Proteolysis of VWF from Tyr/Cys1584 heterozygotes and randomly selected Tyr/Tyr homozygotes. (A) Multimer analysis of each cryoprecipitate at the start (T = 0 hours) of incubation with cryodepleted plasma as a source of ADAMTS13, and after further incubation in the presence (4 hours) and absence (8 hours) of ristocetin. M represents patient M, 2:3 represents the sister of patient M, C154 and C1-3 represent individuals from the random cohort of 200 people and N represents a healthy control. The extent of proteolysis is greater for M, 2:3, and C154 compared with the other samples tested. (B) Densitometric scans of the lanes in panel A. Each panel corresponds with an individual lane. The multimer profiles of all samples are similar at T = 0 hours; however, the extent of proteolysis for the heterozygotes M, 2:3, and C154 is greater than for the homozygotes C1, C2, and C3 after incubation in the presence or absence of ristocetin. In all cases, proteolysis is accompanied by a quantitative increase in the triplet bands. Horizontal axis is optical density: 0 = black, 500 = white.