Kembara Xtra - Medicine - Sickle Cell Anemia

Medicine - Sickle Cell Anemia ​
Basic description: Hereditary hemoglobinopathy with acute episodes of severe crises, chronic hemolytic anemia, and increased susceptibility to infections
 Usually asymptomatic without anemia, sickle cell trait (Hb AS), a heterozygous disorder, is also known as sickle cell disease (SCD) or Hb SS illness.

Child Safety Considerations

 Hand-foot syndrome and sequestration crises, which are frequently encountered in newborns and young children.

Strokes typically happen in children.
Teenage/early adulthood:
- As people age, problems and organ/tissue damage occur more frequently.
- Psychological issues such as body image, missed classes, activity restrictions, disease stigma, and low self-esteem 

pregnant women's issues
Fetal mortality is 35-40%; complicated, especially during the third trimester and delivery. If the fetus survives to the third trimester, the survival rate is >90%.
– High prevalence of small for gestational age (SGA) births and six times the control rate of maternal death
 
Partial exchange transfusion in the third trimester may minimize maternal morbidity and fetal mortality, but it is debatable. Increased risk of thrombosis, premature delivery, pain, toxemia, infection, pulmonary infarction, and phlebitis.
Chronic transfusions have been successful in reducing pregnant women's pain episodes. However, due to the possibility of alloimmunization, this approach should be utilized with caution.

EPIDEMIOLOGY Prevalence 3 million Americans have the sickle cell trait, and 100,000 Americans have sickle cell anemia (SCA). People of African heritage are primarily affected by the illness.
Affected ancestries may also include Mediterranean, Hispanic, Middle Eastern, Asian, and Indian.


PATHOPHYSIOLOGY AND ETIOLOGY
The amino acid valine replaces glutamic acid at the sixth position of the -globin chain to form hemoglobin S (HbS). Valine residues that are hydrophobic interact with other hydrophobic residues to form HbS polymers.
With higher HbS concentrations and in deoxygenated circumstances, HbS polymerization takes place in the RBC, which causes sickling.
Sickle RBCs have enhanced adhesion, are rigid, and have limited ability to move through narrow arteries, increasing blood viscosity, causing stasis, and occluding capillaries and small arterioles, which causes ischemia.
Chronic anemia; emergencies
- Vaso-occlusive crisis: tissue necrosis and ischemia; accumulating organ failure/tissue destruction - Hand-foot syndrome: Small blood vessels in the hands or feet are affected by vascular blockage or ischemia.
- Aplastic crisis: severe illness (such as parvovirus and other viral infections) that suppresses the synthesis of RBCs. - Reduction in RBC production
Sequestration crisis: splenic blood sequestration (only in young children as the spleen is eventually lost to autoinfarction) Hyperhemolytic crisis: rapid hemolysis with reticulocytosis; increased RBC fragility/shortened lifespan 
Splenic dysfunction or absence reduces the body's capacity to fight off infection; a failure in a different pathway for complement activation increases susceptibility to infection. 
Increased red cell oxidation lowers hemoglobin levels, which leads to anemia and weariness.

Autosomal recessive genetics. The heterozygote condition can also be paired with other hemoglobinopathies: homozygous condition, Hb SS; heterozygous condition, Hb AS. Clinically speaking, sickle cell hemoglobin C (HbSC) illness and S+ thalassemia resemble the heterozygous form, whereas S thalassemia resembles the homozygous condition.

Vaso-occlusive crisis (also known as a "painful crisis") risk factors include hypoxia, dehydration, high elevations, stress, fever, infection, acidosis, cold, anesthesia, vigorous exercise, alcohol, and smoking. 
Aplastic crisis (restraining RBC production) is brought on by severe infections, human parvovirus B19 infection, and folic acid deficiency. Hyperhemolytic crisis (accelerated hemolysis with reticulocytosis) is brought on by acute bacterial infections and exposure to oxidants.

DURATIONAL PREVENTION
Avoid hypoxia, dehydration, colds, infections, fevers, acidosis, and anesthesia to prevent crises from occurring.
- Quick treatment for fever, infections, and pain - Refrain from drinking and smoking. Avoid regions with high altitudes.

Using aseptic approach is crucial for reducing trauma.

