Question 1

Can adults present with dactylitis?

Dr. Sukriti Gupta · Accepted Answer

Dactylitis is swelling of the fingers caused by blockage of the small blood vessels of the hands. It is more common in children, in whom collateral vessels are not yet well developed. In adults the vessels are not so small that they clog easily, and collaterals form more readily, so dactylitis is less common.

Question 2

In terms of treatment, how is gene therapy done, and is it possible for all patients?

Dr. Sukriti Gupta · Accepted Answer

Gene therapy needs no donor. The patient's own stem cells are mobilised with filgrastim for four days and collected, then modified in the laboratory, either by gene editing with CRISPR-Cas9 to correct the beta-globin change or by gene addition using a viral vector that adds a functional gene. The laboratory step currently takes around six months. The patient then receives chemotherapy to clear their own stem cells, and the modified cells are infused. Because these are the patient's own cells rather than donor cells, recovery is expected to be faster than after a donor transplant. The FDA first approved these therapies in 2023, for patients aged 12 and older, not for younger children. They are available in the US, European countries, Switzerland, Saudi Arabia and Bahrain. In India, CSIR-IGIB is working on gene therapy, and our centre is collaborating with them by providing autologous cells from our patients.

Question 3

For a positive diagnosis, is the hemoglobin S level the same across all countries?

Dr. Sukriti Gupta · Accepted Answer

Patients who carry both sickle genes usually have an HbS level above 60%, and a level above 60% indicates sickle cell disease (HbSS). Below 60% the manifestations are quite minimal, and a level below 50% is usually seen in sickle cell trait or a combined haemoglobinopathy such as HbSC or HbSE. Symptom severity tends to rise with the proportion of HbS, but there is no exact mathematical correlation between the HbS percentage and the clinical picture.

Question 4

Can you explain the pathogenesis of stroke in children with sickle cell disease?

Dr. Sukriti Gupta · Accepted Answer

Stroke in children with sickle cell disease arises from damage to the arteries at the base of the brain by sickled red cells and chronic haemolysis. Transcranial Doppler is the key tool for spotting this early. It uses ultrasound to measure flow velocity in these vessels, and high velocities identify the children at risk of stroke. It is not yet performed frequently in India, but it is recommended for all children with sickle cell anaemia. The first transcranial Doppler should be done at two years of age. If it is normal, it is repeated every six months to a year; if it is abnormal, it is repeated at two to three months and preventive treatment is started.

Question 5

Can a sickling test be negative while haemoglobin electrophoresis is positive, and in which conditions?

Dr. Sukriti Gupta · Accepted Answer

A negative screening test with a positive haemoglobin electrophoresis is less common. The more common error is a false positive: with dehydration or a febrile illness, the sodium metabisulfite screening test can show a sickle cell trait as positive. False negatives are also seen with the screening test, and there is no clear explanation for them. Haemoglobin electrophoresis is therefore always preferred, particularly when there is a family history.

Question 6

What types of stroke are sickle cell patients most likely to suffer from, and how can it be prevented?

Dr. Sukriti Gupta · Accepted Answer

Most strokes in sickle cell disease are ischaemic. In my experience the posterior and middle cerebral artery territories are most commonly affected, and the anterior territory sometimes. Regular transcranial Doppler screening from two years of age identifies the children at risk of stroke early, so that preventive medication can be started. It may not prevent every stroke, but regular follow-up and monitoring are essential.

Question 7

What is your comment on the use of hydroxyurea in pregnancy, and what are the alternative options?

Dr. Sukriti Gupta · Accepted Answer

Women with sickle cell disease who have done well up to childbearing age and conceived usually have less frequent pain and vaso-occlusive crises. In these women hydroxyurea can be held for a while during pregnancy, because it is not a good option for fetal development. Better hydration and avoiding other stressful conditions are advised instead, and folic acid supplementation must continue.

Question 8

What is the best mode of delivery for a woman with sickle cell disease, considering sickle cell pain and labour pain?

Dr. Sukriti Gupta · Accepted Answer

We always prefer a timely, planned caesarean section, usually electively at 36 to 37 weeks of gestation, so that the stress of labour is minimised. These women are monitored much more frequently in the third trimester, with visits to the gynaecologist twice a month, and any abnormal blood flow is watched for. Steroids (betamethasone or dexamethasone) for fetal lung maturation are given earlier so that delivery can happen earlier whenever needed, and if the blood flow becomes compromised at any point, the delivery is planned earlier.

Question 9

What are the cost implications of a bone marrow transplant for a full-match donor, a half-match donor and a registry donor?

