Interplay between coagulation and vascular inflammation in sickle cell disease

Abstract

Sickle cell disease is the most common inherited haematological disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease, the importance of haemolytic anaemia and vasculopathy has been recently recognized. A hypercoagulable state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease.

Figure 1

Interactions between sickle RBCs, leukocytes and endothelial cells are mediated by multiple adhesion molecules.

Figure 2. Cross-talk between coagulation and vascular inflammation in SCD

Vaso-occlusion (VOC) and hemolysis-dependent endothelial cell (EC) activation and inflammation lead to the increased expression of tissue factor (TF) by various cell types, phosphatidylserine exposure and subsequent activation of coagulation. We propose that activation of coagulation creates a positive feed-back loop that further enhances VOC, EC activation and inflammation via protease activated receptors (PARs) and thrombosis dependent mechanisms.

Figure 3

Proposed mechanism by which TF, FXa and thrombin contribute to the pathology of SCD.