All are true for sickle cell anemia, except
|A||Pulmonary arterial hypertension|
|B||Fish mouth vertebra|
|D||Increased size of heart|
1. Peripheral smear: Shows Howell – Jolly bodies due to autosplenectomy, target cells, nucleated RBCs, RBC fragments, occasional thrombocytosis and leucocytosis (Characteristic).
2. Hb electrophoresis at alkaline pH: HbS can be detected by starch or agar gel electrophoresis
3. “Sickle Prep” test: This is performed by depriving RBCs of oxygen using metabisulfite or dithionite compounds as reducing agents and placing a coverslip over a drop of blood on a glass side. The RBCs sickle in situ.
Gamma Gandy bodies are most characteristic of congestive splenomegaly and sickle cell anemia (so also seen in Portal hypertension, hemolytic anemia, Hemochromatosis)
1. Severity of sickle cell disease may be decreased by HbF
2. Hydroxyurea causes an increase in the levels of HbF in red cells. This may in part, be responsible for the mechanism of action of hydroxyurea in sickle cell disease.
3. Efforts are currently being directed towards gene therapy that would increase the production of HbF.
4. Veno-occlusive crisis is a cause of morbidity
Bone Changes during sickle cell anemia:
1. Crew haircut appearance (Hair on end)
2. Fish mouth vertebrae
1. Infraction crisis: Analgesia (sustained release morphine) IV fluids (100 – 200 ml/hr)
2. Blood transfusion: If PCV or reticulocytes fall sharply, in CNS or lung complications or when Hb level is < 6gm/dl, blood transfusion can be given.
3. Treatment of infection by antibiotics.
4. Antisickling agents
a. Hydroxyurea – increases HbF to 14 – 15%
b. Butyrate compounds – increases HbF by increasing number of erythroblasts expressing gamma globin
Recent Advances: Newer Drug – Decitabine
Recent Advances: (Ref. Hari-18th ed., Pg.- 857)
1. The most significant advance in the therapy of sickle cell anemia has been the introduction of hydroxyurea as a mainstay of therapy for patients with severe symptoms. Hydroxyurea (10–30 mg/kg per day) increases fetal hemoglobin.
2. The antitumor drug 5-azacytidine was the first agent found to elevate HbF. It never achieved widespread use because of concerns about acute toxicity and carcinogenesis. However, low doses of the related agent 5-deoxyazacytidine (decitabine) can elevate HbF with more acceptable toxicity.
3. Reestablishing high levels of fetal hemoglobin synthesis should ameliorate the symptoms of chain hemoglobinopathies.
4. Cytotoxic agents such as hydroxyurea and cytarabine promote high levels of HbF synthesis, probably by stimulating proliferation of the primitive HbF-producing progenitor cell population (i.e., F cell progenitors).
5. Butyrates stimulate HbF production, but only transiently.