Platelet-type von Willebrand disease (PT-VWD IntroductionAs an initiating step in hemostasis, surface-bound von Willebrand factor (VWF) tethers platelets to a damaged vascular surface via the platelet membrane receptor, glycoprotein (GP) Ib-IX. 1 Before the hemostatic or thrombotic response, soluble von Willebrand factor and platelets coexist without a detectable interaction. Indeed, the regulation of binding between VWF and GP Ib-IX is one of key steps controlling hemostasis and thrombosis. 2 Much of our understanding of these processes has been aided by human bleeding disorders representing "experiments of nature" that identify the key proteins. To this end, platelet-type von Willebrand disease (PT-VWD) is a hereditary bleeding disorder caused by point mutations within the extracellular ␣-subunit domain of the GP Ib-IX receptor. [3][4][5][6] A documented result of PT-VWD mutations is an increased affinity between mutant GP Ib-IX and soluble VWF. 7 A mechanistically similar situation exists with type 2B VWD where single mutations in VWF have an increased affinity for a normal platelet GP Ib-IX receptor. 8 Whether the mutation exists in the receptor, PT-VWD, or the ligand, type 2B VWD, the net result in both cases is a bleeding disorder.The bleeding phenotype in PT-VWD and type 2B VWD has been explained as a consequence of circulating platelet microaggregates composed of bridged platelets and VWF. 7,9 The aggregates are removed from the circulation resulting in a thrombocytopenia, albeit borderline in PT-VWD, and this can partially explain bleeding. 3 In addition, there is an absence of the largest circulating plasma VWF multimeric species in both PT-VWD and type 2B VWD. 3,10 The largest VWF multimer species are the most hemostatically efficient, and removal from the circulation would further add to the impairment of normal hemostasis. 11 However, the removal of the largest multimers by binding to platelets is somewhat counterintuitive because these multimers would presumably be bound to platelets and might be expected to preload a platelet for a hemostatic or thrombotic event. Nevertheless, PT-VWD and type 2B VWD remain 2 of the more interesting bleeding phenotypes providing mechanistic clues on the regulation of hemostasis and thrombosis.We have recently reported the development of a mouse expressing a mutant human subunit associated with PT-VWD. 12 The mouse expresses a human ␣-subunit of GP Ib-IX in which Gly 233 is replaced by Val 233 (G233V), the first reported genetic basis for human PT-VWD. 13 The mice display several diagnostic attributes of human PT-VWD, including the ability of platelets to agglutinate in the presence of low doses of ristocetin and a bleeding phenotype as judged by a simple assessment of hemostasis, the tail bleeding time. 12 Similar to human PT-VWD, the mice do not display significant thrombocytopenia, suggesting that the defect observed in the tail bleeding time is not solely explained by a reduced platelet count. In the present manuscript, we have used state-of-the-art imaging anal...

We developed an integrative component of the consult rotation for fellows training in hematology/oncology. This component consisted of triaging all consults to the hematology/oncology service of the CAVHS during a 1-year period of time. The goals of the rotation were to improve timeliness of response to consultation requests, to gain experience in differential diagnosis of patients with potential hematologic/oncologic disorders through of such patients, review of decisions with attending physicians, and communication of such with the referring physician. The major benefits were that fellows integrated didactic learning into real-life clinical cases, selected patients for their continuity clinic to assure sufficient variety and complexity of cases, honed their communication skills, learned about referring and attending physicians' styles, and gained practice in clinical vignettes representative of cases they would be expected to see in clinical practice. Disadvantages were time involvement (approximately 2 h/day) and risks of over- or under-referrals. Administratively, there was a significant decline in the wait time for patients to be seen in the hematology/oncology service. In all, this elective is a valuable integrative experience of senior fellows, but may have less value for first year fellows.