ABSTRACT REFLECTIONS


ARTICLE


Haematology and transfusion science at Congress


Publication of selected summaries from the comprehensive Biomedical Science Congress lecture programme continues in this issue of The Biomedical Scientist.


Invited speakers on the Congress scientific programme are asked to submit brief summaries to support their presentations. Reproduced below are selections compiled from those contributing to the haematology and transfusion science programmes.


HAEMATOLOGY Paediatric complications in sickle cell disease and thalassaemias Sickle cell disease and thalassaemia are the two most important haemoglobinopathies and as such present the most serious clinical phenotypes. Thalassaemia is a deficiency or absence of any of the globin chains; α- and β-chains are the most commonly affected. α-thalassaemia is ether deletional or non- deletional and it may affect one or both chain pairs. The loss of all four chains is generally not compatible with extra-uterine survival even though this may be ameliorated through intrauterine transfusion and subsequent transplantation or transfusion. The absence of α-chains (otherwise hydrops fetalis) is the most severe form, while the loss of three α-chains or haemoglobin H may present with mild to moderate anaemia, splenomegaly and jaundice in childhood. The absence of two or less α-chains rarely shows any significant anaemia. However, less-severe forms of α-thalassaemia that coexist with sickle cell disease alter the clinical phenotypes favourably in most patterns of presentation. β-thalassaemia major is the loss or severe reduction of β-globin chains and is uniformly associated with severe anaemia and transfusion dependence. Therefore long-term blood transfusion, complications of haemolysis and iron overload result. This causes an imbalance of the globin chains. Imbalance of globin chains is responsible for ineffective erythropoiesis


DECEMBER 2013


and toxicity of the excess chains. Sickle cell disease is a qualitative abnormality due to amino acid substitution affecting the β-chain of haemoglobin, valine being substituted by glutamic acid which in a homozygous state is sickle cell anaemia. Sickle cell anaemia is one of the most severe forms of sickle cell disorder. The paediatric presentations vary according to other co-inheritance such as the persistence of haemoglobin F, α-thalassaemia and homozygous or double heterozygous states. The clinical features include anaemia, the risk of infection and stroke in early childhood.


The role of artemisinin and its derivatives in haemato-oncology The semi-synthetic derivatives of artemisinin are highly potent antimalarial drugs, with activity dependent upon ferrous iron (Fe2+


)-


mediated reductive scission of an atypical endoperoxide bridge and the generation of damaging free radicals. It has been proposed that artemisinins’ differential but selective toxicity could be utilised in the formulation of adjuvant components of targeted cancer therapies. This study evaluated three artemisinin derivatives – dihydroartemisinin (DHA), artesunate (ART) and artemether (ARTE) – for their cytotoxic anti-angiogenic, anti-lymphomagenic properties. DHA, ART and ARTE were found to inhibit in vitro cancer cell growth and human umbilical vein endothelial cell (HUVEC) pseudotubule formation in a dose-dependent manner. Although highly active against Plasmodium- infected erythrocytes, artemisinin derivatives have a short half-life in vivo, which may be a limiting factor to their application as a cancer therapy. In order to improve artemisinin derivatives’ bioavailability, slow release or targeted delivery mechanisms could be


Sickle cell disease is a qualitative abnormality due to amino acid substitution affecting the β-chain of haemoglobin.


utilsed. The role of iron in the efficacy and delivery of artemisinins to malignant cells is an interesting area and requires further elucidation. The transferrin/transferrin receptor interaction could provide a targeted drug delivery pathway. However, current understanding regarding artemisinins’ interactions with transferrin, the mechanism and cellular site of the drugs activity is incomplete. To start addressing this, an attempt was made to identify a unique spectral signature for artemisinin derivatives. Using Fourier-transform infrared spectroscopy, absorption spectra were obtained. By spectroscopically analysing erythrocytes treated with artemsinin derivatives, the unique spectra for DHA could be identified with a relatively high percentage of similarity to the spectrum for pure DHA. These initial results suggest the spectra for artemisinin derivatives could be identifiable within a complex mixture and may facilitate future microspectroscopy and live-cell imaging.


THE BIOMEDICAL SCIENTIST 711


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