle cell

Back 15

History of present illness
Family history
Blood counts and peripheral smear
Hemoglobin electrophoresis

Front 16

Managing sickle cell disease

Back 16

Transfusion & RBC exchange
-Used to treat emergent complications
-Also used for prevention (i.e. stroke)
Medications
-Hydroxyurea: chemotherapeutic, increases NO production which increases cGMP which increases HbF, shifts curve to left and reduces hypoxic state
-Folic Acid
-Vaccines & prophylactic antibiotics (newborns to age 5 or beyond)
-Pain medications (chronic & breakthrough)
Health maintenance
-Regular follow-up, screening labs, doppler studies
-Multidisciplinary approach

Front 17

Sickle cell cases

Back 17

Pain in chest, back, legs
-sickle crisis
Illness, hematocrit drops, low retic
-parvo
Hematocrit drop, enlarged spleen
-Splenic sequestration
Sudden hip pain, xray normal
-osteonecrosis
symmetrical swelling in hands and feet with fever
-dactylitis
Sudden LUQ pain and severe tenderness
-Splenic infarction/rupture