SELSEHCC

Aleksander Mijovic

Aleksandar Mijovic, MBBS, PhD, FRCPath, is Consultant Haematologist at King’s College Hospital in London, and at the Tooting Blood centre. He specialised Internal medicine in 1986 and completed his PhD in haematology in 1992, at the University of Belgrade, Serbia.

His main clinical and research interests are transfusion in specific clinical situations (haemopoietic cell transplantation, sickle cell disease, foetal medicine), red cell immunology, and drug-induced blood disorders.

Dr Mijovic has over 50 publications in peer-reviewed journals and books. He authored the book Transfusion medicine: case studies and clinical management (2012). He is a teacher of the European School of Transfusion Medicine and European Haematology Association, and examiner for the Royal College of Pathologists.

Abstract: Update on blood transfusion in sickle cell disease

Red cell transfusions remain the cornerstone of treatment for sickle cell disease (SCD). Red cells may be given to treat acute complications of SCD, or electively, to prevent sickle cell crisis/acute chest syndrome after surgery, or for primary/secondary prevention of cerebral vascular incidents (CVI). The role of elective transfusions in SCD has been the subject of several clinical trials, which continue to shape our management of SCD.

The STOP I randomized, controlled trial (RCT) showed dramatic reduction of the incidence of first stroke in high-risk children transfused regularly to keep Haemoglobin S below 30%. The question when a successfully carried out prevention program may be discontinued was addressed in the STOP II trial. In this RCT, higher proportion of patients randomised to stop transfusions reverted to pre-transfusion stroke risk level, and some developed stroke, unlike patients who continued having regular transfusions.

 

Encouraging results obtained with Hydroxyurea (HU) suggested that it could be used to wean patients off chronic transfusions. A phase III RCT of HU/phlebotomy vs. regular transfusion/iron chelation (SWITCH), enrolled over 130 SCD children with a history of a CVI, who had been maintained on chronic transfusions. The trial was terminated when 7/67 patients in the HU/phlebotomy arm suffered a recurrent stroke.

Preoperative transfusion in SCD was evaluated in the 1995 multicentre RCT which randomised 551 patients into an “aggressively” and a “conservatively” transfused arm. Conservative approach was not associated with inferior outcomes. The hypothesis that preoperative transfusions could be safely omitted was refuted in another RCT (TAPS), which concluded that un-transfused SCD patients had an increased incidence of acute chest syndrome.

 

The mentioned trials indicate that it would be premature to abandon transfusions in certain clinical settings in SCD. At the same time, transfusion has become much safer in the last 10-15 years, with transfusion transmitted infections becoming rare in the UK, and with better control of iron overload using oral iron chelating drugs. So what are the incentives to search for alternatives to transfusion in SCD? One is the increasing cost of management, due to growing numbers of patients on chronic transfusion programs. The other is that “zero-risk” is unattainable. The most common immunological complication of transfusion in SCD is alloimmunisation to red cells, occurring in 10-30% patients. Despite apparent decline in the last decade, due to the practice of broader matching for Rh/Kell antigens, alloimmunisation remains a serious challenge and may preclude regular transfusion programs, or even render the patient “untransfusable”, favouring haemopoietic cell transplantation as the preferred therapeutic option. Advances in molecular genetics have allowed sequencing of numerous RhD and RhCE variant genes, whose carriers are prone to making allo-antibodies against high-frequency antigens (e.g., anti-hrS). Molecular genetic identification of donors lacking these antigens within the same ethnic group, could ensure stable procurement of this rare blood.

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