Summary. The susceptibility of von Willebrand factor (VWF) of blood group O, A, B and AB to proteolysis by the ADAMTS13 metalloprotease was investigated. Multimeric analysis indicated that the rate of VWF proteolysis differed between blood groups and was greater for group O VWF than for non-O VWF in the rank order O ! B > A ! AB. Measurement of the collagen binding activity of VWF of each blood group following proteolysis for a fixed time interval corroborated the results obtained on multimer analysis: the loss of collagen binding activity was greater for VWF of group O compared with non-O VWF, in the rank order O ! B > A ! AB. Ristocetin was found to increase the rate of VWF proteolysis approximately two-fold; the differential between blood groups was retained in the presence of ristocetin.

This review focuses on selected areas that should interest both the scientist and the clinician alike: polymorphisms within the factor VIII and factor IX genes, their linkage, and their ethnic variation; a general assessment of mutations within both genes and a detailed inspection of the molecular pathology of certain mutations to illustrate the diverse cause-effect relations that exist; a summary of current knowledge on molecular aspects of inhibitor production; and an introduction to the new areas of factor VIII and factor IX catabolism. An appendix defining various terms encountered in the molecular genetics of the haemophilias is included, together with an appendix providing accession numbers and locus identification links for accessing gene and sequence information in the international nucleic acid databases.

The hypothesis that increased ADAMTS13 (a disintegrin and metalloprotease with thrombospondin repeats) activity or increased susceptibility of von Willebrand factor (VWF) to proteolysis by ADAMTS13 may underlie type I von Willebrand disease (VWD) in some patients was investigated. Plasma from 4 patients with type I VWD was cryoprecipitated. ADAMTS13 activity in the VWF-poor cryodepleted fraction was assessed by incubation with purified VWF; susceptibility to proteolysis of the VWF in the VWF-rich cryoprecipitate was assessed by incubation with a normal, group O cryodepleted plasma. ADAMTS13 activity was similar in all 4 type I VWD cryodepleted plasmas and comparable to a normal control plasma. In contrast, the VWF of one patient showed increased susceptibility to proteolysis by ADAMTS13. Investigation of additional family members indicated that increased susceptibility was heritable, but it did not track uniquely with type I VWD. Sequence analysis of VWF exon 28 indicated that increased susceptibility to proteolysis tracked with the "G"

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We have compared two groups (n = 22) of unpremedicated patients to determine if the pain caused by injection of propofol could be modified by alfentanil. In group I, alfentanil 1 mg was given as a bolus i.v. injection 15 s before administration of propofol i.v., while group II received saline. Propofol was given in 20-mg increments every 4 s. All injections were given through the same i.v. cannula on the dorsum of one hand. We found that alfentanil pretreatment reduced pain on injection of propofol (P = 0.001).