The hypercoagulable state in thalassemia.

Thalassemia is associated with partial or complete deficiency of α- or β-globin chain synthesis, which leads to denaturation and degradation of the remaining globin chains. This process is associated with loss of the normal asymmetrical distribution of the RBC membrane phospholipids and translocation of PS to the external membrane leaflet (flip-flop). The membrane damage may be related to lipid peroxidation mediated by free iron and increased amounts of membrane-bound hemichromes and immunoglobulins and modifications in the membrane band 3 protein and spectrin. The membrane changes may partly explain the enhanced aggregation of PS-exposing RBCs, their increased adherence to ECs, and their capacity to enhance thrombin generation via the assembly of the prothrombinase complex. The enhanced thrombin generation leads to activation of platelets, monocytes, granulocytes, and ECs and expression of tissue factor, which further enhances the thrombotic process. The low levels of the coagulation inhibitors, protein C and protein S, further facilitate the resultant hypercoagulable state.