However, in vivo VWF first needs to unfold (hence unfolded VWF) to bind to platelets, in which the VWF A1 domain is in the GPIb binding conformation (11) In a research setting, an immunosorbent assay was developed specifically for the measurement of unfolded VWF (11) This assay has shown its clinical applicability in VWD Type 2B, TTP, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, systemic inflammatory response syndrome (SIRS), sickle cell disease, and myocardial infarction (11, 13–16). The gene discussed is VWF; the disease is sickle cell disease.