Platelet adhesion to surface caPtured

Type 2A Von Willebrand disease (VWD) is clinically identified by a loss of high and intermediate Von Willebrand factor (VWF) multimers resulting in a loss of platelet-dependent function. The majority of mutations that cause type 2A disease occur in the A2 domain and are grouped by their effects on cellular retention of VWF or the susceptibility of VWF to proteolysis by ADAMTS13. However, a few mutations also classified as 2A occur in the A1 domain. The most puzzling are those that abolish the single disulfide bond in the A1 domain, which is required to maintain the native structure of the domain. These mutations could cause severe problems in hemostasis that lead to microvascular thrombosis because of the enhanced affinity of this intermediate conformation for platelet GPIba.