Unit III- Sickle Cell Anemia (Clinical) Flashcards
1
Q
Clinical Aspects of Sickle Cell Disease
A
- group of disorders with sickle hemoglobin (Hgb S) in the homozygous state causes diseases
- Hgb S mutation results in polymerization of Hgb upon deoxygentation causing: increased RBC destruction and anemia and blockage of capillaries causing pain and/or organ dysfunction
2
Q
Sickle red blood cell
A
- the formation of linear chains of polymerized hemoglobin S eventually become enough in numbers and length to distort the flexible red blood cells shape
- the identification of sickle-shaped red blood cells as a cause of clinical symptoms was first reported in 1910
3
Q
Sickle Cell Vaso-occlusion
A
- very flexible normal red cells with a diameter of ~7 microns transverse capillaries with a diameter as small as 3 microns
- sickled erythrocytes can cause capillary obstruction leading to localized tissue hypoxia, pain and possible organ dysfunction
4
Q
Frequency and Severity
A
- 1/400 African Americans have sickle cell disease which is often life-threatening
- average life-span close to 50 for females and just over 45 for males
- 30%)
- compare to 1/3000 incidence of cystic fibrosis in US population
- in real world of patient care, racism plays a very large role
5
Q
Clinical Severity
A
- depends on the type of sickle cell disease
- even within a type, great variation in severity
- ~20% of patients have ~80% of complications while the rest have relatively mild disease
- cause of clinical variability still poorly understood:
- likely relates to other genotypes such as RBC or WBC adhesion to endothelial cells enhancing vaso-occlusion
- simply high WBC may increase risk of disease
- improved ability to predict more severe disease may better guide therapy and decrease morbidy/mortality
6
Q
Initial Diagnosis
A
- Fetal Hgb >90% newborns HgB- unaffected by sickle mutation and protects newborn for the first 3-4 months
- in past Dx made when complications arose
- some infants died of bacterial sepsis since Dx unknown and fever not managed appropriately
- NB screening in USA allows Dx, education and prophylactic antibiotics prior to risk of sepsis, decreasing morbidity and mortality
7
Q
Hemoglobin electrophoresis
A
- hemoglobins with different charge can be separated by migration in an electric field
- the B6 mutation in sickle cell changes a negatively charged glutamic acid to a neutral valine, causing a significant shift in electophoretic migration
- hemoglobin C is a distinct mutation which when combined with hemoglobin S results in a form of sickle cell disease
- Hemoglobin C and hemoglobin S are distinct mutations of the 6th amino acid on the beta chain of hemoglobin
8
Q
The Variants of Sickle Cell Disease
A
- Sickle cell trait (AS)
- carrier state in 8-10% African Americans
- 55-65% Hgb A, 35-45% Hgb S
- clinical complications are very rare
- main issue is genetic implications
Homozygous sickle cell anemia (SS)
- > 2/3 of patients and most form of severe sickle cell disease
- both parents AS, 25% risk of child with SS
9
Q
Hemoglobin SC Disease
A
- one parent AS and other AC
- AC found in 2-3% African Americans
- C also defect of beta 6 position (lysine not valine)
- C does not sickle but increases Hgb viscosity
- ~1/4 of patients, milder disease
- 50% S-50% C- No A
10
Q
Sickle beta thalessemia
A
- Hgb S from sickle gene, little or no Hgb A from ineffective beta thalassemia gene
- 1 parent AS trait, 1 parent thalassemia trait
- Sickle beta thalassemia can be very severe if no hemoglobin A is produced by the thalassemic gene or much milder if there is some hemoglobin A production
11
Q
Clinical Complications: Bacterial Sepsis
A
- splenic vaso-occlusion inhibits bacterial clearance
- encapsulated bacteria (pneumococcus) in previously unexposed children require splenic clearance
- risk beings by 4 months; 15% incidence without penicillin prophylaxis
- frightening complication- 30-50% mortality, 2/3 of deaths within 8 hours of 1st symptoms; most common cause of death <5 years of age
- penicillin prophylaxis, aggressive antibiotics Rx of fever (usually cerfrixanone), immunizations greatly decrease risk
12
Q
Painful Vaso-Occulusive Episode
A
- most common complication throughout life
- not clear why they are so episodic and unpredictable, usually lasting a few days
- hand foot syndrome often 1st in 1st-2nd years of life
- episodes can involve almost any area
- pain can be excruciating and often need narcotics- doses are still often inadequate, morphine patient controlled analgesia best, respiratory depression and addition are rare
- supportive care- pain control, fluids, sure oxygenation, control fever, transfusion not usually helpful
13
Q
Stroke
A
- 10% develop stroke with unilateral weakness
- acute unpredictable onset usually in child
- long term neurologic deficits»_space; death
- RBC transfusions as Rx and prophylaxis- exchange transfusion acutely, chronic RBC transfusions to prevent recurrence, indication for bone marrow transplant
- stroke prevention with transcranial Doppler: high cerebral arterial flow rates predict high risk, prevent 80% of strokes with annual studies age 2-16 years
14
Q
Acute Chest Syndrome
A
- unique term for acute lung disease in sickle cell disease because difficult to determine cause
- includes any/all of these etiologies: infection/vaso-occlusion/fat embolus
- most common cause of death > 5 years of age and can cause chronic lung disease/adults
- Rx- antibiotics, oxygenation, incentive spirometry, transfusion acutely if more severe and occasionally chronically to prevent recurrence
15
Q
Acute splenic sequestration crisis
A
- sudden enlargement of the spleen due to acute vaso-occlusion
- occurs in 1st 5 years of life and can rapidly result in hypovolemic shock
- acute treatment involves fluid resuscitation and transfusion
- teaching parents splenic palpation reduces mortality
- just make sure you listen to the family
- it is difficult to palpate the spleen of a crying child
