Sickle Cell

Sickle Cell Definition and Pathophysiology

• Caused by a mutation in HgbS, with HgbSS (Sickle Cell Anemia) accounting for 60-65% of the associated hemoglobinopathies
• In normal Hgb A, the 6th position on the beta chain is glutamic acid. In sickle cell, it is replaced by valine.
• This changes the RBC configuration to form microtubules that create a banana or crescent (sickled) RBC shape that can be brought about by certain extreme condition such as infection, dehydration and extremes in temperature
• RBC lifespan is reduced from 120 days to 10-20 days.
• After repeated sickling episodes, RBCs become irreverisibly sickled
• Sickled RBCs bind to the vascular endothelium leading to inflammation with leukocytosis, hemolysis with nitrous oxide deficiency, and vascular ischemia
• WOODEN RAFTS IN CIRCULAR WATER SLIDE

Sickle Cell Incidence/Genetics

• Mutation that developed in Western Africa as a response to malaria because morbidity and mortality markedly decreased in those who carry sickle cell trait and have disease, therefore it is most prevalent in areas where malaria is endemic
• Generally diagnosed through newborn screening (done in most states), affects 90,000-100,000 people in the US
• Autosomal recessive- 25% of Sickle Cell Disease, 50% chance of being a carrier (assuming both parents are carriers)

Sickle Cell Initial Presentation

• Usually visible between 6-12 months as fetal Hgb is replaced with HgbS.
• This is a CHRONIC disease with ACUTE exacerbations
• Consider that it affects oxygen getting to the body because the RBCs are malformed and unable to carry oxygen effectively and they do not last as well, so it can affect any part of the body.

Sickle Cell Diagnosis

• Hemoglobin Electrophoresis is necessary for a definitive diagnosis of sickle cell
• Other common diagnostic tests include:
• CBC, CMP, LDH, Ferritin, U/A with protein/creatinine ratio and microalbumin, blood cultures
• CXR- in presence of respiratory sx, fever or both
• Abdominal U/S if gallstones are suspected
• TCD annually to assess risk for stroke in children with severe types of SCD
• Echo and EKG
• MRI of joints if avascular necrosis is suspected
• Pulmonary function testing (PFTs)
• Neuropsychological testing
• Opthalmologic testing

Sickle Cell Treatment

• With the development of newborn screening, focus has become less about treating complications and become more about prevention
• Prophylactic penicillin, immunizations (especially pnuemococcal) and family education established early
• Hydroxyurea for severe cases of SCD helps to stimulate production of fetal Hgb, increase nitrous oxide and decrease leukocytosis but needs close monitoring because of its myelosuppressive effects
• Regular RBC transfusions are warranted as treatment for patients with history of stroke, debilitating pain, severe and multiple episodes of ACS or recurrent priapism.

Sickle Cell Future Therapies

• BMT is the only known cure for SCD and used to be reserved for the sickest patients with the best HLA matching
• Some studies are exploring the following use of unrelated donors as well as using nonmyeloablative methods to create a curative chimerism and decreasing toxicity
• Gene therapy
• Manipulation of the RBC to prevent the damage caused by the sickling process
• Other ways to increase fetal Hgb in the body

Sickle Cell Acute Complications

• Fever/Infection
• The spleen suffers major infarction in the first 6-12 months due to lack of oxygen, putting patients with SCD at greater risk for pneumonia, bacteremia, and osteomyelitis
• SCD patients cannot produce specific immunoglobulin antibodies to polysaccharide-encapsulated organisms, particularly Streptococcus pneumoniae (leading cause of death in children with SCD)
• Fever is a medical emergency and requires evaluation and broad spectrum abx

Sickle Cell Acute Complications

• Pain Crisis/Vaso-occlusive crisis (VOC)
• Combination of the following:
• damage to the vascular endothelium
• vascular inflammation
• occlusion of blood vessels resulting in tissue ischemia
• Brought about by infection, stress, high altitude, exposure to the elements, strenuous exercise OR it is completely spontaneous
• "Hand-and-foot syndrome" (dactylitis) occurs in hands/feet of infants and young children, often the first presenting sign for SCD patients
• Treatment of pain crisis includes:
• Increased fluids
• Analgesics- opiods and NSAIDs
• Consider past crises and effectiveness of pain management
• Consider cultural beliefs and family coping with pain mgmt
• Continually be assessing pain and efficacy of treatment plan

Sickle Cell Acute Complications

• Acute Chest Syndrome
• Rapid deterioration in respiratory function with potentially lethal complications
• Greatest incidence occurs in children
• Most common cause is fat/bone emboli and infection, almost always accompanied to some degree with sickling and lung ischemia
• Etiology (depending on the cause) usually includes inflammation, pulmonary vascular occlusion, ventilation/perfusion mismatch, airway hyperactivity, and pulmonary edema
• Risks include:
• Pneumonia
• Pain crisis
• Nursing interventions should include:
• Ambulation, incentive spirometry
• Monitoring pulse ox, respiratory status
• Treatment involves
• Antibiotics
• Supplemental oxygenation and bronchodilators
• Careful pain management with analgesics and fluids
• Blood transfusions or exchange transfusion depending on severity of ACS