DISEASE HISTORY

Due to the existence of fetal hemoglobin, it is frequently asymptomatic in the first few months of life. However, in people older than six months, the first signs include irritability and painful swelling in the hands and feet (hand-foot syndrome). Acute chest syndrome, pallor, jaundice, or splenomegaly may also be present, as well as pneumococcal sepsis or meningitis, severe anemia, acute splenic enlargement (splenic sequestration), and severe anemia. 
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Anemia, severe or persistent musculoskeletal or abdominal discomfort, aplastic crisis, acute chest syndrome, splenomegaly or splenic sequestration, and cholelithiasis are symptoms seen in older children. 90% of all hospital admissions are due to painful crises in the viscera, back, abdomen, joints, bones, and joints.
Tachycardia, fever, and bilateral infiltrates brought on by pulmonary infarctions are symptoms of acute chest syndrome. 

DETECTION & INTERPRETATION OF DIAGNOSIS
Initial examinations (lab, imaging)
Screening test: Hemoglobin electrophoresis and the Sickledex test (diagnostic test of preference); SCA (FS pattern) - 80–100% HbS, varying levels of HbF, and no HbA1
- 30-45% HbS, 50-70% HbA1, and little HbF with the Sickle Cell Trait (FS pattern).
Mean corpuscular volume (MCV) normal to raised; mean corpuscular hemoglobin concentration (MCHC) increased; reticulocytes 3-15%; hemoglobin 5 to 10 g/dL
Leukocytosis; bands without infection, increased platelets; sickled RBCs, nucleated RBCs, and Howell-Jolly bodies in the peripheral smear 
Serum lactate dehydrogenase (LDH) raised, fecal/urinary urobilinogen high; ferritin highly higher in individuals who have received several previous transfusions; serum bilirubin somewhat elevated (2 to 4 mg/dL); 
Very low or nonexistent haptoglobin
Hemoglobinuria, hematuria (sickle cell trait may have painless hematuria), and increased albuminuria (monitor for developing kidney disease) are all found in urine samples. 
Imaging depends on the clinical situation.
- CT/MRI to rule out CVA; high index of suspicion needed for any acute neurologic symptoms other than a mild headache; bone scan to rule out osteomyelitis - Acute chest syndrome on chest x-ray may reveal diffuse alveolar infiltrates and an enlarged heart.
Start using the transcranial doppler at age 2 and repeat it annually.
Children aged 2 to 16 are identified as having a higher risk of stroke by transcranial Doppler ultrasound; this test may be normal in cases of clinically quiet strokes. - ECG to check for pulmonary hypertension and an echocardiography every two years starting at age 15 and above.

Treatment and general precautions
Whether or not the patient is hypoxic, fluids, analgesics, and oxygen are necessary during painful crises. 
To identify proliferative sickle retinopathy, retinal examination should begin in school-age children. 
Cognitive and behavioral therapies, occupational therapy, and support groups 
In accordance with this, all recommended children vaccines should be given.
Specific vaccinations
Conjugated pneumococcal vaccination (PCV13) at ages 2, 4, and 6 months; booster at 12 to 15 months; influenza vaccine every year
- Patients under the age of five who have incomplete immunization records should get the necessary catch-up shots.
– Adults over the age of 19 who have functional asplenia and have never gotten the pneumococcal vaccine should get one dose of PCV13, then get PPSV23 at least eight weeks later. For people with functional or anatomic asplenia aged 19 to 64, a second PPSV23 treatment is advised five years following the initial PPSV23 dose.
Vaccine against meningococci:
Hib-MenCY at ages 2, 4, 6, and 12 months at 6 weeks old. At 9 months old. 2 MCV4 doses given 3 months apart to children under 2 years old: MCV4-D-CRM should be given twice, two months apart, with boosters advised every five years.

First Line: MEDICATION
Starting at 2 months, prophylactic penicillins are recommended for newborns and young children: Children under the age of three should take 125 mg BID. For children aged 3 to 5, a dose of 250 mg BID is advised. A penicillin substitute is amoxicillin 20 mg/kg/day. Unless a child has undergone a splenectomy or has an invasive pneumococcal infection, penicillin can be stopped at age 5.
Additional oxygen
Painful crises (mild, outpatient): nonopioid analgesics (ibuprofen); severe, hospitalized: parenteral opioids (e.g., morphine on fixed schedule); patient-controlled analgesia (PCA) pump may be helpful.
Strong opioids should only be administered to patients under careful supervision in an acute care situation.
Hydroxyurea for the treatment of extremely severe anemia, painful acute chest syndrome, and vaso-occlusive events. increases the concentration of fetal hemoglobin. To avoid problems, hydroxyurea should be begun in infants and children older than 9 months who have SCA. Adults should start with a dose of 15 mg/kg/day and increase it by 1 mg/kg/day every 8 weeks until they reach a maximum dose of 35 mg/kg/day. Keep an eye on blood counts to prevent thrombocytopenia and severe neutropenia.
Chronic chest pain: Patients may swiftly deteriorate; use incentive spirometry to monitor those who are experiencing a vaso-occlusive crisis. Treatment should be aggressive and include oxygen, analgesics, antibiotics, and a straightforward transfusion or exchange.
Cephalosporins or azithromycin as empiric antibiotics to treat Chlamydia pneumoniae and Mycoplasma pneumoniae.
If osteomyelitis, take precautions against Salmonella and Staphylococcus aureus (e.g., ciprofloxacin).
Safety measures: Skip the high-estrogen oral contraceptives and think about Depo-Provera instead. Use of G-CSF is not advised since it can result in multiorgan failure and vaso-occlusive events.
Next Line
Folic acid doses are as follows: 0 to 6 months: 0.1 mg/day; 6 to 12 months: 0.25 mg/day; 1 to 2 years: 0.5 mg/day; >2 years: 1 mg/day.

