Recovered File 2scdppt.pptx

7/27/2019 Recovered File 2scdppt.pptx

1/39

Sickle Cell Disease


2/39

Sickle Cell Disease vs Sickle Cell

Anemia

1. Sickle Cell Anemia

Sickle haemoglobin (HbS) + Sickle haemoglobin (HbS)

Most Severe No HbA

Other types of Hb combine with sickle Hb

2. Hemoglobin S-C disease Sickle haemoglobin (HbS) + (HbC)

3. Hemoglobin S-Beta thalassemia Beta thalassaemia gene reduces the amount of HbA that can bemade

Sickle haemoglobin (HbS) + reduced HbA Milder form of Sickle Cell Disorder than sickle cell anemia


3/39

Molecular pathology of SCDThe sickle mutation

GAG

Glutamic acid

GTG

Valine

The s Mutation

6th Codon of-Globin Gene

F: a2g2

A2: a2d2

A: a22

F: a2g2

A2: a2d2

S:a2

s

2


4/39

Prevalence

More than 2.5 million Americans havethe trait

70,000 or more Americans have sicklecell disease

About 1,000 babies are born with the

disease each year in America In Nigeria, 1/3 population of U.S., 45,000-90,000 babieswith sickle cell disease are born each year


5/39

Among African - Americans

1 in 12 have Sickle Cell Trait (Hb SA)

1 in 600 have Sickle Cell Anemia (Hb SS)

1 in 1500 have Sickle C Disease (Hb SC)

1 in 350 have Sickle Cell Disease (Hb SS, SC, S-Beta-Thal)

Among Latinos

1 in 172 have Sickle Cell Trait (Hb AS)

1 in 1,000 have Sickle Cell Disease (Hb SS, SC, S-Beta-Thal)


6/39

Pathophysiology of SCDIn a red blood cell containing mostly Hb S

single Hb Smolecules in free insolution;allows red cell to besoft, round, and

deformable

When oxygenated

+ O2

- O2

- O2

Hb S moleculespolymerize intolong fibers;mishapen,dehydrated and

adherent sicklecells.

When deoxygenated

+ O2


7/39

Sickle red blood cells become hard and irregularly shaped(resembling a sickle)

Forms long rods form inside RBC

RBC become rigid, inflexible, and sickle-shaped

Become clogged in the small blood vessels and thereforedo not deliver oxygen to the tissues.

Lack of tissue oxygenation can cause excruciating pain,damage to body organs and even death.

When sickle haemoglobin (HbS) gives upits oxygen to the tissues, HbS stickstogether


8/39

RBC containing mostly Hb S

- O2

+ O2

+ O2

RBC containing mostly normal Hb

+ O2

- O2

oxygenated deoxygenated

oxygenated deoxygenated


9/39


10/39


11/39

Clinical Pathology of SCD

1. Anemia

2. Vasoocclusion

3. Chronic organ damage


12/39

1. Anemia

Chronic intravascular hemolytic anemia

Acute episodes of severe anemia

Transient red cell aplasia (parvovirus B19)

Acute splenic sequestration

Acute hemolysis (

hyperhemolysis

)


13/39

2. Vasoocclusive complications

Microvascular occlusion clinically silent

Macrovascular occlusion acute ischemic/infarctive damage

pain episodes stroke priapism acute chest syndrome renal papillary necrosis splenic infarction


14/39

3. Chronic organ damage

Splenic dysfunction high risk of bacterial infection

Gram () encapsulated organisms

Progressive dysfunction of: lungs - oxyhemoglobin

desaturation,pulmonary hypertension

kidneys - proteinuria, renal failure

gallbladder - gallstones eyes - proliferative retinopathy joints - osteonecrosis, arthritis heart - CHF


15/39

Pathophysiology of SCDVasoocclusion (1)

A. Prolongation of the RBC microvascular transit time caused

by:

Enhanced red cell adhesion to endothelium and aggregate

formation

Abnormal cation homeostasis with cell dehydration,

irreversibly sickled cell formation

Abnormal vasomotor tone favoring vasoconstriction (via NO,endothelin-1, and eicosanoid dysregulation)


