Hydroxyurea (HU) is a tremendously important drug in the management of patients with SCD who have severe clinical manifestations. HU inhibits ribonucleotide reductase, leading to S-phase arrest of replicating cells, and is used in SCD because of its ability to stimulate production of HbF. HU increases HbF as a result of stress erythropoiesis induced by its myelosuppress-ive effect. Patients show variable response in the degree of rise in HbF, and some experience no change from the baseline value. Other biological effects of HU play an equally significant role in the beneficial clinical effects observed during HU therapy. Erythrocytes of patients on HU have increased water content and deformability and decreased adherence to vascular endothelium. There is elevation of the haemoglobin level, mean cell volume (MCV), HbF and F cells, whereas total white cell and neutrophil count, reticulocyte count and the number of dense sickle cells decrease. Patients on HU experience 50% reduction in the incidence of acute painful episodes and acute chest syndrome. The transfusion needs and the risk of death are also decreased, but the incidence of stroke remains unaffected.

HU therapy is offered to patients (adults and children over 6 years) with frequent pain episodes or acute chest syndrome. Use of HU in very young children should carefully balance the anticipated benefit with potential unknown risks in this age group. HU is started at a dose of 15 mg/kg per day and increased to 25 mg/kg per day provided that there are no side-effects. Patients require frequent monitoring of blood counts, as well as renal and hepatic function. Myelosuppression is the most commonly encountered side-effect and temporary cessation of therapy and dose reduction is required for neutropenia,

Table 7.4 Advances in the management of sickle cell disease.



1 Newborn screening

2 Infection

3 Brain injury prevention

4 Transfusion safety and iron overload prevention

5 Lung injury prevention

6 Surgery/anaesthesia

7 Avascular necrosis of the hip

8 Priapism

9 Pain

10 Renal

11 Gall bladder disease

12 Severe disease


Comprehensive care

Prophylactic penicillin

Screening with TCD, MRI

Neurocognitive testing

Phenotypically matched RBC


Incentive spirometry

Antibiotics (including macrolides)


Nitric oxide

Prevention with hydroxyurea Preoperative transfusion Decompression coring Adrenergic agonist Anti-androgen therapy Prevention with hydroxyurea Patient-controlled analgesic devices Non-steroidal anti-inflammatory drugs ACE inhibitors for proteinuria Improved renal transplantation Laparoscopic cholecystectomy Allogeneic bone marrow transplantation Chronic transfusions Hydroxyurea

ACE, angiotensin-converting enzyme; MRI, magnetic resonance imaging; TCD, transcranial Doppler.

thrombocytopenia, reticulocytopenia or fall in haemoglobin. Dose modification is necessary for patients with renal failure. Skin pigmentation affecting the nails, palms and soles is commonly observed. Despite concerns about the leukaemogenic and teratogenic effects of HU, no convincing increase has been reported in SCD so far.

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