Supportive Care and Pharmacological Treatment for Sickle Cell Disease

Gene therapy uses the patient's own stem cells rather than a donor, mobilised and collected the same way as for a transplant, then modified in a laboratory using either a viral vector for gene addition or CRISPR-Cas9 editing to correct the underlying genetic change, a process that currently takes around six months. Because the cells being returned are the patient's own, recovery is generally faster than with a donor transplant, but the therapy currently has FDA approval only for patients aged 12 and older, and it remains expensive and not yet widely available outside the US, Europe and a handful of other countries.

If finances are genuinely not a barrier, gene therapy is worth choosing once it is better established, since it avoids the donor-related risks. But where finances are a limiting factor, an experienced allogeneic bone marrow transplant programme should still be trusted: it has decades of mature outcome data behind it, and families should not exhaust all their resources chasing a gene therapy process that could stall partway through. If a patient is having an acute crisis such as a recent stroke, there is also often not enough time to wait the six to eight months gene therapy currently requires, and transplant should be pursued instead.

Parents are usually a half match by default, provided they are not sicklers themselves and have no disqualifying condition such as HIV or organ damage. A full-match sibling occurs in about 25% of cases, and a half-matched sibling is actually a better donor than a half-matched parent, since sibling cells are better tolerated with fewer pre-existing antibody reactions. Beyond parents and siblings, more distant relatives such as aunts, uncles or cousins are rarely even a half match, so realistic donor availability is mostly limited to the immediate family.

Dactylitis, swelling of the fingers from small vessel blockage in the hands, is more commonly seen in children because they have not yet developed collateral blood vessels the way adults have. In adults, the vessels involved are relatively larger and better able to develop collaterals, so dactylitis is much less common in that age group.

Patients carrying both sickle cell genes typically have a haemoglobin S level above 60%, and below that the manifestations are usually milder, seen more in sickle cell trait or a combination haemoglobinopathy such as HbSC or HbSE. There is a general tendency for higher HbS to mean more symptoms, but the correlation is not exact and cannot be relied on mathematically for any individual patient.

A standard transfusion adds donor red cells to reduce the proportion of haemoglobin S. A red cell exchange, used when haemoglobin is already above 10 g%, removes an equivalent volume of the patient's blood while transfusing healthy cells, so haemoglobin does not rise further while the sickled cell proportion still falls.

It increases fetal haemoglobin and nitric oxide levels, helping blood vessels dilate and reducing sickling crises. It can be started as early as the disease is detected, sometimes from two months of age, though its benefit varies from patient to patient.