ADVANCED THERAPIES

Transfusions and other treatments
Prophylactic transfusions for primary or secondary stroke prevention in children; transfusions for aplastic crises, severe complications (such as CVA), before surgery, and as treatment for acute chest syndrome. Preoperative transfusions have been shown to lower the risk of perioperative complications with goal hemoglobin >10 g/dL.
Oral deferasirox chelation if the patient has received many transfusions (after age 2 years).
It is advised to exchange red blood cells to reduce the level of HbS (30%) and avoid iron excess.

SURGICAL AND OTHER PROCEDURE
HSCT: a curative hematopoietic stem cell transplant.
90% of patients with matched sibling allogeneic stem cell transplants experience event-free survival. Cord blood and haploidentical donors are two other potential sources of allogeneic stem cells.
Endothelin-1 has the potential to treat sickle cell disease by preventing its pulmonary and renal consequences.
In patients older than five, L-glutamine oral medication has been demonstrated to lower oxidative stress and result in fewer episodes of sickle cell-related pain.
In addition to hydroxyurea therapy, monoclonal antibodies that bind P-selectin have the potential to be immunologic treatments to decrease the frequency and duration of pain crises.


CONSIDERATIONS FOR ADMISSION, THE INPATIENT, AND NURSING
Initial stabilization and admission requirements: significant pain, suspicion of infection or sepsis, signs of acute chest syndrome

CONTINUING CARE AFTERCARE RECOMMENDATIONS
patient observation
Early infection management. Parents/patients: If your temperature is over 101°F (38.3°C), you should see a doctor right once.
Watch out for hemosiderosis and hepatitis C in individuals who get regular blood transfusions.
Routine eye exams: starting at age 10 to screen for proliferative diabetic retinopathy; repeat screenings every one to two years.
 A twice-yearly checkup for pulmonary, renal, and hepatic impairment Transcranial Doppler imaging is used for neuroimaging stroke risk assessment starting at age 2 and continuing through age 16. 
Baseline pulmonary evaluation performed at each visit to check for wheezing, shortness of breath, or cough (signs of pulmonary hypertension and the severity of the condition). For patients with symptoms, right cardiac catheterization is used for diagnosis. 
SCD may be regarded as a provoking factor for VTE, but decisions on anticoagulation duration and prophylaxis should be made through a shared decision-making process. Albuminuria screening should be done annually beginning at age 10, with the introduction of ACE/ARB therapy for management of confirmed albuminuria.

Avoid alcohol (which dehydrates you); stay hydrated; take a multivitamin without iron; vitamin D deficiency and low bone marrow density are common in SCD patients.



Anemia strikes infants, sickle cell crises strike youngsters between the ages of one and two, and some children die during the first year of life.
Men die on average at age 42 and women on average at age 48.


Cerebral strokes (peak age 6 to 7 years), delayed mental development, even without a history of stroke, alloimmunization, bone infarct and osteomyelitis, and aseptic necrosis of the femoral head are complications. 
Impotence, priapism, hematuria/hyposthenuria, renal problems (proteinuria), cholelithiasis/abnormal liver function, chronic leg ulcers, poor wound healing 
Infections (pneumonia, osteomyelitis, meningitis, pyelonephritis); sepsis (leading cause of morbidity and mortality); retinopathy; splenic infarction (by age 10 years); acute chest syndrome (infection/infarction) leading to chronic pulmonary disease; Hemosiderosis (secondary to multiple transfusions); risk of opioid tolerance and substance abuse in chronic, uncontrolled patients;