16/39

Pathophysiology of SCDVasoocclusion (2)

B. Reduction in delay time to HbS polymer formation caused by:

Red-cell deoxygenation

Increase in intracellular HbS concentration Low concentrations of protective Hb types (eg, HbF, HbA2)

Fall in pH

C. Miscellaneous potential modulators Free-radical release and reperfusion injury

Coagulation activation with proadhesive thrombin formation


17/39

Early Symptoms

and Complications Typically appear during infant's first year

1st symptom: dactylitis and fever (6 mo-2 yrs)

Pain in the chest, abdomen, limbs and joints

Enlargement of the heart, liver and spleen nosebleeds Frequent upper respiratory infections

Chronic anemia as children grow older

Over time Sickle Cell sufferers can experience damage to

organs such as liver, kidney, lungs, heart and spleen

Can result in death


18/39

ACUTE PAINFUL CRISIS

New onset of pain that lasts at least 4 hours

for which there is no explanation other than

vaso-occlusion and which requires therapy

with parenteral opiods or analgesics in amedical setting


19/39

PAINFUL CRISIS

Hallmark of the disease

Episodic and variable in intensity

Unpredictable Triggered by known and unknown risk factors

Prognostic significance more frequent

episodes predict poorer survival


20/39

TRIGGERS

Stress Emotional and physical

Cold weather

Infections Physical exertion

Hypoxia

Menstruation Pregnancy


21/39

Typical baseline abnormalities in the patient with SCD are as follows:

Hemoglobin level is 5-9 g/dL

Hematocrit is decreased to 17-29%

Total leukocyte count is elevated to 12,000-20,000 cells/mm3 (12-20

X 109/L), with a predominance of neutrophils

Platelet count is increased

Erythrocyte sedimentation rate is lowThe reticulocyte count is usually elevated

Peripheral blood smears demonstrate target cells, elongated cells,

and characteristic sickle erythrocytes

Presence of RBCs containing nuclear remnants (Howell-Jolly bodies)indicates that the patient is asplenic

Results of hemoglobin solubility testing are positive, but they do not

distinguish between sickle cell disease and sickle cell trait


22/39

The diagnosis is confirmedwhen electrophoresis

demonstrates the presence of

homozygous HbS


23/39

Medical Complications

1. pain episodes

2. strokes

3. increased infections

4. leg ulcers

5. bone damage

6. yellow eyes or

jaundice7. early gallstones

8. lung blockage

9. kidney damage and

loss of body water in urine

10. painful erections in men

(priapism)

11. blood blockage in the spleen or

liver (sequestration)

12. eye damage13. low red blood cell counts

(anemia)

14. delayed growth


24/39

Infectious complications

Prominent early in life

Leading cause of morbidity and mortality

Great improvement in the prognosis related to newborn

screening for sickle cell disease, vaccination for childhoodillnesses, the use of prophylactic antibiotics, and aggressive

diagnosis and treatment of febrile events

Acute splenic sequestration

Episodes of rapid increase in splenic size and decrease inhemoglobin

Potential source of morbidity and mortality early in life for

children with sickle cell anemia and at any age for those

with Hb SC disease and sickle thalassemia

Serious Complications


25/39

Strokes

Up to 15% of children may have overt or silent strokes

during childhood Chronic transfusion therapy reduces the recurrence rate

of overt stroke which may approach 75% without

intervention

Bone disease

Early risk is primarily from osteomyelitis

Infectious usually painful inflammatory disease of

bone often of bacterial origin and may result in bone

tissue death Avascular necrosis of the femur and humerus

Death of bone tissue due to disrupted blood supply

Marked by severe pain in the affected region and by

weakened bone that may flatten and collapse

Serious Complications


26/39

Serious Complications: PAINRecurrent Pain Episodes or Sickling Crises

Occur at any age but appear to be particularly

frequent during late adolescence and early adult

life Unpredictable

Red Blood Cells get stuck in the small veins and prevent

normal blood flow

Characterized by severe pain in the back, chest,abdomen, extremities, and head

Highly disruptive to life

Most common reasons for individuals to seek health

care


27/39

1. Fever

2. Chest pain

3. Shortness of Breath

4. Increasing tiredness

5. Abdominal swelling

6. Unusual headache

Danger Signs of a Crisis

7. Any sudden weakness or

loss of feeling

8. Pain that will not go away

with home treatment

9. Priapism (painful erection

that will not go down)