Dr. Sukriti Gupta · Accepted Answer

With a full-match donor, the conditioning regimen is less toxic and the hospital stay, medications and supportive care are significantly reduced, so the cost is around USD 24,000 to 25,000. This depends on the patient's age: for a young child of two to four years it is even lower, while for a patient beyond 15 years, whose body weight is equivalent to an adult's, it rises to this level. A half-match transplant or an unrelated-donor transplant from a registry costs around USD 33,000 to 34,000. The cost of the two is usually the same: registry charges are significantly high, but the complications and donor charges are reduced.

Question 10

Is there an upper age limit for bone marrow transplant in sickle cell disease?

Dr. Sukriti Gupta · Accepted Answer

The maximum age at which we have performed a transplant is 26 years, with a full-match donor, and that patient's course was somewhat turbulent. Overall organ function is what matters most in deciding whether an older patient can proceed.

Question 11

A 28-year-old patient had a successful half-match transplant at another centre. Can a transplant be done for patients nearing 30, or was that a lucky case?

Dr. Sukriti Gupta · Accepted Answer

We should not depend on one person's data or a single case. The bigger picture matters: how many patients aged 25 to 30 have been transplanted across Delhi NCR, and what their profiles were. If only four or five of 20 such patients survived well, I would be sceptical about doing it, and the selection and profile of the survivors against those who did not survive would be the important question, because there is a lot of bias in such data. Above 25 we undertake very detailed planning, including a DTPA kidney scan and a cardiac scan, before taking a patient for transplant. With well-preserved kidney and heart function and a family that is fully willing, age is not always a fixed barrier.

Question 12

At what age do we commence hydroxyurea?

Dr. Sukriti Gupta · Accepted Answer

As per the textbooks, as early as the disease is detected; it can be started as young as two months of age.

Question 13

How far is India from gene therapy for sickle cell disease becoming available?

Dr. Sukriti Gupta · Accepted Answer

It is quite difficult to gauge. The government indicates that approval may come in the next two to three years, possibly two. What it will cost is not yet known.

Question 14

What are your views on bone marrow transplant versus gene therapy?

Dr. Sukriti Gupta · Accepted Answer

I extrapolate from other diseases. As a paediatrician I have treated genetic metabolic and immunodeficiency disorders with brain, liver and lung complications, for which there are two therapies: enzyme replacement therapy and bone marrow transplant. Enzyme replacement therapy is followed less often because of its availability and cost, but patients who receive it do beautifully, with minimal side effects; cost is the only prohibitive factor. Bone marrow transplant is somewhat toxic, although protocols, medications and monitoring have significantly reduced that toxicity. On that basis I feel gene therapy should become the best therapy once its cost comes down.

Question 15

Bone marrow transplant also carries a risk of death: with 80% success in early-age full-match transplants, some patients will not survive. How should doctors counsel families on this?

Dr. Sukriti Gupta · Accepted Answer

Whatever treatment decision a family takes, they must see it through to the end, so it has to be an informed decision. If cost is not a barrier at all, I will recommend gene therapy once it is better studied and available in my own practice. If finances may be a barrier, the family must take a very calculated decision. Gene therapy currently takes about six months to prepare, so urgency matters: a patient with recent severe crises or a stroke-like episode cannot wait six to eight months, and a bone marrow transplant should be given a chance.

Question 16

In developing countries where finances are a barrier for most families, would you recommend gene therapy or bone marrow transplant?

Dr. Sukriti Gupta · Accepted Answer

If finances are an issue, I still prefer an allogeneic bone marrow transplant. In experienced hands it has given excellent results, and its data are mature. There will be a 10 to 15% gap, but families should not wait on that margin and risk being unable to complete the gene therapy process, and I do not recommend that a family exhaust all its resources for the disease. If finances are even a slight barrier, trust the treating doctor and go for a transplant. Donor availability, however, is a separate issue that has to be addressed.

Question 17

Are biological parents automatically half-match donors, and what are the realistic chances of finding a match within the immediate family?

Dr. Sukriti Gupta · Accepted Answer

Parents are half matches, but not all parents are fit to donate. In African settings a common issue is that a parent may be HIV positive, which rules them out. If the parents are not sicklers themselves and have no organ compromise or significant comorbidity such as HIV, they are good half-match donors. The chance of a full-match sibling is usually 25%, and a half-matched sibling is better than a parent, because there are fewer antibodies against sibling cells and they are accepted better. Some siblings, however, are no match at all. Other relatives such as aunts, uncles and cousins are usually not even a half match.

Question 18

Compared with donor availability in kidney or liver transplant, is finding at least a half-match donor for bone marrow transplant realistic?

Dr. Sukriti Gupta · Accepted Answer

Because bone marrow donation is non-surgical and carries no significant complication for the donor, it is easier to convince an immediate family member to donate in a half-match case. To be frank, though, finding a donor for a kidney transplant is much more feasible; the families' mindset is the prohibiting factor. Kidney donation carries a risk of perhaps one in 1,000 or one in 10,000, and at such a minimal risk a transplant from any blood relative should be favoured, since kidney donors can include first or second cousins.

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