Question

1) List of drugs that can induce sickle cell anemia

2) mechanism of action of sickle cell anemia

3) treatment options for sickle cell anemia

4) describe polycythemia including definition, causes, mechanism and treatment options

Answer 1

1. Drug induced sickle cell anemia also called drug induced immune haemolytic anemia DIIHA  methyldopa , ceftriaxone, cefotetan, pencillin etc .

2. Basic molecular lesion In HbS, basic genetic defect is the single point mutation in one amino acid out of 146 in haemoglobin molecule—there is substitution of valine for glutamic acid at 6-residue position of the b-globin, producing Hb a2b2s.
Mechanism of sickling During deoxygenation, the red cells containing HbS change from biconcave disc shape to an elongated crescent-shaped or sickle-shaped cell. This process termed sickling occurs both within the intact red cells and in vitro in free solution. The mechanism responsible for sickling upon deoxygenation of HbS-containing red cells is the polymerisation of deoxygenated HbS which aggregates to form elongated rod-like polymers. These elongated fibres align and distort the red cell into classic sickle shape.

3.hydroxyurea 10–30 mg/kg per day PO increases level of HbF and prevents sickling, treat infections early, supplemental folic acid; painful crises treated with oxygen, analgesics (opioids), hydration, and hypertransfusion; consider allogeneic bone marrow transplantation in pts with increasing frequency of crises.

4.POLYCYTHEMIA (ERYTHROCYTOSIS)
Polycythemia is an increase above the normal range of RBCs in the circula- tion. Concern that the Hb level may be abnormally high should be triggered at a level of 170 g/L (17 g/dL) in men and 150 g/L (15 g/dL) in women. Polycythemia is usually found incidentally at routine blood count. Relative erythrocytosis, due to plasma volume loss (e.g., severe dehydration, burns),does not represent a true increase in total RBC mass. Absolute erythrocyto- sis is a true increase in total RBC mass.
? CAUSES
Polycythemia vera (a clonal myeloproliferative disorder), erythropoietin- producing neoplasms (e.g., renal cancer, cerebellar hemangioma), chronic hypoxemia (e.g., high altitude, pulmonary disease), carboxyhemoglobin excess (e.g., smokers), high-affinity hemoglobin variants, Cushing’s syn- drome, androgen excess. Polycythemia vera is distinguished from second- ary polycythemia by the presence of splenomegaly, leukocytosis, thrombo- cytosis, and elevated vitamin B12 levels, and by decreased erythropoietin levels.
COMPLICATIONS
Hyperviscosity (with diminished O2 delivery) with risk of ischemic organ injury and thrombosis (venous or arterial) are most common.
TREATMENT
Phlebotomy recommended for Hct ≥ 55%, regardless of cause, to low- normal range.