Severe disease It is not entirely clear why secondary infection with a different strain of dengue virus places people at risk of dengue hemorrhagic fever and dengue shock syndrome. The most widely accepted hypothesis is that of antibody-dependent enhancement (ADE). The exact mechanism behind ADE is unclear. It may be caused by poor binding of non-neutralizing antibodies and delivery into the wrong compartment of white blood cells that have ingested the virus for destruction.[15][17] There is a suspicion that ADE is not the only mechanism underlying severe dengue-related complications,[2][16] and various lines of research have implied a role for T cells and soluble factors such as cytokines and the complement system.[29] Severe disease is marked by the problems of capillary permeability (an allowance of fluid and protein normally contained within blood to pass) and disordered blood clotting.[8][9] These changes appear associated with a disordered state of the endothelial glycocalyx, which acts as a molecular filter of blood components.[9] Leaky capillaries (and the critical phase) are thought to be caused by an immune system response.[9] Other processes of interest include infected cells that become necrotic—which affect both coagulation and fibrinolysis (the opposing systems of blood clotting and clot degradation)—and low platelets in the blood, also a factor in normal clotting.[29]