10. Sudden vision change

SEEK URGENT HOSPITAL TREATMENT IF IN CRISIS


28/39

Crises

During a crisis

severe pain in the fingers, toes,

arms, joints,legs, back, abdomen, and bones.

Decrease in oxygen to the chest and lungs

May lead to acute chest syndrome

Damage to the lungs

Severe pain and fever Lungs' airways narrow, further reducing O2

Leads to an increased risk of potentially

fatal infections


29/39

Infections

Thirst and dehydration caused by not drinking

enough even if thirst is not felt Over-exertion

Over-excitement

Cold weather and cold drinks and swimming

Bangs, bumps, bruises and strains

Stress triggers pain in adults, but does not seem to

do so inchildren.

Triggers of Pain


30/39

Children and families can often tell when a

severe sickle pain is coming on by

Thirst

Eyes turning yellow (jaundice),

Sufferer being more irritable or tired than

usual.

Predicting Pain


31/39

Alleviating Pain

Warmth: increases blood flow

Massaging and rubbing

Heat from hot water bottles and deep heat creams

Bandaging to support the painful region

Resting the body

Cognitive Behavioral Therapy

Getting the sufferer to relax

deep breathing exercises

distracting the attention

by other psychological methods.

Pain-killing medicines (analgesics): codeine, non-steroidal anti-

inflammatory, morphine if necessary


32/39

1. Taking the folic acid (folate) daily to help make new red

cells

2. Daily penicillin until age six to prevent serious infection

3. Drinking plenty of water daily (8-10 glasses for adults)

4. Avoiding too hot or too cold temperatures

5. Avoiding over exertion and stress

6. Getting plenty of rest

7. Getting regular check-ups from knowledgeable health care

providers

Daily Preventative Measures


33/39

Treating Complications

Pain-killing drugs and oral and intravenous fluids

To reduce pain and prevent complications.

Transfusions Correct anemia

Treat spleen enlargement in children before the condition

becomes life-threatening

Regular transfusion therapy also can help prevent recurring

strokes in children at high risk of crippling nervous systemcomplications.


34/39

SIMPLE BLOOD TRANSFUSION

Higher H/H values areassociated with morepainful episodes

Transfusion dilutes Hb Sbut increases viscosity

Transfusion is needed insymptomatic anemia,

sequestration crisis, and inaplastic crisis

Do not exceed Hb of 10g

or Hct of 30


35/39

EXCHANGE TRANSFUSION

Acute Chest syndrome

Priapism

Stroke

Retinal arterial vaso-occlusion

Hepatic failure

Septic Shock

Refractory painful crisis

Chronic transfusionregimen

Wayne A et al. Blood 1993; 81(5):1109-1123


36/39

16% Early Readmission rate

Inappropriate management of the

hypercoagulable state, evident at the stage of

resolution.

Premature discharge

Opioid withdrawal syndrome after discharge


37/39

Hydroxyurea

The first effective drug treatment for adults with severe

sickle cell anemia reported in early 1995

Daily doses of the anticancer drug, hydroxyurea, reduced

the frequency of painful crises, acute chest syndrome,

needed fewer blood transfusions

Increases production of fetal hemoglobin in the blood

Fetal hemoglobin seems to prevent sickling of red cells

cells containing fetal hemoglobin tend to survive longer

in the bloodstream

Treatments


38/39

Bone marrow transplantation

Shown to provide a cure for severely affectedchildren with sickle cell disease

Only about 18 percent of children with sickle

cell anemia are likely to have a matched

sibling.


39/39

Recovered File 2scdppt.pptx

Documents

Transcript of Recovered File 2scdppt.pptx