Sickle Cell Acute Complications

• Splenic sequestration
• Sickled RBCs in the blood get trapped in the spleen leading to:
• Splenomegaly
• Rapid, severe drop in Hgb with compensatory rise in Reticulocyte count
• Drop in platelets as they get trapped in spleen as well
• Often associated with fever and infection
• Treatment includes:
• Hydration
• CAUTIOUS TRANSFUSION- should be done conservatively to avoid autotransfusion
• Autotransfusion- can occur when the transfused RBCs cause the spleen to release the trapped RBCs back into circulation, potentially leading to increase in the blood's viscosity and volume.
• Splenectomy may be necessary as sequestration is likely to recur

Sickle Cell Acute Complications

• Aplastic Crisis
• Occurs as a result of parvovirus B19 infection or some other viral infection (but usually parvo)- also known as "Fifth Disease"
• Virus leads to temporary shut down of RBC production in bone marrow (reticulocytosis)
• Accompanied with the usual SCD hemolysis, leads to a severe drop in Hgb with an extremely low reticulocyte count
• Treatment:
• Slow and careful transfusion of RBCs to monitor for fluid overload in children who have compensated for

Sickle Cell Acute Complications

• Cerebral vascular accident or stroke
• Sickling process causes inflammation of cerebral vessels combined with sticky, rigid sickle cells that obstruct blood flow to the brain leading to ischemia and infarction of the brain tissue which leads to permanent damage.
• First Goal: Stabilize the patient
• Second Goal: Minimize further damage by rapidly decreasing percentage of Hgb S in the body, this is accomplished by exchange transfusions and should NOT be delayed if stroke is suspected
• Other goals include: oxygenation and circulation support, radiologic evaluation (after patient is stabilized)

Sickle Cell Acute Complications

• Priapism
• Can occur in children as young as 3 years of age
• Sickling leads to obstruction of the blood vessels in the penis, leading to prolonged, unwanted and painful erection
• If not treated, can lead to impotence
• Treatment includes:
• Aggressive hydration
• Vasodilation
• Pain management
• Exercise
• Exchange transfusion or surgical intervention by urologist may be necessary
• Pseudoephedrine or etilefrine have been found to be successful in prevention of priapism.

Sickle Cell Chronic Complications

• Retinopathy
• Often seen with adolescents or adults
• Due to sickling of the blood vessels of the retina, leading to inflammation, vaso-occlusion and ischemia
• Collateral circulation develops but the blood vessels are fragile and have a tendency to hemorrhage and can cause retinal detachment
• May require treatment with laser surgery
• Cardiopulmonary Changes
• Cardiomegaly often results from chronic anemia and may cause EKG changes and eventually congestive heart disease if left untreated
• Pulmonary hypertension can lead to hemolysis, lack of nitric oxide bioavailability, and high mortality in SCD; those measurements of tricuspid regurgitation jet velocity that are considered "normal" for the rest of the population have been linked to a TENFOLD increase in sudden cardiac death in patients with SCD
• Treatments include Viagra, nitrous oxide
• Decreased pulmonary function and restrictive airway disease have been associated with Acute Chest Syndrome (ACS), Vaso-occlusive crisis (VOC) and early death.

Sickle Cell Chronic Complications

• Cholelithiasis (Gallstones)
• Hemolysis of RBCs leads to increase in bilirubin which can cause formation of gallstones
• This can cause the gallbladder to become inflamed and painful, leading to cholecystitis
• May require cholecystectomy (gallbladder removal)
• Avascular necrosis
• Sickling can even effect the sinusoids of the marrow leading to "sludging" and thus causing marrow necrosis in the ball-and-socket joints
• Over time, the ball part of the joint becomes rough and jagged and may even lead to a full collapse of the joint
• In children, rest and PT may be enough to help them recover but adolescents and adults may progress to the point where replacement is the only viable option
• Leg Ulcers
• 10-15% of young adults, resulting from poor tissue perfusion to the legs (much like diabetes patients)
• Regular transfusion with RBCs usually helps to dilute sickle cells and promote healing

Sickle Cell Chronic Complications

• Renal Impairment
• The acidic and hypoxic environment of kidneys means that the sickling process can lead to significant damage of the glomeruli
• Hyposthenuria, or the inability to concentrate urine, is usually the result and is often exhibited in children by nocturnal enuresis (bed wetting) and it can contribute to dehydration
• Extensive damage to glomeruli results in nephropathy which can progress to renal failure; dialysis and transplant are often inevitable
• Delayed Growth and maturation
• Chronic anemia + high caloric need means delayed physical growth and puberty
• However, early interventions with endocrinologist and nutritionist should be considered
• Impaired cognition
• Possibly caused by "silent" infarcts to the brain tissue
• Also related to missed school from hospitalizations and chronic anemia
• Annual transcranial doppler (TCD) should be performed between ages 2 and 16 to assess increased risk for stroke
• Evaluation should be performed by trained neuropsychologist

Sickle Cell Prognosis

• Average life span is 45-65 years
• Three findings are associated with more severe cases of SCD:
• Dactylitis before age 1
• Consistently elevated WBC count
• Baseline Hgb of 7gm/dl or less
• Severity of the disease depends on the subtype inherited (See Table 11-1)
• The following are usually severe:
• HbSS
• Hb SS w/o fetal Hgb F
• Hb SC
• Hb S0-thalassemia