Sickle Cell Disease Flashcards
Etiology
• Autosomal recessive disorder.
caused by genetic mutation causing abnormal β globin chain due to substitution of valine instead of glutamine in the sixth position resulting in Hb S.
- Sickle cell Anemia; SCA → Hb SS ; homozygous
- Sickle cell trait ; SCT → Hb AS ; heterozygous
Clinical picture
- Common in negroes
- Features of anemia
- Features of chronic hemolysis Starting after the 6 th month of age
- Renal disorders p proteinuria, nephrotic syndrome, chronic renal failure.
crisises
- Aplastic
- Hemolytic
- Megaloblastic
- Hyperhemolytic (as before)
- Vaso occlusive crisis ( painful crisis)
- Splenic sequestration crisis
- Infectious crisis
Vaso occlusive crisis ( painful crisis) definition
The cardinal clinical feature of SCA is pain. The pain episode occurs at least once yearly; it usually very severe and characterized by unremitting discomfort that can occur in any part of the body, especially chest, abdomen, or extremities.
The exact etiology of pain is unknown, but the pathogenesis is initiated when blood flow is disrupted in the microvasculature by sickle cells, resulting in tissue ischemia. Precipitating causes may include: physical stress, infection, dehydration, hypoxia, acidosis, and exposure to cold.
WBCs counts are often elevated, adhere to endothelial cells and may further trap sickled red cells, contributing to stasis
• Precipitating factors Fever, Acidosis, Dehydration, Infection & Hypoxia, exposure to cold
Pain crisis (Vaso-occlusive episodes): Pain crisis (Vaso-occlusive episodes):- tx
The majority of painful episodes in patients with SCA are managed at home with comfort measures e.g. heating blanket, relaxation techniques, massage, and pain medication.
Specific therapy for pain varies greatly but generally includes the use of acetaminophen or non-steroidal agent early in the course of pain, followed by escalation to acetaminophen with codeine or a short- or long-acting oralopioid.
Some patients require hospitalization for administration of IV morphine or its derivatives. The incremental increase and decrease in the use of medication to relieve pain requires education of both the parents and patient regarding the recognition of symptoms and a trust between the patient and the treating physician.
Opioid dependency in children with SCA is rare and should never be used as a reason to withhold pain medication. However, patients with multiple painful episodes requiring hospitalization within a year or with pain episodes that require hospital stays for > 1 wk should be evaluated for comorbidities and psychosocial stressors that might contribute to the frequency or duration of pain.
- Blood transfusion should be reserved for patients with a decrease in hemoglobin resulting in hemodynamic compromise. IV hydration does not relieve or prevent pain but is appropriate when the patient is unable to drink as a result of the severe pain or is dehydrated.
Hydroxyurea, a myelosuppressive agent, is the only effective drug proved to reduce the frequency of painful episodes.
Acute chest syndrome (ACS):
Due to pulmonary emboli of necrotic bone marrow (fat emboli) infection or pulmonary infarction
- Clinical Presentation :
- Gradual or catastrophic.
- Severe respiratory distress
- Chest pain, fever Hypoxemia
- CBC: Leucocytosis
- CXR: Lung consolidation.
Splenic infarctions
fibrosis → shrinking → autosplenectomy & hyposplenism
Renal infarction
Hematuria p Chronic renal failure
Hand and foot syndrome:
Ischemia of metacrapal & metatarsal bones
Splenic Sequestration:-
🌻Acute splenic sequestration is a life-threatening Cx occurring primarily in infants and can occur as early as 5 wk of age. About 30% of children with SCA have severe splenic sequestration episode, and a significant percentage of these episodes are fatal. The etiology is unknown but it can be accompanied by infection.
🌻C.M. Engorgement of the spleen with subsequent increase in size, evidence of hypovolemia, and decline in Hb ≥ 2 g/dL from the patient’s baseline hemoglobin; reticulocytosis and ↓ platelet count may be present.
🌻Rx. Early intervention and maintenance of hemodynamic stability by using isotonic fluid or by blood transfusions (packed RBCs) in dose 5 mL/kg but do not ↑ Hb >10 mg/dL. Repeated episodes of splenic sequestration are common, occurring in ≈ half of patients (most within 6 mo of the previous episode). Thus, anticipatory guidance should include teaching parents how to palpate the spleen to determine if the spleen is enlarging.
🌻Prophylactic splenectomy performed after the acute episode is the only effective strategy for preventing future life-threatening episodes.
Priapism
🌹It is a common problem in SCA; it is defined as involuntary penile erection lasting > 30 min, but patients may have persistent painful erection for several hours. The ventral portion and the glans penis is typically not involved, and their involvement necessitates urologic consultation based on the poor prognosis for spontaneous resolution. Priapism occurs in 2 patterns, stuttering and refractory, with both types occurring in patients from early childhood to adulthood with mean age at first episode is 15 yr.
🌹Rx. Supportive e.g. sitz bath or pain medication; priapism lasting >4 hr should be treated by aspiration of blood from the corpora cavernosa followed by irrigation with dilute epinephrine.
Pv. Hydroxyurea appears to have promise, or by Etilefrine, a sympathomimetic amine with both α 1 and β 1 adrenergic effects.
Infectious crisis
- Due to hyposplenism (qopsonization)
- Common organisms: usually encapsulated bacteria Site
- Meningitis (Pneumococci & H. influenza)
- Pneumonia (Pneumococci)
- Osteomyelitis (Salmonella)
Investigations
- For anemia p Low Hb% & Ht value.
- For chronic hemolysis pq RBCs survival & o erythropoiesis.
- For the cause
a) Blood film:
• Detect sickle cells in peripheral blood. If not detected, sickling can be enhanced by adding sodium metabisulfite (Sickling test).
• Howell–Jolly bodies (nuclear remnants) and Sub membranous pits in RBCs may be seen indicating hyposplenism.
b) Hemoglobin electrophoresis: Show HbSS (90%) & Hb F (2-10%).
c) Neonatal screening allows early detection , adequate care and longer survival
Tx
Nelson
