Normal hemoglobin is termed as HbA (A for Adult). But many abnormalities do occur in haemoglobin synthesis. One of those is HbS (S for Sickle), which derives the name from sickle as the RBC becomes sickle shaped in an oxygen deprived condition; and hence called as sickle cell disease.
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HbS may be found in conjunction with other abnormal type of Hbs such as HbF (F for Faetal) in some patients; the type that is seen in Thalassaemia. HbF is normal content in faetal RBC, which carries oxygen comfortably in mother's womb, in a relatively oxygen scarce environment.
After delivery of oxygen to the cells, there develops an oxygen deprived state inside the smallest calibered blood vessels that permanently deforms the RBC with HbS to sickle shape; and damage to their cell membrane make those rigid, hard to pass through those blood vessels. As a result of which those stick together to block the blood vessels and flow of blood; which results in more oxygen deprived environment to facilitate formation of more sickles; and the cascading effect.
The block deprives the tissue of oxygen that results in the death of an area supplied by a particular blood vessel in any organ of body. Commonly affected organs are spleen, bone marrow, lungs, kidneys and liver etc.
This causes various symptoms such as pain arising from the organ, blood in urine, anaemia; and secondary infection of bone and lungs; to be named as sickle cell crisis; which can be aplastic crisis, sequestration crisis, haemolytic crisis and painful crisis etc..
Some time back, FDA has approved hydroxyurea, a chemotherapeutic agent against certain cancers for treatment of sickle cell disease. After certain period of administration of the agent foetal haemoglobin (HbF) appears in the RBCs. As HbF has the quality of working best in oxygen deprived environment that results in lessening the flare up episodes or sickle cell crisis.
Much like hydroxyurea, pomalidomide an analog of thalidomide, whose use as sedative and treating morning sickness in mothers was stopped long back following severe foetal malformations; found to increase production of fetal hemoglobin.
In addition to production of HbF it is seen to be soft on bone marrow, in contrast to hydroxyurea, which causes bone marrow depression leading to neutropenia; and consequent weakening of body defense mechanism.
Despite its notorious reputation for causing birth defects, thalidomide and now its analogs are carving out a potentially positive future for their ability to regulate the immune response. In fact, Lenalidomide is already approved for multiple myeloma and is currently under study for other cancers.
The researchers found that pomalidomide, a more potent and closely related cousin of lenalidomide had the added benefit of increasing fetal hemoglobin expression and proliferation of CD34+ progenitor cells, which make red blood cells.
This drug was at least as much effective as hydroxyurea in producing HbF, additionally found to be bone marrow friendly, the researchers conclude. The laboratory work prompted them to initiate a Phase 1 clinical trial of the drug for sickle cell disease with Wayne State University in Michigan.
We may hope for a new bone marrow friendly drug for sickle cell disease soon