beta-thalassaemia and sickle cell anaemia as paradigms of hypercoagulability

Thalassaemia and sickle cell disease (SCD) represent the most common forms of hereditary haemolytic anaemia and result from a partial or complete lack of synthesis of one of the major α- or β-globin chains of haemoglobin A or from a single amino acid mutation (β6Glu→Val) of the β-globin chain respectively. Although they have different pathophysiologies, patients with these conditions manifest both biochemical and clinical evidence of hypercoagulability. While the frequency of various thrombotic complications may vary in β-thalassaemia and homozygous SCD [sickle cell anaemia (SCA)], patients with both diseases manifest decreased levels of natural anticoagulant proteins, as well as increased markers of thrombin generation and platelet activation. The abnormal phospholipid membrane assymetry present in the red blood cells of β-thalassaemia and SCA patients, with resultant phosphatidylserine exposure appears to play a significant role in the aetiology of the observed hypercoagulable state. This review presents the available data on the aetiology and clinical manifestations of the coagulation and platelet activation that exist in both β-thalassaemia and SCA, as well as the potential therapeutic implications resulting from this hypercoagulability.